We sequenced the alpha-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. Results: Ninety-three of 100 study subjects had normal alpha-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence,

1%; 95% confidence interval, <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of Fabry disease. Investigation Batimastat mouse results suggestive of Fabry disease (idiopathic hypertrophic cardiomyopathy, Fludarabine cell line proteinuria, vertebrobasilar dolichoectasia, and the pulvinar sign) were found only in subjects with normal alpha-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. Conclusions: Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification

of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening.”
“Concanavalin A (ConA)-conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (ConA-NPs) were prepared for targeted drug delivery to the cervical lymph nodes after intranasal administration. ConA, a

lectin specifically binding to alpha-mannose and alpha-glucose, was covalently conjugated on NPs without loss of its carbohydrates binding bioactivity. In vitro cellular uptake experiment demonstrated that NPs could be uptaken by Calu-3 cells in a time-and concentration-dependent manner, and conjugation of ConA on NPs could significantly increase the rate and amount of cellular uptake. ConA-NP showed no obvious toxicity to Calu-3 AZD9291 cells in vitro or to the nasal cilia of rats in vivo. Compared with NPs without ConA, ConA-NP is more effective in targeting drugs to the deep cervical lymph nodes, as evidenced by 1.36-2.52 times increase of targeting efficiency, demonstrating that ConA-NP is a potential carrier for targeted drug delivery to the cervical lymph nodes via nasal route.”
“A 6-year-old girl with type 3 long QT syndrome was safely and successfully implanted with an implantable cardioverter-defibrillator (ICD) system. Prior to implantation, she had experienced uncontrollable life-threatening arrhythmia in spite of high-dose administration of mexiletine. An ICD coil lead for transvenous use was placed in the intrapericardial and retrocardial space and was connected to a generator placed in front of the posterior sheath of the right abdominal rectal muscle.