Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.

Genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2 in Sprague-Dawley rats and Beagle dogs.

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.

Prevalence and characterization of non-typhoidal Salmonella in egg from grading and packing plants in Korea.

Egg washing guidelines vary across countries; however, since 2020, Korea has required that all eggs produced from farms with more than 10,000 laying hens must be washed through egg grading and packing (GP) plant. This study investigated the prevalence and characterization of non-typhoidal Salmonella in eggs after washing at GP plants. In total, 16,800 eggs were collected from 60 egg GP plants located inside commercial layer farms, and 840 pooled eggshell and egg contents were tested for Salmonella, respectively. Of the 60 GP plants tested, 11 (18.3%) and 12 (20.0%) plants were positive for Salmonella spp. In the eggshells and egg contents, respectively. In particular, High Salmonella prevalence in the eggshells and egg contents occurred most often in farms with laying hens older than 80 weeks (33.3% and 40.0%, respectively). However, among 840 pooled eggshells and egg content samples, only 19 (2.3%) of each sample type were positive only for non-typhoidal Salmonella spp. The most common Salmonella serovar in both eggshells and egg contents was S. Infantis, which was found in five (8.3%) of 60 GP plants for both samples types. The other Salmonella serovars detected in eggshells were S. Bareilly (5.0%), S. Agona (3.3%), S. Enteritidis (1.7%), and S. Montevideo (1.7%), whereas those detected in egg contents were S. Enteritidis (5.0%), S. Agona (3.3%), S. Newport (3.3%), S. Senftenberg (3.3%), and S. Derby (1.7%). Of the 19 virulence genes tested, 14 genes were detected in all Salmonella. Interestingly, the spvB gene was detected only in S. Enteritidis, and the sefC gene was detected only in S. Enteritidis and S. Senftenberg. Moreover, all S. Infantis isolates showed multidrug resistance (MDR) against five or more classes, and the other serovars only showed MDR against three to four classes or no MDR. These results suggest that comprehensive surveillance and advanced management approaches for egg GP plants are required to minimize egg contamination with non-typhoidal Salmonella.

Effect of Osteoporosis on Clinical and Radiological Outcomes Following One-Level Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study. PURPOSE: This study aimed to evaluate how osteoporosis affected the clinical and radiological outcomes of patients who underwent anterior cervical discectomy and fusion (ACDF) with plating. OVERVIEW OF LITERATURE: The incidence of complications associated with implants is high when ACDF is performed in patients with poor bone quality. METHODS: In total, 101 patients without (T-score ≥1.0, group A) and 25 with (T-score ≤-2.5, group B) osteoporosis who underwent single-level ACDF with plating were followed up for >2 years. The clinical and radiological outcomes were compared between the two groups. The fusion rate and implant-related complications were evaluated. RESULTS: Although clinical outcomes such as visual analog scale scores for the arm (2.0±2.3 vs. 2.4±2.9, p=0.490) and neck pain (1.4±1.9 vs. 1.8±2.2, p=0.343) and neck disability index (7.7±7.1 vs. 9.9±7.5, p=0.225) were slightly higher in group B, no statistically significant difference was noted. Cage subsidence (13.9% vs. 16.0%, p=0.755) and plate migration (7.9% vs. 8.0%, p=1.000) rates did not differ between the two groups. The fusion rate at 1 year postoperatively was higher in group A than in group B (80.3% vs. 68.2%, p=0.139) and slightly increased in both groups (94.6% vs. 86.4%, p=0.178) at the final follow-up. CONCLUSIONS: Osteoporosis did not significantly affect the rate of cage subsidence or plate migration after cervical fusion. After ACDF, increased cage subsidence and implant migration rates had no significant effect on clinical outcomes.

Emergence of Salmonella Infantis carrying the pESI megaplasmid in commercial farms of five major integrated broiler operations in Korea.

Considering Salmonella transmission occurs through several routes in integrated broiler operations, control of nontyphoidal Salmonella in commercial farms is essential. This study aimed to compare the distribution of persistent Salmonella serovars in environments and dead chickens between 5 major integrated broiler operations in Korea. The prevalence of Salmonella-positive farms in dust prior to placement by operations was 0 to 25%, but the prevalence in dust and feces at the time of depletion was increased to 16.7 to 41.7% and 16.7 to 66.7%, respectively. Moreover, the prevalence of farms with Salmonella in chickens that died within 1 week old and at 4 to 5 weeks old ranged from 8.3 to 58.3% and 16.7 to 41.7%, respectively. The prevalence of Salmonella enterica serovar Infantis-positive farms in dust prior to placement and in chickens that died within 1 week old was 5.2 and 3.4%, respectively, but the prevalence in dust and feces at the time of depletion and in chickens that died at 4 to 5 weeks old was significantly increased to 27.6, 41.4, and 20.7%, respectively (P < 0.05). Interestingly, the plasmid of emerging S. Infantis (pESI) was only identified in S. Infantis, and the prevalence of multidrug-resistance was significantly higher in pESI-positive S. Infantis (99.2%) than in pESI-negative S. Infantis (6.7%) (P < 0.05). The distribution of pulsotypes between pESI-positive and pESI-negative S. Infantis were varied, but a majority of S. Infantis were clustered only 2 pulsotypes. Moreover, pESI-positive S. Infantis harbored more virulence factors than pESI-negative S. Infantis. This study is the first report on characteristics of S. Infantis carrying the pESI plasmid in commercial broiler farms in Korea.

Levels of Indicator Bacteria and Characteristics of Foodborne Pathogens from Carcasses of Cattle Slaughterhouses in Korea.

The initial microbial contamination of carcasses during slaughtering adversely affects spoilage and shelf life and is of global concern for food safety and meat quality. This study evaluated the hygiene and quality using the prevalence of foodborne pathogens and the level of indicator bacteria on 200 carcasses, collecting 10 from each of 20 cattle slaughterhouses in Korea. The distribution of aerobic bacterial count in carcasses was significantly highest at 2.0-3.0 log10 CFU/cm2 (34.1%), whereas the Escherichia coli count was significantly highest at under 1.0 log10 CFU/cm2 (94.0%) (P < 0.05). Clostridium perfringens was most prevalent (60.0% of slaughterhouses; 17.5% of carcasses), followed by Yersinia enterocolitica (30.0% of slaughterhouses; 6.5% of carcasses), Staphylococcus aureus (15.0% of slaughterhouses; 4.0% of carcasses), Listeria monocytogenes 1/2a (5.0% of slaughterhouses; 1.0% of carcasses), Salmonella enterica subsp. enterica serovar Infantis (5.0% of slaughterhouses; 1.0% of carcasses), and Shiga toxin-producing E. coli O:66 (5.0% of slaughterhouses; 0.5% of carcasses). Although 28 C. perfringens isolates from 11 slaughterhouses were divided into 21 pulsotypes, all isolates showed the same toxinotype as type A and only carried the cpa. Interestingly, 83.3% of isolates from two slaughterhouses located in the same province showed resistance to tetracycline. Furthermore, 13 Y. enterocolitica isolates from six slaughterhouses were divided into seven pulsotypes that were divided into biotypes 1A and 2 and serotypes O:5 and O:8, except for isolates that could not be typed. Twelve (92.3%) isolates only carried ystB, but one (7.7%) isolate carried ail and ystA. Moreover, 46.2% of Y. enterocolitica isolates showed multidrug resistance against ampicillin, cefoxitin, and amoxicillin/clavulanic acid. This study supports the need for continuous monitoring of slaughterhouses and hygiene management to improve the microbiological safety of carcasses.

Determination of pepsin in human saliva using pepsin-susceptible peptide reporter and colorimetric dipstick assay: a prospective, cross-sectional study.

A simple and effective pepsin detection assay is reported based on a pepsin-susceptible peptide (PSP) reporter degradation strategy. PSP, which can be specifically cleaved by pepsin, was modified with fluorescein isothiocyanate (FITC) and biotin at the N- and C-terminals to be used as a reporter for colorimetric detection of dipsticks. A universal lateral flow dipstick consisting of a streptavidin test line for biotin binding and a sample pad immobilized with a gold-labeled polyclonal (rabbit) anti-FITC antibody was used to verify PSP-based pepsin detection. When the PSP reporter reacts with pepsin in a tube, it cleaves into two fragments, and the cleaved fragments do not display any color on the test line. Therefore, the higher the concentration of pepsin is, the greater is the decrease in test line intensity (IT-line) and the higher is the control line intensity (IC-line). First, the PSP cleavage and dipstick assay conditions for pepsin detection was optimized. The ratio of color intensity (IT-line/IC-line) of PSP-based dipstick assay showed a linear relationship with log concentration of pepsin ranging between 4 and 500 ng/mL (R2 = 0.98, n = 6), with a limit of detection of 1.4 ng/mL. It also exhibited high specificity and good reproducibility. Finally, pepsin levels were quantified in saliva samples from healthy controls (n = 34) and patients with laryngopharyngeal reflux (LPR, n = 61). Salivary pepsin levels were higher in patients with LPR than in healthy controls. The salivary pepsin levels correlated with those measured using a conventional enzyme-linked immunosorbent assay kit. Therefore, this PSP-based dipstick assay is a convenient tool for assessing salivary pepsin levels.

Genetic and Phenotypic Diversity of Listeria monocytogenes in Pig Slaughterhouses in Korea.

Listeria monocytogenes is a foodborne pathogen that has variable subtypes associated with human listeriosis and occurs in food and processing environments. This study was conducted to provide the genetic and phenotypic characterization of L. monocytogenes in pig carcasses and environments of slaughterhouses in Korea. A total of 22 L. monocytogenes were isolated from eight of 26 pig slaughterhouses between 2020 and 2022, and the most common serotype was 1/2c (40.9%), followed by serotypes 1/2b (31.8%) and 1/2a (27.3%). The isolates showed a significantly high prevalence of virulence genes located in Listeria pathogenicity island-1 (LIPI-1) and internalins (90.9-100%; p < 0.05). However, the prevalence rates of llsX, ptsA, and stress survival islet-1 (SSI-1) located in LIPI-3, LIPI-4, and SSI were only 9.1%, 22.7%, and 31.8%, respectively. In addition, among the epidemic clones (EC), ECI, ECII, ECIII, and ECV, only one isolate was represented as ECV. Isolates identified from the same slaughterhouses were divided into two or more pulsotypes, except for two slaughterhouses. Furthermore, the seven STs were classified into seven clonal complexes (CCs) (CC8, CC9, CC37, CC87, CC121, CC155, and CC288), and all CCs belonged to lineages I (31.8%) and II (68.1%). Interestingly, the isolates showed a high prevalence of oxacillin resistance (59.1%), and most isolates of the serotypes 1/2a and 1/2b exhibited oxacillin resistance, whereas only one of nine serotype 1/2c isolates exhibited oxacillin resistance. These results provide the genetic diversity of L. monocytogenes in pig carcasses and environments of slaughterhouses, and continuous monitoring will be helpful in predicting food safety risks.

ß-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6.

The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with ß-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study.

Current status of ß-lactam antibiotic use and characterization of ß-lactam-resistant Escherichia coli from commercial farms by integrated broiler chicken operations in Korea.

ß-Lactam antibiotics are one of the most clinical importance in human and veterinary medicine because they are used for both preventive and therapeutic purposes against several gram-positive, gram-negative, and anaerobic organisms. In this study, it was confirmed that ß-lactams (81.1%) were found to be significantly prescribed the most among 74 farms in 5 integrated broiler operations, and single prescription (84.6%), 2-day (41.5%) or 3-day (40.0%) administration, and 15 to 22 d of age (67.7%) administration was significantly higher in the farms (P < 0.05). Among the E. coli isolated from 74 farms in 5 integrated broiler operations, ß-lactam-resistant E. coli isolates were detected more frequently in fecal sample (94.6%) than in dust sample (60.8%) (P < 0.05). The prevalence of MDR in ß-lactam-resistant isolates, ranging from 88.1 to 96.5%, was significantly higher than that in non-ß-lactam-resistant isolates (P < 0.05), without significant differences among operations. Of 466 ß-lactam-resistant isolates, 432 (92.7%) isolates harbored ß-lactamase genes. The non-extended-spectrum ß-lactamase (ESBL) gene blaTEM-1 (81.8%) showed the highest prevalence among isolates, followed by the non-ESBL gene blaTEM-135 (6.4%) (P < 0.05). Five ESBL genes, SHV-12, OXA-1, CTX-M-27, CTX-M-55, and CTX-M-65, were found in 0.9 to 6.0% of the isolates. The pAmpC gene blaCMY-2 was detected in 17 isolates (3.6%). These results suggest that feces and dust are important reservoirs of antimicrobial-resistant bacteria, highlighting the need to strengthen farm management regulations, such as cleaning, disinfection, and litter disposal and to reduce the use of antibiotics in broiler operations.

Comprehensive analysis of biosecurity practices and antimicrobial use in broiler chicken production by integrated operations in Korea.

Integrated broiler operations that allow producers to combine various biosecurity and sanitation practices account for approximately 97.6% of chicken meat production in Korea, but it is not well known about the biosecurity level or compliance with regulations for each operation. Therefore, the objective this study was to analyze the current adoption of biosecurity practices and trends in antimicrobial use in 74 farms from 5 major integrated broiler chicken operations (A-E). The highest stock densities of more than 65 birds per 3.3 m2 (0.5 birds/ft2) showed in 66.7 and 33.3% of the farms in operations A and C, respectively. Also, the livability rate of 98% or less was observed in 73.3 and 93.4% of the farms, in operation A and C, respectively, which lower than other operations. Moreover, it was observed that 60.0 and 40.0% of farms in operations B and C reused litter 3 or more times. Among the 74 farms, the most common antimicrobials prescription frequency was 2 times (39.2%), and the prescription to ß-lactams antibiotics (45.3%) showed the significantly highest (P < 0.05). The highest administration of antimicrobials was at 15 to 22-days old (42.7%), and most of them were recommended by veterinarian (80.7%). Footbath disinfectant and spraying outside the poultry house were performed in most of the farms (64.9 and 83.8%, respectively), but the use of quicklime (36.5%) and drinking water disinfectant (18.9%) was low in farms. Most of the farms washed vehicles for transportation of poultry (87.8%) and feed (100%) before arriving at the farms, however, 40.5% of the farms used little or no disinfectants when washing the transport vehicles. Moreover, wild birds, and cats and dogs were well controlled on most of the farms (each 94.6%), but only 74.3% of farms offered rodent control programs. Also, only 27.0% of the farms used farm-specific shoes and clothing as well as footbath disinfection for entrance. These findings can be useful in developing policies and guidelines for sustainable and responsible broiler chicken production and reduction of antimicrobial use in Korea.

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.

Vertigo and Dizziness After Coronavirus Disease-2019 Vaccination: A Nationwide Analysis.

BACKGROUND: Side effects occurring after COVID-19 vaccination can include vertigo and dizziness. Despite its high incidence, few studies to date have assessed dizziness/vertigo after vaccination. The present study investigated the incidence of dizziness/vertigo after COVID-19 vaccination in South Korea. METHODS: Adverse reactions to COVID-19 vaccination reported to the Korea Disease Control and Prevention Agency from February 26, 2021, to July 31, 2022 (week 74) were analyzed. The incidence rates of dizziness/vertigo in subjects vaccinated with 5 COVID-19 vaccines, AZD1222 (AstraZeneca), BNT162b2 (Pfizer-BioNTech), JNJ-78436735 (Janssen), mRNA-1273 (Moderna), and NVX-CoV2373 (Novavax), were determined. RESULTS: A total of 126 725 952 doses of COVID-19 vaccine were administered, with 473 755 suspected adverse reactions (374 per 100 000 vaccinations) reported. Vertigo/dizziness was reported after the administration of 68 759 doses, or 54.3 per 100 000 vaccinations, making it the third most common adverse reaction after headache and muscle pain. CONCLUSION: Dizziness/vertigo was generally a mild adverse reaction after COVID-19 vaccination, but it was the third most common adverse reaction in Korea. Studies are necessary to clarify the causal relationship between vaccination and dizziness/vertigo and to prepare subjects for this possible adverse reaction.

Gene expression of Toll-like receptors, cytokines and a nuclear factor and cytokine secretion in DH82 canine macrophage cells infected with Brucella canis.

Canine brucellosis caused by Brucella canis infection occurs mainly in dogs, and is a zoonotic disease that also has the possibility of infection in humans. Many studies have been conducted to understand the immunopathological mechanism of B. canis infection. However, the precise immune mechanism remains to be elucidated because compared to other Brucella spp., B. canis has different immune evasion mechanisms. In this study, gene expression levels of Toll-like receptors (TLRs) and TLR-associated molecules and cytokine production were analyzed to figure out the roles of immune-related host factors in B. canis infection. Time-dependent gene expression of TLRs (1-10) and TLR-related molecules (TNF-α, IL-5, IL-23, CCL4, CD40 and NFκ-B) and release of Th1, Th2 and Th17-related cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10 and IL-17A) were investigated in DH82 canine macrophages infected with B. canis. Time-dependent induction of TLRs 3, 7 and 8 was observed, and TLR 7 had the highest expression level (p <0.05). The expression levels of all TLR-related genes were significantly increased after infection. In particular, the expression of the CCL4 and IL-23 genes was highly induced. The amounts of IL-1ß, IL-6 and IL-10 were significantly increased by B. canis infection, but the amounts of IL-4 and IL-17A were not. The production of IL-1ß and IL-6 was the highest at 24 hr after B. canis infection (p <0.05). This study demonstrates that TLRs 3, 7 and 8 are prominent sites of to immune response induction with the production of related cytokines and a nuclear factor in DH82 cells infected with B. canis. These results suggest a sequential immune mechanism of B. canis infection, involving TLRs, cytokines and their associated factors.

Positive rates for Enterobius vermicularis eggs among preschool children in Yeosu-si, Jeollanam-do, Korea (2017-2021).

This study aimed to evaluate the positive rates for Enterobius vermicularis eggs among preschool children in Yeosu-si, Jeollanam-do, the Republic of Korea (Korea) over a period of 5 years (2017-2021). Perianal swab samples, obtained using cellotape, from 10,392 preschool children in 26 districts were examined microscopically for E. vermicularis eggs. The test results were notified through the local health center, and the families of children who tested positive were advised to provide them anthelmintics treatment. The annual positive rates were 5.0%, 5.2%, 4.4%, 2.2%, and 1.0% in 2017, 2018, 2019, 2020, and 2021, respectively. The overall positive rate was higher in boys than in girls (P< 0.05), and children aged 5-7 years were at a higher risk of being infected than those aged 0-4 years (P< 0.05). Although the rates of infection by E. vermicularis in the survey area, Yeosu-si, were still in the 1% range , the results of this study suggest that they can be significantly reduced through continuous intervention centered around the test-treatment strategy.

Prevalence and characteristics of foodborne pathogens from slaughtered pig carcasses in Korea.

The introduction of bacteria into slaughterhouses can lead to microbial contamination in carcasses during slaughter, and the initial level of bacteria in carcasses is important because it directly affects spoilage and the shelf life. This study was conducted to investigate the microbiological quality, and the prevalence of foodborne pathogens in 200 carcasses from 20 pig slaughterhouses across Korea. Distribution of microbial counts were significantly higher for aerobic bacteria at 3.01-4.00 log10 CFU/cm2 (42.0%) and 2.01-3.00 log10 CFU/cm2 (28.5%), whereas most of Escherichia coli showed the counts under 1.00 log10 CFU/cm2 (87.0%) (P < 0.05). The most common pathogen isolated from 200 carcasses was Staphylococcus aureus (11.5%), followed by Yersinia enterocolitica (7.0%). In total, 17 S. aureus isolates from four slaughterhouses were divided into six pulsotypes and seven spa types, and showed the same or different types depending on the slaughterhouses. Interestingly, isolates from two slaughterhouses carried only LukED associated with the promotion of bacterial virulence, whereas, isolates from two other slaughterhouses carried one or more toxin genes associated with enterotoxins including sen. In total, 14 Y. enterocolitica isolates from six slaughterhouses were divided into nine pulsotypes, 13 isolates belonging to biotype 1A or 2 carried only ystB, whereas one isolate belonging to bio-serotype 4/O:3 carried both ail and ystA. This is the first study to investigate microbial quality and the prevalence of foodborne pathogens in carcasses from slaughterhouses nationally, and the findings support the need for ongoing slaughterhouse monitoring to improve the microbiological safety of pig carcasses.

Situational analysis on fluoroquinolones use and characterization of high-level ciprofloxacin-resistant Enterococcus faecalis by integrated broiler operations in South Korea.

Fluoroquinolones are classified as "critically important antimicrobials for human medicine"; however, their extensive use in livestock poses a significant health risk to humans as it leads to the rapid spread of antimicrobial resistance. This study confirmed that 40.0%-71.4% of the farms in three of the five integrated broiler operations were administered ciprofloxacin (CIP). Moreover, preventive purposes (60.9%), veterinarian prescriptions (82.6%), drinking water route (100%), and 1 to 3 days (82.6%) of age were significantly highest (P < 0.05). 194 high-level ciprofloxacin-resistant (HLCR) Enterococcus faecalis (E. faecalis) were found in 65 of 74 farms, and of which, the prevalence of qnrA (63.9%), tetM (60.3%), ermB (64.9%), blaz (38.7%), and catA (34.0%) was significantly highest (P < 0.05). 154 (79.4%) isolates showed MDR, and the distribution of MDR was significantly differences among the operations (P < 0.05). All HLCR E. faecalis possessed double mutations in gyrA and parC, and S83I/S80I (90.7%) mutations were most commonly identified. Interestingly, the distribution of isolates with MICs ≥ 512 for both CIP and moxifloxacin was significantly higher in CIP-administered farms (56.5%) than in non-CIP-administered farms (41.4%) (P < 0.05). Also, the prevalence of strong or moderate biofilm formers in HLCR E. faecalis was significantly higher than that of weak and no biofilm formers (P < 0.05). HLCR E. faecalis were heavily distributed in the broiler farms in Korea; therefore, it is necessary to minimize the prevalence of resistant bacteria via structural management regulations such as cleaning and disinfection of farm environments.

Comparing the Clinical Manifestations of Bell's Palsy between Pre-COVID-19 Pandemic and COVID-19 Pandemic Periods.

BACKGROUND: COVID-19 has been shown to affect the onset and severity of various diseases. We examined whether the clinical characteristics of Bell's palsy differed between before and during the COVID-19 pandemic. METHODS: From January 2005 to December 2021, 1839 patients were diagnosed and treated for Bell's palsy at Kyung Hee University Hospital. These patients were divided into a pre-COVID period group and COVID-19 period group, and the clinical characteristics of the two groups were compared. RESULTS: There were 1719 patients in the pre-COVID period group and 120 patients in the COVID-19 period group. There were no between-group differences in sex (p = 0.103) or in the presence of underlying hypertension (p = 0.632) or diabetes (p = 0.807). Regarding symptoms, there were no significant between-group differences in otalgia, dizziness, tinnitus, hyperacusis, or hearing loss (p = 0.304, p = 0.59, p = 0.351, p = 0.605, and p = 0.949). There were also no significant between-group differences in electroneurography results (p = 0.398), electromyography results (p = 0.331), House-Brackmann Grade at visit (p = 0.634), or recovery rate after treatment (p = 0.525). CONCLUSIONS: Contrary to our expectation that Bell's palsy cases during the COVID-19 pandemic would show different clinical features than those occurring before COVID-19, the present study found no differences in clinical features or prognosis.

Dissemination and characteristics of high-level erythromycin-resistant Enterococcus faecalis from bulk tank milk of dairy companies in Korea.

Enterococci are environmental pathogens that can cause bovine mastitis, which is treated with macrolides, one of which is erythromycin (ERY). The aim of this study was to compare the characteristics of high-level erythromycin-resistant (HLER) Enterococcus faecalis (E. faecalis) isolates from bulk tank milk of 4 dairy companies, identified as A to D, in order to assess the threat to public health. Although isolates from company D showed the highest prevalence of E. faecalis, the prevalence of HLER E. faecalis in isolates from company A showed a significant difference. A total of 149 of the 301 HLER E. faecalis isolates showed the highest rate of resistance to tetracycline. In the distribution of antimicrobial resistance genes, 147 isolates carried the ermB gene alone and 2 isolates carried both ermA and ermB genes. Also, 72 and 60 isolates carried both tetM and tetL genes and the tetM gene alone, respectively, and 38 isolates carried the optrA gene. The prevalence of both aac(6')Ie-aph(2″)-la and ant(6')-Ia genes was the highest and 104 isolates harbored the Int-Tn gene carrying the Tn916/1545-like transposon. Although the distribution of the e rmB gene showed no significant difference among dairy companies, the prevalence of other resistance genes and transposons showed significant differences among dairy companies. Virulence genes were highly conserved in the HLER E. faecalis isolates. Our results indicated that there were significant differences in phenotypic and genotypic characteristics of HLER E. faecalis isolates in milk from 4 different dairy companies. A structured management protocol by companies and constant monitoring are therefore necessary to minimize public health hazards.

Les entérocoques sont des agents pathogènes environnementaux qui peuvent causer la mammite bovine, qui est traitée avec des macrolides, dont l'érythromycine (ERY). Le but de cette étude était de comparer les caractéristiques des isolats d'Enterococcus f aecalis (E. faecalis) hautement résistants à l'érythromycine (HLER) provenant du lait de réservoir en vrac de quatre entreprises laitières, identifiées comme A à D, afin d'évaluer la menace pour santé publique. Bien que les isolats de la société D aient montré la prévalence la plus élevée d'E. faecalis, la prévalence d'E. faecalis HLER dans les isolats de la société A montrait une différence significative. Un total de 149 des 301 isolats d'E. faecalis HLER ont montré le taux le plus élevé de résistance à la tétracycline. Dans la distribution des gènes de résistance aux antimicrobiens, 147 isolats portaient le gène ermB seul et deux isolats portaient à la fois les gènes ermA et ermB. En outre, 72 et 60 isolats portaient à la fois les gènes tetM et tetL et le gène tetM seul, respectivement, et 38 isolats portaient le gène optrA. La prévalence des gènes aac(6')Ie-aph(2″)-la et ant(6')-Ia était la plus élevée et 104 isolats portaient le gène Int-Tn portant le transposon de type Tn916/1545. Bien que la distribution du gène ermB n'ait montré aucune différence significative entre les entreprises laitières, la prévalence d'autres gènes de résistance et transposons a montré des différences significatives entre les entreprises laitières. Les gènes de virulence étaient hautement conservés dans les isolats d'E. faecalis HLER. Nos résultats ont indiqué qu'il y avait des différences significatives dans les caractéristiques phénotypiques et génotypiques des isolats d'E. faecalis HLER dans le lait de quatre entreprises laitières différentes. Un protocole de gestion structuré par les entreprises et une surveillance constante sont donc nécessaires pour minimiser les risques pour la santé publique.(Traduit par Docteur Serge Messier).

Therapeutic Efficacy of YM155 to Regulate an Epigenetic Enzyme in Major Subtypes of RCC.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and includes more than 10 subtypes. Compared to the intensively investigated clear cell RCC (ccRCC), the underlying mechanisms and treatment options of other subtypes, including papillary RCC (pRCC) and chromogenic RCC (chRCC), are limited. In this study, we analyzed the public databases for ccRCC, pRCC, and chRCC and found that BIRC5 was commonly overexpressed in a large cohort of pRCC and chRCC patients as well as ccRCC and was closely related to the progression of RCCs. We investigated the potential of BIRC5 as a therapeutic target for these three types of RCCs. Loss and gain of function studies showed the critical role of BIRC5 in cancer growth. YM155, a BIRC5 inhibitor, induced a potent tumor-suppressive effect in the three types of RCC cells and xenograft models. To determine the mechanism underlying the anti-tumor effects of YM155, we examined epigenetic modifications in the BIRC5 promoter and found that histone H3 lysine 27 acetylation (H3K27Ac) was highly enriched on the promoter region of BIRC5. Chromatin-immunoprecipitation analysis revealed that H3K27Ac enrichment was significantly decreased by YM155. Immunohistochemistry of xenografted tissue showed that overexpression of BIRC5 plays an important role in malignancy in RCC. Furthermore, high expression of P300 was significantly associated with the progression of RCC. Our findings demonstrate the P300-H3K27Ac-BIRC5 cascade in three types of RCC and provide a therapeutic path for future research on RCC.