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Background Xanthomas are commonly found in the soft tissues of hyperlipidemic patients. Rarely, they may involve the skeletal system, with various radiographic appearances, mimicking bone malignancies. Case presentation: A 55-year-old woman presented with back pain and bilateral lower limb weakness for several months. After serial imaging studies, multifocal osteolytic lesions were identified in the pelvis and spine, with the largest measuring 94 mm in diameter. An abnormal lipid profile and typical cutaneous presentation aided in the final pathological diagnosis of bone xanthoma. Conclusions Xanthoma of the bone may be confused with aggressive bone lesions radiologically. Clinical, laboratory, and physical findings, in addition to pathological features, are required to make an accurate diagnosis.

Individuals with Rett syndrome (RTT) commonly demonstrate Parkinsonian features and dystonia at teen age; however, the pathological reason remains unclear. Abnormal iron accumulation in deep gray matter were reported in some Parkinsonian-related disorders. In this study, we investigated the iron accumulation in deep gray matter of RTT and its correlation with dystonia severity. We recruited 18 RTT-diagnosed participants with MECP2 mutations, from age 4 to 28, and 28 age-gender matched controls and investigated the iron accumulation by susceptibility weighted image (SWI) in substantia nigra (SN), globus pallidus (GP), putamen, caudate nucleus, and thalamus. Pearson’s correlation was applied for the relation between iron accumulation and dystonia severity. In RTT, the severity of dystonia scales showed significant increase in subjects older than 10 years, and the contrast ratios of SWI also showed significant differences in putamen, caudate nucleus and the average values of SN, putamen, and GP between RTT and controls. The age demonstrated moderate to high negative correlations with contrast ratios. The dystonia scales were correlated with the average contrast ratio of SN, putamen and GP, indicating iron accumulation in dopaminergic system and related grey matter. As the first SWI study for RTT individuals, we found increased iron deposition in dopaminergic system and related grey matter, which may partly explain the gradually increased dystonia.

Recognizing why an infant cries is challenging as babies cannot communicate verbally with others to express their wishes or needs. This leads to difficulties for parents in identifying the needs and the health of their infants. This study used deep learning (DL) algorithms such as the convolutional neural network (CNN) and long short-term memory (LSTM) to recognize infants’ necessities such as hunger/thirst, need for a diaper change, emotional needs (e.g., need for touch/holding), and pain caused by medical treatment (e.g., injection). The classical artificial neural network (ANN) was also used for comparison. The inputs of ANN, CNN, and LSTM were the features extracted from 1607 10 s audio recordings of infants using mel-frequency cepstral coefficients (MFCC). Results showed that CNN and LSTM both provided decent performance, around 95% in accuracy, precision, and recall, in differentiating healthy and sick infants. For recognizing infants’ specific needs, CNN reached up to 60% accuracy, outperforming LSTM and ANN in almost all measures. These results could be applied as indicators for future applications to help parents understand their infant’s condition and needs.

Epilepsy is a chronic neurological disorder that presents as recurrent, unprovoked seizures. Pharmacotherapy is the main treatment for epilepsy, but at least 30% of patients with epilepsy have pharmacoresistant epilepsy. Therefore, non-pharmacological treatments are still required. In addition to electrophysiological aberrations contributing to epileptogenesis and pathophysiology in epilepsy, neuroinflammation, oxidative stress, and metabolic derangement have been investigated as drug targets in the treatment of epilepsy. Vitamins have antioxidant, anti-inflammatory, and immunomodulatory effects, which can be beneficial for the treatment of epilepsy. Herein, we comprehensively review the role of vitamins in epilepsy. Certain epilepsies are vitamin-dependent or vitamin-responsive. Most studies on vitamins in epilepsy are of low evidence level or limited to animal studies. Nevertheless, vitamin supplementation should be considered in epilepsy therapy. Additionally, certain anti-seizure medications may alter the serum levels of certain vitamins. Monitoring the serum levels of vitamins and supplementing vitamins when needed are suggested during the follow-up of patients with epilepsy.

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

Drought and ferulic acid (FA) inhibit plant growth. Here, we investigated whether Bacillus methylotrophicus CSY-F1 alleviates drought stress in cucumber (Cucumis sativus) plants grown in high-FA soil. Cucumber seedlings grown in high-FA soil were inoculated with CSY-F1 for 20 d, and then subjected to drought for 3 d. In rhizospheric soil of drought-stressed seedlings, CSY-F1 decreased FA levels and increased soil water contents, polysaccharide levels, and catalase, phosphatase, urease, and sucrase activities at low or high FA concentrations. In drought-stressed seedlings grown in FA-containing soil, CSY-F1 improved plant growth, and reduced leaf wilting; CSY-F1 decreased superoxide radical, hydrogen peroxide, and malonaldehyde levels. CSY-F1 increased superoxide dismutase (SOD), catalase, guaiacol peroxidase, ascorbate peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione reductase activities in these seedlings. In addition, CSY-F1 elevated plant relative water content and osmotic potential, and enhanced ascorbate and glutathione contents, proline and soluble sugar levels, and catalase, copper/zinc SOD, manganese SOD, CsPYL1, and CsPYL2 transcript levels. CSY-F1 increases the polysaccharide levels and enzyme activities in soil, and enhances antioxidant enzyme activities, proline and soluble sugar levels, and transcript levels of CsPYL1 and CsPYL2 in leaves, thus alleviating drought stress in cucumber under FA conditions.

Purpose Epileptic encephalopathies (EEs) are the severe form of childhood epilepsy and phenotypically heterogeneous disorders with different underlying genetic defects. EEs are always accompanied with developmental delay/mental retardation and behavior problems. Finding the genetic basis of epileptic encephalopathies with developmental delay/mental retardation can be valuable not only for diagnosis but also for guiding treatment and providing disease prognosis. Methods and Results A customized panel of 90 genes related to epileptic encephalopathies was utilized to screen for potential genetic variants via targeted next generation sequencing (NGS). A total of 78 children with epilepsy and developmental delay/mental retardation were analyzed with an average read depth of 265.3 ± 68.3X. Mutations were found in 23 (9 boys and 14 girls) probands, and the overall mutation identification rate was 29.5% (25.0% for males and 33.3% for females). Fifteen (65.2%) mutations involve ion channels, including SCN1A, KCNT1, SCN2A, SCN8, KCNB1 and KCNQ2. The other (34.8%) mutations involve CDKL5, ALG13, GFAP, SNAP25, STXBP1 and SYNGAP1. Sixteen (69.6%) of the identified mutations were confirmed to be de novo and one (4.3%) was found to be paternal mosaicism. Channelopathies were found to be the major cause of both early onset (≤6 months) and later onset of unclassified EE as well as febrile seizure cases. On the contrary, patients with infantile spasms or West syndrome were mainly caused by mutations in non-ion channel proteins, whereas patients of epilepsy with developmental delays and/or mental retardation were caused by mutations in both channel and non-channel genes. Conclusion NGS is a valuable and reliable diagnostic tool to detect the gene mutation in epileptic children with developmental delay/mental retardation. This cost-effective method shortens the course from seizure onset to genetic diagnosis. By understanding the gene mutations and genotypephenotype correlation better, clinical practitioners could provide the optimal anticonvulsant and treatment.

This study investigated how phonological saliency, deviance size, and maturation affect mismatch responses (MMRs) in early infancy. MMRs to Mandarin vowels and initial consonants were measured using a multi-deviant oddball paradigm in adults, newborns, and 6-month-olds. The vowel condition consisted of Mandarin syllable da as the standard, du as the large deviant and di as small deviant. As for initial consonant condition, we took syllable ba as standard, ga as large deviant, and ba as small deviant. While adults showed typical mismatch negativities (MMNs), newborns demonstrated broad positive MMRs (P-MMRs) to both initial consonants and vowels. For 6-month-olds, deviance size affected the polarity of MMRs to vowels. The large deviant du/da contrast elicited an adult-like MMN, while the small deviant di/da contrast elicited a P-MMR. Initial consonant changes elicited only P-MMRs, regardless of deviance size. In summary, MMRs to vowels switched from P-MMR at birth to MMN at 6 months. However, the polarity transition was not found for MMRs to initial consonants. The developmental trajectories of MMRs to vowels and initial consonants further support the phonological saliency hypothesis.

Epileptic encephalopathies are highly heterogeneous and phenotypical disorders with different underlying genetic defects. Mutations in the SCN2A gene cause different epilepsy syndromes, including epilepsy of infancy with migrating focal seizures, Ohtahara syndrome, and West syndrome. We utilized a targeted next generation sequencing (NGS) approach on a girl with early-onset seizures and Rett-like features, including autistic behavior, limited hand function with chorea, and profound intellectual disability, to identify novel missense mutation (c.1270G>A; p.V424M) in the SCN2A gene, which encodes the αII-subunit of the voltage-gated Na+ channel (Nav1.2). The identified SCN2A mutation responsible for the development of the disease is confirmed to be de novo for the proband. Our findings broaden the clinical spectrum of SCN2A mutations, which resembles clinical phenotypes of SCN1A mutations by manifesting as fever sensitive seizures, and highlights that SCN2A mutations are an important cause of early-onset epileptic encephalopathies with movement disorders. In addition, the use of levetiracetam to treat SCN2A epileptic encephalopathy, when Na+ channel-blocking anticonvulsants are ineffective, is also recommended.

To determine the alleviative effects of exogenous sucrose on chilling stress, cucumber seedlings were pretreated with sucrose for 1 day and exposed to 15/8 °C for 3 days. Among the sucrose concentrations, pretreatment with 50 mM sucrose led to the highest levels of plant growth and caused the lowest levels of superoxide radical, hydrogen peroxide and malonaldehyde under chilling stress. The combined effects of 50 mM sucrose pretreatment and chilling stress increased the activities of superoxide dismutase (EC 1.15.1.1), guaiacol peroxidase (EC 1.11.1.7), glutathione peroxidase (EC 1.11.1.9), ascorbate peroxidase (EC 1.11.1.11), glutathione reductase (EC 1.6.4.2), dehydroascorbate reductase (EC 1.8.5.1) and monodehydroascorbate reductase (EC 1.6.5.4) in leaves. This coincided with the increased transcript levels of copper/zinc superoxide dismutase , glutathione peroxidase and ascorbate peroxidase genes and correlated with the elevated contents of reduced glutathione and ascorbate. The combination of the sucrose pretreatment and chilling increased the contents of proline, soluble sugars, fructose, glucose and endogenous sucrose and enhanced the activities of soluble acid invertase (EC 3.2.1.26) and neutral invertase (EC 3.2.1.27) as well. We propose pretreatment with 50 mM sucrose leads to higher contents of endogenous sucrose, thereby activating antioxidant enzymes and enhancing chilling tolerance in cucumber; the induction of proline, soluble sugars, soluble acid invertase and neutral invertase are also related to chilling stress mitigation by the sucrose pretreatment. Exogenous sucrose may have application possibility in nutrient solutions for a future trial of chilling reduction.

Based on the regularities of motion of the rigid polyurethane rubber ultrasonic vibration assisted grinding, combined with the kinematic analysis of the general theory and experiments. This paper analyses the variation in position, velocity and acceleration during the manufacture of single abrasive grinding with and without ultrasonic vibration. The impact of rigid polyurethane rubber micro V - groove process introduced by the ultrasonic vibration is explored to verify the feasibility of the ultrasonic vibration assisted grinding of micro-precision machining of hard polyurethane rubber material.

Acetazolamide (AZ) is an carbonic anhydrase inhibitor, which has been used in the treatment of seizures, mountain sickness and glaucoma. Memory impairment by AZ has been reported in patient interviews; however, the related mechanism is unclear. We applied two fear conditioning paradigms, shuttle avoidance and passive avoidance, in both rats and mice to investigate this clinical anecdote. Adult Wistar rats receiving AZ 1 h before the shuttle avoidance test showed decreased avoidance rates, especially at high dosage. Adult ICR mice receiving AZ both before and after acquisition trials showed the decreased step-through latencies during the passive avoidance test. This impairment of fear memory was corroborated with decreased LTP by AZ in the amygdala. AZ only inhibited fear conditioning-induced ERK phosphorylation and had no effect on Akt phosphorylation. In conclusion, our study confirmed the adverse cognitive effect of AZ in animal and electrophysiological studies. In clinical practice, clinicians should be aware of this side effect in patients taking AZ. In addition, this inhibition of fear memory by AZ could potentially be applied to patients with posttraumatic stress disorder.

Background Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. Methods In vitro, we treated BV2 cells with KA and LPS. In vivo, KA was used to induce seizures on postnatal day 25 in B6.129P-Cx3cr1tm1Litt/J mice. Rapamycin and everolimus were evaluated in their modulation of neuroinflammation detected by real-time PCR, Western blotting, and immunostaining. Results Everolimus was significantly more effective than rapamycin in inhibiting iNOS and mTOR signaling pathways in both models of neuroinflammation (LPS) and seizure (KA). Everolimus significantly attenuated the mRNA expression of iNOS by LPS and nitrite production by KA and LPS than that by rapamycin. Only everolimus attenuated the mRNA expression of mTOR by LPS and KA treatment. In the present study, we also found that the modulation of mTOR under LPS and KA treatment was not mediated by Akt pathway but was primarily mediated by ERK phosphorylation, which was more significantly attenuated by everolimus. This inhibition of ERK phosphorylation and microglial activation in the hippocampus by everolimus was also confirmed in KA-treated mice. Conclusions Rapamycin and everolimus can block the activation of inflammation-related molecules and attenuated the microglial activation. Everolimus had better efficacy than rapamycin, possibly mediated by the inhibition of ERK phosphorylation. Taken together, mTOR inhibitor can be a potential pharmacological target of anti-inflammation and seizure treatment.

Background Increased prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with allergic rhinitis (AR) has been reported. Our previous study showed that children with untreated AR had higher ADHD scores than did the controls. Objective This prospective follow-up study aimed to investigate whether elevated ADHD scores in children with AR could be decreased by AR treatment. Methods Sixty-eight children with AR (age range, 6-14 years) and who were drug naive were enrolled and evaluated by AR symptom score, ADHD symptom scores, and computerized continuous performance test, before and after AR therapy, which included nonpharmacologic intervention, oral antihistamines, and topical steroids. Thirty-one age-matched controls and 13 children with pure ADHD were also enrolled for comparison. The relationship between the AR and ADHD score change was analyzed by a partial correlation test, and univariate and multivariate linear regression models were applied to investigate possible predictors for the improvement of ADHD scores by AR treatment. Results AR symptom scores in children with AR decreased significantly after treatment (p < 0.001), and their ADHD scores also decreased significantly (p < 0.001). An improved AR symptom score was positively correlated with improved detectability (rp = 0.617, p = 0.001) and commission error (rp = 0.511, p = 0.011). Significant predictors for the improvement of ADHD scores included age, AR drugs, AR subtypes, and multiple atopic diseases (ps < 0.05). Conclusion Higher ADHD scores in children with AR compared with healthy controls decreased significantly with AR treatment. For children with AR and borderline ADHD symptoms, who do not meet full ADHD diagnostic criteria, we recommend initially treating their AR and monitoring improvement of ADHD symptoms.

The aim of this paper is to describe the clinical features and molecular findings of a unique case of Leber's hereditary optic neuropathy (LHON)/mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) overlap syndrome presenting as nonischemic central retinal vein occlusion (CRVO).An 11-year-old Chinese girl presented with sudden onset of bilateral blurred vision. The clinical history, imaging studies, and molecular analysis results were reviewed. The PubMed and OVID databases were used for literature review.Nonischemic CRVO in the subject's right eye and tortuosity of small and medium-sized retinal arterioles in the left eye were found at initial presentation. Bilateral optic disc pallor was then noted with recovery of CRVO. Severe headache and several stroke-like episodes occurred subsequently, with elevated lactate levels in serum and cerebrospinal fluid. LHON/MELAS overlap syndrome was diagnosed, and mitochondrial DNA sequencing revealed G13513A heteroplasmic mutation. Vision was 20/30 in the right eye and 20/800 in the left eye at the last visit.Mitochondrial DNA G13513A mutation can cause LHON/MELAS overlap syndrome. Nonischemic CRVO is a rare manifestation of LHON/MELAS. Atypical findings in cases of LHON should raise the suspicion of overlap syndrome or other mitochondrial diseases.

Purpose: To investigate the effectiveness and tolerability of topiramate (TPM) in treating children with CNS anomalies and intractable epilepsy.Methods: We retrospectively searched the patient database in National Taiwan University Hospital for candidate children (younger than 18 years of age) with epilepsy and CNS anomalies from December 2002 to February 2004. The effectiveness and possible side effects of TPM were evaluated by questionnaire.Results: Twenty-two children (9 males, 13 females) aged from five months to fourteen years were enrolled in the present study. Underlying CNS anomalies were proliferation disorders (n=10), migration/organization disorders (n=10), and neurocutaneous syndromes (n=2). Types of epilepsy at TPM add-on were symptomatic partial epilepsy (n=11), infantile spasms (n=7), and Lennox-Gastaut syndrome (n=4). During the follow-up periods of six to 30 months, eight patients (36%) had more than 50% reduction of seizures and four patients (18%) were seizure-free. The average dosages of TPM ranged from 2.5 to 25 mg⁄kg⁄day. Patients with proliferation disorders or infantile spasms responded better to TPM therapy. The most common side effect was oligohidrosis (n=9, 41%).Conclusion: TPM is a safe and promising add-on anticonvulsant for epileptic children with CNS anomalies. Hypohidrosis is one of the major side effects of TPM treatment.

Anaerobic degradation of lignin in waste straw by ruminal microbes was directly observed using atomic force microscope (AFM). A series of high-resolution AFM images of the straw surface in the biodegradation show that the wax flakelets and lignin granules covering the straw surface were removed by the rumen microorganisms. Such degradation resulted in an exposure of cellulose fibers located inside the straw. The appearance of holes and microfibers in fermentation reveals that tunneling might be one of the ways for rumen microorganisms to attack the straw. Increases in the atomic ratio of oxygen to carbon (O/C) and the ratio C2/C3 in C1s spectra of X-ray photoelectron spectroscopy confirm that more cellulose was exposed on the surface after the anaerobic fermentation of straw. Gas chromatography/mass spectrometry analytical results demonstrate the decomposition of lignin by rumen microorganisms. Fourier transform infrared spectroscopy spectra and the measurement of degradation efficiency of the main straw components further verify these microscaled observations.

A series Znl-xMgxO (x=0∼0.16) films grown on Si (100) substrate were prepared by RF magnetron sputtering and annealed at different temperature. The UV emission peaks of free exciton (and assisted phonon replicas) and electron-hole plasma (E-H) are found in the photoluminescence (PL) from the films, where the E-H has a five-time super-linear enhanced lasing effect. The blue shift of the UV peaks in the photoluminescence spectra is found to be associated with increasing Mg content in Znl-xMgxO films, and the peaks intensity is also reinforced significantly as increasing the annealing temperature. Green emission due to the oxygen vacancy was very weak, indicating a well stoichiometry was kept in the films. The minimum lasing threshold of the samples is 35kW/cm2, corresponding to the 100nm hexagonal microstructure.

Inattention (IA) has been a major problem in children with attention deficit/hyperactivity disorder (ADHD), accounting for their behavioral and cognitive dysfunctions. However, there are at least three processing steps underlying attentional control for auditory change detection, namely pre-attentive change detection, involuntary attention orienting, and attention reorienting for further evaluation. This study aimed to examine whether children with ADHD would show deficits in any of these subcomponents by using mismatch negativity (MMN), P3a, and late discriminative negativity (LDN) as event-related potential (ERP) markers, under the passive auditory oddball paradigm. Two types of stimuli—pure tones and Mandarin lexical tones—were used to examine if the deficits were general across linguistic and non-linguistic domains. Participants included 15 native Mandarin-speaking children with ADHD and 16 age-matched controls (across groups, age ranged between 6 and 15 years). Two passive auditory oddball paradigms (lexical tones and pure tones) were applied. The pure tone oddball paradigm included a standard stimulus (1000 Hz, 80%) and two deviant stimuli (1015 and 1090 Hz, 10% each). The Mandarin lexical tone oddball paradigm’s standard stimulus was /yi3/ (80%) and two deviant stimuli were /yi1/ and /yi2/ (10% each). The results showed no MMN difference, but did show attenuated P3a and enhanced LDN to the large deviants for both pure and lexical tone changes in the ADHD group. Correlation analysis showed that children with higher ADHD tendency, as indexed by parents’ and teachers’ ratings on ADHD symptoms, showed less positive P3a amplitudes when responding to large lexical tone deviants. Thus, children with ADHD showed impaired auditory change detection for both pure tones and lexical tones in both involuntary attention switching, and attention reorienting for further evaluation. These ERP markers may therefore be used for the evaluation of anti-ADHD drugs that aim to alleviate these dysfunctions.

To detect expression of Slit2 and Robo4 in mouse ventricular muscle blood vessel and explore the impact of exogenous Slit2 on proliferation and migrate of mouse cardiac microvascular endothelial cells.Slit2 and Robo4 expression in mouse ventricular muscle blood vessel was detected by immunohistochemistry. Slit2 and Robo4 expression in cardiac microvascular endothelial cells isolated from mouse ventricular muscle were detected by euzymelinked immunosorbent assay and immunofluorescence, respectively. The effects of various concentrations exogenous Slit2 on proliferation of mouse cardiac microvascular endothelial cells was examined by CCK-8 cell proliferation kit. Transwell chamber was used to detect migration of mouse cardiac microvascular endothelial cells treated with 800 µl M199 culture medium containing 20%FBS (negative control), 10 ng/ml VEGF(positive control), 100 ng/ml Slit2(Slit2) and 100 ng/ml Slit2+10 ng/ml VEGF (Slit2+VEGF) and incubated for 18 h at 37 °C and 5%CO(2).Both Slit2 and Robo4 protein expressions were detected in ventricular muscle blood vessel. Slit2 protein expression was detected in mouse microvascular endothelial cells. Protein and mRNA Robo4 expressions were also evidenced in mouse microvascular endothelial cells. Proliferation of mouse cardiac microvascular endothelial cells was not affected by exogenous Slit2. Migration of mouse cardiac microvascular endothelial cells was not affected by exogenous Slit2 (22.1 ± 2.8 vs. 23.2 ± 3.8 in negative control, P0.05) and significantly enhanced by VEGF (65.3 ± 3.8, P0.05 vs. Slip2 and negative control), this effect could be blocked by cotreatment with Slip2 (29.2 ± 3.4 in Slip2+VEGF, P0.05 vs.Slit2 and Robo4 are expressed in mouse ventricular muscle blood vessels and cardiac microvascular endothelial cells. Exogenous Slit2 has no impact on the proliferation of mouse cardiac microvascular endothelial cells but could inhibit VEGF-induced mouse cardiac microvascular endothelial cell migration.

Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permeability. In this study, we investigated the effects of MBs/FUS on extending the therapeutic time window of EPO and its neuroprotective effects in both acute and chronic phases. Male Wistar rats were firstly subjected to two common carotid arteries and right middle cerebral artery occlusion (three vessels occlusion, 3VO) for 50 min, and then the rats were treated with hEPO (human recombinant EPO, 5000 IU/kg) with or without MBs/FUS at 5 h after occlusion/reperfusion. Acute phase investigation (I/R, I/R+MBs/FUS, I/R+hEPO, and I/R+hEPO+MBs/FUS) was performed 24 h after I/R; chronic tests including cylinder test and gait analysis were performed one month after I/R. The experimental results showed that MBs/FUS significantly increased the cerebral content of EPO by bettering vascular permeability. In acute phase, both significant improvement of neurological score and reduction of infarct volume were found in the I/R+hEPO+MBs/FUS group, as compared with I/R and I/R+hEPO groups. In chronic phase, long-term behavioral recovery and neuronal loss in brain cortex after I/R injury was significantly improved in the I/R+hEPO+MBs/FUS group. This study indicates that hEPO administration with MBs/FUS sonication even at 5 h after occlusion/reperfusion can produce a significant neuroprotection.

This study examined how maturation and the size of deviance affect the development of mismatch responses to Mandarin lexical tones by a multi-deviant oddball paradigm with both large deviant T1/T3 and small deviant T2/T3 pairs in newborns and 6-month-olds. The T1/T3 pair elicited a positive mismatch response (P-MMR) at birth but an adult-like mismatch negativity (MMN) at 6 months of age. For the T2/T3 pair, no significant MMR was seen in newborns, whereas a P-MMR was found when infants are 6 months old. Results suggest that the developmental trajectories of MMRs are dependent on the neural maturation and the discriminability of tonal changes.

Despite the current standard treatments including surgical resection, radiation therapy and chemotherapy for maliganat gliomas, the survival of these patients remains dismal. More effective therapies are urgently needed to be developed. Integrins affect multiple normal and abnormal CNS functions, including neural development, synaptogenesis, angiogenesis and inflammation. The up-regulation of integrins, focal adhesion complexes and extracellular matrix of laminin, vitronectin and osteopontin in malignant gliomas provides new insights for glioma therapy. There are three major functions of integrins in gliomas including tumor survival and proliferation, tumor invasion and metastasis, and tumor angiogenesis. In addition, the integrin-dependent regulation of hypoxic responses also modulates the tumor radiosensitivity. There are several integrin-targeted anticancer drugs in clinical trial. Furthermore, combination therapy in gliomas with disintegrin and radiotherapy is also available in clinical trial. In conclusion, integrins and cell-matrix adhesion complexes regulate cell proliferation, survival, invasion, migration, angiogenesis and radiosensitivity. To improve the overall survival rate of malignant gliomas, integrin-targeted therapy is a promising adjunctive therapy to standard therapy with surgery, radiotherapy and temozolomide.

We analyze the respective roles of neuro-imaging and EEG in the assessment of 11 children with holoprosencephaly and epilepsy. Seizures were present in seven patients (64%); six were treated with antiepileptic drugs; five had intractable epilepsy. Two of the patients with intractable epilepsy became seizure-free under polytherapy. Fourteen EEG recordings were performed in eight patients. The abnormal EEG findings included slow waves, focal epileptiform discharges, slow spike-and-wave complexes, hypsarrhythmia, frontal fast activity, fronto-occipital gradients of amplitudes (posterior amplitude attenuation), lack of photic driving, periodic discharges, and extremely large amplitudes. A fronto-occipital gradient was found only in alobar and semilobar holoprosencephaly (HPE), while hypsarrhythmia only in lobar HPE. Lack of photic driving was found only in alobar HPE. All EEGs showed diffuse slow waves, and all patients had severe developmental delay. The Deep Gray Score(DGS) in neuroimaging studies, thought to predict clinical outcome, was irrelevant given the presence and intractability of the epilepsies. Patients with higher DGS, nonetheless, tended to have higher mortality rate. In conclusion, EEG evaluation provides additional functional information to neuroimaging studies in the assessment of neurological outcome in patients with HPE. With a more mature and well-formed cerebrum, as found in the lobar and semilobar types, the possibility of hypsarrhythmia and photic driving increased, while that of fronto-occipital gradients decreased.

The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.

We report a case of Schwartz-Jampel syndrome in a 2-year-9-month-old Taiwanese girl and her clinical response to treatment. She had a history of generalized muscle stiffness and hypertrophy since birth. Clinical and electromyographic myotonia were noted. Other clinical features included short stature, unusual facial appearance, ophthalmoplegia, elbow joint contractures, and developmental hip dysplasia. Muscle stiffness and myotonia improved after infusion of lidocaine. She then received oral mexiletine and the symptoms significantly improved.

Background Allergic rhinitis (AR) is the most common chronic allergic disease in school-age children. An increased prevalence of attention deficit hyperactivity disorder (ADHD) in AR patients has been reported; however, inattention and hyperactivity in AR children have not been investigated using objective and scientific measurements. Methods We used AR symptom score, ADHD symptom scale, and computerized continuous performance test (CPT) to study the attention and impulsivity in AR children, age-matched controls, and ADHD children (aged 6–15 years). Univariate and multivariate linear regression analyses were applied to identify risk factors for impulsivity and inattention in AR children. Results Twenty-nine controls, 10 ADHD, and 105 AR children were enrolled. There were no differences in age and sex among the three groups. The scores of Hyperactivity/Impulsivity subscales of ADHD symptoms from both parents and teachers were significantly higher in the AR children. The CPT in AR children revealed higher commission errors, shorter reaction times, and more perseveration. Risk factors for inattention and impulsivity in AR children included younger age, male sex, higher AR symptom scores, persistent AR, moderate/severe AR, multiple atopic diseases, family history of atopy, and possible comorbidity with ADHD. Conclusion Care for AR children should not only involve treating their allergy, but also monitoring the possible comorbidities of impulsivity and inattention. In children with impulsivity, AR should be considered in addition to ADHD.