A Novel Robot-Assisted Kinematic Measure for Children with Attention-Deficit/Hyperactivity Disorder: A Preliminary Study.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. In contrast to neurocognitive measurements of inattention and impulsivity, there has been limited research regarding the objective measurement of hyperactivity in youths with ADHD. The purpose of the present study was to investigate the clinical effectiveness of a newly developed Robot-assisted Kinematic Measure for ADHD (RAKMA) in children with ADHD.

Mapping the Tooth Enamel Proteome and Amelogenin Phosphorylation Onto Mineralizing Porcine Tooth Crowns.

Tooth enamel forms in an ephemeral protein matrix where changes in protein abundance, composition and posttranslational modifications are critical to achieve healthy enamel properties. Amelogenin (AMELX) with its splice variants is the most abundant enamel matrix protein, with only one known phosphorylation site at serine 16 shown to be critical for regulating mineralization. The phosphorylated form of AMELX stabilizes amorphous calcium phosphate, while crystalline hydroxyapatite forms in the presence of the unphosphorylated protein.

Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3.

Inhibition of triacylglycerol (TAG) biosynthetic enzymes has been suggested as a promising strategy to treat insulin resistance, diabetes, dyslipidemia, and hepatic steatosis. Monoacylglycerol acyltransferase 3 (MGAT3) is an integral membrane enzyme that catalyzes the acylation of both monoacylglycerol (MAG) and diacylglycerol (DAG) to generate DAG and TAG, respectively. Herein, we report the discovery and characterization of the first selective small molecule inhibitors of MGAT3.

Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver.

Intrahepatic lipid accumulation is extremely common in obese subjects and is associated with the development of insulin resistance and diabetes. Hepatic diacylglycerol and triacylglycerol synthesis predominantly occurs through acylation of glycerol-3-phosphate. However, an alternative pathway for synthesizing diacylglycerol from monoacylglycerol acyltransferases (MGAT) could also contribute to hepatic glyceride pools.

Local heat application to the leg reduces muscle sympathetic nerve activity in human.

The study was designed to assess the effects of local heat (LH) application on postganglionic muscle sympathetic nerve activity (MSNA) measured by microneurography in healthy men. In the first protocol, MSNA of the left peroneal nerve, blood pressure (BP), heart rate (HR), and skin temperature of the shin (TSK) were recorded in nine men. In the second protocol, leg blood flow (LBF) was measured in the same subjects by strain-gauge plethysmography.

Necrotizing fasciitis in a neonate - the role of keratinocyte allografts.

The authors report the case of a 9-day-old female infant with necrotizing fasciitis of the lower back due to methicillin-resistant Staphylococcus aureus (MRSA) to emphasize the role of keratinocyte allografts. Keratinocyte allografts were found helpful in this case to manage an extensive skin defect.