Immunogenicity dynamics and covariate effects after satralizumab administration predicted with a hidden Markov model.

Immunogenicity is the propensity of a therapeutic protein to generate an immune response to itself. While reporting of antidrug antibodies (ADAs) is increasing, model-based analysis of such data is seldom performed. Model-based characterization of factors affecting the emergence and dissipation of ADAs may inform drug development and/or improve understanding in clinical practice.

Adrenal Insufficiency Associated With Empty Sella Syndrome and Steroid Malabsorption Complicated With Septic Shock Due to Post-transplant Pyelonephritis: A Case Report.

Renal transplant recipients are immunocompromised and predisposed to develop hyponatremia because they are exposed to immunological, infectious, pharmacological, and oncologic disorders. A 61-year-old female renal transplant recipient was admitted with diarrhea, anorexia, and headache for about a week during the tapering of oral methylprednisolone for chronic renal allograft rejection. She also presented hyponatremia and was suspected to have secondary adrenal insufficiency based on a low plasma cortisol level of 1.

Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice.

The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse ("social instigation") resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice.

Diffusion magnetic resonance tractography-based evaluation of commissural fiber abnormalities in a heparan sulfate endosulfatase-deficient mouse brain.

During brain development, neural circuits are formed through cellular differentiation, cell migration, axon guidance, and synaptogenic processes by the coordinated actions of many genes. Abnormalities in neural development, especially connectivity defects, can result in psychiatric disorders, such as schizophrenia and autism. Recent advances in diffusion tensor imaging have enabled us to examine the brain's macroscopic nerve trajectories.

Stepwise synaptic plasticity events drive the early phase of memory consolidation.

Memories are initially encoded in the hippocampus but subsequently consolidated to the cortex. Although synaptic plasticity is key to these processes, its precise spatiotemporal profile remains poorly understood. Using optogenetics to selectively erase long-term potentiation (LTP) within a defined temporal window, we found that distinct phases of synaptic plasticity play differential roles.

Expression of Heparan Sulfate Endosulfatases in the Adult Mouse Brain: Co-expression of and Dopamine D1/D2 Receptors.

The heparan sulfate 6--endosulfatases, Sulfatase 1 (Sulf1), and Sulfatase 2 (Sulf2), are extracellular enzymes that regulate cellular signaling by removing 6--sulfate from the heparan sulfate chain. Although previous studies have revealed that are essential for normal development, their functions in the adult brain remain largely unknown. To gain insight into their neural functions, we used hybridization to systematically examine mRNA expression in the adult mouse brain.

Hereditary spherocytosis diagnosed with extremely low glycated hemoglobin compared to plasma glucose levels.

Glycated hemoglobin (HbA1c) is an important indicator of glycemic control in patients with diabetes. High-performance liquid chromatography (HPLC) is the most commonly used method for measuring HbA1c levels; as HPLC measures all hemoglobin types, the values can be influenced by hemoglobin variants. Moreover, as HPLC-HbA1c levels are low in some diseases, including hemolytic anemia, it may be difficult to differentiate hemoglobin variants from these diseases based on HPLC-HbA1c levels alone.

Deciphering the premature mortality in PIGA-CDG - An untold story.

Objective: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality.

Clinical characteristics associated with 1-year tolvaptan efficacy in autosomal dominant polycystic kidney disease with a wide range of kidney functions.

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR).

Parathyroidectomy for tertiary hyperparathyroidism after second kidney transplantation: a case report.

Successful kidney transplantation usually resolves secondary hyperparathyroidism (SHPT). However, some patients fail to normalize, and their condition is often referred to as tertiary hyperparathyroidism (THPT). Surgical consensus on the timing of post-transplant parathyroidectomy (PTX) for THPT has not been reached.

Learning difficulties in Japanese schoolchildren with focal epilepsy.

Background: Children with epilepsy often show some degree of cognitive impairment. In this study, we investigated their learning skills to clarify the characteristics of the difficulties related to learning in Japanese-speaking children with focal epilepsy.

Methods: The study included 13 boys and 17 girls of mean age 9.

Orphan Nuclear Receptor RORα Regulates Enzymatic Metabolism of Cerebral 24S-Hydroxycholesterol through CYP39A1 Intronic Response Element Activation.

Oxysterols, important regulators of cholesterol homeostasis in the brain, are affected by neurodegenerative diseases. Early-onset Alzheimer's disease is associated with higher levels of circulating brain-derived 24S-hydroxycholesterol (24S-OHC). Conversion of cholesterol to 24S-OHC is mediated by cholesterol 24S-hydroxylase in the brain, which is the major pathway for oxysterol elimination, followed by oxidation through hepatic first-pass metabolism by CYP39A1.

Retinoic acid receptor-related orphan receptor α reduces lipid droplets by upregulating neutral cholesterol ester hydrolase 1 in macrophages.

Background: Neutral cholesterol ester hydrolase 1 (NCEH1) catalyzes the hydrolysis of cholesterol ester (CE) in macrophages. Genetic ablation of NCEH1 promotes CE-laden macrophages and the development of atherosclerosis in mice. Dysregulation of NCEH1 levels is involved in the pathogenesis of multiple disorders including metabolic diseases and atherosclerosis; however, relatively little is known regarding the mechanisms regulating NCEH1.

Cognitive dysfunction during hypoglycemia in an elderly subject without diabetes.

The aim of the present study was to examine whether an elderly subject without diabetes experiences hypoglycemia during his daily life or after an oral glucose tolerance test (OGTT), and investigate whether hypoglycemic episodes affect cognitive function. The 85-year-old healthy subject, who is a sports enthusiast, showed lower than normal (< 80 mg/dl) blood glucose levels on two occasions over 6 days in the early morning. The subject also experienced hypoglycemic episodes and blood glucose levels of 65 and 74 mg/dl, respectively, during the 6-h OGTT given after a 13-h fast.

Toddler Neurodevelopmental Outcomes Are Associated With School-Age IQ in Children With Single Ventricle Physiology.

To examine whether neurodevelopment at preschool age predicts IQ levels and needs for special education services in school-age children with single ventricle (SV) physiology. Thirty-five patients with SV physiology were assessed using the Bayley Scale of Infant and Toddler Development (BSID) II or III at 3 years and the Wechsler Intelligence Scale for Children-Fourth Edition (WISC) at 8 years. Whether the children were receiving special education services was also determined.

Circulating FGF23 is not associated with cardiac dysfunction, atherosclerosis, infection or inflammation in hemodialysis patients.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone regulating serum inorganic phosphate (Pi) concentration. FGF23 is also involved in the development of chronic kidney disease (CKD)-mineral and bone disorder. Serum FGF23 concentration begins to increase early in the progression of CKD and can be remarkably high in hemodialysis patients with end-stage renal disease.

Autophosphorylation of F-actin binding domain of CaMKIIβ is required for fear learning.

CaMKII is a pivotal kinase that plays essential roles in synaptic plasticity. Apart from its signaling function, the structural function of CaMKII is becoming clear. CaMKII - F-actin interaction stabilizes actin cytoskeleton in a dendritic spine.

Non-Compartmental Pharmacokinetics and Safety of Single-Dose Eldecalcitol (ED-71) in Healthy Chinese Adult Males.

Background And Objectives: Eldecalcitol (ED-71) is a novel active vitamin D derivative, used for the treatment of osteoporosis. This is the first clinical study to investigate the pharmacokinetics and safety of eldecalcitol in Chinese subjects.

Methods: This was an open, single-center, randomized, two-dose level, two-period crossover phase I study in 24 healthy Chinese adult males.

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.

Objective: Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients.

Aldosterone and Insulin Resistance: Vicious Combination in Patients on Maintenance Hemodialysis.

Recently, we demonstrated that plasma aldosterone contributed to insulin resistance in chronic kidney disease. The aim of this study is the clinical impact of this relationship in hemodialysis patients. In a cross section study using a total of 128 hemodialysis patients, multiple regression analysis revealed that plasma aldosterone levels were independently associated with HOMA-IR, insulin resistance index.

MODY3, renal cysts, and Dandy-Walker variants with a microdeletion spanning the HNF1A gene.

Heterozygous hepatocyte nuclear factor-1-α gene (HNF1A) mutations are the most common cause of maturity-onset diabetes of the young (MODY), but they rarely involve extrahepatic manifestations. Renal cysts and diabetes syndrome can be caused by HNF1B mutations. No association between MODY3 and Dandy-Walker variants (DWV) has been reported.

Epileptic apnea in a patient with inherited glycosylphosphatidylinositol anchor deficiency and PIGT mutations.

We report an 11-month-old boy with acetazolamide-responsive epileptic apnea and inherited glycosylphosphatidylinositol (GPI)-anchor deficiency who presented with decreased serum alkaline phosphatase associated with compound PIGT mutations. The patient exhibited congenital anomalies, severe intellectual disability, and seizures, including epileptic apnea with epileptiform discharges from bilateral temporal areas. Brain magnetic resonance imaging revealed delayed myelination and progressive atrophy of the brainstem, cerebellum, and cerebrum.