Three-dimensional evaluation of the association between tongue position and upper airway morphology in adults: A cross-sectional study / 대한치과교정학회지

Objective@#This study aimed to evaluate the association between low tongue position (LTP) and the volume and dimensions of the nasopharyngeal, retropalatal, retroglossal, and hypopharyngeal segments of the upper airway. @*Methods@#A total of 194 subjects, including 91 males and 103 females were divided into a resting tongue position (RTP) group and a LTP group according to their tongue position. Subjects in the LTP group were divided into four subgroups (Q1, Q2, Q3, and Q4) according to the intraoral space volume. The 3D slicer software was used to measure the volume and minimum and average cross-sectional areas of each group. Airway differences between the RTP and LTP groups were analyzed to explore the association between tongue position and the upper airway. @*Results@#No significant differences were found in the airway dimensions between the RTP and LTP groups. For both retropalatal and retroglossal segments, the volume and average cross-sectional area were significantly greater in the patients with extremely low tongue position. Regression analysis showed that the retroglossal airway dimensions were positively correlated with the intraoral space volume and negatively correlated with A point-nasion-B point and palatal plane to mandibular plane. Males generally had larger retroglossal and hypopharyngeal airways than females. @*Conclusions@#Tongue position did not significantly influence upper airway volume or dimensions, except in the extremely LTP subgroup.

Impact of the Coronavirus Disease 2019 Pandemic on Pediatric Gastrointestinal Endoscopy:A Questionnaire-based Internet Survey of 162 Institutional Experiences in Asia Pacific / 대한소아소화기영양학회지

Purpose@#The impact of coronavirus 2019 (COVID-19) on gastrointestinal (GI) endoscopy procedures in adults has been reported, with a drastic reduction in the number of procedures.However, there are no sufficient data regarding the impact on pediatric GI endoscopy. Here, we aimed to report that impact in the Asia-Pacific region. @*Methods@#A questionnaire-based internet survey was conducted from June to November 2021 among pediatric endoscopy institutions in the Asia-Pacific region, with each institution providing a single response. Overall, 25 questions focused on the impact of the number of procedures conducted, the usage of personal protective equipment (PPE), and endoscopy training programs during the pandemic. @*Results@#A total of 162 institutions across 13 countries in the Asia-Pacific region participated in the study, and 133 (82.1%) institutions underwent procedure changes since the emergence of COVID-19. The number of esophagogastroduodenoscopy and ileocolonoscopy procedures decreased in 118/133 (88.7%) and 112/133 (84.2%) institutions, respectively. Endoscopy for patient with positive COVID-19 in an emergency or urgent cases still carried out in 102/162 (62.9%) institutions. Screening of COVID-19 for all patients before endoscopy was done across 110/162 (67.9%) institutions. PPE recommendations varied among institutions.Pediatric gastrointestinal endoscopy training programs were discontinued in 127/162 (78.4%) institutions. @*Conclusion@#This study reports the impact of the COVID-19 pandemic on pediatric gastrointestinal endoscopy in the Asia-Pacific region. There has been a significant reduction in the number of endoscopic procedures and relevant training programs.

Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards

This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.

Small-cell Neuroendocrine Carcinoma of the Extrahepatic Bile Duct: A Rare Case Report / 대한소화기학회지

Neuroendocrine carcinoma (NEC) arising from the extrahepatic bile duct is extremely rare and commonly mistaken for cholangiocarcinoma. Therefore, NEC of the bile duct is difficult to diagnose preoperatively. Previously reported cases were resected with a diagnosis of cholangiocarcinoma and diagnosed with NEC after surgery. This paper reports an 84-year-old female with small-cell NEC of the extrahepatic bile duct, confirmed by a biopsy from an ERCP, with a review of the relevant literature. Contrast-enhanced abdomen computed tomography and magnetic resonance cholangiopancreatography revealed an approximately 1.7 cm enhancing intraductal mass in the proximal common bile duct with dilatation of the upstream bile duct. ERCP showed a long strictured segment in the proximal common bile duct with bile duct dilatation. A biopsy was performed at the site of the stricture. Histological examinations and hematoxylin–eosin staining showed the solid proliferation of small tumor cells with irregularly shaped hyperchromatic nuclei.Immunohistochemical examinations showed that the tumor cells were positive for CD56 and synaptophysin. Small-cell NEC of the extrahepatic bile duct was confirmed based on the histology and immunohistochemistry findings. The patient and their family denied treatment because of the patient’s old age.

A Neonate Diagnosed with Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome with PIK3CA Mutation

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare genetic disorder characterized by megalencephaly, polymicrogyria, body overgrowth, and cutaneous capillary malformations. It has been reported recently that MCAP is related to a somatic mosaic mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. We report a case of hemimegalencephaly with polymicrogyria and cutaneous capillary malformations diagnosed by genetic evaluation of MCAP in the neonatal period. The PIK3CA mutation [c.1635G>T (p. Glu545Asp)] was determined by Sanger sequencing. The patient was treated with a ventriculoperitoneal shunt for progressive hydrocephalus. Because of the dynamic, progressive clinical manifestations and tumor-prone traits of MCAP, early diagnosis is important. Moreover, since the phosphoinositide 3-kinase (PI3K)-specific inhibitor, a targeted therapy for the PI3K/AKT/mTOR signaling pathway is emerging as a new therapy, early genetic diagnosis is becoming increasingly important.

Accuracy of attenuation imaging in the assessment of pediatric hepatic steatosis: correlation with the controlled attenuation parameter

Purpose@#This study evaluated the accuracy of attenuation imaging (ATI) for the assessment of hepatic steatosis in pediatric patients, in comparison with the FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP). @*Methods@#Consecutive pediatric patients referred for evaluation of obesity who underwent both ATI and FibroScan between February 2020 and September 2021 were included. The correlation between attenuation coefficient (AC) and CAP values was assessed using the Spearman test. The AC cutoff value for discriminating hepatic steatosis corresponding to a CAP value of 241 dB/m was calculated. Multivariable linear regression analysis was performed to estimate the strength of the association between AC and CAP. The diagnostic accuracy of AC cutoffs was estimated using the imperfect gold-standard methodology based on a two-level Bayesian latent class model. @*Results@#Seventy patients (median age, 12.5 years; interquartile range, 11.0 to 14.0 years; male:female, 58:12) were included. AC and CAP showed a moderate-to-good correlation (ρ =0.646, P<0.001). Multivariable regression analysis affirmed the significant association between AC and CAP (P<0.001). The correlation was not evident in patients with a body mass index ≥30 kg/m2 (ρ=-0.202, P=0.551). Linear regression revealed that an AC cutoff of 0.66 dB/cm/MHz corresponded to a CAP of 241 dB/m (sensitivity, 0.93; 95% confidence interval [CI], 0.85 to 0.98 and specificity, 0.87; 95% CI, 0.56 to 1.00). @*Conclusion@#ATI showed an acceptable correlation with CAP values in a pediatric population, especially in patients with a body mass index <30 kg/m2. An AC cutoff of 0.66 dB/cm/MHz, corresponding to a CAP of 241 dB/m, can accurately diagnose hepatic steatosis.

Changes in the Clinical Characteristics of Kawasaki Disease After Coronavirus Disease (COVID-19) Pandemic: A Database Analysis

Background@#The impact of the coronavirus disease 2019 (COVID-19) pandemic on Kawasaki disease (KD) has not yet been established. We investigated changes in the observed number and severity of KD cases and accompanying coronary artery complications during the COVID-19 pandemic in Korea. @*Methods@#This retrospective observational study included patients aged < 18 years with acute-phase KD diagnosed between March 2018 and February 2021. Data were extracted from the Clinical Data Warehouse that houses data from five affiliated university hospitals in Korea. We analyzed changes in the number of patient admissions and clinical characteristics, including cardiac complications, before and after the onset of the COVID-19 pandemic. @*Results@#A total of 475 admissions were included in the analysis. After March 2020, we observed a significant decrease of 33% in the number of hospitalizations for KD compared with the average number of hospitalizations during the previous 2 years. The number of admissions per month significantly decreased by 7.9 persons/month (95% confidence interval, −13.8 to −2.0; P < 0.05) compared with that before COVID-19. By contrast, the proportion of patients aged < 1 year with KD increased. The proportion of patients with refractory KD and the rate of cardiac complications did not change significantly. @*Conclusion@#Since the onset of the COVID-19 pandemic, the total number of hospital admissions for KD has decreased in Korea. Although the proportion of admissions of infants aged < 1 year increased, no changes were observed in clinical courses and complications.

Clinical Characteristics and Long-term Outcomes of Pediatric Ulcerative Colitis: A Single-Center Experience in Korea

Background/Aims@#Although pediatric ulcerative colitis (UC) has a different phenotype and clinical course than adult UC, its clinical features and outcomes are poorly defined, especially in Asian populations. This study investigated the clinical features and long-term outcomes of pediatric UC in a Korean population. @*Methods@#We retrospectively analyzed 208 patients aged <18 years diagnosed with UC between 1987 and 2013. The patient characteristics at diagnosis according to the Paris classification and the clinical course were analyzed. @*Results@#The male-to-female ratio was 1.3:1, and the median patient age was 15.5 years. At diagnosis, 28.8% of patients had proctitis (E1), 27.8%, left-sided colitis (E2); 5.2%, extensive colitis (E3); and 38.2%, pancolitis (E4). The cumulative probabilities of extension after 5, 10, 15, and 20 years were 32.7%, 40.4%, 52.5%, and 65.8%, respectively. Eighteen patients underwent colectomy, and three patients had colorectal cancer. The cumulative probabilities of colectomy after 5, 10, 15, and 20 years were 7.1%, 8.9%, 12.6%, and 15.6%, and those of colorectal cancer after 10, 15, and 20 years were 0%, 2.1%, and 12.0%, respectively. The disease extent, Pediatric Ulcerative Colitis Activity Index severity, and systemic corticosteroid therapy were significant risk factors for colectomy. The development of primary sclerosing cholangitis was significantly associated with colorectal cancer. @*Conclusions@#This study provides detailed information on the disease phenotype and long-term clinical outcomes in a large cohort of Korean children with UC. They have extensive disease at diagnosis, a high rate of disease extension, and a low rate of cumulative colectomy.

Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial

Background/Aims@#We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). @*Methods@#An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. @*Results@#DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. @*Conclusions@#The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Background@#This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. @*Methods@#The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. @*Results@#Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. @*Conclusions@#SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Evaluation of a multi-stage convolutional neural network-based fully automated landmark identification system using cone-beam computed tomographysynthesized posteroanterior cephalometric images / 대한치과교정학회지

Objective@#To evaluate the accuracy of a multi-stage convolutional neural network (CNN) model-based automated identification system for posteroanterior (PA) cephalometric landmarks. @*Methods@#The multi-stage CNN model was implemented with a personal computer. A total of 430 PA-cephalograms synthesized from cone-beam computed tomography scans (CBCT-PA) were selected as samples. Twenty-three landmarks used for Tweemac analysis were manually identified on all CBCT-PA images by a single examiner. Intra-examiner reproducibility was confirmed by repeating the identification on 85 randomly selected images, which were subsequently set as test data, with a two-week interval before training. For initial learning stage of the multi-stage CNN model, the data from 345 of 430 CBCT-PA images were used, after which the multi-stage CNN model was tested with previous 85 images. The first manual identification on these 85 images was set as a truth ground. The mean radial error (MRE) and successful detection rate (SDR) were calculated to evaluate the errors in manual identification and artificial intelligence (AI) prediction. @*Results@#The AI showed an average MRE of 2.23 ± 2.02 mm with an SDR of 60.88% for errors of 2 mm or lower. However, in a comparison of the repetitive task, the AI predicted landmarks at the same position, while the MRE for the repeated manual identification was 1.31 ± 0.94 mm. @*Conclusions@#Automated identification for CBCT-synthesized PA cephalometric landmarks did not sufficiently achieve the clinically favorable error range of less than 2 mm. However, AI landmark identification on PA cephalograms showed better consistency than manual identification.

Root proximity of the anchoring miniscrews of orthodontic miniplates in the mandibular incisal area: Cone-beam computed tomographic analysis / 대한치과교정학회지

Objective@#This outcome analysis study evaluated the actual positions of the orthodontic miniplate and miniplate anchoring screws (MPASs) and the risk factors affecting adjacent anatomic structures after miniplate placement in the mandibular incisal area. @*Methods@#Cone-beam computed tomographic images of 97 orthodontic miniplates and their 194 MPASs (diameter, 1.5 mm; length, 4 mm) in patients whose miniplates provided sufficient clinical stability for orthodontic treatment were retrospectively reviewed. For evaluating the actual positions of the miniplates and analyzing the risk factors, including the effects on adjacent roots, MPAS placement height (PH), placement depth (PD), plate angle (PA), mental fossa angle (MA), and root proximity were assessed using the paired t-test, analysis of variance, and generalized linear model and regression analyses. @*Results@#The mean PDs of MPASs at positions 1 (P1) and 2 (P2) were 2.01 mm and 2.23 mm, respectively. PA was significantly higher in the Class III malocclusion group than in the other groups. PH was positively correlated with MA and PD at P1. Of the 97 MPASs at P1, 49 were in the no-root area and 48 in the dentulous area; moreover, 19 showed a degree of root contact (19.6%) without root perforation. All MPASs at P2 were in the no-root area. @*Conclusions@#Positioning the miniplate head approximately 1 mm lower than the mucogingival junction is highly likely to provide sufficient PH for the P1-MPASs to be placed in the no-root area.

Quantitative cone-beam computed tomography evaluation of hard and soft tissue thicknesses in the midpalatal suture region to facilitate orthodontic mini-implant placement / 대한치과교정학회지

Objective@#To identify the most favorable sites that optimize the initial stability and survival rate of orthodontic mini-implants, this study measured hard and soft tissue thicknesses in the median and paramedian regions of the palate using cone-beam computed tomography (CBCT) and determined possible sexand age-related differences in these thicknesses. @*Methods@#The study sample comprised CBCT images of 189 healthy subjects. The sample was divided into four groups according to age. A grid area was set for the measurement of hard and soft tissue thicknesses in the palate. Vertical lines were marked at intervals of 0, 1.5, and 3.0 mm lateral to the midpalatal suture, while horizontal lines were marked at 2-mm intervals up to 24 mm from the posterior margin of the incisive foramen. Measurements were made at 65 points of intersection between the horizontal and vertical lines. @*Results@#The palatal hard tissue thickness decreased from the anterior to the posterior region, with a decrease in the medial-to-lateral direction in the middle and posterior regions. While the soft tissue was rather thick around the lateral aspects of the palatal arch, it formed a constant layer that was only 1–2-mm thick throughout the palate. Statistically significant differences were observed according to sex and age. @*Conclusions@#The anterolateral palate as well as the midpalatal suture seem to be the most favorable sites for insertion of orthodontic mini-implants. The thickness of the palate differed by age and sex; these differences should be considered while planning the placement of orthodontic mini-implants.

Part II. What drives Korean adults to seek orthodontic treatment: Factors contributing to orthodontic treatment decisions / 대한치과교정학회지

Objective@#This study aimed to identify the perceptions of orthodontic treatment among Korean adults and determine the factors that drive them to seek orthodontic treatment. @*Methods@#A total of 2,321 adults aged 19–64 years were surveyed using an internet research system from a specialized research company. The participants were divided into the following groups based on their experience of and willingness to undergo orthodontic treatment: experience, acceptance, and non-acceptance groups. The characteristics of the participants were compared using analysis of variance with post-hoc analysis.Multinomial logistic regression analysis was performed in all three models with the non-acceptance group as a reference. @*Results@#In terms of demographic characteristics, age, gender, marital status, and education had significant influences on orthodontic treatment decisions in adults in the experience and acceptance groups (p < 0.001). When all the factors were analyzed, age, marital status, past dental treatment experience, regular oral examinations, demand for orthodontic treatment, optimal treatment period, health insurance coverage, information on orthodontic treatments, perceptions regarding orthodontic treatment, and psychosocial impact of dental esthetics significantly influenced orthodontic treatment decisions in adults in the experience and acceptance groups (p < 0.001). @*Conclusions@#These findings suggest that various factors influence orthodontic treatment decisions in adults. Individuals who seek orthodontic treatment were found to undergo more regular dental treatment and oral examination than those who did not. They also had a better perception of orthodontic treatment and more negative values for the psychosocial impact of dental esthetics.

Effects of Virtual Reality-Based Cognitive Training in the Elderly with and without Mild Cognitive Impairment

Objective@#This study aimed to introduce a 4-week long fully immersive virtual reality-based cognitive training (VRCT) program that could be applied for both a cognitively normal elderly population and patients with mild cognitive impairment (MCI). In addition, we attempted to investigate the neuropsychological effects of the VRCT program in each group. @*Methods@#A total of 56 participants, 31 in the MCI group and 25 in the cognitively normal elderly group, underwent eight sessions of VRCT for 4 weeks. In order to evaluate the effects of the VRCT, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet was administered before and after the program. The program’ s safety was assessed using a simulator sickness questionnaire (SSQ), and availability was assessed using the presence questionnaire. @*Results@#After the eighth session of the VRCT program, cognitive improvement was observed in the ability to learn new information, visuospatial constructional ability, and frontal lobe function in both groups. At the baseline evaluation, based on the SSQ, the MCI group complained of disorientation and nausea significantly more than the cognitively normal elderly group did. However, both groups showed a reduction in discomfort as the VRCT program progressed. @*Conclusion@#We conclude that our VRCT program helps improve cognition in both the MCI group and cognitively normal elderly group. Therefore, the VRCT is expected to help improve cognitive function in elderly populations with and without MCI.

Efficacy of Living Donor Liver Transplantation in Patients with Methylmalonic Acidemia / 대한소아소화기영양학회지

Purpose@#Despite aggressive medical and nutritional management, patients with methylmalonic acidemia (MMA) often suffer from multi-organ damage. Early deceased donor liver transplantation (DDLT) has emerged as an intervention to prevent disease progression. We investigated the efficacy of living donor LT (LDLT) with a potential carrier of MMA and a small volume of graft in patients with MMA as an alternative to DDLT. @*Methods@#Of five patients (three male, two female; median age 5.7 years; range, 1.3–13.7 years), four underwent carrier LDLT, while one underwent non-carrier auxiliary LDLT. All patients received pre- and post-LT continuous renal replacement therapy and were provided with minimal restriction diet according to serum MMA level after LT. MMA levels in the serum and urine, the incidence of metabolic crisis, and clinical findings before and after LT were compared. @*Results@#The survival rate was 100% during 2.2 years of follow up period after LT. In all five cases, MMA titer in the serum after transplantation decreased with less restrictive diet. Metabolic crisis was not observed during the follow-up period. In addition, no patient showed progression of severe renal impairment requiring hemodialysis. Progression of delayed cognitive development was not observed. Social functioning with improved neuropsychiatric development was observed. @*Conclusion@#This study showed that LDLT achieved improved quality of life with less restrictive diet, therefore it could be a feasible alternative option to DDLT for the treatment of patients with MMA, even with an auxiliary LT.

Hypertrophic Cardiomyopathy in Infants from the Perspective of Cardiomyocyte Maturation

Hypertrophic cardiomyopathy (HCM) is characterized by ventricular wall hypertrophy with diastolic dysfunction. Pediatric HCM is distinguished from the adult in many aspects. Most children with HCM do not present clinically until the adolescent period, even when they are born with genetic mutations. Some infants with early-onset HCM present with massive progressive myocardial hypertrophy in the first few months of life, which is often fatal. The mortality of pediatric HCM peaks during the infantile and adolescent periods. These periods roughly correlate with children's growth spurt. Non-sarcomeric causes of HCM are more frequent in pediatric HCM, while sarcomeric causes are more common in adults. From the perspective of cardiac development, the fetal heart has immature cardiomyocytes, which are characterized by proliferation and exit their cell cycles with a decreased regenerative property after birth. In the perinatal period, there is a dynamic change in maturation of cardiomyocytes from immature to mature cells. Infants who are treated with steroids or born to mothers with diabetes or hyperthyroidism often show phenotypes of HCM, which gradually resolve. With remarkable advancement of molecular biology, understanding on maturation of cardiomyocytes has increased. Neonates undergo abrupt environmental changes during the transitional circulation, which is affected by oxygen, metabolic and hormonal fluctuations. Derangement in physiological transition to the normal postnatal environment may influence maturation of proliferative immature cardiomyocytes during early infancy. This article reviews updates of infantile HCM and recent molecular studies related to maturation of cardiomyocytes from the clinical point of view of identifying distinct characteristics of infantile HCM.

Optimal Hypoxic Preconditioning of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells (hES-MSCs) and Their Characteristics

Background and Objectives@#Hypoxia is frequently used to enhance stem cell function. However, the optimal level of hypoxia for growth and function of human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) is yet to be determined. The purpose of this study was to find the optimal level of hypoxia for hES-MSCs and characteristics of hES-MSCs cultured under these optimal hypoxic conditions. @*Methods@#and Results: Cell viability and changes in the morphology of hES-MSCs were determined through cell proliferation and CCK-8 assay. The hES-MSCs were preconditioned under various hypoxic conditions (0.5∼5% O2 and 24∼72 h). The expression of cytokines in each culture condition was compared using cytokine array analysis. The morphology of hES-MSCs did not change under various hypoxic culture conditions. hES-MSCs viability after 48 h incubation in 2% O2condition was higher than that in normoxic condition. HIF1α expression was increased up to six folds after 48 h of hypoxic preconditioning. HIF1α expression in hES-MSCs peaked after 48 h of incubation in 1% O2 condition. The expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin were increased after hES-MSCs were incubated for 48 h in 2% O2 condition. @*Conclusions@#The hES-MSCs viability and expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin increased after 48 h incubation in 2% O2 condition.

Efficacy and safety of autologous adipose tissue-derived stem cell therapy for children with refractory Crohn’s complex fistula: a Phase IV clinical study

Purpose@#Autologous adipose tissue-derived stem cells (ASCs) have been proposed for patients with refractory Crohn disease, but research is lacking in pediatric patients. This Phase IV study evaluated the efficacy and safety of ASCs in children with refractory Crohn’s fistulae. @*Methods@#Patients with a refractory Crohn’s fistula who did not have conventional therapy for more than 3 months or with a recurrent complex Crohn’s fistula were included. All patients were at least 14 years old. Patients with infection, poor condition, or active Crohn disease with a disease activity index of 450 and above were excluded. Five patients were treated with ASCs from 2014 to 2015 in Asan Medical Center. ASC administration was adjusted according to fistula size (1 mL per cm 2 ). We evaluated the efficacy and safety 8 weeks after injection and followed patients for 6 months. @*Results@#Fistulae were healed in 4 patients by 8 weeks after ASC injection. Of these 4 patients, 1 had complete fistula closure and sustainability after 6 months. The other 3 with healing effects had less than 50% fistula closure by 6 months.None of these 4 patients have persistent fistulae. One patient had no healing effect, and seton ligation was performed 8 months after ASC injection. There were no adverse effects related to ASC administration. @*Conclusion@#ASC therapy is a simple and well-tolerated therapeutic option for children with refractory Crohn’s complex fistulae. Complete closure was well-sustained. However, more data from a larger number of patients are needed.

Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Background@#This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. @*Methods@#The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague–Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. @*Results@#Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. @*Conclusions@#SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.