Inflammatory chemokine (C-C motif) ligand 8 inhibition ameliorates peritoneal fibrosis.

Peritoneal fibrosis (PF) is an irreversible complication of peritoneal dialysis (PD) that leads to loss of peritoneal membrane function. We investigated PD effluent and serum levels and the tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with PD. Additionally, we investigated their association with PF in a mouse model. Eighty-two end-stage renal disease (ESRD) patients with PD were examined. CCL8 levels were measured via enzyme-linked immunosorbent assays in PD effluents and serum and analyzed with peritoneal transport parameters. Human peritoneal mesothelial cells (hPMCs) were obtained from the PD effluents of 20 patients. Primary cultured hPMCs were treated with recombinant (r) transforming growth factor (TGF)-ß, and CCL8 expression was assessed via western blotting. As the duration of PD increased, the concentration of CCL8 in PD effluents significantly increased. Correlations between peritoneal transport parameters and dialysate CCL8 levels were observed. Western blotting analysis showed that CCL8 was upregulated via rTGF-ß treatment, accompanied by increases in markers of inflammation, fibrosis, senescence, and apoptosis in hPMCs after induction of fibrosis with rTGF-ß. Anti-CCL8 monoclonal antibody (mAb) treatment suppressed the rTGF-ß-induced increase in all analyzed markers. Immunohistochemical analysis revealed that CCL8 along with fibrosis- and inflammation-related markers were significantly increased in the PF mouse model. Functional blockade of CCL8 using a CCR8 inhibitor (R243) abrogated peritoneal inflammation and fibrosis in vivo. In conclusion, high CCL8 levels in PD effluents may be associated with an increased risk of PD failure, and the CCL8 pathway is associated with PF. CCL8 blockade can ameliorate peritoneal inflammation and fibrosis.

Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Multisample Mass Spectrometry-Based Approach for Discovering Injury Markers in Chronic Kidney Disease.

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome data sets, 38 DEPs were organized; only ten DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin, were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multisample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Clinical Performance of the Osmotic Shock-MALDI MS Method to Detect Klebsiella pneumoniae Carbapenemase in Clinical Isolates.

The World Health Organization recently highlighted the serious worldwide problem of the emergence of antibiotic-resistant or antibiotic multidrug-resistant bacteria. Carbapenem-resistant Enterobacterales, including carbapenemase-producing Enterobacterales (CPE), are major antibiotic-resistant bacteria that can be identified by various methods, including antibiotic susceptibility testing, PCR, and immunologic assays. However, there is a need for a faster, more accurate, low-cost, and easy method to detect CPE strains. We previously developed an osmotic shock matrix-assisted laser desorption/ionization mass spectrometry (OS-MALDI MS) method for directly detecting intact Klebsiella pneumoniae carbapenemase (KPC) using osmotic shock cell lysis. In this study, we evaluated the OS-MALDI MS method and compared it with two other methods (octyl-glucoside-aided direct KPC detection method [OG-MALDI MS] and Bruker's MBT subtyping module indirect method [MBT-SM MALDI MS]). We first completed an analytical performance evaluation of the OS-MALDI MS method according to Clinical and Laboratory Standards Institute guidelines. Clinical testing was performed with 437 clinical isolates, including 292 KPC-producing bacteria and 145 non-KPC-producing bacteria. The OS-MALDI MS method exhibited 95.9% sensitivity, 100.0% specificity, and 100.0% precision for detecting KPC. Accuracy of the OS-MALDI MS, OG-MALDI MS, and MBT-SM MALDI MS methods was 97.3%, 55.9%, and 50.2%, respectively. In conclusion, the OS-MALDI MS method clearly outperformed the other methods, exhibiting the highest accuracy and sensitivity of the three methods. We propose the OS-MALDI MS method as a practical, useful method for clinic environments, which may help guide appropriate antibiotic treatment and contribute to the prevention of the spread of CPE.

Molecular epidemiological study of the G protein of human respiratory syncytial virus detected in patients with acute respiratory infections in Gyeonggi Province, South Korea.

To investigate the molecular characteristics of human respiratory syncytial virus (HRSV) detected in Gyeonggi Province from 2015/16 to 2017/18, 2331 specimens from patients with sporadic acute respiratory illness and 85 specimens from four HRSV outbreaks in the postpartum care center were analyzed by real-time reverse transcription PCR. HRSVs were detected in 97 of the 2416 (4.0%) specimens, and among the positive specimens, 38 (39.2%) were identified as HRSV-A and 59 (60.8%) as HRSV-B. During the study periods, HRSV-B predominated in all seasons, except in 2016/17 during which HRSV-A predominated. Depending on the age groups, HRSV prevalence was the highest in 0- to 2-year-old patients. Comparison of noninfected subjects with HRSV-infected subjects revealed that HRSV infection more frequently resulted in fever, nasal obstruction, and wheezing, although the frequency of sore throat was low; however, comparison of the symptoms between HRSV-A- and HRSV-B-infected patients revealed no significant differences in symptoms. Phylogenetic analysis showed that all HRSV-A patients had an ON1 genotype, and all HRSV-B patients had an BA9 genotype. These results provide a valuable reference regarding the circulating pattern and molecular characterization of HRSV. Continuous monitoring will be essential to detect newly emerging HRSV genotypes.

Coinfections with Respiratory Pathogens among COVID-19 Patients in Korea.

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in upper and lower respiratory specimens and coinfection with other respiratory pathogens in patients with coronavirus disease 2019 (COVID-19) was investigated. Study subjects (N = 342) were retrospectively enrolled after being confirmed as SARS-CoV-2 positive, and their nasopharyngeal swab (NPS), oropharyngeal swab (OPS), and sputum specimens were restored for SARS-CoV-2 retesting and respiratory pathogen detection. The majority of the subjects (96.5%, N = 330) were confirmed as SARS-CoV-2 positive using NPS/OPS specimens. Among the COVID-19 patients (N = 342), 7.9% (N = 27) and 0.9% (N = 3) were coinfected with respiratory viruses and Mycoplasma pneumoniae, respectively, yielding an 8.8% (N = 30) overall respiratory pathogen coinfection rate. Of the respiratory virus coinfection cases (N = 27), 92.6% (N = 25) were coinfected with a single respiratory virus and 7.4% (N = 2) with two viruses (metapneumovirus/adenovirus and rhinovirus/bocavirus). No triple coinfections of other respiratory viruses or bacteria with SARS-CoV-2 were detected. Respiratory viruses coinfected in the patients with COVID-19 were as follows: rhinovirus (N = 7, 2.1%), respiratory syncytial virus A and B (N = 6, 1.8%), non-SARS-CoV-2 coronaviruses (229E, NL63, and OC43, N = 5, 1.5%), metapneumovirus (N = 4, 1.2%), influenza A (N = 3, 0.9%), adenovirus (N = 3, 0.9%), and bocavirus (N = 1, 0.3%). In conclusion, the diagnostic value of utilizing NPS/OPS specimens is excellent, and, as the first report in Korea, coinfection with respiratory pathogens was detected at a rate of 8.8% in patients with COVID-19.

Chemokine receptor 5 blockade modulates macrophage trafficking in renal ischaemic-reperfusion injury.

Chemokine receptor 5 (CCR5) is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade. We investigated the role of CCR5 in experimental ischaemic-reperfusion injury (IRI) pathogenesis. To establish IRI, we clamped the bilateral renal artery pedicle for 30 min and then reperfused the kidney. We performed adoptive transfer of lipopolysaccharide (LPS)-treated RAW 264.7 macrophages following macrophage depletion in mice. B6.CCR5-/- mice showed less severe IRI based on tubular epithelial cell apoptosis than did wild-type mice. CXCR3 expression in CD11b+ cells and inducible nitric oxide synthase levels were more attenuated in B6.CCR5-/- mice. B6.CCR5-/- mice showed increased arginase-1 and CD206 expression. Macrophage-depleted wild-type mice showed more injury than B6.CCR5-/- mice after M1 macrophage transfer. Adoptive transfer of LPS-treated RAW 264.7 macrophages reversed the protection against IRI in wild-type, but not B6.CCR5-/- mice. Upon knocking out CCR5 in macrophages, migration of bone marrow-derived macrophages from wild-type mice towards primary tubular epithelial cells with recombinant CCR5 increased. Phospho-CCR5 expression in renal tissues of patients with acute tubular necrosis was increased, showing a positive correlation with tubular inflammation. In conclusion, CCR5 deficiency favours M2 macrophage activation, and blocking CCR5 might aid in treating acute kidney injury.

Optimal fasting glucose levels with regard to cardiovascular and mortality outcomes in people treated with or without antidiabetic medication.

AIMS: To investigate the optimal fasting blood glucose (FBG) levels among individuals actively treated or untreated with antidiabetic drugs. METHODS: In two population-based cohorts of Korean adults extracted from the National Health Information Database, multivariable-adjusted hazard ratios of outcomes over 10 and 8 years of follow-up were estimated according to achieved FBG levels and antidiabetic drug use. The primary outcomes were major cardiovascular disease (CVD) events and all-cause mortality. RESULTS: In total, 66 533 of 450 537 and 100 556 of 767 382 participants in the respective cohorts received antidiabetic treatment. For untreated FBG, the CVD risk and mortality increased linearly from an FBG threshold of 5.6 mmol/L; however, for FBG treated with antidiabetic drugs there were J-shaped associations with the outcome risks. For treated FBG levels of 4.4 to 5.5 mmol/L, 7.8 to 8.8 mmol/L, 8.9 to 9.9 mmol/L and ≥ 10.0 mmol/L, vs 6.1 to 6.9 mmol/L, the hazard ratios for major CVD events were 1.17 (95% confidence interval [CI] 1.04-1.32), 1.06 (95% CI 0.96-1.18), 1.37 (95% CI 1.22-1.53) and 1.61 (95% CI 1.46-1.78), respectively, and those for all-cause mortality were 1.20 (95% CI 1.11-1.29), 1.05 (95% CI 0.99-1.12), 1.29 (95% CI 1.10-1.50) and 1.69 (95% CI 1.59-1.81), respectively. CONCLUSIONS: These findings indicate that pharmacological therapy achieving FBG levels of <7.8 to 8.9 mmol/L and a non-pharmacological approach to maintaining normal glucose levels help reduce the risk of adverse outcomes, while lowering FBG to normal levels through antidiabetic drugs is not beneficial or may even be harmful.

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE).

BACKGROUNDS: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). METHODS: The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. DISCUSSION: Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. TRIAL REGISTRATION: NCT03929887 .

ST2 blockade mitigates peritoneal fibrosis induced by TGF-ß and high glucose.

Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 in PF using patient samples along with mouse and cell-based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure (P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate-induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human peritoneal mesothelial cells (HPMCs), transforming growth factor-ß treatment increased ST2, fibronectin, ß-galactosidase and Snail protein levels and decreased E-cadherin level. Anti-ST2 antibody administration reversed the up-regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose (100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.

Emergence and Spread of Cephalosporin-Resistant Neisseria gonorrhoeae with Mosaic penA Alleles, South Korea, 2012-2017.

In South Korea, surveillance of antimicrobial drug resistance in Neisseria gonorrhoeae is extremely limited. We describe the emergence and subsequent national spread of N. gonorrhoeae strains with mosaic penA alleles associated with decreased susceptibility and resistance to extended-spectrum cephalosporins. From 2012 through 2017, the proportion of mosaic penA alleles in gonococcal-positive nucleic acid amplification test (NAAT) specimens across South Korea increased from 1.1% to 23.9%. Gonococcal strains with mosaic penA alleles emerged in the international hubs of Seoul in Gyeonggi Province and Busan in South Gyeongsang Province and subsequently spread across South Korea. Most common was mosaic penA-10.001 (n = 572 isolates; 94.7%), which is associated with cefixime resistance. We also identified mosaic penA-34.001 and penA-60.001, both of which are associated with multidrug-resistant gonococcal strains and spread of cefixime and ceftriaxone resistance. Implementation of molecular resistance prediction from N. gonorrhoeae-positive nucleic acid amplification test specimens is imperative in South Korea and internationally.

Synthesis and Evaluation of Multifunctional Fluorescent Inhibitors with Synergistic Interaction of Prostate-Specific Membrane Antigen and Hypoxia for Prostate Cancer.

Prostate cancer is one of the most common cancers in the world. It is widely known that prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, and hypoxia is a common characteristic of many solid tumors, including prostate cancer. In this study, we designed multifunctional fluorescent inhibitors to target PSMA and tumor hypoxia in order to increase the tumor uptake of inhibitors. Novel PSMA inhibitors were prepared using lysine as the backbone to connect three different functional groups: the glutamate-urea-lysine (GUL) structure for inhibiting PSMA, 2-nitroimidazole for the hypoxia-sensitive moiety, and a near-infrared fluorophore (sulfo-Cyanine 5.5). According to the in vitro PSMA binding assay, novel fluorescent inhibitors were demonstrated to have nanomolar binding affinities. Multifunctional inhibitor 2 with one 2-nitroimidazole had a similar inhibitory activity to inhibitor 1 that did not contain the hypoxia targeting moiety, but multifunctional inhibitor 3 with two 2-nitroimidazoles showed lower inhibitory activity than inhibitor 1 due to the bulky structure of the hypoxia-sensitive group. However, in vivo optical imaging and ex vivo biodistribution studies indicated that both multifunctional inhibitors 2 and 3 had higher accumulation in tumors than inhibitor 1 due to a synergistic combination of PSMA and hypoxia targeting moieties. These observations suggest that this novel multifunctional strategy might be a promising approach to improve the diagnosis and therapy of prostate cancer.

Electron Beam Irradiated Al Doped ZnO Thin Films as Efficient Tunnel Recombination Junction for Hydrogenated Amorphous Silicon/Cu(In,Ga)Se2 Tandem Solar Cells.

A tunnel recombination junction (TRJ) layer for hydrogenated amorphous silicon (a-Si:H)/ Cu(In,Ga)Se2 (CIGS) tandem solar cells is investigated. An Al-doped zinc oxide (AZO) thin film is applied to the TRJ, and the influence of electron beam (e-beam) irradiation on defects along the TRJ is investigated. The AZO thin films are prepared using radio frequency (RF) sputtering and the e-beam is irradiated at 200 W RF power and 2 keV DC power for 5 min. In the e-beam irradiated AZO thin film, the number of oxygen vacancies and Zn interstitials increases, which in turn strengthens the effect of defect-enhanced tunnel recombination.

The association of tumor necrosis factor superfamily 13 with recurrence of immunoglobulin A nephropathy in living related kidney transplantation.

BACKGROUND: An increasing amount of evidence has demonstrated an association between an increase in the level of tumor necrosis factor superfamily 13 (TNFSF13) and immunoglobulin A nephropathy (IgAN) progression. We aimed to evaluate if the level of pre-transplant serum TNFSF13 is predictive of IgAN recurrence after kidney transplantation. METHODS: This analysis was based on the clinical and laboratory data of 69 patients with IgAN who underwent first kidney transplantation with no evidence of mesangial IgA deposits in zero-time transplantation biopsy. We measured pre-transplant serum TNFSF13, total IgA, and galactose-deficient IgA1 levels. RESULTS: The recurrence rate of IgAN over a median follow-up duration of 5.1 years was 15.9% (11/69 patients), with a mean time to the first recurrence of 1.7 years. The high pre-transplant TNFSF13 level was associated with IgAN recurrence after kidney transplantation among patients who received a graft from a living related donor. CONCLUSIONS: This study highlights association of TNFSF13 levels in recurrent IgAN patients who undergo living related donor transplantation. Further research is needed to clarify mechanisms by which TNFSF13 affects the recurrence of IgA nephropathy.

Synthesis of novel multivalent fluorescent inhibitors with high affinity to prostate cancer and their biological evaluation.

Prostate-specific membrane antigen (PSMA) is an important biological target for therapy and diagnosis of prostate cancer. In this study, novel multivalent PSMA inhibitors with glutamate-urea-lysine structures were designed to improve inhibition characteristics. Precursors of the novel inhibitors were prepared from glutamic acid with di-tert-butyl ester. A near-infrared molecular dye, sulfo-Cy5.5, was introduced into the precursors to generate the final PSMA fluorescent inhibitors, compounds 12-14, to visualize prostate cancer. Biological behaviors of the inhibitors were evaluated using in vitro inhibition assays, in vivo fluorescent imaging, and ex vivo biodistribution assays. Ki values from inhibition studies indicated that dimeric inhibitor 13 with a glutamine linker showed approximately 3-fold more inhibitory activity than monomeric inhibitor 12. According to other biological studies using a mouse model of prostate cancer, dimeric inhibitor compounds 13 and 14 had higher tumor accumulation than the monomer. However, glutamine-based dimeric inhibitor 13 showed lower liver uptake than dimeric inhibitor 14, which had a benzene structure. Thus, these studies suggest that glutamine-based dimeric inhibitor 13 can be a promising optical inhibitor of prostate cancer.

Design, synthesis, and biological evaluation of novel aminopyrimidinylisoindolines as AXL kinase inhibitors.

A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (4-acetylpiperazin-1-yl)phenyl moiety exhibited extremely excellent efficacy (IC50 = <0.00050 µM). Their in vitro antiproliferative activities were tested over five cancer cell lines. Most compounds showed good antiproliferative activities against HeLa cell line. The kinase panel profiling of 50 different kinases and the selected inhibitory activities for the representative compound 1u were carried out. The compound 1u exhibited excellent inhibitory activities (IC50 = <0.00050, 0.025, and 0.050 µM for AXL, MER, and TYRO3, respectively) against TAM family, together with potent antiproliferative activity against MV4-11 cell line (GI50 = 0.10 µM) related to acute myeloid leukemia (AML).

The product of Kaposi's sarcoma-associated herpesvirus immediate early gene K4.2 regulates immunoglobulin secretion and calcium homeostasis by interacting with and inhibiting pERP1.

Chaperones are proteins that assist the noncovalent folding and assembly of macromolecular polypeptide chains, ultimately preventing the formation of nonfunctional or potentially toxic protein aggregates. Plasma cell-induced-endoplasmic reticulum (ER)-resident protein 1 (pERP1) is a cellular chaperone that is preferentially expressed in marginal-zone B cells and is highly upregulated during plasma cell differentiation. While initially identified as a dedicated factor for the assembly of secreted IgM, pERP1 has since been implicated in suppressing calcium mobilization, and its expression is misregulated in multiple tumors. A number of herpesvirus immediate early gene products play important roles in the regulation of viral gene expression and/or evasion of host immune responses. Here, we report that the Kaposi's sarcoma-associated herpesvirus (KSHV) immediate early viral gene K4.2 encodes an endoplasmic reticulum-localized protein that interacts with and inhibits pERP1. Consequently, K4.2 expression interfered with immunoglobulin secretion by delaying the kinetics of immunoglobulin assembly and also led to increased responsiveness of B-cell receptor signal transduction by enhancing phosphotyrosine signals and intracellular calcium fluxes. Furthermore, K4.2 expression also appeared to contribute to maximal lytic replication by enhancing viral glycoprotein expression levels and ultimately promoting infectious-virus production. Finally, immunohistochemistry analysis showed that pERP1 expression was readily detected in KSHV-positive cells from multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) lesions, suggesting that pERP1 may have potential roles in the KSHV life cycle and malignancy. In conclusion, our data suggest that K4.2 participates in lytic replication by enhancing calcium flux and viral glycoprotein expression, but also by interfering with immunoglobulin assembly to potentially dampen the adaptive immune response.

Development and Implementation of a Mobile-Integrated Simulation for COVID-19 Nursing Practice: A Randomized Controlled Pretest-Posttest Experimental Design.

This study developed and evaluated the effects of a mobile-integrated simulation training program on infection prevention and nursing practices based on past experiences of coronavirus disease (COVID-19) care. We developed mobile videos for the experimental group and an educational booklet for the control group based on the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model. The effects of the simulation program with the use of mobile videos on knowledge of COVID-19 management, infection prevention practice confidence, and clinical decision-making anxiety and confidence were analyzed through a randomized controlled pretest-posttest experimental design. Data from 109 participants were analyzed. Five mobile videos were developed with a total duration of 43 min and 13 s. The experimental group showed significantly greater improvement in knowledge of COVID-19 management (p = 0.002) and infection prevention practice confidence (p < 0.001). Using the mobile-integrated COVID-19 nursing practice simulation program, nurses who have no experience with emerging infectious diseases can increase their infection control knowledge and infection prevention practice confidence. In conclusion, the mobile-integrated COVID-19 nursing practice simulation program was effective in increasing infection control knowledge and infection prevention practice confidence in nurses without COVID-19 care experience.

Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea.

Purpose: The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program. Materials and Methods: Individuals aged ≥50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year's annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥120). Results: A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: Relative risks [RR], 2.15; 95% Confidence Interval [CI], 1.57-2.94; V3: RR, 1.56, 95% CI, 1.15-2.13; V4: RR, 1.18; 95% CI, 0.83-1.67). Conclusion: The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for colorectal cancer, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

Successfully treated Escherichia coli-induced emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotics irrigation in a patient with autosomal dominant polycystic kidney disease.

A 62-yr-old woman with an autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital for further evaluation of intermittent fever, nausea and left flank discomfort. The computed tomography (CT) scan revealed a gas-forming, infectious cyst of approximately 8.1 cm in size in left kidney lower pole. Escherichia coli was identified from the cyst fluid culture examination. Her symptoms improved only after the concomitant use of intravenous ciprofloxacin and an intracystic irrigation of ciprofloxacin through a percutaneous cystostomy drainage. Our case presents the successfully treated emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotic therapy instead of surgical management.