Quantitative PCR for early detection of human cytomegalovirus end-organ disease in immunocompetent host: A retrospective single-center study.

BACKGROUND: Tissue-invasive end-organ disease (EOD) caused by cytomegalovirus (CMV) is less frequently reported in immunocompetent patients compared to immunocompromised patients. In this study, we investigated the association between CMV viremia and CMV end-organ disease in immunocompetent patients. METHODS: Adult patients (≥18 years old) with CMV viremia were screened from January 2010 to June 2022. The primary outcome was the presence of CMV EOD. Risk factors associated with CMV EOD were analyzed, and a receiver operating characteristic curve was plotted to determine the most accurate cutoff value of the CMV titer for the prediction of CMV EOD. RESULTS: Among the 106 immunocompetent patients with CMV viremia, 31 exhibited CMV EOD. Gastrointestinal tract disease was the most common. The log10 value of the CMV titer was significantly associated with the occurrence of CMV EOD in immunocompetent patients with CMV viremia. The optimal cut-off CMV titer for the prediction of CMV EOD was 749 IU/mL. CONCLUSIONS: Our study suggests the potential association between high CMV titers and the development of CMV end-organ diseases and describes the diagnostic performance and utility of quantitative PCR as a surrogate marker for predicting the occurrence of CMV EOD in immunocompetent patients.

Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

Background: The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. Objectives: To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. Methods: A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. Results: The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Conclusion: Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Deep Learning Model Using Stool Pictures for Predicting Endoscopic Mucosal Inflammation in Patients With Ulcerative Colitis.

INTRODUCTION: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. METHODS: This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). RESULTS: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002). DISCUSSION: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC.

Pharmacologic Treatment of Chronic Constipation.

Chronic constipation is a common disease that can impair the quality of life, with a prevalence of 14% globally and 16.5% in South Korea. Straining, hard stools, the sensation of incomplete evacuation, the sensation of anorectal blockage, and manual maneuvers to facilitate defecation are the related symptoms of chronic constipation. On the other hand, medications commonly referred to as laxatives are the essentials of treatment for constipation compared to non-pharmacological treatment, such as lifestyle modifications, biofeedback, or surgery. Unfortunately, there is still an unmet need to determine if pharmacological treatment for constipation is being administered appropriately. Therefore, there are many disadvantages as to whether the indications and side effects of laxatives are adequately considered and prescribed as the primary treatment modality for constipation in a real clinical situation in Korea. Laxatives are generally recommended as the next step for patients in whom organic causes have been excluded and have not responded to initial non-pharmacologic therapies such as dietary fiber intake and exercise. Laxatives can be classified as bulk-forming laxatives, osmotic laxatives, stimulant laxatives, and other novel laxatives. On the other hand, there are distinct mechanisms underlying constipation, and appropriate administration is the most decisive. Therefore, the present investigators prepared this review to discuss appropriate pharmacological strategies for chronic constipation in Korea. Moreover, this paper also includes suggestions for appropriate pharmacological treatment options for special patient populations.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Genotype-phenotype correlations in children with Gitelman syndrome.

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.

Discriminative stimulus and reinforcing effects of diclazepam in rodents.

Diclazepam, a designer benzodiazepine, is a lesser-known novel anxiolytic substance and a structural analog of diazepam. Although several case studies have reported the adverse effects of diclazepam, their potential impacts remain unknown. Therefore, this study aimed to determine the effects of diclazepam in rodents using drug discrimination, locomotor activity, self-administration (SA), and conditioned place preference (CPP) tests. Sprague-Dawley rats (male, 8 weeks old, weighing 220-450 g, n = 12 per group) and C57BL/6 mice (male, 7 weeks old, weighing 20-25 g, n = 7-8 per group) were administered alprazolam, morphine, and diclazepam. Diclazepam fully elicited alprazolam-appropriate dose-dependent lever responses (>80 %) similar to those of alprazolam. In rats administered 0.5 mg/kg of morphine, a partial substitution (80 %-20 %) was observed. Mice receiving intraperitoneal injections of diclazepam (0.05, 0.2, and 2 mg/kg) showed decreased locomotor activity. In the SA experiment, mice that self-administered intravenous diclazepam (2 µg/kg/infusion) showed significantly higher infusion and active lever responses compared to the vehicle group. No statistically significant rewarding effects of diclazepam at the doses of 0.2 and 2 mg/kg evaluated using the CPP paradigm were found. In conclusion, diclazepam has reinforcing effects and shares the interoceptive effects of alprazolam. Therefore, legal restrictions on the use of diclazepam should be carefully considered.

Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

Long-term outcomes and associated prognostic risk factors of childhood-onset lupus nephritis.

Background: This study investigated the clinical characteristics and kidney outcomes of childhood-onset lupus nephritis (LN), and risk factors associated with prognosis. Methods: We enrolled 216 patients with histologically diagnosed LN during childhood. The Korean Society of Pediatric Nephrology organized a retrospective cohort study of childhood-onset LN in 13 major pediatric nephrology centers in South Korea. Results: The mean age at kidney biopsy was 13.2 ± 3.22 years. The main forms of presentation were nephrotic syndrome and/or hematuria in 152 patients (70.4%), and the most common histological finding was World Health Organization (WHO) class IV in 138 patients (63.9%), followed by WHO class III in 34 patients (15.7%). In the outcome analysis, the mean follow-up period of the patients was 7.8 ± 5.11 years. At last follow-up, 32 patients (14.8%) developed advanced chronic kidney disease (CKD). Male sex and failure to achieve remission at 12 months of treatment were significant risk factors for developing advanced CKD (hazard ratio of 2.57 and 2.29, respectively). Conclusion: Our study demonstrated the clinical characteristics and long-term outcomes of patients with childhood-onset LN. Male sex and failure to achieve remission in the first year of treatment were predictive of advanced CKD. Therefore, prompt awareness and close monitoring of these high-risk patients are needed, which may further improve the prognosis of children with LN.

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence.

Oncogenic K-RAS mutations occur in approximately 25% of human lung cancers and are most frequently found in codon 12 (G12C, G12V, and G12D). Mutated K-RAS inhibitors have shown beneficial results in many patients; however, the inhibitors specifically target K-RASG12C and acquired resistance is a common occurrence. Therefore, new treatments targeting all kinds of oncogenic K-RAS mutations with a durable response are needed. RUNX3 acts as a pioneer factor of the restriction (R)-point, which is critical for the life and death of cells. RUNX3 is inactivated in most K-RAS-activated mouse and human lung cancers. Deletion of mouse lung Runx3 induces adenomas (ADs) and facilitates the development of K-Ras-activated adenocarcinomas (ADCs). In this study, conditional restoration of Runx3 in an established K-Ras-activated mouse lung cancer model regressed both ADs and ADCs and suppressed cancer recurrence, markedly increasing mouse survival. Runx3 restoration suppressed K-Ras-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting RUNX3 as a therapeutic tool for the treatment of K-RAS-activated lung cancers with a durable response.

The TGFß→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1.

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor ß (TGFß)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFß-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFß signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFß-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFß signals and the Hippo pathway (TGFß→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study.

BACKGRUOUND: Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes. METHODS: We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41-57 HU), and moderate to severe hepatic steatosis (≤40 HU). RESULTS: During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63). CONCLUSION: We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

Increase of Prevalence of Obesity and Metabolic Syndrome in Children and Adolescents in Korea during the COVID-19 Pandemic: A Cross-Sectional Study Using the KNHANES.

(1) Background: The aim of this study was to evaluate the prevalence of obesity and metabolic syndrome since the COVID-19 pandemic outbreak utilizing representative data on youth aged 2-18 years from the Korean National Health and Nutrition Examination Surveys (KNHANES) conducted in 2019-2020. (2) Methods: The survey consists of three parts: health interviews, health examinations, and nutrition surveys. From the 2019 and 2020 surveys, 1371 (2-9 years = 702 and 10-18 years = 669) and 1124 (2-9 years = 543 and 10-18 years = 581) individuals were included in the analysis. (3) Results: The mean body mass index (BMI) increased significantly among youth aged 2-9 years from 16.53 kg/m2 in 2019 to 17.1 kg/m2 in 2020 (p < 0.01). In youth aged 10-18 years, the BMI was found to increase slightly from 21.25 kg/m2 in 2019 to 21.41 kg/m2 in 2020 (p = 0.64). The increasing prevalence of extreme obesity was significant in girls, especially those aged 2-9 years (p < 0.01). However, extreme obesity had increased in 10-18-year-old boys (p = 0.08). The overall prevalence of metabolic syndrome in adolescents increased from 3.79% to 7.79% during the COVID-19 pandemic (p = 0.01). (4) Conclusions: We observed that the prevalence of obesity and metabolic syndrome among children and adolescents has increased after the COVID-19 outbreak. This is believed to be associated with an increase in the rate of early comorbidities in adulthood. The prevention of the progression of pediatric obesity has recently become an urgent public health concern in Korea.

Genotype-phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea.

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype-phenotype correlation not only in male patients but also in female patients with XLAS.

Role of RUNX3 in Restriction Point Regulation.

A cell cycle is a series of events that takes place in a cell as it grows and divides. At the G1 phase of cell cycle, cells monitor their cumulative exposure to specific signals and make the critical decision to pass through the restriction (R)-point. The R-point decision-making machinery is fundamental to normal differentiation, apoptosis, and G1-S transition. Deregulation of this machinery is markedly associated with tumorigenesis. Therefore, identification of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in tumor biology. RUNX3 is one of the genes frequently inactivated in tumors by epigenetic alterations. In particular, RUNX3 is downregulated in most K-RAS-activated human and mouse lung adenocarcinomas (ADCs). Targeted inactivation of Runx3 in the mouse lung induces adenomas (ADs), and markedly shortens the latency of ADC formation induced by oncogenic K-Ras. RUNX3 participates in the transient formation of R-point-associated activator (RPA-RX3-AC) complexes, which measure the duration of RAS signals and thereby protect cells against oncogenic RAS. This review focuses on the molecular mechanism by which the R-point participates in oncogenic surveillance.

Prevalence and trends of multiple antimicrobial resistance of Helicobacter pylori in one tertiary hospital for 20 years in Korea.

BACKGROUND: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).

Glycogen Synthase Kinase 3ß Is a Key Regulator in the Inhibitory Effects of Accumbal Cocaine- and Amphetamine-Regulated Transcript Peptide 55-102 on Amphetamine-Induced Locomotor Activity.

Microinjection of cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 into the nucleus accumbens (NAcc) core significantly attenuates psychostimulant-induced locomotor activity. However, the molecular mechanism remains poorly understood. We examined the phosphorylation levels of Akt, glycogen synthase kinase 3ß (GSK3ß), and glutamate receptor 1 (GluA1) in NAcc core tissues obtained 60 min after microinjection of CART peptide 55-102 into this site, followed by systemic injection of amphetamine (AMPH). Phosphorylation levels of Akt at Thr308 and GSK3ß at Ser9 were decreased, while those of GluA1 at Ser845 were increased, by AMPH treatment. These effects returned to basal levels following treatment with CART peptide 55-102. Furthermore, the negative regulatory effects of the CART peptide on AMPH-induced changes in phosphorylation levels and locomotor activity were all abolished by pretreatment with the S9 peptide, an artificially synthesized indirect GSK3ß activator. These results suggest that the CART peptide 55-102 in the NAcc core plays a negative regulatory role in AMPH-induced locomotor activity by normalizing the changes in phosphorylation levels of Akt-GSK3ß, and subsequently GluA1 modified by AMPH at this site. The present findings are the first to reveal GSK3ß as a key regulator of the inhibitory role of the CART peptide in psychomotor stimulant-induced locomotor activity.