Impact of IL-1ß on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1ß maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1ß in the host's defense against MAB. The IL-1ß production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1ß production in response to MAB. NLRP3 and IL-1ß deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1ß-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1ß deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1ß-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, in vitro co-culture analysis showed that IL-1ß signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1ß production contribute to MAB-induced lung pathology via the elevation of IL-17 production.

The Role of Measuring Preoperative Social Maturation Score in Children With Additional Needs Who Underwent Cochlear Implantation.

BACKGROUND AND OBJECTIVES: Additional needs refer to specific requirements or support for individuals with disabilities or syndromes. Intellectual ability is a crucial outcome determinant of a cochlear implant. The social quotient (SQ) is an indirect predictor of intellectual capacity and social skills. This study aimed to investigate the clinical significance of the SQ on children with additional needs who received cochlear implants. Subjects and. METHODS: This study included 24 patients with diagnosed developmental delays and syndromes, who demonstrated SQ scores of <70. Preoperative social skills were evaluated using the SQ. All patients underwent cochlear implantation (CI) surgery before 7 years of age. Outcomes were evaluated using the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP) scores. Data were collected through a retrospective chart review. RESULTS: Children were categorized into three groups based on their SQ. There were no correlations between the preoperative SQ and IT-MAIS or CAP scores at 2 and 5 years of follow-up postoperatively. The CI outcomes of children with low SQ (<70) differed from those with normal development (SQ>70). In the low-SQ group, inner ear anomalies were observed in 10 (41.7%) patients. Although not statistically significant, these children exhibited a trend of lower average outcomes than children without inner ear anomalies. CONCLUSIONS: CI outcomes in children with additional needs positively affected auditory performance. Postoperative auditory and language skills tended to improve slowly in children with additional needs and a lower SQ. Over time, development gradually became more comparable to the other groups of children. However, this improvement was less than that observed in children without additional needs. Our findings support CI for children with additional needs as part of long-term auditory rehabilitation following surgery.

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Acetyl-CoA synthetase 2 contributes to a better prognosis for liver cancer by switching acetate-glucose metabolism.

Acetyl-CoA synthetase 2 (ACSS2)-dependent acetate usage has generally been associated with tumorigenesis and increased malignancy in cancers under nutrient-depleted conditions. However, the nutrient usage and metabolic characteristics of the liver differ from those of other organs; therefore, the mechanism of ACSS2-mediated acetate metabolism may also differ in liver cancer. To elucidate the underlying mechanisms of ACSS2 in liver cancer and acetate metabolism, the relationships between patient acetate uptake and metabolic characteristics and between ACSS2 and tumor malignancies were comprehensively studied in vitro, in vivo and in humans. Clinically, we initially found that ACSS2 expression was decreased in liver cancer patients. Moreover, PET-CT imaging confirmed that lower-grade cancer cells take up more 11C-acetate but less 18F-fluorodeoxyglucose (18F-FDG); however, this trend was reversed in higher-grade cancer. Among liver cancer cells, those with high ACSS2 expression avidly absorbed acetate even in a glucose-sufficient environment, whereas those with low ACSS2 expression did not, thereby showing correlations with their respective ACSS2 expression. Metabolomic isotope tracing in vitro and in vivo revealed greater acetate incorporation, greater lipid anabolic metabolism, and less malignancy in high-ACSS2 tumors. Notably, ACSS2 downregulation in liver cancer cells was associated with increased tumor occurrence in vivo. In human patient cohorts, patients in the low-ACSS2 subgroup exhibited reduced anabolism, increased glycolysis/hypoxia, and poorer prognosis. We demonstrated that acetate uptake by ACSS2 in liver cancer is independent of glucose depletion and contributes to lipid anabolic metabolism and reduced malignancy, thereby leading to a better prognosis for liver cancer patients.

Water Extract of Desalted Salicornia europaea Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice.

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.

Treatment outcomes of the external auditory canal and temporal bone malignancy with dura invasion.

Objectives: This study aimed to evaluate the characteristics and surgical outcomes of patients with external auditory canal (EAC) and temporal bone (TB) malignancy with dura invasion. Methods: The medical records of patients with EAC and TB malignancy with dura invasion were retrospectively reviewed. Survival outcomes (overall survival [OS], disease-specific survival [DSS], recurrence-free survival [RFS], and distant metastasis-free survival [DMFS]) were analyzed using the Kaplan-Meier method. Results: A total of eight patients were included in this study. The median age at diagnosis was 49.5 years (range 12-74 years). The median follow-up periods were 46.5 months. Histologically, four out of eight patients were diagnosed with squamous cell carcinoma (SCC; 50%). The 2-year OS and DSS rates of all patients were 62.5%, and those of EAC SCC patients were 50% and 66.7%, respectively; while the 2-year RFS and DMFS rates of all patients were 37.5%. There was one local recurrence at the resection site (12.5%), two regional neck nodal recurrences (25%), and two distant metastases (25%). Dura resection and duroplasty areas were not involved in the local recurrence case. Conclusion: In EAC and TB cancer with dura invasion, radical surgery with dura resection may show similar survival outcomes to previous studies without recurrence at the dura resection site.Level of evidence: IV.

Effectiveness of SBAR-based simulation programs for nursing students: a systematic review.

BACKGROUND: Situation, background, assessment, and recommendation (SBAR) has been extensively used in clinical and nursing education. A structured communication program increases effective communication, positivity, and education satisfaction during inter-professional collaboration among nursing students. This systematic review aimed to identify and synthesize evidence on the effectiveness of SBAR-based simulation training for nursing students. METHODS: A research protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The protocol for this study was registered in PROSPERO (CRD42021234068). Eight bibliographical databases were searched for studies published between 2001 and 2021, using relevant search terms. Searches were conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials for literature in English, and DBpia, Research Information Sharing Service, Korean Studies Information Service System, and Korea Institute of Science and Technology Information for literature in Korean. After screening titles, abstracts, and full-text papers, pertinent data were extracted, and critical appraisals of the retrieved studies were performed. Data were analyzed using the framework approach, and the findings were presented in a narrative summary. The Effective Public Health Practice Project "Quality Assessment Tool for Quantitative Studies" was used to assess the quality of the included studies. RESULTS: Twelve studies were included: 3 randomized controlled trials and 9 quasi-experimental studies. Two overarching themes were noted, namely communication clarity and critical thinking. The results of six out of 12 studies produced significant results in favor of SBAR-based simulation in terms of communication clarity. Divergent results were obtained regarding communication ability, critical thinking, confidence, learning self-efficacy, and attitude toward patient safety. The results of these studies highlight that communication clarity ultimately leads to positive results in terms of nursing students' behaviors related to patient safety. CONCLUSIONS: This review provides a comprehensive update of the literature on the effectiveness of SBAR-based nursing simulation programs for nursing students. These programs were found to have positive learning outcomes because of clear and concise communication. Further studies on the effectiveness of various learning outcomes derived from SBAR-based programs are required.

Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis.

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Anatomical Features of Children With Mondini Dysplasia: Influence on Cochlear Implantation Performance.

OBJECTIVE: To analyze the long-term auditory performance after cochlear implantation (CI) and identify anatomical features of Mondini dysplasia associated with post-CI outcomes. STUDY DESIGN: Retrospective study. SETTING: Tertiary care academic center. PATIENTS: We enrolled 49 ears with Mondini dysplasia who underwent CI with more than 7 years of follow-up and age at CI- and sex-matched control group with radiologically normal inner ears. MAIN OUTCOMES AND MEASURES: The development of auditory skills after CI was evaluated using word recognition scores (WRSs). The anatomical features were measured based on temporal bone computed tomography and magnetic resonance imaging, involving the width of the bony cochlear nerve canal (BCNC), cochlear basal turn, enlarged vestibular aqueduct, cochlear height, and diameter of the cochlear nerve (CN). RESULTS: CI in ears with Mondini dysplasia showed comparable benefits and improvement of auditory performance to controls during the 7 years of follow-up. In Mondini dysplasia, four (8.2%) ears showed narrow BCNC (<1.4 mm) with poorer WRS (58 ± 17%) than those with normal-sized BCNC, which had WRS (79 ± 10%) comparable to that of the control group (77 ± 14%). In Mondini dysplasia, the maximum ( r = 0.513, p < 0.001) and minimum ( r = 0.328, p = 0.021) CN diameters had positive correlations with post-CI WRS. The maximum CN diameter ( ß = 48.347, p < 0.001) and BCNC width ( ß = 12.411, p = 0.041) were significant factors that influence the post-CI WRS in multiple regression analysis. CONCLUSIONS: Preoperative anatomical evaluation, especially BCNC status and CN integrity, may serve as predictive markers for post-CI performance.

Vactosertib, TGF-ß receptor I inhibitor, augments the sensitization of the anti-cancer activity of gemcitabine in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a pronounced extracellular matrix (ECM)-rich response, which is produced by an excessive amount of transforming growth factor ß (TGF-ß), resulting in tumor progression and metastasis. In addition, TGF-ß signaling contributes to rapidly acquired resistance and incomplete response to gemcitabine. Recently, selective inhibitors of the TGF-ß signaling pathway have shown promise in PDAC treatment, particularly as an option for augmenting responses to chemotherapy. Here, we investigated the synergistic anticancer effects of a small-molecule TGF-ß receptor I kinase inhibitor (vactosertib/EW-7197) in the presence of gemcitabine, and its mechanism of action in pancreatic cancer. Vactosertib sensitized pancreatic cancer cells to gemcitabine by synergistically inhibiting their viability. Importantly, the combination of vactosertib and gemcitabine significantly attenuated the expression of major ECM components, including collagens, fibronectin, and α-SMA, in pancreatic cancer compared with gemcitabine alone. This resulted in potent induction of mitochondrial-mediated apoptosis, gemcitabine-mediated cytotoxicity, and inhibition of tumor ECM by vactosertib. Additionally, the combination decreased metastasis through inhibition of migration and invasion, and exhibited synergistic anti-cancer activity by inhibiting the TGF-ß/Smad2 pathway in pancreatic cancer cells. Furthermore, co-treatment significantly suppressed tumor growth in orthotopic models. Therefore, our findings demonstrate that vactosertib synergistically increased the antitumor activity of gemcitabine via inhibition of ECM component production by inhibiting the TGF-ß/Smad2 signaling pathway. This suggests that the combination of vactosertib and gemcitabine may be a potential treatment option for patients with pancreatic cancer.

A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting.

Double hit diffuse large B-cell lymphoma (DLBCL) with rearrangement and overexpression of both c-Myc and Bcl-2 responds poorly to standard R-CHOP therapy. In a recent phase I study, Venetoclax (ABT-199) targeting Bcl-2 also exhibited disappointing response rates in patients with relapsed/refractory DLBCL, suggesting that targeting only Bcl-2 is not sufficient for achieving successful efficacy due to the concurrent oncogenic function of c-Myc expression and drug resistance following an increase in Mcl-1. Therefore, co-targeting c-Myc and Mcl-1 could be a key combinatorial strategy to enhance the efficacy of Venetoclax. In this study, BR101801 a novel drug for DLBCL, effectively inhibited DLBCL cell growth/proliferation, induced cell cycle arrest, and markedly inhibited G0/G1 arrest. The apoptotic effect of BR101801 was also observed by increased Cytochrome C, cleaved PARP, and Annexin V-positive cell populations. This anti-cancer effect of BR101801 was confirmed in animal models, where it effectively inhibited tumor growth by reducing the expression of both c-Myc and Mcl-1. Furthermore, BR101801 exhibited a significant synergistic antitumor effect even in late xenograft models when combined with Venetoclax. Our data strongly suggest that c-Myc/Bcl-2/Mcl-1 triple targeting through a combination of BR101801 and Venetoclax could be a potential clinical option for double-hit DLBCL.

A novel DDR1 inhibitor enhances the anticancer activity of gemcitabine in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extracellular matrix (ECM)-rich carcinoma, which promotes chemoresistance by inhibiting drug diffusion into the tumor. Discoidin domain receptor 1 (DDR1) increases tumor progression and drug resistance by binding to collagen, a major component of tumor ECM. Therefore, DDR1 inhibition may be helpful in cancer therapeutics by increasing drug delivery efficiency and improving drug sensitivity. In this study, we developed a novel DDR1 inhibitor, KI-301690 and investigated whether it could improve the anticancer activity of gemcitabine, a cytotoxic agent widely used for the treatment of pancreatic cancer. KI-301690 synergized with gemcitabine to suppress the growth of pancreatic cancer cells. Importantly, its combination significantly attenuated the expression of major tumor ECM components including collagen, fibronectin, and vimentin compared to gemcitabine alone. Additionally, this combination effectively decreased mitochondrial membrane potential (MMP), thereby inducing apoptosis. Further, the combination synergistically inhibited cell migration and invasion. The enhanced anticancer efficacy of the co-treatment could be explained by the inhibition of DDR1/PYK2/FAK signaling, which significantly reduced tumor growth in a pancreatic xenograft model. Our results demonstrate that KI-301690 can inhibit aberrant ECM expression by DDR1/PYK2/FAK signaling pathway blockade and attenuation of ECM-induced chemoresistance observed in desmoplastic pancreatic tumors, resulting in enhanced antitumor effect through effective induction of gemcitabine apoptosis.

Lidocaine enhances the efficacy of palbociclib in triple-negative breast cancer.

The use of anesthetics in the surgical resection of tumors may influence the prognosis of cancer patients. Lidocaine, a local anesthetic, is known to act as a chemosensitizer and relieve pain in some cancers. In addition, palbociclib, a potent cyclin-dependent kinase (CDK) 4/6 inhibitor, has been approved for chemotherapy of advanced breast cancer. However, recent studies have revealed the acquired resistance of breast cancer cells to palbociclib. Therefore, the development of combination therapies that can extend the efficacy of palbociclib or delay resistance is crucial. This study investigated whether lidocaine would enhance the efficacy of palbociclib in breast cancer. Lidocaine synergistically suppressed the growth and proliferation of breast cancer cells by palbociclib. The combination treatment showed an increased cell cycle arrest in the G0/G1 phase by decreasing retinoblastoma protein (Rb) and E2F1 expression. In addition, it increased apoptosis by loss of mitochondrial membrane potential as observed by increases in cytochrome c release and inhibition of mitochondria-mediated protein expression. Additionally, it significantly reduced epithelial-mesenchymal transition and PI3K/AKT/GSK3ß signaling. In orthotopic breast cancer models, this combination treatment significantly inhibited tumor growth and increased tumor cell apoptosis compared to those treated with a single drug. Taken together, this study demonstrates that the combination of palbociclib and lidocaine has a synergistic anti-cancer effect on breast cancer cells by the inhibition of the PI3K/AKT/GSK3ß pathway, suggesting that this combination could potentially be an effective therapy for breast cancer.

Factors Associated with Gastrointestinal Symptoms among Rotating Shift Nurses in South Korea: A Cross-Sectional Study.

Rotating shift work places a serious burden on nurses' physical and psychological health. Gastrointestinal (GI) symptoms are a common complaint among shift workers. This study assessed GI symptoms and identified the associations between dietary habits, psychological status, and sleep quality among rotating shift nurses. Data from 125 female nurses in rotating shifts who worked at two tertiary hospitals in South Korea were collected using a questionnaire that included the Gastrointestinal Symptoms Questionnaire; the Dietary Habit Questionnaire; the Depression, Anxiety, Stress Scale (DASS)-21; and the Pittsburgh Sleep Quality Index (PSQI). All participants experienced various GI symptoms, and 47% of them complained of at least one severe GI symptom. There were significant differences in GI symptom scores according to the status of depression, anxiety, stress, and sleep quality. In multiple linear regression analysis, the factors associated with an increase in the occurrence and severity of GI symptoms were poor sleep quality and morbid anxiety and stress. The model explained power at 43.2%. As most nurses in rotating shifts experience GI symptoms, they should receive counseling and training programs at work to alleviate psychological symptoms, improve sleep quality, and pay more attention to their health status as well as GI symptom management.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota.

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota.

Interrater reliability of sleep stage scoring: a meta-analysis.

STUDY OBJECTIVES: We evaluated the interrater reliabilities of manual polysomnography sleep stage scoring. We included all studies that employed Rechtschaffen and Kales rules or American Academy of Sleep Medicine standards. We sought the overall degree of agreement and those for each stage. METHODS: The keywords were "Polysomnography (PSG)," "sleep staging," "Rechtschaffen and Kales (R&K)," "American Academy of Sleep Medicine (AASM)," "interrater (interscorer) reliability," and "Cohen's kappa." We searched PubMed, OVID Medline, EMBASE, the Cochrane library, KoreaMed, KISS, and the MedRIC. The exclusion criteria included automatic scoring and pediatric patients. We collected data on scorer histories, scoring rules, numbers of epochs scored, and the underlying diseases of the patients. RESULTS: A total of 101 publications were retrieved; 11 satisfied the selection criteria. The Cohen's kappa for manual, overall sleep scoring was 0.76, indicating substantial agreement (95% confidence interval, 0.71-0.81; P < .001). By sleep stage, the figures were 0.70, 0.24, 0.57, 0.57, and 0.69 for the W, N1, N2, N3, and R stages, respectively. The interrater reliabilities for stage N2 and N3 sleep were moderate, and that for stage N1 sleep was only fair. CONCLUSIONS: We conducted a meta-analysis to generalize the variation in manual scoring of polysomnography and provide reference data for automatic sleep stage scoring systems. The reliability of manual scorers of polysomnography sleep stages was substantial. However, for certain stages, the results were poor; validity requires improvement. CITATION: Lee YJ, Lee JY, Cho JH, Choi JH. Interrater reliability of sleep stage scoring: a meta-analysis. J Clin Sleep Med. 2022;18(1):193-202.

Endoscopic Transcanal Labyrinthectomy for Intractable Meniere's Disease: An Alternative to Transmastoid Labyrinthectomy?

OBJECTIVE: To describe a novel approach for intractable Ménière's disease exclusively through a transcanal endoscopic ear surgery (TEES) approach. PATIENT: A 56-year-old male with intractable Ménière's disease despite conservative treatment and chemical labyrinthectomy. INTERVENTIONS: Transcanal endoscopic labyrinthectomy. MAIN OUTCOME MEASURE: Subjective vertigo control, surgical morbidity. RESULTS: The TEES approach provided a wide exposure of the oval window. This facilitated removal of stapes crura and footplate. After widening of the oval window, the perilymph was suctioned, and gentamicin was injected through the oval window. The oval window was obliterated using the perichondrium of the tragal cartilage and fibrin glue. After 2 years of follow-up, there was no recurrence of vertigo. CONCLUSIONS: As a compelling alternative to the transmastoid approach, we propose endoscopic labyrinthectomy as an option for patients with intractable MD without functional hearing who have failed chemical labyrinthectomy. Additional studies are needed to determine the risk-benefit profile of this technique.

Type I Interferons Are Involved in the Intracellular Growth Control of Mycobacterium abscessus by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.

Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-ß treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/ß receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-ß treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-ß before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-ß did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-ß gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-ß treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.

Stress- and Work-Related Burnout in Frontline Health-Care Professionals During the COVID-19 Pandemic.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic is affecting humankind in unprecedented and monumental ways. Health-care professionals (HCPs) have had to deal with traumatic and complex situations at work. However, the current understanding of the emotional effects on HCPs and their vulnerability during the pandemic is limited. We investigated the effects of HCPs' viral epidemic-related stress, professional quality of life (ProQOL), depression, and anxiety on their health-related quality of life (HRQOL). METHODS: We recruited a convenience sample of 60 HCPs at 2 tertiary hospitals in provinces P and Y, Republic of Korea. We analyzed their demographics, viral epidemic-related distress, ProQOL (compassion satisfaction, burnout, and secondary traumatic stress), depression, anxiety, and HRQOL through self-reported questionnaires. RESULTS: Burnout had a significant direct effect on depression, anxiety, physical health, and psychological HRQOL and indirectly affected all subcategories of HRQOL. Viral epidemic-related stress had no significant direct effect on any variable, but indirectly affected all subcategories of HRQOL. Depression and anxiety were endogenous variables (mediators). Depression was a pathway that directly and significantly affected all subcategories of HRQOL. Burnout had the most significant effect on physical health and psychological HRQOL, whereas depression had the greatest effect on social relationships and environmental HRQOL. CONCLUSIONS: Low compassion satisfaction caused burnout in HCPs, and burnout was significantly associated with depression, anxiety, and HRQOL. Furthermore, HRQOL showed a greater response when affected by indirect burnout through depression and anxiety than when directly affected by burnout.