Abstract: Minimally invasive delivery with intercellular and/or intracellular localization of nano- and micro-particle solar cells within and among excitable biological cells to controllably regulate membrane polarization and enhance function of such cells. The cells include retinal and other excitable cells, and normally non-excitable cells in proximity to partially or wholly non-functional excitable cells.

Abstract: Methods and apparatus are provided for applying an fragment of a neurotoxin such as the active light chain (LC) of the botulinum toxin (BoNT), such as one of the serotype A, B, C, D, E, F or G botulinum toxins, via permeabilization of targeted cell membranes to enable translocation of the botulinum neurotoxin light chain (BoNT-LC) molecule across the targeted cell membrane to the cell cytosol where a therapeutic response is produced in a mammalian system. The methods and apparatus include use of catheter based delivery systems, non-invasive delivery systems, and transdermal delivery systems.

Abstract: As one example, a photodynamic therapy system can include a flexible panel comprising a plurality of light sources distributed across a conformable light delivery surface thereof. The plurality of light sources can be configured to provide a treatment light to achieve a desired therapeutic effect at a predetermined distance from the light delivery surface. The system can also include a spacer configured at the light delivery surface to position the light delivery surface at the predetermined distance from a treatment area of a patient.

Abstract: A hopper having a passage through which a medicine can be passed downward is provided. A part of a lower portion of the hopper is a deformable portion having flexibility, and the deformable portion is deformable so as to open and close the passage. According to this configuration, the deformable portion that is a part of the hopper is deformed to open and close the passage. Thus, there is no portion such as an opening and closing plate on which the medicine remains, thereby preventing a gap in which the medicine remains from being formed in the hopper, and preventing the medicine from easily remaining in the hopper.

Abstract: The present disclosure provides (a) isolated immunogenic PAA polypeptides; (b) isolated nucleic acid molecules encoding immunogenic PAA polypeptides; (c) vaccine compositions comprising an immunogenic PAA polypeptide or an isolated nucleic acid molecule encoding an immunogenic PAA polypeptide; (d) methods relating to uses of the polypeptides, nucleic acid molecules, and compositions; and (e) vaccine-based immunotherapy regimens which involve co-administration of a vaccine in combination with an immune-suppressive-cell inhibitor and an immune-effector-cell enhancer.

Abstract: A user-activated self-contained co-packaged iontophoretic drug delivery system and method of use for treatment of a subject are described.

Abstract: Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated molecule comprising a nucleic acid sequence that codes for light-activated molecule. The light-activated molecule includes a modification to a location near the all-trans retinal Schiff base, e.g., to extends the duration time of the open state. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion channels or pumps or for controlling currents in a cell (e.g., in vivo or in vitro environments).

Abstract: The present invention provides methods and compositions for highly precise spatial and temporal control over cytosolic delivery of compounds, in particular, those compounds that would otherwise be cell-impermeable. Among other things, the present invention provides a composition for targeted drug delivery comprising a nanoparticle, a targeting moiety specific for a cell type of interest, a light-activated drug delivery system, wherein the nanoparticles are associated with the targeting moiety and the light-activated drug delivery system.

Abstract: One aspect of the present disclosure relates to a treatment probe comprising an elongated body member and a needle portion. The elongated body member can have a proximal end portion and a distal end portion. The needle portion can be connected to the distal end portion. The needle portion can include at least one electrode and at least one fluid port. The at least one electrode and the at least one fluid port can be configured to deliver electrical energy and a tumescent fluid, respectively, so that superficial tissue planes overlying a target nerve are protected from inadvertent heat damage as a result of application of electrical energy to a target nerve.

Abstract: The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors. In embodiments, the methods comprise the use of high aspect ratio nanoparticles with or without modified surface chemistry.

Abstract: The present invention provides methods of therapy of cognitive deficits associated with a central nervous system disorder or condition, methods of enhancing cognitive performance and methods for repeated stimulation of neuronal activity or a pattern of neuronal activity, such as that underlying a specific neuronal circuit(s). The methods comprise combining cognitive training protocols and a general administration of CREB pathway-enhancing agents.

Abstract: An implant (10) for implantation in a human or animal bone (11) has a bone area (12), which is in contact with the bone (11), and a light area, which is not covered by the bone (11). It likewise has a photo-activatable substance (14), which is activated when illuminated with light (2) and thereafter destroys microbes and bacteria. The implant (10) is made of a material which is transparent at, at least, one activation wavelength of the photo-activatable substance (14), wherein the photo-activatable substance (14) is applied at least to the surface of the bone area (12) of the implant.

Abstract: Methods, structures, devices and systems are disclosed for implementing a photothermal therapy using nanostructures. In one aspect, a device to produce a photothermal effect includes a particle having a molecular layer functionalized onto the external surface of the particle and structured to attach to one or more targeting molecules capable of binding to a receptor site of a cell, in which the particle is configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the particle to emit heat energy. In some implementations, the device is deployed in an organism having a tumor that includes a plurality of the cell and binds to the receptor site of the tumor by the targeting molecules, in which the light energy is emitted at a region of the organism that contains the tumor and the heat energy causes cellular death of the tumor cell.

Abstract: Methods and apparatus are provided for treating contrast nephropathy, e.g., via a pulsed electric field, via a stimulation electric field, via localized drug delivery, via high frequency ultrasound, via thermal techniques, etc. Such neuromodulation may effectuate irreversible electroporation of electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential attenuation or blockade, changes in cytokine up-regulation and other conditions in target neural fibers. In some embodiments, neuromodulation is applied to neural fibers that contribute to renal function. In some embodiments, such neuromodulation is performed in a bilateral fashion. Bilateral renal neuromodulation may provide enhanced therapeutic effect in some patients as compared to renal neuromodulation performed unilaterally, i.e., as compared to renal neuromodulation performed on neural tissue innervating a single kidney.

Abstract: In a method for treating an affected skin region of a patient having a skin disorder, a vasodilation composition is applied to an affected skin region of a patient, the affected skin region exhibiting a skin disorder characterized by at least one abnormal blood vessel, and the affected skin region is then treated so as to non-invasively disrupt tissue architecture, e.g., by inducing ischemia, of the at least one abnormal blood vessel. A vasoconstriction composition can then be applied to the skin region to cause vasoconstriction of the at least one blood vessel in order to promote healing.

Abstract: The preparation and use of photosensitizer-containing nanoparticles including photoactive vitamin-containing nanoparticles as photodynamic antimicrobial agents are disclosed for tissue repair including the treatment of chronic wounds.

Abstract: In accordance with one aspect, medical devices are provided which comprise an electroactive polymer material and therapeutic-agent containing particles. The device is configured such that the particles are delivered from the device upon actuation of the electroactive polymer material.

Abstract: Provided herein are compositions and methods for treating and/or preventing neurodegenerative disease, such as Alzheimer's disease. In particular aspects, compositions administered herein encode a cellular immune response element. The compositions may be prepared and administered in such a manner that the cellular immune response element coding sequence is expressed in the subject to which the composition is administered. The compositions include expression systems, delivery systems, and certain cellular immune response element genes.

Abstract: This invention relates to pharmaceutical compositions comprising a sulfonated biological precursor of thymidine, such as a precursor of 4-thiothymidine (4-TT), and their use in the photodynamic treatment of skin hyperplasias, including cancer, psoriasis, actinic keratosis and keloids, by topical or systemic administration.

Abstract: The present invention is directed to a method and apparatus for an electrotherapeutic system including a first and second electrode. Each electrode includes a respective resistance wherein during operation of the electrotherapeutic system, an electrochemical reaction involving one or both of the electrodes varies the respective resistance of at least one of the electrodes.

Abstract: A method and apparatus for treatment of skin or other tissue, using a source of thermal, electromagnetic radiation, electrical current, ultrasonic, mechanical or other type of energy, to cause minimally-invasive thermally-mediated effects in skin or other tissue which stimulates a wound-healing response, in conjunction with topical agents or other wound healing compositions, for application on the skin or other tissue which accelerate collagenesis, such as in response to wound healing. The dosage and time period of application of the compositions are adjusted to prevent external or surface tissue damage.

Abstract: The invention relates to combining targeted therapies with selected chemotherapeutics for the treatment of melanoma. The invention provides a method for inducing apoptosis in a melanoma tumor cell by reducing Akt3 activity, a method for inducing apoptosis in a melanoma tumor cell comprising contacting a melanoma tumor cell with an agent that reduces Akt3 activity to restore normal apoptotic sensitivity to a melanoma tumor cell, allowing a lower concentration of chemotherapeutic agents resulting in decreased toxicity to a patient. Also disclosed is a method for treating a melanoma comprising administering an agent that reduces Akt3 activity and an agent that reduces V599E B-Raf activity, thereby treating a melanoma tumor.

Abstract: The invention relates to combining targeted therapies with selected chemotherapeutics for the treatment of melanoma. The invention provides a method for inducing apoptosis in a melanoma tumor cell by reducing Akt3 activity. A method for inducing apoptosis in a melanoma tumor cell comprising contacting a melanoma tumor cell with an agent that reduces Akt3 activity to restore normal apoptotic sensitivity to a melanoma tumor cell, allowing a lower concentration of chemotherapeutic agents resulting in decreased toxicity to a patient. Also disclosed is a method for treating a melanoma comprising administering an agent that reduces Akt3 activity and an agent that reduces V599E B-Raf activity, thereby treating a melanoma tumor.

Abstract: A liquid or ointment formulation for the treatment of a skin condition associated with leukocyte accumulation in the skin includes a therapeutic compound selected to reduce leukocyte accumulation in the skin and an aqueous solution of an organic solvent. The organic solvent increases skin permeability. A method of treating a skin condition associated with leukocyte accumulation in the skin includes the steps of applying topically a liquid formulation of a photosensitizer to a skin lesion of a patient afflicted with the skin condition and exposing the skin lesion to a light source.

Abstract: A device includes a dispensing mechanism that is operable to dispense a substance from a canister that is connected to the device. The device includes at least one iontophoresis electrode that is chargeable to generate an electric field to enable transdermal delivery of an active ingredient of the substance when the substance is dispensed onto skin.

Abstract: The present invention relates to compositions and methods for the treatment of immuno-inflammatory conditions comprising the administration of a polyphenolic phytoalexin compartmentalized in a biocompatible and/or biodegradable polymeric carrier, and to the use of biocompatible and/or biodegradable polymeric carriers comprising resveratrol and block copolymers and these compositions with an additional compartmentalized pharmaceutically active agent.

Abstract: The present invention relates to a therapy for vitiligo. In particular the present invention provides a pharmaceutical composition comprising an alpha melanocyte stimulating hormone (alpha-MSH) analogue either alone, in combination with narrow band UVB and/or in combination with one or more corticosteroids, immunosuppressants, anti-inflammatory agents and/or photochemotherapeutic agents for the treatment or prevention of vitiligo.

Abstract: The present invention relates to an agent for use as a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation, a method of diagnosing or monitoring apoptosis-factor-associated conditions or disorders as well as a method of identifying a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation. Preferably, the invention relates to TRAIL-induced cell death and/or TRAIL-induced apoptosis. Preferably the agents are used to stimulate and/or enable TRAIL-induced cell death or to inhibit TRAIL-induced cell death. The preferable use of the diagnostic tools is to diagnose sensitivity or resistance to TRAIL-induced cell death or induction of sensitivity or resistance to TRAIL-induced cell death by an agent.

Abstract: One aspect of the invention relates to an isolated nuclear targeting molecule that includes a fragment of a mammalian glycoprotein 36 (gp36, also known as T1-? or podoplanin) gene expressed in type I alveolar epithelial cells. Plasmids containing the isolated nuclear targeting molecule which are useful for affording nuclear uptake of the plasmid DNA in type I alveolar epithelial cells but not type II alveolar epithelial cells, and compositions and host cells containing such plasmids are also disclosed. Use of the plasmids for targeting an exogenous DNA into nuclei of type I alveolar epithelial cells is described herein.

Abstract: Core-excited nanoparticle thermotherapy (CENT) represents a new paradigm in thermotherapy. The CENT method employs core-shell nanoparticles. The core of the nanoparticles is formed from one or more core-exciting, energy absorbing materials which absorbs core-exciting energy, either from an external energy source or from an energy source within the nanoparticle core (e.g., one or more radionuclides which undergo decay). Upon excitation by the core-exciting energy, the one or more core-exciting, energy absorbing materials reemit energy. A shell surrounds the particle nanoparticle core. The energy reemitted by the one or more core-exciting, energy absorbing materials is absorbed by the nanoparticle shell, so as to heat the shell of the nanoparticle. The heated nanoparticle then heats the surrounding region, to a temperature sufficient to detect, affect, damage or destroy the targeted cell or material.

Abstract: An apparatus, a system and methods for modulating and monitoring tissue have an elongate member with proximal and distal ends and a plurality of annular stimulating electrodes axially arranged along the elongate member. The stimulating electrodes are disposed near the distal end and are adapted to pass current into tissue. At least one of the annular stimulating electrodes has at least three independent stimulation points on the electrode. The apparatus also includes a plurality of recording electrodes that are adapted to measure local tissue potentials and a plurality of conductors are coupled with the recording and stimulating electrodes. An optional multiple contact connecting terminal may be coupled with the conductors and is disposed near the proximal end of the elongate member.

Abstract: An apparatus for treatment of soft tissue includes a source of radiation, a handpiece which is adapted to transmit radiation emitted from the source of radiation to a region of soft tissue, resulting in irradiated soft tissue, said handpiece being positioned adjacent to or in contact with said soft tissue region, a grid element adapted to hold at least one temperature sensor in contact with or embedded in said region of soft tissue, and a microprocessor, which converts a signal from the at least one temperature sensor into a measure of damage produced in at least two components of the irradiated soft tissue, said components comprising at least one normal tissue component and at least one malignant, hypertrophic, diseased, or unwanted component.

Abstract: A method of treatment includes delivering an agent into a patient, and providing energy inside the patient so that the energy can interact with the agent to treat a nerve. A system for treatment includes a source of agent for delivery into a patient, and an energy source for providing energy inside the patient so that the energy can interact with the agent to treat a nerve.

Abstract: This disclosure is directed to the use of complementary or combination photodynamic therapy and topical therapy with a lower dosage strength imiquimod formulation for treating actinic keratosis.

Abstract: A light generating circuit is implanted in a subject's body and aimed at a target region such as a tumor. A photosensitizer is introduced into the target region, and an AC electric field is induced in the region. The field causes the light generating circuit to generate light, which activates the photosensitizer; and at certain field strengths and frequencies, the field itself has a beneficial effect. The beneficial effects of the field and the activated photosensitizer are thereby obtained simultaneously.

Abstract: A patch for a therapeutic electrical stimulation device includes a shoe connected to the first side of the patch, the shoe including a body extending in a longitudinal direction from a first end to a second end, and having first and second surfaces, the first end of the shoe defining at least two ports, and the first surface of the shoe defining a connection member. The patch also includes at least one conductor positioned in the ports of the first end of the shoe. The shoe is configured for sliding insertion into a receptacle defined by a controller so that the conductor is connected to the controller to deliver electrical current from the controller, through the conductor, and to the electrodes, and the connection member is at least partially captured by a detent defined by the controller in the receptacle to retain the shoe within the receptacle.

Abstract: This invention is directed to a transdermal delivery patch comprising local anesthetic agent and optionally a permeation enhancement agent for reducing neuropathic pain.

Abstract: Ocular iontophoresis device and method for delivering any ionized drug solution to the cornea includes: a reservoir containing a solution suitable to be positioned on the eye; an active electrode disposed in or on the reservoir; and a passive electrode suitable to be placed on the skin of the subject, elsewhere on the body; elements for irradiating the cornea surface with suitable light for obtaining corneal cross-linking after the drug delivery; wherein the reservoir and the active electrode are transparent to UV light and/or visible light and/or IR light. The method includes: positioning the iontophoretic device on the eye to be treated; driving the solution by a cathodic current applied for 0.5 to 5 min, at an intensity not higher than 2 mA; and thereafter irradiating, with UV light for 5 to 30 min at a power of 3 to 30 mW/cm2; thereby obtaining the corneal cross-linking of the solution.

Abstract: A system is provided for healing a wound. The system includes a flexible body, a therapeutic agent delivery mechanism, a suction mechanism, and a power source. The flexible body includes a cover film having oppositely disposed first and second surfaces that define a compartment. The compartment includes a first porous material, a second porous material, and at least one electrode disposed therein. The second porous material is disposed between the first porous material and the at least one electrode. The therapeutic agent delivery mechanism and the suction mechanism are fluidly connected to the compartment. The power source is in electrical communication with the at least one electrode.

Abstract: Cells that are in the process division are vulnerable to damage by AC electric fields that have specific frequency and field strength characteristics. The selective destruction of rapidly dividing cells can therefore be accomplished by imposing an AC electric field in a target region for extended periods of time at particular frequencies with particular filed strengths. Some of the cells that divide while the field is applied will be damaged, but the cells that do not divide will not be harmed. This selectively damages rapidly dividing cells like bacteria, but does not harm normal cells that are not dividing. Since the vulnerability of the dividing cells is strongly related to the alignment between the long axis of the dividing cells and the lines of force of the electric field, improved results can be obtained when the field is sequentially imposed in different directions.

Abstract: Apparatuses and methods for electrokinetic transport of fluids to patients. Drug-containing solutions may be placed in vial-like reservoir, which is connected to an apparatus such as a traditional catheter or other device capable of holding a drug-containing solution. Instead of a vial-like reservoir, a doped infusion pad or a gel may be used as a source of the drug-containing solution. The reservoir and apparatus may thus be the same component. The methods and apparatuses disclosed herein may also be used to transport fluid alone to achieve a clinical effect. The apparatus is placed at the point of drug delivery. The counter-electrode may be placed in or on a patient. Current is passed from the reservoir to the counter-electrode. Through electrokinetic transport, drug-containing solution is delivered along a current path from the drug source to the counter-electrode. A hollow fiber catheter for use in electrokinetic transport is also disclosed.

Abstract: Cells that are in the process division are vulnerable to damage by AC electric fields that have specific frequency and field strength characteristics. The selective destruction of rapidly dividing cells can therefore be accomplished by imposing an AC electric field in a target region for extended periods of time at particular frequencies with particular filed strengths. Some of the cells that divide while the field is applied will be damaged, but the cells that do not divide will not be harmed. This selectively damages rapidly dividing cells like bacteria, but does not harm normal cells that are not dividing. Since the vulnerability of the dividing cells is strongly related to the alignment between the long axis of the dividing cells and the lines of force of the electric field, improved results can be obtained when the field is sequentially imposed in different directions.

Abstract: Described herein are gold particles that can be used to reduce tumor proliferation and treat cancer. In certain aspects, the gold particles can be modified in order to enhance selectivity and uptake of the particles by cancer cells. In certain aspects, the modified gold particles have a targeting group attached to the particle via a linker. The gold particles described herein can be used in combination with other anti-cancer agents in order to enhance overall cancer treatment. Methods for making and using the gold particles are also described herein.

Abstract: The present invention includes methods and devices for non-invasively delivering an active agent to the eye of a subject. In one aspect, for example, a device for delivering an active agent to an eye of a subject may include an ocular lens-shaped housing configured to contact a surface of the eye, and a reservoir coupled to the housing and configured to deliver an active agent to the eye, wherein the reservoir is located entirely within a 180 degree section of the housing. In another aspect, the reservoir is located entirely within a 150 degree section of the housing.

Abstract: A method for constructing a compound of immunologically modified nanotubes and method for using the compound to deliver immunoadjuvants to tumor cells and to produce targeted, synergistic photophysical and immunological reactions for cancer treatment. To prepare the immunologically modified nanotubes, carbon nanotubes are dissolved in a solution of glycated chitosan, an immunostimulant, hence using glycated chitosan as a surfactant for rendering the aqueous solution of nanotubes stable. The compound can be used for treatment of cancer. The method includes steps of intratumorally administering immunologically modified nanotubes and administering laser irradiation of the target tumor. The nanotube serves as a carrier to deliver immunoadjuvants to the tumor cells and serves as a light-absorbing agent in a cell body of a tumor in a host.

Abstract: Methods for enhancing the ability of an individual, exposed to sunlight, to produce vitamin D via the skin. Pharmaceutical compositions comprising provitamin D and at least one of lumisterol and tachysterol and analogs and derivatives thereof are also disclosed.

Abstract: A method of treating a mammal with a tumor by decreasing intratumoral vessels associated with tumor or inhibiting formation of new intratumoral vessels includes injecting tumor with therapeutically effective amount of expression plasmid including polynucleotide coding for therapeutic peptide consisting of SEQ ID NO: 2 absent any operably linked coding sequence, wherein polynucleotide sequence is operably linked to promoter or expression control sequence, followed by application of electric pulses to site of injection in tumor or injecting muscle of mammal with therapeutically effective amount of expression plasmid including polynucleotide coding for therapeutic peptide consisting of SEQ ID NO: 2 absent any operably linked coding sequence, wherein polynucleotide sequence is operably linked to promoter or expression control sequence, followed by applying electric pulses to site of injection in muscle of mammal, whereby expression of SEQ ID NO: 2 decreases intratumoral vessels associated with tumor, or formation

Abstract: A light generating circuit is implanted in a subject's body and aimed at a target region such as a tumor. A photosensitizer is introduced into the target region, and an AC electric field is induced in the region. The field causes the light generating circuit to generate light, which activates the photosensitizer; and at certain field strengths and frequencies, the field itself has a beneficial effect. The beneficial effects of the field and the activated photosensitizer are thereby obtained simultaneously.

Abstract: Disclosed are nanotopography-based methods and devices for interacting with a component of epithelial tissue and increasing the permeability of the tissue. Devices include structures fabricated on a surface to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Microneedles may be beneficially utilized for delivery of an agent to a cell or tissue. Devices may be utilized to directly or indirectly alter cell behavior through the interaction of a fabricated nanotopography with the components of epithelial tissue.

Abstract: Silver and/or zinc ion releasing implants, systems and method of operating, inserting and activating/inactivating them are described. In some variations the implant is configured as a bone implant that includes a bone-screw or intramedullary rod like body configured to receive a treatment cartridge having a plurality of ion-releasing members configured as an anode that can controllably engage with a catheter to turn galvanic release of ions on/off as desired. These devices may be configured to release silver ions (and/or zinc ions) above a predetermined level for a predetermined period of time and may maintain a concentration of ions over a relatively large volume of tissue. The ion-releasing members may be configured to reduce or prevent implant movement.