The HCN1 p.Ser399Pro variant causes epileptic encephalopathy with super-refractory status epilepticus.

HCN1 is one of four genes encoding hyperpolarization-activated cyclic nucleotide-gated channels. The phenotypic spectrum associated with HCN1 variants ranges from neonatal developmental and epileptic encephalopathy to idiopathic generalized epilepsy. We report a Japanese patient with repetitive focal seizures and super-refractory status epilepticus since early infancy caused by a de novo HCN1 variant, NM_021072.

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy.

Objective: To report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment.

Methods: A retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included.

A Case of Septic Pulmonary Embolism Caused by Pyelonephritis With Klebsiella pneumoniae in a Patient With Poorly Controlled Type 2 Diabetes Mellitus.

Septic pulmonary embolism (SPE) is caused by the microbe that is responsible for any clinical condition that may include urinary tract infections as in this case. We report a case of pyelonephritis with that led to SPE in an 80-year-old woman with poorly controlled diabetes mellitus (DM). Computed tomography (CT) revealed multiple nodules in the peripheral area of the bilateral lung and a contrast defect in the right renal vein, which was suspected to be an embolism.

STAT3 suppression and β-cell ablation enhance α-to-β reprogramming mediated by Pdx1.

As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, possible methods to efficiently generate surrogate β cells have attracted a lot of efforts. To date, insulin-producing cells have been generated from various differentiated cell types in the pancreas, such as acinar cells and α cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate β cells can be efficiently generated for establishing future regenerative therapies for diabetes. In this study, we demonstrated that the exogenous expression of PDX1 activated STAT3 in α cells in vitro, and STAT3-null PDX1-expressing α cells in vivo resulted in efficient induction of α-to-β reprogramming, accompanied by the emergence of α-cell-derived insulin-producing cells with silenced glucagon expression.

Cumulative autophagy insufficiency in mice leads to progression of β-cell failure.

Autophagy is known to play a pivotal role in β-cell function. While the lifelong inhibition of autophagy through Atg7 deletion in β cells has been demonstrated to lead to impaired glucose tolerance together with β-cell dysfunction, the temporal association between autophagy inhibition and β-cell dysfunction remains unclear. To address such questions, inducible β-cell-specific Atg7-knockout (iβAtg7) mice were generated, and autophagy inhibition was induced for two different time durations.

De novo ATP1A3 variants cause polymicrogyria.

Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo variants in eight patients. Mutated causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS).

13q13.3 microdeletion associated with apparently balanced translocation of 46,XX,t(7;13) suggests NBEA involvement.

Background: Deletion of 13q13.3 is an extremely rare event.

Case: We report on a 25-month-old girl with neurodevelopmental disorder and intellectual disability.

Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production.

Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While β-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period.

Conversion of pancreatic α cells into insulin-producing cells modulated by β-cell insufficiency and supplemental insulin administration.

The emergence of bihormonal (BH) cells expressing insulin and glucagon has been reported under diabetic conditions in humans and mice. Whereas lineage tracing studies demonstrated that glucagon-producing α cells can be reprogrammed into BH cells, the underlying dynamics of the conversion process remain poorly understood. In the present study, we investigated the identities of pancreatic endocrine cells by genetic lineage tracing under diabetic conditions.

Cellular Autophagy in Cells Plays a Role in the Maintenance of Islet Architecture.

Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining -cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting cells. To investigate the role of autophagy in cells, we generated a mutant mouse model lacking , a key molecule for autophagosome formation, specifically in cells.

Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.

Background: STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, whereas an activating STAT3 mutation has been linked to impaired β-cell function.

Methods: The role of STAT3 in β-cell neogenesis, induced by the exogenous expression of Pdx1, Neurog3, and Mafa, was analyzed in vitro and in vivo.

Findings: The expression of phosphorylated STAT3 (pSTAT3) was induced in both Pdx1-expressing and Mafa-expressing cells, but most of the induced β cells were negative for pSTAT3.

Heterogeneity of autophagic status in pancreatic β cells under metabolic stress.

Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice.

Current Therapeutic Drugs Against Cerebral Vasospasm after Subarachnoid Hemorrhage: A Comprehensive Review of Basic and Clinical Studies.

Background: Cerebral vasospasm (CVS) is well known as a major complication in subarachnoid hemorrhage (SAH) patients, and research has long been focused on improving morbidity and mortality. As CVS commonly develops from day 4 to day 14 after SAH onset, SAH patients require therapies with drugs for preventing CVS after surgical treatment for the source of hemorrhage, mostly ruptured intracranial aneurysms. It is thought that the pathogenesis of CVS is initiated by prolonged smooth muscle contraction, and the subsequent hypoperfusion and cytotoxic responses induce cerebral ischemia.

Bilateral posterior fossa chronic subdural hematoma treated with craniectomy: Case report and review of the literature.

Background: Posterior chronic subdural hematomas (pCSHs) are rare. Their diagnosis and treatment are difficult.

Description: A 69-year-old woman was admitted to our hospital with nausea, headache, and mild consciousness disturbance.

A spontaneous superficial temporal artery pseudoaneurysm possibly related to atherosclerosis: Case report and review of literature.

Background: Spontaneous superficial temporal artery (STA) pseudoaneurysms are very rare; only four cases, including ours, have been reported to date. Therefore, the cause of them has not been studied.

Case Description: A 57-year-old woman was admitted to our hospital with a pulsatile mass in the left preauricular region.

Sequential changes in Rotterdam CT scores related to outcomes for patients with traumatic brain injury who undergo decompressive craniectomy.

OBJECT Rotterdam CT scoring is a CT classification system for grouping patients with traumatic brain injury (TBI) based on multiple CT characteristics. This retrospective study aimed to determine the relationship between initial or preoperative Rotterdam CT scores and TBI prognosis after decompressive craniectomy (DC). METHODS The authors retrospectively reviewed the medical records of all consecutive patients who underwent DC for nonpenetrating TBI in 2 hospitals from January 2006 through December 2013.

[A case of advanced gastric cancer with disseminated carcinomatosis of bone marrow treated by S-1 and CDDP].

A 33-year-old man was admitted to our hospital due to DIC and multiple bone metastasis after distal gastrectomy for gastric cancer (Stage IIIB). We diagnosed disseminated carcinomatosis of bone marrow by gastric cancer. The patient was treated with combination chemotherapy of S-1 and CDDP (S-1 80 mg/m (2), po, day 1-21 and CDDP 60 mg/m(2), iv, day 8).

Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke: their role in the formation of stable and unstable carotid atherosclerotic plaques.

Background: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II in stable and unstable carotid atherosclerotic plaques from symptomatic and asymptomatic patients.

Methods: Using immunohistochemical methods, we studied differences between carotid atherosclerotic lesions obtained at carotid endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28) patients.

Brain metastases from asymptomatic adenocarcinoma of the pancreas: an autopsy case report.

Background: Brain metastasis from pancreatic cancer is extremely rare. Because pancreatic cancer usually has a rapidly progressive nature, the majority of affected patients die from primary lesions before exhibiting clinical signs suggestive of brain metastases.

Case Description: The patient was a 62-year-old man who developed generalized convulsion followed by right hemiparesis accompanied by decreased consciousness level.

Recovery from marked altered consciousness in a patient with adult-onset type II citrullinemia diagnosed by DNA analysis and treated with a living related partial liver transplantation.

A 21-year-old woman was admitted with altered consciousness and hyperammonemia. She was diagnosed as having adult-onset type II citrullinemia (CTLN2) by DNA analysis. The patient had mutations of the SLC25A13 gene, which were compound heterozygotes of 851 del 4 and IVS11+1G>A.