CHARGE syndrome in a child with a variant and a novel pathogenic variant: A case report.

CHARGE syndrome is a clinically heterogeneous condition that typically presents with a loss-of-function mutation in . SOX2 anophthalmia syndrome is a rare condition associated with hypogonadism and hearing loss. Herein, we describe the case of a Japanese boy presenting with a micropenis, bilateral cryptorchidism, cupped ear, right facial nerve palsy, and bilateral hearing loss, clinically meeting the diagnostic criteria for CHARGE syndrome, but with optic nerve hypoplasia, which is atypical for the syndrome.

Coordinated linear and rotational movements of endothelial cells compartmentalized by VE-cadherin drive angiogenic sprouting.

Angiogenesis is a sequential process to extend new blood vessels from preexisting ones by sprouting and branching. During angiogenesis, endothelial cells (ECs) exhibit inhomogeneous multicellular behaviors referred to as "cell mixing," in which ECs repetitively exchange their relative positions, but the underlying mechanism remains elusive. Here we identified the coordinated linear and rotational movements potentiated by cell-cell contact as drivers of sprouting angiogenesis using and approaches.

Persistent homological cell tracking technology.

In this paper, we develop a cell tracking method based on persistent homological figure detection technology. We apply our tracking method to 9 different time-series cell images and extract several kinds of cell movements. Being able to analyze various images with a single method allows researchers to systematically understand and compare different tracking data.

Knowns and unknowns about congenital hypothyroidism: 2022 update.

Several excellent guidelines and expert opinions on congenital hypothyroidism (CH) are currently available. Nonetheless, these guidelines do not address several issues related to CH in detail. In this review, the authors chose the following seven clinical issues that they felt were especially deserving of closer scrutiny in the hope that drawing attention to them through discussion would help pediatric endocrinologists and promote further interest in the treatment of CH.

Acrodysostosis and pseudohypoparathyroidism (PHP): adaptation of Japanese patients with a newly proposed classification and expanding the phenotypic spectrum of variants.

Objective: This study aimed to report on 15 Japanese patients with acrodysostosis and pseudohypoparathyroidism (PHP) and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients.

Design: We divided the patients into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects.

Methods: We carried out clinical, radiological and genetic evaluations of two patients in group A (iPPSD5), six patients in group B (iPPDS4) and seven patients in group C (iPPSD2).

Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic β-cell function under autophagy deficiency.

Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that β-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that β-cell-specific p62 deficiency does not cause any apparent impairment in glucose metabolism.

Experimental study on car collisions with bicycles equipped with child seats.

In Japan, traffic accidents involving bicycles have become a serious problem as a result of the increase in the use of bicycles due to the rising concerns of environmental and health problems. In recent years, bicycles equipped with child seats have become a popular means of transportation for preschool children in urban areas in Japan. Under such adverse circumstances, it is necessary to conduct more studies and evaluations to prevent traffic accidents and the resulting injuries involving bicycles with children.

Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography.

Background: Subclinical diastolic dysfunction in patients with Type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied.

PERK-Mediated Suppression of microRNAs by Sildenafil Improves Mitochondrial Dysfunction in Heart Failure.

Oxidative/nitrosative stress is a major trigger of cardiac dysfunction, involving the unfolded protein response and mitochondrial dysfunction. Activation of nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling by sildenafil improves cardiac mal-remodeling during pressure-overload-induced heart failure. Transcriptome analysis was conducted in failing hearts with or without sildenafil treatment.

Retrospective study of the renal function using estimated glomerular filtration rate and congenital anomalies of the kidney-urinary tract in pediatric Turner syndrome.

Although Turner syndrome (TS) is frequently associated with congenital anomalies of the kidney-urinary tract (CAKUT), which is a major cause of pediatric chronic kidney disease, renal function in TS is usually considered normal. The present study aimed to analyze the frequency of renal dysfunction and CAKUT in pediatric patients with TS. Our study included 122 patients with TS between the ages of 2 and 18 years from 30 hospitals across Japan.

A nationwide questionnaire survey targeting Japanese pediatric endocrinologists regarding transitional care in childhood, adolescent, and young adult cancer survivors.

Existing guidelines recommend long-term follow-up of childhood cancer survivors (CCS). However, in Japan, transitional care for CCS has not been established. To ascertain the current status in Japan, and to cultivate a better understanding, a questionnaire survey was conducted on transitional care in CCS, and adolescent and young adult (AYA) cancer survivors.

Levothyroxine Dosage as Predictor of Permanent and Transient Congenital Hypothyroidism: A Multicenter Retrospective Study in Japan.

Background: Congenital hypothyroidism (CH) can be divided into 2 types, transient CH (T-CH) and permanent CH (P-CH), depending on the requirement of levothyroxine (LT4) for life-long treatment. Several studies have recently reported that the LT4 dosage is useful for predicting the LT4 requirement, but none of the studies followed their patients to puberty.

Objective: To determine the cutoff value for the LT4 dosage as a predictor of the LT4 requirement after puberty in patients with CH.

Establishment of a system for screening autophagic flux regulators using a modified fluorescent reporter and CRISPR/Cas9.

Autophagy is a mechanism of bulk protein degradation that plays an important role in regulating homeostasis in many organisms. Among several methods for evaluating its activity, a fluorescent reporter GFP-LC3-RFP-LC3ΔG, in which GFP-LC3 is cleaved by ATG4 following autophagic induction and degraded in lysosome, has been used for monitoring autophagic flux, which is the amount of lysosomal protein degradation. In this study, we modified this reporter by exchanging GFP for pHluorin, which is more sensitive to low pH, and RFP to mCherry, to construct pHluorin-LC3-mCherry reporter.

Cohesive and anisotropic vascular endothelial cell motility driving angiogenic morphogenesis.

Vascular endothelial cells (ECs) in angiogenesis exhibit inhomogeneous collective migration called "cell mixing", in which cells change their relative positions by overtaking each other. However, how such complex EC dynamics lead to the formation of highly ordered branching structures remains largely unknown. To uncover hidden laws of integration driving angiogenic morphogenesis, we analyzed EC behaviors in an in vitro angiogenic sprouting assay using mouse aortic explants in combination with mathematical modeling.

In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Type 1 Diabetes Mellitus Using Layer-Specific Strain Analysis.

Background: Although the subclinical left ventricular (LV) dysfunction caused by diabetes mellitus (DM) results in a high risk of death and heart failure, the details of cardiac dysfunction across a wide age range remain unclear. The aim of this study was to assess LV dysfunction in patients with type 1 DM (T1DM) using layer-specific strain analysis by echocardiography.

Methods and results: The 52 patients (median age: 23 [range: 5-40] years) with T1DM were divided into 3 age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-40 years); 78 age- and sex-similar controls were divided into 3 corresponding groups (C1, C2, and C3).

Current Vitamin D Status in Healthy Japanese Infants and Young Children.

This study aimed to characterize serum 25-hydroxyvitamin D (25OH-D) values among Japanese children aged ≤48 mo. The study included 290 healthy infants and young children aged 0-48 mo (males/females=166/124) living in Shizuoka or Tokyo. The subjects were divided into three groups by age (Low Age: 0-5, Middle Age: 6-15, High Age: 16-48 mo).

Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan.

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan.

NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features.

Aims: Only a few families with neuronal differentiation 1 (NEUROD1)-deficient diabetes, currently designated as maturity-onset diabetes of the young 6 (MODY6), have been reported, but mostly in Caucasian, and no mutation has been identified by family-based screening in Japanese. Accordingly, the phenotypic details of the disease remain to be elucidated.

Methods: We examined a total of 275 subjects having diabetes suspected to be MODY who were negative for mutations in MODY1-5 referred from 155 medical institutions throughout Japan.

Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs.

Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs).

Nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non-obese diabetic mouse, in patients with type 1 diabetes.

Aims/introduction: Although genome-wide association studies have identified more than 50 susceptibility genes for type 1 diabetes, low-frequency risk variants could remain unrecognized. The present study aimed to identify novel type 1 diabetes susceptibility genes by newly established methods.

Materials And Methods: We carried out whole-exome sequencing and genome-wide copy-number analysis for a Japanese family consisting of two patients with type 1 diabetes and three unaffected relatives.

FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

Aim: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children.

Methods: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined.