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Lymphangioleiomyomatosis is a rare disease characterized by abnormal smooth muscle cell growth. It primarily occurs in the lungs but can also rarely occur in other organs, in which case it is classified as extrapulmonary lymphangioleiomyomatosis. It often accompanies tuberous sclerosis complex. This report concerns a case of uterine lymphangioleiomyomatosis with spontaneous uterine rupture in a young woman with tuberous sclerosis complex. A 27-year-old nulligravida patient presented to the emergency room with vaginal bleeding. She had a history of clinical diagnosis of tuberous sclerosis complex and pulmonary lymphangioleiomyomatosis. Initially, abdominopelvic computed tomography and magnetic resonance imaging suggested a hemorrhagic necrosis and rupture of degenerated uterine myoma. She underwent emergency exploratory laparotomy. The right side of her normal-sized uterus were ruptured without any specific mass. Active bleeding and hematoma from the ruptured uterus and partially ruptured right ovary were noted. The procedure included total hysterectomy and right salpingo-oophorectomy. Pathological analysis confirmed lymphangioleiomyomatosis in the uterine serosa and myometrium. Lymphangioleiomyomatosis mainly occurs in women of reproductive age and worsens with estrogen. Early diagnosis and careful follow-up are necessary due to the risk of worsening gynecological symptoms or even uterine rupture during pregnancy. This case enhances our understanding of extrapulmonary lymphangioleiomyomatosis and highlights the importance of comprehensive evaluation in complex clinical scenarios.

Abstract Previous studies have examined the prevalence of allergic diseases in adolescents 1–2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the β difference (βdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66–6.91) in 2009–2011 to 6.89% (95% CI 6.72–7.05) in 2018–2019, then decreased slightly to 5.82% (95% CI 5.60–6.04) in 2022. Across the 14 years, middle school student status, low parent’s highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.

Abstract The cohort consisted of 9400 exposed children diagnosed with ventricular septal defect (VSD). The risk of community-acquired pneumonia (CAP) or asthma with VSD was assessed using the Cox proportional hazard model with an inverse probability of treatment weighting. During a mean follow-up of 6.67 years (starting from 12 months after birth), there were 2100 CAP admission cases among exposed patients (incidence rate: 33.2 per 1000 person-years) and 20,109 CAP admission cases among unexposed children (incidence rate: 29.6 per 1000 person-years), with hazard ration of 1.09 (95% CI 1.04–1.14).

Background: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. Methods: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. Results: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23–1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. Conclusions: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Pelvic organ prolapse (POP) is a common cause of gynecological disease in elderly women. The prevalence of POP has increased with an aging society. Abdominal sacrocolpopexy (ASC) is safer and more effective than the vaginal approach in patients with apical compartment POP because it has a higher anatomical cure rate, a lower recurrence rate, less dyspareunia, and improved sexual function. Laparoscopic sacrocolpopexy (LSC) has replaced ASC. Robotic sacrocolpopexy (RSC) also helps overcome the challenges of LSC by facilitating deep pelvic dissection and multiple intracorporeal suturing. The RSC is technically easy to apply, has a steep learning curve, and offers many advantages over the LSC. However, insufficient data led us to conclude that the LSC is superior overall, especially in terms of cost-effectiveness. The present review provides insights into different aspects of RSC, highlighting the most common benefits and concerns of this procedure. We searched for eligible articles discussing this issue from January 2019 to March 2022 to reveal the outcomes of RSC.

Abstract Ultrasound-based models exist to support the classification of adnexal masses but are subjective and rely upon ultrasound expertise. We aimed to develop an end-to-end machine learning (ML) model capable of automating the classification of adnexal masses. In this retrospective study, transvaginal ultrasound scan images with linked diagnoses (ultrasound subjective assessment or histology) were extracted and segmented from Imperial College Healthcare, UK (ICH development dataset; n = 577 masses; 1444 images) and Morgagni-Pierantoni Hospital, Italy (MPH external dataset; n = 184 masses; 476 images). A segmentation and classification model was developed using convolutional neural networks and traditional radiomics features. Dice surface coefficient (DICE) was used to measure segmentation performance and area under the ROC curve (AUC), F1-score and recall for classification performance. The ICH and MPH datasets had a median age of 45 (IQR 35–60) and 48 (IQR 38–57) years old and consisted of 23.1% and 31.5% malignant cases, respectively. The best segmentation model achieved a DICE score of 0.85 ± 0.01, 0.88 ± 0.01 and 0.85 ± 0.01 in the ICH training, ICH validation and MPH test sets. The best classification model achieved a recall of 1.00 and F1-score of 0.88 (AUC:0.93), 0.94 (AUC:0.89) and 0.83 (AUC:0.90) in the ICH training, ICH validation and MPH test sets, respectively. We have developed an end-to-end radiomics-based model capable of adnexal mass segmentation and classification, with a comparable predictive performance (AUC 0.90) to the published performance of expert subjective assessment (gold standard), and current risk models. Further prospective evaluation of the classification performance of this ML model against existing methods is required.

Abstract The correlations between activities of daily living (ADL) among patients with spinal cord injury (SCI) and their caregivers’ burden, quality of life (QoL), and presenteeism was investigated. Participants included outpatients and inpatients with SCI at a rehabilitation center and their caregivers, recruited between March 2020 and April 2021. Eighty-seven valid responses were analysed using independent t-tests and Pearson’s correlations. There was a difference in caregiver burden according to patients’ ADL performance. QoL was negatively correlated with caregiver burden and presenteeism. Caregiver burden and presenteeism were positively correlated. Social support can improve caregivers’ QoL and reduce caregiver burden and presenteeism-induced work impairment.

Objective Parametrial tissue ligation during total laparoscopic hysterectomy (TLH) is important in large uteri with large vessels. Methods A retrospective study was performed at Asan Medical Center for comparing TLH performed with a new knotless parametrial tissue ligation method and conventional laparoscopic-assisted vaginal hysterectomy (LAVH) from March 2019 to August 2021. For TLH, after anterior colpotomy, the parametrial tissue was ligated by anchoring the suture and making a loop in one direction three times using 1-0 V-LocTM 180 (Covidien, Mansfield, MA, USA) suture. Subsequently, the cranial part of the loop was cut using an endoscopic device. Results A total of 119 and 178 patients were included in the TLH and LAVH groups, respectively. The maximal diameter of the uterus was larger in the TLH group (106.29±27.16 cm) than in the LAVH group (99.00±18.92 cm, P=0.01). The change in hemoglobin (Hb) level was greater in the LAVH group than in the TLH group (P1,000 g, the operative times and change in Hb levels were similar between the two groups. In both groups, no ureteral complications occurred during or after surgery. Conclusion Knotless parametrial tissue ligation using 1-0 V-LocTM 180 suture in TLH can be safely applied, even in cases with large uteri, without increased risks of ureteral injury or uterine bleeding.

Long coronavirus disease (COVID), also known as postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection, has been defined as signs and symptoms which persist for 4 weeks or even lasting for 6 months after the initial infection. Although the prevalence of long COVID in children is currently unknown, epidemiological investigations have reported cases in pediatric populations. Clinical manifestations of long COVID in children include respiratory symptoms, such as cough and dyspnea, as well as neuropsychiatric and general conditions, including fatigue, headache, and muscle weakness. The pathophysiology of long COVID in children is still being investigated, but potential mechanisms include viral persistence, autoimmunity, and neuroinflammation. Risk factors for long COVID in children are not yet well understood, but studies have suggested that children with a history of severe acute COVID-19 infection or comorbidities may be at increased risk. Evaluation for respiratory symptoms of long COVID in children is essential, including spirometry and imaging studies to assess lung function and any potential damage. Furthermore, long COVID in children has been associated with a higher prevalence of mental health problems than in adults, emphasizing the importance of monitoring and addressing these aspects in pediatric patients. Although our understanding of long COVID in children and adolescents is still evolving, it is clear that the condition can have significant impacts on their health and well-being. The aim of this review is to synthesize the current knowledge on the prevalence, risk factors, and pathophysiology of long COVID in children and adolescents, and to discuss potential management strategies based on existing evidence.

Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.g., steady-state volume of distribution (Vss), clearance (CL), area under the concentration-time curve (AUC), mean residence time (MRT), etc.) of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) were determined by non-compartmental analysis. In addition, one- or two-compartment PK modeling was performed to support inter-species scaling. The PK models appropriately described the blood concentrations of pyronaridine, artesunate, and dihydroartemisinin in all animal species, and the estimated PK parameters in three species were integrated for inter-species allometric scaling to predict human PKs. The simple allometric equation (Y = a × Wb) well explained the relationship between PK parameters and the actual body weight of animal species. The results from the study could be used as a basis for drug repurposing and support determining the effective dosage regimen for new indications based on in vitro/in vivo efficacy data and predicted human PKs in initial clinical trials.

Background The association between dyslipidemia and asthma in children remains unclear. Purpose This study investigated the association between dyslipidemia and cholesterol levels in children. Methods A systematic literature review was performed to identify studies investigating the association between dyslipidemia and asthma in children. The PubMed database was searched for articles published from January 2000–March 2022. Data from a cohort study using electronic health records from 5 hospitals, converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), were used to identify the association between total cholesterol (TC) levels and asthma in children. This cohort study used the Cox proportional hazards model to examine hazard ratio (HR) of asthma after propensity score matching, and included an aggregate meta-analysis of HR. Results We examined 11 studies reporting an association between dyslipidemia and asthma in children. Most were cross-sectional; however, their results were inconsistent. In OMOP-CDM multicenter analysis, the high TC (>170 mg/dL) group included 29,038 children, while the normal TC (≤170 mg/dL) group included 88,823 children including all hospital datasets. In a meta-analysis of this multicenter cohort, a significant association was found between high TC levels and later development of asthma in children

Purpose The aim of this study was to determine the factors that influence safe sexual behaviors of Korean young adults and identify differences by gender. Methods This study aimed to determine which factors affected safe sexual behaviors based on the Theory of Planned Behavior. Data from 437 Korean young adults (in their 20s and 30s) were collected via online survey between January 3 and January 28, 2022. The questionnaire included items on sexual body image, sexual role perception, sexual attitudes, sexual socialization, sexual communication, and safe sexual behaviors. Structural equation modeling was performed. Results According to the overall model fit of the hypothetical model, the final model was acceptable and explained 49% of safe sexual behaviors. Sexual attitudes (β=–.70, p

BackgroundMycoplasma pneumoniae infection is common in the general population and may be followed by immune dysfunction, but links with subsequent autoimmune disease remain inconclusive.ObjectiveTo estimate the association of M. pneumoniae infection with the risk of subsequent autoimmune disease.MethodsThis retrospective cohort study examined the medical records of South Korean children from 01/01/2002 to 31/12/2017. The exposed cohort was identified as patients hospitalized for M. pneumoniae infection. Each exposed patient was matched with unexposed controls based on birth year and sex at a 1:10 ratio using incidence density sampling calculations. The outcome was subsequent diagnosis of autoimmune disease, and hazard ratios (HRs) were estimated with control for confounders. Further estimation was performed using hospital-based databases which were converted to a common data model (CDM) to allow comparisons of the different databases.ResultsThe exposed cohort consisted of 49,937 children and the matched unexposed of 499,370 children. The median age at diagnosis of M. pneumoniae infection was 4 years (interquartile range, 2.5–6.5 years). During a mean follow-up time of 9.0 ± 3.8 years, the incidence rate of autoimmune diseases was 66.5 per 10,000 person-years (95% CI: 64.3–68.8) in the exposed cohort and 52.3 per 10,000 person-years (95% CI: 51.7–52.9) in the unexposed cohort, corresponding to an absolute rate of difference of 14.3 per 10,000 person-years (95% CI: 11.9–16.6). Children in the exposed cohort had an increased risk of autoimmune disease (HR: 1.26; 95% CI: 1.21–1.31), and this association was similar in the separate analysis of hospital databases (HR: 1.25; 95% CI 1.06–1.49).ConclusionM. pneumoniae infection requiring hospitalization may be associated with an increase in subsequent diagnoses of autoimmune diseases.

Background Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). Methods This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. Results After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. Conclusion Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

BackgroundAs digital health services advance, digital health equity has become a significant concern. However, people with disability and older adults still face health management limitations, particularly in the COVID-19 pandemic. An essential area of investigation is proposing a patient-centered design strategy that uses patient-generated health data (PGHD) to facilitate optimal communication with caregivers and health care service providers. ObjectiveThis study aims to conceptualize, develop, and validate a digitally integrated health care service platform for people with disability, caregivers, and health care professionals, using Internet of Things devices and PGHD to contribute to improving digital health equity. MethodsThe methodology consists of 5 stages. First, a collaborative review of the previous app, Daily Healthcare 1.0, was conducted with individuals with disabilities, caregivers, and health care professionals. Secondly, user needs were identified via personas, scenarios, and user interface sketches to shape a user-centered service design. The third stage created an enhanced app that integrated these specifications. In the fourth stage, heuristic evaluations by clinical and app experts paved the way for Daily Healthcare 2.0, now featuring Internet of Things device integration. Conclusively, in the fifth stage, an extensive 2-month usability evaluation was executed with user groups comprising individuals with disabilities using the app and their caregivers. ResultsAmong the participants, “disability welfare information and related institutional linkage” was the highest priority. Three of the 14 user interface sketches the participants created were related to “providing educational content.” The 11 heuristic evaluation experts identified “focusing on a single task” as a crucial issue and advocated redesigning the home menu to simplify it and integrate detailed menus. Subsequently, the app Daily Healthcare 2.0 was developed, incorporating wearable devices for collecting PGHD and connecting individuals with disabilities, caregivers, and health care professionals. After the 2-month usability evaluation with 27 participants, all participants showed an increase in eHealth literacy, particularly those who used the caregiver app. Relatively older users demonstrated improved scores in health IT usability and smartphone self-efficacy. All users’ satisfaction and willingness to recommend increased, although their willingness to pay decreased. ConclusionsIn this study, we underscore the significance of incorporating the distinct needs of individuals with disabilities, caregivers, and health care professionals from the design phase of a digital health care service, highlighting its potential to advance digital health equity. Our findings also elucidate the potential benefits of fostering partnerships between health consumers and providers, thereby attenuating the vulnerability of marginalized groups, even amid crises such as the COVID-19 pandemic. Emphasizing this imperative, we advocate for sustained endeavors to bolster the digital literacy of individuals with disabilities and champion collaborative cocreation, aiming to uphold the collective ethos of health and digital health equity.

Background Recent studies reported that prepregnancy body mass index (BMI) and weight gain during pregnancy affect birth weight and contribute to childhood obesity. However, no such data are available in Korea. Purpose This study gathered data on weight gain during pregnancy and its impact on birth weight and childhood obesity in Korea. Methods We reviewed 1,753 singleton full-term babies born at CHA Bundang Medical Center in 2014–2016. We first review each maternal and baby factor based on prepregnancy BMI (underweight, normal, overweight/obese) and then divided them into low, normal, and excess gestational weight gain (GWG) groups based on the American Institute of Medicine (IOM) guidelines. We reviewed the characteristics of each group and analyzed the association between maternal GWG based on IOM guidelines and child BMI after 6 years. Results The maternal prepregnancy BMI group showed a significant difference in birth weight and child BMI at 6 years. As the prepregnancy BMI increased, the birth weight and BMI at 6 years also increased (P

Background: Few studies have reported an association between atopic dermatitis and cognitive impairment in children. Therefore, we evaluated the association between atopic dermatitis (AD) and neurodevelopmental dysfunction in children. Methods: We analyzed 2,395,966 children born between 2008 and 2012 in Korea. All data were acquired from the databases of the Korean National Health Insurance System. AD was defined as five or more diagnoses before age 24 months. The outcome was suspected neurodevelopmental dysfunction in the gross motor skill, fine motor skill, cognition, language, sociality, and self-care domains of the Korean Developmental Screening Test for Infants and Children at age 6 years. The positive control outcome was defined as attention deficit hyperactive disorder (ADHD). The associations were assessed using ordinal logistic regression, adjusting for asthma and allergic rhinitis. Results: Among the eligible children, 89,452 and 30,557 were allocated to the control and AD groups, respectively. In the weighted data, the AD group showed a higher risk of suspected neurodevelopmental dysfunction in the total score (weighted adjusted odds ratio [95% CI] 1.10 [1.05–1.16]), gross motor skills (1.14 [1.04–1.25]), and fine motor skills (1.15 [1.06–1.25]) than the control group. The AD with steroids or hospitalization groups showed an increased risk of suspected neurodevelopmental dysfunction. In addition, the AD group showed a significant association with mental retardation, psychological development disorder, and behavioral and emotional disorders as well as ADHD. Conclusions: AD before age 2 years may be associated with an increased risk of neurodevelopmental dysfunction including gross and fine motor skills in the young childhood period.

Long acting injectables (LAIs) using polymeric microspheres has been developed to increase patient compliance and reduce side effects. Among many methods for manufacturing polymeric microspheres, microfluidics technology is known to have excellent characteristics in that the produced polymeric microspheres have perfect spherical shape without surface defect and uniform size, and thus have outstanding efficacy without initial burst. However, the mass production of polymeric microspheres was not realized by the inherent limitation that microfluidics is suitable for small quantity manufacturing. Overcoming such limitations, we could show mass production of finasteride-loaded polymeric microspheres (PLGA 7525) for LAIs using our microfluidic manufacturing platform technology, IVL-DrugFluidic®. The microfluidic channels used in manufacturing were optimized through computational fluid dynamics (CFD) simulation to minimize the flow variation between microchannels and eliminated disturbance outside of microchannels by resistance channels. In addition, the solvent removal was improved by applying the baffle and foam breaker system. Therefore, microspheres were mass-produced in the GMP manufacturing environment in perfect spherical shape, smooth surface, and even size distribution. The encapsulation efficiency was almost 100% and the residual solvent was under the Standard of regulation. In the clinical trial using microspheres mass-produced by IVL-DrugFluidic®, we confirmed that the drug release was stably maintained for a month, the target period without initial burst. It was also confirmed that the drug release by dose of microspheres was uniformly proportional. In conclusion, the microsphere manufacturing platform technology, IVL-DrugFluidic® has been proven to be an appropriate system for mass production of polymeric microspheres optimized for LAIs through physicochemical characteristics and clinical trial.

Background Congenital muscular torticollis (CMT) is a common musculoskeletal disorder occurring at birth or in infancy. Purpose This study aimed to investigate the risk of comorbidities in CMT and explore the differences in neurodevelopmental outcomes between children who received physical therapy and those who did not. Methods Children with CMT born in 2008 and 2009 in Korea were included. CMT was defined as a primary diagnosis of congenital deformity of sternocleidomastoid muscle according to the International Classification of Diseases 10th revision. Here we investigated the associated neurological/musculoskeletal comorbidities of children with CMT versus those of the general population. We divided those with torticollis into treatment and nontreatment groups and assessed their developmental outcomes within both groups of children using the Korean-Ages and Stages Questionnaire (K-ASQ). Results Of the 917,707 children, 0.2% (n=1,719) were diagnosed with CMT. In children with torticollis, the prevalence of congenital hip deformities significantly increased to 4.5% (n=78). The prevalence of congenital head/spine deformities and other congenital malformations of the skull and facial bones increased to 2.6% (n=44), while the prevalence of congenital foot deformities was 2.4% (n=42). The risk ratio (RR) for delayed development based on the K-ASQ was higher for the total assessment (adjusted RR=0.97; 95% confidence interval, 0.93–0.99) in the CMT patients without physical therapy than in those with therapy. There was no significant intergroup difference in the assessment of each developmental area. Conclusion The prevalence of comorbid musculoskeletal deformities was higher in children with CMT than in the control group. The risk of developmental delay was higher in children who did not receive physical therapy than in those who did.

Abstract This study analyzed the effect of parental supervision of infants at age 4 to 6 months on injuries at age 4 to 12 months. Among all Korean children born during 2008–2009, 464,326 (50.6%) infant had parents who responded to a questionnaire that surveyed their safety and supervision when infant were 4 to 6 months-old. Based on questionnaire score, infant were divided into “safe” or “unsafe” group. 1:1 propensity score matching was used to balance the groups, and injury diagnosis and treatments were analyzed. After matching, we examined the records of 405,862 infant. The unsafe group had significantly increased risk ratios (RRs) for injury of head/neck (RR: 1.06), trunk/abdominopelvic region (RR: 1.12), upper extremities (RR: 1.04), and from burn and frostbite (RR: 1.10). The risks of a wound and fracture and foreign body injury were significantly greater in infant whose parents sometimes left them alone (RR: 1.15 and 1.06, respectively), and whose parents did not always keep their eyes on them (RR: 1.04 and 1.13, respectively). Infant whose parents had a hot drink when carrying them had an increased risk of burn injuries (RR: 1.21). Injuries were less common in infant whose parents provided more supervision.

Abstract This national administrative investigation of Republic of Korea compared the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders(ASD) in preschool amblyopic children and identified factors that possibly mediate this association. After propensity score (PS) matching, 7762 amblyopic children and 31,030 non-amblyopic children were included. Amblyopia was associated with ADHD (aOR:1.687; 95% CI 1.444, 1.970) but not with ASD (aOR: 0.591; 95% CI 0.341, 1.026). Fine motor skill impairment was a mediating factor in association of amblyopia with ADHD, accounting for 4.2% (95% CI 1.7, 8.0). In conclusion, amblyopic children have a greater risk of ADHD, and deficits in fine motor skills mediate this association. We suggest increased attention given to fine motor skill underdevelopment in amblyopic children to prevent the development of ADHD.

Abstract Background During puberty, changes in body composition due to sex hormones are associated with lung mechanics. However, little is known about the mediation effect of sex differences in body composition during puberty with total airway resistance. Methods We prospectively recruited 620 children (10–12 years old) from the general population and conducted a cross-sectional study. This study assessed pubertal status according to the five Tanner stages using a questionnaire, line drawings, and each subject’s blood sex hormone profile. Both the impulse oscillation system for total lung mechanics and multifrequency bioelectrical impedance for body composition analyses were conducted. The effects of puberty on body composition and subsequent total lung resistance were evaluated using mediation analysis. Results Among the 503 children enrolled, there were 261 males (51.9%) and 242 females (48.1%). In males, higher testosterone levels corresponded with reduced total lung resistance (β = –0.13, 95% CI = –0.21 to –0.05, p

The spatial tumor shape is determined by the complex interactions between tumor cells and their microenvironment. Here, we investigated the role of a newly identified breast cancer‐related gene, calsequestrin 2 (CASQ2), in tumor–microenvironment interactions during tumor growth and metastasis. We analyzed gene expression and three‐dimensional tumor shape data from the breast cancer dataset of The Cancer Genome Atlas (TCGA) and identified CASQ2 as a potential regulator of tumor–microenvironment interaction. In TCGA breast cancer cases containing information of three‐dimensional tumor shapes, CASQ2 mRNA showed the highest correlation with the spatial tumor shapes. Furthermore, we investigated the expression pattern of CASQ2 in human breast cancer tissues. CASQ2 was not detected in breast cancer cell lines in vitro but was induced in the xenograft tumors and human breast cancer tissues. To evaluate the role of CASQ2, we established CASQ2‐overexpressing breast cancer cell lines for in vitro and in vivo experiments. CASQ2 overexpression in breast cancer cells resulted in a more aggressive phenotype and altered epithelial–mesenchymal transition (EMT) markers in vitro. CASQ2 overexpression induced cancer‐associated fibroblast characteristics along with increased hypoxia‐inducible factor 1α (HIF1α) expression in stromal fibroblasts. CASQ2 overexpression accelerated tumorigenesis, induced collagen structure remodeling, and increased distant metastasis in vivo. CASQ2 conferred more metaplastic features to triple‐negative breast cancer cells. Our data suggest that CASQ2 is a key regulator of breast cancer tumorigenesis and metastasis by modulating diverse aspects of tumor–microenvironment interactions.

Objective To evaluate the efficacy of vaginal hysterectomy combined with anterior and posterior colporrhaphy (VH APR) for the management of pelvic organ prolapse (POP). Methods A total of 610 patients with POP who underwent VH APR from January 2010 to June 2019 at Asan Medical Center were included in this study. We analyzed the patient characteristics and surgical outcomes. In addition, we compared the POP quantification system (POP-Q) pre- and postoperatively at 2 weeks, 3 months, and 1 year, and analyzed the risk factors for recurrence. Results The mean age of the patients was 65.5±7.6 years. The most common preoperative POP-Q stage was stage 2 (60.8%), followed by stage 3 (35.9%). Complications were identified during surgery in 1.6% of the patients. The most common postoperative complication (6.4%) was voiding difficulty. All POP-Q scores significantly decreased at 1 year after surgery (P

Objective We compared the efficacy and postoperative complications of tension-free vaginal tape (TVT)-abbrevo® (TVT-A) and TVT-obturator® (TVT-O) surgeries for the treatment of stress urinary incontinence (SUI). Methods We retrospectively analyzed the medical records of 143 female patients with SUI who underwent TVT-A or TVT-O surgery between January 2010 and December 2019 at the Asan Medical Center in Seoul. We evaluated intra- and postoperative complications such as bladder injury, groin pain, urinary retention, and mesh exposure. We also checked the success rate at 6 months after surgery. Results There were no complications, including fever, hematuria, hematoma of the vulva, or bladder injury, immediately after surgery in either group. Postoperative complications 2 weeks post-surgery were groin pain (11.3%), urinary retention (4.9%), and mesh exposure (0.7%). Groin pain was not significantly different between the two groups at 2 weeks, 3 months, and 6 months after surgery (TVT-O vs. TVT-A after 2 weeks: 12.5% vs. 10.3%, P=0.791; 3 months: 0.0% vs. 1.4%, P=0.999; and 6 months: 0.0% vs. 0.0%, P=0.999). Over 90% of the patients reported cure or improved symptoms in both groups. In the univariate logistic analysis, the type of TVT (TVT-O or TVT-A) was not associated with the success rate (odds ratio, 3.21; 95% confidence interval, 0.59–17.40; P=0.175). Conclusion TVT-A surgery is comparable with TVT-O in terms of high success rate and low frequency of complications, including bladder injury and groin pain.

Background An adequate large-scale pediatric cohort based on nationwide administrative data is lacking in Korea. Purpose This study established the National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008) based on data from a nationwide population-based health screening program and data on healthcare utilization for children. Methods The NICKs-2008 study consisted of the Korean National Health Insurance System (NHIS) and the National Health Screening Program for Infants and Children (NHSPIC) databases comprising children born in 2008 (n=469,248) and 2009 (n=448,459) in the Republic of Korea. The NHIS database contains data on age, sex, residential area, income, healthcare utilization (International Classification of Diseases-10 codes, procedure codes, and drug classification codes), and healthcare providers. The NHSPIC consists of 7 screening rounds. These screening sessions comprised physical examination, developmental screening (rounds 2–7), a general health questionnaire, and age-specific anticipatory guidance. Results During the 10-year follow-up, 2,718 children (0.3%) died, including more boys than girls (hazard ratio, 1.145; P

Cardiotoxicity from first-generation H1-antihistamines has been debated since the 1990s. However, large-scale studies on this topic in a general pediatric population are lacking. This study aimed to assess the association between first-generation H1-antihistamine use and cardiovascular events in a nationwide pediatric population. In this case-crossover study, the main cohort included children with cardiovascular events from the National Health Insurance Service database (2008–2012 births in Korea) until 2018. The second cohort excluded children with specific birth histories or underlying cardiovascular diseases from the main cohort. Cardiovascular events of interest included cardiac arrhythmia and ischemic heart disease. Odds ratios (ORs) of cardiovascular events were estimated using conditional logistic regression models, comparing first-generation H1-antihistamine use during 0–15 days before cardiovascular events (hazard period) with use during 45–60 and 75–90 days before events (control periods). Among the participants, 1194 (59.9%) were aged 24 months to 6 years, and 1010 (50.7%) were male. Cardiovascular event risk was increased among users of first-generation H1-antihistamines (adjusted OR [aOR], 1.201; 95% confidence interval, 1.13–1.27). Significant odds of cardiovascular events persisted within 10 and 5 days (aOR, 1.25 and 1.25). In the second cohort, the association was comparable with that in the main cohort. Our findings indicate that cardiovascular event risk is increased in children who are administered first-generation H1-antihistamines.

The timing of complementary food (CF) introduction is closely related to childhood health, and it may vary depending on the region, culture, feeding type, or health condition. Despite numerous studies on the benefits of breastfeeding and the optimal timing of CF introduction, there have been limited investigations regarding delayed CF introduction in exclusively breastfed children. We compared an exposed group (CF introduction ≥7 months) with a reference group (CF introduction at 4 –< 7 months) regarding hospital admission, disease burden, and growth until age 10. Data from a nationwide population-based cohort study involving children born between 2008 and 2012 in the South Korea were analyzed. The final cohort comprised 206,248 children (165,925 in the exposed group and 40,323 in the reference group). Inverse probability of treatment weighting with propensity score matching was used to balance baseline health characteristics in the comparison groups. We estimated the incident risk ratios (IRR) for outcomes using modified Poisson regression and weighted odds ratios (weighted ORs) and their 95% confidence intervals (CIs) using multinomial logistic regression. The exposed group was associated with low height-for-age z-score (HAZ) (IRR (95% CI) for −1.64 < HAZ ≤ −1.03: 1.11 (1.08 to 1.14); HAZ ≤ −1.64: 1.21 (1.14 to 1.27)) and frequent (≥6 events) hospitalizations (weighted OR 1.18 (1.09 to 1.29). The rates of hospital admission, death, and specific medical conditions did not differ between groups. However, delaying the introduction of CF until seven months in exclusively breastfed infants was associated with frequent hospitalization events and lower heights.

(1) Background: Feeding behavior habits have a pattern with a certain tendency during infancy. We aimed to identify the associations between feeding patterns in infancy and the subsequent 10-year childhood disease burden. (2) Methods: Data from 236,372 infants were obtained from the national health insurance and screening program records in South Korea. Parent-administered questionnaires during infancy provided details on the feeding type and types/frequency of complementary food for analyzing feeding patterns. The outcomes were all-cause hospitalization and the development of 15 representative childhood diseases until the age of 10 years. Anthropometric measurements obtained at 6 years of age were analyzed. To estimate outcome risks while considering multiple risk factors, we employed a Cox proportional hazard and modified Poisson regression. (3) Results: Three clusters were identified: high prevalence of breastfeeding with regular exposure to a variety of solid foods (n = 116,372, cluster 1), similar prevalence of breastfeeding and formula feeding with less exposure to solid foods (n = 108,189, cluster 2), and similar prevalence of breastfeeding and formula feeding with the least exposure to solid foods in infancy (n = 11,811, cluster 3). Compared with cluster 1, children in clusters 2 and 3 had increased risks of all-cause hospitalization (hazard ratio (HR), (95% confidence interval (CI)), 1.04 (1.03–1.06) and 1.08 (1.05–1.11), respectively). Children in clusters 2 and 3 had an increased risk of upper respiratory infection, pneumonia, and gastroenteritis, as well as neurobehavioral diseases. Overweight/obesity at the age of 6 years was associated with clusters 2 and 3. (4) Conclusions: Feeding patterns in infancy were associated with an increased risk of childhood disease burden.

Abstract Background The purpose was to determine the association between infant exposure to humidifier disinfectant (HD) with neuropsychiatric problems in pre-school children. Methods A total of 2,150 children (age 4–11 months) were enrolled in the Panel Study of Korean Children (PSKC) study. The Korean version of the Child Behavior Checklist (CBCL) was used for assessments of neuropsychiatric problems. 1,113 children who participated in all the first to third PSKC studies and answered a question about HD exposure were finally enrolled. Results There were 717 (64.5%) children in non-HD group who were not exposed to HD and 396 (35.5%) in HD group with former exposure to HD. Exposure to HD was associated with total neuropsychiatric problems (adjusted odds ratio, aOR = 1.54, 95% CI = 1.15–2.06), being emotionally reactive (aOR = 1.55, 95% CI = 1.00–2.39), having attention problems (aOR = 1.96, 95% CI = 1.10–3.47), having oppositional defiant problems (aOR = 1.70, 95% CI = 1.07–2.71), and having attention deficit/hyperactivity problems (aOR = 11.57, 95% CI = 1.03–2.38). The risks for neuropsychiatric problems were clearly increased in boy, firstborn, and secondary smoker. Conclusions Exposure to HD during early childhood had a potential association with subsequent behavioral abnormalities.

Background There are few studies on the association with Kawasaki disease in children and the family’s history of cardiovascular disease (CVD). The aim of this study was to identify the association of increased risks for Kawasaki disease in children with a family history of CVD. Methods and Results Clinical data of children born in 2008 and 2009 (n=917 707) were obtained from the National Health Insurance Service and the National Health Screening Program for Infants and Children for this study. The cohort consisted of 495 215 participants (53.8%) who completed the family history questionnaire for children 54 to 60 months old. Family history of CVD included 5 medical conditions: hypertension, dyslipidemia, myocardial infarction, stroke, and diabetes. Kawasaki disease was defined using the disease code, intravenous immunoglobulin prescription, and use of antipyretics for more than 25 days. Severe Kawasaki disease was defined as diagnosis of accompanied cardiac/coronary artery complications or intravenous immunoglobulin use ≥2 times. The incidence rate of Kawasaki disease was 124/100 000 person‐years (95% CI, 117.5–131.5) for children 5 years old. After propensity‐score matching, 829 participants with a family history of CVD were diagnosed as having Kawasaki disease (0.68% [95% CI, 0.63–0.72]), and 690 patients with Kawasaki disease (0.56% [95% CI, 0.52–0.61]) had no family history of CVD. The family history of CVD was associated with increased risk for Kawasaki disease (risk ratio, 1.20 [95% CI, 1.08–1.32]) but not for severe Kawasaki disease (risk ratio, 1.23 [95% CI, 0.92–1.65]). Conclusions In this nationwide propensity‐score matched study, those with a family history of CVD had a significantly greater risk of Kawasaki disease compared with those who had no family history of CVD.

A fixed-dose combination of pyronaridine and artesunate, one of the artemisinin-based combination therapies, has been used as a potent antimalarial treatment regimen. Recently, several studies have reported the antiviral effects of both drugs against severe acute respiratory syndrome coronavirus two (SARS-CoV-2). However, there are limited data on the pharmacokinetics (PKs), lung, and trachea exposures that could be correlated with the antiviral effects of pyronaridine and artesunate. The purpose of this study was to evaluate the pharmacokinetics, lung, and trachea distribution of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) using a minimal physiologically-based pharmacokinetic (PBPK) model. The major target tissues for evaluating dose metrics are blood, lung, and trachea, and the nontarget tissues were lumped together into the rest of the body. The predictive performance of the minimal PBPK model was evaluated using visual inspection between observations and model predictions, (average) fold error, and sensitivity analysis. The developed PBPK models were applied for the multiple-dosing simulation of daily oral pyronaridine and artesunate. A steady state was reached about three to four days after the first dosing of pyronaridine and an accumulation ratio was calculated to be 1.8. However, the accumulation ratio of artesunate and dihydroartemisinin could not be calculated since the steady state of both compounds was not achieved by daily multiple dosing. The elimination half-life of pyronaridine and artesunate was estimated to be 19.8 and 0.4 h, respectively. Pyronaridine was extensively distributed to the lung and trachea with the lung-to-blood and trachea-to-blood concentration ratios (=Cavg,tissue/Cavg,blood) of 25.83 and 12.41 at the steady state, respectively. Also, the lung-to-blood and trachea-to-blood AUC ratios for artesunate (dihydroartemisinin) were calculated to be 3.34 (1.51) and 0.34 (0.15). The results of this study could provide a scientific basis for interpreting the dose–exposure–response relationship of pyronaridine and artesunate for COVID-19 drug repurposing.

Abstract Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase reactant that mediates innate immune responses triggered by LPS. Recent studies indicated a positive correlation of circulating LBP level with chronic low-grade inflammation, a condition present in many non-communicable diseases. We determined the association of serum LBP concentration with allergic sensitization in a general pediatric population. Serum LBP was measured in a sample of children (n = 356; mean age = 9.6 ± 0.2 years) in this population-based cross-sectional study. Skin prick tests (SPTs) were performed to assess allergic sensitization to 22 common inhalant and food allergens. One hundred and seven children (30.1%) were nonsensitized, 160 (44.9%) were monosensitized, and 89 (25.0%) were polysensitized. Children who were mono- or polysensitized had a significantly higher median serum LBP level (25.5 ng/mL, inter-quartile range [IQR] 20.3–30.7) than those who were nonsensitized (20.3 ng/mL, IQR = 14.81–25.8, P

Abstract To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell–cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Direct co-culture showed most distinct phenotype changes in MCF10A cells followed by conditioned media treatment and indirect co-culture. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell–cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.

Formononetin is a major isoflavone contained in propolis and is reported to exhibit various pharmacological effects. However, the use of formononetin in pharmaceutical industry is limited due to its low bioavailability and solubility. There had been several efforts on formononetin formulation development, but further study is required to acquire optimal formulation. The aim of this study is to conduct pharmacokinetic (PK) evaluations after the oral administration of three formononetin formulations (20 mg/kg) in male Sprague Dawley rats. Then, a parent-metabolite PK model for formononetin was developed and evaluated for the first time. To do this, a simultaneous analysis method for formononetin and its active metabolites, daidzein, dihydrodaidzein and equol in rat plasma was developed using ultra-performance liquid chromatography tandem mass spectrometry. The separation was performed using a gradient elution of water and acetonitrile and a Kinetex C18 column (2.1 mm × 100 mm, 1.7 µm particle size) at a temperature of 30 ± 5 °C. The simultaneous analytical method developed in this study was validated according to international guidance and was successfully applied for the pharmacokinetic study. The time-plasma concentrations of formononetin and daidzein were well described by a two-compartment model combined with a metabolite compartment. Additionally, plasma protein binding assay was conducted in male rat plasma. The findings from the study could be used as a fundamental for the future development of formononetin as a pharmaceutical product.

During the COVID-19 pandemic, there was a growing awareness about the importance of building a health and safety net based on digital healthcare systems, such as ICT-based local community online services and patient monitoring technology. This study was conducted with the aim of evaluating the formative usability of a three-way digital healthcare system, which had been developed to build a health and safety net for people with disabilities and deriving the directions for system improvement in order for them to be used as basic data for further system enhancement. A formative usability evaluation of a three-way digital healthcare system was performed with the participation of 43 healthcare professionals, using the 10-item System Usability Scale (SUS) and five items for satisfaction evaluation. Each item was rated on a five-point Likert scale, with the result converted to a scale of 100. Analysis was performed using the average score and the acceptable system usability level. The overall mean SUS score was 62.4, which corresponds to Grade D according to the SUS grading scale, and the below-average items were complexity (Q2), convenience (Q8), simplicity (Q3), professionalism (technician support, prior learning) (Q4, Q10), and learnability (Q7). The overall mean user satisfaction was 71.2 points, where overall satisfaction, system architecture and understandability, and continuous use intention were marked with below-average scores. The SUS D grade is interpreted as “fair” and the water solubility is “almost acceptable”. For the usability enhancement of the newly developed a three-way digital healthcare system, the overall direction for system architecture improvement was analyzed centering on complexity (Q2), convenience (Q8), professionalism (technician support, prior learning) (Q4, Q10), learnability (Q7), and simplicity (Q3). Efforts need to be directed at enhancing system satisfaction and continuance rate by deriving detailed system improvement strategies and achieving system enhancement to reflect the opinions of not only experts but also users.

Abstract Berry fruits have attracted attention because of their purported benefits for aging, cardiovascular disease, and cancer. Therefore, highly priced berry fruits might be targets for food adulteration and fraud. In this study, eight species-specific primer sets based on the single nucleotide polymorphism of the chloroplast genomes of four berry fruits (aronia, blackberry, cranberry, and strawberry) were developed for quantitative real-time PCR (qPCR) analysis by SYBR Green staining with the aim of preventing berry fruit food fraud. The developed primer pairs exhibited high efficiencies ranging from 88 to 110% with strong correlation coefficients (R2 > 0.99) for the amplification of each target species. However, no clear correlation coefficients were evident for non-target species. To evaluate the practicality of the developed primers, 18 commercial berry fruit products were verified by qPCR analysis. The developed primer pairs were amplified to a low Ct value (range 16.1–23.3) for the target species and proved capable of detecting target species in berry fruit commercial foods. Therefore, the developed qPCR-based species-specific markers could be suitable for the prevention of berry fruit food fraud and to verify marker reliability.

Purpose: A systematic review and meta-analysis was conducted to evaluate the effects of smartphone-based mobile learning for nurses and nursing students. Methods: Electronic literature search of PubMed, Cochrane Library, Embase, SCOPUS, Web of Science, ProQuest Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Educational Resource Information Center (ERIC) was conducted. Two authors independently reviewed empirical studies for inclusion and extracted the design, sample size, intervention method, outcome variables, and statistical values of them. Methodological quality was assessed using Cochrane collaboration risk of bias tool. To estimate the effect size, meta-analysis was performed using R meta program. Results: Authors identified 11 randomized or nonrandomized controlled trials of a total of 3,419 studies. Overall effect sizes by random-effects model was large [Hedges'g (g) = 1.12, 95% confidence interval (CI) 0.72–1.52], with learning attitude (g = 1.69), skills (g = 1.41), knowledge (g = 1.47), and confidence in performance (g = 1.54). For heterogeneity, subgroup analyses using meta-analysis of variance were performed, but no significant difference was found. Finally, a funnel plot and Egger's regression test along with trim-and-fill analysis and fail-safe N were conducted to check for publication bias, but no significant bias was detected. Conclusion: Smartphone-based mobile learning had significantly positive influence on nursing students' knowledge, skills, confidence in performance, and learning attitude. Smartphone-based mobile learning may be an alternative or supportive method for better education in nursing fields. Keywords: meta-analysis, nursing, review, smartphone

Background: Evidence supporting a tablet personal computer (PC)-based mode for a systemic approach to managing the breast cancer survival is limited. Objective: The objective of this study was to evaluate whether a tablet personal computer (PC) survey is feasible for screening the risks of the recurrence of breast cancer and the survivor issues associated with breast cancer treatment. Materials and methods: A descriptive study design was used. A pilot test of the tablet PC survey for its feasibility was undertaken using 40 breast cancer survivors at a university affiliated cancer management-survivorship clinic. The tablet PC survey was evaluated by structured questionnaires designed to assess patient experiences responding to the tablet PC-based surveys and user friendliness of the device itself. Results: Older patients and those with a lower education were more likely to have difficulty with the tablet PC administration and required assistance. Both physicians and nurses reported that the tablet PC survey was a useful tool that assisted healthcare professionals with providing quality of care. Conclusion: This pilot test supported the feasibility of a tablet PC survey as a vehicle for breast cancer survivorship management. Keywords: Breast cancer, Survivorship, Tablet, Survey

Osteoporosis is a common skeletal disease in post-menopausal women. Palmul-tang, an herbal medicine, has been treated for gynecological disease such as anemia, anorexia, anti-fatigue, unspecified menstruation and female infertility in East Asia. In this study, ameliorative effects of Palmul-tang soft extracts (PMT), a Korean Medicine, on osteoporosis were investigated. Ovariectomized (OVX) osteoporotic ICR mice were intragastrically administrated PMT for 4 weeks. The level of bone mineral density (BMD) was analyzed in bone tissues by dual X-ray absorptiometry. The bone medullary cavity and deposition of collagen were investigated by histological analysis. In addition, the BMP-2 signaling-related molecules, osteoblastic differentiation and formation markers, were determined in femoral tissues. The levels of BMD and bone mineral content were significantly increased in tibia, femurs and LV by treatment of PMT. PMT replenished bone marrow cavity and increased collagen deposition in bone marrow cells of femur. In addition, administration of PMT recovered serum ALP, bALP, osteocalcin and calcium levels in osteoporotic mice. Moreover, PMT treatment up-regulated the expressions of BMP-2, RUNX2 and OSX with its downstream factors, ALP, OPN and BSP-1, in the femoral tissues. Taken together, PMT restored the bone minerals and improvement of bone integrity by bone-forming BMP-2 signaling pathway. These results demonstrate that PMT could be an ameliorative agent for osteoporosis.

Acute myocardial infarction (AMI) is lethal and causes myocardial necrosis via time-dependent ischemia due to prolonged occlusion of the infarct-related artery. No effective therapy or potential therapeutic targets can prevent myocardial ischemia/reperfusion (I/R) injury. Targeted temperature management (TTM) may reduce peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1) as a primary mediator of the innate immune response. We used a rat left anterior descending (LAD) coronary artery ligation model to determine if TTM at 33°C and 36°C had similar myocardial protective effects. Rats were divided into sham, LAD I/R+37°C normothermia, LAD I/R+33°C TTM, and LAD I/R+36°C TTM groups (n = 5 per group). To verify the cardioprotective effect of TTM by specifically inhibiting HMGB1, rats were assigned to sham, LAD I/R, and LAD I/R after pre-treatment with glycyrrhizin (known as a pharmacological inhibitor of HMGB1) groups (n = 5 per group). Different target temperatures of 33°C and 36°C caused equivalent reductions in infarct volume after myocardial I/R, inhibited the extracellular release of HMGB1 from infarct tissue, and suppressed the expression of inflammatory cytokines from peri-infarct regions. TTM at 33°C and 36°C significantly attenuated the elevation of cardiac troponin, a sensitive and specific marker of heart muscle damage, after injury. Similarly, glycyrrhizin alleviated myocardial damage by suppressing the extracellular release of HMGB1. TTM at 33°C and 36°C had equivalent myocardial protective effects by similar inhibiting HMGB1 release against myocardial I/R injury. This is the first study to suggest that a target core temperature of 36°C is applicable for cardioprotection.

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children’s height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted β = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children.

This study estimated the economic burden of people with brain disability in Korea during 2008-2011 using nationally representative data and was conducted to use the results as an evidence for determining the resources allocation of people with brain disability. We used a prevalence-based approach to estimate the economic burden, classified by direct costs (medical costs and nonmedical costs) and indirect costs (productivity loss of morbidity and premature death). Data from the National Health Insurance Service, the National Disability Registry, the National survey on persons with disabilities, the Korea National Statistical Office’s records of causes of death, and the Labor Statistics were used to calculate direct and indirect costs. The treated prevalence of brain disability increased from 0.26% (2008) to 0.35% (2011). Total economic burden of brain-related diseases was US$1.88 billion in 2008 and increased to US$2.90 billion in 2011, with a 54% rate of increase. The economic burden of all diseases, which was 1.2 to 1.4 times higher than that of brain-related diseases, accounted for US$2.61 billion in 2008 and US$3.62 billion in 2011, increasing by 39%. Owing to the growing occurrence of brain disability, the annual prevalence and related costs are increasing. Health management programs are necessary to reduce the economic burden of brain disability in Korea.

This study, conducted in the Republic of Korea, analyzed nursing faculty members’ knowledge of and attitudes toward research ethics according to their characteristics and the institutional environment. A survey was conducted from April 24 to July 23, 2017. The participants were 210 nursing professors from 57 universities in Korea. The survey questionnaire gathered information on participants’ characteristics, their knowledge of and attitudes toward research ethics, and their perceived training needs. A relatively low difficulty index was found for knowledge items dealing with conflicts of interest (0.66), copyright (0.65), and plagiarism and duplicate publications (0.17) than for the other six items. Of the 12 items assessing attitudes toward research ethics, use of a plagiarism-checking program and reviewing manuscripts from members of one’s own research group had the lowest scores. The knowledge level of participants whose institutions provided a plagiarism-checking program was higher than those whose institutions did not. Former group also showed better attitudes toward research ethics. High-priority training needs were obtaining institutional review board (IRB) approval, writing informed consent forms, and obtaining informed consent for studies on children and pregnant women. A more intensive training program for nursing faculty is required on specific topics, including conflicts of interest, copyright, plagiarism, duplicate publications, IRB approval, and informed consent. Furthermore, all nursing institutions in Korea should provide a plagiarism-checking program to faculty members.

YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10–12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C (p=0.017) and high-TG (p=0.010) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group (p=0.007). After adjusting for age, gender, and BMI z-score, the associations between serum YKL-40 levels and TG levels (p=0.003), the TG-to-HDL-C ratio (p=0.019), and the AIP value (p=0.012) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.

Two mRNA COVID-19 vaccines (mRNA-1273, Moderna; and BNT162b2, Pfizer-BioNTech) and one viral vector vaccine (JNJ-78436735, Janssen/Johnson and Johnson) are authorized in the US to hinder COVID-19 infections. We analyzed severe and common adverse events in response to COVID-19 vaccines using real-world, Vaccine Adverse Effect Reporting System (VAERS) data. From 14 December 2020 to 30 September 2021, 481,172 (50.7 ± 17.5 years, males 27.89%, 12.35 per 100,000 people) individuals reported adverse events (AEs). The median time to severe AEs was 2 days after injection. The risk of severe AEs following the one viral vector vaccine (OR = 1.044, 95% CI = 1.005–1.086) was significantly higher than that after the two mRNA vaccines, and the risk among males (OR = 1.374, 95% CI = 1.342–1.406) was higher than among females, except for anaphylaxis. For common AEs, however, the risk to males (OR = 0.621, 95% CI = 0.612–0.63) was lower than to females. In conclusion, we provided medical insight and clinical guidance about vaccine types by characterizing AEs using real-world data. In particular, COVID-19 mRNA vaccines are safer than viral vector vaccines with regard to coagulation disorders, whereas inflammation-related AEs are lower in the viral vaccine. The risk–benefit ratio of vaccines should be carefully considered, and close monitoring and management of severe AEs is needed.

Objective: The objective of this study was to analyze the effect of consuming formula powder prepared with tap water or purified water during the first 4 to 6 months of life on the subsequent development of irritable bowel syndrome (IBS). Study design and setting: A total of 917,707 children who were born in Korea between 2007 and 2008 were analyzed. All children were followed up until they lost eligibility for health care services or until 2017. Data on the water used to prepare formula powder were from questionnaires answered by the parents when the child was 4 to 6 months old. IBS was defined as two or more diagnoses of IBS after the age of 4 years. Inverse probability of treatment weighting (IPTW) using the propensity score was used to balance the two groups. The risk of IBS was evaluated using a Cox proportional hazards model. Results: After weighting, there were 73,355 children in the tap water group and 73,351 in the purified water group. The purified water group had a higher risk of IBS (HR: 1.05; 95% CI: 1.01, 1.09). This relationship was also present after the subgroup analyses of males and females and the sensitivity analysis that used different definitions of IBS. Conclusions: Drinking formula powder prepared with purified water rather than tap water during the first 4 to 6 months of age was found to be associated with IBS.

Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

Purpose: Resilience relates to coping with stressful hospital environment. The purpose of this study was to identify the types of resilience skills of clinical nurses for surviving in a hospital setting. Methods: The Q methodology was used as it helps analyze the participants' subjective perspective on each item. Participants were 32 registered nurses who sorted 38 selected Q statements that were then plotted on a normal distribution using a 9-point scale. The subjective perspectives on the resilience of clinical nurses were analyzed using the PC-QUANAL program. Results: This study revealed four types of resilience in clinical nurses, accounting for 65.2% of the variance: Type I: Reality-harmonic type; Type II: Own will type; Type III: Professionalism-oriented type; and Type IV: Relation-oriented type. Conclusion: The present findings suggest the need to develop interventions for improving clinical nurses' resilience according to their types. Following further investigation of nurses' resilience, it may be necessary for organizations to develop several resilience strategies. Keywords: methods, nurses, resilience, psychological