Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

Background: Clinical ethics support is a form of preventive ethics aimed at mediating ethicsrelated conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. Methods: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultationrelated documents. Results: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/ treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. Conclusion The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.
Comorbidity ; Emergency Service, Hospital ; Employment ; Hospital Mortality ; Hospitalists ; Humans ; Korea ; Length of Stay ; Patients' Rooms ; Pneumonia ; Retrospective Studies ; Urinary Tract Infections

Granulocytic sarcoma is a form of extramedullary involvement of primitive myeloid cells. A 69-year-old male patient, with history of acute myeloid leukemia (AML) in remission state for 4 years, presented numbness, radiating pain and progressive motor weakness in left leg. MRI showed perineural thickening of the left sciatic nerve with increased signal intensity on fat-saturated T2-weighted image. The patient underwent surgical excision and the pathology was confirmed as granulocytic sarcoma. Its involvement of the peripheral nerve is extremely rare and also unusual to be the only evidence of AML relapse. In this case, we figured out the MRI feature of granulocytic sarcoma involving sciatic nerve, emerged as a sole manifestation of AML relapse.

A 41-year-old female presented with complaint of left hip and buttock pain. Magnetic resonance imaging (MRI) showed multi-focal bone marrow signal intensity changes in left iliac bone, sacrum and femur with an area of necrosis. The primary radiological differential diagnosis was multi-focal tuberculous osteomyelitis. Subsequent pelvic bone biopsy and bone marrow biopsy confirmed the diagnosis of B-cell precursor acute lymphoblastic leukemia with extensive necrosis, which is infrequent in leukemia. When musculoskeletal symptoms precede peripheral blood abnormalities and MRI scanning reveals multi-focal necrotic lesions rather than diffuse signal change, it can be difficult to identify and/or advance leukemia as differential diagnosis.

PURPOSE: In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning. MATERIALS AND METHODS: This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis. RESULTS: We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban. CONCLUSION: This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.
Commerce ; Eating ; Emergency Service, Hospital ; Epidemiology ; Herbicides ; Humans ; Intention ; Korea ; Mortality* ; Paraquat* ; Poisoning ; Retrospective Studies

PURPOSE: To evaluate the diagnostic performance of diffusion-weighted steady-state free precession (DW-SSFP) in comparison to diffusion-weighted echo-planar imaging (DW-EPI) for differentiating the neoplastic and benign osteoporotic vertebral compression fractures. MATERIALS AND METHODS: The subjects were 40 patients with recent vertebral compression fractures but no history of vertebroplasty, spine operation, or chemotherapy. They had received 3-Tesla (T) spine magnetic resonance imaging (MRI), including both DW-SSFP and DW-EPI sequences. The 40 patients included 20 with neoplastic vertebral fracture and 20 with benign osteoporotic vertebral fracture. In each fracture lesion, we obtained the signal intensity normalized by the signal intensity of normal bone marrow (SI norm) on DW-SSFP and the apparent diffusion coefficient (ADC) on DW-EPI. The correlation between the SI norm and the ADC in each lesion was analyzed using linear regression. The optimal cut-off values for the diagnosis of neoplastic fracture were determined in each sequence using Youden's J statistics and receiver operating characteristic curve analyses. RESULTS: In the neoplastic fracture, the median SI norm on DW-SSFP was higher and the median ADC on DW-EPI was lower than the benign osteoporotic fracture (5.24 vs. 1.30, P = 0.032, and 0.86 vs. 1.48, P = 0.041, respectively). Inverse linear correlations were evident between SI norm and ADC in both neoplastic and benign osteoporotic fractures (r = −0.45 and −0.61, respectively). The optimal cut-off values for diagnosis of neoplastic fracture were SI norm of 3.0 in DW-SSFP with the sensitivity and specificity of 90.4% (95% confidence interval [CI]: 81.0–99.0) and 95.3% (95% CI: 90.0–100.0), respectively, and ADC of 1.3 in DW-EPI with the sensitivity and specificity of 90.5% (95% CI: 80.0–100.0) and 70.4% (95% CI: 60.0–80.0), respectively. CONCLUSION: In 3-T MRI, DW-SSFP has comparable sensitivity and specificity to DW-EPI in differentiating the neoplastic vertebral fracture from the benign osteoporotic vertebral fracture.
Bone Marrow ; Diagnosis ; Diagnosis, Differential* ; Diffusion ; Diffusion Magnetic Resonance Imaging ; Drug Therapy ; Echo-Planar Imaging* ; Fractures, Compression* ; Fractures, Spontaneous ; Humans ; Linear Models ; Magnetic Resonance Imaging ; Osteoporotic Fractures ; ROC Curve ; Sensitivity and Specificity ; Spine ; Vertebroplasty

Simple methods for measuring the levels of serum antibody against canine distemper virus (CDV) would assist in the effective vaccination of dogs. To develop an enzyme-linked immunosorbent assay (ELISA) specific for CDV, we expressed hydrophilic extra-viral domain (HEVD) protein of the A75/17-CDV H gene in a pET 28a plasmid-based Escherichia (E.) coli vector system. Expression was confirmed by dot and Western blotting. We proposed that detection of E. coli-expressed H protein might be conformation-dependent because intensities of the reactions observed with these two methods varied. The H gene HEVD protein was further purified and used as an antigen for an ELISA. Samples from dogs with undetectable to high anti-CDV antibody titers were analyzed using this HEVD-specific ELISA and a commercial CDV antibody detection kit (ImmunoComb). Levels of HEVD antigenicity measured with the assays and immunochromatography correlated. These data indicated that the HEDV protein may be used as antigen to develop techniques for detecting antibodies against CDV.
Animals ; Antigens, Viral/*diagnostic use ; Distemper/diagnosis/*virology ; Distemper Virus, Canine/*immunology ; Dog Diseases/*diagnosis/virology ; Dogs ; Enzyme-Linked Immunosorbent Assay/*veterinary ; Escherichia coli/genetics ; Genetic Vectors/genetics ; Hemagglutinins, Viral/*diagnostic use

Mitochondrial protein Nfu1 plays an important role in the assembly of mitochondrial Fe-S clusters and intracellular iron homeostasis in the model yeast Saccharomyces cerevisiae. In this study, we identified the Nfu1 ortholog in the human fungal pathogen Cryptococcus neoformans. Our data showed that C. neoformans Nfu1 localized in the mitochondria and influenced homeostasis of essential metals such as iron, copper and manganese. Marked growth defects were observed in the mutant lacking NFU1, which suggests a critical role of Nfu1 in Fe-S cluster biosynthesis and intracellular metal homeostasis in C. neoformans.
Copper ; Cryptococcus neoformans* ; Homeostasis* ; Humans ; Iron ; Manganese ; Metals* ; Mitochondria ; Mitochondrial Proteins* ; Saccharomyces cerevisiae ; Yeasts

BACKGROUND: Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the gamma2 subunit affects the GABA current when applying sevoflurane and midazolam. METHODS: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with alpha1beta2gamma2L or alpha1beta2gamma2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 microM of GABA. RESULTS: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the alpha1beta2gamma2L and alpha1beta2gamma2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the alpha1beta2gamma2S subtype, but not for the alpha1beta2gamma2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes. CONCLUSIONS: These results show that the difference in the gamma2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the gamma2 subunit and the concentration of both drugs.
Alternative Splicing ; Anesthesia ; Child ; Dihydroergotamine ; gamma-Aminobutyric Acid ; Humans ; Kidney ; Methyl Ethers ; Midazolam