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Gene therapy using adeno-associated virus (AAV) is a rapidly developing technology with widespread treatment potential. AAV2 vectors injected directly into the brain by stereotaxic brain surgery have shown good results in treating aromatic l-amino acid decarboxylase deficiency. Moreover, gene therapy using the AAV9 vector, which crosses the blood-brain barrier, has been performed in more than 2000 patients worldwide as a disease-modifying therapy for spinal muscular atrophy. AAV vectors have been applied to the development of gene therapies for various pediatric diseases. Gene therapy trials for hemophilia and ornithine transcarbamylase deficiency are underway. Clinical trials are planned for glucose transporter I deficiency, Niemann-Pick disease type C, and spinocerebellar ataxia type 1. The genome of AAV vectors is located in the episome and is rarely integrated into chromosomes, making the vectors safe. However, serious adverse events such as hepatic failure and thrombotic microangiopathy have been reported, and ongoing studies are focusing on developing more efficient vectors to reduce required dosages.

The COVID-19 pandemic has meant that distance teaching and learning at educational institutions since 2020 has become common place. The Ministry of Education in Bhutan has taken the initiative to educate students using learning television and Internet-based online education instead of traditional classes. Thus, the Royal University of Bhutan (RUB) and its ten constituent colleges have been swift in transitioning to online teaching through Moodle and varieties of other applications such as ZOOM, Big Blue Button and Google classroom since March 2020. Since then, offline and online blended teaching began at the College of Science and Technology (CST) under RUB in January 2021. In this paper, we focus on offline and online teaching and learning practices for assembly language programming with the 8085 microprocessor. A Zoom meeting is used for the online practical. Firstly, a tutor gives an 8085 assembly program lesson, which is common to both offline and online teaching practices. In the case of the offline practice, students assemble the assembly program into Hexadecimal code, by looking up a table of the 8085 instruction set. Finally, the Hexadecimal code is input and executed on an 8085 microprocessor trainer, and students confirm the output from the trainer. Here, the trainer is a small computer composed of a microprocessor, peripheral/communication interfaces, timer, memory, input device and output device. In the case of the online practice, on the other hand, students input the assembly program directly on a Web-based 8085 microprocessor simulator. We developed an 8085 microprocessor simulator using JavaScript. Then, students confirm the output from the simulator on a Web browser. The students took 6 offline learning practices and 4 online out of a total of 10. According to a questionnaire survey about the comparison of the offline and online practices from the students, they say offline practices are much better than online ones, because direct communication is important to understand the learning contents. We conclude that there is room for improvement in the online teaching methods.

Purpose Forced normalization (FN) indicates psychotic episodes associated with seizure remission and disappearance of epileptiform activity on EEG. FN is likely to occur when frequent seizures are abruptly terminated by anti-epileptic drugs (AEDs) or epilepsy surgery. Methods We describe an atypical case of a patient with FN induced by lacosamide (LCM). Results A 23-year-old female patient with Lennox-Gastaut syndrome (LGS) was administered AEDs for LGS and hospitalised with weight loss and abnormal behaviour. Her condition fulfilled the FN criteria, which was considered to be induced by LCM. After a reduction in LCM dose, her abnormal behaviour and appetite improved. During LCM use, the patient developed no seizures, and the high amplitude diffuse sharp and slow wave complexes that were frequently observed before LCM disappeared on EEG. The LCM dose was tapered to 150 mg per day, and she became calmer with socially appropriate behaviours, although a few mild focal seizures relapsed. Conclusion LCM was effective for treating LGS in this patient and induced FN. Initially, it was difficult to recognise FN in cases of psychiatric disorders, especially in patients with intellectual disability. Patients with FN induced by LCM are rare, and only four patients have been previously reported who were treated by antipsychotic drug for psychosis.

Static encephalopathy of childhood with neurodegeneration in adulthood/β-propeller protein-associated neurodegeneration is a neurodegenerative disorder with brain iron accumulation caused by the variants of WDR45, a core autophagy-related gene that encodes WD repeat domain phosphoinositide interacting protein 4. However, the pathophysiology of the disease, particularly the function of WDR45/WD repeat domain phosphoinositide interacting protein 4 in iron metabolism, is largely unknown. As no other variants of core autophagy-related genes show abnormalities in iron metabolism, the relation between autophagy and iron metabolism remains to be elucidated. Since iron deposition in the brain is the hallmark of static encephalopathy of childhood with neurodegeneration in adulthood/β-propeller protein-associated neurodegeneration, iron chelation therapy has been attempted, but it was found to worsen the symptoms; thus, the establishment of a curative treatment is essential. Here, we evaluated autophagy and iron metabolism in patient-derived cells. The expression of ferritin and ferric iron increased and that of ferrous iron decreased in the patient cells with WDR45 variants. In addition, the expression of nuclear receptor coactivator 4 was markedly reduced in patient-derived cells. Furthermore, divalent metal transporter 1, which takes in ferrous iron, was upregulated, while ferroportin, which exports ferrous iron, was downregulated in patient-derived cells. The transfer of WDR45 via an adeno-associated virus vector restored WD repeat domain phosphoinositide interacting protein 4 and nuclear receptor coactivator 4 expression, reduced ferritin levels, and improved other phenotypes observed in patient-derived cells. As nuclear receptor coactivator 4 mediates the ferritin-specific autophagy, i.e. ferritinophagy, its deficiency impaired ferritinophagy, leading to the accumulation of ferric iron-containing ferritin and insufficiency of ferrous iron. Because ferrous iron is required for various essential biochemical reactions, the changes in divalent metal transporter 1 and ferroportin levels may indicate a compensatory response for maintaining the intracellular levels of ferrous iron. Our study revealed that the pathophysiology of static encephalopathy of childhood with neurodegeneration in adulthood/β-propeller protein-associated neurodegeneration involves ferrous iron insufficiency via impaired ferritinophagy through nuclear receptor coactivator 4 expression reduction. Our findings could aid in developing a treatment strategy involving WDR45 manipulation, which may have clinical applications.

Niemann–Pick disease type C1 (NPC1) is a fatal congenital neurodegenerative disorder caused by mutations in the NPC1 gene, which is involved in cholesterol transport in lysosomes. Broad clinical manifestations of NPC1 include liver failure, pulmonary disorder, neurological deficits, and psychiatric symptoms. The main cause of death in NPC1 patients involves central nervous system (CNS) dysfunction; there is no essential treatment. We generated a tyrosine-mutant adeno-associated virus (AAV) 9/3 vector that expresses human NPC1 under a cytomegalovirus (CMV) promoter (AAV-CMV-hNPC1) and injected it into the left lateral ventricle (5 μL) and cisterna magna (10 μL) of Npc1 homo-knockout (Npc1−/−) mice. Each mouse received total 1.35 × 1011 vector genome on days 4 or 5 of life. AAV-treated Npc1−/− mice (n = 11) had an average survival of >28 weeks, while all saline-treated Npc1−/− mice (n = 11) and untreated Npc1−/− mice (n = 6) died within 16 weeks. Saline-treated and untreated Npc1−/− mice lost body weight from 7 weeks until death. However, the average body weight of AAV-treated Npc1−/− mice increased until 15 weeks. AAV-treated Npc1−/− mice also showed a significant improvement in the rotarod test performance. A pathological analysis at 11 weeks showed that cerebellar Purkinje cells were preserved in AAV-treated Npc1−/− mice. In contrast, untreated Npc1−/− mice showed an almost total loss of cerebellar Purkinje cells. Combined injection into both the lateral ventricle and cisterna magna achieved broader delivery of the vector to the CNS, leading to better outcomes than noted in previous reports, with injection into the lateral ventricles or veins alone. In AAV-treated Npc1−/− mice, vector genome DNA was detected widely in the CNS and liver. Human NPC1 RNA was detected in the brain, liver, lung, and heart. Accumulated unesterified cholesterol in the liver was reduced in the AAV-treated Npc1−/− mice. Our results suggest the feasibility of gene therapy for patients with NPC1.

Twin-to-twin transfusion syndrome (TTTS) is a severe gestational complication due to an imbalance of blood flow between monochorionic diamniotic twins. TTTS can cause brain damage, most commonly ischemic lesions, but there are only a few reports of cortical dysplasia. We report the case of a TTTS donor twin with diffuse cortical dysplasia. Fetoscopic laser photocoagulation was performed at 18 weeks of gestation, and no abnormalities were noted in the subsequent course of the pregnancy; however, infantile spasms developed at 4 months after birth, and brain magnetic resonance imaging revealed diffuse cortical dysplasia. It was bilateral and widespread. A genetic abnormality was suspected, but no pathogenic mutation was detected. Hypoperfusion may have altered the expression of guidance factors, resulting in abnormal cortical formation.

To reduce the iron loss and noise of a three-phase reactor composed of grain-oriented (GO) steel plates, two types of core structures are proposed in this article. In the first type, the ordinary brick core model is improved to a hybrid one composed of GO and nonoriented steel plates, and in the second type, the T-joint part of the ordinary oblique-joint core model is improved to a straight joint. To show the effectiveness of the improved models, the iron loss and displacement distributions in the four core structures are evaluated using the 2-D magnetic field and mechanical analyses. In these analyses, the magnetic characteristics of the anisotropic cores are considered in detail. Namely, in the magnetic field analysis, the ${B}$ – ${H}$ curves in the arbitrary directions are considered. In the iron loss calculation, the rotational iron loss is calculated using the iron loss curves in the arbitrary directions. Moreover, the methods of calculating the displacements due to electromagnetism and magnetostriction considering the anisotropic ${B}$ – ${H}$ curves and magnetostriction in the arbitrary directions are proposed. It is shown that the iron losses and displacements of the two proposed core structures can be reduced compared with the ordinary ones. Moreover, the second proposed model is the most attractive one because both the iron loss and displacement are smaller than the other models.

Introduction Metachromatic leukodystrophy (MLD) refers to leukodystrophy caused by the accumulation of sulfatide from arylsulfatase A (ARSA) gene mutations. Sulfatide also accumulates in various organs, including the peripheral nerves, kidney, and gallbladder. Proliferative changes in the gallbladder have been reported in several patients, while gallbladder cancer is reported in only two adult MLD cases. We report what is likely the first pediatric case of MLD with gallbladder cancer. Case report The patient was a 5-year-old girl diagnosed with MLD using head magnetic resonance imaging and detecting a homozygous mutation of c.302G>A (p.Gly101Asp) in ARSA. Abdominal bloating was observed at the age of 4 years; CT revealed a giant tumor in the gallbladder and massive ascites. Cholecystectomy was performed and pathological examination revealed adenocarcinoma. Measurement of serum sulfatide revealed increased levels compared to the average healthy range. Discussion Rapidly increased ascites and large polyps which are reported as risk factors for cancer were characteristic in our MLD case. When such lesions are detected, they should be removed immediately because of the possibility of cancer, even in a pediatric patient.

Actin, alpha, skeletal muscle 1 (ACTA1) is one of the causative genes of nemaline myopathy (NM) and congenital fiber-type disproportion (CFTD). CFTD is characterized by type 1 fiber atrophy and distinguished from NM in the absence of rods. Eight patients with CFTD, including one patient with dilated cardiomyopathy (DCM), have previously been reported. Herein, we report the case of a 10-year-old boy presenting with CFTD and DCM.We performed exome sequencing and analyzed the effect of Met327Lys mutations on cultured C2C12 muscle cells compared with that seen in the wild type (WT, ACTA1) and previously identified Asp294Val mutations associated with a severe phenotype of CFTD without cardiomyopathy.Exome sequencing revealed a de novo mutation, c.980 T A, p.(Met327Lys), in ACTA1 (NM_001100.4). C2C12 cells transfected with the WT plasmid expressed ACTA1 in the nucleus and cytoplasm. Cells with the Asp294Val mutant showed needle-like structures in the cytoplasm, whereas the expression of the Met327Lys mutant resulted in few aggregations but many apoptotic cells.Apoptosis induced in Met327Lys-transfected muscle cells supports the pathogenicity of the mutation and can be implicated as one of the histopathological features associated with CFTD, as in NM.

Previous studies have reported that hypothyroidism can lead to sick sinus syndrome (SSS) or other rhythm disturbances. Variants in the alpha subunit of the cardiac sodium channel (SCN5A) are known to be among the genetic causes of SSS. We encountered an adolescent patient with SSS and hypothyroidism who also harbored an SCN5A variant. The patient was a 13-year-old girl who was referred to our hospital because of bradycardia identified during a school electrocardiography screening. Clinical examination revealed severe hypothyroidism due to Hashimoto thyroiditis and SSS. After levothyroxine supplementation, her symptoms of hypothyroidism improved; however, the SSS did not. Genetic testing revealed a heterozygous variant (c.1066 GA, p.Asp356Asn) in SCN5A. This is the first report of the coexistence of SSS due to an SCN5A variant and severe hypothyroidism in an adolescent patient. While patients with SCN5A variants exhibit phenotypic heterogeneity due to the presence of various modifiers, the presence of severe hypothyroidism may affect the development of SSS. This case highlights the importance of genetic analysis, including testing for SCN5A variants, in patients with hypothyroidism complicated by SSS or cardiac conduction disorders.

Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated.Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments.A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.

People with visual impairment, even if they are availed to voting, they do not have the privilege to vote confidentially, because of their physical disability. Therefore, a user-friendly and confidential voting system is necessary for visually impaired people. In this paper, we build an electronic voting system for visually impaired people is a user-friendly device which can help those group of people vote independently with sound. The system is built on an Arduino Mega 2560 microcontroller board, a SD card module, an LCD module, several buttons, a buzzer, GSM SIM 900A and a headset. The system has a special voice feature stored in SD card to familiarize them with names of candidates. Also, the voice is passed through a headset for secrecy. In addition, a control unit of the system for polling officials is designed separately from a voting unit for the smooth election procedural. Once user votes, a buzzer is turned on and the system cannot accept the voting. If a control button is pushed, the buzzer is turned off and the system accepts voting. This mechanism is to avoid double voting. A result button is implemented to display final votes for each candidate and store them in the SD card. GSM SIM900A is interfaced with Arduino Mega 2560 to disseminate final results. We can encourage mass participation equally in democracy through the system electronic voting system.

Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified. Review of the literature showed that BPAN with RTT-like features is associated with more epileptic seizures and less deceleration of head growth, breathing irregularities, and cold extremities than classic RTT with MECP2 variants. These clinical presentations may provide clues for differentiating between these two disorders. However, both WDR45 and MECP2 should be screened in patients presenting a clinical picture of RTT without specific MRI findings of BPAN.

Objective The early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 μV) fast activity (HAFA) on electroencephalography (EEG). Methods We conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11). Trained electroencephalographers reviewed all of the EEGs. When excessive fast activity was observed, the amplitude, frequency, and locality were assessed. Results All five patients with BPAN underwent initial EEGs at 12–21 months old, and diffuse continuous HAFA (range 20–50 Hz) was observed on both awake and sleep EEGs. In the awake records, there was no clear posterior dominant rhythm in 4 of the 5 patients. Although 28% of the 143 EEGs had continuous excessive fast activity, mainly in the sleep records, only two (1.4%) exhibited HAFA when asleep, and their awake EEGs had clear posterior dominant rhythm. Conclusions The EEGs of children with BPAN showed diffuse HAFA continuously when both awake and asleep, which is uncommon in children with other etiologies. Significance This study provides an important clue for the early diagnosis of BPAN.

A fault current limiter is an effective mean of limiting fault currents. The simultaneous use of three single-phase current limiters requires significant amounts of ferromagnetic material and space. This article proposes a three-phase saturated-core fault current limiter (T-SCFCL) that employs a common yoke and a permanent magnet to mitigate the restrictions of material and space. T-SCFCL delivers good performance for single-phase, two-phase, and three-phase faults. In this configuration, flux flowing through the permanent magnets is generated by a three-phase unbalanced current, thereby reducing the loss in eddy current and improving stability while significantly reducing the volume of the core. An algorithm is provided for use in the design of the FCL structure. A simulation was conducted based on the finite element method and a prototype manufactured and tested to verify effectiveness. The results prove that the proposed method is efficient.

Background A report presenting five heterozygous de novo variants in VAMP2 in unrelated individuals with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features was first published in April 4, 2019. Case report We report the case of a male child with VAMP2 variant who was delivered at 38 weeks and 4 days without neonatal asphyxia. At 4 months of age he showed hypotonia and no visual pursuit and fixation. He presented with infantile spasms at 6 months, and electroencephalography (EEG) showed hypsarrhythmia. His infantile spasms completely disappeared by adrenocorticotropic hormone therapy, but his EEG findings continued to show high voltage slow-waves with multi-focal spikes. At 2 years of age he was non-verbal, had an absence of purposeful hand movements, and no visual fixation. He had somnolence tendency in the daytime. Biochemical and extensive genetic examinations were unrevealed. Magnetic resonance imaging showed slight brain atrophy. At 2 years and 7 months of age, he suffered from myoclonic seizures of the eyelid and tongue, which propagated to unilateral fingers, and sometimes to the bilateral legs. At 8 years of age hyperkinetic movement occurred. At age 13, whole-exome sequence identified a heterozygous missense variant, NM_014232.2:c.199G>C,[p.(Ala67Pro)] in exon 3 of VAMP2 which was a de novo non-synonymous variant. Conclusion This is the first case report of VAMP2 variant in Japan. Hypotonia at early infancy, poor visual fixation, and absence of purposeful hand movements may be indicative of the diagnosis for VAMP2 variant.

With the continuous expansion of power grid capacity, the problem of short-circuit current exceeding the standard is becoming increasingly serious. Fault current limiter is a promising solution and is gradually becoming a research hotspot. In this study, fault current limiters are classified into four categories. And saturated-core fault current limiters are emphatically introduced, including its working principle and comparison with the other three categories. Saturated core fault current limiters are divided into four branches according to the ways leading the core saturated. A comprehensive review of the research activities and emerging technologies of saturated-core fault current limiters for AC power systems is presented in this study. The working principle and typical structure of DC-biased-, permanent-magnet-, superconducting- and hybrid-type saturated-core fault current limiters are introduced. The advantages and disadvantages of four types of saturated core fault current limiters are compared in detail from the aspects of current-limiting performance, iron core size and DC magnetomotive force. Real grid application examples of some types of devices are presented, as well as new progress in the techniques, are covered and discussed in detail. One may find the content of this study helpful as a detailed literature review or as practical technical guidance.

Large fault direct current with fast rising speed has always been a significant threat to high voltage direct current systems. Fault current limiters (FCLs) are one of the most promising solutions. However, the biased permanent magnets (PM)s in traditional FCLs have large magnetic reluctance that causes FCLs to have small inductance changing ratios when a fault occurs. In this study, a novel three-limb topology of a saturated iron core-type fault current limiter (TSFCL) is proposed and a central PM bias limb is inserted to force flux flow through this limb. Therefore, the inductance changing ratio is greatly enhanced and the steep rising trend of fault current will be restrained effectively. The operating principles and characteristics of the TSFCL are analyzed to verify the deductions. Moreover, different lengths and cross-sectional areas of the inserted PM are tested and optimization study is carried out. The results show that the clipping inductance has a 55% increase compared with a traditional two-limb model. Moreover, compared with the existing smoothing reactor and traditional two-limb model, proposed topology can decrease the fault current by 45% and 16% within 5 ms, respectively. Finally, a typical HVDC system was built and the effectiveness of proposed TSFCL was verified.

Soft magnetic composites (SMCs) are composed of ferromagnetic particles surrounded by electrical insulation. To establish a homogenization technique for the magnetic field analysis of an electrical machine with an SMC core, we have already proposed a method to evaluate the effective permeability and iron loss of the SMC core using a cell model of one particle taking into account the nonlinear magnetic characteristics and eddy currents. However, the measured eddy current loss cannot be represented by using the proposed method. In this article, a 3-D eddy current analysis method modeling the anomalous eddy current loss due to the movement of domain walls in the cell model is developed based on the Pry and Bean magnetic domain model. The effect of the non-uniformity of the domain structure on the anomalous eddy current loss is investigated. It is shown that the measured eddy current loss can be almost represented by adding the anomalous eddy current loss to the classical one.

The large current generated by a direct start of the super-large-capacity high-voltage induction motor would have a huge impact on the power grid as well as the motor itself. Traditional soft starters have the shortcomings of discontinuous adjustment, voltage sags, sudden torque mutation, secondary current impact and high cost. To resolve this issue, the authors propose a novel coupled autotransformer and magnetic-control (CATMC) soft-start method. The structure of the new CATMC soft starter combines the functions of the autotransformer and magnetic control reactor via an innovative electric and magnetic circuit design. In this study, the authors analyse the magnetic circuit structure and working principles of the CATMC soft starter. Then, to validate its principle and performance, the authors conduct a simulation study using ANSYS software and design and test an 18 MW/10 kV CATMC soft starter prototype. The simulation results demonstrate that the CATMC soft starter effectively avoids secondary current impact and constrains the motor starting current to

A 7-week-old girl with a normal birth history suddenly developed respiratory distress while feeding. Cardiopulmonary resuscitation was initiated at home after she had a cardiac arrest and was continued in the emergency room but all efforts at resuscitation proved unsuccessful and she died 2 h after presentation. Investigations performed in the emergency room revealed that she had a significantly high white blood cell count and severe anaemia. The cause of death was identified as KMT2A-rearranged infantile acute lymphoblastic leukaemia based on cytogenetic tests. She had no abnormalities at the 4-week check-up; however, she developed a skin nodule on her abdomen thereafter, and the family did not consult a doctor for fear of contracting COVID-19. Early detection and diagnosis could have changed the prognosis of the patient. The present case highlights the negative impact of the reduction of outpatient consultations during the COVID-19 pandemic.

Mutations in the mitochondrial tRNAMet gene have been reported in only five patients to date, all of whom presented with muscle weakness and exercise intolerance as signs of myopathy. We herein report the case of a 12-year-old girl with focal epilepsy since the age of eight years. At age 11, the patient developed sudden visual disturbances and headaches accompanied by recurrent, stroke-like episodes with lactic acidosis (pH 7.279, lactic acid 11.6 mmol/L). The patient frequently developed a delirious state, exhibited regression of intellectual ability. Brain magnetic resonance imaging revealed high-intensity signals on T2-weighted images of the left occipital lobe. Mitochondrial gene analysis revealed a heteroplasmic m.4450G > A mutation in the mitochondrial tRNAMet. The heteroplasmic rate of the m.4450G > A mutation in blood, skin, urinary sediment, hair, saliva, and nail samples were 20, 38, 59, 41, 27, and 35%, respectively. The patient’s fibroblast showed an approximately 53% reduction in the oxygen consumption rate, compared to a control, and decreased complex I and IV activities. Stroke-like episodes, lactic acidosis, encephalopathy with brain magnetic resonance imaging findings, and declined mitochondrial function were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. To our knowledge, the findings associated with this first patient with MELAS syndrome harboring the m.4450G > A mutation in mitochondrial tRNAMet expand the phenotypic spectrum of tRNAMet gene.

To reduce the iron loss of a three-phase reactor composed of grain-oriented (GO) silicon steel plates, we proposed two reactor models. One applies oblique joints between the legs and the yokes, and the other applies butt joints composed of non-oriented (NO) silicon steel plates at the L and T joint parts. The proposed models are aimed to relax the flux concentration inside the iron cores that occurs due to the anisotropic magnetic characteristics of GO silicon steel plates. The effectiveness of the proposed models are investigated through magnetic field and iron loss analyses considering the anisotropic magnetic characteristics of the iron cores. It is found that the flux concentration in the yoke can be relaxed in both proposed models. And iron loss of the proposed model with NO steel plates at the L- and T-shaped joints can be reduced about 12% compared with the ordinary one.

Local high iron loss may occur due to the deviation of magnetic flux from the rolling direction of electrical steel in the T-joint area of the transformer core. In this paper, to reduce the iron core loss in the T-joint region, a hybrid iron core model using nonoriented and grain-oriented magnetic materials is proposed. Three-dimensional magnetic field analysis considering the nonlinearity and laminated structure of the original and proposed iron core models is carried out by using the finite element analysis. The flux and iron loss distributions of the original and the hybrid cores are compared. The results show that approximately 2% iron loss reduction can be achieved by using the proposed hybrid structure.

BackgroundCongenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is not well yet investigate.MethodsWe performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment.ResultsOf the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their intelligence quotient. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00–14.37, OR = 4.65; 95% CI: 1.11–19.37). There was no significant difference in physical development (P = 0.64).ConclusionsThe best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is scarce. Methods: We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment. Results: Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their IQ. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00–14.37, OR = 4.65; 95% CI: 1.11–19.37). There was no significant difference in physical development (P = 0.64). Conclusions: The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.

Ring chromosome 20 syndrome is an epileptic and neurodevelopmental encephalopathy that occurs in children, characterised by a triad of refractory frontal lobe seizures, recurrent non-convulsive status epilepticus and frontal lobe-dominant paroxysmal discharges. However, details of other clinical features associated with ring chromosome 20 syndrome remain unknown. Here, we report two patients with ring chromosome 20 syndrome who had praxis-induced reflex seizures. Case 1 was an 11-year-old girl who presented with seizures triggered by specific activities such as mental and written calculations, writing, decision-making, recall, sudden changes in routine or ambient temperature and bathing. During calculations, left frontal lobe-dominant, 3-Hz slow-wave bursts were observed on EEG. Lacosamide effectively suppressed her tonic seizures. Case 2 was a six-year-old boy who presented with seizures triggered by specific activities such as calculations, recall and bathing. During calculations, frontal lobe-dominant, 3-Hz spike and slow-wave bursts were observed on EEG. Although his epilepsy was refractory, gabapentin reduced the frequency of focal seizures. In both cases, the hyperexcitability in the frontal lobe may have spread to the motor cortex and precipitated praxis-induced seizures. Therefore, in addition to the known characteristic triad, praxis-induced reflex seizures may also be a feature of ring chromosome 20 syndrome.

To investigate the noise reduction of an electrical machine, the deformation and vibration of the cores are evaluated by using the coupled magnetic and mechanical analyses [1]. In these analyses, the local force calculated by using the flux distribution obtained from the magnetic field analysis is required in the mechanical analysis. In the local force calculation [2], the Maxwell stress tensor is usually used. The Maxwell stress tensors are often represented by the Minkowski and Chu models with linear and nonlinear energy expressions, respectively. In the nonlinear magnetic field analysis, the volume forces, which move the magnetic bodies, obtained from both models coincide with each other, whereas their local forces, which deform the magnetic bodies, are different. Therefore, more investigation is required to clarify the suitable expression of the Maxwell stress tensor. In this paper, to clarify the proper expression of the Maxwell stress tensor for the local force calculation of a nonlinear magnetic body, the Maxwell stress tensors are derived from the Fleming’s left hand rule because the volume current density can be used to determine the magnetization in the nonlinear magnetic body. As a result, a new Maxwell stress tensor is derived. The surface force obtained from the new Maxwell stress tensor is compared with those obtained from the ordinary Minkowski and Chu models, and the equivalent magnetizing current method [3] to show the effectiveness and validity of the proposed Maxwell stress tensor.