Risk Factors for Replacement of Tympanostomy Tubes After Surgical Removal for Pediatric Patients.

Objectives: Ear tube removal and patch myringoplasty are frequently performed. The indication and timing for surgery varies among otolaryngologists. This study identifies risk factors associated with the need for the replacement of tympanostomy tubes after tube removal and myringoplasty.

Sebaceous Carcinoma of the Middle Ear: A Case Report.

Here we present the first case of sebaceous carcinoma of the middle ear. We discuss the treatment course and post treatment results after 11 years of follow up. We further summarize the available literature of sebaceous carcinoma of the temporal bone, which prior to this case was exclusively limited to the external auditory canal.

Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis.

Objective: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures.

The parietal notch (Brammer's pointer): Accuracy of a surface landmark for temporal bone surgery.

Hypothesis: The parietal notch is a reliable surface landmark of the sigmoid sinus at the sinodural angle.

Background: Currently no surface landmark approximates the anterior border of the sigmoid sinus. Additionally, the temporal line may not accurately identify the tegmen near the sinodural angle.

Intersectional targeting of defined neural circuits by adeno-associated virus vectors.

The mammalian nervous system is a complex network of interconnected cells. We review emerging techniques that use the axonal transport of adeno-associated virus (AAV) vectors to dissect neural circuits. These intersectional approaches specifically target AAV-mediated gene expression to discrete neuron populations based on their axonal connectivity, including: (a) neurons with one defined output, (b) neurons with one defined input, (c) neurons with one defined input and one defined output, and (d) neurons with two defined inputs or outputs.

Oronasal Fistula Incidence Associated With Vomer Flap Repair of Cleft Palate: A Systematic Review and Meta-Analysis.

Objectives: To determine the incidence of oronasal fistulas (ONF) associated with primary repair of the anterior palate using a single-layered, superiorly based, vomer mucoperiosteal flap.

Design: A systematic review of MEDLINE, PubMed, Cochrane, and Web of Science databases using the keywords: "vomer flap" and "cleft palate repair" were carried out. A meta-analysis was performed using random effect modeling with stratified analysis by syndromic diagnosis, number of surgeons, and mean age.

Postmortem Analysis in a Clinical Trial of AAV2-NGF Gene Therapy for Alzheimer's Disease Identifies a Need for Improved Vector Delivery.

Nerve growth factor (NGF) gene therapy rescues and stimulates cholinergic neurons, which degenerate in Alzheimer's disease (AD). In a recent clinical trial for AD, intraparenchymal adeno-associated virus serotype 2 (AAV2)-NGF delivery was safe but did not improve cognition. Before concluding that NGF gene therapy is ineffective, it must be shown that AAV2-NGF successfully engaged the target cholinergic neurons of the basal forebrain.

In Situ Hybridization for Detection of AAV-Mediated Gene Expression.

Techniques to localize vector transgenes in cells and tissues are essential in order to fully characterize gene therapy outcomes. In situ hybridization (ISH) uses synthesized complementary RNA or DNA nucleotide probes to localize and detect sequences of interest in fixed cells, tissue sections, or whole tissue mounts. Variations in techniques include adding labels to probes, such as fluorophores, which can allow for the simultaneous visualization of multiple targets.

Physical positioning markedly enhances brain transduction after intrathecal AAV9 infusion.

Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard intrathecal AAV9 infusions predominantly drive reporter gene expression in brain regions where gravity might cause cerebrospinal fluid to settle, we tested the hypothesis that counteracting vector "settling" through animal positioning would enhance vector delivery to the brain.

Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids.

More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity.

Adeno-associated virus serotypes 1, 8, and 9 share conserved mechanisms for anterograde and retrograde axonal transport.

Adeno-associated virus (AAV) vectors often undergo long-distance axonal transport after brain injection. This leads to transduction of brain regions distal to the injection site, although the extent of axonal transport and distal transduction varies widely among AAV serotypes. The mechanisms driving this variability are poorly understood.

Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment.

Adeno-associated virus (AAV) vectors can move along axonal pathways after brain injection, resulting in transduction of distal brain regions. This can enhance the spread of therapeutic gene transfer and improve treatment of neurogenetic disorders that require global correction. To better understand the underlying cellular mechanisms that drive AAV trafficking in neurons, we investigated the axonal transport of dye-conjugated AAV9, utilizing microfluidic primary neuron cultures that isolate cell bodies from axon termini and permit independent analysis of retrograde and anterograde axonal transport.

Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey.

Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors that can transduce photoreceptor cells.

Transient receptor potential vanilloid 1 agonists modulate hippocampal CA1 LTP via the GABAergic system.

Transient receptor potential vanilloid 1 (TRPV1) was shown to modulate hippocampal CA1 pyramidal cell synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Synaptic plasticity is the cellular mechanism thought to mediate declarative learning and memory in the hippocampus. Although TRPV1 is involved in modulating hippocampal plasticity, it has yet to be determined how TRPV1 mediates its effects.

Health reform: a bipartisan view.

This optimistic assessment of the prospects for health reform from senior Democratic and Republican congressmen spells out several reasons why reform can be achieved early in the first year of the Obama administration. Political and policy factors suggest that President-elect Barack Obama is in a much better position than his predecessors to achieve comprehensive health reform, including universal coverage. The Obama administration will have to overcome numerous obstacles and resistance to enact reform.