Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children

Unexplained or idiopathic ketotic hypoglycemia (KH) is the most common type of hypoglycemia in children. The diagnosis is based on the exclusion of routine hormonal and metabolic causes of hypoglycemia. We aimed to identify novel genes that cause KH, as this may lead to a more targeted treatment. Deep phenotyping of ten preschool age at onset KH patients (boys, n = 5; girls, n = 5) was performed followed by trio exome sequencing and comprehensive bioinformatics analysis. Data analysis revealed four novel candidate genes: (1) NCOR1 in a patient with KH, iron deficiency and loose stools; (2) IGF2BP1 in a proband with KH, short stature and delayed bone age; (3) SLC5A2 in a proband with KH, intermittent glucosuria and extremely elevated p-GLP-1; and (4) NEK11 in a proband with ketotic hypoglycemia and liver affliction. These genes are associated with different metabolic processes, such as gluconeogenesis, translational regulation, and glucose transport. In conclusion, WES identified DNA variants in four different genes as potential novel causes of IKH, suggesting that IKH is a heterogeneous disorder that can be split into several novel diseases: NCOR1-KH, IGF2BP1-KH, SGLT2-KH or familial renal glucosuria KH, and NEK11-KH. Precision medicine treatment based on exome sequencing may lead to advances in the management of IKH

Fast Super Resolution Ultrasound Imaging using the Erythrocytes

Super resolution (SR) imaging is currently conducted using fragile ultrasound contrast agents. This precludes using the full acoustic pressure range, and the distribution of bubbles has to be sparse for them to be isolated for SR imaging. Images have to be acquired over minutes to accumulate enough positions for visualizing the vasculature. A new method for SUper Resolution imaging using the Erythrocytes (SURE) as targets is introduced, which makes it possible to maximize the emitted pressure for good signal-to-noise ratios. The abundant number of erythrocyte targets make acquisition fast, and the SURE images can be acquired in seconds. A Verasonics Vantage 256 scanner was used in combination with a GE L8-18iD linear array probe operated at 10 MHz for a wavelength of 150 μm. A 12 emissions synthetic aperture ultrasound sequence was employed to scan the kidney of a Sprague-Dawley rat for 24 seconds to visualize its vasculature. An ex vivo micro-CT image using the contrast agent Microfil was also acquired at a voxel size of 22.6 μm for validating the SURE images. The SURE image revealed vessels with a size down to 29 μm, five times smaller than the ultrasound wavelength, and the dense grid of vessels in the full kidney was reliably shown for scan times between 1 to 24 seconds. Visually the SURE images revealed the same vasculature as the micro-CT images. SURE images are acquired in seconds rather than minutes without contrast injection for easy clinical use, and they can be measured at full regulatory levels for pressure, intensity, and probe temperature.<br/

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes