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Gender-independent efficacy of mesenchymal stem cell therapy in sex hormone-deficient bone loss via immunosuppression and resident stem cell recovery

  • Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.12.1-12.14
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    • 2018
  • Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

Differences in Clinical Characteristics of Invasive Tracheobronchial Aspergillosis according to the Presence of Invasive Pulmonary Aspergillosis

  • Pak, Chuiyong;Jo, Woori;Kim, Jin Hyoung;Im, Jae Uk;Jeong, Joseph;Cha, Hee Jeong;Choi, Eun-Young;Ra, Seung Won
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.4
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    • pp.326-332
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    • 2021
  • Background: The association of invasive tracheobronchial aspergillosis (ITBA) with invasive pulmonary aspergillosis (IPA) is not well established. We aimed to compare clinical characteristics between patients who exhibited ITBA with IPA and those who exhibited isolated ITBA (iITBA). Additionally, the usefulness of serum or bronchial galactomannan (GM) tests in diagnosing ITBA was evaluated. Methods: This retrospective single-center case-control study was conducted over a period of 4 years. Fifteen patients were enrolled after confirming the presence of ITBA using bronchoscopy-guided biopsy (iITBA, 7 vs. ITBA+IPA, 8). Clinical characteristics of patients and results obtained from serum or bronchial GM tests were compared between the two groups. Mortality was assessed using data collected from a 6-month follow-up period. Results: The ITBA+IPA group showed a higher prevalence of hematologic malignancy (75% vs. 14%, p=0.029), a greater number of patients with multiple bronchial ulcers (75% vs. 14%, p=0.029), lower platelet counts (63,000/μL vs. 229,000/μL, p<0.001), and a mortality rate which was significantly higher (63% vs. 0%, p=0.026) than the iITBA group. In the ITBA+IPA group, 57% of patients tested positive according to the serum GM assay, whereas in the iITBA group, all patients tested negative (p=0.070). The bronchial GM level was high in both groups, but there was no significant difference between them. Conclusion: Patients with ITBA+IPA had a greater number of hematologic malignancies with lower platelet counts and a poorer prognosis than patients diagnosed with iITBA. Findings obtained from bronchoscopy and bronchial GM tests were more useful in diagnosing ITBA than the serum GM test results.

Characteristics, Management, and Clinical Outcomes of Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: A Multicenter Cohort Study in Korea

  • Ko, Ryoung-Eun;Min, Kyung Hoon;Hong, Sang-Bum;Baek, Ae-Rin;Lee, Hyun-Kyung;Cho, Woo Hyun;Kim, Changhwan;Chang, Youjin;Lee, Sung-Soon;Oh, Jee Youn;Lee, Heung Bum;Bae, Soohyun;Moon, Jae Young;Yoo, Kwang Ha;Jeon, Kyeongman
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.4
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    • pp.317-325
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    • 2021
  • Background: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are significant public health issues in the world, but the epidemiological data pertaining to HAP/VAP is limited in Korea. The objective of this study was to investigate the characteristics, management, and clinical outcomes of HAP/VAP in Korea. Methods: This study is a multicenter retrospective cohort study. In total, 206,372 adult patients, who were hospitalized at one of the 13 participating tertiary hospitals in Korea, were screened for eligibility during the six-month study period. Among them, we included patients who were diagnosed with HAP/VAP based on the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) definition for HAP/VAP. Results: Using the IDSA/ATS diagnostic criteria, 526 patients were identified as HAP/VAP patients. Among them, 27.9% were diagnosed at the intensive care unit (ICU). The cohort of patients had a median age of 71.0 (range from 62.0 to 79.0) years. Most of the patients had a high risk of aspiration (63.3%). The pathogen involved was identified in 211 patients (40.1%). Furthermore, multidrug resistant (MDR) pathogens were isolated in 138 patients; the most common MDR pathogen was Acinetobacter baumannii. During hospitalization, 107 patients with HAP (28.2%) had to be admitted to the ICU for additional care. The hospital mortality rate was 28.1% in the cohort of this study. Among the 378 patients who survived, 54.2% were discharged and sent back home, while 45.8% were transferred to other hospitals or facilities. Conclusion: This study found that the prevalence of HAP/VAP in adult hospitalized patients in Korea was 2.54/1,000 patients. In tertiary hospitals in Korea, patients with HAP/VAP were elderly and had a risk of aspiration, so they were often referred to step-down centers.

Clinical Characteristics of NSSI and Predictors of Suicide Attempts in Clinically Depressed Korean Adolescents (일 대학병원에 방문한 우울한 청소년에서 비자살성 자해행동의 임상적 특성과 자살 시도 예측요인)

  • Kim, Gyung-Mee
    • Korean Journal of Psychosomatic Medicine
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    • v.27 no.1
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    • pp.69-76
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    • 2019
  • Objectives : The purpose of this study was to examine the prevalence and clinical characteristics of nonsuicidal self-injury (NSSI), and its association with suicide attempts among clinically depressed adolescents in Korea. Methods : In total, 113 depressed adolescents aged 12-18 years in South Korea were enrolled in this study. We assessed sociodemographic and clinical characteristics including suicidality and non-suicidal self-injury (NSSI) using various self-reported scales and semi-structured interview for diagnosis of psychiatric disorders. Demographic and clinical characteristics of the subjects were compared between NSSI and non-NSSI groups. We examined significant predictors of suicide attempts using logistic regression analysis. Results : Among 113 depressed participants, 48 (42.1%) adolescents were classified into the NSSI group. In the NSSI group, there were significantly more females, showed higher depression, higher state-anxiety, and more suicide ideation. The most predictive factors of suicide attempts were history of NSSI, observed suicide/NSSI behaviors of their family or friends, and total state anxiety score. Conclusions : NSSI is more common problem among clinically depressed adolescents and history of NSSI is a significant predictor of present suicide attempts. To include the assessment of NSSI for clinically depressed adolescent may be crucial for intervention programs for high risk adolescents of suicide in Korea.

Molecular Analysis of Carbapenem-Resistant Pseudomonas aeruginosa Isolated from Patients Hospitalized in Daejeon between 2008 and 2014 Years (대전지역의 입원환자에서 분리된 Carbapenem 내성 Pseudomonas aeruginosa의 분자역학조사(2008년에서 2014년까지))

  • Cho, Hye Hyun
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.406-413
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    • 2018
  • The emergence of carbapenem resistance among Pseudomonas aeruginosa has become an increasing problem worldwide. In particular, $metallo-{\beta}-lactamases$ (MBLs) are responsible for the high-level resistance to carbapenem. Sequence type 235 (ST235) has been found internationally in a multidrug-resistant clone and is involved in the dissemination of genes encoding IMP-6 and VIM-2. This study examined the prevalence of MBLs and the epidemiological relationship in carbapenem-resistant P. aeruginosa (CRPA) isolates obtained from a tertiary hospital in Daejeon, Korea, between March 2008 and June 2014. The antimicrobial susceptibilities were determined using the disk-diffusion method and PCR and DNA sequencing were used to identify the MBL genes. In addition, an epidemiological relationship was investigated by multilocus sequence typing (MLST). Among the 110 CRPA isolates, 32 isolates (29.1%) were MBL-producers; the major type was IMP-6 (29 isolates, 90.6%). VIM-2 was identified in 3 isolates (9.4%) of ST357. IMP-6-producing isolates were multidrug-resistant (MDR) and belonged to ST235. ST235 (55 isolates, 50.0%) was the clone most frequently detected and has gradually emerged during a seven-year period. To prevent the spread of MDR ST235 P. aeruginosa isolates, the current widespread use of carbapenems needs to be curtailed, and novel continuous monitoring strategies should be developed as soon as possible.

Association Between Airborne Pollen Counts and Sensitization Rate in Elementary School Children in Ulsan (울산지역 초등학교 학생에서 대기중 꽃가루 비산 수준과 흡입 알레르겐 감작률과의 관련성)

  • Oh, Yeonsuh;Choi, Seung Won;Oh, Inbo;Lee, Jiho;Sim, Chang Sun;Bang, Jin-Hee;Kim, Yangho
    • Journal of Environmental Health Sciences
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    • v.46 no.6
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    • pp.735-749
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    • 2020
  • Objectives: The aim of this study was to investigate airborne pollen counts, inhalant allergen sensitization rate, and allergic disease prevalence among elementary school children in Ulsan, South Korea during 2012-2018. Methods: Burkard samplers for pollen were installed on rooftops in suburban and urban areas in Ulsan. A 24-hour sampling of airborne allergens was conducted six days/week from January 1, 2013 to November 31, 2018. Skin prick tests were done with a total of 4,246 primary school students residing in urban and suburban areas in 2012, 2014, 2016, and 2018. This study examined sensitization to 20 major inhalant allergens. Results: The highest monthly counts of airborne pollen were observed in April and September each year. Among the pollen identified over the six years, pine showed the highest pollen counts (44.3%), followed by oak (22.3%), alder (6.3%) and Japanese hops (4.3%). Tree pollen predominated from March to June, and weed pollen predominated from August to October. Higher sensitization rates for inhalant allergens were observed in Dermatophagoides farinae (42.4%), Dermatophagoides pteronyssinus (43.6%), cat fur (12.1%), birch (9.9%), oak (9.6%), and alder (8.7%). The inhalant allergen sensitization rate was highest in the group with comorbidity (asthma and/or rhinitis and atopic dermatitis), and respiratory allergic disease (asthma and/or rhinitis) was higher than that of atopic dermatitis. Conclusion: Both the counts of tree pollen in the air and the sensitization rate for tree pollen were high in Ulsan. The temporal change in respiratory allergic diseases was similar to that for the sensitization rate of tree pollen, such as oak. In the future, it is considered that additional continuous research on various inhalant allergens and pollen should be conducted.

Efficacy and Safety of Daclatasvir and Asunaprevir Combination Therapy in Elderly Chronic Hepatitis C Patients (고령의 만성 C형 간염 환자에서 Daclatasvir와 Asunaprevir 병용 요법의 유효성 및 안전성 평가)

  • Park, You Kyung;Shin, Su Jin;Choi, You Ock;Choi, Hye Jung;Kang, Jin Suk;Hwangbo, Shin-Yi
    • Journal of Korean Society of Health-System Pharmacists
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    • v.35 no.4
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    • pp.453-462
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    • 2018
  • Background : The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly. Pegylated interferon and ribavirin therapy (Peg-IFN/RBV) was recommended as the first-line treatment in the past decades, but this regimen showed unsatisfactory results in terms of safety and efficacy especially in elderly patients. Recently, it was demonstrated that dual therapy with daclatasvir and asunaprevir was well tolerated and led to high sustained virological response (SVR) rates, irrespective of age. We conducted a study to evaluate the efficacy and safety of daclatasvir plus asunaprevir by involving elderly patients aged above 65 years. Methods : We retrospectively analyzed clinical data from chronic hepatitis C virus (HCV) genotype 1b patients treated with daclatasvir plus asunaprevir from September 2015 to December 2016 at Seoul St. Mary's hospital. The patients were divided into two groups as elderly patients (older than 65 years) and non-elderly patients (younger than 65 years) and compared the efficacy and safety. Results : A total of 112 patients were treated with daclatasvir plus asunaprevir for chronic hepatitis C. Among them, 101 patients completed the whole treatment, and in 88 patients the amount of HCV RNA was measured after 12 weeks of treatment. There was no significant difference in SVR at 12 weeks between both the groups (p=0.68). Typically, 91.4%(32/35) of elderly patients and 94.3%(50/53) of non-elderly patients achieved SVR12. Common adverse events included elevation in transaminase level, headache, and gastrointestinal disorders. There was no statistical difference in the symptoms between the two groups. Conclusions : The combination therapy with daclatasvir plus asunaprevir exhibited similar rates of SVR12 in HCV elderly patients without leading to further adverse events compared to non-elderly patients. Therefore, it is proposed that daclatasvir plus asunaprevir therapy could be considered as an effective and safe treatment, even in patients aged over 65 years.

The Association between Regular Physical Activity Types And Metabolic Syndrome in Fertile Women (가임기 여성의 규칙적 운동 및 운동종류에 따른 대사증후군 간의 관련성)

  • Lee, Guna
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.1
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    • pp.94-103
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    • 2021
  • The purpose of this study was to identify the association between regular physical activity (PA) types and metabolic syndrome (MetS) in fertile women. Data were obtained from the seventh Korea National Health and Nutrition Examination Survey (KNHANES VII-3, 2018). The sample consisted of 4,172 fertile women over 19 years of age. The data were analyzed using an independent t-test, χ2 test, and multiple logistic regression analysis for examining the association of regular PA and MetS. The prevalence of MetS in fertile women was 3.1% (n =128), and 1,972 fertile women (47.2%) practiced regular PA. Compared to the non-regular PA group, regular PA resulted in a significantly lower systolic blood pressure (p =.002), lower waist circumference (p <.001), lower fasting blood sugar (p =.007), and higher high-density lipoprotein cholesterol (p <.001). After controlling the confounding variables, multiple logistic regression showed that the regular PA group (odds ratio 0.59, 95% confidence interval 0.35-0.98, p =.040) and the regular muscle-strengthen PA group (odds ratio 0.34, 95% confidence interval 0.14-0.80, p =.013) were associated with a decreased risk of MetS. Therefore, regular PA, including muscle-strengthen PA should be considered to develop effective MetS intervention in fertile women.

Factors Associated with the Use of Medical Care at Hospitals among Outpatients with Hypertension: A Study of the Korea Health Panel Study Dataset (2010-2016) (우리나라 고혈압 환자의 병원급 의료기관 외래이용 관련 요인: 한국의료패널자료(2010-2016)를 이용하여)

  • Lee, Sumi;Park, Sohee;Kimm, Heejin;Lee, Yongjae;Chung, Woojin
    • Health Policy and Management
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    • v.30 no.4
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    • pp.479-492
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    • 2020
  • Background: As the prevalence of hypertension is increasing in Korea, the government is seeking policy actions to manage patients with hypertension more efficiently. In this paper, we aimed to identify factors associated with the use of medical care at hospitals among outpatients with hypertension. Methods: We analyzed a total of 15,040 cases of 3,877 outpatients with hypertension obtained from the Korea Medical Panel database from 2010 to 2016. The dependent variable was whether a patient with hypertension visited a hospital or not; and independent variables were the patient's various socio-demographic, health-related, and heath-status characteristics. We conducted a generalized linear mixed model analysis with logit link for all the cases and then conducted it stratified by gender. Results: As a result of a multivariable analysis, women were less likely than to visit at a hospital (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.32-0.61) and people aged 65 years and older than those aged less than 65 years (OR, 0.71; 95% CI, 0.57-0.89). Residents in Busan, Ulsan, and Gyeongnam were more likely than those in than Seoul, Gyeonggi, Incheon, and Jeju to visit a hospital (OR, 1.40; 95% CI, 1.05-1.86). The likelihood of visiting a hospital was high in people belonging to a group of: the highest level of annual household income (OR, 1.73; 95% CI, 1.30-2.29); Medical care aid recipients (OR, 1.94; 95% CI, 1.34-2.83); people having three or more complex chronic diseases (OR, 1.59; 95% CI, 1.19-2.11); people having diabetes (OR, 1.81; 95% CI, 1.41-2.32); or people having ischemic heart disease or cerebrovascular disease (OR, 6.80; 95% CI, 5.28-8.76). Also, we found that factors associated with the use of medical care at hospitals among outpatients with hypertension differed between genders. Conclusion: A variety of factors seem to be associated with the use of medical care at hospitals among outpatients with hypertension. Future research needs to find a way to help patients with hypertension visit an appropriate medical institution between clinics and hospitals.

Prevalence of JAK2 V617F, CALR, and MPL W515L Gene Mutations in Patients with Essential Thrombocythemia in Kurdistan Region of Iraq

  • Saeed, Bestoon Muhammad;Getta, Hisham Arif;Khoshnaw, Najmaddin;Abdulqader, Goran;Abdulqader, Aveen M. Raouf;Mohammed, Ali Ibrahim
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.1
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    • pp.41-48
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    • 2021
  • Essential thrombocythemia (ET) is a clonal bone marrow stem cell disorder, primarily involving the megakaryocytic lineage. The WHO 2016 guidelines include the molecular detection of JAK2, MPL, and CALR mutations as a major diagnostic criterion for ET. This study aimed to determine the frequency of JAK2 V617F, MPL W515L, and CALR mutations in Iraqi Kurdish patients afflicted with ET, and to analyze their clinical and hematological features. A total of 73 Iraqi Kurdish patients with ET were enrolled as subjects, and analysis was achieved utilizing real-time PCR. The frequency of JAK2 V617F, CALR, and MPL W515L mutations was determined to be 50.7%, 22%, and 16.4%, respectively. No statistically significant difference was obtained when considering the age and gender among different genotypes. The JAK2 V617F mutated patients had significantly higher white blood cell counts and hemoglobin levels than the CALR-positive patients (P-value=0.000, 0.007, respectively), MPL W515L-positive patients (P-value=0.000, 0.000, respectively), and triple negative patients (P-value=0.000, 0.000, respectively). Also, the JAK2 V617F mutated patients showed higher platelet count as compared to the MPL W515L-positive patients (P-value=0.02) and triple negative patients (P-value=0.04). Furthermore, significantly lower white blood cell count and hemoglobin levels were associated with CALR positivity (P-value=0.000, 0.01, respectively), MPL W515L-positivity (P-value=0.001, 0.000, respectively), and triple negativity (P-value=0.000, 0.000, respectively), as compared to patients with combined mutations. In conclusion, apart from a relatively high frequency of MPL W515L mutation, our data is comparable to earlier reports, and highlights the importance of genotyping the JAK2 V617F, MPL W515L, and CALR mutations for accurate diagnosis of patients with ET.