Comparing fine motor performance among young children with autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity disorder, and specific developmental disorder of motor function.

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

MRI predictors of long-term outcomes of neonatal hypoxic ischaemic encephalopathy: a primer for radiologists.

This review aims to serve as a foundational resource for general radiologists, enhancing their understanding of the role of Magnetic Resonance Imaging (MRI) in early prognostication for newborns diagnosed with hypoxic ischaemic encephalopathy (HIE). The article explores the application of MRI as a predictive instrument for determining long-term outcomes in newborns affected by HIE. With HIE constituting a leading cause of neonatal mortality and severe long-term neurodevelopmental impairments, early identification of prognostic indicators is crucial for timely intervention and optimal clinical management. We examine current literature and recent advancements to provide an in-depth overview of MRI predictors, encompassing brain injury patterns, injury scoring systems, spectroscopy, and diffusion imaging. The potential of these MRI biomarkers in predicting long-term neurodevelopmental outcomes and the probability of epilepsy is also discussed.

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

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

A novel CPR-assist device vs. established chest compression techniques in infant CPR: A manikin study.

INTRODUCTION: Guidelines for infant CPR recommend the two-thumb encircling hands technique (TTT) and the two-finger technique (TFT) for chest compression. Some devices have been designed to assist with infant CPR, but are often not readily available. Syringe plungers may serve as an alternative infant CPR assist device given their availability in most hospitals. In this study, we aimed to determine whether CPR using a syringe plunger could improve CPR quality measurements on the Resusci-Baby manikin compared with traditional methods of infant CPR. METHODS: Compression area with a diameter of 1 to 2 cm is recommended in previous infant CPR device researches. In this is a randomized crossover manikin study, we examined the efficacy of the Syringe Plunger Technique (SPT) which uses the plunger of the 20 ml syringe with a 2 cm diameter flat piston, commonly available in hospital, for infant External Chest Compressions (ECC). Participants performed TTT, TFT and SPT ECC on Resusci® Baby QCPR® according to 2020 BLS guidelines. RESULTS: Sixty healthcare providers participated in this project. The median (IQR) ECC depths in the TTT, TFT and SPT in the first minute were 41 mm (40-42), 40 mm (38-41) and 40 mm (39-41), respectively, with p < 0.001. The median (IQR) ECC recoil in the TTT, TFT and SPT groups in the first minute was 15% (1-93), 64% (18-96) and 53% (8-95), respectively, with p = 0.003. The result in the second minute had similar findings. The SPT had the best QCPR score and less fatigue. CONCLUSION: The performance of chest compression depth and re-rebound ratio was statistically different among the three groups. TTT has good ECC depth and depth accuracy but poor recoil. TFT is the complete opposite. SPT can achieve a depth close to TTT and has a good recoil performance as TFT. Regarding comprehensive performance, SPT obtains the highest QCPR score, and SPT is also less fatigued. SPT may be an effective alternative technique for infant CPR.

Age and prior vaccination determine the antibody level in children with primary SARS-CoV-2 Omicron infection.

BACKGROUND: Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection relies on immunity generated after primary infection. However, humoral immunity following primary infection with the Omicron variant is not well understood. METHODS: We prospectively recruited children <19 years with virologically-confirmed SARS-CoV-2 infection at National Cheng Kung University Hospital from February 2022 to September 2022 during the first wave of Omicron BA.2 outbreak in Taiwan. Serum samples were collected one month after acute infection to measure anti-spike protein receptor binding domain antibody levels and surrogate virus neutralizing antibody (NAb) levels against wild type disease and variants. RESULTS: Of the 164 patients enrolled, most were under 5 years (65.2%) with a diagnosis of upper respiratory tract infection. Children under 6 months with maternal coronavirus disease 2019 (COVID-19) vaccination had higher levels of both anti-SARS-CoV-2 spike antibody (119.0 vs 27.4 U/ml, p < 0.05) and anti-wild type NAb (56.9% vs 27.6% inhibition, p = 0.001) than those without. Children aged 5-12 years with prior vaccination had higher anti-spike antibody, anti-wild type, and anti-Omicron BA.2 NAb levels than those without (all p < 0.05). In previously naïve children without maternal or self-vaccination, those 6 months to 2 years had the highest antibody levels. Multivariable linear regression analysis showed age was the only independent factor associated with antibody level. CONCLUSIONS: In our study, children aged 6 months to 2 years have the highest antibody responses to SARS-CoV-2 Omicron variant infection. Age and prior vaccination are the main factors influencing the immunogenicity of SARS-CoV-2 infection.

The B56γ3-containing protein phosphatase 2A attenuates p70S6K-mediated negative feedback loop to enhance AKT-facilitated epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A. PP2A has been thought to play a tumor suppressor and the B56γ3 regulatory subunit was shown to play a key tumor suppressor regulatory subunit of PP2A. Nevertheless, we uncovered a molecular mechanism of how B56γ3 may act as an oncogene in colorectal cancer (CRC). METHODS: Polyclonal pools of CRC cells with stable B56γ3 overexpression or knockdown were generated by retroviral or lentiviral infection and subsequent drug selection. Co-immunoprecipitation(co-IP) and in vitro pull-down analysis were applied to analyze the protein-protein interaction. Transwell migration and invasion assays were applied to investigate the role of B56γ3 in affecting motility and invasive capability of CRC cells. The sensitivity of CRC cells to 5-fluorouracil (5-FU) was analyzed using the PrestoBlue reagent assay for cell viability. Immunohistochemistry (IHC) was applied to investigate the expression levels of phospho-AKT and B56γ3 in paired tumor and normal tissue specimens of CRC. DataSets of TCGA and GEO were analyzed to investigate the correlation of B56γ3 expression with overall survival rates of CRC patients. RESULTS: We showed that B56γ3 promoted epithelial-mesenchymal transition (EMT) and reduced the sensitivity of CRC cells to 5-FU through upregulating AKT activity. Mechanistically, B56γ3 upregulates AKT activity by targeting PP2A to attenuate the p70S6K-mediated negative feedback loop regulation on PI3K/AKT activation. B56γ3 was highly expressed and positively correlated with the level of phospho-AKT in tumor tissues of CRC. Moreover, high B56γ3 expression is associated with poor prognosis of a subset of patients with CRC. CONCLUSIONS: Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC. Video Abstract.

Case report: Distinct neurologic manifestation and cytokine profile of a child with COVID-19-associated acute fulminant encephalitis.

The neurologic manifestations of coronavirus disease 2019 (COVID-19) may range from mild symptoms such as headache or confusion to profound encephalopathy with variable outcomes and sequelae. Here, we reported a case of fatal COVID-19-associated encephalitis with acute fulminant cerebral edema, presenting first with visual hallucination and then a rapid progression into comatose status in a few hours. Serial brain computed tomography depicted cerebral edematous changes from bilateral ventral temporal lobe to the whole brain leading to brain herniation. Multiple cytokines in serum and cerebrospinal fluid (CSF) were increased, with a more prominent rise in the CSF. Therefore, we postulated a hypothesis regarding the mechanism of this fulminant encephalitis that the SARS-CoV-2 virus attacked ventral temporal lobes initially, triggered a severe cytokine storm, and then led to subsequent disruption of the blood-brain barrier, diffuse brain edema, and brain herniation. The trend of cytokine profiles over time may aid in diagnosing and evaluating the severity and prognosis of COVID-19-associated encephalitis.

Development and Utility of Practical Indicators of Critical Outcomes in Dengue Patients Presenting to Hospital: A Retrospective Cross-Sectional Study.

Global travel and climate change have drastically increased the number of countries with endemic or epidemic dengue. The largest dengue outbreak in Taiwan, with 43,419 cases and 228 deaths, occurred in 2015. Practical and cost-effective tools for early prediction of clinical outcomes in dengue patients, especially the elderly, are limited. This study identified the clinical profile and prognostic indicators of critical outcomes in dengue patients on the basis of clinical parameters and comorbidities. A retrospective cross-sectional study was conducted in a tertiary hospital from 1 July 2015 to 30 November 2015. Patients diagnosed with dengue were enrolled, and the initial clinical presentations, diagnostic laboratory data, details of the underlying comorbidities, and initial management recommendations based on 2009 World Health Organization (WHO) guidelines were used to evaluate prognostic indicators of critical outcomes in dengue patients. Dengue patients from another regional hospital were used to evaluate accuracy. A group B (4 points) classification, temperature < 38.5 °C (1 point), lower diastolic blood pressure (1 point), prolonged activated partial thromboplastin time (aPTT) (2 points), and elevated liver enzymes (1 point) were included in the scoring system. The area under the receiver operating characteristic curve of the clinical model was 0.933 (95% confidence interval [CI]: 0.905-0.960). The tool had good predictive value and clinical applicability for identifying patients with critical outcomes.

Association of Cystic Periventricular Leukomalacia and Postnatal Epilepsy in Very Preterm Infants.

INTRODUCTION: Cystic periventricular leukomalacia (PVL) is the most common white matter injury and a common cause of cerebral palsy in preterm infants. Postnatal epilepsy may occur after cystic PVL, but their causal relationship remains uncertain. Our aim was to validate the contribution of cystic PVL to postnatal epilepsy in very preterm infants and demonstrate their seizure characteristics. METHODS: This prospective cohort study enrolled 1,342 preterm infants (birth weight <1,500 g and gestational age <32 weeks) from 2003 to 2015. Cystic PVL was diagnosed by serial cerebral ultrasound, and other comorbidities were recorded during hospitalization. Neurological developments and consequences, including epilepsy, were serially accessed until the age of 5. RESULTS: A total of 976 preterm infants completed a 5-year neurological follow-up; 47 (4.8%) had cystic PVL. Preterm infants with cystic PVL were commonly associated with other comorbidities, including necrotizing enterocolitis stage III, neonatal seizures, and intraventricular hemorrhage during hospitalization. At age 5, 14 of the 47 (29.8%) preterm infants with cystic PVL had postnatal epilepsy. After adjusting for gender, gestational age, and three common comorbidities, cystic PVL was an independent risk factor for postnatal epilepsy (adjust OR: 16.2; 95% CI: 6.8-38.4; p < 0.001). Postnatal epilepsy after cystic PVL was commonly the generalized type (13 of 14, 92.9%), not intractable and most occurred after 1 year of age. DISCUSSION/CONCLUSION: Cystic PVL would independently lead to postnatal epilepsy. Preterm infants with cystic PVL are at risk of postnatal epilepsy after age 1 in addition to cerebral palsy.

Fatal Fulminant Cerebral Edema in Six Children With SARS-CoV-2 Omicron BA.2 Infection in Taiwan.

Acute fulminant cerebral edema in children following SARS-CoV-2 infection has been rarely reported. Such patients frequently demonstrate rapid progression and are usually fatal. In this retrospective study, we describe the detailed clinical, laboratory, and neuroimaging features of six fatal cases in Taiwan. All patients had shock initially, five showed rapid progression to multiorgan failure and disseminated intravascular coagulation, and three developed acute respiratory distress syndromes. The inflammatory biomarkers in the first 3 days, including interleukin 6, ferritin, lactate dehydrogenase, and D-dimer, showed significant elevation in all cases. The hyperinflammatory response may play a role in the pathophysiology.

Effective Modulation by Lacosamide on Cumulative Inhibition of INa during High-Frequency Stimulation and Recovery of INa Block during Conditioning Pulse Train.

The effects of lacosamide (LCS, Vimpat®), an anti-convulsant and analgesic, on voltage-gated Na+ current (INa) were investigated. LCS suppressed both the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa with the IC50 values of 78 and 34 µM found in GH3 cells and of 112 and 26 µM in Neuro-2a cells, respectively. In GH3 cells, the voltage-dependent hysteresis of persistent INa (INa(P)) during the triangular ramp pulse was strikingly attenuated, and the decaying time constant (τ) of INa(T) or INa(L) during a train of depolarizing pulses was further shortened by LCS. The recovery time course from the INa block elicited by the preceding conditioning train can be fitted by two exponential processes, while the single exponential increase in current recovery without a conditioning train was adequately fitted. The fast and slow τ's of recovery from the INa block by the same conditioning protocol arose in the presence of LCS. In Neuro-2a cells, the strength of the instantaneous window INa (INa(W)) during the rapid ramp pulse was reduced by LCS. This reduction could be reversed by tefluthrin. Moreover, LCS accelerated the inactivation time course of INa activated by pulse train stimulation, and veratridine reversed its decrease in the decaying τ value in current inactivation. The docking results predicted the capability of LCS binding to some amino-acid residues in sodium channels owing to the occurrence of hydrophobic contact. Overall, our findings unveiled that LCS can interact with the sodium channels to alter the magnitude, gating, voltage-dependent hysteresis behavior, and use dependence of INa in excitable cells.

Effective Perturbations by Phenobarbital on INa, IK(erg), IK(M) and IK(DR) during Pulse Train Stimulation in Neuroblastoma Neuro-2a Cells.

Phenobarbital (PHB, Luminal Sodium®) is a medication of the barbiturate and has long been recognized to be an anticonvulsant and a hypnotic because it can facilitate synaptic inhibition in the central nervous system through acting on the γ-aminobutyric acid (GABA) type A (GABAA) receptors. However, to what extent PHB could directly perturb the magnitude and gating of different plasmalemmal ionic currents is not thoroughly explored. In neuroblastoma Neuro-2a cells, we found that PHB effectively suppressed the magnitude of voltage-gated Na+ current (INa) in a concentration-dependent fashion, with an effective IC50 value of 83 µM. The cumulative inhibition of INa, evoked by pulse train stimulation, was enhanced by PHB. However, tefluthrin, an activator of INa, could attenuate PHB-induced reduction in the decaying time constant of INa inhibition evoked by pulse train stimuli. In addition, the erg (ether-à-go-go-related gene)-mediated K+ current (IK(erg)) was also blocked by PHB. The PHB-mediated inhibition on IK(erg) could not be overcome by flumazenil (GABA antagonist) or chlorotoxin (chloride channel blocker). The PHB reduced the recovery of IK(erg) by a two-step voltage protocol with a geometrics-based progression, but it increased the decaying rate of IK(erg), evoked by the envelope-of-tail method. About the M-type K+ currents (IK(M)), PHB caused a reduction of its amplitude, which could not be counteracted by flumazenil or chlorotoxin, and PHB could enhance its cumulative inhibition during pulse train stimulation. Moreover, the magnitude of delayed-rectifier K+ current (IK(DR)) was inhibited by PHB, while the cumulative inhibition of IK(DR) during 10 s of repetitive stimulation was enhanced. Multiple ionic currents during pulse train stimulation were subject to PHB, and neither GABA antagonist nor chloride channel blocker could counteract these PHB-induced reductions. It suggests that these actions might conceivably participate in different functional activities of excitable cells and be independent of GABAA receptors.

Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line.

Carbamazepine (CBZ, Tegretol®) is an anticonvulsant used in the treatment of epilepsy and neuropathic pain; however, several unwanted effects of this drug have been noticed. Therefore, the regulatory actions of CBZ on ionic currents in electrically excitable cells need to be reappraised, although its efficacy in suppressing voltage-gated Na+ current (INa) has been disclosed. This study was undertaken to explore the modifications produced by CBZ on ionic currents (e.g., INa and erg-mediated K+ current [IK(erg)]) measured from Neuro-2a (N2a) cells. In these cells, we found that this drug differentially suppressed the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa in a concentration-dependent manner with effective IC50 of 56 and 18 µM, respectively. The overall current-voltage relationship of INa(T) with or without the addition of CBZ remained unchanged; however, the strength (i.e., ∆area) in the window component of INa (INa(W)) evoked by the short ascending ramp pulse (Vramp) was overly lessened in the CBZ presence. Tefluthrin (Tef), a synthetic pyrethroid, known to stimulate INa, augmented the strength of the voltage-dependent hysteresis (Hys(V)) of persistent INa (INa(P)) in response to the isosceles-triangular Vramp; moreover, further application of CBZ attenuated Tef-mediated accentuation of INa(P)'s Hys(V). With a two-step voltage protocol, the recovery of INa(T) inactivation seen in Neuro-2a cells became progressively slowed by adding CBZ; however, the cumulative inhibition of INa(T) evoked by pulse train stimulation was enhanced during exposure to this drug. Neuro-2a-cell exposure to CBZ (100 µM), the magnitude of erg-mediated K+ current measured throughout the entire voltage-clamp steps applied was mildly inhibited. The docking results regarding the interaction of CBZ and voltage-gate Na+ (NaV) channel predicted the ability of CBZ to bind to some amino-acid residues in NaV due to the existence of a hydrogen bond or hydrophobic contact. It is conceivable from the current investigations that the INa (INa(T), INa(L), INa(W), and INa(P)) residing in Neuro-2a cells are susceptible to being suppressed by CBZ, and that its block on INa(L) is larger than that on INa(T). Collectively, the magnitude and gating of NaV channels produced by the CBZ presence might have an impact on its anticonvulsant and analgesic effects occurring in vivo.

Agreement Between Caregivers' Concerns of Children's Developmental Problems and Professional Identification in Taiwan.

Objective: Early detection of developmental delays relies on the accuracy of the caregivers' concerns of children's developmental problems. The aim of this study was to investigate the agreement between the caregivers' awareness of children's developmental problems and professional identification. Methods: Caregivers of 1,963 children (age range: 5-71 months; mean: 38.4 months) younger than 6 years old who were at risk of developmental delays and referred to the center for a comprehensive evaluation were enrolled in this study. Children were identified by a transdisciplinary team including a pediatric neurologist, a pediatric psychiatrist, two psychologists, two occupational therapists, two physical therapists, two speech therapists, a social worker, and a special instructor. A series of standardized developmental assessments were used to identify children with developmental delay. Retrospective chart reviews were conducted on all children to confirm specific developmental disorders. Results: The caregivers' initial concerns of cognitive, speech/language, emotional/behavioral, and motor and global development showed low agreement with the results of professional identification. The major disagreement was observed in the cognitive domain. Speech/language developmental concern was an important red-flag indicator of cognitive and emotional/behavioral developmental delays. The presence of intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder was high in this study. When having caregivers' concerns about speech/language and emotional/behavioral development, the odds of children with autism spectrum disorder was 2.37 and 2.17 times greater than those without autism spectrum disorder, respectively. The presence of attention deficit hyperactivity disorder was significantly associated with concerns about cognitive and emotional/behavioral developmental delays. Child's age and mothers' level of education were significant indicators for detecting the child's developmental problems. Conclusion: It is recommended that assessing the cognitive developmental status is essential for all children in the identification process. Practitioners should not overlook caregivers' concern about speech/language and emotional/behavioral development. Transdisciplinary practitioners provide educational guidance to caregivers, especially in the domains of cognitive, speech/language, and emotional/behavioral development.

Biomechanical analysis of force distribution in one-handed and two-handed child chest compression- a randomized crossover observational study.

BACKGROUND: Even force distribution would generate efficient external chest compression (ECC). Little research has been done to compare force distribution between one-hand (OH) and two-handed (TH) during child ECC. Therefore, this study was to investigate force distribution, rescuer perceived fatigue and discomfort/pain when applying OH and TH ECC in children. METHODS: Crossover manikin study. Thirty-five emergency department registered nurses performed lone rescuer ECC using TH and OH techniques, each for 2 min at a rate of at least 100 compressions/min. A Resusci Junior Basic manikin equipped with a MatScan pressure measurement system was used to collect data. The perceived exertion scale (modified Borg scale) and numerical rating scale (NRS) was applied to evaluate the fatigue and physical pain of delivering chest compressions. RESULTS: The maximum compression force (kg) delivered was 56.58 ± 13.67 for TH and 45.12 ± 7.90 for OH ECC (p <  0.001). The maximum-minimum force difference force delivered by TH and OH ECC was 52.24 ± 13.43 and 41.36 ± 7.57, respectively (p <  0.001). The mean caudal force delivered by TH and OH ECC was 29.45 ± 16.70 and 34.03 ± 12.01, respectively (p = 0.198). The mean cranial force delivered by TH and OH ECC was 27.13 ± 11.30 and 11.09 ± 9.72, respectively (p <  0.001). The caudal-cranial pressure difference delivered by TH and OH ECC was 19.14 ± 15.96 and 26.94 ± 14.48, respectively (p = 0.016). The perceived exertion and NRS for OH ECC was higher than that of the TH method (p < 0.001, p = 0.004, respectively). CONCLUSIONS: The TH method produced greater compression force, had more efficient compression, and delivered a more even force distribution, and produced less fatigue and physical pain in the rescuer than the OH method. TRIAL REGISTRATION: The Cheng Kung University Institutional Review Board A-ER-103-387. http://nckuhirb.med.ncku.edu.tw/sitemap.php.

Novel Variations in the KDM5C Gene Causing X-Linked Intellectual Disability.

BACKGROUND AND OBJECTIVES: To investigate the pathogenicity of 2 novel KDM5C variations, report the clinical and neuroimaging findings, and review the available literature. METHODS: Physical examinations, structural neuroimaging studies, and exome sequence analysis were performed. KDM5C constructs were used to study the effect of the variations in transfected cells. RESULTS: We identified 2 novel variations c.2233C>G and c.3392_3393delAG in the KDM5C gene harboring from 2 Chinese families with X-linked intellectual disability (ID). The affected male patients exhibited severe ID, short stature, and facial dysmorphism. The 1 with c.3392_3393delAG additionally had epilepsy and autistic spectrum disorder (ASD). Transiently transfected mutant KDM5C constructs both reduced protein expression and stability and decreased histone demethylase activities in cells. Reviewing the available literature, we found that the associated ASD tended to occur in patients with variations near the C-terminus of KDM5C. DISCUSSION: We report the clinical, molecular genetic, and pathologic features in patients with novel variations of KDM5C. The variability of the clinical phenotype in addition to an ID may associate with altered particular parts of KDM5C.

Lactate Predicts Neurological Outcomes after Perinatal Asphyxia in Post-Hypothermia Era: A Prospective Cohort Study.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. METHODS: A prospective cohort study enrolled neonates with perinatal asphyxia. Biochemical blood tests and cerebral Doppler ultrasound were measured within 6 h of age and at the 4th day old. Neurological outcomes were assessed at 1 year old. RESULTS: Sixty-four neonates with perinatal asphyxia were enrolled. Fifty-eight (90%) had hypoxic-ischemic encephalopathy (HIE) including 20 (34%) Stage I, 21 (36%) Stage II, and 17 (29%) Stage III. In the asphyxiated infants without therapeutic hypothermia, HIE stage, PH, and base excess levels within 6 h of age were the predictors of adverse outcomes. In the asphyxiated infants receiving therapeutic hypothermia, HIE stage failed to predict outcomes. Instead, blood lactate levels and pulsatility index (PI) of medial cerebral arteries (MCA) either in 6 h of age or at the 4th day old independently predicted adverse outcomes. CONCLUSIONS: Blood lactate, which is a common accessible test at the hospital and MCA PI on cerebral ultrasound could predict adverse outcomes in asphyxiated infants receiving therapeutic hypothermia.

Clinical spectrum and the comorbidities of Dravet syndrome in Taiwan and the possible molecular mechanisms.

Dravet syndrome (DS) is an uncommon epilepsy syndrome that may negatively affect the patients and their caregivers. However, reliable and valid measures of its impact on caregivers and the characteristics of patients with DS in Taiwan are lacking. This study aimed to describe the characteristics of patients with DS and concerns of their caregivers and establish a baseline frequency of disease characteristics using a cross-sectional survey in Taiwan. We assessed the caregivers of patients with DS using an online anonymous questionnaire. The seizure frequency decreased with age, although lacking statistical significance. Vaccines show no influence on the condition of patients with DS. Our findings revealed the highest impact on the domains affecting the caregivers' daily life, including additional household tasks, symptom observation, further medical plan, and financial issues. Caregivers also expressed concerns regarding the lack of independence/constant care, seizure control, speech/communication, and impacts on siblings because of long-term care of the patients in parents' absence. Our findings highlight the significant effects of caring for a child with DS on the lives of their caregivers in Taiwan; these findings will help raise awareness regarding the needs of these families. Furthermore, we discussed the possible pathophysiological mechanisms of associated comorbidities.

Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly.

Hypoxic-ischemic (HI) encephalopathy is the major cause of mortality and disability in newborns. The neurovascular unit is a major target of acute and chronic brain injury, and therapies that protect simultaneously both neurons and vascular endothelial cells from neonatal HI injury are in demand. Insulin receptors and its key downstream molecule-insulin receptor substrate -1 (IRS-1) are potential neuroprotective targets and expressed both in neuron and endothelial cells. To investigate whether IRS-1 can act similarly in neurons and vascular endothelial cells in protecting neurovascular units and brain form HI injury, we found that neuron-specific IRS-1 transgenic rats showed reduced neurovascular injury and infarct volumes, whereas endothelial-specific IRS-1 transgenic rats showed increased blood-brain barrier (BBB) disruption and exaggerated neurovascular injury after neonatal HI brain injury. Endothelial-specific IRS-1 overexpression increased vascular permeability and disassembled the tight junction protein (zonula occludens-1) complex. Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Together, our findings suggested that neuronal and endothelial IRS-1 had opposite effects on the neurovascular integrity and damage after neonatal HI brain injury and that endothelial IRS-1 worsens neurovascular integrity after HI via mTOR-mediated tight junction protein disassembly.