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Abstract Catheter-based approaches may have inherent limitations in achieving effective renal denervation (RDN) and treatment of atrial fibrillation (AF). This study aimed to investigate the acute effects of novel laparoscopic RDN on modulating AF inducibility using a swine model. Four and five swine were randomly allocated to the sham and RDN groups, respectively. Each swine underwent measurement of the atrial effective refractory period (AERP) and AF induction tests using burst atrial pacing before and immediately after sham or RDN procedures with and without vagal nerve stimulation (VNS). A laparoscopic RDN procedure circumferentially ablated the renal nerves round the renal arteries using radiofrequency energy. There was no significant difference in the baseline AERP between the two groups (p > 0.05). Under VNS, AERP was significantly increased by 20 ms after laparoscopic RDN (95% CI = 0–30, p = 0.004). Compared to the sham group, the RDN group showed significantly reduced AF inducibility [OR (95% CI) = 0.32 (0.13–0.76) and 0.24 (0.11–0.57) with and without VNS, respectively]. After laparoscopic RDN, the duration of inducible AF episodes was significantly shortened from 28 (10–77) s to 7 (3–11) s (p

Abstract Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists—BMK-C203 and BMK-C205—and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

Purpose: About one-third of patients who undergo radical nephroureterectomy (RNUx) for upper tract urothelial carcinoma (UTUC) experience intravesical recurrence (IVR). This study investigated whether pyuria is a feasible predictor of IVR after RNUx in patients with UTUC. Materials and Methods: Seven hundred forty-three patients with UTUC who underwent RNUx at a single institute were analyzed in this study. The participants were divided into two groups: those without pyuria (non-pyuria) and those with pyuria. Kaplan–Meier survival analysis was performed, and p-values were assessed using the log-rank test. Cox regression analyses were performed to identify the independent predictors of survival. Results: The pyuria group had a shorter IVR-free survival period (p=0.009). The five-year IVR-free survival rate was 60.0% in the non-pyuria group vs. 49.7% in the pyuria group according to the Kaplan-Meier survival analysis. After the multivariate Cox regression analysis, pyuria (hazard ratio [HR]=1.368; p=0.041), a concurrent bladder tumor (HR=1.757; p=0.005), preoperative ureteroscopy (HR=1.476; p=0.013), laparoscopic surgery (HR=0.682; p=0.048), tumor multiplicity (HR=1.855; p=0.007), and a larger tumor (HR=1.041; p=0.050) were predictors of risk for IVR. There was no association between pyuria and recurrence-free survival (p=0.057) or cancer-specific survival (p=0.519) in the Kaplan–Meier survival analysis. Conclusions: This study concluded that pyuria was an independent predictor of IVR in patients with UTUC after RNUx.

Abstract Background Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. Methods This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients’ pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. Results Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2 cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5 min and the estimated blood loss was 100 cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. Conclusions The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. Trial registration Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371).

Adverse events following vaccination with the ChAdOx1 COVID-19 vaccine may be associated with the titer of neutralizing antibodies (NAbs) against SARS-CoV-2. In this cross-sectional study, a total of 82 HCWs who received the ChAdOx1 COVID-19 vaccine and did not have previous COVID-19 history were enrolled during March 2021. Blood samples were collected from HCWs 3 weeks after the first and second doses of vaccine, and NAbs were estimated using two types of commercially available kits, the cPass™ SARS-CoV-2 NAbs Kit (Genscript Biotech, Piscataway, NJ, USA) and R-FIND SARS-CoV-2 NAbs ELISA (SG Medical, Seoul, Korea). Median percent signal inhibition of NAbs was significantly higher after the second than after the first dose of vaccine, as determined using both the Genscript (median 43.1[IQR 71.2] vs. 93.6[83.1], p = 0.004) and R-FIND (53.2[82.6] vs. 76.8 [90.6], p = 0.03) kits. The percent signal inhibition of NAbs after the second dose of vaccine was higher in HCWs with than without systemic adverse events after the second dose, as determined using both the Genscript (p = 0.03) and R-FIND (p = 0.07) kits. The two doses of the ChAdOx1 vaccine induced high value of NAbs 3 weeks after vaccination. Immune responses were stronger in HCWs with than without adverse reactions after the second dose of ChAdOx1 vaccine.

Background: The hospital environment can be an important source for the transmission of pathogens, However, there are rare reports revealing the contamination of carbapenemase-producing enterobacterales (CPE) in the hospital environment. The aim of this study was to investigate the presence of CPE in hospital environments and their relation to clinical strains. Methods: Environmental samples were collected from three tertiary university hospitals between June 2017 and August 2019. The environmental samples were inoculated on CHROMagar™ KPC plates. A multiplex PCR and sequencing were used for six carbapenemase genes. Multi-locus sequence typing (MLST) was performed for CPE of Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae complex from the environmental and clinical specimens. Results: 20 carbapenem-resistant Enterobacteriaceae (CRE) strains were detected in the beds of patients, toilet bowl, sink, patient’s gown, electromanometer, and keyboard. K. pneumoniae was the most common, followed by Serratia marcescens, E. cloacae complex, E. coli, and Citrobacter freundii. Nineteen CRE were CPE. Eighteen of 19 CPEs produced KPC-2 carbapenemase, and one CPE (E. coli) produced NDM-5. We confirmed that the STs of K. pneumoniae-producing KPC-2 (ST 307 and ST11) and E. coli producing KPC-2 (ST648) from hospital environment were the same as those from patients. Conclusion: We believe that the hospital environment can be an important route for CPE transmission. Therefore, continuous surveillance and management are needed to prevent hospital-acquired infections (HAI) by transmission of CPE.

BackgroundKidney tubular damage markers are biomarkers of acute or chronic kidney injury. Hypothetically, upper tract urothelial cancer (UTUC), which induces obstructive uropathy or direct invasion of the renal parenchyma, may also induce increased excretion of urinary tubular damage proteins. Therefore, this study aimed to investigate the use of tubular damage biomarker as prognostic markers for UTUC.MethodsThe records of 417 surgically resected patients with UTUC were obtained from the Seoul National University Prospectively Enrolled Registry for urothelial cancer-upper tract urothelial cancer (SUPER-UC-UTUC) between January 2016 and December 2020. Patients with non-urothelial cancer or without urinary tubular injury marker measurement were excluded, and finally, 296 patients were finally included. B2-microglobulin (B2-MG) was an injury marker, and a value higher than 0.3 was considered abnormally elevated, according to previous studies.ResultsThe mean age was 70.9 years, and the male sex was predominant (n = 211, 71.3%). The incidences of renal pelvis and ureter cancer were similar (50.7% vs. 49.3%). Most patients had high-grade diseases (n = 254, 88.8%). The high urine B2-MG group was older, had decreased renal function, and had a higher pathologic T stage than did the low group. Multivariate Cox regression analysis of disease-free survival (DFS), open surgical method (Hazard ratio (HR) 1.52, p = 0.027), large tumor size (HR 1.06, p = 0.017), tumor multifocality (HR 1.90, p = 0.038), lymphovascular invasion (HR 2.19, p < 0.001), and high urine B2-MG (HR 1.57, p = 0.021) were significantly associated with shortened metastasis-free survival (MFS). Kaplan–Meier curve analysis revealed short DFS (median survival 15.5 months vs. unattained, log-rank p = 0.001) and MFS (unattained median survival in both groups, log-rank p = 0.003) for the high urine B2-MG group compared to the low urine B2-MG group.ConclusionPatients with UTUC presenting with increased pre-operative urine B2-MG levels were associated with disease recurrence and metastasis. This biomarker may aid in performing pre-operative risk stratification and in assessing the individual prognosis of patients with UTUC.

Urachal adenocarcinoma is rare, accounting for only 10% of adenocarcinomas of the bladder and the prognosis of urachal adenocarcinomas is poor since most cases are detected late. Since urachal adenocarcinoma is a rare disease, no effective standard treatment has yet been established. However, in recent studies, resection of carcinoma is considered the only treatment considered for non-metastatic cases. Although for large sized urachal adenocarcinoma, open surgery or laparoscopic surgery is usually considered, we have recently experienced huge urachal carcinoma by robotic surgery. We used cystoscopy and the robot to assess the cancer margins and safely perform the operation. A 71-year-old man with a medical history of hypertension and arrhythmia visited our urology department with urachal cancer detected by computed tomography (CT). CT showed a lobulated low-density mass, most likely urachal carcinoma, abutting the anterior dome of the bladder and anterior abdominal wall. We performed preoperative cystoscopy to assess the extent of the protrusion of the urachal cancer into the bladder wall and the area requiring resection during surgery. We confirmed the size and extent of the mass protruding into the anterior wall of the urinary bladder and Robot-assisted laparoscopic intracorporeal urachal mass resection and partial cystectomy using cystoscopy together was performed. After one month, the patient has no complications and no complaining symptoms complaints without any abnormal finding of follow up imaging test. Although more procedures must be performed to ensure the safety of robotic surgery as a treatment strategy for large urachal carcinomas, we confirm that robotic surgery can replace open or laparoscopic surgery for such tumors.

BackgroundThe spread of carbapenem-resistant Enterobacterales (CRE) strains has caused treatment failure and is a worldwide threat to public health. However, there are limited reports on the prevalence of carbapenemase-producing Enterobacterales (CPE) in aquatic environments and its association with clinical isolates. This study aimed to investigate the prevalence of CPE in a stream environment and its genetic relationship with clinical isolates in Korea.MethodsA total of 4,582 water samples were collected from 94 streams. Multiplex PCR and sequencing were used to detect and identify six carbapenemase genes. Multi-locus sequence typing (MLST) was performed to investigate the genetic relatedness between the environmental strains and clinical isolates.ResultsA total of 133 CRE strains were isolated from the streams. Klebsiella pneumoniae was the most common CRE (45.9%), followed by Enterobacter cloacae complex (29.3%), Escherichia coli (13.5%), Raoultella ornithinolytica (5.3%), and Citrobacter freundii (2.3%). Ninety (67.7%) isolates carried carbapenemase genes. K. pneumoniae carbapenemase-2 (36.7%) and New Delhi metallo-β-lactamase-5 (32.2%) were the common carbapenemases detected. Sequence type (ST)307 and ST11 K. pneumoniae strains harboring the blaKPC-2 gene were the most prevalent in stream and patient samples.ConclusionCPE was highly prevalent in streams and closely related to the isolates obtained from patients. Therefore, continuous monitoring of stream environments is required to control the spread of carbapenem resistance.

Abstract Background Several approaches for urethral catheterization after the failure of initial urethral catheterization have been introduced. However, standard procedures regarding what should be done after failed conventional urethral catheterization have been not established. Therefore, we investigated the clinical efficacy of retrograde urethrography (RGU)-assisted urethral catheterization after failed conventional urethral catheterization. Methods Between July 2015 and July 2018, 136 patients who underwent RGU-assisted urethral catheterization after failed conventional urethral catheterization were included in this retrospective study. Patients’ clinical data, such as age, catheterization site, and previous history of urologic operations, were collected and assessed via chart review. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for the failure of this procedure. Results Of the 136 patients, 94 (69.1%) experienced successful RGU-assisted urethral catheterization. Having a previous history of urologic operations, such as urethrotomy and transurethral prostatectomy, was identified as an independent predictive factor for the failure of RGU-assisted urethral catheterization (odds ratio = 9.453, 95% confidence interval = 2.703–33.063, p

Salmonella is a major pathogen causing foodborne infections in humans. Salmonella isolates are identified using biochemical and serological tests, including automated systems such as the VITEK2 system. However, there are few reports on Salmonella identification using VITEK MS. Therefore, we aimed to evaluate the usefulness of MALDI-TOF VITEK MS for Salmonella identification. A total of 1389 Salmonella isolates were identified using VITEK MS ver3.0 or ver3.2. All Salmonella isolates were confirmed by serotyping using the Kauffmann-White scheme, and the results were compared with the VITEK MS results. A total of 1389 Salmonella isolates, including 66 serotypes, were correctly identified at the genus level by VITEK MS. However, these systems failed to correctly identify typhoidal Salmonella. Among the five Salmonella enterica ssp. diarizonae isolates, only one was correctly identified, whereas one and three isolates were partially identified and misidentified, respectively. On the other hand, the VITEK2 system successfully identified all typhoidal Salmonella (Typhi and Paratyphi A) and Salmonella enterica ssp. diarizonae isolates. VITEK MS was useful for identifying Salmonella species isolated from clinical specimens; however, additional biochemical tests, such as the VITEK2 System, should be considered to accurately identify Salmonella ser. Typhi, and Salmonella ser. Paratyphi A.

Background: Salmonella is an important pathogen that causes gastroenteritis and sepsis in humans. Recently, changes in serotype prevalence and an increase in antimicrobial resistance have been reported. This study investigated the distribution of Salmonella serotypes and determined the antimicrobial susceptibility of various strains. Methods: We collected 113 Salmonella isolates other than Salmonella serotype Typhi from 18 university hospitals in 2015. The serotypes were identified by Salmonella antisera O and H according to the Kauffman White scheme. Antimicrobial susceptibility tests for 12 antibiotics were performed using the disk diffusion method or E-test. Results: We identified 22 serotypes. Serotype group B (44.2%) was the most common, followed by groups C (34.5%) and D (21.2%). Salmonella I 4,[5],12:i:- (23.0%), S. Enteritidis (16.8%), and S. Typhimurium (12.4%) were the most common species. Resistance rates for ampicillin, chloramphenicol, ceftriaxone, and trimethoprim/sulfamethoxazole were 46.9%, 18.5%, 8.8%, and 5.3%, respectively. The intermediate resistance rate to ciprofloxacin was 29.2%. Six isolates were extended-spectrum β-lactamase (ESBL) producers, including 5 blaCTX-M-15 and 1 blaCTX-M-55. Conclusion: There have been changes in the serotype prevalence and antimicrobial resistance of Salmonella in Korea, with a high prevalence of CTX-M 15-positive strains. Continuous monitoring of Salmonella serotypes and antimicrobial resistance is warranted. (Ann Clin Microbiol 2019;22:55-60)

Abstract Background As strawberries are susceptible to somaclonal variation when propagated by tissue culture techniques, it is challenging to obtain the true-to-type plants necessary for continuous production of fruits of stable quality. Therefore, we aimed to develop an in vitro propagation method for the production of true-to-type plants of five different strawberry cultivars from meristems cultured in media containing different concentrations of kinetin (Kn). Results For all the cultivars, shoot induction was successful only in the meristems cultured in the medium without Kn and the medium containing 0.5 mg L−1 Kn. The shoots obtained from explants cultured in media supplemented with 0.5 mg L−1 Kn exhibited better plant growth parameters than those cultured in media without Kn and were genetically stable when compared with conventionally propagated plants for all the cultivars. Vegetative and sexual characters and fruit quality attributes observed in the plants derived from meristems cultured on 0.5 mg L−1 Kn and the conventionally propagated plants were not significantly different when grown for three continuous growing seasons under greenhouse conditions. Conclusion The culture of meristems in the medium containing 0.5 mg L−1 Kn is suitable for the efficient propagation of true-to-type plants of different strawberry cultivars and continuous production of fruits with stable quality. Hence, we expect that the method presented in this study will be helpful for the commercial production of true-to-type plants generated in vitro for other strawberry cultivars.

Objective: To compare the therapeutic efficacy after suburethral adjustable sling (Remeex system) for female stress urinary incontinence (SUI) between pure intrinsic s phincter deficiency (ISD) and ISD with overactive bladder (OAB) group. Methods: The study subjects were 86 female patients with ISD who underwent Remeex system to treat female SUI and who were available for 12 months follow-up. We retrospectively studied both patients who underwent Remeex system due to pure ISD (group I) and those who underwent Remeex system due to ISD with OAB (group II). Improvement in objective and subjective symptoms were retrospectively evaluated using a 1hr pad weight test, global response assessment (GRA) and overactive bladder symptom score (OABSS). Results: Group I included 43 patients and group II included 43 patients of mean ages 56.8 ± 7.5 and 57.4 ± 6.6 years, respectively. Use of 1 hr pad weight test showed that incontinence decreased after the procedures in both groups, and that of group I patients was significantly lower than that of group II patients. The mean GRA score was significant a higher score in group I. The OABSS of patients in group II were 8.2 ± 1.1 and 7.2 ± 1.1, respectively, before and at 12 months after operation, did differ significantly. The mean change of OABSS of group II patients was significantly more decreased than that of group I patients. Conclusions: The Remeex system showed a greater patient satisfaction and a higher cure rate in pure ISD than ISD with OAB in female patients with urinary incontinence.

Background: Renal agenesis is a congenital malformation that occurs due to the inhibition of metanephric blastema induction due to a decrease in ureteric bud activity. Although renal agenesis is not very rare, unilateral renal agenesis with ureterocele occurs rarely, and the coexistance of unilateral renal agenesis, ureterocele, and blind ended proximal ureter is very rare. Recently, we experienced a case of left renal agenesis with huge ureterocele, blind ended proximal ureter, and duplicated ureter on Computed tomography (CT) of a 17-year-old man who visited our emergency department with hematuria. Ureterocelectomy and nephrectomy were performed, and a translocation of seminal vesicle was also observed. This case is a very rare case, so we judged that it may be helpful in making treatment decisions in similar cases later. Case summary: A 17-year-old man without specific medical history visited our emergency department with hematuria and voiding difficulty. CT showed left ectopic kidney, megaureter and the blind ended proximal ureter. After ureterocelectomy and nephrectomy, pathological examination revealed seminal vesicles in the periphery of the kidney. After one year, the patient has no complications and no complaining symptoms complaints without any abnormal finding of follow up imaging test. Conclusions: This case report focuses on the treatment of renal agenesis with ureterocele, blind ended proximal ureter, duplicated megaureter and translocation of seminal vesicle. This rare case of treatment will be helpful in the determination of treatment for similar cases in the future. To establish standard treatment, data accumulation and well-designed studies are required.

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether β-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

Backgrounds: Engaging in light activity, moderate-to-vigorous physical activity (MVPA), or sedentary behavior can influence the health status of older adults. The purpose of this study was to examine the relationship between frailty and the daily amount of physical activity, as measured by an activity tracker, and to identify frail older adults based on the tracker data. Methods: The participants were community-dwelling older adults (aged ≥ 65 years) classified as frail or non-frail. Frailty was defined by the presence of three or more of the following: weight loss, exhaustion, low energy expenditure, slow gait speed, and weak grip strength. Physical activity was monitored using the activity tracker, and the daily durations of MVPA, light activity, and sedentary activity were measured over a 7-day period. Results: The duration of MVPA was significantly associated with frailty status (unadjusted odds ratio = .936, p = .018; adjusted odds ratio = .935, p = .039). There was no significant association between frailty and the duration of light or sedentary activity. However, classification and regression tree analysis generated cutoff points of ≥ 29.65 min/day and ≥ 156.93 min/day of MVPA and light activity, respectively, for determining frailty in older adults with an accuracy of 87.7%. Conclusions: Durations of MVPA and light activity, as measured using an activity tracker, differentiated frail and non-frail older adults. The classification and regression tree analysis yielded cutoff points that could inform recommendations regarding the daily amount of physical activity for older people. [ABSTRACT FROM AUTHOR]

Several companies have migrated their existing monolithic web applications to microservice architectures. Consequently, research on the identification of microservices from monolithic web applications has been conducted. Meanwhile, the use-case model plays a crucial role in outlining the system’s functionalities at a high level of abstraction, and studies have been conducted to identify microservices by utilizing this model. However, previous studies on microservice identification utilizing use-cases did not consider the components executed in the presentation layer. Unlike existing approaches, this paper proposes a technique that considers all three layers of web applications (presentation, business logic, and data access layers). Initially, the components used in the three layers of a web application are extracted by executing all the scenarios that constitute its use-cases. Thereafter, the usage rate of each component is determined for each use-case and the component is allocated to the use-case with the highest rate. Then, each use-case is realized as a microservice. To verify the proposed approach, microservice identification is performed using open-source web applications. [ABSTRACT FROM AUTHOR]