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Chul-Young Bae,1 Young Gon Kang,2 Young-Sung Suh,3 Jee Hye Han,4 Sung-Soo Kim,5 Kyung Won Shim61MediAge Research Center, Seoul, Korea; 2Chaum Power Aging Center, College of Medicine, CHA University, Seoul, Korea; 3Health Promotion Center, Keimyung University Dongsam Medical Center, Daegu, Korea; 4Department of Family Medicine, College of Medicine, Eulji University, Seoul, Korea; 5Department of Family Medicine, College of Medicine, Chungnam National University, Daejeon, Korea; 6Department of Family Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University, Seoul, KoreaBackground: To date, no studies have attempted to estimate body shape biological age using clinical parameters associated with body composition for the purposes of examining a person's body shape based on their age.Objective: We examined the relations between clinical parameters associated with body composition and chronological age, and proposed a model for estimating the body shape biological age.Methods: The study was conducted in 243,778 subjects aged between 20 and 90 years who received a general medical checkup at health promotion centers at university and community hospitals in Korea from 2004 to 2011.Results: In men, the clinical parameters with the highest correlation to age included the waist-to-hip ratio (r = 0.786, P < 0.001), hip circumference (r = −0.448, P < 0.001), and height (r = −0.377, P < 0.001). In women, the clinical parameters with the highest correlation to age include the waist-to-hip ratio (r = 0.859, P < 0.001), waist circumference (r = 0.580, P < 0.001), and hip circumference (r = 0.520, P < 0.001). To estimate the optimal body shape biological age based on clinical parameters associated with body composition, we performed a multiple regression analysis. In a model estimating the body shape biological age, the coefficient of determination (R2) was 0.71 in men and 0.76 in women.Conclusion: Our model for estimating body shape biological age might be a novel approach to variation in body shape that is due to aging. We assume that our estimation model would be used as an adjunctive measure in easily predicting differences in body shape with the use of clinical parameters that are commonly used to assess the status of obesity in a clinical setting.Keywords: chronological age, body shape, biological age

Abstract Cerium-doped Tb3Al5O12(TAG:Ce3+) colloidal nanocrystals were synthesized by pulsed laser ablation (PLA) in de-ionized water and lauryl dimethylaminoacetic acid betain (LDA) aqueous solution for luminescent bio-labeling application. The influence of LDA molecules on the crystallinity, crystal morphology, crystallite size, and luminescent properties of the prepared TAG:Ce3+colloidal nanocrystals was investigated in detail. When the LDA solution was used, smaller average crystallite size, narrower size distribution, and enhanced luminescence were observed. These characteristics were explained by the effective role of occupying the oxygen defects on the surface of TAG:Ce3+colloidal nanocrystal because the amphoteric LDA molecules were attached by positively charged TAG:Ce3+colloidal nanocrystals. The blue-shifted phenomena found in luminescent spectra of the TAG:Ce3+colloidal nanocrystals could not be explained by previous crystal field theory. We discuss the 5d energy level of Ce3+with decreased crystal size with a phenomenological model that explains the relationship between bond distance with 5d energy level of Ce3+based on the concept of crystal field theory modified by covalency contribution.

Background: Diabetes mellitus (DM) is a significant public health concern, particularly in the elderly population. Absolute handgrip strength (HGS) serves to quantify muscle strength. It is recommended that the risk of low muscle strength and increased body mass index be concurrently evaluated using relative HGS. There are currently insufficient evidence regarding the relationship between relative HGS and DM in the elderly Korean population. Therefore, the association between relative HGS and the development of DM in Korean elderly was investigated., Methods: Data from the Korean Longitudinal Study of Ageing were used to determine the odds ratio (OR) between relative HGS and DM during the follow-up period from 2006-2020 among Korean men and women aged ≥65 years without DM when they first participated in this survey. Analysis was conducted using the Generalized Estimating Equation method. Trend analysis was performed for DM development based on relative HGS., Results: Among elderly males, higher relative HGS groups had reduced odds of developing DM (Middle tertile: OR 0.87, 95% CI 0.61-1.23, p = 0.419.) (Upper tertile: OR 0.82, 95% CI 0.56-1.18, p = 0.281.) Among elderly females, the reductions were similar. (Middle tertile: OR 0.82, 95% CI 0.66-1.03, p = 0.087.) (Upper tertile: OR 0.79, 95% CI 0.50-1.25, p = 0.306.) However, these differences were not statistically significant. Significant predictors of new-onset DM included age, BMI (overweight/obese), household income, alcohol consumption, hypertension, and chronic liver disease. Trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05)., Conclusion: Relative HGS did not achieve statistical significance. Our findings indicate that BMI, particularly overweight and obesity, significantly predicts new-onset DM. However, trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05), even after adjusting for BMI categories. Despite the lack of statistical significance in some cases, the trend suggests that promoting resistance exercises to enhance HGS could be beneficial in DM prevention. Comprehensive DM prevention strategies should include managing obesity and chronic conditions for elderly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sohn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras/MAPK pathways. Recently, a novel disease-gene association was implicated in MAPK kinase kinase kinase 4 (MAP4K4), which regulates the upstream signals of the MAPK pathways. However, to our knowledge, only two studies have reported the genotype-phenotype relationships in the MAP4K4-related disorder. This study reports on a Korean boy harboring a novel de novo missense variant in MAP4K4 (NM&#95;001242559:c.569G>T, p.Gly190Val), revealed by trio exome sequencing, and located in the hotspot of the protein kinase domain. The patient exhibited various clinical features, including craniofacial dysmorphism, language delay, congenital heart defects, genitourinary anomalies, and sagittal craniosynostosis. Our study expands the phenotypic association of the MAP4K4-related disorder to include syndromic craniosynostosis, thereby providing further insights into the role of the RAS/MAPK pathways in the development of premature fusion of calvarial sutures., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC., Materials and Methods: Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment., Results: In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively., Conclusion: High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.

Background: Moyamoya disease (MMD) is a rare and complex pathological condition characterized by an abnormal collateral circulation network in the basal brain. The diagnosis of MMD and its progression is unpredictable and influenced by many factors. MMD can affect the blood vessels supplying the eyes, resulting in a range of ocular symptoms. In this study, we developed a deep learning model using real-world data to assist a diagnosis and determine the stage of the disease using retinal photographs., Methods: This retrospective observational study conducted from August 2006 to March 2022 included 498 retinal photographs from 78 patients with MMD and 3835 photographs from 1649 healthy participants. Photographs were preprocessed, and an ResNeXt50 model was developed. Model performance was measured using receiver operating curves and their area under the receiver operating characteristic curve, accuracy, sensitivity, and F1-score. Heatmaps and progressive erasing plus progressive restoration were performed to validate the faithfulness., Results: Overall, 322 retinal photographs from 67 patients with MMD and 3752 retinal photographs from 1616 healthy participants were used to develop a screening and stage prediction model for MMD. The average age of the patients with MMD was 44.1 years, and the average follow-up time was 115 months. Stage 3 photographs were the most prevalent, followed by stages 4, 5, 2, 1, and 6 and healthy. The MMD screening model had an average area under the receiver operating characteristic curve of 94.6%, with 89.8% sensitivity and 90.4% specificity at the best cutoff point. MMD stage prediction models had an area under the receiver operating characteristic curve of 78% or higher, with stage 3 performing the best at 93.6%. Heatmap identified the vascular region of the fundus as important for prediction, and progressive erasing plus progressive restoration result shows an area under the receiver operating characteristic curve of 70% only with 50% of the important regions., Conclusions: This study demonstrated that retinal photographs could be used as potential biomarkers for screening and staging of MMD and the disease stage could be classified by a deep learning algorithm., Competing Interests: Disclosures None.

The three-dimensional (3D) printing itself is not a novel technology, it is more than 30 years old. Stereolithographic (SLA) technology has been used as the first and popular technology for medical application of 3D printing. Since 1991 Radiology and Plastic Surgery have published articles about SLA for rapid prototyping anatomical 3D models. Medical applications of 3D printing have been popularizing and stabilizing so far. Implantable medical devices such as metal or absorbable implants, surgical guide systems, prosthesis and orthosis, and 3D anatomical models for normal or diseased anatomy have been developing and expanding its markets so far. There are many obstacles, such as insurance, authorization as a medical device, and lack of standards technology for further expansion of medical applications. Many technical specifications and guidelines for authorization as medical device have been published by regulatory bodies from many countries. Even though international standards for 3D printing have been developing more and more, there have been few standards for medical application of 3D printing. In this harsh environment academia, company, research institute, regulatory bodies, and government have been doing good job for the development of 3D printing industry., Competing Interests: The author has no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Post-hemorrhagic hydrocephalus (PHH) in preterm infant is common, life-threatening and the main cause of bad developmental outcomes. Ventriculoperitoneal (VP) shunt is used as the ultimate treatment for PHH. Low birth weight and low gestational age are the combination of worse prognostic factors while the single most important prognostic factor of VP shunting is age. Aggressive and early intervention have better effect in intraventricular hemorrhage and intracranial pressures control. It reduces infection rate and brain damage resulted in delayed shunt insertion. It is extremely important to let PHH infants get older and gain weight to have internal organs to be matured before undergoing VP shunt. As premature infants undergo shunt after further growth, shunt-related complications would be reduced. So temporary surgical intervention is critical for PHH infants to have them enough time until permanently shunted.

Background: Periodontitis is initiated or accelerated by dysbiosis of oral microorganisms. When hypertension is accompanied in periodontitis patients, changes of oral microbiota occur. Since there are no reports on antihypertensives, we assessed their effect on the oral microbial profiles of patients with periodontitis., Methods: This study involved 95 participants divided into two groups: those with periodontitis and hypertension (P&#95;HT), and those with periodontitis and taking medications for hypertension (P&#95;mHT). Plaque samples were collected from the buccal, supragingival, and subgingival sites of the oral cavities of these patients. DNA was extracted, and the V3-V4 region of the 16S ribosomal RNA was sequenced and analyzed., Results: The P&#95;HT and P&#95;mHT groups were similar with respect to the alpha- and beta-diversity as well as the dominant phyla and genera, but differed in the relative abundance of bacterial species (85 species). In the P&#95;mHT group, the relative abundance of major periodontal pathogens was greatly increased. In particular, Tannerella forsythia, Treponema denticola, and Fretibacterium fastidiosum increased nearly three times in the linear discriminant analysis score in the supragingival plaque. Also, there was an increase in the relative abundance of Prevotella spp., associated with periodontitis and nitrate reduction, which was also evident in the supragingival plaque., Conclusions: These findings indicate that antihypertensives induce dysbiotic changes in the oral microbiota of patients with periodontitis, which are associated with increases in the relative abundance of periodontal pathogens. Therefore, more active periodontal treatment and supportive periodontal therapy are required in patients taking antihypertensives., (© 2022 American Academy of Periodontology.)

Purpose: This study aimed to analyze the effect of foramen magnum decompression with C1 laminectomy (C1L) for Chiari malformation type 1 (CM-1) in terms of improving clinical symptoms, expanding posterior fossa volume, and decreasing syrinx volume., Materials and Methods: Between January 2007 and June 2019, 107 patients with CM-1 were included. The median patient age was 13±13 years (range: 9 months-60 years), female-to-male ratio was 1:1, and average length of tonsil herniation was 13±5 mm (range: 5-24 mm). Surgical techniques were divided into four groups based on duraplasty or C1L usage. Among the study subjects, 38 patients underwent duraplasty and had their syrinx volumes measured separately on serial magnetic resonance imaging. A three-dimensional visualization software was used to evaluate the syrinx-volume decrease rate., Results: Bony decompression exhibited a mere 20% volume expansion of the lower-half posterior fossa. C1L offered a 3% additional volume expansion, which rose to 5% when duraplasty was added ( p =0.029). There were no significant differences in complication rate when C1L was combined with duraplasty ( p =0.526). Syrinx volumes were analyzed in 38 patients who had undergone duraplasty. Among them, 28 patients who had undergone duraplasty without C1L demonstrated a 5.9% monthly decrease in syrinx volume, which was 7.5% in the remaining 10 patients with C1L ( p =0.040)., Conclusion: C1L was effective in increasing posterior fossa volume expansion, both with and without duraplasty. A more rapid decrease in syrinx volume occurred when C1L was combined with duraplasty., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Purpose: To identify the risk and protective factors affecting a salutogenic sense of health in adolescents with Moyamoya disease based on Antonovsky's salutogenesis theory., Methods: This study used a qualitative descriptive design. We interviewed adolescents diagnosed with Moyamoya disease and their parents and experts with experience in treating them from 4 July 2019 to 10 October 2019. Data analysis was performed according to the process of deductive content analysis based on Antonovsky's salutogenesis theory., Results: This study identified risk and protective factors affecting a salutogenic sense of health in adolescents with Moyamoya disease. Risk factors were closely related to problems with friends, parent relationships and academic work. Protective factors were identified as emotional support through interpersonal relationships, positive attitudes to the disease situation, ability to understand and predict patterns of symptoms, increasing strength to resolve the state of tension and developing available resources., Conclusion: The factors affecting a salutogenic sense of health in adolescents were identified reflecting on the characteristics of the developmental stage of adolescents and the symptoms and situations that are unique to adolescents. It is important for adolescents with Moyamoya disease to recognize available resources and use them appropriately to successfully manage the state of tension caused by stress., (© 2022 John Wiley & Sons Australia, Ltd.)

The 3D modeling of orbital bones in facial CT images is essential to provide a customized implant for reconstructions of orbit and related structures during surgery. However, 3D models of the orbital bone show an aliasing effect and disconnected thin bone in the inter-slice direction because the slice thickness is two to three times larger than the pixel spacing. To improve the inter-slice resolution of facial CT images, we propose a method based on a 2D convolutional neural network (CNN) that uses the spatial information on the sagittal and axial planes and the orbital bone edge-aware (OBE) loss. First, intermediate slices are generated on the sagittal plane. Second, the generated intermediate slices are transformed to an axial image, which is then compared with the original axial image. To generate intermediate slices with an accurate orbital bone structure, the OBE loss considering the orbital bone structure on the sagittal and axial planes is used. To improve the perceptual quality of the generated intermediate slices, the feature map difference loss is additionally used on the axial plane. In the experiment, the proposed method showed the best performance among bilinear and bicubic interpolations, 3D SRGAN, and a 2D CNN-based method. Experimental results confirmed that the proposed method can generate intermediate slices with clear edges of thin bones as well as cortical bones on both the sagittal and the axial plane., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Purpose: Multiple burr hole surgery is considered to be an option for achieving indirect revascularization in patients with ischemic Moyamoya disease (MMD). We aimed to investigate the efficacy of stand-alone multiple burr hole surgery for salvage revascularization in patients with MMD by assessing the hemodynamic changes via normalized time-to-peak (nTTP) analysis and independent component analysis (ICA) of preoperative and postoperative dynamic susceptibility contrast (DSC) perfusion MRI data., Methods: The DSC perfusion MRI data of 25 hemispheres from 21 patients with MMD, who underwent multiple burr hole surgery for salvage revascularization due to persistent or recurrent symptoms after primary revascularization with modified encephaloduroarteriosynangiosis (mEDAS), were analyzed. The nTTP, which was measured using the region of interests covering the entire surgical hemisphere, was compared between the preoperative and postoperative images. ICA was used to compare the relative arterial and venous components of the surgical hemispheres between the respective preoperative and postoperative images., Results: The median postoperative nTTP (1.80 s) was significantly shorter than the median preoperative nTTP (4.10 s) (P < 0.001). The postoperative relative arterial component of the surgical hemisphere (median: 0.04) was significantly higher than the preoperative relative arterial component (median: - 0.02, P < 0.001). In contrast, the postoperative relative venous component of the surgical hemisphere (median: - 0.05) was significantly lower than the preoperative value (median: 0.05, P < 0.001)., Conclusion: The improvement in cerebral perfusion parameters observed on postoperative DSC perfusion MRI demonstrated that stand-alone multiple burr hole surgery could be a favorable salvage revascularization technique after mEDAS failure in patients with ischemic MMD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function., (© 2021. The Author(s).)

Objective: To investigate the feasibility and clinical effectiveness of performing multiple burr hole surgery in pediatric moyamoya patients as a response to failed modified encephaloduroarteriosynangiosis (mEDAS)., Methods: From January 2014 to May 2018, multiple burr hole surgery (MBS) was conducted on 16 hemispheres in 12 patients as a secondary treatment following mEDAS. The male-to-female ratio was 1:2 and the average age at the time of mEDAS was 6 years old. The average patient age was 9 ± 3 years olds (range 7-17) at the time of MBS which occurred an average of 46 months after mEDAS. An average of 10 ± 1 holes (range 8-13) were made. Time-to-peak (TTP) magnetic resonance images (MRI) were taken along 20 axial cuts. Of these cuts, two consecutive cuts on the lateral ventricle were selected to calculate the average value of the region of interest (ROI). The value of the cerebellum was subtracted from the average value of two consecutive cuts. The ROI value was analyzed using a paired t test by SPSS 20 (SPSS Inc., Chicago, IL, USA)., Results: All 16 cases presented improvement of clinical symptoms as determined by ROI analysis of the TTP MRI images. The average ROI value was 5.03 ± 6.36 before MBS and - 15.54 ± 9.42 after MBS. The average change in the ROI value was - 20.58 ± 12.59. The ROI value decreased in all cases after MBS. Magnetic resonance angiography (MRA) also showed a positive effect on vascularization., Conclusion: In pediatric moyamoya patients, MBS is recommended as secondary option as a response to failed mEDAS. Its clinical effectiveness was shown by analyzing TTP images and assisted by MRA and digital subtraction angiography.

Aims: The purpose of this study is to explore the symptoms experienced by adolescents with moyamoya disease and to identify the characteristics of each symptom cluster associated with moyamoya disease., Design: A retrospective and descriptive design, which is a secondary data analysis study based on electronic medical record data from hospitals., Methods: To assess the symptoms associated with moyamoya disease, a qualitative study was conducted on 12 adolescents, 12 caregivers and 12 experts on moyamoya disease. According to a qualitative study, 12 main symptoms (limb weakness, numbness, pins and needles, difficulty in speech, blurred vision, facial paralysis, hand tremors, involuntary movements, convulsions, dizziness, nausea/vomiting and headaches) were selected. Data were collected around these symptoms. The data collection was carried out through the Electronic Medical Record (EMR) data of 303 adolescents aged 13-19 who were diagnosed with moyamoya disease (ICD 10 Code: I67.5) between January 2010-December 2019 in a hospital in Seoul, South Korea. Cluster analysis was applied to identify symptom clusters with the hierarchical cluster agglomerative approach. We used the log-likelihood distance to measure the similarity of variables. Proximity between groups of variables was measured using the two-step method., Results: The physical symptoms experienced by adolescents with moyamoya disease were 'limb weakness' - the most common - followed by a 'headache,' 'difficulty in speech,' and 'nausea/vomiting.' A total of five symptom clusters were derived: cluster 1 was characterized by 'limb weakness'; cluster 2 participants were asymptomatic or experienced 'convulsions'; cluster 3 experienced 'difficulty in speech' and 'facial paralysis'; cluster 4 is prone to 'dizziness' and 'pins and needles'; and cluster 5 displays 'headaches' and 'nausea/vomiting'., Conclusion: This study offers a multidimensional approach for identifying differences in clinical symptoms of moyamoya disease among adolescents., Impact: These results will help provide interventions concerning the characteristics of the symptoms of moyamoya disease among adolescents., (© 2021 John Wiley & Sons Ltd.)

Clinical practitioners treating moyamoya disease recognize the need for a systematic approach to better manage the disease in adolescent patients with the disease. Methods : This study aimed to develop and evaluate the validity and reliability of a disease scale which measures the health-related behaviors of adolescents with moyamoya disease. Results : The final 12-item Moyamoya-HB Scale for adolescents was categorized by three sub-domains: implementation of treatment for moyamoya disease (four items); health promoting behavior for moyamoya disease (four items); and health coping behavior for moyamoya disease (four items). Overall, these factors explained 68.97% of the total variance. The results of the confirmative factor analysis supported the construct, convergent and discriminant validity of the three sub-domains. The Moyamoya-HB Scale for adolescents also demonstrated a concurrent validity with the Korean Adolescents' Health Behaviors Tool (r = 0.59, p < 0.001). Reliability analysis showed an acceptable-to-high Cronbach's alpha of 0.865 in total, and the subscales ranged from 0.800 to 0.841. Conclusions : Initial findings support the Moyamoya-HB Scale as a reliable and valid measure of health behaviors in adolescents with moyamoya disease.

Purpose: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx)., Methods and Materials: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis., Results: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively., Conclusions: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Moyamoya disease (MMD) is a rare form of intracranial stenoocclusive disease that can be associated with intracranial aneurysms. We evaluated the clinical features and outcomes of MMD-associated aneurysms while focusing on their locations., Methods: Between January 1998 and December 2018 there were 1,302 adult and pediatric patients diagnosed as MMD at a single institution. These patients included 38 with 44 MMD-associated aneurysms. The MMD-associated aneurysms were classified into two groups based on their locations: major-artery aneurysms and non-major-artery aneurysms. The clinical and radiological data for patients with MMD-associated aneurysms were reviewed retrospectively., Results: The 44 MMD-associated aneurysms comprised 28 in major arteries and 16 in nonmajor arteries. All of the major-artery aneurysms were initially unruptured lesions, and follow-up angiography showed that 23 (82.1%) had an improved or stable status and 5 (17.9%) had a worse status. The non-major-artery aneurysms comprised 10 ruptured and 6 unruptured lesions, and follow-up angiography showed that 11 (68.8%) had improved or were stable and 5 (31.2%) had worsened. At the latest follow-up, there were four cases of unfavorable outcome: two initial hemorrhagic insults, one treatment-related morbidity, and one repeated-hemorrhage case., Conclusions: MMD-associated aneurysms occurred in 3.3% of the MMD cohort in this study, of which 63.6% were major-artery aneurysms and 36.4% were non-major-artery aneurysms. The major-artery group included 17.9% that became angiographically worse, while 31.2% were growing or hemorrhaging in the non-major-artery group., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Purpose: The purpose of this study was to identify the optimal timing for screening spinal cord ultrasonography (US) to detect filum terminale lipoma in infants., Methods: We retrospectively reviewed infants (<12 months old) who underwent repeated spinal cord US between April 2011 and January 2019. We excluded infants if they only had one US examination, or if they had lesions other than filum terminale lipoma. Infants with filum terminale lipoma on magnetic resonance imaging were included in the lipoma group and the others in the control group. A linear mixed model was used to assess differences in the growth pattern of filum terminale thickness by age and group. The cutoff thickness on US and its diagnostic performance were assessed according to age., Results: Among 442 infants with 901 US examinations, 46 were included in the lipoma group and 58 in the control group. Sixty-seven infants had unmeasurable filum terminale thickness on initial US, including 55 neonates (82.1%) before 1 month of age. The lipoma group had significantly greater filum terminale thickness than the control group (P<0.001). Thickness increased with age in the lipoma group (P=0.027). The sensitivity of US was 87.5% and the area under the receiver operating characteristic curve was 0.949 (95% confidence interval, 0.849 to 0.991) with a cutoff value of 1.1 mm in 4- to 6-month-old infants., Conclusion: Screening spinal cord US could effectively diagnose filum terminale lipoma in 4- to 6-month-old infants with a cutoff thickness of 1.1 mm. Spinal cord US can be used to screen young infants with intraspinal abnormalities.

Purpose: To provide the insight for postoperative hypotonia. Selective posterior rhizotomy (SPR) has been proved as a powerful tool for reducing spasticity. And also, its functional benefit and long-term effect are also well-known., Results: The most considered side effect of this procedure is postoperative hypotonia. However, some extent of temporary postoperative hypotonia can be the marker of the long-term success of this procedure. While the return of spasticity is the most unwanted side effect, some kind of overfitting, temporary postoperative hypotonia, can be the solution for that., Conclusion: For severely deformed patients, postoperative hypotonia may not be problematic, because severe spasticity makes them deformed and disabled. Deformed body will not show a definite disability from postoperative hypotonia.

Moyamoya disease in adults is a chronic, progressive disorder characterized by fine collateral vessel networks in the brain. The disorder can lead to negative mood and stress, which, left unresolved, may increase adverse health outcomes. We conducted a cross-sectional survey to examine stress and mood of adults with moyamoya disease. Participants were recruited at a university hospital in Seoul, Korea. Data were collected through questionnaires and review of participants' electronic medical records. A total of 109 adults participated. Significant correlations were found between perceived stress, anxiety, and depression. Adults with moyamoya disease experience anxiety, depression, and stress related to the risk of cerebral hemorrhage or ischemia, similar to those with other cerebrovascular disease. If negative mood and stress were uncontrolled, those can cuase adverse health outcomes. Health professionals caring for people with moyamoya disease should carefully observe their stress and mood and develop interventions tailored to stages of disease to help them manage. The study results provide baseline information for understanding the level of, and the factors associated with, stress and mood., (© 2020 John Wiley & Sons Australia, Ltd.)

Background: Genetic factors play an important role in the pathogenesis of craniosynostosis (CRS). However, the molecular diagnosis of CRS in clinical practice is limited because of its heterogeneous etiology., Objective: To investigate the genomic landscape of CRS in a Korean cohort and also to establish a practical diagnostic workflow by applying targeted panel sequencing., Methods: We designed a customized panel covering 34 CRS-related genes using in-solution hybrid capture method. We enrolled 110 unrelated Korean patients with CRS, including 40 syndromic and 70 nonsyndromic cases. A diagnostic pipeline was established by combining in-depth clinical reviews and multiple bioinformatics tools for analyzing single-nucleotide variants (SNV)s and copy number variants (CNV)s., Results: The diagnostic yield of the targeted panel was 30.0% (33/110). Twenty-five patients (22.7%) had causal genetic variations resulting from SNVs or indels in 9 target genes (TWIST1, FGFR3, TCF12, ERF, FGFR2, ALPL, EFNB1, FBN1, and SKI, in order of frequency). CNV analysis identified 8 (7.3%) additional patients with chromosomal abnormalities involving 1p32.3p31.3, 7p21.1, 10q26, 15q21.3, 16p11.2, and 17p13.3 regions; these cases mostly presented with syndromic clinical features., Conclusion: The present study shows the wide genomic landscape of CRS, revealing various genetic factors for CRS pathogenesis. In addition, the results demonstrate that an efficient diagnostic workup using target panel sequencing provides great clinical utility in the molecular diagnosis of CRS., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Aim: To understand the daily lived experiences of adult moyamoya disease patients., Methods: This qualitative study involved a purposive sample of 14 adult moyamoya disease patients diagnosed after 19 years or older at one university hospital in Seoul. Interviews conducted with patients included open-ended questions about the experience of living with moyamoya disease. The data were analyzed using Colaizzi's seven-step method, which derives the theme., Results: Participants' experiences were divided into three themes and eight sub-themes. "Having an unexpected disease that suddenly struck my life" refers to confusion and depression due to the diagnosis of the unexpected illness; "being occasionally anxious about the illness" describes patients' uncertainty about the disease and worrying about passing the disease on to their child; and "living with the disease by going through the disease experience" refers to the process of accepting and adapting to the illness., Conclusions: The findings provide a better understanding of the life changes and lived experiences of adult patients with moyamoya disease. Nurses should consider various aspects when providing care to adult moyamoya disease patients., (© 2020 Japan Academy of Nursing Science.)

Background: Moyamoya disease (MMD) is a known progressive obstructive cerebrovascular disorder. Monitoring and managing mood and stress are critical for patients with MMD, as they affect clinical outcomes. The ecological momentary assessment (EMA) method is a longitudinal study design by which multiple variable assessments can be performed over time to detect momentary fluctuations and changes in psychological dimensions such as mood and stress over time., Objective: This study aimed to identify predicting factors associated with momentary mood and stress at both the within-person and between-person levels and to examine individual fluctuation of mood over time in the short term using an EMA method combined with a mobile phone app., Methods: Participants aged older than 18 years were recruited from a tertiary hospital in Seoul, Korea, between July 2018 and January 2019. The PsyMate scale for negative affect (NA) and positive affect (PA) and the Trier Inventory for Chronic Stress Scale were uploaded on patient mobile phones. Using a mobile app, data were collected four times a day for 7 days. Pearson correlations and mixed modeling were used to predict relationships between repeatedly measured variables at both the between-person and within-person levels., Results: The mean age of the 93 participants was 40.59 (SD 10.06) years, 66 (71%) were female, and 71 (76%) were married. Participants provided 1929 responses out of a possible 2604 responses (1929/2604, 74.08%). The mean momentary NA and PA values were 2.15 (SD 1.12) and 4.70 (SD 1.31) out of 7, respectively. The momentary stress value was 2.03 (SD 0.98) out of 5. Momentary NA, PA, and stress were correlated (P<.001) and varied over time in relation to momentary variables. Common momentary variables associated with momentary mood and stress at both the within-person (level 1) and between-person (level 2) levels were identified. Momentary NA increased when being alone and being at the hospital at both levels, whereas momentary PA increased when eating or drinking, resting, being at a café, restaurant or a public place but decreased when being alone at both levels. Momentary stress increased when being at the office, at a public place, or as the time of the day went by but decreased when resting or during the weekend. Different factors affecting mood and stress at different levels were identified. Fluctuations in individual momentary mood over time at the within-person level were captured., Conclusions: The EMA method using a mobile phone app demonstrated its ability to capture changes in mood and stress in various environmental contexts in patients with MMD. The results could provide baseline information for developing interventions to manage negative mood and stress of patients with MMD based on the identified predictors affecting mood and stress at two different levels., (©Yong Sook Yang, Gi Wook Ryu, Chang Gi Park, Insun Yeom, Kyu Won Shim, Mona Choi. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 25.05.2020.)

Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with healthy blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol ( p = 0.042) and apolipoprotein (Apo)B-100 ( p = 0.003) levels, and decreased postprandial maximum concentrations (C max ) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels ( p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites. This study suggests that LPQ180 might be developed as a functional ingredient to help maintain healthy postprandial lipid levels through modulating gut environment.

Low-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking. In total, 446 tissues samples from 232 intractable epilepsy patients with various brain pathologies were analyzed using deep sequencing (average read depth, 1112x) of known epilepsy-related genes (up to 28 genes) followed by confirmatory site-specific amplicon sequencing. Pathogenic mutations were discovered in 31.9% (74 of 232) of the resected epilepsy brain tissues and were recurrently found in only eight major focal epilepsy genes, including AKT3, DEPDC5, MTOR, PIK3CA, TSC1, TSC2, SCL35A2, and BRAF. Somatic mutations, two-hit mutations, and germline mutations accounted for 22.0% (51), 0.9% (2), and 9.1% (21) of the patients with intractable epilepsy, respectively. The majority of pathogenic somatic mutations (62.3%, 33 of 53) had a low variant allelic frequency of less than 5%. The use of deep sequencing replicates in the eight major focal epilepsy genes robustly increased PPVs to 50-100% and sensitivities to 71-100%. In an independent FCDII cohort of only unmatched FFPE brain tissues, deep sequencing replicates in the eight major focal epilepsy genes identified pathogenic somatic mutations in 33.3% (5 of 15) of FCDII individuals (similar to the genetic detecting rate in the entire FCDII cohort) without any false-positive calls. Deep sequencing replicates of major focal epilepsy genes in unmatched FFPE brain tissues can be used to accurately and efficiently detect low-level somatic mutations, thereby improving overall patient care by enriching genetic counseling and informing treatment decisions.

Background: Temporalis muscle (TM) hollowing is a complication of cranioplasty which diminishes the aesthetical outcome of the surgery and results in suboptimal functional outcome. We present and compare a modified split-temporalis muscle elevated margin cranioplasty using 3-dimensional printed titanium implant with conventional 3-dimensional printed titanium implant cranioplasty to determine an effective treatment method., Methods: A modified 3-dimensional printed cranial implant was designed where the anteroinferior border of the implant was extended and elevated between the frontozygomatic suture and root of zygomatic process. Furthermore, the implant was placed in between superficial and deep layers of the temporalis muscle. Aesthetical evaluation was carried out at the outpatient clinic, and a quantitative analysis showing the percentage difference in length of the operated and nonoperated sides was performed., Results: For both conventional and augmented groups, there were 0% major or minor complications. Out of 10 conventional cranioplasty patients, there were 3 cases of mild and 1 case of severe TM hollowing, whereas for 10 augmented cranioplasty patients, there was only 1 patient with mild TM hollowing. When a quantitative analysis was carried out, the overall percentage difference in length at the coronal view for conventional and augmented cranioplasty was -2.17% and 0.07%, respectively., Conclusions: The augmented cranioplasty leads to superior aesthetical outcome, and the quantitative analysis also supports the efficacy of augmented cranioplasty. The surgery is technically simpler than the conventional method, therefore lowering the risk of surgical complications. Therefore, we hope that the modified cranioplasty method will be considered as an effected cranioplasty method for preventing TM hollowing., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Long-term results following bariatric surgery compared to conventional treatments has never been reported in morbidly obese Korean patients. This study aimed to evaluate the long-term efficacy of bariatric surgery in morbidly obese Korean patients compared to conventional medical treatments., Methods: In this multicenter retrospective cohort study, we reviewed 137 obese subjects between January 2008 and February 2011 with a body mass index (BMI) > 30 kg/m 2 who had more than 5 years of follow-up clinical data after bariatric surgery (surgery group, n = 49) or conventional treatment (conventional treatment group, n = 88). Anthropometric data and the status of comorbidities were compared between the 2 groups., Results: The median follow-up period was 72.1 months (range 19.3-109.7 months). At the last follow-up, the surgery group showed a greater amount of total weight loss than the conventional treatment group (24.9% vs. 2.8%, P < 0.001). The prevalence of diabetes and hypertension significantly decreased in the surgery group, while the conventional treatment group showed a marked increase in these comorbidities. In the surgery group, Roux-en-Y gastric bypass and sleeve gastrectomy achieved comparable long-term weight loss (26.5% vs. 22.4%, respectively; P = 0.087)., Conclusion: In the long-term, bariatric surgery achieved and maintained significantly greater weight reduction, as well as a decrease in obesity-related comorbidities, than did conventional medical therapy in morbidly obese Korean patients., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: Low-grade epilepsy-associated tumors (LEATs) are associated with childhood seizures that are typically drug-resistant, necessitating surgical interventions. In this study, we aimed to investigate the efficacy of surgical intervention in children with LEATs and to identify factors associated with seizure and cognitive outcomes., Methods: We reviewed 58 children less than 18 years of age who underwent epilepsy surgery due to histopathologically confirmed LEATs and had a minimum postoperative follow-up duration of 24 months., Results: Of the 58 patients who were followed for a median duration of 5.6 (IQR 3.2 to 10.0) years, 51 (87.9%) were seizure-free after surgery. In univariate analysis, shorter epilepsy duration, fewer antiepileptic drugs at time of surgery, gross total resection, and unilobar tumor involvement were associated with seizure freedom. In multivariate analysis, gross total resection was independently associated with seizure freedom. The preoperative and postoperative full-scale intelligence quotient (FSIQ) scores were 78.9 ± 27.1 and 80.9 ± 28.7, respectively. In univariate analysis, younger age at seizure onset, longer epilepsy duration, more antiepileptic drugs at time of surgery, multilobar tumor involvement, and presence of generalized epileptic discharges were associated with lower preoperative FSIQ. In multivariate analysis, longer epilepsy duration was independently associated with lower preoperative FSIQ scores. Postoperative FSIQ scores were significantly influenced by preoperative FSIQ scores., Conclusions: Epilepsy surgery for LEATs in children resulted in excellent seizure outcome. Gross total resection was the only independent factor associated with favorable seizure outcome. Preoperative and postoperative cognitive abilities were significantly influenced by epilepsy duration, so early surgical intervention should be considered., (Copyright © 2018. Published by Elsevier Inc.)

Objective: With the recognition of epilepsy as a network disease that disrupts the organizing ability of resting-state brain networks, vagus nerve stimulation (VNS) may control epileptic seizures through modulation of functional connectivity. We evaluated preoperative 2-deoxy-2[ 18 F]fluoro-D-glucose (FDG) positron emission tomography (PET) in VNS-implanted pediatric patients with refractory epilepsy to analyze the metabolic connectivity of patients and its prognostic role in seizure control., Methods: Preoperative PET data of 66 VNS pediatric patients who were followed up for a minimum of 1 year after the procedure were collected for the study. Retrospective review of the patients' charts was performed, and five patients with inappropriate PET data or major health issues were excluded. We conducted an independent component analysis of FDG-PET to extract spatial metabolic components and their activities, which were used to perform cross-sectional metabolic network analysis. We divided the patients into VNS-effective and VNS-ineffective groups (VNS-effective group, ≥50% seizure reduction; VNS-ineffective group, <50% reduction) and compared metabolic connectivity differences between groups using a permutation test., Results: Thirty-four (55.7%) patients showed >50% seizure reduction from baseline frequency 1 year after VNS. A significant difference in metabolic connectivity evaluated by preoperative FDG-PET was noted between groups. Relative changes in glucose metabolism were strongly connected among the areas of brainstem, cingulate gyrus, cerebellum, bilateral insula, and putamen in patients with <50% seizure control after VNS., Significance: This study shows that seizure outcome of VNS may be influenced by metabolic connectivity, which can be obtained from preoperative PET imaging. This study of metabolic connectivity analysis may contribute in further understanding of the mechanism of VNS in intractable seizures., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Aim: The main purposes of the study were (i) to evaluate serum vitamin D concentration in the forms of 25(OH)D 2 , 25(OH)D 3 and total 25(OH)D in Korean postmenopausal women using the LC-MS/MS method, which offers increased sensitivity and selectivity; (ii) to determine the relationship between the bone turnover marker, parathyroid hormone (PTH) and 25(OH)D 3 , total 25(OH)D separately; and (iii) to determine the factors that may be associated with vitamin D deficiency using body composition analysis and laboratory blood tests., Method: A total of 200 postmenopausal women were recruited from November 2012 to March 2014. To control for seasonal ultraviolet exposure time differences in serum 25(OH)D, laboratory tests were performed only from November to March when vitamin D is not synthesized. Independent relationships between 25(OH)D 3 , total 25(OH)D and other variables were assessed by multiple regression analysis., Results: The mean serum 25(OH)D 2 , 25(OH)D 3 and total 25(OH)D levels were 0.51 (±0.44) ng/mL, 14.23 (±7.05) ng/mL and 14.69 (±7.13) ng/mL, respectively. Both 25(OH)D 3 and total 25(OH)D were positively correlated with erythrocyte sedimentation rate (ESR), Apo A-I and C-terminal cross-linked telopeptides of type I collagen in Korean postmenopausal women. Both serum 25(OH)D 3 and total 25(OH)D were negatively correlated with alkaline phosphatase , PTH and percent body fat. However, osteocalcin showed a negative correlation (r = -0.451; P = 0.041) with only 25(OH)D 3 and not with total 25(OH)D (r = -0.417; P = 0.064)., Conclusion: Both 25(OH)D 3 and total 25(OH)D were negatively correlated with PTH, a bone formation marker (alkaline phosphatase) and percent body fat. Both 25(OH)D 3 and total 25(OH)D were positively correlated with a bone resorption marker (C-terminal cross-linked telopeptides of type I collagen), ESR and Apo A-I after multiple regression analysis., (© 2018 Japan Society of Obstetrics and Gynecology.)

OBJECTIVE For patients with moyamoya disease (MMD), surgical intervention is usually required because of progressive occlusion of the internal carotid artery. The indirect bypass method has been widely accepted as the treatment of choice in pediatric patients. However, in adult patients with MMD, the most effective treatment method remains a matter of debate. Here, the authors compared the clinical outcomes from MMD patients treated with either extracranial-intracranial arterial bypass (EIAB; 43 hemispheres) or modified encephaloduroarteriosynangiosis (mEDAS; 75 hemispheres) to investigate whether mEDAS is an effective surgical method for treating adults with symptomatic MMD. METHODS A comparative analysis was performed in patients treated using either mEDAS or EIAB. Collateral grading, collateral vein counting, and symptom analysis were used to assess the outcome of surgery. RESULTS Seventy-seven percent (58/75) of mEDAS cases and 83.7% (36/43) of EIAB cases in the analysis experienced improvement in their symptoms after surgery. Furthermore, patients in 98.7% (74/75) of mEDAS cases and those in 95.3% (41/43) of EIAB cases exhibited improved collateral grades. Increases in regions of perfusion were seen after both procedures. CONCLUSIONS Modified EDAS and EIAB both result in positive outcomes for symptomatic adults with MMD. However, when considering the benefit of both surgeries, the authors propose mEDAS, a simpler and less strenuous surgery with a lower risk of complications, as a sufficient and safe treatment option for symptomatic adults with MMD.

Hemispherectomy constitutes an established surgical method in the management of patients with medically intractable epilepsy secondary to severe unilateral hemisphere damage. As opposed to focal resections, in hemispherotomies, the entire hemisphere is disconnected from the remaining nervous system, including the functional regions and fibers. Despite this, hemispherotomy is recommended for certain indications, and has good functional and epilepsy outcomes. Here we describe the indications, epilepsy outcomes, and surgical techniques for several hemispheric surgeries.

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases.

Purpose: Moyamoya disease (MMD) commonly leads to neurocognitive impairment. This study was carried out to show that temporal encephaloduroarteriosynangiosis (EDAS) has a positive neuropsychological impact on pediatric MMD patients., Methods: Fifty-five participants diagnosed with MMD from 2008 to 2014 were included in this retrospective study. The mean age at the preoperative evaluation was 9.5 years and the mean age at postoperative evaluation was 10.4. The average interval of initial and follow-up test was 10 months. K-WISC-III, Rey-Kim memory test, Children's Color Trails test (CCTT), Wisconsin Card Sorting Test (WCST), and Advanced Test of Attention (ATA) were used to evaluate patient's neurocognitive profile., Results: In this study, preoperative and postoperative neuropsychological fields were compared. Prior operation, pediatric MMD patients showed 54.2% deficit of inattention but only around 2.5% deficit in verbal memory recall function. There was a significant increase of performance IQ and PO score component of PIQ improved almost 10 scores after surgery. For memorial function, there was an improvement of approximately 10 scores in MQ after the surgery. This study also showed parietal activation following surgical treatment which enhanced the ability to interpret visual materials, to register and to retrieve visual information. Interestingly, despite the parietal cover surgery, there was a significant improvement of performance on WCST and CCTT measuring the prefrontal executive function. Concerning failure to maintain set, no significant postoperative improvements were made. However, simple and selective visual attention on ATA was significantly improved postoperatively., Conclusions: The results from neuropsychological field comparison testifies the effectiveness of temporal EDAS in pediatric MMD patients. The surgery not only enhances the blood flow in operative regions, but it also improves the broad cerebral function including frontoparietal domains. Such alteration leads to overall advancement in cognitive function which are impaired due to MMD.

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not. SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms., (Copyright © 2018 the authors 0270-6474/18/385042-11$15.00/0.)

Background : Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods : Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEM TM ) was conducted to monitor changes in coagulation perioperatively. Results : Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions : TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Cranial surgical site infection is a significant cause of morbidity and mortality in hospitals. Preoperative hair shaving for cranial neurosurgical procedures is performed traditionally in an attempt to protect patients against complications from infections at cranial surgical sites. However, preoperative shaving of surgical incision sites using traditional surgical blades without properly washing the head after surgery can cause infections at surgical sites. Therefore, a rapid protocol in which the scalp remains unshaven and absorbable sutures are used for scalp closure with early postoperative shampooing is examined in this study., Methods: A retrospective comparative study was conducted from January 2008 to December 2012. A total of 2,641 patients who underwent unshaven cranial surgery with absorbable sutures for scalp closure were enrolled in this study. Data of 1,882 patients who underwent surgery with the traditional protocol from January 2005 to December 2007 were also analyzed for comparison., Results: Of 2,641 patients who underwent cranial surgery with the rapid protocol, all but 2 (0.07%) patients experienced satisfactory wound healing. Of 1,882 patients who underwent cranial surgery with the traditional protocol, 3 patients (0.15%) had infections. Each infection occurred at the superficial incisional surgical site., Conclusion: Unshaven cranial surgery using absorbable sutures for scalp closure with early postoperative shampooing is safe and effective in the cranial neurosurgery setting. This protocol has a positive psychological effect. It can help patients accept neurosurgical procedures and improve their self-image after the operation., (© 2017 S. Karger AG, Basel.)

Normal pressure hydrocephalus (NPH) is a chronic disorder caused by interrupted CSF absorption or flow. Generally, shunt placement is first option for NPH treatment. Due to complications of ventriculo-peritoneal (VP) shunt placement, endoscopic third ventriculostomy (ETV) can be considered as an alternative treatment option. Here we report the efficacy of ETV especially in old aged patients with normal pressure hydrocephalus. Total 21 old aged patients with communicating hydrocephalus with opening pressure, measured via lumbar puncture, less than 20cm H 2 O underwent ETV. 15 patients had primary/idiopathic NPH and 6 patients had secondary NPH. All patients were studied with a MRI to observe the flow void at aqueduct and the fourth ventricle outflow. And all of them underwent ETV. In a group with peak velocity was higher than 5cm/s, nine patients (75%) were evaluated was 'favorable' and three of them (25%) was scored 'poor'. In another group with peak velocity less than 5cm/s, three of them were scored 'poor' and two of them were scored 'stable'. None of them was evaluated as 'favorable'. We also evaluated the outcomes according to etiology: 12 patients (80% of the patients with primary NPH) were evaluated with 'favorable' after ETV treatment. Two patients (13.3%) were as 'stable'. And one patient was as 'poor' evaluated. Five patients (83.3%) among patients with secondary NPH were as 'poor' evaluated and one of them was stable and no patient was as 'favorable' evaluated. 4 patients, which was as 'poor' evaluated in the group with the secondary NPH, underwent additional VP shunt implantation. Overall, the outcomes of the group with the idiopathic NPH after ETV treatment were more favorable than of the group with the secondary NPH. Our study suggest that ETV can be effective for selected elderly patients with primary/idiopathic NPH, when they satisfy criteria including positive aqueduct flow void on T2 Sagittal MRI and the aqueductal peak velocity, which is greater than 5cm/s on cine MRI., (Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.)

Purpose: Cranioplasty for recovering skull defects carries the risk for a number of complications. Various materials are used, including autologous bone graft, metallic materials, and non-metallic materials, each of which has advantages and disadvantages. If the use of autologous bone is not feasible, those artificial materials also have constraints in the case of complex anatomy and/or irregular defects., Material and Methods: This study used metal 3D-printing technology to overcome these existing drawbacks and analyze the clinical and mechanical performance requirements. To find an optimal structure that satisfied the structural and mechanical stability requirements, we evaluated biomechanical stability using finite element analysis (FEA) and mechanical testing. To ensure clinical applicability, the model was subjected to histological evaluation. Each specimen was implanted in the femur of a rabbit and was evaluated using histological measurements and push-out test., Results and Conclusion: We believe that our data will provide the basis for future applications of a variety of unit structures and further clinical trials and research, as well as the direction for the study of other patient-specific implants.

Purpose: The purpose of this study was to evaluate the association between ascending aortic diameter (AAD) as measured with low-dose chest computed tomography (LDCT) and hypertension in Korean men., Methods: Korean men (n=1,050) who were screened for lung cancer using LDCT imaging at a health promotion center in Seoul, Korea between January 1 and December 31were recruited for the study. AAD is the longest length of ascending aorta measured from approximately 15 mm above left main coronary ostium to the mid-slice level of the right pulmonary artery., Results: AAD were divided into quartiles, and the degree of hypertension was determined based on the quartiles of the AAD using logistic regression. Odds ratios (OR) for the proportion of hypertension in Q2 (1.70, 95% CI: 1.11-2.59), Q3 (2.72, 95% CI: 1.81-4.09) and Q4 (3.94, 95% CI: 2.63-5.89) were significantly greater than that of Q1 (P for trend < 0.001). Even after controlling for confounding covariates of age, BMI, total cholesterol, HDL-cholesterol, fasting glucose, GGT, ALT, eGFR, smoking status and alcohol intake, there was significant correlation., Conclusion: AAD was significantly associated with the degree of hypertension.

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.

Background: The sodium intake of Koreans was higher than that recommended by the World Health Organization. Urinary sodium, which is correlated with sodium intake, can be easily calculated by the Tanaka's equation. This study aimed to evaluate the association between urinary sodium and metabolic syndrome in Korean adults using the 2010-2011 Korean National Health and Nutrition Examination Survey (KNHANES)., Methods: A total of 5,870 participants from the 2010-2011 KNHANES were included in this study. Twenty-four hour urinary sodium was calculated by the Tanaka's equation using spot urine. Participants were divided into tertiles based on urinary sodium levels. The association between urinary sodium and metabolic syndrome was analyzed using multivariate logistic regression analysis., Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome for the 2nd and 3rd tertile of urinary sodium levels was 1.51 (1.16-1.97) and 1.56 (1.23-1.97) compared to the lowest tertile of urinary sodium in men. The ORs and 95% CIs of metabolic syndrome in women were 1.20 (0.95-1.51) for the 2nd tertile and 2.16 (1.68-2.78) for the 3rd tertile. These associations remained statistically significant, even after adjusting for multiple covariates such as age, education, regular exercise, smoking, and alcohol consumption., Conclusion: These findings indicate that urinary sodium is significantly associated with metabolic syndrome in Korean adults., Competing Interests: CONFLI CT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Introduction: The object of this study is to understand abnormal dynamic of cerebrospinal fluid (CSF) in patients with neurofibromatosis type 1 (NF1), which may cause temporal lobe herniation and bulging of temporal fossa., Methods: Four patients, three females and one male, with NF1 were studied retrospectively. They presented with a similar craniofacial deformity, which consisted of pulsatile exophthalmos, an enlarged bony orbit, dysplasia of the sphenoid wing with the presence of a herniation of the temporal lobe into the orbit, and a bulging temporal fossa., Results and Discussion: Surgical exploration demonstrated abnormally thickened arachnoid membrane in one case. Protruding temporal lobe, which was one of the main symptoms in NF1 patients, could be stopped by control of intracranial pressure (ICP) via programmable ventriculoperitoneal shunt (VPS) or extra ventricle drainage implantation. The dense fibrosis of the arachnoid membrane and consequent altered hemispheric CSF dynamics may cause symptoms including pulsatile exophthalmos and consequent worsening of vision, prolapse of the temporal lobe, and enlargement of the temporal fossa. This finding may not present with general features of hydrocephalus, so that delays in diagnosis often result., Conclusion: For the NF1 patients with cranio-orbito-temporal deformities, prior to any surgical reconstruction, control of increased ICP (IICP) should be primarily considered.

Hypothalamic hamartoma (HH) is a benign indolent lesion despite the presentation of refractory epilepsy. Behavioral disturbances and endocrine problems are additional critical symptoms that arise along with HHs. Due to its nature of generating epileptiform discharge and spreading to cortical region, various management strategies have been proposed and combined. Surgical approaches with open craniotomy or endoscopy, stereotactic approaches with radiosurgery and gamma knife surgery or radiofrequency thermos-coagulation, and laser ablation have been introduced. Topographical dimension and the surgeon's preference are key factors for treatment modalities. Endoscopic disconnection has been one of the most favorable options performed in treating HHs. Here we discuss presurgical evaluation, patient selection, surgical procedures, and complications.

Neuroendoscopic surgery is performed because it causes minimal damage to normal structures, carries a lower rate of complications, and achieves excellent outcomes. Surgeons using an endoscope and related instruments can perform complex operations through very small incisions, which is especially useful for minimally invasive procedures for the brain and spine. Neuroendoscopic surgery is now performed in cases of obstructive hydrocephalus, various intraventricular lesions, hypothalamic hamartomas, craniosynostosis, skull base tumors, and spinal lesions. This review discusses the brief history of neuroendoscopy and the current state and future perspectives of endoscopic surgery.

Background: In evaluation of craniosynostosis patients in terms of neurodevelopmental delay, positron emission tomography computed tomography (PET-CT) scan can be used to assess brain abnormalities through glucose metabolism. We aimed to determine the unnecessity of PET-CT in this study., Methods: Thirty-eight patients diagnosed with craniosynostosis who underwent distraction osteogenesis from October, 2010 to November, 2013 were reviewed. Magnetic resonance imaging (MRI) and PET-CT scan were carried out for evaluation of the brain structure and function, whereas X-ray and CT scan were taken for evaluation of the skull., Results: Nine patients reported abnormal MRI findings which were not significant, and five patients showed local problem on brain on PET-CT scan. No correlation was found among them., Conclusion: PET-CT evaluation of possible abnormal brain findings do not affect surgical planning or require additional therapy. Preoperative PET-CT scan is not the essential study to get any etiologic information of the disease consequences or to establish the treatment plan., Competing Interests: No potential conflict of interest relevant to this article was reported.