Echocardiographic Strain Evaluation Shows Persistent Echocardiographic Changes at 1 Year after Diagnosis of Multisystem Inflammatory Syndrome in Children.

Coronavirus disease (COVID-19) is a global pandemic causing multisystem inflammatory syndrome in children (MIS-C). This study evaluated the long-term echocardiographic impact of MIS-C on patients and compared it with that in a healthy control group. Data from 22 children with MIS-C admitted to Jeonbuk National University Hospital and 22 healthy children (control group) were retrospectively analyzed. Echocardiographic data were compared at two distinct time points: diagnosis and 1-year follow-up. At diagnosis, the MIS-C cohort exhibited significantly reduced left ventricular ejection fraction (LVEF), longitudinal strain across the apical 4- and 2-chamber views, and global longitudinal strain (GLS). At 1-year follow-up, the reduced LVEF in the apical 4-chamber, overall longitudinal strain in the apical 4-chamber, and GLS persisted. However, the right ventricular free wall and global strain remained diminished compared with those in the control group. Despite significant changes over time, the LVEF and longitudinal strain in the apical 4-chamber and z-scores of all coronary arteries were normal at baseline and 1-year follow-up. Persistent cardiac alterations were observed in patients with MIS-C, particularly in both ventricular functions. Therefore, middle- to long-term echocardiographic follow-up may help improve understanding and management of long-term echocardiographic implications in patients with post-COVID-19 syndrome.

Comparison of Clinical Manifestations of Kawasaki Disease According to SARS-CoV-2 Antibody Positivity.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in paediatric patients, with infectious agents being the main cause. This study aimed to determine whether there are differences in the clinical manifestations of KD between patients with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: From January 1, 2021 to August 15, 2022, 82 patients with analysable echocardiographic data were diagnosed with KD. Twelve patients with multisystem inflammatory syndrome in children were excluded. Serologic tests were performed by chemiluminescence immunoassay for both the nucleocapsid (N) and the spike (S) proteins in blood samples. Among the 70 patients diagnosed with KD at Jeonbuk University Children's Hospital, the SARS-CoV-2 antibody test was performed in 41 patients. RESULTS: The SARS-CoV-2 antibody test results for the N antigen were positive in 12 patients, while those for S protein were positive in 14 patients. N antigen SARS-CoV-2 antibody-positive KD was different from N antigen SARS-CoV-2 antibody-negative KD in terms of sex (male predominance in the positive group, 83.3% vs. female predominance in the negative group 62.1%, P = 0.008) and the incidence of refractory KD (41.7% vs. 10.3%, P = 0.034). The pro-B-type natriuretic peptide level was lower in the N-antigen SARS-CoV-2 antibody-positive KD group than that in the negative group (518.9 ± 382.6, 1,467.0 ± 2,417.6, P = 0.049). No significant differences in the echocardiographic findings between both groups were noted. In the multi-variable analysis, SARS-CoV-2 antibody (N antigen) was the only predictor of refractory KD (odds ratio, 13.70; 95% confidence interval, 1.63-115.44; P = 0.016). CONCLUSION: High incidence of intravenous immunoglobulin-refractory KD may occur in up to 40% of the patients having recent history of coronavirus disease 2019. For patients having KD with N-type SARS-CoV-2 antibody positivity, adjunctive treatment, such as corticosteroids, can be considered as the first line of treatment.

Clinical characteristics and short-term outcomes of multisystem inflammatory syndrome in a country with a high prevalence of KD.

Background: The COVID-19 pandemic has spread continuously. Multisystem inflammatory syndrome in children (MIS-C), like Kawasaki disease (KD), is a potentially severe illness in children that appears to be a delayed, post-infectious complication of COVID-19. However, based on the relatively low MIS-C prevalence and high KD prevalence in Asian children, the clinical features of MIS-C are not fully recognized, especially after the spread of the Omicron variant. Here, we aimed to identify the clinical characteristics of MIS-C in a country with high KD prevalence. Methods: We retrospectively analyzed 98 children diagnosed with KD and MIS-C admitted to Jeonbuk National University Hospital between January 1, 2021, and October 15, 2022. Twenty-two patients were diagnosed with MIS-C, following CDC diagnostic criteria for MIS-C. We reviewed medical records for clinical features, laboratory findings, and echocardiography. Results: Age, height, and weight were higher for patients with MIS-C than for those with KD. Lymphocytes percentage was lower, and the segmented neutrophil percentage was higher in the MIS-C group. The inflammation marker C-reactive protein was higher in the MIS-C group. Prothrombin time was prolonged in the MIS-C group. Albumin level was lower in the MIS-C group. The MIS-C group had lower potassium, phosphorus, chloride, and total calcium. Twenty-five percent of patients diagnosed with MIS-C had positive RT-PCR, and all the patients were N-type SARS-CoV-2 antibody-positive. Albumin ≤3.85 g/dl effectively predicted MIS-C. Regarding echocardiography, the right coronary artery z-score, the absolute value of apical 4-chamber left ventricle longitudinal strain, and the ejection fraction (EF) was significantly lower in the MIS-C group. A month after diagnosis using echocardiographic data, all coronary artery z-scores had reduced significantly. EF and fractional shortening (FS) also improved one month after diagnosis. Conclusion: Albumin values can differentiate MIS-C and KD. In addition, a decrease in the absolute LV longitudinal strain value, EF, and FS was observed in the MIS-C group using echocardiography. Coronary artery dilatation was not evident at the initial diagnosis; however, a change in coronary artery size, EF, and FS was observed on follow-up echocardiography a month after diagnosis.

Analysis of Cause-of-Death Mortality in Children and Young Adults with Diabetes: A Nationwide 10-Year Follow-Up Cohort Study.

We examined the associations of clinical characteristics and cause-of-death patterns with mortality in children and young adults (<30 years) with diabetes. We analyzed a nationwide cohort sample from the KNHIS database using propensity score matching from a sample of 1 million people from 2002 to 2013. There were 10,006 individuals in the diabetes mellitus (DM) group and 10,006 in the control (no DM) group. The numbers of deaths were 77 in the DM group and 20 in the control group. The deaths of patients in the DM Group were 3.74 (95% confidence interval (CI) = 2.25-6.21) times higher than in the control group. Type 1 DM, type 2 DM and unspecified DM were 4.52 (95% CI = 1.89-10.82) times, 3.25 (95% CI = 1.95-5.43) times and 10.20 (95% CI = 5.24-20.18) times higher, respectively. Mental disorders were 2.08 times higher in the risk of death (95% CI = 1.27-3.40). Mortality rates have increased in children and young adults with diabetes alone. Therefore, in the future, it is necessary to identify the cause of the increased mortality rate among young diabetic people and select vulnerable groups among them so that early prevention can be achieved.

Identification of cell-biologic mechanisms of coronary artery spasm and its ex vivo diagnosis using peripheral blood-derived iPSCs.

BACKGROUND: Although vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA. METHODS AND RESULTS: With 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51, p < 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier (SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13, p < 0.01). CONCLUSIONS: Our findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA.

Resistin impairs mitochondrial homeostasis via cyclase-associated protein 1-mediated fission, leading to obesity-induced metabolic diseases.

OBJECTIVE: One of the suggested mechanisms of obesity-induced insulin resistance is mitochondrial dysfunction in target tissues such as skeletal muscle. In our study, we examined whether resistin, an adipokine associated with obesity-mediated insulin resistance, induced metabolic disorders by impairing mitochondrial homeostasis. METHODS: The morphology and function of mitochondria of skeletal muscle were examined in resistin-knockout and humanized resistin mice that were subjected to high-fat diet for 3 months. Morphology was examined by transmission electron microscopy. Mitochondria bioenergetics of skeletal muscle were evaluated using a Seahorse XF96 analyzer. Human skeletal myoblasts were used for in vitro studies on signaling mechanisms in responses to resistin. RESULTS: A high-fat diet in humanized resistin mice increased fragmented and shorter mitochondria in the skeletal muscle, whereas resistin-knockout mice had healthy normal mitochondria. In vitro studies showed that human resistin treatment impaired mitochondrial homeostasis by inducing mitochondrial fission, leading to a decrease in ATP production and mitochondrial dysfunction. Induction of mitochondrial fission by resistin was accompanied by increased formation of mitochondria-associated ER membranes (MAM). At the same time, resistin induced up-regulation of the protein kinase A (PKA) pathway. This activation of PKA induced phosphorylation of Drp1 at serine 616, leading to Drp1 activation and subsequent induction of mitochondrial fission. The key molecule that mediated human resistin-induced mitochondrial fission was adenylyl cyclase-associated protein 1 (CAP1), which was reported as a bona fide receptor for human resistin. Moreover, our newly developed biomimetic selective blocking peptide could repress human resistin-mediated mitochondrial dysfunction. High-fat diet-fed mice showed lower exercise capacity and higher insulin resistance, which was prevented by a novel peptide to block the binding of resistin to CAP1 or in the CAP1-knockdown mice. CONCLUSIONS: Our study demonstrated that human resistin induces mitochondrial dysfunction by inducing abnormal mitochondrial fission. This result suggests that the resistin-CAP1 complex could be a potential therapeutic target for the treatment of obesity-related metabolic diseases such as diabetes and cardiometabolic diseases.

Two Case Reports of Life-Threatening Croup Caused by the SARS-CoV-2 Omicron BA.2 Variant in Pediatric Patients.

Croup is a common upper airway infection characterized by a barking cough, stridor, and hoarseness. It is usually caused by viral infection. A small number of croup caused by coronavirus disease 2019 (COVID-19) has been reported in children before the omicron variant surge. Previously reported cases indicated that croup caused by COVID-19 can be treated in the same manner as those with other viral causes. We describe two cases (9-month-old girl and 11-month-old boy) of previously healthy infants who presented with a barking cough and chest retraction and required endotracheal intubation and cardiopulmonary resuscitation. Despite receiving dexamethasone and nebulized racemic epinephrine (NRE) treatment for croup in the emergency department, these patients still developed acute respiratory failure. Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal samples revealed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron BA.2 variant (Stealth omicron) and no other common respiratory viral pathogens. Both patients were treated with mechanical ventilation, dexamethasone, and NRE in the pediatric intensive care unit. The duration of intubation was 112 hours and 80 hours, respectively. Both patients were discharged without complications. To the best of our knowledge, this is the first report of life-threatening croup produced by the omicron BA.2 variant and confirmed by RT-PCR. We suggest that this SARS-CoV-2 variant may cause severe croup that may not improve with conventional treatment, even in children without underlying diseases.

A Case of Myocarditis Presenting With a Hyperechoic Nodule After the First Dose of COVID-19 mRNA Vaccine.

Myocarditis and/or pericarditis have been reported as adverse events following coronavirus disease 2019 (COVID-19) messenger RNA vaccination, with most cases occurring within 1 week after the second dose. We report a rare case of myocarditis after the first dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in a 17-year-old boy. Here, we describe the laboratory, electrocardiographic, and imaging findings of myocarditis.

A Case Report for Using Methylprednisolone for Severe ARDS Caused by SARS-CoV-2 Delta Variant in a Pediatric Patient With Lennox-Gastaut Syndrome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 can result in fatal comorbidities, including acute respiratory distress syndrome (ARDS). Several reports suggest that children have milder illness, though severe cases have still been reported. We report a 9-year-old boy with ARDS caused by the SARS-CoV-2 delta (B.1.617.2) variant. He was admitted to our hospital and carefully observed due to underlying Lennox-Gastaut syndrome. He developed intractable seizures with a high fever. Although the seizures were controlled, his respiratory condition deteriorated to severe ARDS. High-dose methylprednisolone was administered with high positive end-expiratory pressure and low tidal volume. After ARDS treatment, oxygenation improved sufficiently to permit extubation. This case suggests that close observation is required in pediatric patients with neurologic comorbidities because of an increased risk for severe COVID-19.

Enhanced Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood and Using Their Mesoderm Differentiation Ability to Regenerate Infarcted Myocardium.

Тhe most pressing issue in generating induced pluripotent stem cells (iPSCs) in clinical practice is the cell source. Compared to human dermal fibroblasts (HDFs), which have been widely used, human peripheral blood could be a more easily obtainable alternative. However, iPSCs generated from fresh peripheral blood require inconvenient specific methods including isolation. Recently, we succeeded in isolating and culturing human heart-derived circulating cells called circulating multipotent stem (CiMS) cells. Here, we investigated the generation efficiency of CiMS-derived iPSCs (CiMS-iPSCs) and tested their differentiation potential into mesodermal lineages and cardiovascular cells. We isolated and cultured CiMS cells from peripheral mononuclear cells with a high efficiency. Moreover, our method succeeded in reprogramming the CiMS cells and generating iPSCs with higher efficiency compared to when HDFs were used. Compared to HDF-iPSCs or human embryonic stem cells (hESCs), CiMS-iPSCs showed high differentiation potential into mesodermal lineage cells and subsequently into endothelial cells, vascular smooth muscle cells, and cardiomyocytes. Further, we checked the epigenetic status of each cell type. While methylation of the CpG site of the brachyury T promoter did not differ between cell types, the histone H3 lysine 4 trimethylation level in the brachyury T promoter region was enhanced in CiMS-iPSCs, compared to that in other cell types. In contrast, histone H3 lysine 9 acetylation was downregulated during the differentiation process of the CiMS-iPSCs. In the myocardial infarction model, the CiMS-iPSCs group showed more therapeutic potential in regenerating the myocardium than other cell types. Our study showed a new method to isolate human heart-derived stem cells from human peripheral blood and to generate iPSCs efficiently. Due to epigenetic memory, these CiMS-iPSCs easily differentiated into cardiovascular lineage cells, resulting in improved efficiency in vivo. These results suggest that our new method using CiMS cells has therapeutic potential in regenerative medicine using cell therapy.

Predictive Parameters of Decreased Left Ventricular Global Longitudinal Strain at 1 Month After Pediatric Heart Transplantation.

Previous reports indicate that the decreased left ventricular global longitudinal strain (LVGLS) seen in the early postoperative period of pediatric heart transplant patients generally recovers over the course of 1-2 years. In this study, we investigate the predictive capacity of preoperative parameters on the LVGLS decline seen at 1 month post transplant. Forty-six transplant subjects with 2D echocardiographic images sufficient for speckle tracking echocardiography were enrolled. We excluded patients diagnosed with cardiac allograft vasculopathy or with an episode of rejection 1 month before or after their echocardiographic examinations. The mean LVGLS was significantly reduced at 1 month when compared to 1 year following transplant (- 15.5% vs. - 19.4%, respectively, p < 0.001). The predictors of LVGLS that decline at 1 month were the LV mass z-score [odds ratio (OR) 1.452; 95% confidence interval (CI) 1.007-2.095, p = 0.046], recipient age (OR 1.124; 95% CI 1.015-1.245, p = 0.025), and donor age (OR 1.081; 95% CI 1.028-1.136, p = 0.002) in the univariate logistic regression analyses. Although multivariate analysis yielded no significant predictors, higher LV mass z-scores showed a trend associated with the decline of LVGLS (p = 0.087). The donor/recipient weight ratio was associated with the LV mass z-score (R2 = 0.412, p < 0.001).

Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9.

AIMS: Proprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9. Herein, we investigated the role of CAP1 in PCSK9-mediated lysosomal degradation of LDLR and plasma LDL cholesterol (LDL-C) levels. METHODS AND RESULTS: The direct binding between PCSK9 and CAP1 was confirmed by immunoprecipitation assay, far-western blot, biomolecular fluorescence complementation, and surface plasmon resonance assay. Fine mapping revealed that the CRD of PCSK9 binds with the Src homology 3 binding domain (SH3BD) of CAP1. Two loss-of-function polymorphisms found in human PCSK9 (S668R and G670E in CRD) were attributed to a defective interaction with CAP1. siRNA against CAP1 reduced the PCSK9-mediated degradation of LDLR in vitro. We generated CAP1 knock-out mice and found that the viable heterozygous CAP1 knock-out mice had higher protein levels of LDLR and lower LDL-C levels in the liver and plasma, respectively, than the control mice. Mechanistic analysis revealed that PCSK9-induced endocytosis and lysosomal degradation of LDLR were mediated by caveolin but not by clathrin, and they were dependent on binding between CAP1 and caveolin-1. CONCLUSION: We identified CAP1 as a new binding partner of PCSK9 and a key mediator of caveolae-dependent endocytosis and lysosomal degradation of LDLR.

Coronary artery status of patients with transient fever 24-36 h after first IVIG infusion did not differ from that seen in responsive patients.

BACKGROUND: Current management guidelines for patients with Kawasaki disease (KD) differ in their recommendations for fever observation times when determining resistance to initial intravenous immunoglobulin (IVIG). This retrospective study assessed coronary artery status in patients with transient fever 24-36 h after the completion of a first IVIG infusion. METHODS: Children with KD treated with IVIG between January 2006 and February 2017 were included. Subjects were divided into three groups according to response following the completion of initial IVIG treatment (Group 1, no fever after 24 h; Group 2, transient fever at 24-36 h; Group 3, others). RESULTS: A total of 879 children were evaluated (Group 1, n = 663; Group 2, n = 54; Group 3, n = 162). During the subacute phase, the left main coronary artery (LMCA) diameter z score in both groups was significantly lower than that in Group 3 (Group 1: 1.02, Group 2: 0.87, Group 3: 1.24; Group 1 vs 2, P = 0.298; Group 1 vs 3, P = 0.025; Group 2 vs 3, P = 0.042); similar results were seen with the left anterior descending coronary artery (LAD) diameter z score (Group 1: 0.64, Group 2: 0.38, Group 3: 0.98; Group 1 vs 2, P = 0.083; Group 1 vs 3, P = 0.001; Group 2 vs 3, P = 0.004). The coronary artery (CA) status also did not differ between Groups 1 and 2 during the convalescent phase (z score of LMCA was 0.70 in Group 1 and 0.74 in Group 2, P = 0.790; z score of LAD was 0.42 and 0.46 respectively, P = 0.796; z score of right CA was 0.07 and 0.00 respectively, P = 0.630). A multivariate logistic regression analysis identified total bilirubin level (OR, 2.472; 95% CI, 1.284-4.762; P = 0.007) as the only significant predictor of persisting fever over 36 h in patients with fever 24 h after the completion of initial IVIG. CONCLUSIONS: The CA status of patients with transient fever 24-36 h after the first IVIG infusion did not differ from that seen in responsive patients.

Epstein-Barr virus infection in children with renal transplantation: A single-centre experience.

AIM: This study aimed to investigate the incidence, timing, manifestations, managements, and outcomes of Epstein-Barr virus (EBV) infection in paediatric renal transplant recipients in Korea. METHODS: We retrospectively evaluated 70 patients aged <18 years who had undergone renal transplantation between January 1990 and November 2014 at a single centre in Korea. EBV infection was diagnosed via serological test or real-time quantitative polymerase chain reaction (PCR). The diagnosis of post-transplant lymphoproliferative disorder (PTLD) was based on biopsy findings. RESULTS: In total, 21 patients (30.0% of renal transplant recipients) had EBV infection. EBV infection occurred at an average age of 12.6 ± 4.5 (median, 12.0; range, 7.0-24.0 years, with a mean period of 28.3 ± 27.2 (median, 14.0; range, 2.0-75.0) months for developing EBV infection after transplantation. EBV infection developed 12 times more frequently in pre-transplant EBV-seronegative recipients. Eight patients (38% of EBV-infected patients) had EBV disease, and six patients (75% of patients with EBV disease) had PTLD. The maximum EBV PCR titer was greater in patients with EBV disease than in the asymptomatic EBV infection group. The main treatment for EBV infection was the reduction in immunosuppressants. Asymptomatic EBV infection resolved in approximately 80% of the patients. One patient (17% of the patients with PTLD) expired. The glomerular filtration rate did not deteriorate during the treatment of EBV infection. CONCLUSION: Regular EBV monitoring in renal transplant recipients is mandatory for early diagnosis and treatment of EBV infections and prevention of PTLD, especially in pre-transplant EBV IgG-negative patients.

Selective inhibitory effects of machilin A isolated from Machilus thunbergii on human cytochrome P450 1A and 2B6.

BACKGROUND: The bark of Machilus thunbergii (Lauraceae) has been used as a folk medicine to treat abdominal pain and distension, and leg edema in Korea. Machilin A (MA), a lignan isolated from Machilus thunbergii, exhibits several biological activities including anti-oxidant and stimulatory effects on cell differentiation and proliferation. PURPOSE: Potential drug-interactions with MA via inhibition of cytochrome P450 (CYP) activity in human liver microsomes (HLMs), have not been investigated. STUDY DESIGN: The inhibitory effects of MA on the activities of CYPs were investigated using cocktail probe substrates in pooled HLMs and on human recombinant cDNA-expressed CYP isoforms. METHODS: The nine CYP-specific substrates were incubated in HLM or recombinant cDNA-expressed CYP 1A1, 1A2 and 2B6 with MA. After incubation, the samples were injected onto a C18 column for liquid chromatography-tandem mass spectrometry analysis. To investigate the binding poses between MA and CYP, we carried out structure-based docking simulations by using software and scripts written in-house (ALIS-DOCK; Automatic pLatform for Iterative Structure-based DOCKing). RESULTS: MA strongly inhibited CYP1A2-mediated phenacetin O-deethylation and CYP2B6-mediated bupropion hydroxylation with IC50 values of 3.0 and 3.9 µM, respectively, while it did not significantly inhibit other CYPs. A Dixon plot indicated that MA competitively inhibits CYP1A2 and CYP2B6 with Ki values of 0.71 and 4.1 µM, respectively. CONCLUSION: Overall, this was the first investigation of the inhibitory effects of MA on CYP1A2 and CYP2B6 in HLMs, and it has identified that MA acts via competitive inhibition.

Effects of distraction task on driving: a functional magnetic resonance imaging study.

This study investigated neuronal activation differences under two conditions: driving only and distracted driving. Driving and distraction tasks were performed using a Magnetic Resonance (MR)-compatible driving simulator with a driving wheel and pedal. The experiment consisted of three blocks, and each block had both a Rest phase (1 min) and a Driving phase (2 min). During the Rest phase, drivers were instructed to simply look at the stop screen without performing any driving tasks. During the Driving phase, each driver was required to drive at 110 km/h under two conditions: driving only and driving while performing additional distraction tasks. The results show that the precuneus, inferior parietal lobule, supramarginal gyrus, middle frontal gyrus, cuneus, and declive are less activated in distracted driving than in driving only. These regions are responsible for spatial perception, spatial attention, visual processing and motor control. However, the cingulate gyrus and sub-lobar regions (lentiform nucleus and caudate), which are responsible for error monitoring and control of unnecessary movement, show increased activation during distracted driving compared with driving only.

Development of a simultaneous vibration and pressure stimulation system for cognitive studies.

In this study, a tactile stimulator that could separately or simultaneously display the vibrotactile and pressure sense was developed. The developed system consisted of a control unit, a drive unit, and an actuator, and can be operated with PC or manually. This system quantitatively controls the stimulation parameters such as the stimulation intensity, duration, frequency, and stimulation type. A preliminary electroencephalogram (EEG) experiment for three types of stimulation (vibrotactile, pressure sense, vibrotactile + pressure sense) highlights that the system could be used in complex tactile cognitive studies. An event-related desynchronization (ERD) and synchronization (ERS) were measured at the area of C3 and C4 for all three types of stimulation, and a clear response was identified in the contralateral somatosensory area from the brain topology. Therefore, it is expected that this system could be widely used in single and complex human tactile cognition and perception studies for vibrotactile and pressure sensation.

Development of the Real-Time Subjective Emotionality Assessment (RTSEA) system.

A new Real-Time Subjective Emotionality Assessment (RTSEA) system was developed for this study. The system is composed of two parts: an emotionality input and evaluation parts. An experiment was conducted in order to investigate the effectiveness of the RTSEA system. The present study compared Galvanic Skin Response (GSR) with the RTSEA by presenting 28 subjects with pictures that aroused either positive or negative emotion. Following the experiment, a subjective assessment using a questionnaire was given to the same subjects. According to the correlation coefficients, changes of the RTSEA had strong correlations with the changes of the GSR. Also, the questionnaire results showed marked similarity to the average responses of the RTSEA. In conclusion, the most remarkable characteristic of the present system is that it not only assesses the average emotionality when stimuli are presented, but also shows the trend of change in emotionality over time.

A comparison of the mean signal change method and the voxel count method to evaluate the sensitivity of individual variability in visuospatial performance.

This study compared the mean signal change method and the voxel count method in evaluating the sensitivity of individual variability in visuospatial performance using functional Magnetic Resonance Imaging (fMRI). Sixteen right-handed male college students (mean age 23.2 years) participated in this study as subjects. Functional brain images were scanned with a 3T MRI single-shot EPI method during a visuospatial task. No correlation was found between visuospatial performance and the number of activated voxels in the activated brain areas. Significant positive correlations, however, were found between visuospatial performance and the mean signal changes of activated voxels in the parietal, frontal and other areas. In conclusion, the mean signal change is more sensitive to individual variability in visuospatial performance than the number of activated voxels.

Effect of 30% oxygen administration on verbal cognitive performance, blood oxygen saturation and heart rate.

This study investigated the effect of 30% oxygen administration on verbal cognitive performance, blood oxygen saturation, and heart rate. Five male (24.6(+/-0.9) years) and five female (22.2(+/-1.9) years) college students were selected as the subjects for this study. Two psychological tests were developed to measure the performance level of verbal cognition. The experiment consisted of two runs: one was a verbal cognition task, with normal air (21% oxygen) administered and the other was with hyperoxic air (30% oxygen) administered. The experimental sequence in each run consisted of Rest 1 (1 min), Control (1 min), Task (4 min), and Rest 2 (4 min). Blood oxygen saturation and heart rate were measured throughout the four phases. The results of the verbal behavioural analysis reveal that accuracy rates were enhanced with 30% oxygen administration compared to 21% oxygen. When 30% oxygen was supplied, blood oxygen saturation was increased significantly compared to that with 21% oxygen administration, whereas heart rate showed no significant difference. Significant positive correlations were found between changes in oxygen saturation and cognitive performance. This result supports the hypothesis that 30% oxygen administration would lead to increases in verbal cognitive performance.