Histopathological and Immunohistochemical Characterization of Sebaceous Adenoma and Epithelioma in Dogs.

Sebaceous gland tumors are neoplasms originating from the sebaceous gland and are the third most common type of skin tumor, accounting for 21-35% of all cutaneous neoplasms in dogs. According to their histopathological characteristics, sebaceous gland tumors can be classified into adenoma as a benign tumor and epithelioma as a malignant tumor. Sebaceous epithelioma is distinguished from sebaceous adenoma by containing 90% or more reserve cells. However, this simple numerical criterion is insufficient to histologically distinguish between epitheliomas and adenomas. In addition, sebaceoma in humans, a similar tumor to sebaceous epithelioma, is a term used for tumors with more than 50% of reserve cells, unlike epithelioma. Therefore, we aimed to compare and characterize the histological and immunohistochemical profiles of comprehensive sebaceous adenoma, epithelioma, and borderline tumors that have more than 50% but less than 90% of reserve cells. A total of 14 canine sebaceous tumors were diagnosed as seven adenomas, four borderline tumors, and three epitheliomas. Histologically, the sebaceous adenomas showed nodules consisting of mature sebocytes surrounded by monolayer basaloid cells. In contrast, the portion of the reserve cells was increased, the portion of lipidized cells was decreased, and the majority of lipidized cells were found to be immature in sebaceous epithelioma. In the sebaceous adenomas, necrosis was not observed and mitotic figures were rarely seen. However, necrosis and mitotic figures were highly frequent in both borderline tumor and sebaceous epithelioma. Immunohistochemistry revealed that borderline tumor and sebaceous epithelioma showed significantly higher expression against Ki-67 than sebaceous adenoma. We conclude that it is more accurate to employ the cut-off value of 50% reserve cells in humans rather than the current 90% reserve cells for classifying sebaceous gland tumors in dogs, thereby providing new insight into the characterization of the sebaceous gland tumors.

Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea.

INTRODUCTION: Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of coronavirus disease 2019 (COVID-19) in South Korea in 2021. The Ministry of Food and Drug Safety in South Korea mandate that new medications be re-examined for safety and effectiveness post-approval in at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate the safety and effectiveness of regdanvimab in real-world clinical care. METHODS: This prospective, multicentre, phase 4 PMS study was conducted between February 2021 and March 2022 in South Korea. Eligible patients were aged ≥ 18 years with confirmed mild COVID-19 at high risk of disease progression or moderate COVID-19. Patients were hospitalised and treated with regdanvimab (40 mg/kg, day 1) and then monitored until discharge, with a follow-up call on day 28. Adverse events (AEs) were documented, and the COVID-19 disease progression rate was used to measure effectiveness. RESULTS: Of the 3123 patients with COVID-19 infection identified, 3036 were eligible for inclusion. Approximately 80% and 5% of the eligible patients were diagnosed with COVID-19 during the delta- and omicron-dominant periods, respectively. Median (range) age was 57 (18-95) years, and 50.6% of patients were male. COVID-19 severity was assessed before treatment, and high-risk mild and moderate COVID-19 was diagnosed in 1030 (33.9%) and 2006 (66.1%) patients, respectively. AEs and adverse drug reactions (ADRs) were experienced by 684 (22.5%) and 363 (12.0%) patients, respectively. The most common ADR was increased liver function test (n = 62, 2.0%). Nine (0.3%) patients discontinued regdanvimab due to ADRs. Overall, 378 (12.5%) patients experienced disease progression after regdanvimab infusion, with extended hospitalisation/re-admission (n = 300, 9.9%) as the most common reason. Supplemental oxygen was required by 282 (9.3%) patients. Ten (0.3%) patients required intensive care monitoring and 3 (0.1%) died due to COVID-19. CONCLUSION: This large-scale PMS study demonstrated that regdanvimab was effective against COVID-19 progression and had an acceptable safety profile when used in real-world clinical practice.

Effects of Antimicrobial Administration Route on Growth and Antimicrobial Resistance in Weaned Piglets.

This study aimed to determine how the route of antimicrobial administration affected the growth performance of weaned piglets. Additionally, we aimed to investigate potential differences between antimicrobial resistance developed by antimicrobials administered orally through drinking water, and those administered through feed, in weaned piglets. The research was undertaken on a farm housing 500 sows and involved 150 weaned piglets at 21 days of age. These piglets were evenly distributed into three groups of equal size: water, feed, and control. Antimicrobials were administered through drinking water and feed in the water and feed groups, respectively, while the control group received no antimicrobial treatment. The observation of piglets continued until they reached 70 days of age. The feed conversion ratio in the water group (1.7 ± 0.78) was significantly higher than in the control (2.4 ± 1.77) and feed (2.7 ± 1.68) groups. Additionally, the route of administration did not affect antimicrobial resistance rates. Based on these results, it can be inferred that administering antimicrobials through drinking water is advantageous for pig farming.

Comparative Genetic Characterization of CTX-M-Producing Escherichia coli Isolated from Humans and Pigs with Diarrhea in Korea Using Next-Generation Sequencing.

Pathogenic E. coli causes intra- and extraintestinal diseases in humans and pigs and third-generation cephalosporins are the primary option for the treatment of these diseases. The objective of this study was to investigate the characteristics and correlation between CTX-M-producing E. coli from humans and pigs regarding CTX-M-producing E. coli using next-generation sequencing and bioinformatic tools. Among the 24 CTX-M-producing E. coli, three types of CTX-M genes (CTX-M-12, CTX-M-14, and CTX-M-15) were detected in humans and four types of CTX-M genes (CTX-M-14, CTX-M-15, CTX-M-55, and CTX-M-101) were detected in pigs. A total of 24 CTX-M-producing E. coli isolates also showed the following antimicrobial resistance genes: other B-Lactam resistance gene (75.0%); aminoglycoside resistance genes (75.0%); phenicol resistance genes (70.8%); tetracycline resistance genes (70.8%); sulfonamide resistance genes (66.7%); quinolone resistance genes (62.5%); trimethoprim resistance genes (54.2%); and fosfomycin resistance genes (8.3%). FII (92.3%) and FIB (90.9%) were the most common plasmid replicon in humans and pigs, respectively. A total of thirty-eight different genes associated with virulence 24 CTX-M-producing E. coli and all isolates contained at least more than one virulence gene. A total of 24 CTX-M-producing E. coli isolates showed 15 diverse sequence types (STs): thirteen isolates from human belonged to 6 different STs, and 11 isolates from pig belonged to 9 different STs. The presence of virulence genes in E. coli together with antimicrobial resistance genes (including CTX-M genes) emphasizes the necessity of comprehensive surveillance and persistent monitoring of the food chain to avoid all types of bacterial contamination, regardless of human or pig origin.

Comparative genetic characterisation of third-generation cephalosporin-resistant Escherichia coli isolated from integrated and conventional pig farm in Korea.

OBJECTIVES: Pig-farming systems consist of integrated or conventional farms, and many antimicrobials are used to treat bacterial infections. The objective of this study was to compare characteristics of third-generation cephalosporin resistance and extended-spectrum ß-lactamase (ESBL)/pAmpC ß-lactamase-producing Escherichia coli between integrated and conventional farms. METHODS: Third-generation cephalosporin-resistant E. coli was collected from integrated and conventional pig farms from 2021 to 2022. Polymerase chain reaction and DNA sequencing were performed for the detection of ß-lactamase-encoding genes, molecular analysis, and identification of genetic relationships. To determine the transferability of ß-lactamase genes, conjugation assays were conducted. RESULTS: Antimicrobial resistance rates were higher in conventional farms than in integrated farms; ESBL- and pAmpC-lactamase-producing E. coli rates were higher in conventional farms (9.8%) than in integrated farms (3.4%). Fifty-two (6.5%) isolates produced ESBL/pAmpC ß-lactamase genes. Isolates from integrated farms harboured CTX-15 (3 isolates), CTX-55 (9 isolates), CTX-229 (1 isolate), or CMY-2 (1 isolate) genes; isolates from conventional farms harboured CTX-1 (1 isolate), CTX-14 (6 isolates), CTX-15 (2 isolates), CTX-27 (3 isolates), CTX-55 (14 isolates), CTX-229 (1 isolate), and CMY-2 (11 isolates) genes. Of the 52 ESBL/pAmpC ß-lactamase-producing E. coli isolates, class 1 integrons with 11 different gene cassette arrangements were detected in 39 (75.0%) isolates, and class 2 integrons were detected in 3 isolates. The most common sequence type in both integrated and conventional farms was ST5229, followed by ST101, and then ST10. CONCLUSION: Third-generation cephalosporin-resistant patterns and molecular characteristics differed between integrated and conventional farms. Our findings suggest that continuous monitoring of third-generation cephalosporin resistance on pig farms is necessary to prevent the dissemination of resistant isolates.

Development of a Method for the Fast Detection of Extended-Spectrum ß-Lactamase- and Plasmid-Mediated AmpC ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae from Dogs and Cats in the USA.

Antibiotic resistance, such as resistance to beta-lactams and the development of resistance mechanisms, is associated with multifactorial phenomena and not only with the use of third-generation cephalosporins. Many methods have been recommended for the detection of ESBL and pAmpC ß-lactamase production but they are very subjective and the appropriate facilities are not available in most laboratories, especially not in clinics. Therefore, for fast clinical antimicrobial selection, we need to rapidly detect ESBL- and pAmpC ß-lactamase-producing bacteria using a simple method with samples containing large amounts of bacteria. For the detection of ESBL- and pAmpC phenotypes and genes, the disk diffusion test, DDST and multiplex PCR were conducted. Of the 109 samples, 99 (90.8%) samples were grown in MacConkey broth containing cephalothin, and 71 samples were grown on MacConkey agar containing ceftiofur. Of the 71 samples grown on MacConkey agar containing ceftiofur, 58 Escherichia coli and 19 Klebsiella pneumoniae isolates, in particular, harbored ß-lactamase genes. Of the 38 samples that did not grow in MacConkey broth containing cephalothin or on MacConkey agar containing ceftiofur, 32 isolates were identified as E. coli, and 10 isolates were identified as K. pneumoniae; ß-lactamase genes were not detected in these E. coli and K. pneumoniae isolates. Of the 78 ESBL- and pAmpC ß-lactamase-producing E. coli and K. pneumoniae, 55 (70.5%) isolates carried one or more ESBL genes and 56 (71.8%) isolates carried one or more pAmpC ß-lactamase genes. Our method is a fast, and low-cost tool for the screening of frequently encountered ESBL- and pAmpC ß-lactamase-producing bacteria and it would assist in diagnosis and improve therapeutic treatment in animal hospitals.

Comparative genetic characterization of CMY-2-type beta-lactamase producing pathogenic Escherichia coli isolated from humans and pigs suffering from diarrhea in Korea.

BACKGROUND: Pathogenic Escherichia coli are an important cause of bacterial infections in both humans and pigs and many of antimicrobials are used for the treatment of E. coli infection. The objective of this study was to investigate the characteristics and relationship between humans and pigs regarding third-generation cephalosporin resistance and CMY-2-producing E. coli in Korea. RESULTS: All 103 third-generation cephalosporin-resistant E. coli isolates showed multidrug resistance. Also, except for ß-lactam/ß-lactamase inhibitor combinations, all antimicrobials resistant rates were higher in pigs than in humans. A total of 36 isolates (humans: five isolates; pigs: 31 isolates) were positive for the CMY-2-encoding genes and thirty-two (88.9%) isolates detected class 1 integrons with 10 different gene cassette arrangements, and only 1 isolate detected a class 2 integron. The most common virulence genes in pigs were LT (71.0%), F18 (51.6%), and STb (51.6%), while stx2 (80.0%) was the most frequently detected gene in humans. Stx2 gene was also detected in pigs (6.5%). Interestingly, 36 CMY-2-producing E. coli isolates showed a high diversity of sequence types (ST), and ST88 was present in E. coli from both pigs (11 isolates) and humans (one isolate). CONCLUSION: Our findings suggest that a critical need for comprehensive surveillance of third-generation cephalosporin resistance is necessary to preserve the usefulness of third-generation cephalosporins in both humans and pigs.

Relationship between virulence factors and antimicrobial resistance genes of pathogenic Escherichia coli from diarrheic weaned piglets.

A total of 690 pathogenic Escherichia (E.) coli isolates from weaned piglets were examined for antimicrobial resistance phenotypes, resistance genes, and virulence gene profiles. Also, 29 enterotoxigenic E. coli (ETEC) and 35 Shiga-toxin producing E. coli (STEC) isolates were analyzed using multi-locus sequence typing (MLST). Comparisons of the associations between antimicrobial resistance phenotypes, resistance genes, and virulence genes were performed separately by assessing odds ratio (OR). Although majorities of associations were not confirmed however, we found that associations between specific virulence factors-antimicrobial resistance. F18 encoding isolates showed association with resistance to cefazolin (OR = 3.08) and cefoxitin (OR = 3.65), and also with antimicrobial resistance gene mcr-3 (OR = 4.58). There was a high correlation between F4-STb (OR = 13.56), F4-LT (OR = 8.77), F4-EAST-I (OR = 4.97), and F18-Stx2e (OR = 3.83). Most of ETEC (21 of 29, 72.4%) isolates were assigned to ST100, and 20 of 35 STEC isolates (57.1%) were ST1. There were 5 clusters, and each cluster showed specific antimicrobial resistance patterns. Cluster I showed resistance to gentamicin, streptomycin, neomycin, nalidixic acid, ciprofloxacin, norfloxacin, trimethoprim / sulfamethoxazole, and tetracyclines whereas, cluster V showed resistance to ampicillin, amoxicillin / clavulanic acid, cephalothin, cefoxitin, cefazolin, norfloxacin, and colistin. Although there is need to do more experiments to clarify why certain virulence factors showed relationship with antimicrobial resistance, it is clear that there is a significant association between specific virulence genes and antimicrobial resistance in E. coli from weaned piglets with enteric colibacillosis in Korea.

GSPE Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice via Ameliorating Epithelial Apoptosis through Inhibition of Oxidative Stress.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause which leads to alveolar epithelial cell apoptosis followed by basement membrane disruption and accumulation of extracellular matrix, destroying the lung architecture. Oxidative stress is involved in the development of alveolar injury, inflammation, and fibrosis. Oxidative stress-mediated alveolar epithelial cell (AEC) apoptosis is suggested to be a key process in the pathogenesis of IPF. Therefore, the present study investigated whether grape seed proanthocyanidin extract (GSPE) could inhibit the development of pulmonary fibrosis via ameliorating epithelial apoptosis through the inhibition of oxidative stress. We found that GSPE significantly ameliorated the histological changes and the level of collagen deposition in bleomycin (BLM)-induced lungs. Moreover, GSPE attenuated lung inflammation by reducing the total number of cells in bronchoalveolar lavage (BAL) fluid and decreasing the expression of IL-6. We observed that the levels of H2O2 leading to oxidative stress were increased following BLM instillation, which significantly decreased with GSPE treatment both in vivo and in vitro. These findings showed that GSPE attenuated BLM-induced epithelial apoptosis in the mouse lung and A549 alveolar epithelial cell through the inhibition of oxidative stress. Furthermore, GSPE could attenuate mitochondrial-associated cell apoptosis via decreasing the Bax/Bcl-2 ratio. The present study demonstrates that GSPE could ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibition of epithelial apoptosis through the inhibition of oxidative stress.

Comparison of antimicrobial resistance and molecular characterization of Escherichia coli isolates from layer breeder farms in Korea.

In Korea, 4 big layer companies that possess one grandparent and 3 parent stocks are in charge of 100% of the layer chicken industry. In this study, we investigated the antimicrobial resistance of commensal 578 E. coli isolated from 20 flocks of 4-layer breeder farms (A, B, C, and D), moreover, compared the characteristics of their resistance and virulence genes. Isolates from farms B and D showed significantly higher resistance to the ß-lactam antimicrobials (amoxicillin, ampicillin, and 1st-, 2nd-, and 3rd-generation cephalosporins). However, resistance to ciprofloxacin, nalidixic acid, and tetracycline was significantly higher in the isolates from farm A (P < 0.05). Interestingly, the isolates from farm C showed significantly lower resistance to most antimicrobials tested in this study. The isolates from farms B, C, and D showed the high multiple resistance to the 3 antimicrobial classes. Furthermore, the isolates from farm A showed the highest multiple resistance against the 5 classes. Among the 412 ß-lactam-resistant isolates, 123 (29.9%) carried blaTEM-1, but the distribution was significantly different among the farms from 17.5% to 51.4% (P < 0.05). Similarly, the most prevalent tetracycline resistance gene in the isolates from farms B, C, and D was tetA (50.0-77.0%); however, the isolates from farm A showed the highest prevalence in tetB (70.6%). The distribution of quinolone (qnrB, qnrD, and qnrS) and sulfonamide (su12)-resistant genes were also significantly different among the farms but that of chloramphenicol (catA1)- and aminoglycoside (aac [3]-II, and aac [6']-Ib)-resistant genes possessed no significant difference among the farms. Moreover, the isolates from farm C showed significantly higher prevalence in virulence genes (iroN, ompT, hlyF, and iss) than the other 3 farms (P < 0.05). Furthermore, the phenotypic and genotypic characteristics of E. coli isolates were significantly different among the farms, and improved management protocols are required to control of horizontal and vertical transmission of avian disease, including the dissemination of resistant bacteria in breeder flocks.

Detection of Linezolid-Resistant Enterococcus faecalis and Enterococcus faecium Isolates from the Layer Operation System in Korea.

Linezolid (LNZ) is one of the most important antimicrobial agents against infections caused by gram-positive bacteria, including enterococci. In a layer operation system, antimicrobial resistance can be transferred to commercial layers via the fecal-oral route. This study investigated the presence and distribution of LNZ-resistant Enterococcus faecalis and Enterococcus faecium in a layer operation system. Among 117 E. faecalis and 154 E. faecium, 10 (8.5%) E. faecalis and 5 (3.2%) E. faecium isolates showed resistance to LNZ and chloramphenicol, and they exhibited multidrug resistance against 5 or more classes of antimicrobial agents. Among the resistant isolates, 9 (90.0%) and 2 (20.0%) E. faecalis harbored optrA and cfr genes, respectively. The optrA and fexA genes were not detected in five LNZ-resistant E. faecium. None of the 15 LNZ-resistant isolates harbored the fexA gene, and no mutations were observed in the genes encoding domain V of 23S ribosomal RNA (rRNA) and ribosomal proteins L3 (rplC) and L4 (rplD). Transferability was identified in three of the nine optrA-positive LNZ-resistant isolates. The tetM, tetL, and ermB genes were cotransferred with the optrA gene in all optrA-positive transconjugants. The results indicate that optrA is well-distributed in E. faecalis, implying a greater level of transferability. Thus, enhanced surveillance efforts are needed to monitor the emergence and spread of optrA in enterococci in layer operation system.

Molecular characterization of fluoroquinolone-resistant Escherichia coli from broiler breeder farms.

Fluoroquinolones (FQs) have been used effectively antimicrobial agents of choice for treatment of various infections caused by E. coli and FQs-resistance of E. coli from broiler breeders has been implicated in its vertical transmission to their offspring. The objective of this study investigated the phenotypic and genotypic characteristics of FQ-resistant E. coli isolates from broiler breeder farms in Korea. A total of 106 FQ-resistant E. coli isolates were tested in this study and all isolates had mutations in quinolone resistance determining regions; all (100%) had mutations in gyrA, 89 (84.0%) had mutations in parE, 8 (7.5%) isolates showed the mutations with parC and parE, and none had mutations in gyrB. The predominant mutation type was double mutation in gyrA (S83L and D87N), and all FQ-resistant E. coli isolates that had mutations in parC or parE also had double mutations in gyrA. Especially, FQ-resistant E. coli isolates which possessed double mutations in gyrA in combination with double mutations in parC or single mutations in both parC and parE were shown high levels of minimum inhibitory concentrations rage. Of the 23 plasmid-mediated quinolone resistance (PMQR)-positive E. coli isolates, qnrS was detected in 10 (9.4%) isolates, and followed by qnrA (7 isolates, 6.6%), qnrB (4 isolates, 3.8%), and aac(6')-Ib-cr (2 isolates, 1.9%). Sixteen (69.6%) of the 23 PMQR-positive E. coli isolates harbored class 1 integrons with four different gene cassette arrangements and total of 9 plasmid replicon types were also identified in 23 PMQR-positive E. coli isolates. This is the first study to investigate the prevalence and characteristics of FQ-resistant and PMQR-positive E. coli isolated from the broiler breeder in Korea; it supports that constant monitoring and studies at the broiler breeder level are required to prevent the pyramidal transmission of FQ-resistant E. coli.

Histiocytic pleural effusion: the strong clue to malignancy.

BACKGROUND: There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. METHODS: In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. RESULTS: Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology. CONCLUSIONS: The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

The occurrence of CTX-M-producing E. coli in the broiler parent stock in Korea.

A large number of antimicrobials are used for the treatment of bacterial infections, and the emergence of antimicrobial-resistant Escherichia coli (E. coli) in livestock and the transfer of resistant isolates to humans poses a serious potential risk to public health. In particular, broiler parent stock produce thousands of eggs for commercial broiler chickens and can transfer antimicrobial-resistant bacteria and drug-resistance genes to chicks. This study was conducted to investigate the prevalence and characteristics of third-generation cephalosporin-resistant and extended-spectrum ß-lactamases (ESBL)-producing E. coli isolated from the broiler parent stock in Korea. Among 51 cefotaxime-resistant E. coli isolates, 45 (88.2%) isolates were identified as multidrug resistant and 21 isolates showed phenotypic and genotypic characteristics of CTX-M-producing E. coli. The CTX-M genes CTX-M-14, CTX-M-15, CTX-M-1, and CTX-M-1 were detected in 10, 7, 3, and 1 isolates, respectively. ISEcp1 or IS26 + ISEcp1 were identified upstream of all CTX-M-type genes, and orf477 and IS903 were detected downstream of 9 and 10 CTX-M-type genes, respectively. Thirteen (61.9%) of the 21 CTX-M-producing E. coli isolates harbored class 1 integrons with 4 different gene cassette arrangements. Among the plasmid replicons, CTX-M-1 was located on I1, F, and FIB; CTX-M-14 on F and FII; CTX-M-15 on FII, FIA, and FIB; and CTX-M-65 on FIB. This is the first study to investigate the presence and distribution of third-generation cephalosporin-resistant and CTX-M-producing E. coli isolated from the broiler parent stock level in Korea, and the results indicate that comprehensive surveillance and persistent monitoring systems in broiler parent stock farms are necessary to prevent the dissemination of resistant isolates.

Clinical Importance of Work-Exacerbated Asthma: Findings From a Prospective Asthma Cohort in a Highly Industrialized City in Korea.

PURPOSE: Work-related asthma (WRA) occupies about 10%-30% of all asthma cases. Among 2 subtypes of WRA (occupational asthma [OA] and work-exacerbated asthma [WEA]), the rate of WEA has been reported to increase recently. WRA is described as having worse characteristics than non-WRA (NWRA), while WEA is known to show similar severity to OA in terms of symptoms and exacerbations. However, these data were mainly based on indirect surveys. Ulsan is a highly industrialized city in Korea; therefore, it is estimated to have a high incidence of WRA. This study aimed to identify the characteristics of WRA in the city. METHODS: This was a prospective asthma cohort study of individuals diagnosed with asthma and treated at Ulsan University Hospital between Jan 2015 and Dec 2016. Baseline characteristics and work-related inquiry (9 questionnaires) were investigated at enrollment. Various severity indices and job change were then investigated for the longitudinal analysis at 12 months after enrollment. RESULTS: In total, 217 asthma patients completed the study. WRA accounted for 17% (36/217), with an equal number of WEA and OA (18 patients each). Before the work-related survey, only 33% (n = 12) of WRA patients (22% [4/18] of WEA and 44% [8/18] of OA) were diagnosed with WRA by the attending physicians. Compared to the NWRA group and the OA subgroup, the WEA subgroup had more outpatient visits, more oral corticosteroids prescriptions, and trends of low asthma control test scores and severe asthma. The rate of job change was markedly lower in the WEA subgroup than in the OA subgroup (20% vs. 5%). CONCLUSIONS: The overall prevalence of WRA (17%) was similar to those of previous studies, but the share of WEA was high (50% of WRA). WEA was more severe than OA or NWRA. The possible reason for this severity is ongoing workplace exposure.

Characteristics of linezolid-resistant Enterococcus faecalis isolates from broiler breeder farms.

Linezolid is an oxazolidinone class antibiotic used for treatment infections caused by various multidrug-resistant gram-positive pathogens including enterococci. However, recently, linezolid-resistant isolates in animals are considered as a human health hazard. In a broiler operation system, antimicrobial resistance can be transferred to the environment and commercial broiler via the fecal-oral route. Therefore, this study was conducted to investigate the prevalence and characteristics of linezolid-resistant Enterococcus faecalis (E. faecalis) from broiler parent stock in a broiler operation system. Among 297 E. faecalis isolates from 85 flocks in 8 broiler breeder farms, the prevalence of chloramphenicol- and linezolid-resistant isolates was 0 to 12.1% and 0 to 8.0%, respectively; however, there were no significant differences between farms. Therefore, a total of 14 (4.7%) chloramphenicol- and/or linezolid-resistant E. faecalis showed resistance to 7 or more antimicrobial classes. The drug-resistance gene optrA, which can confer resistance to linezolid, tedizolid, and phenicols, was found in 8 (2.69%) isolates, and 7 (2.36%) of the 8 optrA-positive isolates co-carried the phenicol exporter gene fexA. However, E. faecalis isolates from 3 of 8 broiler breeder farms only carried the optrA and/or fexA genes. As linezolid is one of the last antimicrobial treatments of choice for multidrug-resistant gram-positive pathogens including E. faecalis, the presence of antibiotic-resistant E. faecalis in broiler breeder farms should be monitored to prevent the introduction of linezolid-resistant strains to the food chain.

Molecular characteristics of optrA-carrying Enterococcus faecalis from chicken meat in South Korea.

The purpose of this study was to identify the genetic environment of optrA gene in linezolid (LZD)-resistant Enterococcus faecalis from chicken meat and to describe the probable mechanism of dissemination of the optrA gene through plasmid or chromosomal integration. Whole genome sequencing and analysis revealed that all 3 E. faecalis isolates confirmed as LZD- and chloramphenicol-resistant carried fexA adjacent to the optrA gene as well as a variety of resistance genes for macrolides, tetracyclines, and aminoglycosides, simultaneously. But, the other genes conferring LZD resistance, cfr and poxtA, were not detected in those strains. Two isolates harboring the optrA gene in their chromosomal DNA showed >99% similarity in arrangement to the transposon Tn6674 and the transposase genes, tnpA, tnpB, and tnpC and were located in the first open reading frame for transposase. One isolate harboring an optrA-carrying plasmid also showed >99% similarity with the previously reported pE439 plasmid but had 2 amino acid changes (Thr96Lys and Tyr160Asp) and a higher minimum inhibitory concentration against LZD of 16 mg/L than that of pE439 (8 mg/L). Mobile genetic elements such as transposons or plasmids flanking the optrA gene conduct a crucial role in the dissemination of antimicrobial resistance genes. Further investigations are required to identify the way by which optrA is integrated into chromosomal DNA and plasmids.

Active tuberculosis risk associated with malignancies: an 18-year retrospective cohort study in Korea.

BACKGROUND: Active tuberculosis (TB) develops in approximately 10% of people with a latent tuberculosis infection (LTBI). TB guidelines recommend that LTBI screening and treatments target high-risk patients. Malignancies are not universally considered a high-risk factor for active TB. This study aimed to determine the degrees to which active TB risk was associated with various cancers in a Korean population. METHODS: This study involved patients aged ≥20 years who were diagnosed with cancer at Ulsan University Hospital (UUH) from January 2000 to December 2014 and individuals who visited UUH for health screening and were age- and sex-matched randomly with cases in a 1:2 ratio. Using retrospective cohort study, the development of bacteriologically confirmed TB (BCTB) within 3 years after enrollment was investigated. The relative risks of BCTB were estimated using incidence rate ratios (IRRs) and a Poisson regression analysis. RESULTS: During the study period, 380 of 34,783 cancer patients and 79 of 69,566 control subjects developed BCTB, yielding respective incidence rates of 535 and 37/100,000 person-years, respectively. In all cancer cases, the IRR of BCTB was 14.30, and especially high rates were associated with the following cancers: esophageal cancer (74.72), multiple myeloma (70.76), lung cancer (50.35), pancreatic cancer (46.04), leukemia (40.45), head and neck cancer (24.60), and lymphoma (22.67). CONCLUSIONS: The incidence of active TB was higher in cancer patients than in control subjects. In particular, lung cancer, esophageal cancer, pancreatic cancer, hematologic malignancy and head and neck cancer were identified as high-risk factors for active TB, as indicated by IRRs of 20-75. These findings suggest that patients with high-risk cancers should be targeted for LTBI screening and treatment.

Human Leukocyte Antigen Class I Pseudo-Homozygous Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells.

Mesenchymal stem cells (MSC) are an important type of cell that are highly recognized for their safety and efficacy as a cell therapy agent. In order to obtain MSC, primary tissues (adipose tissue, bone marrow, and umbilical cord blood) must be used; however, these tissues, especially umbilical cord blood, are difficult to obtain due to various reasons, such as the low birth rate trend. In addition, to maximize the safety and efficacy of MSC as allogenic cell therapeutic agents, it is desirable to minimize the possibility of an immune rejection reaction after in vivo transplantation. This study tried to establish a novel method for producing induced pluripotent stem cells (iPSC)-derived MSC in which the human leukocyte antigen (HLA)-class I gene is knocked out. To do so, dermal fibroblast originated iPSC generation using Yamanaka 4-factor, HLA class I gene edited iPSC generation using CRISPR/Cas9, and differentiation from iPSC to MSC using MSC culture medium was utilized. Through this, HLA-A, B, and C pseudo-homozygous iPSC-derived MSC (KO iMSC) were produced by monoallelically knocking out the polymorphic HLA-A, B, and C genes, which are the major causes of immune rejection during allogenic cell transplantation. Produced KO iMSC possesses multipotency and it was safe in vivo to be able to be differentiated to cartilage. In addition, it was not attacked by natural killer cells unlike HLA class I null cells. In conclusion, KO iMSC that do not induce immune rejection during allogenic cell transplantation can be produced. In the future, KO iMSC can be successfully utilized as allogenic cell therapeutic agents for many recipients through HLA screening.

Molecular characteristics of fluoroquinolone-resistant avian pathogenic Escherichia coli isolated from broiler chickens.

Avian pathogenic Escherichia coli (APEC) is a major pathogen in the poultry industry worldwide including Korea. In this study, the phenotypic and genotypic characteristics of 33 fluoroquinolone (FQ)-resistant APEC isolates from broilers were analyzed. All FQ-resistant APEC isolates showed amino acid exchanges at both gyrA and parC and high minimal inhibitory concentrations for FQs. A total of 11 (33.3%) isolates were positive for the plasmid-mediated quinolone resistance (PMQR) genes, qnrA (8 isolates) and qnrS (3 isolates), and showed multidrug resistance. Among the 11 PMQR-positive isolates, 1 and 2 isolates carried blaCTX-1 and blaCTX-15, respectively, as extended-spectrum ß-lactamase (ESBL) producers, and the non-ESBL gene, blaTEM-1, was found in 4 isolates. Among 3 aminoglycoside-resistant isolates, aac(3)-II was only detected in 1 isolate. All 8 APEC isolates with resistance to tetracycline carried the tetA gene. Overall, 6 of the 7 trimethoprim-sulfamethoxazole-resistant isolates carried the sul1 or sul2 genes, while only 2 of the 8 chloramphenicol-resistant isolates carried the catA1 gene. Although 9 isolates carried class I integrons, only 4 isolates carried the gene cassettes dfrA12-aadA2 (2 isolates), dfrA17-aadA5 (1 isolate), extX-psp-aadA2 (1 isolate), and dfrA27 (1 isolate). The most common plasmid replicon was FIB (8 isolates, 72.7%), followed by K/B (4 isolates, 36.4%). Antimicrobial resistance monitoring and molecular analysis of APEC should be performed continuously to surveil the transmission between poultry farms.