Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Background: A healthcare system’s collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. Methods: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. Results: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. Conclusion In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

BACKGROUND: Timely intervention in the treatment of bloodstream infection is important for prescription of appropriate antimicrobials. With prompt determination of the antimicrobial susceptibility of a causative agent, rapid antimicrobial susceptibility test (AST) can help select the appropriate antimicrobial therapy. This clinical study is for evaluation of the clinical performance of the QMAC-dRAST for rapid AST directly from positive blood culture (PBC)s with Gram-positive cocci. METHODS: A total of 115 PBC samples with Gram-positive organisms (76 Staphylococcus spp. and 39 Enterococcus spp.) were evaluated by the QMAC-dRAST system, and their pure culture isolates were evaluated by the MicroScan WalkAway (Beckman Coulter, USA) as the comparative AST system. Thirteen antimicrobial agents were included, and the agreement and discrepancy rates of the QMAC-dRAST system (Quantamatrix Inc., Republic of Korea) compared to the MicroScan WalkAway were calculated. To resolve discrepancies, the broth microdilution method was performed. RESULTS: The QMAC-dRAST system exhibited a categorical agreement rate of 94.9% (1,126/1,187) and an essential agreement rate of 98.3% (1,167/1,187). The QMAC-dRAST system yielded very major (false-susceptible) errors at 1.0% (5/485), major (false-resistant) errors at 1.3% (9/693), and minor errors at 4.0% (47/1,187) compared to the MicroScan WalkAway. The QMAC-dRAST system significantly eliminated 30 hours of total turnaround time by combination of direct inoculation of PBC and an image-based approach. CONCLUSION: The results of the QMAC-dRAST system were highly accurate. Thereby, the QMAC-dRAST may provide essential information to accelerate therapeutic decisions for earlier and adequate antibiotic treatment and patient management in clinical settings.
Anti-Infective Agents ; Bacteremia ; Bioengineering ; Clinical Study ; Drug Resistance, Microbial ; Enterococcus ; Gram-Positive Cocci* ; Humans ; Methods ; Microbial Sensitivity Tests ; Prescriptions ; Staphylococcus

There was an error in the article, the names of manufacturers and countries of equipments in the Korean abstract were reversed.

Nocardia species are aerobic, gram-positive, filamentous, partially acid-fast actinomycetes which are found worldwide in soil and decaying organic plant matter. When they infect human beings, they generally enter through the respiratory tract and then disseminate systemically. Rarely has a primary infection occurred as the result of direct inoculation. Isolation of Nocardia from clinical specimens and identification of species are difficult. But, with the introduction of new genetic technologies, reports of novel species of Nocardia have increased. We describe a case of cutaneous nocardiosis caused by Nocardia takedensis in an 87-year-old woman who was diagnosed by bacterial culture and 16S ribosomal RNA sequencing. N. takedensis has been described as a new species. This report describes the first clinical isolate of N. takedensis from a skin specimen in Korea.
Actinobacteria ; Aged, 80 and over ; Female ; Humans ; Korea ; Nocardia Infections* ; Nocardia* ; Plants ; Respiratory System ; RNA, Ribosomal, 16S ; Skin ; Soil

Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder of unknown origin that affects healthy children. It is characterized by multiplication of transient papules and nodules on the head and periarticular area. Histopathologically, lesions show mucin deposition in the dermis or subcutis. A 9-year-old male patient presented with multiple skin-colored papules and nodules on the face and both hands. These papules and nodules had appeared over the preceding months and had been increasing in number. He was otherwise healthy and had no underlying systemic disorders. Skin biopsy in the right thenar nodule revealed deposition of amorphous material stained positively with Alcian blue (pH 2.5) within the dermis and subcutis. Spontaneous resolution occurred over several months without sequelae.
Alcian Blue ; Biopsy ; Child ; Dermis ; Hand ; Head ; Humans ; Male ; Mucinoses* ; Mucins ; Skin

Cutaneous and systemic plasmacytosis (CSP) is a rare disorder of unknown etiology characterized by cutaneous polyclonal plasma cell infiltrates associated with various extracutaneous involvement and polyclonal hypergammaglobulinemia. Here, we report on a 54-year-old male patient with chronic renal insufficiency who presented with disseminated reddish-brown macules and plaques on the face and trunk. In our evaluation, he was found to have lymphadenopathy, polyclonal hypergammaglobulinemia; benign plasma cell infiltration involving the skin, bone marrow, and retroperitoneal area; and renal amyloidosis. To the best of our knowledge, this is the first reported case of CSP associated with renal amyloidosis.
Amyloidosis* ; Bone Marrow ; Humans ; Hypergammaglobulinemia ; Lymphatic Diseases ; Male ; Middle Aged ; Plasma Cells ; Renal Insufficiency, Chronic ; Skin

PURPOSE: Systemic inflammatory responses, which are defined in terms of the Glasgow prognostic score (GPS), have been reported to be independent predictors of unfavorable outcomes in various human cancers. We assessed the utility of the GPS as a predictor of intravesical recurrence after radical nephroureterectomy (RNU) in upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS: We collected data for 147 UTUC patients with no previous history of bladder cancer who underwent RNU from 2004 to 2012. Associations between perioperative clinicopathological variables and intravesical recurrence were analyzed by using univariate and multivariate Cox regression models. RESULTS: Overall, 71 of 147 patients (48%) developed intravesical recurrence, including 21 patients (30%) diagnosed with synchronous bladder tumor. In the univariate analysis, performance status, diabetes mellitus (DM), serum albumin, C-reactive protein, GPS, and synchronous bladder tumor were associated with intravesical recurrence. In the multivariate analysis, performance status (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.41-3.85; p=0.001), DM (HR, 2.04; 95% CI, 1.21-3.41; p=0.007), cortical thinning (HR, 2.01; 95% CI, 1.08-3.71; p=0.026), and GPS (score of 1: HR, 6.86; 95% CI, 3.69-12.7; p=0.001; score of 2: HR, 5.96; 95% CI, 3.10-11.4; p=0.001) were independent predictors of intravesical recurrence. CONCLUSIONS: Our results suggest that the GPS as well as performance status, DM, and cortical thinning are associated with intravesical recurrence after RNU. Thus, more careful follow-up, coupled with postoperative intravesical therapy to avoid bladder recurrence, should be considered in these patients.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell/pathology/secondary/*surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*etiology ; Neoplasm Staging ; Nephrectomy/*methods ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Systemic Inflammatory Response Syndrome/etiology ; Ureter/surgery ; Urinary Bladder Neoplasms/secondary ; Urologic Neoplasms/pathology/*surgery

No abstract available.
Epidermal Cyst*

BACKGROUND AND OBJECTIVES: It is unclear which plaque component is related with long-term clinical outcomes in patients with coronary artery occlusive disease (CAOD). We assessed the relationship between plaque compositions and long-term clinical outcomes in those patients. SUBJECTS AND METHODS: The study subjects consisted of 339 consecutive patients (mean 61.7+/-12.2 years old, 239 males) who underwent coronary angiogram and a virtual histology-intravascular ultrasound examination. Major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, non-fatal myocardial infarction, cerebrovascular events, and target vessel revascularization were evaluated during a mean 28-month follow-up period. RESULTS: Patients with high fibrofatty volume (FFV, >8.90 mm3, n=169) had a higher incidence of MACCE (25.4% vs. 14.7%, p=0.015), male sex (75.7% vs. 65.3%, p=0.043), acute coronary syndrome (53.3% vs. 35.9%, p=0.002), multivessel disease (62.7% vs. 41.8%, p<0.001) and post-stent slow flow (10.7% vs. 2.4%, p=0.002) than those with low FFV (FFV< or =8.90 mm3, n=170). Other plaque composition factors such as fibrous area/volume, dense calcified area/volume, and necrotic core area/volume did not show any impact on MACCE. Cardiogenic shock {hazard ratio (HR)=8.44; 95% confidence interval (CI)=3.00-23.79; p<0.001} and FFV (HR=1.85; 95% CI=1.12-3.07; p=0.016) were the independent predictors of MACCE by Cox regression analysis. Thin-cap fibroatheroma, necrotic core area, and necrotic core volume were not associated with MACCE. CONCLUSION: FFV of a culprit lesion was associated with unfavorable long-term clinical outcomes in patients with CAOD.
Acute Coronary Syndrome ; Coronary Artery Disease ; Coronary Vessels ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Incidence ; Male ; Myocardial Infarction ; Plaque, Atherosclerotic ; Shock, Cardiogenic ; Ultrasonography, Interventional