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A Novel Method for the Isolation and Purification of Extracellular Vesicles (ECV) for Use as Potential Biomarkers

Extracellular vesicles (ECV) reflect the physiological or pathological condition of the cell. Therefore, they have emerged as potential biomarkers for disease. They can be obtained from a variety of body fluids, particularly urine that is an ideal source because it can be obtained in great quantities, recurrently and with minimal intervention. However, the characterization of urine ECV is challenging because the preparation is usually contaminated with soluble proteins. Therefore, approaches to obtain cleaner preparations of urine ECV are important for any proteomic analysis.

Method for Assessing Risk of Genetic Defects in Children by Identifying De Novo Mutations in Male Sperm

In general, the risk of having a child with autism spectrum disorder (ASD) is about 1 in 68, or 1.5%. But the risk goes up for families who already have a child with ASD. If a family has one child with ASD, the chance of the next child having ASD is about 20%. If the next child is a boy, the risk is 26%, whereas if it’s a girl the risk is 10%. About 47% of families had more than one child with autism. Currently if a child has a birth defect or autism, the emerging trend is to perform whole exome sequencing to identify genetic mutations. These mutations overwhelmingly come from the father, because sperm cells but not egg cells continue to divide through the life of adults. Once the mutation is identified, the diagnosis can be made in the child, but the parents are left wondering if this genetic event could recur in future children. Currently there is no genetic assessment of sperm available commercially, and no publications on the application of using sperm as a way to assess risk of childhood disease, nor is there a risk assessment available for couples that have had a child with a genetic disease due to de novo genetic mutation.

Novel Method for the Active Delivery of Drugs Across the Intact Round Window Membrane to the Inner Ear of Mammals

There are many diseases of the inner ear that may be preventable or treatable pharmaceutically or by gene therapy. These include sensorineural hearing loss, “hidden hearing loss” due to neural damage, Meniere’s disease, dizziness, and tinnitus. There are difficulties that could be improved or resolved by local therapies. The bony capsule of the inner ear and the round window membrane that separates the middle ear form the inner hear hamper noninvasive delivery of medications or gene therapy vectors. The round window membrane is passively permeable to some drugs, depending upon size and charge.  However, large molecules and particles cross much less readily. Opening up the cochlea is required for delivery of such potential therapies. Thus, what is needed is an alternative method for delivery of drug across the intact round window membrane.

Development of a Diagnostic Test to Differentiate Bradykinin with Normal C1 Inhibitor from Histamine-Mediated Angioedema

Angioedema is a non-itchy, pale swelling of subcutaneous or submucosal tissue that tends to recur chronically and can become life-threatening if the swelling occurs in the upper airways or can be very painful if it occurs in the gastrointestinal tract. Angioedema presenting together with urticarial (hives) usually responds well to antihistamines and corticosteroids, whereas angioedema without urticarial (hives) is frequently resistant to such therapy but may respond to a C1 esterase inhibitor, tranexamic acid, or both therapies that can reduce bradykinin generation. Differentiating bradykinin-from histamine-mediated angioedema is of critical importance to prevent morbidity and mortality. The ability to diagnose bradykinin-mediated angioedema with normal C1 inhibitor (C1INH), however has been severely limited by the lack of any available diagnostic test. Current genetic tests only identify a tiny fraction of the affected patients. Due to the lack of a known biomarker or assay, many patients without bradykinin-mediated angioedema are treated with unnecessary medications (often approaching $1,000,000/year or more in costs).

Histology Thin Sectioning Method for Soft, Unfixed Tissues

Before microscopic analysis, tissue specimens are typically prepared for sectioning by initial fixation, freezing, and/or embedding in a mounting medium. There have been no cutting blocks for vibratome that allow the use of fresh soft tissues into thin slices (with micrometer thickness) such as intestines and other soft tissues (brain, heart, blood vessels, liver, spleen, lung, skin etc.).These traditional techniques can limit the ability of scientists to carry out molecular analysis on the tissue.

Development of Novel Beta-Adrenergic Receptor Allosteric Modulators

The G protein-coupled receptors (GPCRs) are a very important family of cell surface receptors that respond to extracellular signals which then transduce those signals into intracellular responses.  They are also the largest family of targets of currently available therapeutics. Adrenergic receptors belong to the GPCR superfamily and their natural ligands are the catecholamines, epinephrine and norepinephrine. Adrenergic receptors can be further divided into two receptor subfamilies, α and β that exhibit differences in tissue distribution, ligand specificity and cellular output. The β adrenergic receptors (βARs) are important mediators in diseases like asthma, Parkinson’s disease, hypertension and heart failure. Therefore, there is a direct need for new modulators for the βARs receptors.

Development of a Potential Therapeutic for the Treatment of Alcoholism

Alcohol consumption is a major public health concern in the United States and according to the National Institute on Alcohol Abuse and Alcoholism, it is estimated that over 88, 424 people die on average for the years 2006-2010. Aside from death, excess alcohol consumption is linked with a host of other health-related problems, including Alcoholic Liver Disease (ALD) or alcohol-induced brain injury and alcohol-induced neuronal death, cirrhosis and astrogliosis. Therefore, there is an urgent need for a therapeutic which could potentially reduce addiction to alcohol. 

Airway Manikin With Realistic Mobility

Training for direct laryngoscopy relies heavily on practice with patients. The necessity for human practice might be supplanted to some extent by an intubation manikin with accurate airway anatomy, a realistic “feel” during laryngoscopy, the capacity to model many patient configurations, and a means to provide feedback to trainees and instructors. The realism and mobility of the anatomical features of current models limits the effectiveness of training intubation skills. Current models provide only one set of anatomic features, but patients present innumerable combinations of size, shape, proportion, and tissue stiffness. Thus, a novice who trains on a particular model merely learns how to intubate that particular model, but has minimal ability to transfer the learned skills to the multiplicity of anatomies in patients. Furthermore, most models approximate a normal anatomic configuration that poses no problem for intubation, so novices do not gain experience with difficult situations