A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity.

Virtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.

Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

Reasons for using e-cigarettes among adults who smoke: comparing the findings from the 2016 and 2020 ITC Korea Surveys.

INTRODUCTION: Dual use of e-cigarettes and cigarettes is a growing usage pattern in adults, but little is known about the motivations underlying this trend. We investigated the reasons for e-cigarette use among adults who smoke, considering variation in sociodemographic subgroups. METHODS: This repeated cross-sectional study analysed adults who smoked at least weekly and vaped at any frequency. Data were from the International Tobacco Control Korea Surveys conducted in 2016 (n=164) and 2020 (n=1088). Fourteen reasons for e-cigarette use were assessed in both waves. Subgroup analyses were performed by age, sex and educational level. RESULTS: The top reasons for e-cigarette use in 2020 were curiosity (62.8%), less harmful than smoking (45.4%) and taste (43.2%). Curiosity was the most cited across age, sex and education subgroups. Significant differences were observed in 2020 compared with 2016, with lower percentages in goal-oriented reasons: helping quit smoking (36.3% vs 48.9%; p=0.017), helping cut down smoking (35.3% vs 52.7%; p=0.001), less harmful to others (39.0% vs 54.6%; p=0.003) and more acceptable (31.6% vs 61.2%; p<0.001). By contrast, non-goal-oriented reasons showed higher percentages in 2020, such as curiosity (62.8% vs 27.9%; p<0.001), taste (43.2% vs 22.1%; p<0.001) and enjoyment (26.8% vs 8.6%; p<0.001). In 2020, a majority of adults who smoked and vaped (53.3%) reported no intention to quit or reduce smoking. CONCLUSIONS: E-cigarette use for curiosity and pleasure predominated among adults who smoked. The reasons for dual use in adults have shifted from goal-oriented to non-goal-oriented.

Public support for tobacco endgame policies in South Korea: Findings from the 2020 International Tobacco Control Korea Survey.

BACKGROUND: Strong public support can increase the likelihood of adopting tobacco control policies. We assessed support for six commercial tobacco endgame policies in South Korea: limiting the nicotine in cigarettes, banning all additives in cigarettes, restricting the number of places where cigarettes are sold, and banning the manufacture and sales of cigarettes (unconditionally, with the provision of cessation support and with alternative tobacco products available). METHODS: Data were obtained from 4740 adults who completed the 2020 International Tobacco Control Korea Survey. Participants were categorised based on their nicotine use: (1) did not use any products, (2) vaped and/or used heated tobacco products (HTPs) but did not smoke cigarettes, (3) smoked cigarettes only and (4) smoked cigarettes and vaped and/or used HTPs. Attitudes towards the policies were classified as supportive, undecided or opposed. Weighted multinomial logistic regression models assessed support levels according to nicotine use. RESULTS: Support was highest for limiting the nicotine content in cigarettes (68.4%; 95% CI 64.6% to 72.3%) and restricting the number of retailers (68.1%; 95% CI 64.5% to 71.7%), and lowest for banning cigarette sales if alternative products are made available (45.0%; 95% CI 40.9% to 49.1%). People who did not use any products were most likely to support endgame policies, except for banning cigarette sales with alternatives available. The proportion of undecided participants exceeded 10% (range 13%-25%) for all policies. CONCLUSION: There is a strong public support for tobacco endgame policies in South Korea. Further research should prioritise the development of strategies to ensure the effective implementation of highly supported policies.

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors.

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Anti-pollutant effect of oleic acid against urban particulate matter is mediated via regulation of AhR- and TRPV1-mediated signaling in vitro.

Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene. However, oleic acid treatment attenuated the UPM effects on AhR signaling. Furthermore, while UPM induced activation of TRPV1 and MAPKs signaling which activated the downstream molecules NFκB and AP-1, these effects were reduced by cotreatment with oleic acid. UPM-dependent generation of reactive oxygen species (ROS) and reduction of cellular proliferation were also attenuated by the treatment of oleic acid. These data reveal that cell damage induced by UPM treatment occurs through AhR signaling and TRPV1 activation which in turn activates ERK and JNK, ultimately inducing NFκB and AP-1 activation. These effects were reduced by the cotreatment of oleic acid on HaCaT cells. These suggest that oleic acid reduces UPM-induced cell damage through inhibiting both the AhR signaling and activation of TRPV1 and its downstream molecules, leading to a reduction of pro-inflammatory cytokine and recovery of cell proliferation.

Oral ß-lactam pairs for the treatment of Mycobacterium avium complex pulmonary disease.

Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While ß-lactam are front line antibiotics against M. abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral ß-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual ß-lactam combinations include tebipenem and sulopenem, both in Phase 3, and FDA-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.

In Vitro Activity of Rifamycin Derivatives against Nontuberculous Mycobacteria, including Macrolide-/Amikacin-Resistant Clinical Isolates.

We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy.

We report long-term follow-up of the phase 1b study of venetoclax and rituximab (VenR) in patients with relapsed chronic lymphocytic leukemia (CLL), including outcomes with continuous or limited-duration therapy. Patients received venetoclax daily (200-600 mg) and rituximab over 6 months and then received venetoclax monotherapy. Patients achieving complete response (CR), CR with incomplete marrow recovery (CRi), or undetectable minimal residual disease (uMRD) assessed by flow cytometry (<10-4 cutoff) were allowed, but not required, to discontinue therapy, while remaining in the study and could be retreated with VenR upon progression. Median follow-up for all patients (N = 49) was 5.3 years. Five-year rates (95% CI) for overall survival, progression-free survival, and duration of response were 86% (72-94), 56% (40-70), and 58% (40-73), respectively. Of the 33 deep responders (CR/CRi or uMRD), 14 remained on venetoclax monotherapy (continuous therapy), and 19 stopped venetoclax therapy (limited-duration therapy) after a median of 1.4 years. Five-year estimates of ongoing response were similar between continuous (71%; 95% CI, 39-88) or limited-duration therapy (79% [49-93]). Six of 19 patients in the latter group had subsequent disease progression, all >2 years off venetoclax (range, 2.1-6.4). Four patients were retreated with VenR, with partial responses observed in the 3 evaluable to date. VenR induced deep responses that were highly durable with either continuous or limited-duration therapy. Retreatment with VenR induced responses in patients with CLL progression after discontinuing therapy. Continuous exposure to venetoclax in deep responders does not appear to provide incremental benefit.

Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: Results of a 12-week, multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIMS: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with glycated haemoglobin (HbA1c) of 7.0-10.0%, entered a 2-week placebo run-in period, and were randomized to receive once-daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. RESULTS: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (-0.79%, -0.89%, -0.92% and -0.08%, respectively; p < .001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were -30.5, -31.1, -35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. CONCLUSIONS: Once-daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well-tolerated treatment for Korean patients with type 2 diabetes mellitus.

Comparison of factors associated with postpartum depression from two cohorts of nurses: the Korea Nurses' Health Study and the Nurses' Health Study 3.

OBJECTIVES: This study aimed to identify whether differences exist in postpartum depression (PPD) in US and Korean nurses and its related factors. Identifying occupational and personal factors that underlie potential differences will be helpful for women's occupational health. METHODS: Baseline and postpartum survey data from employed nurses in the Korea Nurses' Health Study and Nurses' Health Study 3 (1244 Korean; 2742 US nurses) were analysed. Postpartum data collection was done via online survey. PPD was analysed based on cultural validation from prior studies using the Edinburgh Postnatal Depression Scale (cut-off of 10 for Korea and 13 for USA); depressive symptoms prior to pregnancy and childbirth, general characteristics and sleep satisfaction were also measured. Descriptive statistics, χ2 tests and t-tests and multivariate ordinal logistic regression analysis were performed. RESULTS: 45.9% of Korean participants had clinical symptoms of PPD (≥10), whereas US participants presented with 3.4% (≥13). Prior depressive symptoms were also higher in Korean participants (22.5%) compared with their US counterparts (4.5%). Prior depressive symptoms and poor sleep satisfaction were significant risk factors of PPD in both cohort groups, and vaginal birth was an additional influencing factor in Korean participants. CONCLUSIONS: Differences in PPD rates and related factors suggest the role of stress, cultural variation and differing work systems. Nurses and other women shift-workers noted to have depressive symptoms before and during pregnancy and exhibit PPD symptoms should especially be followed closely and offered supportive mental health services that include greater flexibility in returning to work.

A comparison of dyeing efficacy between hair-oxidation-based and hair-coating-based shampoos for the treatment of gray hair.

BACKGROUND: The process of hair dyeing causes hair damage, and periodic re-dyeing is required for newly grown hair. To avoid these hassles, hair color shampoos have been developed and are widely used. In this study, we compared the effects of two hair color shampoos with different dyeing principles to analyze the function of hair color shampoos. We analyzed hair tresses treated by hair-oxidation- and hair-coating-based shampoos. MATERIALS AND METHODS: We measured the color, tensile properties, softness, elasticity, gloss, moisture content, and protein content of the hair tresses dyed with color shampoos. The hair structures were analyzed by scanning and transmission electron microscopies (SEM and TEM) and a hydroxy radical-based method. RESULTS: The shampoo based on hair coating enhanced the hair dyeing effect and roughness, whereas that based on hair oxidation improved the color retention and moisture content in the hair tresses. Frictional resistance, gloss, and elasticity of the hair tresses were similar for the two products. However, according to the results of the protein loss test, TEM, and hydroxyl radical staining, the shampoo based on hair oxidation showed a longer dyeing retention compared to that based on hair coating but caused cuticle damage. CONCLUSION: These results show that the two shampoos with different dyeing principles exhibit different hair dyeing abilities and hair health indices. Therefore, we recommend that hair color shampoos should be used according to the requirements of an individual.

Outcomes of Short-Term Tigecycline-Containing Regimens for Mycobacterium abscessus Pulmonary Disease.

Short-term intravenous tigecycline therapy during a 1-month initial phase may improve early microbiological response in patients with Mycobacterium abscessus pulmonary disease (PD). However, short-term use of tigecycline did not improve the long-term culture conversion rate of M. abscessus PD. Further studies on the efficacy of prolonged intravenous tigecycline-containing regimens are needed.

Relationship between Resistance to Ethambutol and Rifampin and Clinical Outcomes in Mycobacterium avium Complex Pulmonary Disease.

We evaluated the associations between the in vitro activities of ethambutol and rifampin and clinical outcomes of Mycobacterium avium complex (MAC) pulmonary disease (PD). Among 158 patients with MAC-PD, there was no relationship between high MICs for ethambutol and/or rifampin and treatment failure for MAC-PD. Ethambutol and rifampin resistance was common among MAC isolates (rates of 87% and 59%, respectively), but mutations in embB, rpoB, and rpoC were rare, with detection in only 4% of the drug-resistant MAC isolates.

Risk of Metachronous Colorectal Advanced Neoplasia and Cancer in Patients With 3-4 Nonadvanced Adenomas at Index Colonoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review and meta-analysis evaluated the available evidence on the risk of metachronous advanced neoplasia (AN) and colorectal cancer (CRC) in patients with 3-4 nonadvanced adenomas (NAAs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases up to January 2021 for studies evaluating metachronous AN and CRC risk by comparing 3 groups (1-2 vs 3-4 vs ≥5 NAAs) at index colonoscopy. The estimates for risk of metachronous AN and CRC were evaluated using random-effects models. RESULTS: Fifteen studies (n = 36,375) were included. The risk of metachronous AN was significantly higher in the 3-4 NAAs group than in the 1-2 NAAs group (relative risk [RR] 1.264, 95% confidence interval [CI] 1.053-1.518, P = 0.012; I2 = 0%); there was no difference between the ≥ 5 NAAs and 3-4 NAAs groups (RR 1.962, 95% CI 0.972-3.958, P = 0.060; I2 = 68%). The risks of metachronous CRC between the 1-2 NAAs and 3-4 NAAs groups (RR 2.663, 95% CI 0.391-18.128, P = 0.317; I2 = 0%) or the 3-4 NAAs and ≥ 5 NAAs groups (RR 1.148, 95% CI 0.142-9.290, P = 0.897; I2 = 0%) were not significantly different. DISCUSSION: Although the risk of metachronous AN was greater in the 3-4 NAAs group than in the 1-2 NAAs group, the risk of metachronous AN and CRC between the 3-4 NAAs and ≥ 5 NAAs groups was not different. This suggests that further studies on metachronous AN and CRC risk in the 3-4 NAAs group are warranted to confirm a firm ≥5-year interval surveillance colonoscopy.

Prognosis and risk factors of electrocoagulation syndrome after endoscopic submucosal dissection in the colon and rectum. Large cohort study.

BACKGROUND: There are few studies on electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD). This study aimed to investigate the various risk factors associated with thermal injury and to determine the prognosis of post-colorectal ESD electrocoagulation syndrome (PECS). METHODS: We conducted a retrospective analysis of the medical records of 395 colorectal neoplasms of 508 patients who were treated with colorectal ESD between January 2013 and December 2019. The incidence, risk factors, and clinical outcomes of colorectal PECS were evaluated and analyzed. RESULTS: Colorectal PECS occurred in 25 patients (6.3%). The PECS group had a larger lesion size (≥ 40 mm), lesions with fibrosis, longer procedure time, older age, and a larger amount of submucosal injection per square meter than the non-PECS group. In multivariate analysis, lesion with size ≥ 40 mm (odds ratio [OR] 16.941, 95% confidence interval [CI] 3.869-74.178), lesions with fibrosis (OR 7.127, 95% CI 2.541-19.984), old age (OR 1.068, 95% CI 1.010-1.130), and amount of submucosal injection per square meter (OR 1.067, 95% CI 1.015-1.121) were independent risk factors. The PECS group had more fasting days (3.08 vs 1.56 days, P < 0.001), longer hospital stays (7.04 vs 4.09 days, P < 0.001), and higher medical costs (2367 vs 2046, US$, P = 0.004) than the non-PECS group. CONCLUSION: Lesions with size ≥ 40 mm, lesions with fibrosis, old age, and amount of submucosal injection per square meter were independent risk factors. Therefore, caution should be exercised when performing colorectal ESD in patients with these risk factors.

Therapeutic Potential of Human Nasal Inferior Turbinate-Derived Stem Cells: Microarray Analysis of Multilineage Differentiation.

INTRODUCTION: Human nasal inferior turbinate-derived stem cells (hNTSCs) are attractive sources of adult stem cells for medical application because they can be easily obtained and cultivated with a highly proliferative capacity. The ability of hNTSCs to differentiate into chondrocytes, osteocytes, and neural cells makes them potential replacement therapeutic candidates in intractable disease. Nevertheless, detailed expression pattern of genes associated with trilineage differentiation (osteogenesis, chondrogenesis, and neurogenesis) in hNTSCs has not been revealed yet. METHODS: In this study, we aimed to evaluate gene expression patterns of various transcription factors and marker genes associated with a particular lineage (osteogenesis, chondrogenesis, and neurogenesis) of differentiation of hNTSCs by DNA microarrays. RESULTS: In microarrays, 36 transcripts such as E2F transcription factor 1, activating transcription factor 5, and AKR1B10 were upregulated and 36 transcripts such as CA9, PPFIA4, HAS2, and COL4A4 were downregulated in osteogenically differentiated hNTSCs. In chondrogenically differentiated hNTSCs, 3 transcripts (NUDT14, CPA4, and heparin-binding epidermal growth factor-like growth factor) were upregulated and 82 transcripts such as PTGS1, CLEC2D, and TET1 were downregulated. In neurally differentiated hNTSCs, 61 transcripts such as insulin-like growth factor-binding protein-1, nerve growth factor receptor, FGF1, OLFML1, and EPGN were upregulated and 98 transcripts such as ACAN, RUNX2, and C21orf96 were downregulated. In gene ontology (GO) analysis, cell signal-related GO terms were highly expressed. By contrast, catalysis GO terms and GO terms related to oxidoreductase were overrepresented in chondrogenically differentiated hNTSCs and osteogenically differentiated hNTSCs, respectively. CONCLUSION: Considering overall results, hNTSCs-specific genetic information may promote further studies on intracellular mechanisms defining key features of these cells.

In Vitro Activity of Oxazolidinone against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates.

We evaluated the in vitro activities of oxazolidinone antibiotics, including linezolid, sutezolid, and delpazolid, against clinical nontuberculous mycobacteria (NTM) isolates. Regardless of macrolide resistance, for Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii, sutezolid showed the lowest MIC and minimal bactericidal concentration (MBC) values among oxazolidinone antibiotics. However, for Mycobacterium abscessus and Mycobacterium massiliense, the MIC and MBC for all oxazolidinone antibiotics showed similar values. Oxazolidinone antibiotics warrant further investigation as potential treatment for NTM.

Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease.

RATIONALE: Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear. OBJECTIVES: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen. METHODS: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping. RESULTS: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry. CONCLUSIONS: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.