Music and movement therapy improves quality of life and attention and associated electroencephalogram changes in patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Treatments for ADHD include pharmacological and nonpharmacological therapy. However, pharmacological treatments have side effects such as poor appetite, sleep disturbance, and headache. Moreover, nonpharmacological treatments are not effective in ameliorating core symptoms and are time-consuming. Hence, developing an alternative and effective treatment without (or with fewer) side effects is crucial. Music therapy has long been used to treat numerous neurological diseases. Although listening to music is beneficial for mood and cognitive functions in patients with ADHD, research on the effects of music and movement therapy in children with ADHD is lacking. METHODS: The present study investigated the effects of an 8-week music and movement intervention in 13 children with ADHD. The Pediatric Quality of Life Inventory (PedsQL) was used to evaluate changes in participants' quality of life. Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Swanson, Nolan, and Pelham rating scale (SNAP-IV) were used to assess core symptoms. Electroencephalogram (EEG) recordings were analyzed to determine neurophysiological changes. RESULTS: The results revealed that the participants' quality of life increased significantly after the 8-week intervention. Furthermore, the participants' hit reaction times in the block 1 and block 2 tests of K-CPT 2 decreased significantly after the intervention. EEG analysis demonstrated an increase in alpha power and Higuchi's fractal dimension and a decrease in delta power in certain EEG channels. CONCLUSION: Our music and movement intervention is a potential alternative and effective tool for ADHD treatment and it can significantly improve patients' quality of life and attention.

Predicting the therapeutic response to valproic acid in childhood absence epilepsy through electroencephalogram analysis using machine learning.

Childhood absence epilepsy (CAE) is a common type of idiopathic generalized epilepsy, manifesting as daily multiple absence seizures. Although seizures in most patients can be adequately controlled with first-line antiseizure medication (ASM), approximately 25 % of patients respond poorly to first-line ASM. In addition, an accurate method for predicting first-line medication responsiveness is lacking. We used the quantitative electroencephalogram (QEEG) features of patients with CAE along with machine learning to predict the therapeutic effects of valproic acid in this population. We enrolled 25 patients with CAE from multiple medical centers. Twelve patients who required additional medication for seizure control or who were shifted to another ASM and 13 patients who achieved seizure freedom with valproic acid within 6 months served as the nonresponder and responder groups. Using machine learning, we analyzed the interictal background EEG data without epileptiform discharge before ASM. The following features were analyzed: EEG frequency bands, Hjorth parameters, detrended fluctuation analysis, Higuchi fractal dimension, Lempel-Ziv complexity (LZC), Petrosian fractal dimension, and sample entropy (SE). We applied leave-one-out cross-validation with support vector machine, K-nearest neighbor (KNN), random forest, decision tree, Ada boost, and extreme gradient boosting, and we tested the performance of these models. The responders had significantly higher alpha band power and lower delta band power than the nonresponders. The Hjorth mobility, LZC, and SE values in the temporal, parietal, and occipital lobes were higher in the responders than in the nonresponders. Hjorth complexity was higher in the nonresponders than in the responders in almost all the brain regions, except for the leads FP1 and FP2. Using KNN classification with theta band power in the temporal lobe yielded optimal performance, with sensitivity of 92.31 %, specificity of 76.92 %, accuracy of 84.62 %, and area under the curve of 88.46 %.We used various EEG features along with machine learning to accurately predict whether patients with CAE would respond to valproic acid. Our method could provide valuable assistance for pediatric neurologists in selecting suitable ASM.

Connectivity Disturbances in Self-Limited Epilepsy with Centrotemporal Spikes: A Partial Directed Coherence Analysis of Electroencephalogram.

Although the remission of self-limited epilepsy with centrotemporal spikes (SeLECTS) usually occurs by adolescence, deficits in cognition and behavior are not uncommon. Several functional magnetic resonance imaging (fMRI) studies have revealed connectivity disturbances in patients with SeLECTS associated with cognitive impairment. However, the disadvantages of fMRI are expensive, time-consuming, and motion sensitive. In the current study, we used a partial directed coherence (PDC) method to analyze electroencephalogram (EEG) for exploring brain connectivity in patients with SeLECTS. This study enrolled 38 participants (19 patients with SeLECTS and 19 healthy controls) for PDC analysis. Our results demonstrated that the controls had significantly higher PDC inflow connectivity in the F7, T3, FP1, and F8 channels than patients with SeLECTS. By contrast, the patients with SeLECTS demonstrated significantly higher PDC inflow connectivity than did the controls in the T5, Pz, and P4 channels. We also compared the PDC connectivity in different Brodmann areas between the patients with SeLECTS and the controls. The results revealed that the inflow connectivity in the BA9_46_L area was significantly higher in the controls than in the patients with SeLECTS, whereas the inflow connectivity in the MIF_L area 4 was significantly higher in the patients with SeLECTS than in the controls. Our proposed approach of combining EEG with PDC provides a convenient and useful tool for investigating functional connectivity in patients with SeLECTS. This approach is time-saving and inexpensive compared with fMRI, but it achieves similar results to fMRI.

Advanced Detection Method for Dengue NS1 Protein Using Ultrasensitive ELISA with Thio-NAD Cycling.

Dengue fever, a mosquito-borne disease in tropical and subtropical climates caused by the dengue virus (DENV), has become a major social and economic burden in recent years. However, current primary detection methods are inadequate for early diagnosis of DENV because they are either time-consuming, expensive, or require training. Non-structural protein 1 (NS1) is secreted during DENV infection and is thus considered a suitable biomarker for the development of an early detection method. In the present study, we developed a detection method for the NS1 protein based on a previously reported thio-NAD cycling ELISA (i.e., ultrasensitive ELISA) and successfully achieved a LOD of 1.152 pg/mL. The clinical diagnosis potential of the detection system was also evaluated by using 85 patient specimens, inclusive of 60 DENV-positive and 25 DENV-negative specimens confirmed by the NAAT method. The results revealed 98.3% (59/60) sensitivity and 100% (25/25) specificity, which was in almost perfect agreement with the NAAT data with a kappa coefficient of 0.972. The present study demonstrates the diagnostic potential of using an ultrasensitive ELISA as a low-cost, easy-to-use method for the detection of DENV compared with NAAT and could be of great benefit in low-income countries.

Heat shock protein 70 protects the lungs from hyperoxic injury in a neonatal rat model of bronchopulmonary dysplasia.

Hyperoxia plays a significant role in the pathogenesis of lung injury, such as bronchopulmonary dysplasia (BPD), in premature infants or newborns. BPD management aims to minimize further injury, provide an optimal environment to support growth and recovery. In clinic neonatal care, we need a new therapy for BPD. Heat shock protein 70 (Hsp70) inhibit cell apoptosis and promote cell repair allowing cells to survive lethal injury. We hypothesized that Hsp70 could be used to prevent hyperoxia related BPD in the neonatal rat model through its anti-apoptotic and anti-inflammatory effects. In this study, we explored the effect of Hsp70 on hyperoxia-induced lung injury using neonatal rats. Neonatal Wistar rats were delivered naturally at full term of gestation and were then pooled and randomly assigned to several groups to receive heat stimulation (41°C for 20 min) or room temperature conditions. The Hsp70 group received recombinant Hsp70 intraperitoneally (200 µg/kg, daily). All newborn rats were placed under hyperoxic conditions (85% oxygen) for 21 days. Survival rates in both heat-hyperoxia and Hsp70-hyperoxia groups were higher than those in the hyperoxia group (p < 0.05). Both endogenous and exogenous Hsp70 could reduce early apoptosis of alveolar cells under hyperoxia. Additionally, there were less macrophage infiltration in the lung of the Hsp70 groups (p < 0.05). Heat stress, heat shock proteins, and exogenous recombinant Hsp70 significantly increased the survival rate and reduced pathological hyperoxia induced lung injuries in the development of BPD. These results suggest that treating hyperoxia-induced lung injury with Hsp70 may reduce the risk of developing BPD.

Objective diagnosis of ADHD through movement analysis by using a smart chair with piezoelectric material.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in schoolchildren. ADHD diagnoses are generally made based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The diagnosis is made clinically based on observation and information provided by parents and teachers, which is highly subjective and can lead to disparate results. Considering that hyperactivity is one of the main symptoms of ADHD, the inaccuracy of ADHD diagnosis based on subjective criteria necessitates the identification of a method to objectively diagnose ADHD. METHODS: In this study, a medical chair containing a piezoelectric material was applied to objectively analyze movements of patients with ADHD, which were compared with those of patients without ADHD. This study enrolled 62 patients-31 patients with ADHD and 31 patients without ADHD. During the clinical evaluation, participants' movements were recorded by the piezoelectric material for analysis. The variance, zero-crossing rate, and high energy rate of movements were subsequently analyzed. RESULTS: The results revealed that the variance, zero-crossing rate, and high energy rate were significantly higher in patients with ADHD than in those without ADHD. Classification performance was excellent in both groups, with the area under the curve as high as 98.00%. CONCLUSION: Our findings suggest that the use of a smart chair equipped with piezoelectric material is an objective and potentially useful method for supporting the diagnosis of ADHD.

Prediction of seizure recurrence using electroencephalogram analysis with multiscale deep neural networks before withdrawal of antiepileptic drugs.

BACKGROUND: The decision to continue or discontinue antiepileptic drug (AED) treatment in patients who are seizure free for a prolonged time is critical. Studies have used certain risk factors or electroencephalogram (EEG) findings to predict seizure recurrence after the withdrawal of AEDs. However, applicable biomarkers to guide the withdrawal of AEDs are lacking. METHODS: In this study, we used EEG analysis based on multiscale deep neural networks (MSDNN) to establish a method for predicting seizure recurrence after the withdrawal of AEDs. A total of 60 patients with epilepsy were divided into two groups (30 in the recurrence group and 30 in the non-recurrence group). All patients were seizure free for at least 2 years. Before AED withdrawal, an EEG was performed for each patient, which showed no epileptiform discharges. These EEG recordings were classified using MSDNN. RESULTS: We found that the performance indices of classification between recurrence and non-recurrence groups had a mean sensitivity, mean specificity, mean accuracy, and mean area under the receiver operating characteristic curve of 74.23%, 75.83%, 74.66%, and 82.66%, respectively. CONCLUSION: Our proposed method is a promising tool to help physicians to predict seizure recurrence after AED withdrawal among seizure-free patients.

Early and Objective Evaluation of the Therapeutic Effects of ADHD Medication through Movement Analysis Using Video Recording Pixel Subtraction.

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5−7% of school-age children. ADHD is usually marked by an ongoing pattern of inattention or hyperactivity−impulsivity, leading to functioning or developmental problems. A common ADHD assessment tool is the Swanson, Nolan, and Pelham (SNAP) questionnaire. However, such scales provide only a subjective perspective, and most of them are used to evaluate therapeutic effects at least 3−12 months after medication initiation. Therefore, we employed an objective assessment method to provide more accurate evaluations of therapeutic effects in 25 children with ADHD (23 boys and 2 girls). To evaluate the participants' improvement and treatment's effectiveness, the pixel subtraction technique was used in video analysis. We compared the efficacy of 1-month Ritalin or Concerta treatment by evaluating the movement in each video within 3 h of medication administration. The movement value was defined as the result of a calculation when using the pixel subtraction technique. Based on behavior observation and SNAP scores, both parent- and teacher-reported scores decreased after 1 month of medication (reduction rates: 19.61% and 16.38%, respectively). Specifically, the parent-reported hyperactivity subscale and teacher-reported oppositional subscale decreased more significantly. By contrast, the reduction rate was 39.27%, as evaluated using the average movement value (AMV). Considering symptomatic improvement as a >25% reduction in scores, the result revealed that the AMV decreased in 18 patients (72%) compared with only 44% and 56% of patients based on parent- and teacher-reported hyperactivity subscale scores. In conclusion, the pixel subtraction method can serve as an objective and reliable evaluation of the therapeutic effects of ADHD medication in the early stage.

Using a neonatal rat model to explore the therapeutic potential of coenzyme Q10 in prematurity under hyperoxia.

Hyperoxia, is often used in preterm supportive care, leading to high oxygen exposure in neonates. Coenzyme Q10 (CoQ10) is a free radical scavenger that has been studied in older children but never be investigated for its role in preterm care. We hypothesize that the administration of exogenous CoQ10 would raise serum concentrations of CoQ10 and mitigate the adverse effects of hyperoxia on the organs by reducing oxygen-free radicals and inflammation. The aim of this study was to evaluate the effects of oxidative stress, inflammatory response, and survival in neonatal rats after CoQ10 treatment. Neonatal rats delivered from four pregnant Wistar rats were randomly divided into four groups: (a) control, (b) CoQ10, (c) hyperoxia (O2 group), and (d) treatment (CoQ10 + O2 ) groups. The dose of CoQ10 injected was 30 mg/kg. The CoQ9, CoQ10, cytokines, oxidative stress, and antioxidant enzyme activity were measured. Tissue samples were histologically examined and mortality was monitored for 16 days. The level of CoQ9 significantly increased in the liver, kidney, and plasma, while the level of CoQ10 significantly increased in most organ tissues in the CoQ10 + O2 group. Additionally, CoQ10 decrease oxidative stress in the liver, increase antioxidant enzyme activity in the heart, kidney, and brain, and reverse an inclined level of hematopoietic growth factors. However, CoQ10 had no effect on inflammation, organ damage, or mortality. Therefore, the use of CoQ10 in potential adjuvant therapy for neonatal hyperoxia requires further research.

Evaluating Therapeutic Effects of ADHD Medication Objectively by Movement Quantification with a Video-Based Skeleton Analysis.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children. Several scales are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In the present study, we proposed an objective and automatic approach for evaluating the therapeutic effects of medication in patients with (ADHD). The approach involved using movement quantification of patients' skeletons detected automatically with OpenPose in outpatient videos. Eleven skeleton parameter series were calculated from the detected skeleton sequence, and the corresponding 33 features were extracted using autocorrelation and variance analysis. This study enrolled 25 patients with ADHD. The outpatient videos were recorded before and after medication treatment. Statistical analysis indicated that four features corresponding to the first autocorrelation coefficients of the original series of four skeleton parameters and 11 features each corresponding to the first autocorrelation coefficients of the differenced series and the averaged variances of the original series of 11 skeleton parameters significantly decreased after the use of methylphenidate, an ADHD medication. The results revealed that the proposed approach can support physicians as an objective and automatic tool for evaluating the therapeutic effects of medication on patients with ADHD.

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia.

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD). Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay. Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.

Curcumin induces apoptosis by inhibiting BCAT1 expression and mTOR signaling in cytarabine­resistant myeloid leukemia cells.

Cytarabine is a key chemotherapy drug for treating leukemia; however, chemotherapy­induced multidrug resistance is a major cause of therapy failure or tumor recurrence. Current medical treatment strategies still cannot address the issue of multidrug resistance phenotypes in the treatment of leukemia. Curcumin counteracts tumor development by inducing apoptosis in cytarabine­resistant acute myeloid leukemia cells. Branched­chain amino acid transaminase 1 (BCAT1), an aminotransferase enzyme, acts on branched­chain amino acids. Moreover, the aberrant expression of BCAT1 has been observed in numerous cancer cells, and BCAT1 serves a critical role in the progression of myeloid leukemia. BCAT1 can interfere with cancer cell proliferation by regulating mTOR­mediated mitochondrial biogenesis and function. The present study aimed to investigate whether curcumin induces apoptosis by regulating BCAT1 expression and mTOR signaling in cytarabine­resistant myeloid leukemia cells. Four leukemia cell lines and three primary myeloid leukemia cells were treated with curcumin, and the expression and activity of BCAT1 and mTOR were investigated by reverse transcription­quantitative PCR, western blotting and α­KG quantification assay. The results demonstrated that curcumin inhibited BCAT1 expression in Kasumi­1, KG­1, HL60, cytarabine­resistant HL60, and cytarabine­resistant primary myeloid leukemia cells. Notably, tetrahydrocurcumin, a major metabolite of curcumin, and cytarabine had no inhibitory effect on BCAT1 expression. Furthermore, BCAT1 and mTOR signaling may modulate each other in cytarabine­resistant HL60 cells. The present results indicated that curcumin may induce apoptosis by inhibiting the BCAT1 and mTOR pathways. Thus, understanding the mechanism underlying curcumin­induced apoptosis in cytarabine­resistant cells can support the development of novel drugs for leukemia.

Determination of Antiepileptic Drugs Withdrawal Through EEG Hjorth Parameter Analysis.

The decision to continue or to stop antiepileptic drug (AED) treatment in patients with prolonged seizure remission is a critical issue. Previous studies have used certain risk factors or electroencephalogram (EEG) findings to predict seizure recurrence after the withdrawal of AEDs. However, validated biomarkers to guide the withdrawal of AEDs are lacking. In this study, we used quantitative EEG analysis to establish a method for predicting seizure recurrence after the withdrawal of AEDs. A total of 34 patients with epilepsy were divided into two groups, 17 patients in the recurrence group and the other 17 patients in the nonrecurrence group. All patients were seizure free for at least two years. Before AED withdrawal, an EEG was performed for each patient that showed no epileptiform discharges. These EEG recordings were classified using Hjorth parameter-based EEG features. We found that the Hjorth complexity values were higher in patients in the recurrence group than in the nonrecurrence group. The extreme gradient boosting classification method achieved the highest performance in terms of accuracy, area under the curve, sensitivity, and specificity (84.76%, 88.77%, 89.67%, and 80.47%, respectively). Our proposed method is a promising tool to help physicians determine AED withdrawal for seizure-free patients.

Increased Temporal Lobe Beta Activity in Boys With Attention-Deficit Hyperactivity Disorder by LORETA Analysis.

Aim: Attention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that affects 6.1 million US children. The mechanism of ADHD is currently unclear. Differences in ADHD presentations between boys and girls are well-established. In the present study, we used quantitative electroencephalography (EEG) to investigate the brain area and EEG bands of boys with ADHD. Methods: This study enrolled 40 boys with ADHD and 40 age-matched controls without ADHD. Low-resolution electromagnetic tomography (LORETA) and instantaneous frequency were used to analyze EEG data to reveal the mechanisms underlying ADHD in boys. Results: We found that the instantaneous frequencies in the T3 and T4 EEG channels in boys with ADHD were significantly higher than those in the controls. The beta band showed significant difference in current density between the ADHD and control groups. In the entire brain area, the bilateral inferior and middle temporal gyrus exhibited the most significant difference between the ADHD and control groups in the EEG beta band. Connectivity analysis revealed an increase in connectivity between the left middle frontal gyrus and fusiform gyrus of the temporal lobe in boys with ADHD. Conclusions: LORETA is a promising tool for analyzing EEG signals and can be used to investigate the mechanism of ADHD. Our results reveal that the inferior temporal gyrus, middle temporal gyrus, and fusiform gyrus of the temporal lobe are potentially involved in the pathogenesis of ADHD in boys. In comparison with other imaging methods, such as magnetic resonance imaging, EEG is easy to perform, fast, and low cost. Our study presents a new approach for investigating the pathogenesis of ADHD in boys.

Two hits to the renin-angiotensin system may play a key role in severe COVID-19.

The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID-19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID-19 who have comorbidities and may serve as a therapeutic target for COVID-19 treatment.

Extracellular heat shock protein HSC70 protects against lipopolysaccharide-induced hypertrophic responses in rat cardiomyocytes.

We have recently shown that exogenous administration of extracellular heat shock protein HSC70, a previously recognized intracellular chaperone protein, can protect against LPS-induced cardiac dysfunction through anti-inflammatory actions. However, whether it can also exert anti-hypertrophic effect is unknown. The present study was aimed to investigate the efficacy of HSC70 against cardiac hypertrophy and its underlying molecular mechanisms. Cardiomyocytes were isolated from the cardiac ventricles of neonatal Wistar rats and LPS (1 µg/mL) was used to induce the hypertrophic responses. We found that HSC70 (0.1, 1 and 5 µg/mL) pretreatment attenuated LPS-induced cardiomyocyte hypertrophy dose-dependently. In addition, HSC70 mitigated LPS-induced inflammatory mediators including TNF-α, IL-6, NO, iNOS and COX-2, with down-regulated protein expression of MMP-2 and MMP-9. Moreover, HSC70 repressed LPS-induced signaling of MAPK and Akt. Finally, HSC70 inhibited NF-κB subunit p65, and the DNA binding activity of NF-κB. Taken together, these findings suggest that in vitro HSC70 can exert anti-hypertrophic effects through inhibition of pro-inflammatory mediators, which are potential mediated by the down-regulation of MAPK, Akt and NF-κB signaling pathways. In conclusion, extracellular HSC70 may be a novel pharmacologic strategy in the management of cardiac hypertrophy.

Vagus nerve stimulation for patients with refractory epilepsy: Demographic features and neuropsychological outcomes of the VNS Taiwan child neurology society database.

OBJECTIVES: Vagus nerve stimulation (VNS) is an established adjunctive therapy for medically refractory epilepsy, which is commonly associated with cognitive impairment, especially in children in whom seizures may disrupt development that is essential to their intellectual and social maturation. The Taiwan Child Neurology Society intends to expand the use of VNS by reporting the experience in a nationwide population, displaying the demographic features and neuropsychological outcomes of VNS. METHODS: The enrollment included 105 patients of all ages and seizure types who underwent VNS implantation for refractory epilepsy. Basic data included etiology, past history, seizure phenotypes, and epileptiform syndromes. For efficacy analysis, seizure frequencies were recorded at the baseline and at 3, 12, 24, and 36 months after VNS implantation. For psychological assessment, intelligence quotients (IQ) and Parental Stress Index (PSI) scores were evaluated before and after the VNS. RESULTS: During the study period, 95 patients with VNS had followed seizure frequency, IQ and PSI recording. After implantation, there was a decreased frequency at 3 (P < .001), 12 (P < .001), 24 (P = .010), and 36 (P < .01) months. After implantation, the reduction rate (0-50%) of seizure frequency ranged around 26.1-36.1% from 3 to 36 months. For PSI scores, the VNS significantly improved the PSI- total score (P = .001) and PSI-parent domain (P = .001) but not the PSI-children domain (P = .052). No significant improvement in the IQ test performance was observed. CONCLUSIONS: This prospective nationwide database of VNS in Taiwan indicates long-term efficacy of VNS therapy, which has achieved a trend of seizure frequency reduction over a period of up to 36 months. It also shows the trend of decreased parental stress after VNS implantation.

EEG autoregressive modeling analysis: A diagnostic tool for patients with epilepsy without epileptiform discharges.

OBJECTIVE: Numerous types of nonepileptic paroxysmal events, such as syncopes and psychogenic nonepileptic seizures, may imitate epileptic seizures and lead to diagnostic difficulty. Such misdiagnoses may lead to inappropriate treatment in patients that can considerably affect their lives. Electroencephalogram (EEG) is a commonly used tool in assisting diagnosis of epilepsy. Although the appearance of epileptiform discharges (EDs) in EEG recordings is specific for epilepsy diagnosis, only 25%-56% of patients with epilepsy show EDs in their first EEG examination. METHODS: In this study, we developed an autoregressive (AR) model prediction error-based EEG classification method to distinguish EEG signals between controls and patients with epilepsy without EDs. Twenty-three patients with generalized epilepsy without EDs in their EEG recordings and 23 age-matched controls were enrolled. Their EEG recordings were classified using AR model prediction error-based EEG features. RESULTS: Among different classification methods, XGBoost achieved the highest performance in terms of accuracy and true positive rate. The results showed that the accuracy, area under the curve, true positive rate, and true negative rate were 85.17%, 87.54%, 89.98%, and 81.81%, respectively. CONCLUSIONS: Our proposed method can help neurologists in the early diagnosis of epilepsy in patients without EDs and might help in differentiating between nonepileptic paroxysmal events and epilepsy. SIGNIFICANCE: EEG AR model prediction errors could be used as an alternative diagnostic marker of epilepsy.

Quantitative electroencephalogram analysis of frontal cortex functional changes in patients with migraine.

The functional abnormality of brain areas accounting for the migraine remains to be elucidated. Most related studies have used functional magnetic resonance imaging to investigate brain areas involved in migraine. However, the results are heterogeneous. In this study, we used a convenient tool to explore the brain regions involved in migraine. In this study, 40 children with migraine and 40 sex- and age-matched health controls were enrolled, and electroencephalogram was used to explore the functional abnormal areas of migraine through electroencephalogram bands and low-resolution electromagnetic tomography analysis. The results revealed that spectrum edge frequency 50 in all electroencephalogram channels in patients with migraine were lower than those in controls. Significant differences were discovered over frontal areas. In addition, significantly higher current density over the frontopolar prefrontal cortex and orbitofrontal cortex and higher connectivity over the left prefrontal cortex were observed in patients with migraine. We suggest that functional disturbance of the prefrontal cortex may play a potential role in children with migraine, and that low-resolution electromagnetic tomography is a reliable and convenient tool for studying the functional disturbance of migraine.

M2-like polarization of THP-1 monocyte-derived macrophages under chronic iron overload.

Macrophages are characterized by phenotypical and functional heterogeneity. In different microenvironments, macrophages can polarize into two types: classically activated macrophages (M1) or alternatively activated macrophages (M2). M1 macrophages are a well-known bacteriostatic macrophage, and conversely, M2 macrophages may play an important role in tumor growth and tissue remodeling. M1 macrophages have been reported to have high intracellular iron stores, while M2 macrophages contain lower intracellular iron. It has been well-described that disturbances of iron homeostasis are associated with altered immune function. Thus, it is important to investigate if chronic iron overload is capable of polarizing macrophages. Human monocytic leukemia THP-1 cells were maintained in culture medium that contained 100 µM ferrous sulfate heptahydrate (FeSO4) (I-THP-1) and differentiated into THP-1-derived macrophages (I-TDMs) by induction with phorbol 12-myristate 13-acetate (PMA). We characterized that I-TDMs not only enhanced the surface expression of CD163 and CD206 but also increased arginase and decreased iNOS protein expression. I-TDMs enhanced pSTAT6 expression and decreased pSTAT1 and NF-κB expressions. Furthermore, the gene expression profile of I-TDMs was comparable with M2 macrophages by performing human oligonucleotide DNA microarray analysis. Finally, functional assays demonstrated I-TDMs secreted higher levels of IL-10 but not M1 cytokines. Additionally, the conditional medium of I-TDMs had enhanced migration and increased invasion of A375 melanoma cells which was similar to the characteristics of tumor-associated macrophages. Taken together, we demonstrated that THP-1-derived macrophages polarized to a phenotype of M2-like characteristics when subjected to chronic iron overload.