Background: Blastocystis is a genus of intestinal, anaerobic protozoan parasites that can be isolated from humans, animals, and the environment. We aimed to determine the distribution of Blastocystis and subtypes (STs) using stool samples obtained from healthy volunteers at collection centers in South Korea. Methods: A total of 478 stool samples from volunteers were collected at five collection centers throughout South Korea. The presence of Blastocystis was determined using PCR based on the small subunit (SSU) rRNA gene, and Blastocystis STs were confirmed through sequencing of the SSU rRNA gene. Results: Molecular analysis revealed the presence of Blastocystis in 27 (5.6%) of the enrolled participants. Two STs were identified: ST3 (66.7%) and ST1 (33.3%). The positive rates of Blastocystis varied by geographical region, ranging from 1.2%–12.0%. ST3 was the predominant subtype in all centers except one, where only ST1 was isolated. Phylogenic analysis showed clustering based on ST, but no significant differences were found among the regions. There was no association between Blastocystis colonization and either age or sex of the participants. Conclusions The results of this multicenter study demonstrated colonization by Blastocystis, mainly ST3, in the gastrointestinal tracts of asymptomatic individuals in South Korea.

Background: Intestinal protozoa are potential diarrhea-causing pathogens and monitored worldwide. The Korea Centers for Disease Control and Prevention has also been monitoring intestinal protozoa causing diarrhea for many years. Recently, the overall protozoa detection rate has decreased to less than 1%, but whether protozoa infection causing diarrhea has declined or is being underestimated has not been studied. This study aimed to investigate the molecular epidemiology of intestinal protozoan pathogens in stool samples collected from multiple Korean centers. Methods: Stool samples were collected from five university hospitals and a commercial laboratory. Direct smear and trichrome staining were performed on all samples. The presence of Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, Cyclospora cayetanensis, Dientamoeba fragilis, and Blastocystis hominis were detected using Allplex™ Gastrointestinal Parasite Assays (Seegene Inc., Korea). Microsporidia species and Kudoa septempunctata were detected using PowerChek™ Microsporidia Multiplex and Kudoa Real-time PCR kits (Kogene Biotech, Korea), respectively. Results: The collected samples included 279 diarrheal and 51 non-diarrheal samples. Among the 279 diarrheal samples, nine samples [B. hominis (n=7), C. parvum (n=1), and Microporidia species (n=1)] were positive, but there were no positive samples for K. septempunctata. We could not detect any protozoa by direct smear and trichrome staining. Among the 51 nondiarrheal samples, 10 (19.6%) samples were positive for B. hominis, but no other protozoa were observed Conclusion This multicenter study showed that the detection rate of intestinal protozoa is currently low in diarrheal samples from Korea. However, B. hominis was frequently detected in non-diarrheal samples, indicating their low pathogenicity.

Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006–2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1 , MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.

Background/Aims: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

Purpose: This study is to understand the experiences of people with serious mental illness following adjustment to independent living. Methods: Aphenomenological research approach was used. Research participants were recruited from community psychiatric rehabilitation centers where they received the support for successfully independent living in the community. In-depth interviews were conducted with a total of 20 research participants from September 2019 to August 2021. The collected data were analyzed using the phenomenological analysis method previously described by Giorgi. Results: Four major themes emerged from our analysis: (1) feeling free in everyday life changed when they started living independently; (2) being the owner of my life; (3) feeling surrounded by barriers at the start of independent living; and (4) required efforts and support for fully living independently. Conclusion Our study findings encourage fundamental understanding of benefits and difficulties in adjusting to independent living and the adjustment process among people with serious mental illness through in-depth analysis of their experiences. It is necessary to conduct further studies to develop interventions to support people with serious mental illness once they start living independently and instruments to measure their independence.

Background: Multidrug-resistant Acinetobacter baumannii (MDRAB) is widespread among intensive care units worldwide, posing a threat to patients and the health system. We describe the successful management of a MDRAB outbreak by implementing an infection-control strategy in a pediatric intensive care unit (PICU). Methods: This retrospective study investigated the patients admitted to the PICU in periods 1 (8 months) and 2 (7 months), from the index MDRAB case to intervention implementation, and from intervention implementation to cessation of MDRAB spread. An infection-control strategy was designed following six concepts: 1) cohort isolation of colonized patients, 2) enforcement of hand hygiene, 3) universal contact precautions, 4) environmental management, 5) periodic surveillance culture study, and 6) monitoring and feedback. Results: Of the 427 patients, 29 were confirmed to have MDRAB colonization, of which 18 had MDRAB infections. Overall incidence per 1,000 patient days decreased from 7.8 (period 1) to 5.8 (period 2). The MDRAB outbreak was declared terminated after the 6-month followup following period 2. MDRAB was detected on the computer keyboard and in condensed water inside the ventilator circuits. The rate of hand hygiene performance was the lowest in the three months before and after index case admission and increased from 84% (period 1) to 95% (period 2). Patients with higher severity, indicated by a higher Pediatric Risk of Mortality III score, were more likely to develop colonization (P = 0.030), because they had invasive devices and required more contact with healthcare workers. MDRAB colonization contributed to an increase in the duration of mechanical ventilation and PICU stay (P < 0.001), but did not affect mortality (P = 0.273). Conclusion The MDRAB outbreak was successfully terminated by the implementation of a comprehensive infection-control strategy focused on the promotion of hand hygiene, universal contact precautions, and environmental management through multidisciplinary teamwork.

Purpose: To assess characteristics the application of mobile medication system and medication administration error (MAE) alerts in a general hospital. Methods: The subject hospital adopted a mobile medication system in 2016. All medication administrations in the general wards and ICUs were automatically recorded in real-time using identification barcodes, drug barcodes, and hand-held point-of-care devices. MAE alert logs were recorded from April 1st 2017 to March 31st 2018. For this study analysis was done using Pearson’s chi-squared test for potentially related factors of MAE alerts included administration time, order type, medication route, and length of nurse’s employment. Results: The total number of medications during the period of this study was 3,227,990. Among them, 2,698,317 medication doses were recorded, resulting in the system application rate of 83.6%. The system application rate was significantly correlated with all factors related to potential MAE alters. In this study 23,314 MAE alerts(0.9% of the total medication doses) were identified. The MAE alerts were related to new (OR=2.26, p<.001) and emergency (OR=2.25, p<.001) orders, and administration at a non-standard time (OR=2.032, p<.001). Medication route (p<.001), and nurse’s employment duration(p<.001) were also related. Conclusion A mobile medication system contributes to improving patient safety by preventing potential MAEs. The MAE alerts were related to administration time, order type, medication route, and duration of nurse’s employment. In order to prevent medication administration errors, it is necessary to standardize the process of medication and create an environment in which medication administration can be performed in a planned situation.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.