Publications by authors named "Rei-Cheng Yang"

109 Publications

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

Front Pediatr 2021 26;9:616452. Epub 2021 May 26.

Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.

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). 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. 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 ( = 0.47) and Day 28 of life ( = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.
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http://dx.doi.org/10.3389/fped.2021.616452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187579PMC
May 2021

Curcumin induces apoptosis by inhibiting BCAT1 expression and mTOR signaling in cytarabine‑resistant myeloid leukemia cells.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan, R.O.C.

Cytarabine is a key chemotherapy drug for treating leukemia; however, chemotherapy‑induced 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 cytarabine‑resistant acute myeloid leukemia cells. Branched‑chain amino acid transaminase 1 (BCAT1), an aminotransferase enzyme, acts on branched‑chain 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 mTOR‑mediated mitochondrial biogenesis and function. The present study aimed to investigate whether curcumin induces apoptosis by regulating BCAT1 expression and mTOR signaling in cytarabine‑resistant 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 transcription‑quantitative PCR, western blotting and α‑KG quantification assay. The results demonstrated that curcumin inhibited BCAT1 expression in Kasumi‑1, KG‑1, HL60, cytarabine‑resistant HL60, and cytarabine‑resistant 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 cytarabine‑resistant HL60 cells. The present results indicated that curcumin may induce apoptosis by inhibiting the BCAT1 and mTOR pathways. Thus, understanding the mechanism underlying curcumin‑induced apoptosis in cytarabine‑resistant cells can support the development of novel drugs for leukemia.
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http://dx.doi.org/10.3892/mmr.2021.12204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201441PMC
August 2021

Determination of Antiepileptic Drugs Withdrawal Through EEG Hjorth Parameter Analysis.

Int J Neural Syst 2020 Nov 19;30(11):2050036. Epub 2020 Aug 19.

Department of Pediatrics, School of Medicine, College of Medicine, Departments of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Kaohsiung 80708, Taiwan.

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.
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http://dx.doi.org/10.1142/S0129065720500367DOI Listing
November 2020

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

Front Behav Neurosci 2020 30;14:85. Epub 2020 Jun 30.

Departments of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fnbeh.2020.00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340165PMC
June 2020

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

Clin Neurophysiol 2020 08 8;131(8):1902-1908. Epub 2020 Jun 8.

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC; Departments of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan, ROC. Electronic address:

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.
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http://dx.doi.org/10.1016/j.clinph.2020.04.172DOI Listing
August 2020

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

Epilepsy Behav 2020 10 10;111:107186. Epub 2020 Jun 10.

Vagus Nerve Stimulation Study Group of Taiwan Child Neurology Society.

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.
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http://dx.doi.org/10.1016/j.yebeh.2020.107186DOI Listing
October 2020

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

Biomed Pharmacother 2020 Aug 7;128:110370. Epub 2020 Jun 7.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopha.2020.110370DOI Listing
August 2020

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

Kaohsiung J Med Sci 2020 Jun 3;36(6):389-392. Epub 2020 Jun 3.

Department of Medicine, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1002/kjm2.12237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300771PMC
June 2020

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

Kaohsiung J Med Sci 2020 Jul 7;36(7):543-551. Epub 2020 Apr 7.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC.

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.
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http://dx.doi.org/10.1002/kjm2.12213DOI Listing
July 2020

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

Ann Hematol 2020 Mar 1;99(3):431-441. Epub 2020 Feb 1.

Institute of Biomedical Sciences, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City, 402, Taiwan (Republic of China).

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 (FeSO) (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.
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http://dx.doi.org/10.1007/s00277-020-03916-8DOI Listing
March 2020

Systemic hypertension followed by insidious stroke in a 12-year-old boy with childhood neurofibromatosis type 1 presenting with renal and cerebral artery vasculopathy.

Turk J Pediatr 2019 ;61(4):629-634

Departments of Medical Imaging, Changhua Christian Children's Hospital, Changhua.

Lee ML, Chang TM, Yang RC, Yang AD, Chen M. Systemic hypertension followed by insidious stroke in a 12-year-old boy with childhood neurofibromatosis type 1 presenting with renal and cerebral artery vasculopathy. Turk J Pediatr 2019; 61: 629-634. Neurofibromatosis type 1 (NF1)-associated vasculopathy is usually diagnosed decades after the clinical diagnosis of NF1. Childhood NF1-associated renal artery vasculopathy or moyamoya-like brain vasculopathy could be clinically silent for a long time. We report a 12-year-old boy who had systemic hypertension found incidentally at a routine check-up. Physical examination showed caféau- lait spots and strong radial pulses. Abdominal computerized tomography angiography showed severe right ostial renal artery stenosis. Genomic study showed a heterozygous mutation c.5902C > T (p.R1968*) and two heterozygous single nucleotide polymorphisms (NCBI: SNP rs18011052 and rs2905876) of NF1 gene. After endovascular revascularization for renovascular hypertension caused by renal artery stenosis, including percutaneous transluminal renal angioplasty and stent implantation, blood pressure dropped effectively from 205/143 mmHg to 130/90 mmHg. Supine renin level dropped from 87.2 pg/ mL to 47.9 pg/mL. Unfortunately, right hemiplegia, transient visual loss with blind spots (scotomas), and clumsiness of extremities emerged insidiously 3.5 months later. Brain magnetic resonance imaging and magnetic resonance angiography showed ischemic infarction involving the watershed area of the anterior and middle cerebral arteries, indicating presence of moyamoya-like brain vasculopathy. A dilemma is that a significant decrease of blood pressure after endovascular revascularization for renal artery stenosis may have potentially unmask the moyamoya-like brain vasculopathy in this patient. Vasculopathy could be heralding childhood NF1 in the young patients without full-fledged clinical features. Endovascular revascularization for renal artery stenosis could be a double-edge sword in childhood NF1 presenting with concomitant renal and cerebral artery vasculopathy.
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http://dx.doi.org/10.24953/turkjped.2019.04.026DOI Listing
May 2020

Delay Maturation in Occipital Lobe in Girls With Inattention Subtype of Attention-Deficit Hyperactivity Disorder.

Clin EEG Neurosci 2020 Sep 14;51(5):325-330. Epub 2020 Jan 14.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. Differences in the presentations of ADHD between boys and girls have been well established. Three subtypes of ADHD exist. In addition to sex difference, different mechanisms may underlie different subtypes. The present study enrolled 30 girls with the inattentive subtype of ADHD and 30 age-matched controls. Low-resolution electromagnetic tomography (LORETA) and instantaneous frequency were used to analyze electroencephalography (EEG) for investigating the brain area and EEG bands involved in girls with inattentive ADHD. We found that the instantaneous frequencies in all EEG channels in girls with ADHD were lower than those in controls. Alpha 2 was the only EEG band that showed significant difference in current density between the ADHD and control groups ( = .0014). In the entire brain area, the posterior cingulate cortex, cingulate gyrus, and precuneus demonstrated the most significant difference between the ADHD and control groups. Our results suggest that brain maturation delay in the posterior areas might result in the inattention subtype of ADHD. In addition, posterior cingulate cortex, cingulate gyrus, and precuneus may play a critical role in the pathogenesis of ADHD. Our study provides a new approach method and possible mechanism of girls with inattentive subtype ADHD.
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http://dx.doi.org/10.1177/1550059419899328DOI Listing
September 2020

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model.

Kaohsiung J Med Sci 2020 Mar 6;36(3):186-195. Epub 2020 Jan 6.

Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan.

Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA-specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL-13, RANTES, MIP-1β and increased IFN-γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA-induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.
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http://dx.doi.org/10.1002/kjm2.12163DOI Listing
March 2020

Impairment of mitochondrial unfolded protein response contribute to resistance declination of H O -induced injury in senescent MRC-5 cell model.

Kaohsiung J Med Sci 2020 Feb 17;36(2):89-97. Epub 2019 Nov 17.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

Accumulation of oxidative proteins within mitochondria leads to loss of mitochondrial function, which may lead to age-related degenerative diseases. Mitochondrial antioxidant defense capacity reflects the expression of mitochondrial unfolded protein response (mtUPR)-related proteins. Senescent cells are considered to be less resistant to cellular stress stimuli than exponentially growing cells. In this study, we aimed to investigate the ability of mitochondrial stress response in senescent cells to cope with the accumulation of mitochondrial unfolded proteins induced by hydrogen peroxide (H O ) and to understand the relevant molecular mechanisms. We report here that senescence-associated β-galactosidase (SA-β-gal) and senescence marker protein-30 (SMP-30), commonly used replicative senescence biomarkers, changed remarkably between population doubling (PD) 25 (exponentially growing cells) and PD50 (senescent cells) of MRC-5 fibroblasts. Mitochondrial unfolded proteins were significantly accumulated in H O -treated senescent cells, whereas mtUPR-related molecular chaperones (heat shock protein Hsp60 and Hsp10) and proteases (caseinolytic Clp protease) were not concomitantly elevated in senescent cells. In addition, decreased expression of stromal interacting molecule 1-Orai1-mediated store-operated Ca entry following an declined intracellular calcium level after 2 mM calcium treatment together with H O addition, implying impairment of calcium influx in senescent MRC-5 during H O -induced injury. These findings suggest that senescent fibroblasts expressed higher vulnerability to H O -induced injury involving the imbalance of calcium homeostasis and impaired mitochondrial nuclear communication. This may provide useful information for the future development of therapeutic agents to prevent the adverse effects of aging on cells and the potential for treatment of proteinopathies in the elderly.
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http://dx.doi.org/10.1002/kjm2.12146DOI Listing
February 2020

A New Method of Diagnosing Attention-Deficit Hyperactivity Disorder in Male Patients by Quantitative EEG Analysis.

Clin EEG Neurosci 2019 Sep 19;50(5):339-347. Epub 2019 Jul 19.

4 Departments of Pediatrics, Kaohsiung Medical University, Kaohsiung.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood. Diagnosis of ADHD is based on core symptoms and checklists. However, these are both subjective, which can lead to the problems of overdiagnosis and underdiagnosis. Elevated theta/beta ratio (TBR) of EEG band has been approved by the US Food and Drug Administration as a tool to assist in the diagnosis of ADHD. However, several recent studies have demonstrated that there are no significant differences in TBR between people with and without ADHD. In this study, we attempted to develop a new method for differentiating between male with and without ADHD by analyzing EEG features. Thirty boys with ADHD combined type (aged 8 years 5 months ± 1 year 11 months) and 30 age-matched controls (aged 8 years 5 months ± 1 year 8 months) were enrolled in this study. A classification analysis-based approach comprising training and classification phases was developed for classifying each subject's EEG features as ADHD or non-ADHD. Eight crucial feature descriptors were selected and ranked based on the test. Compared with TBR in our study, the developed method had a higher area under the curve (87.78%), sensitivity (80.0%), and specificity (80.0%). Our method is more precise than using TBR in the diagnosis of ADHD. This newly developed method is a useful tool in identifying patients with ADHD and might reduce the possibility of overdiagnosis and underdiagnosis.
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http://dx.doi.org/10.1177/1550059419859164DOI Listing
September 2019

Adhesive pyramidal thorn patches provide pain relief to athletes.

Kaohsiung J Med Sci 2019 Apr 19;35(4):230-237. Epub 2019 Mar 19.

Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.

Pain in athletes is ideally treated without systemic medicine. Therefore, complementary and alternative medicine, including patch treatments, is often used. The physiologic mechanisms of pain relief produced by patch treatment, however, are not well elucidated. In the present study, we introduce a pyramidal thorn (PT) patch that we developed, demonstrate the effects of this PT patch for the treatment of various types of pain in 300 subjects, and suggest a physiologic mechanism for the pain relief effects. One treatment with the PT patch effectively relieved pain in almost half the subjects evaluated. Except for pain generated deeply under the skin, such as low-back pain, pain was eliminated within four treatments with the PT patch in almost all of the subjects. Interestingly, the pain-sensing region moved along the nerve fibers after each trial. Further, patches without PT also provided some pain relief. We considered that this effect was due to hair deflection on the skin; that is, adhesion of the PT patch activates Merkel cells directly as well as Merkel cell-neurite complexes around the hair follicles by deflecting the hair follicles, whereas adhesion of a patch without PT only activates the Merkel cell-neurite complexes. In any case, patch adhesion stimulates Aβ fibers to alleviate pain. Finally, we found that the pain threshold is increased by electric stimulation, suggesting that the gentle adhesion of a PT patch would be more effective. To our knowledge, this is the first study to demonstrate physiologically the validity of an adherent patch for pain relief.
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http://dx.doi.org/10.1002/kjm2.12044DOI Listing
April 2019

Alternative Diagnosis of Epilepsy in Children Without Epileptiform Discharges Using Deep Convolutional Neural Networks.

Int J Neural Syst 2020 May 8;30(5):1850060. Epub 2019 Jan 8.

Department of Computer and Communication, National Pingtung University, 51 Min Sheng East Road, Pingtung, 90003, Taiwan.

Numerous nonepileptic paroxysmal events, such as syncope and psychogenic nonepileptic seizures, may imitate seizures and impede diagnosis. Misdiagnosis can lead to mistreatment, affecting patients' lives considerably. Electroencephalography is commonly used for diagnosing epilepsy. Although on electroencephalograms (EEGs), epileptiform discharges (ED) specifically indicate epilepsy, only approximately 50% of patients with epilepsy have ED in their first EEG. In this study, we developed a deep convolutional neural network (ConvNet)-based classifier to distinguish EEG between patients with epilepsy without ED and controls. Overall, 25 patients with epilepsy without ED in their EEGs and 25 age-matched patients with Tourette syndrome or syncope were enrolled. Their EEGs were classified using the deep ConvNet. When the EEG data without overlapping were used, the accuracy, sensitivity, and specificity were 65.00%, 48.00%, and 82.00%, respectively. The performance measures improved when the input EEG data were augmented through overlapping. With 95% EEG data overlapping, the accuracy, sensitivity, and specificity increased to 80.00%, 70.00%, and 90.00%, respectively. The proposed method could be regarded as a pilot study to demonstrate a proof of concept of a potential diagnostic value of deep ConvNet in patients with epilepsy without ED. Further studies are needed to assist neurologists in distinguishing nonepileptic paroxysmal events from epilepsy.
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http://dx.doi.org/10.1142/S0129065718500600DOI Listing
May 2020

Entropy-Based Quantitative Electroencephalogram Analysis for Diagnosing Attention-Deficit Hyperactivity Disorder in Girls.

Clin EEG Neurosci 2019 May 29;50(3):172-179. Epub 2018 Nov 29.

5 Departments of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.

Diagnosis of attention-deficit hyperactivity disorder (ADHD) is currently based on core symptoms or checklists; however, the inevitability of practitioner subjectivity leads to over- and underdiagnosis. Although the Federal Drug Administration has approved an elevated theta/beta ratio (TBR) of the electroencephalogram (EEG) band as a tool for assisting ADHD diagnosis, several studies have reported no significant differences of the TBR between ADHD and control subjects. This study detailed the development of a method based on approximate entropy (ApEn) analysis of EEG to compare ADHD and control groups. Differences between ADHD presentation in boys and girls indicate the necessity of separate investigations. This study enrolled 30 girls with ADHD and 30 age-matched controls. The results revealed significantly higher ApEn values in most brain areas in the control group than in the ADHD group. Compared with TBR-related feature descriptors, ApEn-related feature descriptors can produce the higher average true positive rate (0.846), average true negative rate (0.814), average accuracy (0.817), and average area under the receiver operating characteristic curve value (0.862). Therefore, compared with TBR, ApEn possessed the better potential for differentiating between girls with ADHD and controls.
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http://dx.doi.org/10.1177/1550059418814983DOI Listing
May 2019

Novel method using Hjorth mobility analysis for diagnosing attention-deficit hyperactivity disorder in girls.

Brain Dev 2019 Apr 22;41(4):334-340. Epub 2018 Nov 22.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan. Electronic address:

Background: Attention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. Diagnosis of ADHD is based on core symptoms or checklists; however, practitioner subjectivity inevitably results in instances of over- or under-diagnosis. Although an elevated theta/beta ratio (TBR) of the electroencephalography (EEG) band has been approved by the Food and Drug Administration as a factor that may be used in diagnosis of ADHD, several studies have reported no significant differences between the TBR of patients with ADHD and controls.

Purpose: In this study, a method was developed based on Hjorth Mobility (M) analysis of EEG to compare patients with ADHD and controls.

Methods: Differences in the presentations of ADHD between boys and girls are well established; therefore, separate investigations are required. The present study enrolled 30 girls with ADHD and 30 age-matched controls.

Results: The results revealed that the control group had significantly higher Hjorth M values in most brain areas in EEG readings compared with the values for the ADHD group. Compared with TBR, our method revealed a greater number of more significant differences between the girls in the ADHD group and the controls. Moreover, our method can produce the higher average sensitivity (0.796), average specificity (0.796), average accuracy (0.792), and average area under the curve of receiver operating characteristic curve (AUC) value (0.885). Therefore, compared with TBR, Hjorth M possessed the better potential for differentiating between girls with ADHD and controls.

Conclusion: The proposed method was more accurate than the TBR in diagnosing ADHD. Therefore, Hjorth M may be a promising tool for differentiating between children with ADHD and controls.
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http://dx.doi.org/10.1016/j.braindev.2018.11.006DOI Listing
April 2019

Effects of vitamin B-6 supplementation on oxidative stress and inflammatory response in neonatal rats receiving hyperoxia therapy.

J Food Drug Anal 2018 07 2;26(3):1086-1096. Epub 2018 Feb 2.

Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan; Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address:

Hyperoxia is often used in the treatment of neonates. However, protracted use of hyperoxia leads to significant morbidity. The purpose of this study was to evaluate the effects of vitamin B-6 supplementation on oxidative stress and inflammatory responses in neonatal rats undergoing hyperoxia therapy. The study consisted of 2 parts: a survival study and a vitamin B-6 efficacy study for 16 days. Neonatal rats were randomly divided into either the control group, B-6 group (subcutaneously injected with 90 mg/kg/d of pyridoxal 5'-phosphate [PLP]), O group (treated with 85% oxygen), or O + B-6 group (simultaneously treated with 85% oxygen and 90 mg/kg/d PLP). After the survival study was done, the vitamin B-6 efficacy study was performed with duplicate neonatal rats sacrificed on the 3rd, 6th, 9th, and 16th day. Serum inflammatory cytokines, tissue pathology, and malondialdehyde (MDA) levels were measured. In the survival study, the survival rate of neonatal rats in the control, B-6, O, and O + B-6 group on the 16th day were 100%, 100%, 25%, and 62.50%, respectively. The efficacy study showed lung polymorphonuclear granulocyte (PMN) and macrophage infiltration, increased liver hemopoiesis, and higher MDA levels in liver homogenates at days 3 through 16 in the O group. Vitamin B-6 supplementation considerably increased serum inflammatory cytokines in either the 6th or 9th day and decreased liver MDA level before the 6th day. These results indicate that neonatal rats receiving hyperoxia treatment suffered divergent serum inflammatory responses and were in increased liver oxidative stress. Vitamin B-6 supplementation seemed to improve survival rates, change systemic inflammatory response, and decrease liver oxidative stress while neonatal rats were under hyperoxia treatment.
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http://dx.doi.org/10.1016/j.jfda.2018.01.004DOI Listing
July 2018

Cumulative effect of transcranial direct current stimulation in patients with partial refractory epilepsy and its association with phase lag index-A preliminary study.

Epilepsy Behav 2018 07 26;84:142-147. Epub 2018 May 26.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan.

There is an urgent need for alternative treatments for refractory epilepsy. We investigated the effect of two courses of cathodal transcranial direct current stimulation (tDCS) in nine patients with partial refractory epilepsy. A two-course treatment (1 month per course, with six sessions of stimulation per course within the first 2 weeks by 2-mA cathodal tDCS for 20 min) was administered to each patient. After the first course of tDCS, the average seizure frequency had decreased by 37.8 ± 21.9% compared with baseline (p = 0.001). After the second course, the average seizure frequency had decreased by 48.9 ± 31.2% compared with baseline (p = 0.002). Only seven of the nine patients maintained the same state of wakefulness in three electroencephalogram (EEG) recordings. We analyzed the EEG recordings of these seven patients on day 0 immediately posttreatment and on days 4 and 9 in the first course of tDCS. When compared with baseline, no significant change in the number of epileptiform discharges was observed. The day 9 phase lag index (PLI) decreased in five patients with seizure reduction after tDCS but increased in two patients without seizure reduction after tDCS. A significant negative correlation was observed between the day 9 PLI of alpha band and first-course seizure reduction (R = 0.6515) (p = 0.028). The results revealed that tDCS may be considered as an alternative treatment option for patients with refractory epilepsy, and its effect might be cumulative after repeated stimulations and associated with a decrease in PLI.
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http://dx.doi.org/10.1016/j.yebeh.2018.04.017DOI Listing
July 2018

Revascularization of Concurrent Renal and Cerebral Artery Stenosis in a 14-Year-Old Girl with Takayasu Arteritis and Moyamoya Syndrome.

J Korean Med Sci 2018 Mar 5;33(10):e76. Epub 2018 Mar 5.

Department of Medical Imaging, Changhua Christian Hospital, Changhua, Taiwan.

Concurrent involvement of bilateral renal and cerebral arteries, usually incurred as stenosis, is rare in childhood-onset Takayasu arteritis (c-TA). We report the case of a 14-year-old girl, with c-TA, presenting with transient ischemic attack after endovascular revascularization for renal artery stenosis and cerebrovascular stroke after surgical revascularization for cerebral artery stenosis associated with childhood-onset moyamoya syndrome. We deem that decrease of blood pressure by endovascular revascularization and improvement of cerebral perfusion by surgical revascularization may have jeopardized the cerebral deep watershed zone to cerebral ischemia followed by cerebral hyperperfusion syndrome and caused transient ischemic attack and cerebrovascular stroke in our patient. Revascularization could be a double-edge sword for c-TA patients presenting with concomitant renal artery stenosis and cerebral artery stenosis, and should be performed with caution. Quantitative analysis of cerebral blood flow by brain magnetic resonance imaging and angiography should be performed within 48 hours after surgical revascularization in c-TA.
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http://dx.doi.org/10.3346/jkms.2018.33.e76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832941PMC
March 2018

Quantitative EEG findings and response to treatment with antiepileptic medications in children with epilepsy.

Brain Dev 2018 Jan 28;40(1):26-35. Epub 2017 Jul 28.

Departments of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan. Electronic address:

Background: Epilepsy is a common chronic disorder in pediatric neurology. Nowadays, a variety of antiepileptic drugs (AEDs) are available. A scientific method designed to evaluate the effectiveness of AEDs in the early stage of treatment has not been reported.

Purpose: In this study, we try to use quantitative EEG (QEEG) analysis as a biomarker to evaluate therapeutic effectiveness.

Methods: 20 epileptic children were enrolled in this study. Participants were classified as effective if they achieved a reduction in seizure frequency over 50%. Ineffective was defined as a reduction in seizure frequency less than 50%. Eleven participants were placed in the effective group, the remaining 9 participants were placed in the ineffective group. EEG segments before and after 1-3months of antiepileptic drugs start/change were analyzed and compared by QEEG analysis. The follow-up EEG segments after the 2nd examinations were used to test the accuracy of the analytic results.

Results: Six crucial EEG feature descriptors were selected for classifying the effective and ineffective groups. Significantly increased RelPowAlpha_avg_AVG, RelPowAlpha_snr_AVG, HjorthM_avg_AVG, and DecorrTime_snr_AVG values were found in the effective group as compared to the ineffective group. On the contrary, there were significantly decreases in DecorrTime_std_AVG, and Wavelet_db4_EnergyBand_5_avg_AVG values in the effective group as compared to the ineffective group. The analyses yielded a precision rate of 100%. When the follow-up EEG segments were used to test the analytic results, the accuracy was 83.3%.

Conclusion: The developed method is a useful tool in analyzing the effectiveness of antiepileptic drugs. This method may assist pediatric neurologists in evaluating the efficacy of AEDs and making antiepileptic drug adjustments when managing epileptic patients in the early stage.
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http://dx.doi.org/10.1016/j.braindev.2017.07.004DOI Listing
January 2018

Postnatal Changes in Tibial Bone Speed of Sound of Preterm and Term Infants during Infancy.

PLoS One 2016 10;11(11):e0166434. Epub 2016 Nov 10.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = 65) infants were enrolled in this study. Tibial bone SOS was measured using quantitative ultrasonography (QUS) on the left tibia of newborn infants after birth (within 7 days), at 1 month old, and then every 2 months until subjects were approximately 12-15 months old. Follow-up checks included anthropometric measurements and tibial bone SOS. Mean tibial bone SOS at birth was significantly higher in term infants (mean ± SD, 2968.5 ± 99.7 m/s) than in preterm infants (2912.2 ± 122.6 m/s). Values of follow-up tibial bone SOS declined for the first 4 months, and then increased gradually until 12-15 months old. This increasing trend was greater in preterm infants after 2 months of corrected age than in term infants. There were no significant differences by 12-15 months of age between preterm and term infants. A longitudinal mixed-effect model controlling for internal correlations and other covariates in the two groups showed that age and the SOS value at birth were important factors affecting the tibial bone SOS in both preterm and term newborn infants during infancy. There are significant differences in the pattern of change in tibial bone SOS values between preterm and term infants during the first 12-15 months of life. Age and SOS value at birth were important factors affecting the pattern of tibial bone SOS change in both preterm and term newborn infants during infancy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166434PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104474PMC
June 2017

Correlates of Elevated Interleukin-6 and 8-Hydroxy-2'-Deoxyguanosine Levels in Tracheal Aspirates from Very Low Birth Weight Infants Who Develop Bronchopulmonary Dysplasia.

Pediatr Neonatol 2017 02 30;58(1):63-69. Epub 2016 May 30.

Department of Pediatrics, Changhua Christian Children's Hospital, Changhua City, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; School of Medicine, Chung Shan Medical University, Taichung City, Taiwan. Electronic address:

Background: Bronchopulmonary dysplasia (BPD) remains the most common complication of very low birth weight (VLBW) preterm infants, and inflammatory regulation plays a role in the development of the BPD. Interleukin-6 (IL-6) has an important role in airway inflammation and therefore can be used as a marker of airway injury. The study aimed to compare the changes between IL-6 and oxidative stress marker with 8-hydroxy-2'-deoxyguanosine (8-OHdG) from serum and tracheal aspiration (TA) in VLBW preterm infants following development of BPD.

Methods: This birth cohort study enrolled 80 VLBW preterm infants, including 26 who developed BPD. All infants completed the study and survived at 36 weeks postmenstrual age. IL-6 and 8-OHdG concentrations from serum and TA on Day 1 and Day 28 after birth were measured using immunoassay.

Results: IL-6 and 8-OHdG in serum and TA were higher in the BPD group than in the non-BPD group on the 1 day after birth (p < 0.05). The IL-6 and 8-OHdG levels in TA fluid were persistently increased on the 28 day of life in the BPD group (p < 0.05). The TA IL-6 was positively correlated with 8-OHdG levels on the 1 day (r = 0.64, p < 0.05) and 28 day of life (r = 0.76, p < 0.05). Based on receiver operating characteristic curves as a predictor of BPD development, TA IL-6 (cutoff, 456.8 pg/mg) had 81.5% sensitivity and 77.8% specificity, whereas TA 8-OHdG (cutoff, 4.4 ng/mg) had a sensitivity of 81.5% and a specificity of 64.4%.

Conclusion: Persistent inflammation with oxidative DNA damage in the respiratory tract may be a crucial mechanism in BPD.
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http://dx.doi.org/10.1016/j.pedneo.2016.01.004DOI Listing
February 2017

Chronic Iron Overload Results in Impaired Bacterial Killing of THP-1 Derived Macrophage through the Inhibition of Lysosomal Acidification.

PLoS One 2016 31;11(5):e0156713. Epub 2016 May 31.

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Iron is essential for living organisms and the disturbance of iron homeostasis is associated with altered immune function. Additionally, bacterial infections can cause major complications in instances of chronic iron overload, such as patients with transfusion-dependent thalassemia. Monocytes and macrophages play important roles in maintaining systemic iron homoeostasis and in defense against invading pathogens. However, the effect of iron overload on the function of monocytes and macrophages is unclear. We elucidated the effects of chronic iron overload on human monocytic cell line (THP-1) and THP-1 derived macrophages (TDM) by continuously exposing them to high levels of iron (100 μM) to create I-THP-1 and I-TDM, respectively. Our results show that iron overload did not affect morphology or granularity of I-THP-1, but increased the granularity of I-TDM. Bactericidal assays for non-pathogenic E. coli DH5α, JM109 and pathogenic P. aeruginosa all revealed decreased efficiency with increasing iron concentration in I-TDM. The impaired P. aeruginosa killing ability of human primary monocyte derived macrophages (hMDM) was also found when cells are cultured in iron contained medium. Further studies on the bactericidal activity of I-TDM revealed lysosomal dysfunction associated with the inhibition of lysosomal acidification resulting in increasing lysosomal pH, the impairment of post-translational processing of cathepsins (especially cathepsin D), and decreased autophagic flux. These findings may explain the impaired innate immunity of thalassemic patients with chronic iron overload, suggesting the manipulation of lysosomal function as a novel therapeutic approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156713PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886970PMC
July 2017

Classification Preictal and Interictal Stages via Integrating Interchannel and Time-Domain Analysis of EEG Features.

Clin EEG Neurosci 2017 Mar 10;48(2):139-145. Epub 2016 Jul 10.

6 Department of Information Engineering, I-Shou University, Kaohsiung, Taiwan.

The life quality of patients with refractory epilepsy is extremely affected by abrupt and unpredictable seizures. A reliable method for predicting seizures is important in the management of refractory epilepsy. A critical factor in seizure prediction involves the classification of the preictal and interictal stages. This study aimed to develop an efficient, automatic, quantitative, and individualized approach for preictal/interictal stage identification. Five epileptic children, who had experienced at least 2 episodes of seizures during a 24-hour video EEG recording, were included. Artifact-free preictal and interictal EEG epochs were acquired, respectively, and characterized with 216 global feature descriptors. The best subset of 5 discriminative descriptors was identified. The best subsets showed differences among the patients. Statistical analysis revealed most of the 5 descriptors in each subset were significantly different between the preictal and interictal stages for each patient. The proposed approach yielded weighted averages of 97.50% correctness, 96.92% sensitivity, 97.78% specificity, and 95.45% precision on classifying test epochs. Although the case number was limited, this study successfully integrated a new EEG analytical method to classify preictal and interictal EEG segments and might be used further in predicting the occurrence of seizures.
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http://dx.doi.org/10.1177/1550059416649076DOI Listing
March 2017

Mozart's music in children with epilepsy.

Transl Pediatr 2015 Oct;4(4):323-6

1 Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; 2 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan ; 3 Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.

Coppola et al. reported 5 out of 11 patients suffering from drug-resistant epileptic encephalopathy associated with cerebral palsy had a ≥50% reduction in the total number of seizures after listening a set of Mozart's compositions 2 h per day for 15 days. Our previous studies also revealed that both seizure frequencies, recurrence of first unprovoked seizure, and epileptiform discharges are significant reduced after listening to Mozart K.448. Until now, the real mechanism of music effect on epilepsy is still unclear. In this article, in addition to showing the beneficial effects of music on seizure, and epileptiform discharges, we are going to discuss the possible mechanism of music. The possible mechanisms include dopaminergic pathways, mirror neurons, and parasympathetic activation after listening to music.
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http://dx.doi.org/10.3978/j.issn.2224-4336.2015.09.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729000PMC
October 2015

Lung function in very preterm infants with patent ductus arteriosus under conservative management: an observational study.

BMC Pediatr 2015 Oct 24;15:167. Epub 2015 Oct 24.

School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Persistent patent ductus arteriosus (PDA) during hospitalization is thought to be associated with adverse pulmonary outcomes in very preterm infants. This observational study aimed to compare the lung function in very preterm infants with and without PDA at discharge.

Methods: Very preterm infants, admitted to our neonatal intensive unit, who required respiratory support soon after birth and had undergone a lung function test at discharge, were enrolled. Infants with a need for positive-pressure support (either an invasive ventilator, or nasal continuous positive airway pressure without oxygen) or supplemental oxygen at a postmenstrual age of 36 weeks were defined as having bronchopulmonary dysplasia (BPD). Echocardiography was performed weekly for each of the very preterm infants with PDA to confirm closure of the PDA. The data were collected retrospectively.

Results: Fifty-two very preterm infants received lung function tests before discharge during the study period, 28 of whom had PDA and received conservative management, and 20 who did not. The other 4 infants who were given active treatment for PDA were excluded. Gestational age was significantly smaller in the PDA group than in the no-PDA group (27.1 ± 2.0 vs. 28.6 ± 1.6 weeks, p = 0.009). Birth weight did not differ significantly in those with and those without PDA (0.98 ± 0.26 vs. 1.12 ± 0.26 kg, p = 0.074). Significantly more infants with PDA had BPD (p = 0.002) and required respiratory support for a longer period (p = 0.001) than those without PDA. However, functional residual capacity (ml/kg) at discharge was comparable between the two groups after adjusting for gestational age and postmenstrual age at testing (21.6 ± 8.4 vs. 21.5 ± 6.7 ml/kg, p = 0.894). Other lung function test parameters were also comparable.

Conclusion: Under a definition of BPD (including infants needing CPAP but without oxygen) other than the conventional definition, the very preterm infants in our study who received conservative management for PDA had a higher percentage of BPD than the infants without PDA. The parameters of the lung function test and lung clearance index were comparable between these two groups at discharge.
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http://dx.doi.org/10.1186/s12887-015-0480-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620001PMC
October 2015

Heat-shock pretreatment reduces expression and release of TSLP from keratinocytes under Th2 environment.

Pediatr Allergy Immunol 2016 Feb 30;27(1):62-9. Epub 2015 Sep 30.

Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan.

Background: Atopic dermatitis is a chronic, relapsing inflammatory disease of the skin. Current therapy is not curative, and recalcitrant disease is a big stress and challenge for parents and physicians. This study explored the potential role of heat-shock protein 70 (HSP-70) and its anti-inflammatory effects on keratinocyte under TH2 environment.

Methods: Human keratinocyte cell line (HaCa T) was stimulated with IL-4, IL-13, and TNF-α to synthesize and secrete thymic stromal lymphopoietin (TSLP), an important cytokine of immunopathogenesis in atopic dermatitis. Heat shock was performed by immersing the cell-contained flash into a water bath of 45°C for 20 min. Cell viability, TSLP expression, and secretion of HaCa T cells were measured and compared. Possible regulatory mechanisms influencing the expression of TSLP, such as the STAT6 and NF-κB signal pathways, were investigated.

Results: Heat-shock treatment induced intracellular HSP-70 expression in HaCa T cells without affecting cell viability. The induced expression and secretion of TSLP in HaCa T cells were suppressed by heat shock. The NF-κB signal pathway was inhibited by heat shock, leading to decreased TSLP expression and secretion.

Conclusion: Heat stress-induced HSPs can significantly reduce the production and secretion of TSLP from HaCaT cells under Th2 environment. Thus, the evidence highlights the potential role of HSP-70 for atopic dermatitis in the future.
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http://dx.doi.org/10.1111/pai.12482DOI Listing
February 2016
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