Abstract: A method of inserting an intervertebral disc implant into a disc space includes accessing a spinal segment having a first vertebral body, a second vertebral body and a disc space between the first and second vertebral bodies. The method includes securing a first pin to the first vertebral body and a second pin to the second vertebral body, using the first and second pins for distracting the disc space, and providing an inserter holding the intervertebral disc implant. The method also desirably includes engaging the inserter with the first and second pins, and advancing the inserter toward the disc space for inserting the intervertebral disc implant into the disc space, whereby the first and second pins align and guide the inserter toward the disc space.

Abstract: Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

Abstract: Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

Abstract: Instrumentation for implanting an artificial intervertebral disc includes repositioners/extractors for repositioning and extracting the static trials or the artificial intervertebral discs, each of the repositioners/extractors including a shaft and at least two pins coupled to the shaft distal end and extending in a same direction and perpendicular to a plane passing through the shaft longitudinal axis, each pin being parallel to all others of the pins, wherein the disc includes at least two holes, at least two of the pins being sized, directed, and spaced for simultaneous engagement with at least two of the holes, and wherein such simultaneous engagement enables repositioning of the implant via application of pressure to the shaft.

Abstract: Methods and devices for treating anaphylaxis, anaphylactic shock, bronchial constriction, and/or asthma include providing an electrical impulse to a selected region of the vagus nerve of a patient suffering from anaphylaxis to block and/or modulate nerve signals that would regulate the function of, for example, myocardial tissue, vasodilation/constriction and/or pulmonary tissue.

Abstract: Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

Abstract: Devices, systems and methods are disclosed that allow a patient to self-treat a medical condition, such as migraine headache, by electrical noninvasive stimulation of a vagus nerve. The system comprises a stimulator that is applied to the surface of the patient's neck, as well as a docking station that is used to charge a rechargeable battery within the stimulator. The docking station and stimulator housing transmit data to one another regarding the status of a stimulation session, as well as to a computer program in a patient interface device such as a mobile phone or computer. The interface device in turn communicates with medical record and billing databases contained within other computers, via the internet. The system is designed to address problems that arise particularly during self-treatment, when a medical professional is not present.

Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Abstract: The present invention includes methods and devices for treating hypotension, such as in cases of shock, including septic shock, anaphylactic shock and hypovolemia. The method includes the step of applying at least one electrical impulse to at least one selected region of a parasympathetic nervous system of the patient. The electrical impulse is sufficient to modulate one or more nerves of the parasympathetic nervous system to increase the ratio of blood pressure to heart rate and relieve the condition and/or extend the patient's life.

Abstract: Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: Transcutaneous electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including nasal or paranasal sinus symptoms that resemble an immune-mediated response (“sinus” headaches). The devices and methods may also be used to treat rhinitis, sinusitis, or rhinosinusitis, irrespective of whether those disorders are co-morbid with a headache. They may also be used to treat other disorders that may be co-morbid with migraine or cluster headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Abstract: The present invention provides systems and methods for treating and controlling obesity and/or type II diabetes. In one aspect of the invention, a device comprises a hollow sleeve sized and shaped for positioning within a duodenum of the patient, an anchor coupled to the proximal end of the sleeve and being sized and shaped to inhibit distal migration of the sleeve and a plurality of elastomeric objects coupled to the distal end of the sleeve and being sized and shaped to inhibit proximal migration of the sleeve through a pylorus of the patient. The bypass device can be placed and removed endoscopically through the patient's esophagus in a minimally invasive outpatient procedure and it is “self-anchoring” and does not require invasive tissue fixation within the patient's GI tract, thereby reducing collateral tissue damage and minimizing its impact on the digestive process.

Abstract: Instrumentation for implanting an artificial intervertebral disc includes a leveler for setting the proper position of the artificial intervertebral disc, the leveler including at least two tines extending parallel to one another from the leveler shaft distal end, wherein the tines are spaced and sized to be insertable and fittable between baseplates of the disc and to substantially fill at least a height of a separation space volume between the baseplates, and to straddle a central coupling of the baseplates during the insertion and when so fitted, such that when the baseplates are substantially non-parallel to one another in the intervertebral space, insertion of the tines into the intervertebral space between the baseplates and straddling the central coupling forces the baseplates into a substantially parallel orientation relative to one another.

Abstract: Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

Abstract: An artificial disc having a pair of opposing baseplates, for seating against opposing vertebral bone surfaces, separated by a ball and socket joint that includes a solid ball mounted to protrude from one of the baseplates. The ball is captured within a curvate socket formed in a peak of a convex structure integral with the other of the baseplates. The socket is formed by opposing curvate pockets, one on the convex structure and one on a retaining cap that is secured to the other of the baseplates. The ball rotates and angulates in the socket. The ball and socket joint therefore permits the baseplates to rotate and angulate relative to one another.

Abstract: The present invention includes methods and devices for treating hypotension, such as in cases of shock, including septic shock, anaphylactic shock and hypovolemia. The method includes the step of applying at least one electrical impulse to at least one selected region of a parasympathetic nervous system of the patient. The electrical impulse is sufficient to modulate one or more nerves of the parasympathetic nervous system to increase the ratio of blood pressure to heart rate and relieve the condition and/or extend the patient's life.