Heterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cells.

Excessive mitochondrial fission is associated with the pathogenesis of neurodegenerative diseases. Dynamin-related protein 1 (Drp1) possesses specific fission activity in the mitochondria and peroxisomes. Various post-translational modifications of Drp1 are known to modulate complex mitochondrial dynamics. However, the post-transcriptional regulation of Drp1 remains poorly understood. Here, we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) regulates Drp1 expression at the post-transcriptional level. hnRNP A1 directly interacts with Drp1 mRNA at its 3'UTR region, and enhances translation potential without affecting mRNA stability. Down-regulation of hnRNP A1 induces mitochondrial elongation by reducing Drp1 expression. Moreover, depletion of hnRNP A1 suppresses 3-NP-mediated mitochondrial fission and dysfunction. In contrast, over-expression of hnRNP A1 promotes mitochondrial fragmentation by increasing Drp1 expression. Additionally, hnRNP A1 significantly exacerbates 3-NP-induced mitochondrial dysfunction and cell death in neuroblastoma cells. Interestingly, treatment with 3-NP induces subcellular translocation of hnRNP A1 from the nucleus to the cytoplasm, which accelerates the increase in Drp1 expression in hnRNP A1 over-expressing cells. Collectively, our findings suggest that hnRNP A1 controls mitochondrial dynamics by post-transcriptional regulation of Drp1.This research was supported by a grant of the Korea–UK Collaborative Alzheimer's Disease Research Project by Ministry of Health & Welfare, Republic of Korea (A120196, HI14C1913) and was supported by the Basic Science Research Program of the National Research Foundation, Republic of Korea (2014R1A2A1A11053431). We are grateful to Wellcome Trust, Principal Research Fellowship to DCR (095317/Z/11/Z)This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.bbagrm.2015.10.01

Transcatheter Closure of Multiple Atrial Septal Defects With the Amplatzer Device

Percutaneous device occlusion of secundum atrial septal defect (ASD) has become an accepted alternative to surgical repair. A variety of devices have been used successfully. However, all of them have limitations. We report our experience with two devices used to close multiple ASDs

Korean speech sound development in children from bilingual Japanese-Korean environments

PurposeThis study investigates Korean speech sound development, including articulatory error patterns, among the Japanese-Korean children whose mothers are Japanese immigrants to Korea.MethodsThe subjects were 28 Japanese-Korean children with normal development born to Japanese women immigrants who lived in Jeonbuk province, Korea. They were assessed through Computerized Speech Lab 4500. The control group consisted of 15 Korean children who lived in the same area.ResultsThe values of the voice onset time of consonants /ph/, /t/, /th/, and /k*/ among the children were prolonged. The children replaced the lenis sounds with aspirated or fortis sounds rather than replacing the fortis sounds with lenis or aspirated sounds, which are typical among Japanese immigrants. The children showed numerous articulatory errors for /c/ and /l/ sounds (similar to Koreans) rather than errors on /p/ sounds, which are more frequent among Japanese immigrants. The vowel formants of the children showed a significantly prolonged vowel /o/ as compared to that of Korean children (P<0.05). The Japanese immigrants and their children showed a similar substitution /n/ for /ɧ/ [Japanese immigrants (62.5%) vs Japanese-Korean children (14.3%)], which is rarely seen among Koreans.ConclusionThe findings suggest that Korean speech sound development among Japanese-Korean children is influenced not only by the Korean language environment but also by their maternal language. Therefore, appropriate language education programs may be warranted not only or immigrant women but also for their children

Clinical Analysis and Red Flag Signs in Pediatric Headache According to Age

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

Is Electroencephalography Useful in Children with Developmental Delays but without Overt Seizures?

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<0.001). Of 22 patients with ASD, five (12.8%) had abnormal EEGs. Of 13 patients with ADHD, five (36.4%) had abnormal EEGs, all with epileptiform discharges. Two patients with ASD and two with ADHD exhibited rhythmic slowing. Abnormal EEG findings were significantly more common among those with genetic abnormalities compared to genetically normal patients (26 vs. 13, P=0.017). Conclusion EEG represents a potential screening tool for children with DD. Abnormal EEG findings are associated with increased epilepsy risk, informing diagnosis and treatment planning

Anti-allergic Inflammatory Effects of the Essential Oil From Fruits of Zanthoxylum coreanum Nakai

Zanthoxylum coreanum Nakai is a rare shrub which grows in Korea and China. Pericarp of Z. coreanum has been used as a crude medicine, but there are few researches about the pharmacologic activities. The present study was designed to investigate the anti-allergic inflammatory activities of the essential oil from fruits of Zanthoxylum coreanum Nakai (ZCO). Our findings showed that ZCO inhibited both the IgE-antigen complex or PMA/A23187-induced β-hexosaminidase release and IL-4 production dose-dependently in RBL-2H3 mast cells, and confirmed that ZCO at the tested concentrations did not show cytotoxicity to RBL-2H3 cells by MTS assay. Additionally, we found that ZCO showed the significant inhibition on LPS-induced overproduction of TNF-α, IL-6 and NO. Consistently, the protein levels of iNOS and COX-2 were also remarkably decreased by ZCO treatment. Herein, Our mechanistic studies revealed that ZCO significantly suppressed the activation of transcription factor NF-κB in PMA-activated 293T cells, and further inhibited NF-κB p65 translocation into the nucleus in LPS-stimulated RAW264.7 cells. Further investigation identified that ZCO down-regulated LPS-induced phosphorylation of MAPK (JNK, ERK, and p38) signal pathway. For incremental research, we established an DNCB-induced atopic dermatitis model in BALB/c mice, and found that ZCO remarkably inhibited DNCB-induced ear swelling and AD-like symptoms. Based on these findings, ZCO is suggested to have a therapeutic potential for the allergic inflammatory diseases

Asthma diagnosis and treatment – 1023. The implementation of asthma management guideline and the obstacle factors in Korea

Background Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. We evaluated whether extracellular vesicles (EV) in indoor air are causally related to the pathogenesis of asthma and/or emphysema. Methods EV were prepared by sequential ultrafiltration and ultracentrifugation from indoor dust collected from a bed. Innate and adaptive immune responses were evaluated after once or 4 weeks airway exposure of EV, respectively. Results Vesicles 50-200 nm in diameter were present (102.5 microgram [based on protein concentration]/g dust) in indoor dust, and inhalation of 1 microgram of these vesicles for 4 weeks caused neutrophilic pulmonary inflammation. Additionally, polymyxin B (an antagonist of endotoxin, a cell wall component of Gram-negative bacteria) reversed the inflammation induced by the dust EV. Indoor dust harbors Esherichia coli-derived vesicles; airway exposure to the vesicles for 4 weeks induced neutrophilic inflammation and emphysema, which were partially eliminated by the absence of IFN-gamma or IL-17. Interestingly, serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis. Moreover, serum dust EV-reactive IgG1 levels were also elevated in adult asthma or COPD patients than in healthy controls. Conclusions EV in indoor dust, especially derived from Gram-negative bacteria, appear to be an important causative agent in the pathogenesis of asthma and/or emphysema

Risk Factors for Delayed Post-Polypectomy Bleeding

Background/AimsAmong the many complications that can occur following therapeutic endoscopy, bleeding is the most serious, which occurs in 1.0-6.1% of all colonoscopic polypectomies. The aim of this study was to identify risk factors of delayed post-polypectomy bleeding (PPB).MethodsWe retrospectively reviewed the data of patients who underwent colonoscopic polypectomy between January 2003 and December 2012. We compared patients who experienced delayed PPB with those who did not. The control-to-patient ratio was 3:1. The clinical data analyzed included polyp size, number, location, and shape, patient' body mass index (BMI), preventive hemostasis, and endoscopist experience.ResultsOf 1,745 patients undergoing colonoscopic polypectomy, 21 (1.2%) experienced significant delayed PPB. We selected 63 age- and sex-matched controls. Multivariate logistic regression analysis showed that polyps >10 mm (odds ratio [OR], 2.605; 95% confidence interval [CI], 1.035-4.528; P=0.049), a pedunculated polyp (OR, 3.517; 95% CI, 1.428-7.176; P=0.045), a polyp located in the right hemicolon (OR, 3.10; 95% CI, 1.291-5.761; P=0.013), and a high BMI (OR, 3.681; 95% CI, 1.876-8.613; P=0.013) were significantly associated with delayed PPB.ConclusionsAlthough delayed PPB is a rare event, more caution is needed during colonoscopic polypectomies performed in patients with high BMI or large polyps, pedunculated polyps, or polyps located in the right hemicolon