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Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.
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BACKGROUND/OBJECTIVES@#The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage.MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/ kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. @*RESULTS@#ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. @*CONCLUSIONS@#Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.
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BACKGROUND/OBJECTIVES@#Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism.Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells.MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry.Mitochondrial reactive oxygen species generation was measured using the 2′7′-dichlorofluorescein diacetate assay. @*RESULTS@#GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolismregulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domaincontaining 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2/i>. @*CONCLUSIONS@#The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.
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Background@#We analyzed the International Classification of Diseases, 10th edition (ICD-10) diagnostic codes, procedure codes, and radiographic image codes for vertebral fracture (VF) used in the database of Health Insurance Review and Assessment Service (HIRA) of Korea to establish a validated operational definition for identifying patients with osteoporotic VF in claims data. @*Methods@#We developed three operational definitions for detecting VFs using 9 diagnostic codes, 5 procedure codes and 4 imaging codes. Medical records and radiographs of 2,819 patients, who had primary and subordinated codes of VF between January 2016 and December 2016 at two institutions, were reviewed to detect true vertebral fractures. We evaluated the sensitivity and positive predictive value (PPV) of the operational definition in detecting true osteoporotic VF and obtained the receiver operating characteristic (ROC) curve. @*Results@#Among the 2,819 patients who had primary or secondary diagnosis codes for VF, 995 patients satisfied at least one of the criteria for the operational definition of osteoporotic VF. Of these patients, 594 were judged as having true fractures based on medical records and radiographic examinations. The sensitivity and PPV were 62.5 (95% confidence interval [CI], 59.4–65.6) and 59.7(95% CI, 56.6–62.8) respectively. In the receiver operating characteristic analysis, area under the curve (AUC) was 0.706 (95% CI, 0.688–0.724). @*Conclusion@#Our findings demonstrate the validity of our operational definitions to identify VFs more accurately using claims data. This algorithm to identify VF is likely to be useful in future studies for diagnosing osteoporotic VF.
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BACKGROUND/OBJECTIVES@#The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G.pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. @*RESULTS@#The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferatoractivated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. @*CONCLUSIONS@#These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.
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Lobelia chinensis Lour. has commonly been used in traditional Chinese medicine for the treatment of antidote, diuretic, diarrhea, and inflammation. This study aimed to identify the active compounds in an aqueous extract of L. chinensis responsible for its anti-atopic effect in vitro using RBL-2H3 cells. A chemical investigation of secondary metabolites in an aqueous extract of L. chinensis led to the isolation of nine chemical constituents, which included the four marker compounds, and these were evaluated for their inhibitory effects on IL-4 mRNA expression and the release of β-hexosaminidase in propidium iodide-induced RBL-2H3 cells. We found diosmetin and fraxidin inhibited cellular IL-4 mRNA expression, and that diosmetin and 6,8-dimethoxycoumarin inhibited DNP-specific IgE-induced degranulation in these cells. Our study suggests that diosmetin, fraxidin, and 6,8-dimethoxycoumarin are potential candidates for the treatment of atopic diseases.
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Purpose@#To report a successful case of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy performed in a noncompliant pediatric patient using the lateral decubitus position and a conventional slit-lamp-based laser system under general anesthesia.Case summary: Progression of a thick posterior capsular opacity with associated vision loss (best-correct visual acuity of 0.1) was detected in a nine-year-old child with a past history of cataract surgery in his right eye. Diagnosed with pediatric uveitis at the age of five, he had been treated previously using a combination of topical and systemic corticosteroids, which led to the development of the cataract and subsequent surgery 16 months later. Severe photophobia prevented outpatient-based laser treatment, and the patient underwent our modified procedure. Under general anesthesia, the patient was placed in a lateral decubitus position with the use of a long intubation tube. The height of the bed and table-based laser system was adjusted so as to minimize strain when positioning the child’s head. Successful laser capsulotomy was performed within 10 minutes, and the entire anesthesia time was less than 30 minutes. The patient experienced immediate improvement in symptoms, showing a visual acuity of 1.0, which has been sustained as of his most recent visit, 3 months postoperatively. The patient experienced no ocular or anesthesia- related complications. @*Conclusions@#Nd:YAG laser capsulotomy performed by careful positioning (lateral decubitus) under general anesthesia is a viable strategy for the safe and efficient removal of posterior capsular opacities in children with poor compliance.
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Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.
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Background@#Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. @*Methods@#This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. @*Results@#The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40–1.28) in the SERMs group compared to BP group. Older age (60–69 vs. 50–59 years: HR, 3.77; 95% CI, 2.07–6.86 and 70–79 vs. 50–59 years: HR, 5.88; 95% CI, 3.14–11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35–8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01–5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02–4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29–14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05–7.0) increased VTE risk. @*Conclusion@#SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.
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This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
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Objectives@#Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. @*Methods@#Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. @*Results@#In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. @*Conclusions@#Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.
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Purpose@#To report a successful case of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy performed in a noncompliant pediatric patient using the lateral decubitus position and a conventional slit-lamp-based laser system under general anesthesia.Case summary: Progression of a thick posterior capsular opacity with associated vision loss (best-correct visual acuity of 0.1) was detected in a nine-year-old child with a past history of cataract surgery in his right eye. Diagnosed with pediatric uveitis at the age of five, he had been treated previously using a combination of topical and systemic corticosteroids, which led to the development of the cataract and subsequent surgery 16 months later. Severe photophobia prevented outpatient-based laser treatment, and the patient underwent our modified procedure. Under general anesthesia, the patient was placed in a lateral decubitus position with the use of a long intubation tube. The height of the bed and table-based laser system was adjusted so as to minimize strain when positioning the child’s head. Successful laser capsulotomy was performed within 10 minutes, and the entire anesthesia time was less than 30 minutes. The patient experienced immediate improvement in symptoms, showing a visual acuity of 1.0, which has been sustained as of his most recent visit, 3 months postoperatively. The patient experienced no ocular or anesthesia- related complications. @*Conclusions@#Nd:YAG laser capsulotomy performed by careful positioning (lateral decubitus) under general anesthesia is a viable strategy for the safe and efficient removal of posterior capsular opacities in children with poor compliance.
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Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.
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Background@#Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. @*Methods@#This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. @*Results@#The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40–1.28) in the SERMs group compared to BP group. Older age (60–69 vs. 50–59 years: HR, 3.77; 95% CI, 2.07–6.86 and 70–79 vs. 50–59 years: HR, 5.88; 95% CI, 3.14–11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35–8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01–5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02–4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29–14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05–7.0) increased VTE risk. @*Conclusion@#SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.
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This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
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Objectives@#Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. @*Methods@#Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. @*Results@#In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. @*Conclusions@#Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.
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Objectives@#Many deep learning-based predictive models evaluate the waveforms of electrocardiograms (ECGs). Because deep learning-based models are data-driven, large and labeled biosignal datasets are required. Most individual researchers find it difficult to collect adequate training data. We suggest that transfer learning can be used to solve this problem and increase the effectiveness of biosignal analysis. @*Methods@#We applied the weights of a pretrained model to another model that performed a different task (i.e., transfer learning). We used 2,648,100 unlabeled 8.2-second-long samples of ECG II data to pretrain a convolutional autoencoder (CAE) and employed the CAE to classify 12 ECG rhythms within a dataset, which had 10,646 10-second-long 12-lead ECGs with 11 rhythm labels. We split the datasets into training and test datasets in an 8:2 ratio. To confirm that transfer learning was effective, we evaluated the performance of the classifier after the proposed transfer learning, random initialization, and two-dimensional transfer learning as the size of the training dataset was reduced. All experiments were repeated 10 times using a bootstrapping method. The CAE performance was evaluated by calculating the mean squared errors (MSEs) and that of the ECG rhythm classifier by deriving F1-scores. @*Results@#The MSE of the CAE was 626.583. The mean F1-scores of the classifiers after bootstrapping of 100%, 50%, and 25% of the training dataset were 0.857, 0.843, and 0.835, respectively, when the proposed transfer learning was applied and 0.843, 0.831, and 0.543, respectively, after random initialization was applied. @*Conclusions@#Transfer learning effectively overcomes the data shortages that can compromise ECG domain analysis by deep learning.
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Enamel knot (EK)—a signaling center—refers to a transient morphological structure comprising epithelial tissue. EK is believed to regulate tooth development in early organogenesis without its own cellular alterations, including proliferation and differentiation. EKs show a very simple but conserved structure and share functions with teeth of recently evolved vertebrates, suggesting conserved signaling in certain organs, such as functional teeth, through the course of evolution. In this study, we examined the expression patterns of key EK-specific genes including Dusp26 , Fat4, Meis2, Sln , and Zpld1 during mice embryogenesis. Expression patterns of these genes may reveal putative differentiation mechanisms underlying tooth morphogenesis.
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Purpose@#We sought to evaluate the long-term outcomes for patients with exudative age-related macular degeneration (AMD) undergoing vitrectomy for breakthrough vitreous hemorrhage and to investigate possible prognostic factors. @*Methods@#Consecutive patients treated at two high-volume referral-based tertiary hospitals between July 2006 and Decem-ber 2019 were retrospectively reviewed. Surgery was performed using the standard three-port vitrectomy. The primary out-come was the change in best-corrected visual acuity (BCVA) over long-term follow-up, while secondary outcomes included the assessment of possible prognostic factors. @*Results@#Among 50 eyes from 50 patients included in this study, 23 (46%) were diagnosed with polypoidal choroidal vascu-lopathy (PCV) and 27 (54%) were diagnosed with neovascular AMD. Preoperative vision at the time of vitreous hemorrhage onset was 20 / 3,027 (logarithm of the minimum angle of resolution [logMAR], 2.18 ± 0.34). At 12 months after surgery, the mean BCVA improved to 20 / 873 (logMAR, 1.64 ± 0.76; p < 0.001). At 24 months, the BCVA was 20 / 853 (logMAR, 1.63 ± 0.75; p < 0.001). Univariate analysis revealed that older age (odds ratio [OR], 0.879; p = 0.007] and the presence of submac-ular hemorrhage (OR, 0.081; p= 0.022) were factors associated with a poor 2-year visual outcome. Multivariable regression showed that older age (OR, 0.876; p= 0.026) and neovascular AMD (as compared with PCV) (OR, 0.137; p= 0.014) were significant negative factors influencing the 2-year visual outcome. The mean injection interval prior to vitrectomy was 4.53 months, which extended to 27.64 months after vitrectomy ( p = 0.028). @*Conclusions@#Younger age, the absence of submacular hemorrhage, and PCV type were associated with a favorable 2-year visual outcome after vitrectomy for vitreous hemorrhage in patients with exudative AMD. Overall, vitrectomy resulted in im-proved visual acuity and patients showed a decreased need for anti-vascular endothelial growth factor therapy thereafter.
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Biosignals such as electrocardiogram or photoplethysmogram are widely used for determining and monitoring the medical condition of patients. It was recently discovered that more information could be gathered from biosignals by applying artificial intelligence (AI). At present, one of the most impactful advancements in AI is deep learning. Deep learning-based models can extract important features from raw data without feature engineering by humans, provided the amount of data is sufficient. This AI-enabled feature presents opportunities to obtain latent information that may be used as a digital biomarker for detecting or predicting a clinical outcome or event without further invasive evaluation. However, the black box model of deep learning is difficult to understand for clinicians familiar with a conventional method of analysis of biosignals. A basic knowledge of AI and machine learning is required for the clinicians to properly interpret the extracted information and to adopt it in clinical practice. This review covers the basics of AI and machine learning, and the feasibility of their application to real-life situations by clinicians in the near future.