Role of interleukin-10 in endochondral bone formation in mice: Anabolic effect via the bone morphogenetic protein/Smad pathway

Objective: Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with a chondroprotective effect that is elevated in cartilage and synovium in patients with osteoarthritis. However, the role of IL-10 during endochondral bone formation and its mechanism of action have not been elucidated. Methods: IL-10-/- mice and IL-10-treated tibial organ cultures were used to study loss and gain of IL-10 functions, respectively, during endochondral bone formation. Primary chondrocytes from the long bones of mouse embryos were cultured with and without IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted mesenchymal cell micromass cultures. Results: The lengths of whole skeletons from IL-10-/- mice were similar to those of their wild-type littermates, although their skull diameters were smaller. The tibial growth plates of IL-10-/- mice showed shortening of the proliferating zone. Treatment with IL-10 significantly increased tibial lengths in organ culture. IL-10 also induced chondrocyte proliferation and hypertrophic differentiation in primary chondrocytes in vitro. Mechanistically, IL-10 activated STAT-3 and the Smad1/5/8 and ERK-1/2 MAP kinase pathways and induced the expression of bone morphogenetic protein 2 (BMP-2) and BMP-6 in primary chondrocytes. Furthermore, the blocking of BMP signaling attenuated the IL-10-mediated induction of cyclin D1 and RUNX-2 in primary chondrocytes and suppressed Alcian blue and alkaline phosphatase staining in mesenchymal cell micromass cultures. Conclusion: These results indicate that IL-10 acts as a stimulator of chondrocyte proliferation and chondrogenic or hypertrophic differentiation via activation of the BMP signaling pathway. © 2013, American College of Rheumatology

Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen

Primary splenic tumors are rare and mainly found incidentally on radiologic studies. Among them, sclerosing angiomatoid nodular transformation (SANT) of the spleen is a new entity defined as a benign pathologic lesion. Most SANTs have no clinical symptoms and are occasionally accompanied by other splenic diseases such as malignancies. So, the exact diagnosis of the nature of the splenic tumor is mandatory for further treatment. But, preoperative diagnosis is not easy since it is difficult to obtain the tissue from the spleen for pathological study. Recently, laparoscopic splenectomy has become the more standard procedure for the spleen for diagnosis and treatment. Here, we report a rare case of SANT diagnosed following laparoscopic splenectomy

Population health outcomes in South Korea 1990-2019, and projections up to 2040: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: South Korea has one of the longest operating universal health coverage (UHC) systems. A comprehensive analysis of long-term trajectories of morbidity and mortality in the South Korean population after the inception of UHC is needed to inform health-care policy and practice. METHODS: We used data from the Global Burden of Disease Study (GBD) 2019 to present estimates of cause-specific mortality, incidence, prevalence, years of life lost (YLLs), years of life lived with disability, and disability-adjusted life-years (DALYs) in South Korea from 1990 to 2019. We also examined forecasted estimates of YLLs up to 2040 to investigate likely future changes in disease burden. Finally, we evaluated GBD estimates from seven comparator countries to place disease burden in South Korea within a broader context. FINDINGS: Age-standardised DALYs related to non-communicable diseases (NCDs) decreased by 43·6% (95% uncertainty interval [UI] 39·4-47·9) and mortality by 58·8% (55·9-60·5) from 1990 to 2019. In 2019, the ratio of male to female age-standardised rates of YLLs in South Korea was higher than the global average for 75·9% (22 of 29 diseases) of leading causes, indicating a disproportional disease burden on males in South Korea. Among risk factors, tobacco use accounted for the highest number of 2019 deaths (44 470 [95% UI 37 432-53 989]) in males and high systolic blood pressure for the highest number (21 014 [15 553-26 723]) in females. Among the top ten leading causes of YLLs forecast in South Korea in 2040, nine were NCDs, for both males and females. INTERPRETATION: Our report shows a positive landscape of population health outcomes in South Korea following the establishment of UHC. However, due in part to the effects of population ageing driving up medical expenditures for NCDs, financial pressures and sustainability challenges associated with UHC are pressing concerns. Policy makers should work to tackle population ageing and allocate resources efficiently by prioritising interventions that address the leading causes of death and disability identified in this study. FUNDING: Bill & Melinda Gates Foundation

Diagnostic Benefit of Thyroglobulin Measurement in Fine-Needle Aspiration for Diagnosing Metastatic Cervical Lymph Nodes from Papillary Thyroid Cancer: Correlations with US Features

Objective: Our goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer. Materials and Methods: We retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated. Results: The accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology. Conclusion: Combined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes

Characteristics and psychiatric symptoms of Internet Gaming Disorder among adults using self-reported DSM-5 criteria

Objective: The Section III of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine diagnostic criteria and five cut-point criteria for Internet Gaming Disorder (IGD). We aimed to examine the efficacy of such criteria. Methods: Adults (n=3041, men: 1824, women: 1217) who engaged in internet gaming within last 6 months completed a self-report online survey using the suggested wordings of the criteria in DSM-5. Major characteristics, gaming behavior, and psychiatric symptoms of IGD were analyzed using ANOVA, chi-square, and correlation analyses. Results: The sociodemographic variables were not statistically significant between the healthy controls and the risk group. Among the participants, 419 (13.8%) were identified and labeled as the IGD risk group. The IGD risk group scored significantly higher on all motivation subscales (p<0.001). The IGD risk group showed significantly higher scores than healthy controls in all nine psychiatric symptom dimensions, i.e., somatization, obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism (p<0.001). Conclusion: The IGD risk group showed differential psychopathological manifestations according to DSM-5 IGD diagnostic criteria. Further studies are needed to evaluate the reliability and validity of the specific criteria, especially for developing screening instruments

Prediction of cognitive impairment via deep learning trained with multi-center neuropsychological test data

Background Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. Methods Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimers disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. Results The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The time orientation and 3-word recall score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. Conclusions The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.The publication costs, design of the study, data management and writing the manuscript for this article were supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2017S1A6A3A01078538), Korea Ministry of Health & Welfare, and from the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Korean Government (MSIP; No. 2014M3C7A1064752)