Search

Background and ObjectivesWhite matter hyperintensities (WMHs) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiologic heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMHs and its clinical implications in the MMD trajectory.MethodsAdult patients with MMD without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the 2 groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes.ResultsA total of 161 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total WMH volume (B [standard error], 0.126 [0.030];p< 0.001), periventricular WMH volume (0.114 [0.027];p< 0.001), and periventricular-to-subcortical ratio (0.090 [0.034];p= 0.009). In the MMD subgroup (n = 187), advanced MMD had an independent association with the total WMH volume (0.120 [0.035];p< 0.001), periventricular WMH volume (0.110 [0.031];p< 0.001), and periventricular-to-subcortical ratio (0.139 [0.038];p< 0.001). Periventricular WMH volume (adjusted hazard ratio [95% confidence interval], 5.12 [1.26–20.79]) and periventricular-to-subcortical ratio (3.80 [1.51–9.56]) were associated with future ischemic events in patients with medically followed up MMD. However, no demonstrable association was found between subcortical WMH volume and MMD, MMD severity, or future ischemic events.DiscussionPeriventricular WMHs, but not subcortical WMHs, may represent the main pathophysiology of MMD. Periventricular WMHs may be used as a marker for ischemic vulnerability in patients with MMD.

Background and Objectives The aim of this study was to identify the frequency of indicators of National Health Insurance (NHI) coverage for positive airway pressure (PAP) therapy and to investigate the changes in patients receiving coverage for PAP therapy after the alterations were made in the insurance benefit standards for mild obstructive sleep apnea (OSA).Subjects and Method We divided the mild OSA patients into two groups according to altered categorization in insurance benefit standards (Mild1: 5≤AHI

Information on obstructive sleep apnea (OSA) is often latently detected in diagnostic tests conducted for other purposes, providing opportunities for maximizing value. This study aimed to develop a convolutional neural network (CNN) to identify the risk of OSA using lateral cephalograms.The lateral cephalograms of 5,648 individuals (mean age, 49.0±15.8 years; men, 62.3%) with or without OSA were collected and divided into training, validation, and internal test datasets in a 5:2:3 ratio. A separate external test dataset (n=378) was used. A densely connected CNN was trained to diagnose OSA using a cephalogram. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Gradient-weighted class activation mapping (Grad-CAM) was used to evaluate the region of focus, and the relationships between the model outputs, anthropometric characteristics, and OSA severity were evaluated.The AUROC of the model for the presence of OSA was 0.82 (95% confidence interval [CI], 0.80-0.84) and 0.73 (95% CI, 0.65-0.81) in the internal and external test datasets, respectively. Grad-CAM demonstrated that the model focused on the area of the tongue base and oropharynx in the cephalogram. Sigmoid output values were positively correlated with OSA severity, body mass index, and neck and waist circumference.Deep learning may help develop a model that classifies OSA using a cephalogram, which may be clinically useful in the appropriate context. The definition of ground truth was the main limitation of this study.

The damp-heat stability and photostability of solar cells were investigated depending on the ZnO fabrication methodology. Although the initial PCEs of the devices were similar, the ZnOs affected the solar cell performance after the aging process.

Background and Objectives The aim of this study was to evaluate the effect of sleep position and nasal cavity dimension according to minimal cross-sectional area (MCA) on the severity of obstructive sleep apnea (OSA).Subjects and Method This study enrolled 528 consecutive patients who completed overnight polysomnography (PSG) and acoustic rhinometry. Positional sleep time and apnea-hypopnea index (AHI) were compared between the right and left lateral sleep positions (RLSP vs. LLSP), and between the wide and narrow lateral side sleep position (WLSP vs. NLSP) according to MCA.Results The sleep time was longer for LSP than for WLSP (20.35%±19.69% and 15.92%±16.35%, respectively) with a statistically significant difference (p=0.001). However, the AHI was not significantly different between the two groups. The sleep time was longer for RLSP than for LLSP (20.65%±19.31% and 15.39%±16.05%, respectively) with a statistically significant difference (pp=0.001). However, we found that the AHI value was not significantly different according to sleep posture and nasal cavity dimension.Conclusion Snoring patients preferred RLSP to LLSP, and preferred to sleep on the lateral side of the narrow nasal cavity. The OSA severity was not different according to sleep position and nasal cavity dimension.

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models, and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared to HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared to controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. This article is protected by copyright. All rights reserved.

Objective To identify the factors affecting anger in post-traumatic stress disorder (PTSD) patients who underwent Clinician-Administered PTSD Scale (CAPS) and Minnesota Multiphasic Personality Inventory-2 (MMPI-2).Methods We retrospectively reviewed patients who underwent CAPS and MMPI-2 at Veteran Health Service Medical Center, Seoul, Korea. Based on the CAPS score, the patients were divided into the PTSD group (n=46) and the trauma exposed without PTSD group (n=29). After checking the correlation between anger, CAPS, and MMPI-2 scales, logistic regression analysis was performed to identify the risk factors for clinically relevant symptoms.Results The PTSD group showed significant differences in schizophrenia-related symptoms, ideas of persecution, aggressiveness, psychoticism, and anger scales compared to the trauma-exposed without PTSD group. There was a significant correlation between anger, CAPS, and MMPI-2 except masculinity/femininity, disconstraint, and MacAndrew Alcoholism-Revised. In particular, anger has been shown to have a substantial connection with paranoia, schizophrenia-related symptoms, ideas of persecution, aberrant experiences, and psychoticism. Multiple regression analysis identified that the only significant risk factor for anger was the negative emotionality/neuroticism scale (odds ratio=1.152, p

The human papillomavirus (HPV)-18 E7 (E7) oncoprotein is a major transforming protein that is thought to be involved in the development of cervical cancer. It is well-known that E7 stimulates tumour development by inactivating pRb. However, this alone cannot explain the various characteristics acquired by HPV infection. Therefore, we examined other molecules that could help explain the acquired cancer properties during E7-induced cancer development. Using the yeast two-hybrid (Y2H) method, we found that the Elk-1 factor, which is crucial for cell proliferation, invasion, cell survival, anti-apoptotic activity, and cancer development, binds to the E7. By determining which part of E7 binds to which domain of Elk-1 using the Y2H method, it was found that CR2 and CR3 of the E7 and parts 1-206, including the ETS-DNA domain of Elk-1, interact with each other. As a result of their interaction, the transcriptional activity of Elk-1 was increased, thereby increasing the expression of target genes EGR-1, c-fos, and E2F. Additionally, the colony forming assay revealed that overexpression of Elk-1 and E7 promotes C33A cell proliferation. We expect that the discovery of a novel E7 function as an Elk-1 activator could help explain whether the E7 has novel oncogenic activities in addition to p53 inactivation. We also expect that it will offer new methods for developing improved strategies for cervical cancer treatment.

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

The scalp nerve block, created by injecting local anesthetics around the scalp nerves, is reported to effectively reduce pain after surgery. In this study, we evaluated the efficacy of scalp nerve block in patients with hemifacial spasm (HFS) undergoing microvascular decompression (MVD). Seventy-four patients who underwent MVD for HFS were enrolled. The block group received scalp nerve block with 0.5% ropivacaine before surgery. The primary outcome was cumulative dose of rescue analgesics 24 h postoperatively. The secondary outcomes were included pain scores, postoperative antiemetic consumption, and Quality of Recovery-15 scale. The cumulative dose of rescue analgesics at 24 h postoperatively was not significantly different between the two groups (4.80 ± 3.64 mg vs. 5.92 ± 3.95 mg, p = 0.633). However, the pain score was significantly reduced in the block group at 6, 12, and 24 h postoperatively. Postoperative antiemetic consumption was lower in the block group than the control group at 12 h. There were no significant differences between the two groups for other secondary outcomes. In MVD for HFS, a preoperative scalp nerve block might reduce postoperative pain in the early postoperative period, but a larger study using a multimodal approach is needed to confirm the efficacy of a scalp block.

Schaaf-Yang syndrome (SYS) is a rare genomic imprinting disorder caused by truncating mutations in the paternally derived MAGE family member L2 (MAGEL2) allele. It is also responsible for Prader-Willi syndrome, characterized by neonatal hypotonia, developmental delay, intellectual disability, respiratory distress in early infancy, and arthrogryposis. More than 250 individuals with approximately 57 different molecular variants have been reported since 2013, but the phenotype-genotype association in SYS is not yet fully understood. Here, we describe the case of a Korean patient diagnosed with SYS harboring a mutation in the paternal allele of MAGEL2: c.2895G>A, resulting in a protein change of p.Trp965*. The patient’s phenotype included respiratory distress, arthrogryposis, hypotonia, and feeding difficulty in the early neonatal period. Mild renal dysfunction and hearing impairment were observed during infancy.

Seung Hoon Lee,1,&ast; Hyung-Jin Kim,1,&ast; Gi-Su Oh,1 Su-Bin Lee,1 Dipendra Khadka,1 Wal Cao,1 Seong-Kyu Choe,1 Hyeok Shim,2 Chang-Deok Kim,3 Tae Hwan Kwak,4 Hong-Seob So1,4 1Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea; 2Department of Hemato-Oncology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea; 3Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea; 4R&D Center, NADIANBIO Ltd, Iksan, Jeonbuk, 54538, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hong-Seob So, Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 54538, Republic of Korea, Tel +82-63-850-6950, Fax +82-63-855-6777, Email jeanso@wku.ac.krBackground: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD+/NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD+ levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD+/NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice.Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting.Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD+/NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23.Conclusion: Pharmacological modulation of cellular NAD+ levels could be a promising therapeutic approach for psoriasis-like skin disease.Keywords: psoriasis, NQO1, NAD+, SIRT1, inflammatory cytokine

Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage–inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973–84. ©2017 AACR.

Supplementary Figure 1 related to Figure 1. TGM2 is highly expressed in the necrotic region of MES GBM. Supplementary Figure 2 related to Figure 2. TGM2 regulates stemness of MES, PN, and CL GSCs. Supplementary Figure 3 related to Figure 4. A negative correlation between C/EBPβ and GADD153.

The stability of wild-type p53 is critical for its apoptotic function. In some cancers, wild-type p53 is inactivated by interaction with viral and cellular proteins, and restoration of its activity has therapeutic potential. Here, we identify homeobox Msx1 as a p53-interacting protein and show its novel function as a p53 regulator. Overexpression of homeobox Msx1 induced apoptosis of cancer cells harboring nonfunctional wild-type p53 and suppressed growth of human tumor xenografts in nude mice. The homeodomain of Msx1 functions as a protein-protein interacting motif rather than a DNA-binding domain and is essential for stabilization, nuclear accumulation, and apoptotic function of wild-type p53. The identification of a novel function of Msx1 as a p53 regulator may open new avenues for developing improved molecular therapies for tumors with a nonmutational p53 inactivation mechanism.