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OBJECTIVE: Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. METHODS: Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. CONCLUSION: Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.
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Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Secuenciación Completa del Genoma , Humanos , Niño , Preescolar , Lactante , República de Corea/epidemiología , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/farmacología , Femenino , Masculino , COVID-19/epidemiología , Colistina/farmacología , Acinetobacter calcoaceticus/genética , Acinetobacter calcoaceticus/efectos de los fármacos , Acinetobacter calcoaceticus/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana Múltiple/genética , SARS-CoV-2/genética , SARS-CoV-2/efectos de los fármacos , Estudios Prospectivos , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Bacteriemia , Análisis de Series de Tiempo Interrumpido , Klebsiella pneumoniae , Humanos , Estudios Retrospectivos , Niño , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Bacteriemia/microbiología , Femenino , Masculino , Preescolar , Antibacterianos/uso terapéutico , Lactante , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Adolescente , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Hospitales PediátricosRESUMEN
PURPOSE: Patients with STAT1 gain-of-function (GOF) mutations often exhibit autoimmune features. The JAK1/2 inhibitor ruxolitinib can be administered to alleviate autoimmune symptoms; however, it is unclear how immune cells are molecularly changed by ruxolitinib treatment. Then, we aimed to investigate the trnscriptional and epigenetic status of immune cells before and after ruxolitinib treatment in a patient with STAT1 GOF. METHODS: A patient with a heterozygous STAT1 GOF variant (p.Ala267Val), exhibiting autoimmune features, was treated with ruxolitinib, and peripheral blood mononuclear cells (PBMCs) were longitudinally collected. PBMCs were transcriptionally analyzed by single-cell cellular indexing of the transcriptomes and epitopes by sequencing (CITE-seq), and epigenetically analyzed by assay of transposase-accessible chromatin sequencing (ATAC-seq). RESULTS: CITE-seq analysis revealed that before treatment, the patient's PBMCs exhibited aberrantly activated inflammatory features, especially IFN-related features. In particular, monocytes showed high expression levels of a subset of IFN-stimulated genes (ISGs). Ruxolitinib treatment substantially downregulated aberrantly overexpressed ISGs, and improved autoimmune features. However, epigenetic analysis demonstrated that genetic regions of ISGs-e.g., STAT1, IRF1, MX1, and OAS1-were highly accessible even after ruxolitinib treatment. When ruxolitinib was temporarily discontinued, the patient's autoimmune features were aggravated, which is in line with sustained epigenetic abnormality. CONCLUSIONS: In a patient with STAT1 GOF, ruxolitinib treatment improved autoimmune features and downregulated aberrantly overexpressed ISGs, but did not correct epigenetic abnormality of ISGs.
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Mutación con Ganancia de Función , Pirazoles , Factor de Transcripción STAT1 , Humanos , Mutación con Ganancia de Función/genética , Leucocitos Mononucleares/metabolismo , Nitrilos/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Factor de Transcripción STAT1/genéticaRESUMEN
BACKGROUND: Headaches are the most common neurologic symptoms in the pediatric population. Most primary headache in children and adolescents focuses on associated factors, including noise. Auditory discomfort is related to recognizing the pain. We aimed to analyze the headache profile of pediatric populations and the connection between noise exposure and head pain in children and adolescents. METHODS: We reviewed retrospectively medical records of the pediatric population with headaches in Gyeongsang National University Changwon Hospital from January 2022 to April 2023. Personal headache profiling from self-questionnaires and environmental noise data from the National Noise Information System (NNIS) were used to analyze each variable, and chi-square tests and linear regression models by SAS were used to analyze the statistical correlation. RESULTS: Of the 224 participants, 125 were clinically diagnosed with headaches. Of the 104 pubertal subjects, 56.7% were diagnosed with headaches, compared to 60% in the prepubertal group. Both daytime and nighttime noise was significantly higher in the diagnosed headache group than in the non-diagnosed group. Headache duration increased by daytime and nighttime noise with statistical significance in age-adjusted models. CONCLUSION: We found that noise exposure is correlated to headaches in children and adolescents. Daytime and nighttime environmental noise exposure was significantly associated with the duration of headaches through our data. Therefore, we assume that noise exposure is vitally relevant to prolonged headaches in the pediatric population. Further research is needed to improve our data.
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Cefalea , Dolor , Adolescente , Humanos , Niño , Estudios Retrospectivos , Cefalea/etiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Pediatric urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). METHODS: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. RESULTS: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 µg/mL and 2 µg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 µg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 µg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 µg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 µg/mL and 32 µg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 µg/mL and 128 µg/mL, respectively. CONCLUSION: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.
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Infecciones por Escherichia coli , Fosfomicina , Infecciones Urinarias , Humanos , Niño , Adolescente , Adulto , Recién Nacido , Lactante , Fosfomicina/farmacología , Fosfomicina/uso terapéutico , Nitrofurantoína/farmacología , Nitrofurantoína/uso terapéutico , Escherichia coli , Klebsiella pneumoniae , beta-Lactamasas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. METHODS: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. RESULTS: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised. The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients). Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. CONCLUSION: ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.
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Enfermedades del Sistema Nervioso Central , Resfriado Común , Infecciones por Coronavirus , Coronavirus , Encefalitis , Niño , Humanos , Estudios Retrospectivos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/diagnóstico , Sistema Nervioso Central , Convulsiones/etiologíaRESUMEN
OBJECTIVE: TissueGene-C (TG-C), a combination of human allogeneic chondrocytes and irradiated GP2-293 cells engineered to overexpress transforming growth factor-ß1 (TGF-ß1), has been developed as a novel cell-based gene therapy and a candidate for disease modifying osteoarthritis drug (DMOAD). We aim to investigate analgesic mechanism of TG-C in a pre-clinical animal model with monoiodoacetate (MIA)-induced pain. DESIGN: We used a rat MIA model of osteoarthritis (OA) pain. We examined that TG-C can regulate pain by inhibiting the upregulation of various pain mediators in both knee joint tissue and dorsal root ganglia (DRG) (n = 112) and alleviating pain behavior (n = 41) and neuronal hyperexcitability in DRG (n = 60), afferent nerve fiber (n = 24), and spinal cord (n = 35). RESULTS: TG-C significantly alleviated pain-related behavior by restoring altered dynamic weight bearing and reduced mechanical threshold of the affected hindlimb. TG-C significantly suppressed the expression of nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) in inflamed joint tissue. TG-C significantly suppressed the upregulation of tropomyosin receptor kinase A (TrkA) and nerve injury/regeneration protein (GAP43) and activation of Iba1-positive microglial cells in DRG. TG-C significantly recovered neuronal hyperexcitability by restoring RMP and firing threshold and frequency of DRG neurons, attenuating firing rates of mechanosensitive C- or Aδ-nerve fiber innervating knee joint, and lowering increased miniature and evoked excitatory postsynaptic currents (mEPSCs and eEPSCs) in the spinal cord. CONCLUSION: Our results demonstrated that TG-C exerted potent analgesic effects in a rat MIA model of OA pain by inhibiting the upregulation of pain mediators and modulating neuronal sensitization.
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Osteoartritis , Dolor , Ratas , Humanos , Animales , Ratas Sprague-Dawley , Dolor/metabolismo , Osteoartritis/terapia , Osteoartritis/tratamiento farmacológico , Analgésicos/uso terapéutico , Neuronas/metabolismo , Ganglios Espinales/metabolismo , Modelos Animales de EnfermedadRESUMEN
Although peripheral neuropathic pain is caused by peripheral nerve injury, it is not simply a peripheral nervous system disease. It causes abnormalities in both the central and peripheral nervous systems. Pathological phenomena, such as hyperactivation of sensory neurons and inflammation, are observed in both the dorsal root ganglion and spinal cord. Pain signals originating from the periphery are transmitted to the brain via the SC, and the signals are modulated by pathologically changing SC conditions. Therefore, the modulation of SC pathology is important for peripheral NP treatment. We investigated the effects of KLS-2031 (recombinant adeno-associated viruses expressing glutamate decarboxylase 65, glial cell-derived neurotrophic factor, and interleukin-10) delivered to the dorsal root ganglion on aberrant neuronal excitability and neuroinflammation in the SC of rats with peripheral NP. Results showed that KLS-2031 administration restored excessive excitatory transmission and inhibitory signals in substantia gelatinosa neurons. Moreover, KLS-2031 restored the in vivo hypersensitivity of wide dynamic range neurons and mitigated neuroinflammation in the SC by regulating microglia and astrocytes. Collectively, these findings demonstrated that KLS-2031 efficiently suppressed pathological pain signals and inflammation in the SC of peripheral NP model, and is a potential novel therapeutic approach for NP in clinical settings. PERSPECTIVE: Our study demonstrated that KLS-2031, a combination gene therapy delivered by transforaminal epidural injection, not only mitigates neuroinflammation but also improves SC neurophysiological function, including excitatory-inhibitory balance. These findings support the potential of KLS-2031 as a novel modality that targets multiple aspects of the complex pathophysiology of neuropathic pain.
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Neuralgia , Enfermedades Neuroinflamatorias , Ratas , Animales , Neuralgia/terapia , Médula Espinal , Terapia Genética , Inflamación , Células Receptoras Sensoriales , Hiperalgesia , Ganglios EspinalesRESUMEN
Since October 2021, severe acute hepatitis of unknown etiology in pediatric patients has been observed in many countries around the world. Adenovirus (mainly enteric adenovirus) was detected in more than 50% of the cases. Nationwide surveillance on acute hepatitis of unknown etiology in pediatric patients was started in May 2022 in Korea. Taking into account the severity of the illness and the urgency of the epidemiological situation worldwide, we report a summary of changes in adenovirus epidemiology during the past five years and six months in Korea.
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Adenoviridae , Frecuencia Respiratoria , Humanos , Niño , Adenoviridae/genética , República de Corea/epidemiologíaRESUMEN
The birth prevalence of symptomatic congenital cytomegalovirus (cCMV) disease among live birth in Korea from a multicenter study was 0.06% during 2001-2015 with increasing frequency. The administrative prevalence of cCMV infection by big-data analysis from the national health insurance system was 0.01% and the average healthcare cost was US$2010 per person.
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Infecciones por Citomegalovirus , Pérdida Auditiva Sensorineural , Humanos , Lactante , Citomegalovirus , Pérdida Auditiva Sensorineural/epidemiología , Prevalencia , Macrodatos , República de CoreaRESUMEN
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. OBJECTIVE: To investigate the survival rate and long-term outcome of DBS. METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Niño , Preescolar , Femenino , Humanos , Masculino , Enfermedad de Parkinson/cirugía , Periodo Posoperatorio , Núcleo Subtalámico/fisiología , Resultado del TratamientoRESUMEN
The aim of this study was to determine the muscle load reduction of the upper extremities and lower extremities associated with wearing an exoskeleton, based on analyses of muscle activity (electromyography: EMG) and the AnyBody Modeling System (AMS). Twenty healthy males in their twenties participated in this study, performing bolting tasks at two working heights (60 and 85 cm). The muscle activities of the upper trapezius (UT), middle deltoid (MD), triceps brachii (TB), biceps brachii (BB), erector spinae (ES), biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) were measured by EMG and estimated by AMS, respectively. When working at the 60 cm height with the exoskeleton, the lower extremity muscle (BF, RF, TA) activities of EMG and AMS decreased. When working at the 85 cm height, the lower extremity muscle activity of EMG decreased except for TA, and those of AMS decreased except for RF. The muscle activities analyzed by the two methods showed similar patterns, in that wearing the exoskeleton reduced loads of the lower extremity muscles. Therefore, wearing an exoskeleton can be recommended to prevent an injury. As the results of the two methods show a similar tendency, the AMS can be used.
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Dispositivo Exoesqueleto , Músculos Superficiales de la Espalda , Electromiografía/métodos , Ergonomía , Humanos , Extremidad Inferior/fisiología , Masculino , Músculo Esquelético/fisiologíaRESUMEN
OBJECTIVE: Despite the clinical significance of cancer-associated cognitive decline (CACD), no longitudinal study has evaluated CACD in gastric cancer patients. This preliminary study explored structural and functional neural changes of CACD in gastric cancer patients focusing on the effects of chemotherapy. METHODS: 13 gastric cancer patients who received adjuvant chemotherapy (CTx+ group), 9 gastric cancer patients who did not receive adjuvant chemotherapy (CTx- group), and 10 healthy controls (HCs) were enrolled in this study. We performed self-report questionnaires, neurocognitive tests, voxel-based morphometry (VBM), and resting-state functional magnetic resonance imaging (rsfMRI) analyses before and 3 months after chemotherapy. RESULTS: Compared to the CTx- group, the CTx+ group exhibited statistically significant decrease in attention and executive function over time and dysfunction in delayed recognition performance. The results of the rsfMRI analysis showed a significant group-by-time interaction in the left hippocampus-anterior thalamus. However, no significant structural change was observed in the VBM analysis. CONCLUSION: To the best of our knowledge, this is the first longitudinal neuroimaging study on CACD in gastric cancer patients. Based on the results of our preliminary study, we suggest that the neuropathological processes and clinical presentation of CACD in gastric cancer patients is similar to those of patients associated with age-related neurodegenerative disorders.
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Disfunción Cognitiva , Neoplasias Gástricas , Encéfalo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Humanos , Imagen por Resonancia Magnética/métodos , Neuroimagen , Pruebas Neuropsicológicas , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021. However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population. METHODS: A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019. RESULTS: Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6-12.9 years; range, 11 days-17.8 years), and male was 61%. In adolescents aged 12-17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1-5 years), 0.67 (6-11 years) and 1.22 (12-17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014). CONCLUSION: The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.
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Vacunas contra la COVID-19/efectos adversos , Miocarditis/epidemiología , Miocarditis/patología , Pericarditis/epidemiología , Pericarditis/patología , Adolescente , Vacuna BNT162 , COVID-19/prevención & control , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , República de Corea/epidemiología , Estudios Retrospectivos , Vacunación/efectos adversosRESUMEN
Calbindin, a major Ca2+ buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+ signals, yet how it regulates neuronal function remains largely unknown. Here, we found that calbindin knockout (CBKO) mice exhibited dentate GC hyperexcitability and impaired pattern separation, which co-occurred with reduced K+ current due to downregulated surface expression of Kv4.1. Relatedly, manipulation of calbindin expression in HT22 cells led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO mice. We also discovered that Ca2+ buffering capacity was significantly reduced in the GCs of Tg2576 mice to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that the regulation of CaMKII signaling by Ca2+ buffering is crucial for neuronal excitability regulation.
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Calbindinas/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Giro Dentado/metabolismo , Animales , Antioxidantes/farmacología , Bencilaminas/farmacología , Calbindinas/genética , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Condicionamiento Psicológico , Giro Dentado/citología , Giro Dentado/efectos de los fármacos , Miedo/fisiología , Células HT29 , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Transporte de Proteínas , Serina/metabolismo , Sulfonamidas/farmacologíaRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes memory loss. Most AD researches have focused on neurodegeneration mechanisms. Considering that neurodegenerative changes are not reversible, understanding early functional changes before neurodegeneration is critical to develop new strategies for early detection and treatment of AD. We found that Tg2576 mice exhibited impaired pattern separation at the early preclinical stage. Based on previous studies suggesting a critical role of dentate gyrus (DG) in pattern separation, we investigated functional changes in DG of Tg2576 mice. We found that granule cells in DG (DG-GCs) in Tg2576 mice showed increased action potential firing in response to long depolarizations and reduced 4-AP sensitive K+-currents compared to DG-GCs in wild-type (WT) mice. Among Kv4 family channels, Kv4.1 mRNA expression in DG was significantly lower in Tg2576 mice. We confirmed that Kv4.1 protein expression was reduced in Tg2576, and this reduction was restored by antioxidant treatment. Hyperexcitable DG and impaired pattern separation in Tg2576 mice were also recovered by antioxidant treatment. These results highlight the hyperexcitability of DG-GCs as a pathophysiologic mechanism underlying early cognitive deficits in AD and Kv4.1 as a new target for AD pathogenesis in relation to increased oxidative stress.
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Giro Dentado/fisiopatología , Memoria/fisiología , Canales de Potasio Shal/biosíntesis , Potenciales de Acción , Enfermedad de Alzheimer , Péptidos beta-Amiloides/genética , Animales , Antioxidantes/farmacología , Condicionamiento Clásico/fisiología , Giro Dentado/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Electrochoque , Miedo , Reacción Cataléptica de Congelación , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Transgénicos , Estrés Oxidativo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes/genética , Canales de Potasio Shal/genéticaRESUMEN
Data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from preschool-age children to children and adults are limited. We investigated SARS-CoV-2 exposure at a childcare center in South Korea. A 4-year-old child, probably infected by his grandmother, attended the center during the presymptomatic period (February 19-21, 2020). Fever developed on February 22, and he was given a diagnosis SARS-CoV-2 infection on February 27. At the center, 190 persons (154 children and 36 adults) were identified as contacts; 44 (23.2%) were defined as close contacts (37 children and 7 adults). All 190 persons were negative for SARS-CoV-2 on days 8-9 after the last exposure. Two close contacts (1 child and 1 adult) showed development of symptoms on the last day of quarantine. However, subsequent test results were negative. This investigation adds indirect evidence of low potential infectivity in a childcare setting with exposure to a presymptomatic child.
Asunto(s)
COVID-19/transmisión , Exposición a Riesgos Ambientales/análisis , SARS-CoV-2 , Adulto , COVID-19/prevención & control , Guarderías Infantiles , Preescolar , Trazado de Contacto , Transmisión de Enfermedad Infecciosa , Femenino , Humanos , Masculino , Cuarentena , República de CoreaRESUMEN
BACKGROUND: Data on severe acute respiratory syndrome coronavirus-2 transmission from a pediatric index patient to others at the school setting are limited. Epidemiological data on pediatric coronavirus disease 2019 (COVID-19) cases after school opening are warranted. METHODS: We analyzed data of the pediatric patients with COVID-19 collected from the press release of the Korea Centers for Disease Control and Prevention. Information on the school opening delay and re-opening policies were achieved from the press release of the Korean Ministry of Education. RESULTS: The school openings were delayed three times in March 2020. Online classes started from April 9, and off-line (in-person) classes started from May 20 to June 8 at four steps in different grades of students. There was no sudden increase in pediatric cases after the school opening, and the proportion of pediatric cases among total confirmed cases in the nation around 7.0%. As of July 31, 44 children from 38 schools and kindergartens were diagnosed with COVID-19 after off-line classes started. More than 13,000 students and staffs were tested; only one additional student was found to be infected in the same classroom. The proportions of pediatric patients without information on infection sources were higher in older age groups than in younger age groups (17.4% vs. 52.4%, P = 0.014). In the younger age group, 78.3% of children were infected by family members, while only 23.8% of adolescents in the older age group were infected by family members (P < 0.001). CONCLUSION: Korea had a successful transition from school closure to online and off-line school opening, which did not cause significant school-related outbreak among the pediatric population.