Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Background and Objectives@#O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung.Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. @*Methods@#and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P ), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. @*Conclusions@#Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

Clinical Implication of Maumgyeol Basic Service–the 2 Channel Electroencephalography and a Photoplethysmogram–based Mental Health Evaluation Software

Objective@#Maumgyeol Basic service is a mental health evaluation and grade scoring software using the 2 channels EEG and photoplethysmogram (PPG). This service is supposed to assess potential at-risk groups with mental illness more easily, rapidly, and reliably. This study aimed to evaluate the clinical implication of the Maumgyeol Basic service. @*Methods@#One hundred one healthy controls and 103 patients with a psychiatric disorder were recruited. Psychological evaluation (Mental Health Screening for Depressive Disorders [MHS-D], Mental Health Screening for Anxiety Disorders [MHS-A], cognitive stress response scale [CSRS], 12-item General Health Questionnaire [GHQ-12], Clinical Global Impression [CGI]) and digit symbol substitution test (DSST) were applied to all participants. Maumgyeol brain health score and Maumgyeol mind health score were calculated from 2 channel frontal EEG and PPG, respectively. @*Results@#Participants were divided into three groups: Maumgyeol Risky, Maumgyeol Good, and Maumgyeol Usual. The Maumgyeol mind health scores, but not brain health scores, were significantly lower in the patients group compared to healthy controls. Maumgyeol Risky group showed significantly lower psychological and cognitive ability evaluation scores than Maumgyeol Usual and Good groups. Maumgyel brain health score showed significant correlations with CSRS and DSST. Maumgyeol mind health score showed significant correlations with CGI and DSST. About 20.6% of individuals were classified as the No Insight group, who had mental health problems but were unaware of their illnesses. @*Conclusion@#This study suggests that the Maumgyeol Basic service can provide important clinical information about mental health and be used as a meaningful digital mental healthcare monitoring solution to prevent symptom aggravation.

Reduced receptor for advanced glycation end products is associated with α-SMA expression in patients with idiopathic pulmonary fibrosis and mice / 한국실험동물학회지

Background@#Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Despite alveolar epithelial cells is crucial role in lung, its contribution and the associated biomarker remain unknown in the pathogenesis of IPF. Recently, environmental factors including stone dust, silica and cigarette smoking were found as risk factors involved in IPF. Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface receptors. It has been shown that interaction between RAGE and its ligands on immune cells mediates cellular migration and regulation of pro-inflammation. RAGE is highly expressed in the lung, in particular, alveolar epithelial cells. Therefore, we determined whether RAGE expression is associated with fibrosis-associated genes in patients with IPF and mice. @*Results@#When bleomycin (BLM) was intratracheally administered to C57BL/6 mice for 1, 2 weeks, macrophage and neutrophils were significantly increased. The fibrotic nodule formed and accumulation of collagen was determined after BLM injection in H&E- and Masson’s trichrome staining. Levels of elastin, Col1a1 and fibronectin were increased in quantitative real-time PCR and protein levels of α-SMA was increased in western blot analysis. In the lung tissues of 1 mg/kg BLM-induced mice, RAGE expression was gradually decreased in 1- and 2 weeks in immunohistochemistry and western blot analysis, and 3 mg/kg of BLM-induced mice exhibited decreased RAGE levels while α-SMA expression was increased. We next determined RAGE expression in the lungs of IPF patients using immunohistochemistry.As a result, RAGE expression was decreased, while α-SMA expression was increased compared with non-IPF subjects. @*Conclusions@#Our findings suggest that reduced RAGE was associated with increased fibrotic genes in BLM-induced mice and patients with IPF. Therefore, RAGE could be applied with a biomarker for prognosis and diagnosis in the pathogenesis of IPF.

Interactions between NCR + ILC3s and the Microbiome in the Airways Shape Asthma Severity

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR) + ILC3s in the lung.Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR + ILC3 frequencies and microbial diversity in the lung. Sputum NCR + ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR + ILC3s may contribute to a healthy commensal diversity and normal lung function.

Effect of the hedgehog signaling pathway on hair formation-related cells

Alopecia has emerged as one of the biggest interests in modern society. Many studies have focused on the treatment of alopecia, such as transplantation of hair follicles or inhibition of the androgen pathway. Hair growth is achieved through proper proliferation of the components such as keratinocytes and dermal papilla cells (DPCs), movement, and interaction between the two cells. The present study examined the effect of the hedgehog (Hh) signaling pathway, which is an important and fundamental signal in the cell, on the morphology and the viability of human keratinocytes and DPCs. Upregulation of Hh signaling caused a morphological change and an increase in epithelium-mesenchymal transition-related gene expression but reduced the viability of keratinocytes, while the alteration of Hh signaling did not cause any change in DPCs. The results show the possibility that the regulation of Hh signaling can be applied for the treatment of alopecia.

Association between Metabotropic Glutamate Receptor 1 Polymorphism and Cardiovascular Disease in Korean Adults

OBJECTIVE: The mGluR1 (metabotropic glutamate receptor 1) gene, a G protein–coupled receptor, is known to mediate perceptions of umami tastes. Genetic variation in taste receptors may influence dietary intake, and in turn have an impact on nutritional status and risk of chronic disease. We investigated the association of mGluR1 rs2814863 polymorphism with lipid profiles and cardiovascular disease (CVD) risk, together with their modulation by macronutrient intake in Korean adults. METHODS: The subjects consisted of 8,380 Koreans aged 40-69 years participating in the Anseong and Ansan Cohort Study, which was a part of the Korean Genome Epidemiology Study (KoGES). Data was collected using self-administered questionnaires, anthropometric measurements, and blood chemical analysis. RESULTS: Carriers of C allele at mGluR1 rs2814863 was associated with decreased high density lipoprotein cholesterol (HDL-C) and increased triglyceride as compared to carriers of TT. Also, carriers of the C allele showed higher fat intake and lower carbohydrate intake than those with carriers of TT. After adjustment for multiple testing using false-discovery rate method, the significant difference of HDL-C, triglyceride, dietary fat, and carbohydrate across genotypes disappeared. Gene-diet interaction effects between rs2814863 and macronutrients intake were not significantly associated with HDL-C and triglyceride levels. However, carriers of C allele demonstrated significantly higher odds of CVD {odds ratio=1.13, 95% CI=1.02-1.25} compared with carriers of TT. CONCLUSIONS: Our findings support significant associations between the mGluR1 rs2814863 genotype and CVD-related variables in Korean adults. However, these associations are not modified by macronutrient intake.

Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature

Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery.

Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature

Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery.

Neuropathic Arthropathy of the Shoulder Associated with Cervical Syringomyelia: A Case Report

Neuropathic shoulder arthropathy or Charcot's shoulder is an extremely rare disease, and sometimes it is associated with cervical syringomyelia. Clinical symptoms of the disease include edema of the shoulder and restriction in range of motion. Radiological diagnosis can be made through plain radiography through a characteristic, atrophic destruction of the joint. We experienced a Charcot's joint of the shoulder wherein destruction of the joint progressed extremely quickly and reviewed the literature concerning this condition.

Neuropathic Arthropathy of the Shoulder Associated with Cervical Syringomyelia: A Case Report

Neuropathic shoulder arthropathy or Charcot's shoulder is an extremely rare disease, and sometimes it is associated with cervical syringomyelia. Clinical symptoms of the disease include edema of the shoulder and restriction in range of motion. Radiological diagnosis can be made through plain radiography through a characteristic, atrophic destruction of the joint. We experienced a Charcot's joint of the shoulder wherein destruction of the joint progressed extremely quickly and reviewed the literature concerning this condition.

Faculty Observer and Standardized Patient Accuracy in Recording Examinees' Behaviors Using Checklists in the Clinical Performance Examination / 한국의학교육

PURPOSE: The purpose of the study was to examine the recording accuracy of faculty observers and standardized patients (SPs) on a clinical performance examination (CPX). METHODS: This was a cross-sectional study of a fourth-year medical students' CPX that was held at a medical school in Seoul, Korea. The CPX consisted of 4 cases and was administered to 118 examinees, with the participation of 52 SP and 45 faculty observers. For the study we chose 15 examinees per case, and analyzed 60 student-SP encounters in total. To determine the recording accuracy level, 2 SP trainers developed an answer key for each encounter. First, we computed agreement rates (P) and kappa coefficient (K) values between the answer key-SPs and the answer key-faculty observers. Secondly, we analyzed variance (ANOVA) with repeated measures to determine whether the mean percentage of the correct checklist score differed as a function of the rater, the case, or the interaction between both factors. RESULTS: Mean P rates ranged from 0.72 to 0.86, while mean K values varied from 0.39 to 0.59. The SP checklist accuracy was higher than that of faculty observersat the level of item comparison. Results from ANOVA showed that there was no significant difference between the percentage of correct scores by the answer key, faculty observers and SPs. There was no significant interaction between rater and case factors. CONCLUSION: Acceptable levels of recording accuracy were obtained in both rater groups. SP raters can replace faculty raters in a large-scale CPX with thorough preparation.

Development and Validation of a Questionnaire to Evaluate Medical Students' Evidence-Based Medicine Competencies / 한국의학교육

PURPOSE: The purpose of the study was to develop and validate a questionnaire to evaluate medical students' knowledge of, attitude towards and practice of evidence-based medicine (EBM). METHODS: The participants of the study were 418 medical students enrolled in the Kyung Hee University School of Medicine in Seoul, Korea. To examine construct validity of the questionnaire, an exploratory factor analysis (EFA) was performed with 118 participants; a confirmatory factor analysis (CFA) was conducted with the remaining 281 participants. We developed 41 items with a 4-point Likert scale. An EFA was performed to verify the emergence of four dimensions of EBM competencies. The principal axis factoring method and the direct oblimin rotation method were used. To confirm construct validity, a CFA was conducted with the remaining 281 participants. To evaluate model fitness, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used as fit indices. We conducted ANOVA with Scheffe as discriminant validation, and calculated Cronbach's alpha of 4 subscales as reliability checkup. RESULTS: After refinement procedure, factor analysis of the 32 items in therevised questionnaire yielded 4 factors. The Scree plot supported a 4 factor solution explaining 53.5% of the variance. The 4 components derived were: factor 1_knowledge on EBM (11 items; Cronbach's alpha=0.92); factor 2_ pursuit towards EBM (10; 0.88); factor 3_reluctance on EBM (7; 0.78); factor 4_practice of EBM (4; 0.75). The questionnaire could discriminate competence differences among 1-3 yr students. Satisfactory Cronbach's alpha scores were noted for each factor as well. CONCLUSION: The EBM competency questionnaire was validated.

Development and Validation of a Questionnaire to Evaluate Medical Students' Evidence-Based Medicine Competencies / 한국의학교육

PURPOSE: The purpose of the study was to develop and validate a questionnaire to evaluate medical students' knowledge of, attitude towards and practice of evidence-based medicine (EBM). METHODS: The participants of the study were 418 medical students enrolled in the Kyung Hee University School of Medicine in Seoul, Korea. To examine construct validity of the questionnaire, an exploratory factor analysis (EFA) was performed with 118 participants; a confirmatory factor analysis (CFA) was conducted with the remaining 281 participants. We developed 41 items with a 4-point Likert scale. An EFA was performed to verify the emergence of four dimensions of EBM competencies. The principal axis factoring method and the direct oblimin rotation method were used. To confirm construct validity, a CFA was conducted with the remaining 281 participants. To evaluate model fitness, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used as fit indices. We conducted ANOVA with Scheffe as discriminant validation, and calculated Cronbach's alpha of 4 subscales as reliability checkup. RESULTS: After refinement procedure, factor analysis of the 32 items in therevised questionnaire yielded 4 factors. The Scree plot supported a 4 factor solution explaining 53.5% of the variance. The 4 components derived were: factor 1_knowledge on EBM (11 items; Cronbach's alpha=0.92); factor 2_ pursuit towards EBM (10; 0.88); factor 3_reluctance on EBM (7; 0.78); factor 4_practice of EBM (4; 0.75). The questionnaire could discriminate competence differences among 1-3 yr students. Satisfactory Cronbach's alpha scores were noted for each factor as well. CONCLUSION: The EBM competency questionnaire was validated.

Inter-rater Reliability in a Clinical Performance Examination Using Multiple Standardized Patients for the Same Case / 한국의학교육

PURPOSE: The "standardization" of standardized patients (SP) is one of the most crucial factors for a successful clinical performance examination (CPX). This study aimed to examine the inter-rater reliability among SPs who portrayed the same case during a CPX. METHODS: The context was a CPX conducted under the supervision of CPX Seoul-Gyeonggi Consortium in K medical school in August 2007. K medical school ran 12 stations consisting of duplicated sets of 6 cases. In total, thirty SPs participated with 5 SPs acting each of the 6 cases. The SPs evaluated the student's performances in addition to portraying the cases. ANCOVA (analysis of covariance) was used to compare scores rated by the different SPs. The dependent variables were the case scores and the 4 subcomponent (history taking, physical examination, Clinical courtesy, and Patient-physician interaction) scores for each case; the independent variable was the SPs; and the covariate was the CPX total score. RESULTS: The Headache and Cough stations showed an acceptable level of reliability. Otherwise, Weight Loss and Facial Flushing failed to show consistent scores in all 4 subcomponents. Diarrhea and Lt. hemiparesis showed partial consistency. In terms of the subcomponents, the physical exam scores were most consistent and the patient-physician interaction scores were most inconsistent. CONCLUSION: This study tested the level of "standardization" of one set of CPX cases with mixed results. The authors hope that our results will contribute to quality assurance of CPX.

Medical Students' Attitudes Toward the Patient-Doctor Relationship / 한국의학교육

PURPOSE: This study investigated the attitudes of medical students toward physicians and the roles which the doctors and patients should play in the health care process. METHODS: Attitudes toward the patient-doctor relationship of 436 medical students of the K university in Seoul were measured using the Patient-Practitioner Orientation Scale(PPOS), a validated instruments designed to measure individual preferences toward various aspects of the patient-doctor relationship. The PPOS was composed of Sharing(sharing information, take part in decision making) and Caring(respect one's feelings, interpersonal relationship) subscale. Total PPOS scores can range from patient-centered(egalitarian, whole person oriented) to disease- or doctor-centered(paternalistic, less attuned to psychosocial issues). Socio-demographic data including gender, age, school year, marital status, undergraduate major, student's and her/his family medical background and specialty choice were collected and it was investigated the possible impact of socio-demographic factors on students' attitudes. RESULTS: The PPOS score was 3.82. The Sharing and Caring scores were 3.74 and 3.90, respectively. Female gender and students of graduate entry program were significantly associated with patient-centered attitudes. Age, school year, marital status, academic background, student's and her/his family medical background, and specialty choice did not show significant associations with PPOS scores. CONCLUSION: Female and graduate students showed more patient-centered attitudes than male and undergraduate students, respectively. Given the emphasis placed on patient-centered care in the current medical environment, our results suggest further research to explore the dynamics in medical education that may foster or inhibit student attitudes toward patient-centered care.

The Effects of Coping Style on Subjective Well-Being Among Medical Students / 한국의학교육

PURPOSE: This study aims to explore which coping strategies medical students use more often, and how coping styles account for medical students' subjective well-being. METHODS: Subjects included 249 medical students from undergraduate and Graduate Entry Programme of a medical school in Seoul, Korea. Coping style was measured using the Ways of Coping Checklist. Subjective well-being was measured with Positive/Negative Affect Scale and Satisfaction with Life Scale. Analysis of Variance(ANOVA) was used to compare four coping strategies, and stepwise multiple regression was used to analyze the accountability of each of the coping strategy for subjective well-being. RESULTS: Medical students used avoidance and problem-focused coping strategy more often than they used emotion-focused coping strategy and seeking social support. Graduate Entry Programme students used avoidance less often and seeking social support more often than undergraduate students. Among subscales of subjective well-being, positive affect can be accounted for by problem-focused coping and seeking social support, and negative affect can be accounted for by problem-focused coping and avoidance. Life satisfaction can be accounted for by problem-focused coping as well. CONCLUSION: The results of this study showed that medical students had high adaptability as well as strong anxiety toward stressful situations in medical school. Moreover, three among the four coping strategies accounted for medical students' subjective well-being. These findings should be considered as a baseline for future research looking into additional variables affecting medical students' well-being.

Hemodynamics of Milrinone and Low-Dose Vasopressin Infusion during OPCAB / 대한마취과학회지

BACKGROUND: AVP (arginine vasopressin) shows unique hemodynamic characteristics, as a vasopressor. AVP has been tried in many cathecholamine refractory vasodilatory situations, and sometimes resulted in effective hemodynamic improvement. In this study, we hypothesized that low dose AVP infusion could recover the decreased SVR (systemic vascular resistance) induced by milrinone infusion with minimal effect on PVR (pulmonary vascular resistance). METHODS: Sixteen patients undergoing OPCAB participated in this study. After a loading dose milrinone was infused, low dose vasopressin infusion was started and titrated until the systemic blood pressure increased by 20%. During the study, hemodynamic factors including pulmonary capillary wedge pressure and cardiac output were measured using a continuous thermodilution technique with a Swan-Ganz catheter. RESULTS: Milrinone infusion reduced both SVR and PVR. And vasopression infusion increased SVR, but show relatively less effect on PVR. CONCLUSIONS: Low-dose vasopressin infusion could be used to recover the SVR decrease caused by milirinone infusion with little effect on PVR.