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Objectives: Lack of physical activity has a critical effect on the physical and mental health of adolescents. This study examined the influence of family adversities on the longitudinal changes in physical inactivity among adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: The study used multi-wave data from the Korean Children and Youth Panel Survey, including 2590 Korean adolescents aged 12-14 years. The longitudinal trajectory of physical inactivity among adolescents and the effects of related factors were estimated using a latent growth modeling method. Results: Our results revealed a significant increase in physical inactivity among adolescents over time. At the onset of the pandemic, approximately one-seventh of Korean middle schoolers reported a lack of physical activity. However, 3 years later, during the quarantine, nearly one-fifth of these adolescents reported a significant increase in their physical inactivity. Initially, low level parental education was predictive of adolescents’ physical inactivity, but this effect diminished over time, becoming statistically insignificant by the end of the 3-year period. Moreover, the increase in physical inactivity over the 3 years was significantly influenced by parental rejection. Conclusions: These findings suggest that adolescents who experience parental rejection are more likely to report an increase in sedentary behaviors in contexts such as the COVID-19 pandemic.

Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. Methods: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Results: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. Conclusion: The diagnostic yield of WES was 48.8 %. We conclude that patients’ characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.

Abstract Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra −/− ) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Purpose The rapid expansion of robotic surgical equipment necessitates a review of the needs and challenges faced by hospitals introducing robots for the first time to compete with experienced institutions. The aim of this study was to analyze the impact of robotic surgery on our hospital compared to open and laparoscopic surgery, examine internal transformations, and assess regional, domestic, and international implications. Methods A retrospective review was conducted of electronic medical records (EMRs) from 2019 to 2022 at Inha University Hospital, including patients who underwent common robotic procedures and equivalent open and laparoscopic operations. The study investigated clinical and operational performance changes in the hospital after the introduction of robotic technology. It also evaluated the operational effectiveness of robot implementation in local, national, and international contexts. To facilitate comparison with other hospitals, the data were transmitted to Intuitive Surgical, Inc. for analysis. The study was conducted in compliance with domestic personal information regulations and received approval from our Institutional Review Board. Results We analyzed EMR data from 3,147 patients who underwent surgical treatment. Over a period of 3.5 years, the adoption of robotic technology in a hospital setting significantly enhanced the technical skills of all professors involved. The introduction of robotic systems led to increased patient utilization of conventional surgical techniques, as well as a rise in the number of patients choosing robotic surgery. This collective trend contributed to an overall increase in patient numbers. This favorable evaluation of the operational effectiveness of our hospital’s robot implementation in the context of local, national, and global factors is expected to positively influence policy changes. Conclusions Stakeholders should embrace data science and evidence-based techniques to generate valuable insights from objective data, assess the health of robot-assisted surgery programs, and identify opportunities for improvement and excellence.

Abstract Distant metastasis is a significant hallmark affecting to the high death rate of patients with triple-negative breast cancer (TNBC). Thus, it is crucial to identify and develop new therapeutic strategies to hinder cancer metastasis. While emerging studies have hinted a pivotal role of glucose-regulated protein 94 (GRP94) in tumorigenesis, the exact biological functions and molecular mechanisms of GRP94 in modulating cancer metastasis remain to be elucidated. Our study demonstrated an increased expression of GRP94 in TNBC correlated with metastatic progression and unfavorable prognosis in patients. Functionally, we identified that GRP94 depletion significantly diminished TNBC tumorigenesis and subsequent lung metastasis. In contrast, GRP94 overexpression exacerbated the invasiveness, migration, and lung metastasis of non-TNBC cells. Mechanistically, we found that casein kinase 2 alpha (CK2α) active in advanced breast cancer phosphorylated GRP94 at a conserved serine 306 (S306) residue. This phosphorylation increased the stability of GRP94 and enhanced its interaction with LRP6, leading to activation of canonical Wnt signaling. From a therapeutic standpoint, we found that benzamidine, a novel CK2α inhibitor, effectively suppressed GRP94 phosphorylation, LRP6 stabilization, and metastasis of TNBC. Our results point to the critical role of CK2α-mediated GRP94 phosphorylation in TNBC metastasis through activation of Wnt signaling, highlighting GRP94 as a therapeutic target to impede TNBC metastasis.

Purpose The clinical characteristics of headaches vary by age among pediatric patients. Red flag signs are key factors in differentiating secondary headaches and should be considered in the context of the patient’s age. Methods This study involved a retrospective chart review of pediatric patients presenting with headaches. Patients were categorized by age into three groups: pre-school age (under 6 years), school-age (6 to 12 years), and adolescence (over 12 years). Demographic data, headache characteristics, laboratory findings, and neuroimaging results were evaluated. Overall, 17 potential red flags were assessed. Results A total of 687 patients were included, of whom 102 were of pre-school age, 314 were school-aged, and 271 were adolescents. The frequency of overweight/obesity was found to increase with age. The pre-school age group experienced a shorter period from symptom onset to presentation and a briefer duration of pain. In contrast, adolescents displayed a longer period from symptom onset, a greater frequency of headaches occurring at least three times per week, and a higher rate of headache episodes lasting over 3 days. Children under 6 years old were more commonly diagnosed with secondary headaches than older children. Across age groups, secondary headaches were suspected when systemic symptoms such as fever were present, when the headache had a sudden onset, when the patient responded poorly to medication, or when abnormal neurological signs and symptoms were observed. Conclusion The clinical features of pediatric patients vary by age group. Clinicians should consider red flag signs in the context of patient age and individual characteristics.

Purpose Electroencephalography (EEG) is useful for clarifying the association between cortical activity and cognitive processes in children. We investigated whether EEG abnormalities were correlated with developmental delay/intellectual disability (DD/ID) in the absence of clinical seizures. Methods We retrospectively identified 166 children with DD/ID who underwent EEG at Pusan National University Hospital between January 2011 and December 2021. We compared clinical characteristics and test results between those with normal and those with abnormal EEGs. Additionally, we analyzed EEG abnormalities in relation to neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Results Of the 166 patients, 39 (23.5%) displayed abnormal EEGs, while 127 (76.5%) had normal EEGs. Of the former, 25 (64.1%) patients exhibited epileptiform discharges, including 22 (56.3%) with focal and three (7.7%) with generalized discharges. Focal discharges most frequently affected the central area (35.9%). Twenty patients (51.3%) exhibited rhythmic slowing patterns. Epilepsy diagnoses were significantly more common among patients with abnormal EEGs (n=8, 20.5%) than among those with normal EEGs (n=9, 7.1%) (P

Abstract Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210s and the role of ILC210s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210s are extensively included in PD-L1highSca-1+ ILCs and that IL-27 amplifies the development of PD-L1highSca-1+ ILCs and ILC210s. Adoptive transfer of PD-L1highSca-1+ ILCs suppressed oxazolone-induced CHS in an IL-10-dependent manner Taken together, our results demonstrate that ILC210s are critical for the control of CHS and suggest that ILC210s can be used as target cells for the treatment of CHS.

IntroductionIn 2016, UNAIDS set ambitious targets to reduce global HIV infections by 75% by 2020 and 90% by 2030, based on the 2.1 million new infections reported in 2010. However, by 2022, new HIV infections had only decreased by 38%, from 2.1 million in 2010 to 1.3 million in 2022, raising concerns about reaching the 2030 goal. Female sex workers (FSWs) in sub-Saharan Africa face a disproportionately high risk of HIV acquisition, contributing 5%–20% of all new infections in several countries in the region. This analysis investigates HIV seroconversion and associated factors among FSWs, offering insights into critical interventions for preventing HIV transmission in this population and advancing the goal of ending the HIV pandemic by 2030.MethodsWe conducted a retrospective cohort study involving 17,977 FSWs who initially tested HIV negative upon enrollment in the Sauti project between October 2016 and September 2018. HIV incidence rates were calculated by dividing the number of new HIV cases by observed person-time within the cohort. Cox regression analysis identified factors associated with seroconversion.ResultsThe study revealed an HIV incidence rate of 8.6 per 100 person-years among FSWs [95% confidence interval (CI): 8.1–9.1]. Factors independently associated with HIV seroconversion included age 35 years or older [adjusted hazard ratio (aHR): 2.53; 95% CI: 2.03–3.14], unprotected sex (aHR: 1.27; 95% CI: 1.13–1.42), STI symptoms (aHR: 1.99; 95% CI: 1.67–2.38), and alcohol consumption before sex (aHR: 1.20; 95% CI: 1.07–1.34).ConclusionTargeted interventions are vital in curbing HIV transmission among FSWs, with a focus on expanding access to primary HIV prevention services, particularly for older FSWs who face heightened risk. Tailored sexual health education programs are imperative to encourage consistent condom use and enable informed decision-making. Accessible and timely STI screening and treatment services are crucial to mitigate HIV transmission risk. Collaborative partnerships between healthcare providers, community organizations, and government agencies are essential in implementing these interventions among FSWs.

During testing, an error in software can either propagate to the output variables or be masked before it reaches them. Error propagation and masking characteristics are crucial in software testing because they directly influence testing effectiveness. The testing community has hence focused on developing test mechanisms to promote the propagation and reduce masking of errors in software under test. However, little is known about how severely the errors propagate and are masked during software execution. Moreover, little is known about what influences software’s propagation and masking characteristics. Thus, in this study, we performed experiments to investigate the behavior of errors during software execution. We chose six case examples and created mutants per case example by seeding an error into each one. We then executed the mutants with randomly selected test cases and investigated how many errors were propagated and masked. If an error was masked, we examined the cause. In addition, we investigated what percentage of errors in the mutants reached the output variables. This study provides insight into the characteristics of errors in terms of propagation and masking, which will help testers design test inputs and choose monitoring variables to properly handle the masking of errors during testing.

Abstract Background Respectful maternity care (RMC) remains a key challenge in Afghanistan, despite progress on improving maternal and newborn health during 2001—2021. A qualitative study was conducted in 2018 to provide evidence on the situation of RMC in health facilities in Afghanistan. The results are useful to inform strategies to provide RMC in Afghanistan in spite of the humanitarian crisis due to Taliban’s takeover in 2021. Methods Focus group discussions were conducted with women (4 groups, 43 women) who had used health facilities for giving birth and with providers (4 groups, 21 providers) who worked in these health facilities. Twenty key informant interviews were conducted with health managers and health policy makers. Motivators for, deterrents from using, awareness about and experiences of maternity care in health facilities were explored. Results Women gave birth in facilities for availability of maternity care and skilled providers, while various verbal and physical forms of mistreatment were identified as deterrents from facility use by women, providers and key informants. Low awareness, lack of resources and excessive workload were identified among the reasons for violation of RMC. Conclusion Violation of RMC is unacceptable. Awareness of women and providers about the rights of women to respectful maternity care, training of providers on the subject, monitoring of care to prevent mistreatment, and conditioning any future technical and financial assistance to commitments to RMC is recommended.

ARS-interacting multifunctional proteins 2 (AIMP2) is known to be a powerful tumour suppressor. However, the target AIMP2-DX2, AIMP2-lacking exon 2, is often detected in many cancer patients and cells. The predominant approach for targeting AIMP-DX2 has been attempted via small molecule mediated inhibition, but due to the lack of satisfactory activity against AIMP2-DX2, new therapeutic strategies are needed to develop a novel drug for AIMP2-DX2. Here, we report the use of the PROTAC strategy that combines small-molecule AIMP2-DX2 inhibitors with selective E3-ligase ligands with optimised linkers. Consequently, candidate compound 45 was found to be a degrader of AIMP2-DX2. Together, these findings demonstrate that our PROTAC technology targeting AIMP2-DX2 would be a potential new strategy for future lung cancer treatment.

The incidence of colitis‐associated colorectal cancer (CAC) has increased due to a high‐nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin‐protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING‐type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3‐deficient mice in an azoxymethane/dextran sulphate sodium‐induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll‐like receptor 4 (TLR4)‐mediated inflammation through ubiquitination‐dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation‐mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.

Purpose The aim of this study was to evaluate the efficacy and safety of adjunctive lacosamide therapy in pediatric patients aged ≥4 years with drug-resistant epilepsy (DRE). Methods Medical records of children aged 4 to 19 years treated with lacosamide as adjunctive therapy for DRE were retrospectively reviewed. The patients were divided into two groups according to their age at the start of lacosamide treatment: group A (aged 4–15 years) and group B (aged 16–19 years). Changes in seizure frequency from baseline, adverse events, and the retention rate were evaluated at each follow-up visit. Results Sixty-two patients (33 males and 29 females) with a mean age of 11.4 years (range, 4 to 19) were included. The mean duration of follow-up was 20.1±12.9 months. The mean maintenance dose of lacosamide was 6.7±4.8 mg/kg/day. Forty-two patients (67.7%) were responders (≥50% reduction in seizures) with 19.4% (12/62) achieving freedom from seizures. The response rate did not differ significantly between groups A and B (67.6% vs. 68.0%, P=0.795) and was not affected by the concomitant use of sodium channel blockers. Significant independent factors associated with a good response to lacosamide treatment were a shorter duration of epilepsy (P=0.035) and fewer concomitant anti-seizure medications (P=0.002). Mild transient adverse events were observed in 20 patients (32.3%). Conclusion Lacosamide adjunctive therapy was efficacious and tolerated in children aged ≥4 years with DRE. Early use of lacosamide may be helpful for a good response to drug-resistant seizures.

Background The World Health Organization recommends the implementation of maternity waiting homes (MWH) to reduce delays in access to obstetric care, particularly for high-risk pregnancies and mothers living far from health facilities, and as a result, several countries have rolled out MWHs. However, Rwanda has not implemented this recommendation on a large scale. There is only one MWH in the country, hence a gap in knowledge regarding the potential utilisation and benefits of MWHs. Objective To explore providers’ and clients’ perspectives on facilitators and barriers to the use of MWH in rural Rwanda. Methods We conducted a qualitative study to explore health providers’ and clients’ perspectives on facilitators and barriers to the use of MWH in Rwanda, between December 2020 and January 2021. We used key informant interviews and focus group discussions to collect data. Data were analysed using NVivo qualitative analysis software version 11. Results Facilitators included perceptions that the MWH offered either a peaceful and home-like environment, good-quality services, or timely obstetric services, and was associated with good maternal and neonatal outcomes. Barriers included limited awareness of the MWH among pregnant women, fear of health providers to operate the MWH at full capacity, women’s lack of autonomy, uncertainty over funding for the MWH, and perceived high user fees. Conclusion The Ruli MWH offers a peaceful environment for pregnant women while providing quality and timely obstetric care, resulting in positive maternal and neonatal outcomes for women. However, its existence and benefits are not widely known, and its use is limited due to inadequate resources. There is a need for increased awareness of the MWH among healthcare providers and the community, and lessons from this MWH could inform the scale up of MWHs in Rwanda.

Purpose The purpose of our study was to evaluate the usefulness of the BiofireFilmArray Meningitis/Encephalitis (FA ME) panel and identify factors associated with positive FA ME panel results. Methods We retrospectively analyzed the medical records of 129 patients (45 children, 84 adults) with central nervous system infections and FA ME panel test results. We compared the results of the FA ME panel and the diagnostic yield between pediatric and adult patients with positive and negative FA ME panel results. Positive FA ME panel results were compared with conventional microbiological testing. Results Forty-three patients (33.3%) had positive results on the FA ME panel. The detected pathogens were enterovirus (n=17, 39.5%), varicella zoster virus (n=10, 23.3%), herpes simplex virus-2 (n=2, 16.3%), herpes simplex virus-1 (n=2, 4.7%), human parechoviruses (n=2), Cryptococcus neoformans/gattii (n=2), Streptococcus agalactiae (n=1, 2.3%), Streptococcus pneumoniae (n=1), and Haemophilus influenzae (n=1). The time to detection of the FA ME panel (4.9±6.6 hours) was significantly shorter than that of conventional culture (77.4±48.2 hours) (P=0.005). Fever was more common in the positive FA ME group than in the negative FA ME group (81.4% vs. 41.9%) and in pediatric patients than in the adult patients (93.3% vs. 34.5%) (P

Purpose The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). Methods The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. Results PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. Conclusions Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

Background The primary aim of this study was to investigate the final adult height (FAH) of girls diagnosed with central precocious puberty (CPP) who were untreated. Methods We retrospectively analyzed the medical records of 36 girls diagnosed with CPP between 8 and 9 years of age who did not receive treatment, and 206 girls diagnosed with CPP within the same age range who received gonadotropin-releasing hormone (GnRH) agonist treatment. Midparental height (MPH), predicted adult height (PAH) obtained using height and bone age (BA) at the time of diagnosis (PAH for BA), and PAH obtained using the Bayley-Pinneau method (PAH by BP) were calculated. Additionally, height at the time of growth completion was compared with the predicted height. Results The FAHs were 160.71±4.56 cm in the untreated group and 159.31±4.26 cm in the treated group. In the untreated group, the FAH was 0.99±4.50 cm shorter than the MPH but 4.29±3.33 cm and 3.46±3.93 cm greater than the PAH for BA and PAH by BP, respectively. Conclusion In children diagnosed with CPP between 8 and 9 years of age who were untreated, FAH was greater than PAH for BA and PAH by BP at the time of diagnosis, indicating that the prognosis of FAH was not poor. Therefore, for girls diagnosed with CPP, it is recommended to consider various conditions, such as pubertal onset, height at diagnosis, BA, peak luteinizing hormone level, predicted height, and speed of puberty, when deciding whether to administer GnRH agonists.

Background Congenital hypothyroidism (CH) is the leading cause of preventable physical and intellectual disabilities. This study aimed to assess the incidence and clinical characteristics of CH in newborns. Methods We retrospectively reviewed the medical records of all newborns delivered at the Pusan National University Hospital between January 2011 and March 2021. The incidence of CH was compared according to gestational age, birth weight, and small for gestational age (SGA). The patients aged ≥3 years who could not maintain normal thyroid function and required levothyroxine treatment were diagnosed with permanent CH. Logistic regression analysis was performed to compare CH risks. Results Of 3,722 newborns, 40 were diagnosed with CH (1.07%). Gestational age and birth weight were significantly associated with CH incidence. The odds ratios (ORs) of CH in infants delivered at 32–37, 28–31, and

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE), derived from an edible marine alga known for its anti-inflammatory and antioxidant properties, in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity, as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE alleviated dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathways known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

IntroductionFever without a focus is a common reason for medical evaluations, hospitalizations, and the antimicrobial treatment of infants younger than 90 days. The presence of cerebrospinal fluid (CSF) pleocytosis could be challenge for clinicians who treat febrile young infants with urinary tract infection (UTI). We evaluated the factors associated with sterile CSF pleocytosis and the clinical outcomes of the patients.MethodsA retrospective review of patients aged 29–90 days with febrile UTIs who underwent a non-traumatic lumbar puncture (LP) at Pusan National University Hospital from January 2010 to December 2020 was conducted. CSF pleocytosis was defined as white blood cell (WBC) counts ≥9/mm3.ResultsA total of 156 patients with UTI were eligible for this study. Four (2.6%) had concomitant bacteremia. However, no patients had culture-proven bacterial meningitis. In correlation analysis, although weak strength, CSF WBC counts were positively correlated with C-reactive protein (CRP) level (Spearman r = 0.234; P = 0.003). Thirty-three patients had CSF pleocytosis [21.2%; 95% confidential interval (CI), 15.5–28.2]. The time from fever onset to the hospital visit, peripheral blood platelet counts, and CRP level at admission were statistically significant in patients with sterile CSF pleocytosis compared to those without CSF pleocytosis. In the multiple logistic regression, only CRP was independently associated with sterile CSF pleocytosis (cutoff, 3.425 mg/dl; adjusted odds ratio, 2.77; 95% CI, 1.19–6.88). The proportion of fever defervescence by hospital day 2 was 87.9% in patients with CSF pleocytosis and 89.4% in those without CSF pleocytosis (P = 0.759). There was no statistical difference in the fever defervescence curves between the two patient groups (P = 0.567). No patients had neurological manifestations or complications.ConclusionsCoexisting sterile CSF pleocytosis among febrile infants with UTIs suggest a systemic inflammatory response. However, the clinical outcomes between the two groups were similar. A selective LP should be considered in young infants with evidence of UTI, and inappropriate antibiotic therapy for sterile CSF pleocytosis should be avoided.

The signaling pathways and networks regulating expression of chondroitin sulfate proteoglycan 4 (CSPG4), a cancer-related protein that serves as a receptor for Clostridiodes difficile TcdB, are poorly defined. In this study, TcdB-resistant/CSPG4-negative HeLa cells were generated by exposure to increasing concentrations of the toxin. The cells that emerged (HeLa R5) lost expression of CSPG4 mRNA and were resistant to binding by TcdB. mRNA expression profiles paired with integrated pathway analysis correlated changes in the Hippo and estrogen signaling pathways with a CSPG4 decrease in HeLa R5 cells. Both signaling pathways altered CSPG4 expression when modulated chemically or through CRISPR-mediated deletion of key transcriptional regulators in the Hippo pathway. Based on the in vitro findings, we predicted and experimentally confirmed that a Hippo pathway inactivating drug (XMU-MP-1) provides protection from C. difficile disease in a mouse model. These results provide insights into key regulators of CSPG4 expression and identify a therapeutic for C. difficile disease.

Purpose Epilepsy is one of the most common neurological disorders in both adults and children. After detailed history-taking, electroencephalography (EEG) is the most important investigation in the evaluation of epilepsy patients. Polyspikes, defined as a sequence of two or more spikes, are among the findings that can be seen on EEGs of epilepsy patients, but the literature on their significance in focal epilepsy patients is scarce. Therefore, in the current study, we investigated the significance of polyspikes on EEG in childhood focal epilepsy. Methods A retrospective analysis was conducted of data from children who were diagnosed with focal epilepsy and received anti-seizure medications at Pusan National University Children’s Hospital. Results Among the 1,125 children included in this study, 468 (41.6%) showed interictal polyspikes on their EEGs. In the multivariate analysis, only the presence of brain magnetic resonance imaging (MRI) abnormalities was significantly associated with the presence of interictal polyspikes on EEGs. Among patients with brain MRI abnormalities, localized polyspikes were significantly associated with focal cortical dysplasia, while multifocal polyspikes were significantly associated with perinatal insults (hypoxic-ischemic encephalopathy and destructive encephalomalacia). Conclusion Focal epilepsy patients with interictal polyspikes were more likely to have a structural etiology. Furthermore, patients with localized polyspikes were more likely to have focal cortical dysplasia as the structural etiology, while patients with multifocal polyspikes were more likely to have perinatal insults as the structural etiology. This study demonstrates that focal polyspikes can be used as markers of the possible presence of a structural etiology in routine practice.

Abstract Background Partial trisomy of the long arm of chromosome 11 is a rare cytogenetic abnormality. It has been characterized by variable sized duplications that lead to a range of phenotypes including growth retardation, developmental delay/intellectual disability, and distinctive craniofacial abnormalities. Congenital heart defects, skeletal abnormalities, urogenital anomalies, and hypotonia are found in some affected individuals. Methods We describe a 16-year-old patient presented with most of the hallmark phenotypes of trisomy 11q syndrome as well as exhibiting symptoms of hearing loss, seizures, and abnormal endocrinological and ophthalmological findings. Routine chromosome analysis and subsequent chromosomal microarray analysis (CMA) were performed to detect genetic abnormalities in this patient. Results We identified an abnormal male karyotype with a derivative chromosome 4 due to an unbalanced translocation between chromosomes 4 and chromosome 11. The CMA results revealed a 56 Mb duplication of chromosome 11q14.1-qter and a 874 Kb terminal deletion of the short arm of chromosome 4. Conclusion A genomic imbalance resulting in partial trisomy 11q was found in a patient with multiple congenital anomalies. We compared the phenotypes of all known “pure” trisomy 11q cases in the literature and find that trisomy 11q23-qter is both recurrent and the most common cytogenetic abnormality found in the reported cases. It is associated with the core features of trisomy 11q syndrome. Graphical abstract

Abstract Background Midwives are the key skilled birth attendants in Afghanistan. Rapid assessment of public and private midwifery education schools was conducted in 2017 to examine compliance with national educational standards. The aim was to assess midwifery education to inform Afghanistan Nurses and Midwives Council and other stakeholders on priorities for improving quality of midwifery education. Methods A cross-sectional assessment of midwifery schools was conducted from September 12–December 17, 2017. The Midwifery Education Rapid Assessment Tool was used to assess 29 midwifery programs related to infrastructure, management, teachers, preceptors, clinical practice sites, curriculum and students. A purposive sample of six Institute of Health Sciences schools, seven Community Midwifery Education schools and 16 private midwifery schools was used. Participants were midwifery school staff, students and clinical preceptors. Results Libraries were available in 28/29 (97%) schools, active skills labs in 20/29 (69%), childbirth simulators in 17/29 (59%) and newborn resuscitation models in 28/29 (97%). School managers were midwives in 21/29 (72%) schools. Median numbers of students per teacher and students per preceptor were 8 (range 2–50) and 6 (range 2–20). There were insufficient numbers of teachers practicing midwifery (132/163; 81%), trained in teaching skills (113/163; 69%) and trained in emergency obstetric and newborn care (88/163; 54%). There was an average of 13 students at clinical sites in each shift. Students managed an average of 15 births independently during their training, while 40 births are required. Twenty-four percent (7/29) of schools used the national 2015 curriculum alone or combined with an older one. Ninety-one percent (633/697) of students reported access to clinical sites and skills labs. Students mentioned, however, insufficient clinical practice due to low case-loads in clinical sites, lack of education materials, transport facilities and disrespect from school teachers, preceptors and clinical site providers as challenges. Conclusions Positive findings included availability of required infrastructure, amenities, approved curricula in 7 of the 29 midwifery schools, appropriate clinical sites and students’ commitment to work as midwives upon graduation. Gaps identified were use of different often outdated curricula, inadequate clinical practice, underqualified teachers and preceptors and failure to graduate all students with sufficient skills such as independently having supported 40 births.

Introduction Tanzania had an estimated 5.400 maternal deaths in 2020. Suboptimal quality of antenatal care (ANC) presents a major challenge. It is not known what precisely the uptake of the various ANC components is, such as counseling on birth preparedness and complication readiness, preventive measures and screening tests. We assessed the level of receiving the various ANC components and associated factors in order to identify opportunities to improve ANC. Methods A cross-sectional household survey using a structured questionnaire through face-to-face interviews, was conducted in April 2016 in Mara and Kagera regions, Tanzania, applying a two-stage, stratified-cluster sampling design. The analysis included 1,162 women aged 15–49 years who attended ANC during their last pregnancy and had given birth not longer than two years prior to the survey. To account for inter- and intra-cluster variations, we used mixed-effect logistic regression to examine factors associated with receiving essential ANC components: counseling around birth preparedness and complication readiness (with presumed effects on knowledge about danger signs) and preventive measures. Results About In 878 (76.1%) women preparedness for birth and its complications was observed to exist. Overall counseling was low where 902 (77.6%) women received adequate counseling. Overall knowledge of danger signs was low in 467 women (40.2%). Uptake of preventive measures was low, with presumptive malaria treatment in 828 (71.3%) and treatment of intestinal worms in 519 (44.7%) women. Screening test levels varied for HIV in 1,057 (91.2%), any blood pressure measurement in 803 (70.4%), syphilis in 367 (32.2%) and tuberculosis in 186 (16.3%) women. After adjusting for age, wealth and parity, the likelihood of receiving adequate counseling on essential topics was less in women without education versus primary education (aOR 0.64; 95% CI 0.42–0.96) and in women who had Conclusion Overall uptake of various essential ANC components was low. Frequent ANC visits and ensuring privacy are all essential to improve the uptake of ANC.

Idiopathic intracranial hypertension (IIH) is a syndrome defined by elevated intracranial pressure without any abnormal findings. In the present study, we report a rare case of IIH in a patient after ventriculoperitoneal shunt (VPS) due to infant hydrocephalus. A 13-year-old girl with a history of VPS due to infant hydrocephalus was admitted to emergency room with the complaint of severe headache and visual disturbance. Brain computed tomography showed normal findings. However, based on the measurement by lumbar puncture, her cerebrospinal fluid (CSF) pressure was observed to be very high. The shunt function test revealed a VPS malfunction. Thus, we conducted VPS revision in this patient. All symptoms improved immediately after the revision. Thus, it is proposed that IIH should be considered for patients with visual disturbance and severe headache after VPS due to infant hydrocephalus without ventriculomegaly.

Purpose: Most breast cancers are hormone-receptor-positive, and thus the first-line therapy for them is an anti-estrogen medication such as tamoxifen. If metastasis occurs or resistance to tamoxifen develops, the 5-year survival rates for breast cancer patients significantly decrease. Hence, a better understanding of the molecular mechanisms that contribute to breast cancer aggressiveness is of great importance. ERα36 is an estrogen receptor variant that is known to be upregulated in breast cancer patients receiving tamoxifen treatment or in triple-negative breast cancer cells. However, the specific molecular mechanism underlying ERα36-induced tamoxifen-resistance is not yet fully understood.Methods: ERα36-overexpressing MCF-7 cells were constructed by either plasmid transfection using ERα36 vector or retroviral infection using ERα36-V5-His vector. Target-gene expression was assessed by Western blot analysis and real-time PCR, and YAP activation was evaluated by luciferase assays and immunofluorescence. Cell proliferation and formation of three-dimensional spheroids were evaluated using the IncuCyte S3 Live Cell Analysis System.Results: We found that the expression patterns of Hippo signaling-related genes were significantly changed in ERα36-overexpressing MCF-7 cells compared to MCF-7 cells, which were also similarly observed in tamoxifen-resistant MCF-7 cells. Specifically, the protein expression level and activity of YAP, the core downstream protein of the Hippo pathway, were significantly increased in ERα36-overexpressing MCF-7 cells compared with MCF-7 cells. The aggressive phenotypes acquired by ERα36 overexpression in MCF-7 cells were destroyed by YAP knockout. On this basis, we propose that ERα36 regulates YAP activity by a new mechanism involving Src kinase.Conclusion: Our results suggest that YAP targeting may be a new therapeutic approach to the treatment of advanced breast cancers overexpressing ERα36.

Using mouse models of liver fibrosis, Kim et al examined the mechanisms underlying the antifibrotic inhibition of the NLRP3 inflammasome by auranofin. They demonstrated that auranofin-induced inhibition of the NLRP3 inflammasome in bone marrow-derived macrophages and kupffer cells was mediated via inhibition of the cystine-glutamate antiporter, system Xc, which advances our understanding of the mechanism by which auranofin exerts its therapeutic effects.

Abstract DNAJB9, a member of the heat shock protein 40 family, acts as a multifunctional player involved in the maintenance of their client proteins and cellular homeostasis. However, the mechanistic action of DNAJB9 in human malignancies is yet to be fully understood. In this study, we found that ectopic restoration of DNAJB9 inhibits the migration, invasion, in vivo metastasis, and lung colonization of triple-negative breast cancer (TNBC) cells. Mechanistically, DNAJB9 stabilizes FBXO45 protein by suppressing self-ubiquitination and reduces the abundance of ZEB1 by Lys48-linked polyubiquitination to inhibit the epithelial–mesenchymal transition (EMT) and metastasis. Clinically, the reduction of DNAJB9 expression, concomitant with decreased FBXO45 abundance in breast cancer tissues, correlates with poorer clinical outcomes of patients with breast cancer. Taken together, our results provide a novel insight into the metastasis of TNBC and define a promising therapeutic strategy for cancers with overactive ZEB1 by regulating the DNAJB9–FBXO45 signaling axis.

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.

Purpose Trauma is the leading cause of death and disability in children. We aimed to compare the clinical characteristics of children with trauma and disease. Methods We reviewed the medical records of children (< 19 years) who visited the emergency department of Pusan National University Hospital from 2016 through 2018. Data on the age, age group, sex, details of trauma or disease, severe trauma or disease (Korean Triage Acuity Scale 1-2), hospitalization rate (overall and intensive care unit [ICU]), hospital length of stay, in-hospital mortality, and the Injury Severity Score were compared between the children with trauma and those with disease. Results In a total of 10,205 children, 3,028 (29.7%) had trauma. The children with trauma were older than those with disease (median age, 78.5 months [interquartile range, 35.0-165.0] vs. 49.0 [16.0-120.0]; P < 0.001). Boys were more common in the former group than the latter (63.7% vs. 56.3%; P < 0.001). The most common injury mechanism was traffic accident (16.0%), followed by fall and foreign body. The overall hospitalization rate was higher in the children with disease (17.1% vs. 35.9%; P < 0.001). However, the children with trauma underwent more frequent ICU hospitalization, and showed higher in-hospital mortality rate and longer hospital length of stay than those with disease (all P < 0.001). The children with severe trauma showed higher median age, percentage of boys, in-hospital mortality, and ICU hospitalization rate, and longer hospital length of stay than those with severe disease (all P < 0.001). Conclusion Children with trauma tend to be older, and their condition may be more critical in severity than those with disease. This difference is more prominent in those with severe trauma or disease.

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of non-autoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial non-autoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Abstract Background Helping Babies Breathe (HBB) is a competency-based educational method for an evidence-based protocol to manage birth asphyxia in low resource settings. HBB has been shown to improve health worker skills and neonatal outcomes, but studies have documented problems with skills retention and little evidence of effectiveness at large scale in routine practice. This study examined the effect of complementing provider training with clinical mentorship and quality improvement as outlined in the second edition HBB materials. This “system-oriented” approach was implemented in all public health facilities (n = 172) in ten districts in Rwanda from 2015 to 2018. Methods A before-after mixed methods study assessed changes in provider skills and neonatal outcomes related to birth asphyxia. Mentee knowledge and skills were assessed with HBB objective structured clinical exam (OSCE) B pre and post training and during mentorship visits up to 1 year afterward. The study team extracted health outcome data across the entirety of intervention districts and conducted interviews to gather perspectives of providers and managers on the approach. Results Nearly 40 % (n = 772) of health workers in maternity units directly received mentorship. Of the mentees who received two or more visits (n = 456), 60 % demonstrated competence (received > 80% score on OSCE B) on the first mentorship visit, and 100% by the sixth. In a subset of 220 health workers followed for an average of 5 months after demonstrating competence, 98% maintained or improved their score. Three of the tracked neonatal health outcomes improved across the ten districts and the fourth just missed statistical significance: neonatal admissions due to asphyxia (37% reduction); fresh stillbirths (27% reduction); neonatal deaths due to asphyxia (13% reduction); and death within 30 min of birth (19% reduction, p = 0.06). Health workers expressed satisfaction with the clinical mentorship approach, noting improvements in confidence, patient flow within the maternity, and data use for decision-making. Conclusions Framing management of birth asphyxia within a larger quality improvement approach appears to contribute to success at scale. Clinical mentorship emerged as a critical element. The specific effect of individual components of the approach on provider skills and health outcomes requires further investigation.

Abstract Background Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared with recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group but is very rare and typically associated with poor prognosis. Methods Conventional cytogenetic studies were performed among 1,824 AML patients recorded in our oncology database over the last 20 years. Fluorescence in situ hybridization (FISH) was carried out to detect the translocation fusion. Array comparative genome hybridization (aCGH) was carried out to further characterize the duplication of chromosomes. Results We identified three AML patients with t(8;16)(p11.2;p13.3) by chromosome analysis. Two of the three patients, who harbored an additional 1q duplication, were detected by FISH and aCGH. aCGH characterized a 46.7 Mb and 49.9 Mb gain in chromosome 1 at band q32.1q44 separately in these two patients. One patient achieved complete remission (CR) but relapsed 3 months later. The other patient never experienced CR and died 2 years after diagnosis. Conclusion A 1q duplication was detected in two of three AML patients with t(8;16)(p11.2;p13.3), suggesting that 1q duplication can be a recurrent event in AML patients with t(8;16). In concert with the findings of previous studies on similar patients, our work suggests that 1q duplication may also be an unfavorable prognostic factor of the disease.

Purpose Multiple independent spike foci (MISF) have been reported to be associated with hypsarrhythmia and slow spikes and waves. However, some patients with MISF demonstrate a good prognosis, such as benign focal epilepsy. This study aimed to elucidate the prognosis of epileptic children with MISF and to analyze the prognostic factors. Methods The subjects were 115 epileptic children aged 1 to 18 years who visited Pusan National University Children’s Hospital between November 2008 and July 2016 and in whom MISF were noted on electroencephalography. We excluded patients with infantile spasms, congenital metabolic diseases, neurodegenerative diseases, or post-encephalitic epilepsy. We retrospectively reviewed participants’ clinical information. Seizure control was defined as no seizures over 6 months at the last visit. Prognostic factors were analyzed in the seizure control (group A; 84 [73%]) and no seizure control (group B; 31 [27%]) groups. Results Generalized seizure (P=0.033), intellectual disability (P

Purpose To investigate the effect of lifestyle changes on patterns of carbon monoxide (CO) exposure and the association between neurologic symptoms and outcomes in Korean children with CO intoxication. Methods We reviewed the medical records of patients (< 18 years) with CO intoxication who visited the emergency department of Pusan National University Hospital between February 2012 and January 2020. We collected clinical findings, including age and sex, transfer from other hospitals, source, time and duration of exposure, manifestations with neurologic symptoms (syncope, seizure, and altered mental status), intensive care unit hospitalization, hospital length of stay, implementation of hyperbaric oxygen therapy, and findings of neuroimaging. These variables were compared between children with and without neurologic symptoms. In addition, levels of carboxyhemoglobin and lactate were compared between patients with and without specific manifestations. Results The enrolled 47 patients’ median age was 10 years (interquartile range, 4.5-14.0). The most common source of exposure was fire (46.8%), followed by camping (23.4%). The most common times of exposure were night (44.7%) and winter (44.7%). The patients with neurologic symptoms (14 [29.8%]) showed longer duration of exposure and hospital length of stay (P < 0.001 and P = 0.007, respectively). Of the 14 patients, 2 were hospitalized to the intensive care unit without an in-hospital mortality. A significant association was found between dyspnea and lactate level (P = 0.049), also between syncope or presyncope and carboxy hemoglobin level (P = 0.017). Conclusion CO intoxication in Korean children is most often caused by fire and camping, and at night and in winter. There is a correlation between neurologic symptoms and duration of exposure to CO.

Abstract Background Hemorrhage is the leading cause of maternal mortality worldwide and accounts for 56% of maternal deaths in Afghanistan. Postpartum hemorrhage (PPH) is commonly caused by uterine atony, genital tract trauma, retained placenta, and coagulation disorders. The purpose of this study is to examine the quality of prevention, detection and management of PPH in both public and private hospitals in Afghanistan in 2016, and compare the quality of care in district hospitals with care in provincial, regional, and specialty hospitals. Methods This study uses a subset of data from the 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment. It covers a census of all accessible public hospitals, including 40 district hospitals, 27 provincial hospitals, five regional hospitals, and five specialty hospitals, as well as 10 purposively selected private hospitals. Results All public and private hospitals reported 24 h/7 days a week service provision. Oxytocin was available in 90.0% of district hospitals, 89.2% of provincial, regional and specialty hospitals and all 10 private hospitals; misoprostol was available in 52.5% of district hospitals, 56.8% of provincial, regional and specialty hospitals and in all 10 private hospitals. For prevention of PPH, 73.3% women in district hospitals, 71.2% women at provincial, regional and specialty hospitals and 72.7% women at private hospital received uterotonics. Placenta and membranes were checked for completeness in almost half of women in all hospitals. Manual removal of placenta was performed in 97.8% women with retained placenta. Monitoring blood loss during the immediate postpartum period was performed in 48.4% of women in district hospitals, 36.9% of women in provincial, regional and specialty hospitals, and 43.3% in private hospitals. The most commonly observed cause of PPH was retained placenta followed by genital tract trauma and uterine atony. Conclusion Gaps in performance of skilled birth attendants are substantial across public and private hospitals. Improving and retaining skills of health workers through on-site, continuous capacity development approaches and encouraging a culture of audit, learning and quality improvement may address clinical gaps and improve quality of PPH prevention, detection and management.

Patients with neurological disorders are at high risk of developing osteoporosis, as they possess multiple risk factors leading to low bone mineral density. Such factors include inactivity, decreased exposure to sunlight, poor nutrition, and the use of medication or treatment that can cause lower bone mineral density such as antiepileptic drugs, ketogenic diet, and glucocorticoids. In this article, mechanisms involved in altered bone health in children with neurological disorders and management for patients with epilepsy, cerebral palsy, and Duchenne muscular dystrophy regarding bone health are reviewed.

Familial hypophosphatemic rickets (FHR) is a disorder characterized by phosphate wasting and hypophosphatemia due to defects in renal phosphate transport regulation. There are 4 known inherited forms of FHR that differ in their molecular causes. Very few studies have been conducted that focused on the molecular analysis of FHR in Koreans. Eighteen mutations of the PHEX gene have been identified to this date in Korea. Herein, we report the clinical case of a 24-month-old boy presenting with bowed legs and short stature. The biochemical profile showed hypophosphatemia with decreased tubular reabsorption of phosphate. Several family members were identified with short stature and genu varum. Therefore, he was diagnosed with FHR. To identify the molecular causes of FHR, we performed targeted gene panel sequencing and found a novel hemizygous missense variant, c.1949T>C (p.Leu650Pro), in the PHEX gene. This variant was also detected in the boy’s mother who exhibited genu varum and short stature.

Software-defined networking (SDN) has generated increased interest due to the rapid growth in the amount of data generated by the development of the Internet and communications, the commercialization of 5G, and increasingly complex networks. While SDN is more advantageous than traditional networks in terms of efficient network management, rapid deployment, and dynamic scalability, the correctness of a network configuration must be ensured in advance. In other words, SDN components such as network devices, SDN controllers, and applications need to be deployed correctly and must be free of rule conflicts, particularly between various application policies; otherwise, it may result in network paralysis in the worst case. This paper assumes that the SDN network is free of rule conflicts when the rules in the SDN switches correctly obey firewall application or policies. To solve this problem, this paper proposes a verification framework for SDN using TLA+. We show that the firewall rule behavior of switches can be formalized using TLA+, and this is verified with the TLC model checker that uses TLA+ as the model description language. We check two different types of topology models through our verification framework to ensure that the same firewall rules are maintained even if the topology changes. The findings show that the firewall rules may be inconsistent as the topology changes.

Purpose Guillain-Barré syndrome (GBS) is a group of clinical syndromes involving acute polyneuropathy secondary to an immune-mediated process. Although affected children generally tend to have a good prognosis, a small subset of children experience residual symptoms that require lengthy and costly rehabilitation. Therefore, we aimed to describe the clinical findings of children with GBS and to investigate factors associated with their outcomes. Methods A retrospective study was conducted of previously healthy children ≤18 years of age diagnosed with GBS and admitted to Pusan National Children’s Hospital between 2009 and 2018. Results Of the 38 patients included in the study (23 boys [60.5%]; median age, 4.3 years [interquartile range, 2.8 to 9.7 years]), 28 (73.7%) fully recovered without any residual symptoms, while 10 (26.3%) had residual symptoms more than 6 months after the onset of GBS. The presence of autonomic dysfunction and a ≥50% decrease in compound muscle action potential (CMAP) amplitude from the lower limit of normal were associated with functional deficits at 6 months. Age, sex, type of antecedent illness, cranial nerve involvement, the need for mechanical ventilation, and the subtype of GBS were not significantly associated with functional outcomes. Post-gadolinium enhancement of nerve roots was seen in 71.1% of patients on initial spine magnetic resonance imaging (MRI). Conclusion Contrast enhancement of nerve roots on MRI was the most helpful initial finding for diagnosing GBS. The presence of autonomic dysfunction and a ≥50% decrease in CMAP from the lower limit of normal were poor prognostic factors for functional outcomes.

Purpose Recognition of cardiogenic syncope caused by acute myocarditis masquerading as febrile seizures (FS) in children can be difficult in the emergency department (ED) before a cardiac work-up. We aimed to identify clinical and laboratory characteristics of children with seizure-like activity and fever caused by myocarditis that would enable their condition to be distinguished from benign FS. Methods We identified seven children who visited the ED for paroxysmal seizure-like activity with fever and were diagnosed with acute myocarditis between 2012 and 2015, as well as 204 children who were diagnosed with benign FS during the same period. A detailed retrospective review of the medical charts of both groups was conducted. Results Age at onset of seizure-like activity was much higher in the myocarditis group than in the FS group (4.4±1.9 years vs. 2.4±1.1 years, P=0.033). Body temperature at seizure-like activity onset was significantly lower in the myocarditis group than in the FS group (37.9°C±0.2°C vs. 38.7°C±0.6°C, P