Minimum Effective Dose to Achieve Biochemical Correction with Adeno-Associated Virus Vector-Mediated Gene Therapy in Mice with Pompe Disease.

Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA), resulting in skeletal muscle weakness and cardiomyopathy. Muscle weakness progresses despite currently available therapy, which has prompted the development of gene therapy with adeno-associated virus (AAV) type 2 vectors cross-packaged as AAV8 (2/8). Preclinical studies of gene therapy demonstrated that the minimum effective dose (MED) for biochemical correction with AAV2/8-LSPhGAA was ∼2 × 10 vector genomes (vg)/kg body weight.

Efficacious Androgen Hormone Administration in Combination with Adeno-Associated Virus Vector-Mediated Gene Therapy in Female Mice with Pompe Disease.

Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA), resulting in skeletal muscle weakness and cardiomyopathy that progresses despite currently available therapy in some patients. The development of gene therapy with adeno-associated virus (AAV) vectors revealed a sex-dependent decrease in efficacy in female mice with Pompe disease. This study evaluated the effect of testosterone on gene therapy with an AAV2/8 vector containing a liver-specific promoter to drive expression of GAA (AAV2/8-LSPhGAA) in female GAA-knockout (KO) mice that were implanted with pellets containing testosterone propionate before vector administration.

Temporal and spatial earthquake clustering revealed through comparison of millennial strain-rates from Cl cosmogenic exposure dating and decadal GPS strain-rate.

To assess whether continental extension and seismic hazard are spatially-localized on single faults or spread over wide regions containing multiple active faults, we investigated temporal and spatial slip-rate variability over many millennia using in-situ Cl cosmogenic exposure dating for active normal faults near Athens, Greece. We study a ~ NNE-SSW transect, sub-parallel to the extensional strain direction, constrained by two permanent GPS stations located at each end of the transect and arranged normal to the fault strikes. We sampled 3 of the 7 seven normal faults that exist between the GPS sites for Cl analyses.

Insights on Hysteroscopic Procedures and Their Place in Romanian Gynecologic Practice-The Experience of Two Medical Units.

Hysteroscopy has known an increasing use in Romania over the last decade, succeeding to mark an impact on lowering the costs of medical services. The strategy of this study was to present the experience of two Romanian medical units with different experiences using inpatient regimen hysteroscopy, and to further compare it with current worldwide tendencies. Strong points in our practice were sought, as well as components that require improvement.