A mouse xenograft long-term replication yields a SARS-CoV-2 Delta mutant with increased lethality.

We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta-10 and Delta-12, with both predominant mutations and some additional mutations. Delta-10 and Delta-12 showed lower replication capacity compared with SARS-CoV-2 Delta in cultured cells; however, Delta-12 was more lethal in K18-hACE2 mice compared with SARS-CoV-2 Delta and Delta-10. Mice infected with Delta-12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta-12 was associated with lung and brain pathology. Our long-term infection model can provide mutant viruses derived from SARS-CoV-2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.

Effects of parental holding on pain response in young children during cystometry: A randomized controlled trial.

INTRODUCTION: Cystometry is essential for evaluating bladder function. However, children may react negatively to the physical pain of urethral catheterization or anxiety and fear of an unfamiliar environment. These pain responses during the cystometry procedure may interfere with the cystometry procedure and make it difficult to interpret the cystometry result. In this regard, the International Children's Continence Society has advised performing cystometry while holding infants as an effective nonpharmacological pain management method, but there is insufficient evidence to support this. PURPOSE: This study aimed to analyze the effect of parental holding on reducing pain in children during cystometry. METHODS: This was an experimental study in a randomized controlled pre-post test design. A total of 64 participants aged 6-18 months were recruited. During cystometry, the participants in the experimental group were placed on the parent's laps and held in the parents' arms. The participants in the control group were laid down on the examination table. During the procedure, both groups of parents were allowed to touch their children in all ways except holding them and to use the pacifier if they wished. The behavioral (face, leg, activity, cry, consolability scale) and physiological (oxygen saturation and heart rate) pain responses were measured at three-time points (immediately, 3, and 10 min after urethral catheter insertion). RESULTS: Comparing the two groups, in the experimental group, the behavioral pain response at 3 min after urethral catheter insertion (t = -2.165, p = 0.034) and 10 min after (t = -3.155, p = 0.002) was decreased compared with that immediately after urethral catheter insertion. In addition, oxygen saturation increased more (t = 2.021, p = 0.048), and the heart rate decreased more (t = -2.033, p = 0.047) at 10 min than at 3 min after urethral catheter insertion in the experimental group. CONCLUSIONS: This study revealed that parental holding could reduce pain responses during cystometry in children. Further research is required to confirm the applicability and usefulness of parental holding during cystometry.

Investigating family resilience factors for enhancing family adaptation in children with epilepsy.

PURPOSE: To identify and understand the key family resilience factors that contribute to the improved family adaptation of children with epilepsy. METHODS: Parent of children with epilepsy treated in the outpatient unit and general ward at Severance Children's Hospital in Seoul, Korea, completed a structured online questionnaire between April and May 2023. This study examined risk (epilepsy severity, time since diagnosis, parental depression, and perceived stigma) and protective factors (child temperament, epilepsy knowledge, family communication skills, parent's educational level, monthly household income, and social support) of family adaptation based on Patterson's Family Resilience Model. Furthermore, general characteristics such as daily caregiving time, perceived parental health, family type, and primary caregiver role were analyzed. RESULTS: This study included 131 participants with a mean age of 41.79 ± 5.77 years, with children having an average age of 9.19 ± 4.94 years. The regression model was significant, and revealed the impact of communication skills, social support, and primary caregivers other than parents. Moreover, a shorter time since diagnosis has a more positive impact on family adaptation. CONCLUSIONS: To improve family adaptation in children with epilepsy, the focus should be placed on improving communication skills, increasing social support, and providing access to external support services. Furthermore, families expecting longer illness duration require proactive measures to support them. These findings could guide future strategies to enhance adaptation in families with children with epilepsy.

Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

Non-pharmacological interventions for delirium in the pediatric population: a systematic review with narrative synthesis.

BACKGROUND: Delirium is a serious complication experienced by hospitalized children. Therefore, preventive management strategies are recommended for these patients. However, comprehensive analyses of delirium interventions in children remain insufficient. Specifically, this systematic review aimed to summarize non-pharmacological interventions for pediatric delirium, addressing the urgent need for a comprehensive understanding of effective strategies. We also explored frequently measured outcome variables to contribute evidence for future research on delirium outcomes in children. METHODS: This systematic review searched articles from PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medica databases. The eligibility criteria were formed under the population, intervention, comparator, outcome, and study design framework. Studies were included if they involved (1) children aged under 18 years receiving hospital care, (2) non-pharmacological delirium interventions, (3) comparators involving no intervention or pharmacological delirium interventions, and (4) outcomes measuring the effectiveness of non-pharmacological delirium interventions. Only peer-reviewed articles published in English were included. RESULTS: Overall, 16 studies were analyzed; of them, 9 assessed non-pharmacological interventions for emergence delirium and 7 assessed interventions for pediatric delirium. The intervention types were grouped as follows: educational (n = 5), multicomponent (n = 6), and technology-assisted (n = 5). Along with pediatric and emergence delirium, the most frequently measured outcome variables were pain, patient anxiety, parental anxiety, pediatric intensive care unit length of stay, agitation, analgesic consumption, and postoperative maladaptive behavior. CONCLUSIONS: Non-pharmacological interventions for children are effective treatments without associated complications. However, determining the most effective non-pharmacological delirium intervention for hospitalized children based on current data remains challenging.

Digital health intervention on patient safety for children and parents: A scoping review.

AIM: To explore digital health interventions on patient safety for children and their parents. DESIGN: A scoping review. METHODS: The PCC 'Participants, Concepts, and Contexts' guided the selection of studies that focused on children under 19 years of age or their parents, patient safety interventions for children, and digital health technology for patient safety interventions. This study was conducted using the Arksey and O'Malley framework's five steps. We reported the review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist. DATA SOURCES: PubMed, CINAHL, Embase, Web of Science, and Cochrane were searched for articles published up to November 2022. RESULTS: A total of 13 articles were included and categorized according to the following criteria to describe the results: intervention characteristics, type of digital technology, and outcome characteristics. Regarding intervention characteristics, we identified two categories, prevention and risk management. Additionally, we identified four types of digital technology, mobile applications, web-based technologies, computer kiosks and electronic health records. Finally, in studies focussing on child safety, parental safety behaviours were used to assess injury risk or detect changes related to prevention. CONCLUSION: Patient safety interventions provided through appropriate digital technologies should be developed to enhance continuum of care for children from hospitalization to home after discharge. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Digital health interventions can bolster the role of healthcare providers in patient safety in and out of hospitals, thus improving children's safety and quality of care. IMPACT: What problem did the study address? Although the various advantages of digital health technology have been demonstrated, the potential role of digital technology in patient safety interventions for children has not been explored. What were the main finding? Preventive patient safety interventions and risk management for children have been developed. Where and on whom will the research have an impact? Digital health interventions on patient safety can improve children's safety and quality of care by promoting non-face-to-face engagement of children and parents after discharge and expanding healthcare providers' roles. TRIAL AND PROTOCOL REGISTRATION: Registered on the Open Science Framework (https://osf.io/dkvst). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Foot deformity and quality of life among independently ambulating children with spina bifida in South Korea.

BACKGROUND: Children with spina bifida (SB) may have congenital or acquired foot deformities due to neurological defects in the spinal cord. As the musculoskeletal system keeps growing, foot deformities can develop or become aggravated. Thus, healthcare providers should provide constant monitoring and proper orthopedic management. Since foot deformities can affect not only the gait but also the daily life of children with SB, it is necessary to investigate the impact of foot deformities on everyday life. The purpose of this study was to examine the relationship between foot deformity and health-related quality of life (HRQoL) among independently ambulating children with SB. METHODS: This cross-sectional study examined the associations between foot deformity and HRQoL using two patient-reported outcome measures (Oxford Ankle Foot Questionnaire, Pediatric Outcomes Data Collection Instrument) in 93 children with SB aged 7-18 years between January 2020 and July 2021. RESULTS: Children with foot deformity (n = 54) reported lower scores in all subscales (physical, school and play, emotional, and footwear) of the Oxford Ankle Foot Questionnaire for children than those without foot deformity (n = 39; p < 0.001). Additionally, in terms of the Pediatric Outcomes Data Collection Instrument, children with foot deformity also reported poorer scores in four subscales (transfer and basic mobility, sports and physical functioning, comfort and pain, happiness with physical functioning; p < 0.001) than those without foot deformity, whereas upper extremity functioning was not significantly affected. Children with foot deformities, particularly those with bilateral foot deformities, equinus deformities, or mixed deformities, which are different types of right and left foot deformities, have a lower perceived HRQoL (p < 0.05). CONCLUSIONS: Among independently ambulating children with SB, those with foot deformities showed lower HRQoL. Moreover, children with foot deformities tend to have other clinical problems, including bladder and bowel dysfunction. Therefore, orthopedic management should consider the multifaceted factors that affect children's daily life and HRQoL.

Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

The association between nurse continuity and hypospadias repair patient outcomes: A retrospective study.

BACKGROUND: Recently, nurse continuity, the intensity and consistency of a patient's exposure to nurses during hospitalization, has been shown to be associated with patient outcomes. However, little is known about how nurse continuity is related to patients' surgical outcomes. AIMS: To examine the association between nurse continuity and outcomes of hypospadias repair to clarify the importance of nurse continuity as a nursing practice. DESIGN: This is a retrospective study. METHODS: We analysed the data from electronic health records of patients under 1 year who had undergone proximal hypospadias repair between January 2014 and December 2016. Nurse continuity was measured using the Continuity of Care Index. Since approximately half of the patients reportedly needed further operations in the long term, the primary outcome was whether patients with proximal hypospadias repair had two or more additional operations within 3 years of discharge. RESULTS: The rate of undergoing two or more follow-up operations in 3 years was significantly higher in patients with low nurse continuity-38.6% versus 12.8% for high continuity. CONCLUSION: This study identified nurse continuity as an important factor related to patients' surgical outcomes. These findings suggest that nurse continuity be considered an important nursing strategy for patient outcomes and further research is needed on this topic. IMPACT STATEMENT: As empirical evidence regarding the association between nurse continuity and patient outcomes grows, nurse managers and policymakers should view nurse continuity as a critical factor for positive patient outcomes when considering nursing workforce regulations. NO PATIENT OR PUBLIC CONTRIBUTION: The data for this study were obtained from electronic health records, and the entire process of this study did not involve patient or public participation.

Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Factors affecting the transition to adulthood of Korean young adults with spina bifida: a qualitative study.

BACKGROUND: Transition to adulthood to live independently while self-managing health and daily life without parental help is crucial for young adults with chronic conditions. Despite its importance as a precursor to effectively managing lifelong conditions, little is known about the experiences of young adults with spina bifida (SB) in transition to adulthood in Asian countries. This study aimed to explore the experiences of Korean young adults with SB to identify the facilitators or barriers to the transition from adolescence to adulthood from their perspectives. METHODS: This study used a qualitative descriptive design. The data were collected in South Korea through three focus group interviews with 16 young adults with SB, aged 19-26, from August to November 2020. We conducted a qualitative content analysis using a conventional approach to identify the factors that facilitated and hindered the participants' transition to adulthood. RESULTS: Two themes emerged as facilitators and barriers to the transition to adulthood. a) Facilitators: understanding and acceptance of SB, acquiring self-management skills, parenting styles encouraging autonomy, parents' emotional support, school teachers' thoughtful consideration, and participation in self-help groups. b) Barriers: overprotective parenting style, experience of being bullied by peers, damaged self-concept, concealing one's chronic condition from others, and the lack of privacy in school restrooms. CONCLUSIONS: Korean young adults with SB shared their experiences of struggling to properly manage their chronic conditions on their own, particularly concerning regular bladder emptying, during the transition from adolescence to adulthood. To facilitate the transition to adulthood, education on the SB and self-management for adolescents with SB and on parenting styles for their parents are important. To eliminate barriers to the transition to adulthood, improving negative perceptions of disability among students and teachers and making school restrooms CIC-friendly are needed.

Factors Associated With Media Addiction in Korean Elementary School Children.

The aim of this study was to identify the prevalence of media addiction and its associated factors in elementary school children based on the problem behavior theory. This cross-sectional study was a secondary data analysis using national data from the 10th Panel Study on Korean Children 2017, which included 1,078 families of third-grade students (8-9 years of age). Descriptive statistics were used to examine the prevalence of media addiction, and logistic regression analysis was conducted to identify factors associated with media addiction. Prevalence of media addiction was 22.91% in this sample. Media addiction was significantly associated with general characteristics (gender, education level of mother, and time spent without parents), socialization (media use time), factors in the personal system (happiness), and factors in the perceived-environment system (parenting style). More comprehensive, tailored education may prevent elementary school children's media addiction. In addition, parents should participate in media addiction education with their children.

Sensorial saturation improves infants' procedure-related pain behaviour in the cardiac intensive care unit: A quasi-experimental study.

BACKGROUND: Painful procedures are unavoidable when providing critical care to infants in intensive care units. These adverse experiences during infancy can lead to later hyperalgesia and poor neurodevelopmental outcomes. Thus, appropriate interventions are required to relieve infant pain during these procedures. OBJECTIVES: This study evaluated the effectiveness of sensorial saturation in reducing pain for infants during jugular central venous catheter removal procedures in intensive care units. METHODS: This study involved a quasi-experimental, repeated-measures design. Data were collected from participants sequentially recruited from April to June 2019 (control period) and July to September 2019 (experimental period). Participants included 78 infants younger than 1 year with congenital heart disease. The control group (n = 38) received a general nursing intervention using swaddling, a common child-care practice that consists of wrapping infants to restrict movements, whereas the experimental group (n = 40) received sensorial saturation using oral sugar, body massage, and verbal interaction. Infants' physiological reactions to procedural pain were measured by changes in heart rate, oxygen saturation, and respiratory rate. Infants' procedural pain and behavioural indicators were measured using the Modified Behavioural Pain Scale. Data were analysed using descriptive statistics, independent t-tests, χ2 tests, and repeated-measures analysis of variance. RESULTS: Compared with the control group, the experimental group had lower heart rates (F = 53.15, p < .001), respiratory rates (F = 15.19, p < .001), and behavioural pain scores (F = 45.21, p < .001), both during and after the procedure. CONCLUSIONS: Sensorial saturation can be used as a nursing intervention in infants. Given the many invasive procedures that are part of infant clinical care, sensorial saturation may be a safe analgesic alternative. The findings of this study could lead to the development of evidence-based clinical practice guidelines for the nonpharmacological management of acute pain in infants.

Nurse-led eHealth transition care program for adolescents with spina bifida: A feasibility and acceptability study.

PURPOSE: This study aimed to evaluate the feasibility and acceptability of a nurse-led eHealth transition care program for adolescents with spina bifida. DESIGN AND METHODS: This study used a single-arm, pretest-posttest intervention study. Adolescents with spina bifida, aged 12-15 years, and their parents participated in the program. A 6-week program was delivered through an online platform in real-time by nurses. We evaluated feasibility and acceptability using criteria such as the completion rate, program satisfaction, changes in transition readiness, social support, career preparation behavior, sexual knowledge, and sexual worries at three time points from July to September 2021. RESULTS: Thirteen adolescents completed all sessions and surveys (13/14, 92.9%). All adolescents expressed high satisfaction with both the content and delivery methods of the program. Significant benefits in transition readiness, career preparation behavior, and sexual knowledge were identified over the study period. However, the evaluation of social support and sexual worries did not demonstrate any significant improvements. Additionally, through family counseling, adolescents benefited from experiences such as reflecting on their current transition readiness, setting and achieving individualized goals and plans using a self-checklist with their parents and nursing professionals. CONCLUSION: This nurse-led eHealth intervention was feasible and acceptable for adolescents with spina bifida. Furthermore, our results highlight the practicability and the potential for strategic dissemination of using this eHealth program in transitional care during the COVID-19 pandemic. PRACTICE IMPLICATIONS: The eHealth transition care program contributes to broadening existing nursing interventions not only in medical areas but also in daily life areas.

An educational design and development project for pediatric heart transplant recipients and their families.

PURPOSE: The purpose of this project is to systematically derive and develop educational content for children who have undergone heart transplants and their families to improve the families' and caregivers' ability to manage child health in South Korea. DESIGN AND METHODS: This project developed educational content through the first three steps: "Analysis," "Design," and "Development" of the five steps outlined in the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model. The educational contents were derived from an analysis of six literature reviews and six studies, seven websites, and interviews with six caregivers of children who have undergone a heart transplant. Based on these analyses, educational items were designed. When a draft of the education contents was developed, the content validity was validated by ten experts. RESULTS: Educational items were designed in nine major categories and 40 sub-categories. All contents were validated with a content validity index of at least 0.8 or higher and included in the education content for pediatric heart transplant families, with recommendations for further modification based on expert advice. PRACTICE IMPLICATIONS: This project is meaningful in that it has developed health management education contents suitable for the situation in South Korea through analyzing previous studies and educational contents of domestic and international medical centers as well as an in-depth interview with caregivers.

Workplace bullying and different levels of post-traumatic stress symptoms of nurses: A quantile regression approach for effective coping strategies.

AIM: This study aimed to investigate effects of workplace bullying on different post-traumatic stress symptoms and coping among hospital nurses. BACKGROUND: Workplace bullying is a traumatic event that negatively affects the quality of patient care and nurses' mental health. METHOD: This cross-sectional, correlational study used an online survey among hospital nurses. Ordinary least square and quantile regression analyses were conducted using Stata version 16. RESULTS: The study included 233 registered nurses from South Korea who had provided direct care to patients in a hospital for at least 6 months. Overall, 28% self-identified as victims or witnesses and 37% as victims and witnesses simultaneously. 'Victim' and 'passive coping' were significantly associated with the 25th, 50th and 75th percentiles groups of post-traumatic stress symptoms, while 'witness' was significant in the 95th percentile group. CONCLUSION: Our study findings explore nurses' workplace bullying, detect high-risk subgroups and suggest the development of coping interventions for reducing workplace bullying and post-traumatic stress symptoms. IMPLICATIONS FOR NURSING MANAGEMENT: The study identified associations among bullying experience types, severity of post-traumatic stress symptoms and passive coping. It is critical to explore traumatic experience types and severity of post-traumatic stress symptoms for nurses at risk of workplace bullying.

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). METHODS: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. RESULTS: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. CONCLUSION: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Transition programs for adolescents and young adults with spina bifida: A mixed-methods systematic review.

AIMS: To identify the components of transition programs for the successful transition of adolescents and young adults with spina bifida and to synthesize the literature findings on the transition outcomes of the programs. DESIGN: Mixed-methods systematic review. DATA SOURCES: PubMed, CINAHL, PsycINFO, and Web of Science (January 2010-June 2019). REVIEW METHODS: The methodological quality was appraised using the Mixed Methods Appraisal Tool and Cochrane Risk of Bias Tool. Extracted data were summarized as tables. For data synthesis, a sequential explanatory design was used. RESULTS: Eight studies were selected. The main components of the transition programs identified the participants' characteristics and intervention strategies. Quantitative studies reported only positive transition outcomes, including independence and satisfaction with social support and transition experience, whereas negative outcomes such as negative experiences communicating with providers and uncertainty were further reported in qualitative studies. CONCLUSION: For development and implementation of a successful transition program, it is necessary to assess the characteristics and needs of the participants and incorporate their needs with input from parents and trained healthcare providers. IMPACT: When planning transition programs, a comprehensive effort that encompasses program development, implementation, and evaluation, based on developmental tasks and long-term perspectives, is needed. Transition program that reflect the cultural characteristics of Eastern and developing countries are needed.

Discrepancies in Educational Needs for Transition in Adolescents and Young Adults with Spina Bifida in South Korea: Use of the Borich Needs Assessment Model.

PURPOSE: Transition is an important goal for ensuring that adolescents and young adults (AYAs) with spina bifida (SB) lead autonomous lives. This study aimed to identify the educational needs of AYAs with SB based on the discrepancies between perceived importance and proficiency levels during the transition process. DESIGN AND METHODS: A cross-sectional study was conducted through face-to-face and online surveys from Jan-Dec 2020 of AYAs aged 13-25 years who had previously been diagnosed with SB. The survey consisted of 37 transition-related questions, of which 11 pertained to healthcare environments and 26 pertained to transition education needs SPSS and Excel were used for statistical analysis. Transition educational needs were analyzed by the Borich Needs Assessment Model. Higher the mean weighted discrepancy scores, lower the proficiency as compared to the perceived importance, indicating that the educational needs were high. RESULTS: Overall, 108 responses were analyzed, and 56 (51.9%) AYAs were diagnosed with lipomyelomeningocele. The highest ranked educational needs were for "Health insurance system", "SB related urinary system diseases management", "SB related nervous system symptoms", and "Self-catheterization management". "The demands for 'SB related work life", "Urinary incontinence management", and "Constipation management" were significantly higher in young adults than adolescents. CONCLUSIONS: During the transition process, activities perceived as important by AYAs with SB may differ from the activities that they can actually perform proficiently. It is important to assess their needs based on these discrepancies. PRACTICE IMPLICATIONS: Transition education programs are needed that consider the individual educational needs and developmental stage-specific characteristics of AYAs with SB.

The matricellular protein CCN5 prevents adverse atrial structural and electrical remodelling.

Atrial structural remodelling including atrial hypertrophy and fibrosis is a key mediator of atrial fibrillation (AF). We previously demonstrated that the matricellular protein CCN5 elicits anti-fibrotic and anti-hypertrophic effects in left ventricles under pressure overload. We here determined the utility of CCN5 in ameliorating adverse atrial remodelling and arrhythmias in a murine model of angiotensin II (AngII) infusion. Advanced atrial structural remodelling was induced by AngII infusion in control mice and mice overexpressing CCN5 either through transgenesis (CCN5 Tg) or AAV9-mediated gene transfer (AAV9-CCN5). The mRNA levels of pro-fibrotic and pro-inflammatory genes were markedly up-regulated by AngII infusion, which was significantly normalized by CCN5 overexpression. In vitro studies in isolated atrial fibroblasts demonstrated a marked reduction in AngII-induced fibroblast trans-differentiation in CCN5-treated atria. Moreover, while AngII increased the expression of phosphorylated CaMKII and ryanodine receptor 2 levels in HL-1 cells, these molecular features of AF were prevented by CCN5. Electrophysiological studies in ex vivo perfused hearts revealed a blunted susceptibility of the AAV9-CCN5-treated hearts to rapid atrial pacing-induced arrhythmias and concomitant reversal in AngII-induced atrial action potential prolongation. These data demonstrate the utility of a gene transfer approach targeting CCN5 for reversal of adverse atrial structural and electrophysiological remodelling.