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Purpose: Genital injury is a common pediatric injury. Given the lack of nationwide data, the authors aimed to show age group-related epidemiologic features of genital injury in Korea.Methods:We reviewed the data from 2011-2016 Emergency Department-based Injury In-depth Surveillance registry, which involves 23 emergency departments in Korea. From the dataset, we included children (< 18 years) with the International Classification of Diseases, 10th Revision codes related to genital injury as the final diagnosis with excluding those with other codes or combined injuries. Age groups were defined as follows; infants (< 1 year), toddlers (1-3), preschoolers (4-6), schoolers (7-12), and adolescents (13-17). The clinical features and outcomes were analyzed.Results: A total of 3,030 children were included with the median age of 6 years (interquartile range, 4-10) and the proportion of girls of 53.0%. Only 144 children (4.8%) were transported by the emergency medical service providers. The most common mechanism and place were blunt injury (1,826 [60.3%]) and home (1,535 [50.7%]), respectively. Of the codes, “Contusion of external genital organs (S30.2)” was most common (1,574 [51.9%]). As for outcomes, 2,770 children (91.4%) were discharged, 252 (8.3%) were hospitalized (intensive care units, 1 child [0.03%]), and 108 (3.6%) underwent surgery. Severe injury occurred in 111 children (3.7%) without a mortality. With increasing age in the age groups, non-accidental injury, school and sports-related injuries, hospitalization, and surgery (All Ps < 0.001).Conclusion: Genital injury may occur at evening, in spring and summer, at home, and in the form of accidental or blunt injury. Most children are discharged. Contrary to these general features, older children tend to undergo more frequently non-accidental injury, school and sports-related injuries, hospitalization, and surgery. Thus, we need age-specific strategies for injury prevention.

Purpose: In Korea, the Broselow tape (BT) is widely used to estimate weight in resuscitation. Validation of BT in Korean children is essential because the tool was developed based on children’s weight and height in the United States. The validation was previously performed in a small-scale dataset. The authors aimed to validate BT using the 2005 Korean nationwide anthropometric survey data.Methods: From the population used for the survey, we sampled children aged 0-12 years. The weights estimated by BT were compared with measured weights of the children using Bland-Altman analysis with results recorded as percentage differences. We measured the accuracy of BT, defined as within a 10% error of the measured weight, and the concordance of the color-coded zones derived from the estimated and measured weights. The accuracy and concordance were further assessed according to the age groups and body mass index-for-age Z-score (< -2, underweight; > 2, overweight or obese). Results: A total of 108,128 children were enrolled. The mean age was 55.2 ± 37.5 months. The bias was –5.4% (P < 0.001), and the limits of agreement were –28.3% and 17.6%, respectively. The accuracy and concordance of BT were 64.4% and 67.2%, respectively. Differences of no more than 1 color-coded zone between estimated and measured weights accounted for 89.8% and 84.1% of the under- and overweight (or obese) children, respectively.Conclusion: BT accurately estimates weight in approximately two-thirds of Korean children. In addition, adjustment of 1 color-coded zone may be considered in children with extreme weight.

Food allergy is a hypersensitive immune reaction to food proteins including cow’s milk protein. Extracellular vesicles (EVs), such as exosomes, are newly discovered intercellular conveyors of functional molecular mechanisms and mediated intercellular interactions involving mast cells and are particularly relevant to allergy. In this study, we investigated whether cow’s milk casein-induced allergy (CIA)-derived EVs can modulate mast cell activation. EVs in CIA mice and control mice were isolated using the ultracentrifugation method and the isolated EVs were quantified using BCA analysis. CIA responses were determined through changes in body temperature and systemic symptom score. The number of EVs was higher in CIA-derived EVs compared to normal EVs. EVs marker proteins such as CD63 and CD9 were elevated in CIA-derived EVs. The levels of EV-associated cytokines such as IL-6, IL-8, and TNF-α were significantly elevated in CIA-derived EVs. In addition, CIA-derived EVs significantly induced degranulation via Lyn kinase activation in mouse bone marrow-derived mast cells and human mast cells. Our results demonstrate that CIA-derived EVs can induce a reaction similar to cow’s milk allergic reaction via mast cell activation. These results provide an insight into the pathology of cow’s milk allergy and a potential therapeutic approach through targeting EV release and/or uptake.

An adaptable algorithm is proposed in this study, which can predict the complete load-shortening curve of a stiffened panel subjected to uniaxial longitudinal compression. The algorithm provides an extension to existing empirical formulae initially derived for predicting the ultimate compressive strength of stiffened panels. Based on observations from a series of nonlinear finite element analyses, the compressive load-shortening behaviour of stiffened panels is idealised with a linear pre-collapse response, an arc-shaped nonlinear ultimate collapse region and an asymptotic post-collapse decay. The algorithm allows direct modification of the elastic stiffness, ultimate strain, ultimate strength and post-collapse characteristics of the load shortening curve. This enables the load shortening curve to incorporate characteristics specific to the type of stiffened panel under analysis. The capability of the algorithm is demonstrated through an application with the simplified progressive collapse method to calculate the ultimate ship hull strength of four merchant ships and one naval vessel.

Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-30a and miRNA-23a, increased in SM-EVs and neoplastic mast cell-derived EVs, attenuate osteoblast maturation by suppressing expression of RUNX2 and SMAD1/5, essential drivers of osteogenesis. Thus, SM-EVs carry and deliver miRNAs that epigenetically interfere with bone formation and can contribute to bone mass reduction in SM. These findings also suggest possibilities for novel approaches to the management of bone disease in mast cell proliferative disorders., Osteoporosis and bone disease are common in patients with systemic mastocytosis. Here, the authors show that extracellular vesicles released by neoplastic mast cells of the patients block osteoblast differentiation and bone mineralization when injected into mice, via a mechanism involving suppression of osteogenic factors via miRNA-30a and miRNA-23a.

Background/Aims We investigated the efficiency of the indirect ratio of anti-HBc IgG at predicting HBsAg seroclearance in patients with nucleos(t)ide analogue (NA)-induced HBeAg seroclearance. Methods We performed a retrospective study that included 366 chronic hepatitis B patients (March 2007 to December 2016) at a single tertiary hospital. These patients were HBsAg seropositive, and experienced NA-induced HBeAg seroclearance. The indirect ratio of light absorbance of anti-HBc IgG levels were measured with chemiluminescent microparticle immunoassay using the Architect Anti-HBc assay (Abbott Laboratories, IL, USA) as a qualitative method prior to antiviral therapy. We calculated the cumulative incidences of HBsAg seroclearance based on the anti-HBc IgG levels. Results After a 10-year follow-up, 48 patients experienced HBsAg seroclearance (13.1%). Thirty-three of 179 patients who had an indirect ratio of light absorbance of anti-HBc IgG

Background In the emergency department (ED), adequate pain control is essential for managing patients; however, children with pain are known to receive less analgesia than adults with pain. We introduce the Pain Passport to improve pain management in paediatric patients with suspected fractures in the ED. Methods This was a before-and-after study. We reviewed the medical records of paediatric patients who were primarily diagnosed with fractures from May to August 2015. After the introduction of the Pain Passport, eligible children were enrolled from May to August 2016. Demographics, analgesic administration rates, time intervals between ED arrival and analgesic administration, and satisfaction scores were obtained. We compared the analgesic prescription rate between the two periods using multiple logistic regression. Results A total of 58 patients were analysed. The baseline characteristics of subjects during the two periods were not significantly different. Before the introduction of the Pain Passport, 9 children (31.0%) were given analgesics, while after the introduction of the Pain Passport, a significantly higher percentage of patients (24/29, 82.8%) were treated with analgesics (P < 0.001). The median administration times were 112 (interquartile range [IQR], 64-150) minutes in the pre-intervention period and 24 (IQR, 20-74) minutes in the post-intervention period. The median satisfaction score for the post-intervention period was 4 (IQR, 3-5). The adjusted odds ratio for providing analgesics in the post-intervention period was 25.91 (95% confidence interval, 4.36-154.02). Conclusions Patient-centred pain scoring with the Pain Passport improved pain management in patients with suspected fractures in the paediatric ED.

Objective Trampoline-related injuries have increased in South Korea. However, little research has been conducted on this topic. This study aimed to show the characteristics of pediatric trampoline-related injuries in South Korea and to investigate the factors associated with admission. Methods A retrospective, cross-sectional study was conducted using data from South Korea’s Emergency Department-based Injury In-depth Surveillance registry for dates between January 2011 and December 2016. All patients under 18 years of age with trampoline-related injuries were included. We divided the patients into two groups based on whether they were admitted or discharged. Odds ratios with 95% confidence intervals were calculated to evaluate the factors associated with hospital admission for pediatric trampoline-related injuries. Results A total of 2,745 patients were enrolled and the incidence increased over time (P for trend

Background Extracellular vesicle (EV)–mimetic nanovesicles (NVs) from embryonic stem cells have been observed to stimulate neurovascular regeneration in the streptozotocin-induced diabetic mouse. Pericytes play important roles in maintaining penile erection, yet no previous studies have explored the effects of pericyte-derived NVs (PC-NVs) in neurovascular regeneration in the context of erectile dysfunction. Aim To investigate the potential effect of PC-NVs in neurovascular regeneration. Methods PC-NVs were isolated from mouse cavernous pericytes, and neurovascular regeneration was evaluated in an in vitro study. Twelve-week-old C57BL/6J mice were used to prepare cavernous nerve injury model. Erectile function evaluation, histologic examination of the penis, and Western blots were assessed 2 weeks after model creation and PC-NVs treatment. Outcomes The main outcomes of this study are PC-NVs characterization, intracavernous pressure, neurovascular regeneration in the penis, and in vitro functional evaluation. Results The PC-NVs were extracted and characterized by cryotransmission electron microscopy and EV-positive (Alix, TSG101, CD81) and EV-negative (GM130) markers. In the in vivo studies, PC-NVs successfully improved erectile function in cavernous nerve injury mice (∼82% of control values). Immunofluorescence staining showed significant increases in pericytes, endothelial cell, and neuronal contents. In the in vitro studies, PC-NVs significantly increased mouse cavernous endothelial cells tube formation, Schwann cell migration, and dorsal root ganglion and major pelvic ganglion neurite sprouting. Finally, Western blot analysis revealed that PC-NVs upregulated cell survival signaling (Akt and eNOS) and induced the expression of neurotrophic factors (brain-derived neurotrophic factor, neurotrophin-3, and nerve growth factor). Clinical Implications PC-NVs may be used as a strategy to treat erectile dysfunction after radical prostatectomy or in men with neurovascular diseases. Strengths & Limitations We evaluated the effect of PC-NVs in vitro and in a mouse nerve injury model, cavernous nerve injury. Additional studies are necessary to determine the detailed mechanisms of neurovascular improvement. Further study is needed to test whether PC-NVs are also effective when given weeks or months after nerve injury. Conclusion PC-NVs significantly improved erectile function by enhancing neurovascular regeneration. Local treatment with PC-NVs may represent a promising therapeutic strategy for the treatment of neurovascular diseases.

Background: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE), especially the KPC-2-producing Klebisella pneumoniae, is rapidly increasing and becoming a menace to global public health. This study aims to present the molecular epidemiology of the KPC-2-producing K. pneumoniae isolates emerged in a tertiary hospital in South Korea and describe its clinical significance. Methods: This study included carbapenem-resistant K. pneumoniae isolates collected from a tertiary hospital from April to December in 2018. Antimicrobial susceptibility of K. pneumoniae isolates was tested using disk diffusion method. PCR and DNA sequence analyses were performed to identify the resistance genotype. In addition, the molecular epidemiology was investigated using pulsed-field gel electrophoresis (PFGE) and multilocus sequencing typing (MLST). Results: Total 100 KPC-2-producing K. pneumoniae isolates were collected, which were mainly classified into two pulsotypes according to the XbaI restriction digestion pattern by PGFE analysis (pulsotype A, n = 31; pulsotype B, n = 63). The isolates exhibiting pulsotype A belonged to ST395 and the remaining isolates exhibiting pulsotype B were attributed to ST307 by MLST analysis. Conclusion: This study investigated clinical information and molecular bacterial profiles for KPC-2-producing K. pneumoniae isolates. These findings indicate that the proper infection control activities are needed to prevent the spread of multidrug-resistant organisms such as CPE, which could cause high mortality in clinical field.

Background Isolated true aneurysms in the superficial femoral artery (SFA) have rarely been reported. Most cases are undiagnosed until rupture or the occurrence of complications. Case summary A 36-year-old woman presented with a palpable, pulsating mass on her right thigh which had increased in size over 2 months. She also had a swollen right leg and mild claudication (Stage II in Rutherford classification). For 2 months, the patient was treated by manual massage, acupuncture, and extracorporeal shock wave therapy in local clinics. Bed-side ultrasonography identified a 3.4-cm sized true aneurysm of the right SFA. There were no other aneurysms in arteries from head to toe. There was no evidence of atherosclerotic risk factors or connective tissue disease. The patient was successfully treated by a covered stent graft implantation without any complications. Discussion Isolated true aneurysm in the SFA is rare and tends to go undiagnosed especially in young women. Ultrasonography is an easy and useful diagnostic tool for differential diagnosis of thigh mass. In this case, endovascular treatment was safely applied for a true aneurysm without rupture.

The Pediatric Emergency Care Applied Research Network (PECARN) rule is commonly used for predicting the need for computed tomography (CT) scans in children with mild head trauma. The objective of this study was to validate the PECARN rule in Korean children presenting to the pediatric emergency department (PED) with head trauma. This study was a multicenter, retrospective, observational cohort study in two teaching PEDs in Korea between August 2015 and August 2016. In this observational study, 448 patients who visited PEDs were included in the final analysis. Risk stratification was performed with clinical decision support software based on the PECARN rule, and decisions to perform CT scans were subsequently made. Patients were followed-up by phone call between 7 days and 90 days after discharge from the PED. The sensitivity and specificity were analyzed. The sensitivity was 100% for all age groups, and no cases of clinically important traumatic brain injury (ciTBI) were identified in the very-low-risk group. CT scans were performed for 14.7% of patients in this study and for 33.8% in the original PECARN study. The PECARN rule successfully identified low-risk patients, and no cases of ciTBI were missed despite the reduced proportion of patients undergoing CT scans.

Croup treatment usually involves a single dose of systemic dexamethasone combined with nebulized epinephrine. However, the optimal dose of l-epinephrine remains unclear. We examined whether a low dose (0.1 mg/kg) was inferior to the conventional dose (0.5 mg/kg) of 1:1000 nebulized l-epinephrine in patients with moderate to severe croup.This randomized double-blind clinical non-inferiority trial was conducted in three pediatric emergency departments from May 2015 to October 2017. Children 6 months to 5 years old with moderate to severe croup (Westley scale scores 3-11) were eligible. Subjects were randomly assigned to the conventional dose (0.5 mg/kg: maximum 5 mg) or low dose (0.1 mg/kg; maximum 1 mg) group. All subjects received 0.6 mg/kg dexamethasone. Croup scores and other vital signs were measured before and at 30, 60, 90, and 120 min after nebulized l-epinephrine administration. The primary outcome was the change in croup score after 30 min.The final analysis included 84 patients. The groups did not differ significantly in terms of demographic parameters. At 30 min after treatment with nebulized l-epinephrine, the croup scores in both groups were significantly reduced from the baseline values (p 0.05) and did not differ between the two groups (p = 0.42). Neither blood pressure nor heart rate differed between the two groups.Low-dose 1:1000 l-epinephrine was not inferior in croup score reduction to the conventional dose in patients with moderate to severe croup. Clinical trial No: NCT01664507, KCT0002318.

Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies transmission and geographic diffusion patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of interspecies transmission were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between regions (negative correlation) and summer temperature at origin (positive correlation) were strong predictors of diffusion. Taken together, this study demonstrates that host diversity and ecology can determine evolutionary processes that underlie AIV natural history and spread. Understanding these processes can provide important insights for effective control of AIV.

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

Background: Antimicrobial resistant continues to pose a threat to public health. Therefore, rapid and accurate antimicrobial susceptibility testing is very important. The objectives of this study were to evaluate the performance of the MicroScan system (Beckman Coulter, USA) with newly developed Korean Antimicrobial Susceptibility Testing Panels (KSCM panels) for antimicrobial susceptibility testing (AST) against clinical isolates in South Korea.Methods: Three KSCM panels were designed in this study. For the performance evaluation, a total of 1,325 clinical isolates including 1,027 of Gram-negative bacilli and 298 Gram-positive cocci collected from eight general hospitals in South Korea were used. The results by KSCM panels were compared with those by conventional methods.Results: By KSCM-1 panel for Gram-positive cocci, the rates of categorical agreement (CA) were ＞90% in all the antimicrobials tested in this study. The rates of major error (ME) were also 90%, ME rates

Objectives The aim of this study was to evaluate the effects of a practice guideline of postreduction management of intussusception in children on the length of stay (LOS) from reduction in the pediatric emergency department (PED) and on the incidence of recurrence. Methods We developed a practice guideline of postreduction management of intussusception in the PED. The practice guideline involved feeding 2 hours after reduction and discharge 2 hours after successful feeding. The guideline was implemented on October 1, 2012. Retrospective quasi-experimental study was conducted for evaluation of the difference in LOS in the PED after reduction of intussusceptions, and the recurrence rate of intussusceptions between the preimplementation and postimplementation periods. Piecewise regression was performed to determine the differences between groups. Results In total, 45 and 52 patients were included in the preimplementation and postimplementation periods, respectively. The median LOS in the postimplementation period was significantly shorter than that in the preimplementation period (289 vs 532 minutes, respectively; P = 0.001). The slope of the LOS changed from 0.68 to -0.29. The slope decreased by 0.97 after practice guideline implementation. This difference was not statistically significant (P = 0.123), but it changed from a positive to negative gradient. The recurrence rate was not significantly different between the 2 periods (P = 0.605). Conclusions Implementation of a practice guideline involving early feeding and discharge after reduction of intussusception resulted in a reduced LOS from reduction of intussusception in the PED and was not associated with recurrence of intussusception.

Persistent dysregulation of IL-6 production and signaling have been implicated in the pathology of various cancers. In systemic mastocytosis, increased serum levels of IL-6 associate with disease severity and progression, although the mechanisms involved are not well understood. Since systemic mastocytosis often associates with the presence in hematopoietic cells of a somatic gain-of-function variant in KIT, D816V-KIT, we examined its potential role in IL-6 upregulation. Bone marrow mononuclear cultures from patients with greater D816V allelic burden released increased amounts of IL-6 which correlated with the percentage of mast cells in the cultures. Intracellular IL-6 staining by flow cytometry and immunofluorescence was primarily associated with mast cells and suggested a higher percentage of IL-6 positive mast cells in patients with higher D816V allelic burden. Furthermore, mast cell lines expressing D816V-KIT, but not those expressing normal KIT or other KIT variants, produced constitutively high IL-6 amounts at the message and protein levels. We further demonstrate that aberrant KIT activity and signaling are critical for the induction of IL-6 and involve STAT5 and PI3K pathways but not STAT3 or STAT4. Activation of STAT5A and STATB downstream of D816V-KIT was mediated by JAK2 but also by MEK/ERK1/2, which not only promoted STAT5 phosphorylation but also its long-term transcription. Our study thus supports a role for mast cells and D816V-KIT activity in IL-6 dysregulation in mastocytosis and provides insights into the intracellular mechanisms. The findings contribute to a better understanding of the physiopathology of mastocytosis and suggest the importance of therapeutic targeting of these pathways This work was supported by the Division of Intramural Research within the National Institute of Allergy and Infectious Diseases (NIAID), at the National Institutes of Health. SI

Background Coronary artery dilatation (CAD) is a great concern with Kawasaki disease (KD). This study aimed to investigate the relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and CAD in patients with the hyperacute phase (≤4 days of fever) of KD. Methods Serum NT-proBNP levels were compared between patients with and those without CAD, who underwent transthoracic echocardiography (TTE) within 24 h of the hyperacute phase of KD in the pediatric emergency department (PED). Electronic medical records of patients aged 1 month to 15 years who visited the PED were retrospectively assessed from January 2010 to December 31, 2014. Results One hundred nine patients were enrolled in the study. Twenty-three of those patients had CAD within 24 h of TTE. Median serum NT-proBNP levels were significantly higher in patients with CAD (824.1 pg/ml; interquartile range [IQR], 515.4–1570.0184.8–767.8 pg/ml) than in patients without CAD (396.4 pg/ml; IQR, 184.8–767.8 pg/ml) (p ≤ 0.001). The cutoff value of serum NT-proBNP, which predicted CAD during the hyperacute phase of KD, was 515.4 pg/ml, which yielded sensitivity of 78.26% and specificity of 61.63%. The area under the curve for NT-proBNP for predicting CAD during hyperacute KD was 0.749 (95% CI, 0.642–0.856). Conclusion Serum NT-proBNP might be an additional laboratory marker for detecting early CAD during the hyperacute phase of KD in the PED.

We performed a large, population-based study to analyze the risk factors of the febrile seizures and the subsequent afebrile epileptic seizures.Relevant data from children born between 2002-2007 were retrieved from the Korean National Health Insurance Service-National Sample Cohort 2002-2013. Children who did not survive the first five years were excluded from the analysis. The risk factors for febrile seizures were assessed separately in per-person and per-febrile case analyses, and factors contributing to an increased risk of subsequent afebrile epileptic seizures were identified.A total of 54,233 children were included and the five-year prevalence rate of febrile seizure was 11.19%. In the per-person analysis, male sex, preterm birth and brain injury at birth increased the risk of febrile seizure with odds ratios of 1.17, 1.40 and 1.97 (all p 0.001), respectively. A high household income level was associated with reduced odds of febrile seizure. In the per-febrile illness analysis, male sex, brain injury at birth, presumed bacterial infection, gastrointestinal or genitourinary infection and unspecified sepsis were independent risk factors of a febrile seizure during febrile illness. The cumulative number of febrile seizure episodes, especially more than the third episodes, was associated with a new diagnosis of an afebrile epileptic seizure within one year.Sex, preterm birth, brain injury at birth, presumed bacterial infection, genitourinary and gastrointestinal infections and unspecified sepsis were identified as likely risk factors for febrile seizures. A greater number of febrile seizure episodes was associated with a higher probability of subsequent afebrile epileptic seizures.

Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.

Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton’s jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis.

Background Understanding the changes in emergency department (ED) visit patterns during the coronavirus disease 2019 (COVID-19) outbreak is important for effectively operating EDs during the pandemic. We aimed to analyze the changes in pediatric ED visits during the COVID-19 pandemic and examine the relationship between the number of ED visits and the stringency of government social distancing measures. Methods This multicenter retrospective study used data of pediatric (age < 18 years) ED visits in Seoul metropolitan area from June 1, 2018, to May 31, 2020. Patient demographics, ED results, and diagnoses were compared during the COVID-19 period and the previous year. To evaluate the effect of the stringency of social distancing measures on the number of ED visits, a Poisson regression model was developed with month, year, and the average monthly Government Response Stringency Index (GRSI) as fixed effects. Results In total, 190,732 patients were included. The number of pediatric ED visits during the COVID-19 period was 58.1% lower than in the previous year. There were disproportionate decreases in the numbers of ED visits for children in early childhood (66.5%), low-acuity children (55.2-63.8%), those who did not use an ambulance (59.0%), and those visiting the ED for noninjury complaints (64.9%). The proportion of admissions increased from 11.9% to 16.6%. For every 10-point increase in the GRSI, there was a 15.1% decrease in monthly ED visits. Conclusion A striking decrease in pediatric ED visits was observed during the COVID-19 outbreak, the scale which was associated with the stringency of government policies. Changes in the number and characteristics of children visiting the ED should be considered to facilitate the effective operation of EDs during the pandemic., Graphical Abstract

Background Peyronie’s disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction. The role of pericytes in the pathogenesis of fibrosis has recently been determined. Extracellular vesicle (EV)–mimetic nanovesicles (NVs) have attracted attention regarding intercellular communication between cells in the field of fibrosis. However, the global gene expression of pericyte-derived EV–mimetic NVs (PC–NVs) in regulating fibrosis remains unknown. Here, we used RNA-sequencing technology to investigate the potential target genes regulated by PC–NVs in primary fibroblasts derived from human PD plaque. Methods Human primary fibroblasts derived from normal and PD patients was cultured and treated with cavernosum pericytes isolated extracellular vesicle (EV)–mimetic nanovesicles (NVs). A global gene expression RNA-sequencing assay was performed on normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC–NVs. Reverse transcription polymerase chain reaction (RT-PCR) was used for sequencing data validation. Results A total of 4135 genes showed significantly differential expression in the normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC–NVs. However, only 91 contra-regulated genes were detected among the three libraries. Furthermore, 20 contra-regulated genes were selected and 11 showed consistent changes in the RNA-sequencing assay, which were validated by RT-PCR. Conclusion The gene expression profiling results suggested that these validated genes may be good targets for understanding potential mechanisms and conducting molecular studies into PD.

Governments throughout the world can learn many critical lessons from examining instances of ineffective communication with the public during the global coronavirus disease (COVID-19) pandemic. Ineffective government communication has resulted in a great deal of public confusion and misunderstanding, as well as serious errors in responding to this evolving health threat, leading to disastrous health and social outcomes for the public and prolonging the pandemic, especially within the United States. This article uses systems theory as a template for analyzing government communication in the United States during the COVID-19 pandemic, providing governments with recommendations for establishing effective health risk communication strategies for use with the public. The communication strategies offered here promote the delivery of relevant, accurate, and sensitive information to key public groups, minimizing communication noise to guide desirable coordinated actions. These communication strategies can be applied locally, nationally, and internationally.

Decommissioning of the offshore platform as an artificial reef, known as Rigs-to-Reefs (R2R), has become a sustainable approach for oil companies. The platform was reused to serve the underwater ecosystem as an artificial reef for a new marine ecosystem which helps to tackle food security issue. This paper presents the findings of the formulation of the reefing viability index to recognize an offshore region that can be used for R2R projects within the South China Sea. The combined effects of spatial data, numerical modelling, and geographic system (GIS) are proposed to study the relationship of spawning ground coral reefs, diversity, and planula larvae in the process of colonization to establish a map of the reef potential environment. Coral connectivity and spawning behaviour were studied to determine the possible source of coral seedling released during the spawning season, twice a year. A geographic reef viability index was established consisting of seven parameters which are coral larval density, pelagic larval length, sea currents, temperature, chlorophyll-a, depth, and substrate availability. The ocean hydrodynamic model was designed to resemble the pattern of larval scattering. By using the simulations and rankings, there were 95 (21%) sites which could probably be used for in situ reefing, whereas 358 (79%) sites were likely ideal for ex situ reefing. Validation of the viability index was carried out using media footage assessment of remotely operated vehicle (ROV).

Background Previous studies on inter-rater reliability of pediatric triage systems have compared triage levels classified by two or more triage providers using the same information about individual patients. This overlooks the fact that the evaluator can decide whether or not to use the information provided. The authors therefore aimed to analyze the differences in the use of vital signs for triage modification in pediatric triage. Methods This was an observational cross-sectional study of national registry data collected in real time from all emergency medical services beyond the local emergency medical centers (EMCs) throughout Korea. Data from patients under the age of 15 who visited EMC nationwide from January 2016 to December 2016 were analyzed. Depending on whether triage modifications were made using respiratory rate or heart rate beyond the normal range by age during the pediatric triage process, they were divided into down-triage and non-down-triage groups. The proportions in the down-triage group were analyzed according to the triage provider's profession, mental status, arrival mode, presence of trauma, and the EMC class. Results During the study period, 1,385,579 patients' data were analyzed. Of these, 981,281 patients were eligible for triage modification. The differences in down-triage proportions according to the profession of the triage provider (resident, 50.5%; paramedics, 47.7%; specialist, 44.9%; nurses, 44.2%) was statistically significant (P < 0.001). The triage provider's professional down-triage proportion according to the medical condition of the patients showed statistically significant differences except for the unresponsive mental state (P = 0.502) and the case of air transport (P = 0.468). Conclusion Down-triage proportion due to abnormal heart rates and respiratory rates was significantly different according to the triage provider's condition. The existing concept of inter-rater reliability of the pediatric triage system needs to be reconsidered., Graphical Abstract

Background A kids café is a popular indoor playground in Korea that combines a playground for young children and a café for their caregivers. There have been no national reports about kids café-related injuries in Korea. This study investigated kids café-related injuries in Korea registered in a multicenter injury surveillance database and analyzed the risk factors for significant kids café-related injuries. Methods A multicenter cross-sectional study was performed using the Emergency Department-based Injury In-depth Surveillance registry in Korea between 2011 and 2016. Significant injury was defined as an injury requiring hospitalization or surgery. A multivariable logistic regression model was used to obtain the adjusted odds ratios (aORs) for factors associated with significant kids café-related injuries. Results Among 1,537,617 injured patients, we extracted 891 patients who were injured in kids cafés. Of these, 46 (5.2%) were admitted, and 39 (4.4%) underwent surgery. The most common injured anatomical site, injury type, and mechanism were lower extremity (28.2%), superficial injury (27.2%), and slip (27.1%), respectively. Among injury-inducing factors, significant injuries were most commonly caused by a trampoline (28.1%), and rock climbing equipment was the only risk factor in a kids café that led to significant injury after adjusting for age, sex, injury mechanism, and injured anatomical sites (aOR, 14.94; 95% confidence interval, 1.51–147.72). Conclusion The rock climbing equipment in a kids café can cause serious injury to children. Establishing safety regulations for rock climbing equipment in kids cafés may have the greatest impact in reducing significant injuries requiring hospitalization or surgery., Graphical Abstract

Background This study examined the role of superficial vein surgery in patients with combined superficial venous reflux and segmental popliteal vein reflux. Methods We retrospectively reviewed 42 limbs in 38 patients with combined superficial venous reflux and segmental popliteal vein reflux who underwent saphenous vein ablation between January 2014 and February 2017. Patients underwent outpatient follow-up duplex ultrasonography at 3, 6, and 12 months postoperatively. Resolution of deep vein reflux was defined as reversed blood flow in a popliteal segment for less than 1.0 second and a decrease in the reflux time of more than 20% of the preoperative reflux time. Results The mean follow-up period was 9 months (range, 3-23 months). Saphenous vein ablations were performed by stripping in 24 limbs and radiofrequency ablation in 18 limbs. Preoperative segmental popliteal vein reflux resolved in 21 of the 42 limbs (50%). Conclusion This study demonstrated that superficial venous surgery corrected segmental popliteal vein reflux in 50% of limbs with combined superficial venous reflux and segmental popliteal vein reflux. Other prospective studies are necessary to elucidate the etiology of the non-reversible cases.

Objective: We developed a novel compression assist device (palm presser) to perform chest compressions using a palm in infant cardiopulmonary resuscitation (CPR). We hypothesized that the p...

Mitochondrial aldehyde dehydrogenase (ALDH2) metabolizes endogenous and exogenous aldehydes and protects cells against oxidative injury. Inactivating genetic polymorphisms in humans are common and associate with alcohol flush reactions. However, whether mast cell Aldh2 activity impacts normal mast cell responses is unknown. Using bone marrow-derived mast cells from Aldh2 knockout mice, we found evidence for a role of mast cell Aldh2 in Kit-mediated responses. Aldh2-deficient mast cells showed enhanced Kit tyrosine kinase phosphorylation and activity after stimulation with its ligand (stem cell factor) and augmentation of downstream signaling pathways, including Stat4, MAPKs, and Akt. The activity of the phosphatase Shp-1, which attenuates Kit activity, was reduced in Aldh2&minus, /&minus, mast cells, along with an increase in reactive oxygen species, known to regulate Shp-1. Reduced Shp-1 activity concomitant with sustained Kit signaling resulted in greater proliferation following Kit engagement, and increased mediator and cytokine release when Aldh2&minus, mast cells were co-stimulated via Kit and Fc&epsilon, RI. However, Fc&epsilon, RI-mediated signaling and responses were unaffected. Therefore, our findings reveal a functional role for mast cell intrinsic Aldh2 in the control of Kit activation and Kit-mediated responses, which may lead to a better understanding of mast cell reactivity in conditions related to ALDH2 polymorphisms.

Pain scales using faces are commonly used tools for assessing pain in children capable of communicating. However, some children require other types of pain scales because they have difficulties in understanding faces pain scales. The goal of this study was to develop and validate the "Pain Block" concrete ordinal scale for 4- to 7-year-old children. This was a multicenter prospective observational study in the emergency department. Psychometric properties (convergent validity, discriminative validity, responsivity, and reliability) were compared between the "Pain Block" pain scale and the Faces Pain Scale-Revised (FPS-R) to assess the validity of the "Pain Block" scale. A total of 163 children (mean age, 5.5 years) were included in this study. The correlation coefficient between the FPS-R and the Pain Block scale was 0.82 for all participants which increased with age. Agreement between the 2 pain scales was acceptable, with 95.0% of the values within the predetermined limit. The differences in mean scores between the painful group and nonpainful group were 3.3 (95% confidence interval, 2.6-4.1) and 3.8 (95% confidence interval, 3.1-4.6) for FPR-S and Pain Block, respectively. The pain scores for both pain scales were significantly decreased when analgesics or pain-relieving procedures were administered (difference in Pain Block, 2.4 [1.4-3.3]; and difference in FPS-R, 2.3 [1.3-3.3]). The Pain Block pain scale could be used to assess pain in 4- to 7-year-old children capable of understanding and counting up to the number 5, even if they do not understand the FPS-R pain scale.

We assessed the feasibility and potential efficacy of a virtual reality (VR) environment using a dome screen as a distraction method in young children during intravenous (IV) placement in the pediatric emergency department. This randomized controlled pilot study enrolled children aged 2 to 6 years who underwent IV placement into either the intervention group or the control group. Children in the intervention group experienced VR using a dome screen during IV placement. The child’s pain intensity was measured using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale at four time points of IV placement: immediately after arrival to the blood collection room (base); immediately after the child laid down on the bed (preparation); when the tourniquet was applied (tourniquet); and the moment at which the needle penetrated the skin (venipuncture). The guardian’s satisfaction and rating of the child’s distress were assessed using a 5-point Likert-type questionnaire. We recruited 19 children (9 in the intervention group and 10 in the control group). Five children in the control group were excluded from the analysis because of missing video recordings (n = 3), failed first attempt at IV placement (n = 1), and the child’s refusal to lie on the bed during the procedure (n = 1). No side effects of VR were reported during the study period. Although the average FLACC scale score at each time point (preparation, tourniquet, venipuncture) was lower in the intervention group than the control group, the difference was not statistically significant (2.3, interquartile range [IQR]: 2.0–3.0; vs. 3.3, IQR: 2.7–6.7, P = 0.255). There were no statistically significant differences between the groups in the guardian’s satisfaction and anxiety or his/her rating of the child’s pain and anxiety. The guardians and emergency medical technicians reported satisfaction with the use of VR with a dome screen and considered it a useful distraction during the procedure. VR using a dome screen is a feasible distraction method for young children during IV placement. A larger clinical trial with further development of the VR environment and study process is required to adequately evaluate the efficacy of VR using a dome screen.

Urethral catheterization (CATH) and suprapubic aspiration (SA) are reliable methods of collecting urine for the diagnosis of urinary tract infections (UTIs), but both are invasive and difficult. Therefore, urine collection through a sterile urine bag (SUB) is commonly used for UTI screening. However, when pyuria is found in SUB specimens, it is difficult to interpret whether this result is true or false.We aimed to determine the diagnostic performance of the urinary NAG/Cr ratio in detecting true pyuria in SUB specimens for children with suspected UTIs.This retrospective study included children 2-24 months of age presenting to the pediatric emergency department (PED) and in whom urinary NAG and creatinine levels were measured and a urine culture was performed between January 1, 2018, and December 31, 2019. Children with the presence of pyuria in SUB specimens were categorized into true or false pyuria groups depending on whether pyuria was present in CATH specimens. The diagnostic performance of the urinary NAG/Cr ratio in detecting true pyuria was identified using receiver operating characteristic (ROC) curve analysis. The optimal cutoff was calculated based on ROC curve analysis. Sensitivity, specificity, and positive and negative likelihood ratios were assessed for optimal cutoff values.Among 606 children with measured urinary NAG levels, 144 children with pyuria in SUB specimens were included in the analyses. Pyuria was consistently present in the CATH specimens of 67 (46.5%) children and absent in those of 77 (44.5%) children. The urinary NAG/Cr ratio was significantly higher in the true pyuria group than in the false pyuria group (21.5 IU/g; 95% confidence interval [CI]: 12.3-35.6; vs 9.6 IU/g; 95% CI: 6.7-16.1, P 0.001). The area under the ROC curve (AUC) for the urinary NAG/Cr ratio was 0.776 (95% CI: 0.700-0.851). The optimal cutoff of 18.85 IU/g corresponded to the best combination of sensitivity (58.2, 95% CI: 46.4-70.0) and specificity (83.3, 95% CI: 74.7-91.6), with positive and negative likelihood ratios of 3.49 (95% CI: 2.04-5.97) and 0.50 (95% CI: 0.37-0.68), respectively.The urinary NAG/Cr ratio may be a potential indicator discriminating true pyuria from false pyuria in SUB specimens in the PED. However, large prospective studies are required to implement the NAG/Cr ratio in clinical practice.

The effects of blue light on the promotion of the bactericidal action of plasma-activated water (PAW) against Staphylococcus aureus by inducing the photolysis of staphyloxanthin (STX) were examined. A light-emitting diode (466 nm) and atmospheric-pressure plasma were applied. The degradation of STX pigments extracted through pure methanol was facilitated by increased dosage of blue light (30, 60, 90, and 150 J/cm2). After combined treatment with blue light (150 J/cm2) and PAW (10 min), the surviving population of S. aureus in liquid decreased by 2.70 log CFU/mL, which was about 40 times greater than that of single PAW treatment. Blue light (150 J/cm2) treatment induced leakage of intracellular substances, indicating potential damage to the cell membrane, which was also confirmed as an increase in the SYTOX™ green fluorescence signal. The synergistic bactericidal effect of blue light and PAW was also observed for S. aureus attached to the surface of stainless steel.

High-quality cardiopulmonary resuscitation is a significant factor for increasing the survival rate of paediatric patients. This study is to investigate the effectiveness of finger-marker stickers for maintaining the correct compression point during simulated infant cardiopulmonary resuscitation (CPR).This crossover simulation study was conducted with 40 emergency physicians and paramedics at emergency departments of 2 tertiary hospitals. We used a remodeled infant CPR manikin developed to measure CPR quality indicators. After random coupling of participants (20 pairs), the pre-group (10 pairs) performed conventional 2-rescuer infant manikin CPR, then performed sticker-applied CPR after 1month. The post-group (10 pairs) performed the process in the opposite order. The participants placed finger-marker stickers to indicate the appropriate compression point before starting CPR. We compared accurate finger placement rates and other CPR quality indicators (compression depth, rate, complete chest recoil, and hands-off time) with and without the finger-marker sticker.All finger-marker stickers were correctly attached within 5s (4.88±1.28s) of approaching the model. There were significant differences in the rate of correct finger compression position between conventional and sticker-applied CPR (25.4% [IQRs 7.6-69.8] vs. 88.2% [IQRs 69.6-95.5], P0.001). Results did not differ according to sex, career, and job of the participants. There were no significant differences in mean compression rate, depth, hands-off times, and rate of fully recoiled compression between the 2 groups.Finger-marker stickers can be used to maintain correct finger positioning during 2-rescuer infant manikin CPR.

Recently, UVC-LED technology has been validated as an alternative to irradiation with conventional mercury UV lamps. In this study, we sought to determine primary factors affecting reduction trends shown in several microorganisms. Four major foodborne pathogens (Escherichia coli O157:H7, Salmonella spp. Listeria monocytogenes, Staphylococcus aureus) and spoilage yeasts (Saccharomyces pastorianus, Pichia membranaefaciens), important to the brewing industry, were inoculated onto selective and non-selective media in order to investigate reduction tendencies at 4 different peak wavelengths (266 to 279nm). As irradiation dose increased, inactivation levels for every microorganism were enhanced, but there were different UV-sensitivities in Gram positive bacteria (GP), Gram negative bacteria (GN), and yeasts (Y). Loss of membrane integrity measured by propidium iodide (PI) increased as peak wavelength increased for every microorganism studied. Similar results were observed in membrane potential measured by DiBAC4(3). However, there were contrasting results which showed that greater DNA damage occurred at a lower peak wavelength as measured by Hoechst 33,258. The level of DNA damage was strongly related to trends of microbial inactivation. This study showed that even though membrane damage was present in every microorganism studied, DNA damage was the primary factor for inactivating microorganisms through UVC-LED treatment.

Objective To investigate the contributing factors of carpal tunnel syndrome (CTS), electrodiagnostic and ultrasonographic findings of median nerve, and median nerve change after exercise in wheelchair basketball (WCB) players. Methods Fifteen WCB players with manual wheelchairs were enrolled in the study. Medical history of the subjects was taken. Electrodiagnosis and ultrasonography of both median nerves were performed to assess CTS in WCB players. Ultrasonographic median nerves evaluation was conducted after wheelchair propulsion for 20 minutes. Results Average body mass index (BMI) and period of wheelchair use of CTS subjects were greater than those of normal subjects. Electrodiagnosis revealed CTS in 14 of 30 hands (47%). Cross-sectional area (CSA) of median nerve was greater in CTS subjects than in normal subjects at 0.5 cm and 1 cm proximal to distal wrist crease (DWC), DWC, 1 cm, 2 cm, 3 cm, and 3.5 cm distal to DWC. After exercising, median nerve CSAs at 0.5 cm and 1 cm proximal to DWC, DWC, and 3 cm and 3.5 cm distal to DWC were greater than baseline CSAs in CTS subjects; and median nerve CSAs at 1 cm proximal to DWC and DWC were greater than baseline CSAs in normal subjects. The changes in median nerve CSA after exercise in CTS subjects were greater than in normal subjects at 0.5 cm proximal to DWC and 3 cm and 3.5 cm distal to DWC. Conclusion BMI and total period of wheelchair use contributed to developing CTS in WCB players. The experimental exercise might be related to the median nerve swelling around the inlet and outlet of carpal tunnel in WCB athletes with CTS.

Objective We studied the effect of a dispatcher-assisted cardiopulmonary resuscitation (CPR) program on paediatric out-of-hospital cardiac arrest (OHCA) outcomes by age groups. Methods All emergency medical services (EMS)-treated paediatric OHCAs in Korea were enrolled between 2012 and 2014, excluding cases witnessed by EMS providers and those with unknown outcomes. The cases were divided into three groups: bystander CPR with dispatcher assistance, bystander CPR without dispatcher assistance, and no-bystander CPR. The endpoint was survival until discharge from hospital. Multivariable logistic regression analysis was performed. The final model with an interaction term was evaluated to compare the effects across age groups. Results A total of 1529 patients (32.8% bystander CPR with dispatcher assistance, 17.3% without dispatcher assistance, and 54.6% no-bystander CPR) were included. Both bystander CPR groups were more likely to have higher rate of survival to discharge (8.8% and 12.1%) compared to no-bystander CPR (3.9%). The adjusted OR (95% CI) for survival to discharge were 1.77 (1.04-3.00) in bystander CPR with dispatcher assistance and 2.86 (1.61-5.08) in without dispatcher assistance compared with no-bystander CPR. By age groups, the adjusted OR (95% CI) in bystander CPR with and without dispatcher assistance were 2.18 (1.07-4.42) and 2.27 (1.01-5.14) for the group aged 9-18 years; 2.32 (0.64-8.44) and 6.21 (1.83-21.01) for the group aged 1-8 years; 1.06 (0.41-2.77) and 2.00 (0.64-6.18) for the group aged 0-12 months, respectively. Conclusions Bystander CPR, regardless of dispatcher assistance, was associated with improved survival outcomes after OHCA in the paediatric population. However, the associations between dispatcher-assisted bystander CPR and survival outcomes varied by age.