Comparison of orthopaedic manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study

Background : Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones. However, it is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. In surveys conducted in East Asia, MATN3 was the most common causative gene, followed by COMP. In this study, the authors compared clinical manifestation of MED patients caused by MATN3 and COMP gene mutations, as well as subsequent orthopaedic interventions. Methods : Fifty nine molecularly-confirmed MED patients were subjects of this study. The MATN3 gene mutation group comprised of 37 patients (9 female, 28 male). The COMP gene mutation consisted of 22 cases (15 females, 7 males). Medical records and radiographs were reviewed, and questionnaire surveys or telephone interviews were conducted. Results : At the first presentation, the mean age was 8.8 ± 2.8 years (mean ± standard deviation) in the MATN3 group, and 8.5 ± 3.5 years in the COMP group (p = 0.670). The height in the COMP group was significantly shorter than those in the MATN3 group (p < 0.001). Gait abnormality at the first visit (p = 0.041) and the lastest follow-up (p = 0.037) were statistically significant difference. Hip pain (p = 0.084), limitation of daily activity (p = 0.075) at the latest follow-up tended to be more frequent in the COMP group. Hip dysplasia was more common in the COMP group, having significantly larger acetabular angle (p = 0.037), smaller center-edge angle (p = 0.002), severe Stulberg classification (p < 0.001), and smaller femoral head coverage (p < 0.001). Conclusions : Clinical manifestations of MED caused by MATN3 were milder than manifestations of the COMP mutation group. These differences in clinical manifestation and prognosis justify molecular differentiation between the two genotypes.This study was supported by a grant from the SNUH Research Fund (No. 04-2013-0640).Peer Reviewe

Comparison of orthopaedic manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study

Background : Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones. However, it is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. In surveys conducted in East Asia, MATN3 was the most common causative gene, followed by COMP. In this study, the authors compared clinical manifestation of MED patients caused by MATN3 and COMP gene mutations, as well as subsequent orthopaedic interventions. Methods : Fifty nine molecularly-confirmed MED patients were subjects of this study. The MATN3 gene mutation group comprised of 37 patients (9 female, 28 male). The COMP gene mutation consisted of 22 cases (15 females, 7 males). Medical records and radiographs were reviewed, and questionnaire surveys or telephone interviews were conducted. Results : At the first presentation, the mean age was 8.8 ± 2.8 years (mean ± standard deviation) in the MATN3 group, and 8.5 ± 3.5 years in the COMP group (p = 0.670). The height in the COMP group was significantly shorter than those in the MATN3 group (p < 0.001). Gait abnormality at the first visit (p = 0.041) and the lastest follow-up (p = 0.037) were statistically significant difference. Hip pain (p = 0.084), limitation of daily activity (p = 0.075) at the latest follow-up tended to be more frequent in the COMP group. Hip dysplasia was more common in the COMP group, having significantly larger acetabular angle (p = 0.037), smaller center-edge angle (p = 0.002), severe Stulberg classification (p < 0.001), and smaller femoral head coverage (p < 0.001). Conclusions : Clinical manifestations of MED caused by MATN3 were milder than manifestations of the COMP mutation group. These differences in clinical manifestation and prognosis justify molecular differentiation between the two genotypes.This study was supported by a grant from the SNUH Research Fund (No. 04-2013-0640).Peer Reviewe

Comparison of orthopaedic manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones. However, it is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. In surveys conducted in East Asia, MATN3 was the most common causative gene, followed by COMP. In this study, the authors compared clinical manifestation of MED patients caused by MATN3 and COMP gene mutations, as well as subsequent orthopaedic interventions. Methods Fifty nine molecularly-confirmed MED patients were subjects of this study. The MATN3 gene mutation group comprised of 37 patients (9 female, 28 male). The COMP gene mutation consisted of 22 cases (15 females, 7 males). Medical records and radiographs were reviewed, and questionnaire surveys or telephone interviews were conducted. Results At the first presentation, the mean age was 8.8 ± 2.8 years (mean ± standard deviation) in the MATN3 group, and 8.5 ± 3.5 years in the COMP group (p = 0.670). The height in the COMP group was significantly shorter than those in the MATN3 group (p < 0.001). Gait abnormality at the first visit (p = 0.041) and the lastest follow-up (p = 0.037) were statistically significant difference. Hip pain (p = 0.084), limitation of daily activity (p = 0.075) at the latest follow-up tended to be more frequent in the COMP group. Hip dysplasia was more common in the COMP group, having significantly larger acetabular angle (p = 0.037), smaller center-edge angle (p = 0.002), severe Stulberg classification (p < 0.001), and smaller femoral head coverage (p < 0.001). Conclusions Clinical manifestations of MED caused by MATN3 were milder than manifestations of the COMP mutation group. These differences in clinical manifestation and prognosis justify molecular differentiation between the two genotypes

Establishment of particulate matter-induced lung injury model in mouse

Background Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.This research was supported by Univera Co., Ltd., as one of the CAP projects and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1A6A1A03043708)

Toll-like Receptors 2 and 4 and Their Mutations in Patients with Otitis Media and Middle Ear Effusion

ObjectivesToll-like receptors (TLRs) detect microbial infections and they can directly induce innate host defense responses. TLR 2 has been shown to be primarily involved in the recognition of peptidoglycans and lipoteichoic acid of gram positive bacteria. TLR 4 recognizes lipopolysaccharides and lipoteichoic acids from both gram-negative and gram-positive bacteria. Both mutations lead a reduced capacity to elicit inflammation and they increase the risk for gram-positive and negative infections. This study was performed to investigate the expressions of TLR 2 and 4 and their mutations in patients suffering with otitis media and middle ear effusion.MethodsMiddle ear fluid samples were collected from 40 otitis media effusion (OME) patients who had ventilating tubesinserted. Bacteria in the effusion fluid were detected by standard bacterial culture. The secreted IgG, IgA and IgM were measured by Enzyme-linked immunosorbent assay. TLR 2 and 4 were assessed by performing RT-PCR. The genomic DNA from each patient was isolated from the middle ear fluid samples that were collected from 60 OME patients, and the presence of mutations was determined by performing restriction digestion and DNA sequencing analysis.ResultsAmong the 40 middle ear fluid samples, bacteria were detected in 13 middle ear fluid samples. The amounts of IgM, IgA, and IgG were 151.20±60.94 ng/mL, 21.59±7.96 ng/mL and 11.55±16.98 ng/mL, respectively. TLR 2 and 4 were expressed in the middle ear fluid and the expression of TLR 2 was higher than that of TLR 4. However, there was no correlation between the expressions of TLR 2 and 4, and the concentration of immunoglobulin or the presence of bacteria (P>0.05). There ware no mutations of TLR 2 (Arg753Gln, Arg677Trp) and TLR 4 (Asp299Gly, Thr399Ile).ConclusionTLR 2 and 4 were expressed in all the middle ear fluid samples of OME, but the mutations of TLR 2 and 4 were not detected. TLR 2 and 4 may play a vital role in the immunological responses of patients with OME

Antidepressants and Mood Stabilizers: Novel Research Avenues and Clinical Insights for Bipolar Depression

The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk. In these patients, a combination of ADs plus MSs or atypical antipsychotics is recommended, rather than AD monotherapy. Studies evaluating MSs for bipolar depression suggest that lamotrigine is the most reliable treatment and lithium has modest effects; there is a lack of clear evidence regarding the efficacy of valproate and carbamazepine. Recently, significant progress has been made with respect to the pathophysiology of mood disorders and the application of potential biomarkers. There is an opportunity to study novel drug mechanisms through the rediscovery of fast-acting drugs such as ketamine. It is anticipated that future research developments will involve the discovery of potential targets for new drugs and their application to personalized treatments