A new validated HPLC method for the determination of levodopa: Application to study the impact of ketogenic diet on the pharmacokinetics of levodopa in Parkinson's participants.

A simple, accurate, and reproducible HPLC-UV method has been developed and validated for the quantification of levodopa (l-Dopa) in human plasma. The method involves a simple protein precipitation procedure to extract both l-Dopa and methyldopa, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an isocratic mobile phase consisting of 20 mm KH2 PO4 (pH 2.5) and methanol (95:5, v/v) run at a flow rate of 1 mL/min. The UV detection wavelength was set at 230 nm. The method exhibited good linearity (R2 > 0.999) over the assayed concentration range (0.1-10 µg/mL) and demonstrated good intra- and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were <15%). This method was also successfully applied for studying the potential effect of ketogenic diet on the pharmacokinetics of l-Dopa in Parkinson's participants. Our data analysis indicates that ketogenic diet does not significantly affect the pharmacokinetics of l-Dopa.

Mutation Update for UBE3A variants in Angelman syndrome.

Angelman syndrome is a neurodevelopmental disorder caused by a deficiency of the imprinted and maternally expressed UBE3A gene. Although de novo genetic and epigenetic imprinting defects of UBE3A genomic locus account for majority of Angelman diagnoses, approximately 10% of individuals affected with Angelman syndrome are a result of UBE3A loss-of-function mutations occurring on the expressed maternal chromosome. The variants described in this manuscript represent the analysis of 2,515 patients referred for UBE3A gene sequencing at our institution, along with a comprehensive review of the UBE3A mutation literature. Of these, 267 (10.62%) patients had a report issued for detection of a UBE3A gene nucleotide variant, which in many cases involved family studies resulting in reclassification of variants of unknown clinical significance (VUS). Overall, 111 (4.41%) probands had a nucleotide change classified as pathogenic or strongly favored to be pathogenic, 29 (1.15%) had a VUS, and 126 (5.0%) had a nucleotide change classified as benign or strongly favored to be benign. All variants and their clinical interpretations are submitted to NCBI ClinVar, a freely accessible human variation and phenotype database.

Can medical schools teach high school students to be scientists?

The preeminence of science in the United States is endangered for multiple reasons, including mediocre achievement in science education by secondary school students. A group of scientists at Oregon Health and Science University has established a class to teach the process of scientific inquiry to local high school students. Prominent aspects of the class include pairing of the student with a mentor; use of a journal club format; preparation of a referenced, hypothesis driven research proposal; and a "hands-on" laboratory experience. A survey of our graduates found that 73% were planning careers in health or science. In comparison to conventional science classes, including chemistry, biology, and algebra, our students were 7 times more likely to rank the scientific inquiry class as influencing career or life choices. Medical schools should make research opportunities widely available to teenagers because this experience dramatically affects one's attitude toward science and the likelihood that a student will pursue a career in science or medicine. A federal initiative could facilitate student opportunities to pursue research.

Neuromuscular disorders in pregnancy.

Many neuromuscular conditions occur more frequently during pregnancy and include carpal tunnel syndrome, Bell's palsy, lumbosacral radiculopathy, meralgia paresthetica, intercostal neuralgia, and other compression neuropathies. Preexisting or coincident neuromuscular diseases, including demyelinating polyneuropathies, inflammatory muscle disease, myasthenia gravis, and inherited nerve and muscle disease present specific problems during pregnancy. We review management of neuromuscular disorders during pregnancy, labor, delivery, and the early postpartum period.