We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.
The validity of the ES3 as an effective surgical trainer was verified in multiple instances, including those not depending on subjective rater evaluations. The ES3 is one of the few virtual reality simulators with a comprehensive validation record. Advanced simulation technologies need more rapid implementation in otolaryngology training, as they present noteworthy potential for high-quality surgical education while meeting the necessity of patient safety.
Many mild symptoms previously thought to be associated with teething were found in this study to be temporally associated with teething. However, no symptom cluster could reliably predict the imminent emergence of a tooth. Before caregivers attribute any infants' signs or symptoms of a potentially serious illness to teething, other possible causes must be ruled out.teething, tooth eruption, teeth, deciduous dentition.
In a patient population with sinus and nasal symptoms, the height and contour of the right and left fovea ethmoidalis were symmetric in less than 50% of individuals. The asymmetry was most often the result of a difference in contour with flattening of the fovea on one side. This underscores the importance of careful preoperative and intraoperative review of paranasal sinus CT scans in patients undergoing endoscopic sinus surgery.
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