Discovery of 5-phenyl-3-ureidothiophene-2-carboxamides as protective agents for ALS patient iPSC-derived motor neurons.

We discovered novel neuroprotective compounds by phenotypic screening using SOD1-mutant amyotrophic lateral sclerosis (ALS) patient induced pluripotent stem cell (iPSC)-derived motor neurons. Mechanistic analysis showed that the protective effect of initial hit compound 1 was likely due to the inhibition of MAP4Ks, including MAP4K4, a member of the MAP4K kinase family. Structural transformation led to compound 15f, which showed improved MAP4K4 inhibitory activity and superior neuroprotective effects compared to 1 in motor neurons.

Nonconvulsive status epilepticus following rotavirus gastroenteritis in two pediatric patients.

Background: Nonconvulsive status epilepticus (NCSE) comprises a range of conditions in which prolonged electrographic seizures result in nonconvulsive clinical symptoms. An understanding of NCSE is especially important in emergency care. Among the various causes of NCSE, an infectious etiology has been rarely reported to date.

Rare case of gastric inflammatory fibroid polyp located at the fornix of the stomach and mimicking gastric cancer: a case report.

Background: Gastric inflammatory fibroid polyp (IFP) is a rare polypoid lesion of the stomach that is characterized pathologically by the presence of spindle cells, a prominent network of blood vessels, and inflammatory infiltration of eosinophils. IFP is mainly located in the gastric antrum and is usually semi-pedunculated and covered with normal mucosa. There have been several reports of large IFPs with ulceration on the surface, at the apex, but no report of the IFP with ulceration at the fornix of the stomach.

Long-Term Evaluation of Low-Dose Betamethasone for Ataxia Telangiectasia.

Background: Ataxia telangiectasia is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Quality of life is severely impaired by neurological symptoms. However, curative options for the neurological symptoms are limited.

De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies.

Potocki-Shaffer syndrome (PSS) is a contiguous gene syndrome caused by 11p11.2 deletions. PSS is clinically characterized by intellectual disability, craniofacial anomalies, enlarged parietal foramina, and multiple exostoses.

Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders.

Objectives: Defects in DNA damage responses or repair mechanisms cause numerous rare inherited diseases, referred to as "DNA-repair defects" or "DNA damage deficiency", characterized by neurodegeneration, immunodeficiency, and/or cancer predisposition. Early accurate diagnosis is important for informing appropriate clinical management; however, diagnosis is frequently challenging and can be delayed, due to phenotypic heterogeneity. Comprehensive genomic analysis could overcome this disadvantage.

De novo PHACTR1 mutations in West syndrome and their pathophysiological effects.

Trio-based whole exome sequencing identified two de novo heterozygous missense mutations [c.1449T > C/p.(Leu500Pro) and c.

Discovery of Peripheral κ-Opioid Receptor Agonists as Novel Analgesics.

κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective κ-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10α-hydroxy derivatives.

Discovery of highly selective κ-opioid receptor agonists: 10α-Hydroxy TRK-820 derivatives.

κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor are attractive targets in the development of drugs for pain and pruritus. We previously reported the synthesis of 10α-hydroxy TRK-820 (1). In this study, we elucidated the biological properties of 1 and optimized its 6-acyl unit by modifying our synthetic route.

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms.

Immediate suppression of seizure clusters by corticosteroids in PCDH19 female epilepsy.

Purpose: The pathomechanism and treatment of PCDH19 female epilepsy (PCDH19-FE) remain unclear. Here, we report that corticosteroids are effective for control of the seizure clusters or other acute symptoms of PCDH19-FE and argue for the possible involvement of a compromised blood-brain barrier (BBB) in its pathogenesis.

Methods: The efficacy of corticosteroids was retrospectively reviewed in five Japanese patients with PCDH19-FE.

Aicardi-Goutières syndrome is caused by IFIH1 mutations.

Aicardi-Goutières syndrome (AGS) is a rare, genetically determined early-onset progressive encephalopathy. To date, mutations in six genes have been identified as etiologic for AGS. Our Japanese nationwide AGS survey identified six AGS-affected individuals without a molecular diagnosis; we performed whole-exome sequencing on three of these individuals.

Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement.

Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated concentration of circulating serum anti-thyroid antibodies usually responsive to steroid therapy. We report a 13-year-old girl with Hashimoto encephalopathy and peripheral nervous system involvement. The child had experienced high-grade pyrexia, global headache and sleeplessness.

Recurrent upside-down stomach after endoscopic repositioning and gastropexy treated by laparoscopic surgery.

Patients with an upside-down stomach usually receive surgical treatment. In high-risk patients, endoscopic repositioning and gastropexy can be performed. However, the risk of recurrence after endoscopic treatment is not known.

PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy.

Abnormalities in the protocadherin 19 (PCDH19) gene cause early-onset epilepsy exclusively in females. We aimed to explore the genetic and clinical characteristics of PCDH19-related epilepsy by focusing on its early features and treatment efficacy. PCDH19 was analyzed in 159 Japanese female patients with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis.

Kawasaki disease complicated by mild encephalopathy with a reversible splenial lesion (MERS).

We reported four patients (2 to 10 years) with Kawasaki disease complicated by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). All were treated with γ-globulin (2 to 6 g/kg) after the diagnosis of Kawasaki disease, the fever being alleviated between day 6 and 25. One of two patients exhibiting a poor response to γ-globulin had a cardiac aneurysm as a sequela.

Knockdown of XAB2 enhances all-trans retinoic acid-induced cellular differentiation in all-trans retinoic acid-sensitive and -resistant cancer cells.

Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis. Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging.

Sibling cases of Vici syndrome: sleep abnormalities and complications of renal tubular acidosis.

Vici syndrome is a rare congenital disorder characterized by albinism, agenesis of the corpus callosum, and developmental delays. Cardiac complications usually cause poor prognosis. We report sibling cases of Vici syndrome, and address complications of renal tubular acidosis.

Cold spinoplegia and transvertebral cooling pad reduce spinal cord injury during thoracoabdominal aortic surgery.

Objective: We examined the protective effects of the new selective spinal cord cooling by using cold saline infusion into the cross-clamped aorta and a transvertebral cooling pad placed over the lumbar vertebral column from paraplegia caused by ischemic spinal cord injury on thoracoabdominal aortic surgery.

Methods: Eighteen rabbits were divided into three groups: groups I, II, and III (n = 6 for each group). In group I (37 degrees C; 5 mL) and group II (3 degrees C; 5 mL), saline was infused into the isolated aortic segment twice, at 0 and 5 minutes after aortic cross clamping.

Intra-aortic injection of propofol prevents spinal cord injury during aortic surgery.

Objective: We investigated whether propofol, a widely used anesthetic, injected into clamped aortic segments quickly attenuated transcranial spinal motor-evoked potential (MEP) amplitudes and protected against spinal cord injury during thoracoabdominal aortic surgery.

Methods: Eighteen beagle dogs were divided into three groups (n=6, each group): group 1 (20 ml of saline, intra-aortic injection), group 2 (1.5 mg/kg of propofol, intravenous injection), and group 3 (1.

Cold saline injection attenuates motor-evoked potential in the spinal cord by cortical electrical stimulation in the dog.

Changes in the motor-evoked potential of the spinal cord with transcranial stimulation are monitored for spinal cord function during thoracoabdominal aortic aneurysm surgeries. We examined the effects of changes in motor-evoked potential with cold saline injected into the clamped segment of the aorta, and compared the effects to lidocaine and warm saline injection. Eighteen dogs were divided into three groups according to the injected agents: Warm saline group (37 degrees C, 20 ml), Cold saline group (4 degrees C, 20 ml), and Lidocaine group (5.