Abstract: The present disclosure relates to novel cleavable conjugates of antibiotics and an antibacterial cell-penetrating peptide, and methods to make and use the novel cleavable conjugates of antibiotics and an antibacterial cell-penetrating peptide.

Abstract: The invention provides methods of delivering pharmacologic agents linked to an internalization peptide, in which an inflammatory response inducible by the internalization peptide is inhibited by co-administration of an anti-inflammatory or by linking the internalization peptide to biotin or similar molecule. Such methods are premised in part on the results described in the examples whereby administration of a pharmacological agent linked to tat at high dosages is closely followed by an inflammatory response, which includes mast cell degranulation, histamine release and the typical sequelae of histamine release, such as redness, heat, swelling, and hypotension.

Abstract: This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, including, for example, reducing chemotherapy-related toxicity (e.g., liver toxicity).

Abstract: This invention relates to antibody-drug conjugates capable of delivering cytotoxic compounds to cancers expressing the guanylyl cyclase C (GCC) transmembrane cell surface receptor.

Abstract: The present invention relates to methods and pharmaceutical composition for the treatment of cancer. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen for cancer, the method comprising: administering a pharmaceutically effective amount of a TNF? blocking agent to a subject in combination with the immune checkpoint inhibitor.

Abstract: Provided are bispecific conjugates having the general formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancer.

Abstract: The invention relates to a novel linker for use in bioconjugates such as antibody-drug-conjugates. The linker according to the invention is represented by formula: (I) wherein: —BM is a branching moiety; —E is a capping group; —SG is a sulfamide group; —b, c, d, e, g, i, k, l are independently 0 or 1; —f is an integer in the range of 1 to 10; —Sp1, Sp2, Sp3, Sp4, Sp5 and Sp6 are a spacer moieties; —Z and Z2 are connecting groups. The linker according to the invention is useful in the preparation of linker-conjugates and bioconjugates, and can be used for (a) improving conjugation efficiency in the preparation of the bioconjugate, (b) reducing aggregation during the preparation of the bioconjugate and/or of the bioconjugate, (c) increasing stability of the bioconjugate, and/or (d) increasing therapeutic index of the bioconjugate.

Abstract: Principles of the present disclosure are directed to novel methods and devices for efficient and targeted delivery of impermeable exogenous materials such as small molecules, proteins, antibodies, and genes into cells, both in vitro as well as in vivo, which is of great importance for drug, vaccine and gene delivery for various therapeutic applications. Specifically, the invention provides device and method for targeted nano-enhanced optical delivery of opsins for vision restoration in patients with retinal photodegeneration by conventional intravitreal/sub-retinal injection of gold nano-rods and opsin plasmids followed by scanned/spatially modulated laser beam matching the pathological areas determined by Fundoscopy, OCT or scanning ophthalmoscope.

Abstract: The present invention provides for a novel liquid formulation for solubilizing poorly soluble ST-246 in cyclodextrins and a novel process of making the formulation.

Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Abstract: Compositions and methods for treating a disease are described herein. Compositions having plant preparations, microRNAs, and one or more rate limiters are administered to a patient to promote DNA damage repair and modulate endothelial and mitochondrial function, thereby allowing for healing to occur.

Abstract: The present invention includes methods and compositions for elimination of polyoma viruses, such as John Cunningham Virus (JVC), from host cells, and the treatment of polyoma-virus related diseases, such as progressive multifocal leukoencephalopathy (PML). The compositions include isolated nucleic acid sequences comprising a CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a polyoma virus.

Abstract: The present application provides materials and methods for treating a patient with severe combined immunodeficiency (SCID) or Omenn Syndrome, both ex vive and in vive. In addition, the present application provides materials and methods for editing to modulate the expression, function or activity of the Recombination Activating Gene 1 (RAG1) gene in a cell by genome editing.

Abstract: A suspension useful for AAV9-mediated intrathecal/intracisternal and/or systemic delivery of an expression cassette containing a hIDUA gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating MPSI and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

Abstract: The disclosure relates, in some aspects, to compositions and methods for enhanced delivery of a transgene to the central nervous system (CNS) of a subject. In some embodiments, the transgene is delivered by recombinant AAV (rAAV). In some embodiments, the method of enhancing transgene delivery comprises administering a blood brain barrier (BBB)-crossing molecule (e.g., K16ApoE) and an rAAV comprising a transgene to a subject.

Abstract: The invention relates to compositions, compounds, methods, and uses for the treatment of amyotrophic lateral sclerosis. In particular, the invention relates to compounds, compositions, methods, and uses for the treatment of amyotrophic lateral sclerosis by increasing the expression of the MHC class I molecule, HLA-F, in motor neurons of the patient.

Abstract: Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Abstract: The present disclosure provides a method of modifying a mutant dystrophin gene in the genome of a cell. The present disclosure further provides compositions and kits for modifying a mutant dystrophin gene in the genome of a cell.

Abstract: It is disclosed herein that ssAAV and scAAV vectors of the same serotype administered by injection into the cerebrospinal fluid (CSF) via the intracerebroventricular (ICV) or intrathecal (cisternal or lumbar) route exhibit different cellular tropisms in the central nervous system. Thus, a subject can be treated by injection into the CSF of ssAAV or scAAV vector encoding a therapeutic protein, such as an ssAAV9 or scAAV9 vector. The therapeutic protein can be targeted to specific cells using these vectors. In some embodiments, scAAV9 is utilized to achieve superior transduction in the hippocampus, cerebellum and cerebral cortex where both neurons, particularly Purkinje neurons, and glial cells (such as astrocytes) are transduced. In other embodiments, ssAAV9 is utilized to minimize transduction of astrocytes. In further embodiments, an immunosuppressive agent is also administered to the subject.

Abstract: Methods for introducing a gene into a cell of the inner ear, e.g., a cochlear or vestibular cell, e.g., a hair cell, e.g., for therapy, that include the use of exosomes associated with one or more adeno-associated viral (AAV) particles.

Abstract: Indirect chromoendoscopy is performed by providing a subject with an orally administered composition which includes indigo carmine dye mixed with polyethylene glycol (PEG). Preferably, the subject ingests at least 160 mg of indigo carmine prior to the endoscopic procedure. This is accomplished by ingesting 1 ml to 6 L of a premixed or reconstituted indigo carmine and PEG composition up to twenty four hours prior to the endoscopic procedure.

Abstract: A polynucleotide that modulates transcription from a plurality of genomic targets can include, generally, a polynucleotide encoding a gRNA array and a polynucleotide sequence encoding a nuclease-deficient Cas9 polypeptide. The polynucleotide encoding a gRNA array generally includes polynucleotides encoding at least two gRNAs operably linked to an inducible regulatory sequence.

Abstract: There are provided methods for diagnosing coronary heart disease in a subject in need thereof comprising administering an admixture comprising CO2 to a subject to reach a predetermined PaCO2 in the subject to induce hyperemia, monitoring vascular reactivity in the subject and diagnosing the presence or absence of coronary heart disease in the subject, wherein decreased vascular reactivity in the subject compared to a control subject is indicative of coronary heart disease. There are also provided methods for increasing sensitivity and specificity of BOLD MRI.

Abstract: Disclosed are methods, compositions, reagents, systems, and kits to prepare nitroxide-functionalized brush-arm star polymer organic radical contrast agent (BASP-ORCA) as well as compositions and uses thereof. Various embodiments show that BASP-ORCA display unprecedented per-nitroxide and per-molecule transverse relaxivities for organic radical contrast agents, exceptional stability, high water solubility, low in vitro and in vivo toxicity, and long blood compartment half-life. These materials have the potential to be adopted for tumor imaging using clinical high-field 1H MRI techniques.

Abstract: The present invention provides compositions and methods for detecting GluA1, as a subunit protein and/or as a GluA1-containing, GluA2-lacking AMPAR complex. The invention further provides composition and methods for detecting and/or diagnosing PTSD. The invention further relates to compositions that can be detected using radiological imaging techniques, and processes for performing such imaging techniques using the compositions, to identify elevated GluA1 expression or activity in a subject, which is a biological marker of PTSD.

Abstract: The present invention relates to novel, selective radiolabelled tau ligands which are useful for imaging and quantifying tau aggregates, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue or a subject, in vitro or in vivo, and to precursors of said compounds.

Abstract: Disclosed are novel compounds, complexes, compositions and methods using Zirconium-89 combined with azamacrocyclic chelators in connection with PET. The compositions and methods should provide better diagnostic, prognostic and therapeutic oncology treatments relative to the presently available chelator compositions due to a variety of superior properties of the disclosed compositions. The present invention also relates to a superior method of making these compounds, complexes, compositions that allows one to make compounds/complexes (and thus, compositions) that were previously unattainable.

Abstract: A method of damaging a parasite while being a resident in or on a surface of a body of a mammal. The method comprises irradiating the parasite with ultrasound radiation at a frequency of from about 1 MHz to about 2.6 MHz for a period of at last one second.

Abstract: An antibacterial fiber that includes a plurality of charge generation fibers. The plurality of charge generation fibers generate electric charges with application of external energy thereto, and the space between the plurality of charge generation fibers is not uniform.

Abstract: A gas-permeable filter system for a sterile container includes a filter element and a seal portion that sealingly surrounds a gas exchange opening provided in a sterile container wall section in such a manner that the seal portion rests against the sterile container wall section so that a sterile flow path is formed through the gas exchange opening and the filter element. A temperature-sensitive adjusting section releases at least the seal portion from the sterile container wall section when a specified temperature is reached or exceeded such that a non-sterile flow path is formed which allows fluid to be supplied or discharged via the gas exchange opening while bypassing the filter element. The sterile container includes a base and walls that define a receiving space. The sterile container also includes a cover for closing the receiving space. At least one filter system is preferably secured to the sterile container base.

Abstract: Provided are an apparatus and method for sterilizing an internal channel surface of an endoscope, and more particularly, to an apparatus and method for sterilizing an internal channel surface of an endoscope, in which ultrasonic and infrared rays are irradiated to an internal channel of the endoscope to partially or entirely sterilize and removing a biofilm generated on the internal channel surface of the endoscope during a procedure or diagnosis.

Abstract: A method for sterilizing a drug delivery device may comprise disposing a liquid drug container, a needle conduit and a cap in a sterilization enclosure so that a mouth portion of the liquid drug container is registered with, and spaced apart from, a circumferential lip of the cap; disposing a cover over the liquid drug container, the needle conduit, and the cap, sealing the sterilization enclosure; subjecting the interior of the sterilization enclosure to a sterilization process in which the liquid drug container, the needle conduit, and the cap are exposed to the sterilization fluid and are sterilized; and applying a downward force to the liquid drug container to move the mouth portion into engagement with the circumferential lip of the cap and to snap the cap onto the liquid drug container to seal the cap and needle conduit to the liquid drug container in an assembled configuration.

Abstract: A method of ensuring the structural integrity and decontamination of a medical device includes inserting a distal end of a borescope into a lumen of the medical device, where the distal end of the borescope has an imaging portion and at least one decontamination portion, typically a UV light and a fluid sterilant or bactericide. The method includes determining both whether the lumen wall has been damaged, and whether contaminants reside on the wall, by visually inspecting the wall with the imaging portion of the borescope, and then decontaminating the wall with the decontaminating portion of the borescope. Device processing data digitally associated with the medical device is retrieved with a unique device identifier, and additional device processing data resulting from the current inspection and sterilization process is added for use by subsequent device handlers, typically by adding it to a distributed ledger, such as a blockchain.

Abstract: Various devices for sterilizing a surface and an object in contact with the surface are disclosed. For example, a first device includes an ultraviolet light source, a touch sensor, a processing system, and a computer-readable medium. The computer-readable medium stores instructions which, when executed by the processing system, cause the processing system to perform operations that include detecting, via the touch sensor, a tactile state of the device, detecting a tactile state of at least one additional device, determining, based upon the tactile states, that the device is on an edge of a pattern of contact between an object and a surface comprising the device and the at least one additional device, and implementing an action associated with the ultraviolet light source in response to determining that the device is on the edge of the pattern of contact.

Abstract: Vapor generation and distribution devices, systems, and methods. An exemplary system of the present disclosure comprises a vapor generation system configured to volatilize or vaporize liquid chemical within a tank as volatilized or vaporized chemical, and a vapor distribution system configured to receive the volatilized or vaporized chemical from the vapor generation system and distribute the volatilized or vaporized chemical through a distribution conduit coupled to the second air flow generator.

Abstract: A long-acting ultrasonic dispenser that effuses a water-based deodorizer solution into ambient air as a dry fog in a closed environment, and a method for deodorizing noxious odors in that closed environment by the dry fog. The dry fog, containing the deodorizer, chemically reacts with materials producing the odors, thereby neutralizing them. The dispenser contains an electronic ultrasonic wave generator comprising a piezoelectric crystal and an ultrasonic membrane, which is always submerged under liquid. As the liquid evaporates, droplets larger than five microns are filtered out, and the remaining dry fog is emitted into the air. The dispenser is connected to a large reservoir. When the liquid level reaches a minimum permissible height, additional deodorizer solution is pumped into the dispenser. This system is ideal for use with central air conditioners in large office buildings to eliminate odors over a long period of time with minimum maintenance.

Abstract: The invention is directed to a method of cleaning and disinfecting a contact lens. The method includes instructing a consumer to disinfect their contact lens comprising the following steps: remove a contact from an eye and position the lens in a lens assembly that includes a cap member; add a disinfection solution to the lens case such that the lens is submerged in the solution upon closure of the lens case with the cap member. The disinfection solution will comprise 0.5 wt. % to 6 wt. % hydrogen peroxide or a chemical precursor of hydrogen peroxide, and a P-metal modulating compound. The presence of the P-metal modulating compound in the disinfection solution decreases the neutralization rate of the hydrogen peroxide. The disinfection system exhibits a pseudo first-order, half-life of hydrogen peroxide from 12 minutes to 30 minutes over an initial sixty minutes of neutralization following exposure of the disinfection solution to a catalyst comprising a P-metal.

Abstract: A polymer nanofiber scaffold includes a plurality of melt extruded nanofibers that are chemically modified to append surface functionality to the nanofibers.

Abstract: A sanitary napkin, towel, or pad having one or more of Manuka honey, Tourmaline powder, Jade powder, Amethyst powder, or silver applied to or sewn into a layer of the napkin.

Abstract: A tissue adhesive with healing promotion properties formed from a mixture of natural polymers and an activating agent that enhances the adhesive properties of the natural polymer mixture is described. Use of an activating agent and a combination of the natural polymers is unique. The natural polymer tissue adhesive may be useful as a post-operative application for tonsillectomy or adenoidectomy surgery, as an internal tissue adhesive for surgery or wound repair or for application to a burn or skin donor site. For internal use, an optional treatment to improve resistance of the activated adhesive to body fluids is also described. The adhesive described not only functions as an adhesive but would also serve as a protective barrier when applied to surgery or skin sites. In addition, the natural polymers would promote healing due to the inherent properties of the polymers selected.

Abstract: Polymeric materials are disclosed herein that include a Polymer A, a Polymer B, and an oxalate ester or reaction product thereof. Polymer A contains electrophilic reactive groups, and Polymer B contains nucleophilic groups. In certain embodiments, the polymeric materials are free-flowing liquids at 100% solids that can be used, for example, as topical skin adhesives.

Abstract: One aspect of the invention provides a method of sequentially inducing macrophage conversion in a wound. The method includes: (a) administering IL-4 to induce conversion of a first population of wound macrophages in the wound to M2A macrophages; and then (b) administering IL-10, dexamethasone, or a dexamethasone analog to induce conversion of a second population of wound macrophages in the wound to M2C macrophages.

Abstract: [Problem to be Solved] To provide a porous composite that has excellent uniform dispersability of OCP and that comprises OCP and collagen in a sufficiently mixed state; and a bone regeneration material comprising the porous composite. [Means for Solution] A porous composite comprising octacalcium phosphate and collagen, characterized in that in an image obtained by enlarging a 5.0-mm×5.0-mm range of a plane of the porous composite 15 times with a scanning electron microscope (SEM), agglomerated particles of octacalcium phosphate have a fractal dimension (D) of 0.70 or more; and the area of c) portions consisting of collagen accounts for 5% or less of the total area of a) portions consisting of agglomerated particles of octacalcium phosphate, b) portions consisting of octacalcium phosphate microparticles and collagen, and the c) portions consisting of collagen.

Abstract: The present invention relates to a process of treating an implant, comprising a step of treating the surface of the implant with at least one phosphonic acid compound or a pharmaceutically acceptable salt, ester or amide thereof under sonication at a temperature of about 50° C. to about 90° C. This process is highly advantageous in that it allows the formation of a monolayer of the phosphonic acid compound on the implant surface, having a particularly dense surface coverage which, in turn, results in an improved implant biocompatibility and improved osseointegration.

Abstract: Provided are methods for preparing gelled, solubilized extracellular matrix (ECM) compositions useful as cell growth scaffolds. Also provided are compositions prepared according to the methods as well as uses for the compositions. In one embodiment a device, such as a prosthesis, is provided which comprises an inorganic matrix into which the gelled, solubilized ECM is dispersed to facilitate in-growth of cells into the ECM and thus adaptation and/or attachment of the device to a patient.

Abstract: Disclosed are tissue graft compositions made of particles having different densities, methods of making these compositions, and methods of using these compositions for promoting tissue restoration in a patient.

Abstract: Disclosed are products and methods for treating soft tissue injuries. The provided methods include the production of processed or cryopreserved microvascular tissue. Also provided are products and methods of using processed or cryopreserved microvascular tissue for the treatment of soft tissue injuries.

Abstract: A prosthetic implant comprising a biocompatible three-dimensional scaffold and at least two cell types selected from the group consisting of osteoblasts, osteoclasts, and endothelial cells or progenitors thereof.

Abstract: The present invention relates generally to methods and materials for use in the production of implants, particularly luminal tissue implants, where the implants are engineered by seeding of an acellular scaffold or matrix with muscle cell precursors and fibroblasts, for example injection seeding using particular ratios of cells. The present invention provides methods for producing tissue engineered constructs for implantation into a subject which can utilise novel seeding processes described herein for improved cell engraftment and differentiation. In addition, the invention describes methods for treating an individual by implantation of the engineered constructs or tissues of the invention.

Abstract: Devices and methods for the treatment of open and closed wound spinal cord injuries are disclosed. For example, described herein are devices and methods for mitigating secondary injury to, and promoting recovery of, spinal cord primary injuries. More particularly, certain embodiments of the present invention are directed to polymeric mini-tubes that may be used for the treatment of spinal cord injuries. In addition, other embodiments are directed to polymeric “fill-in” bandages that may be used for the treatment of spinal cord injuries. For example, an erodible, or biodegradable, form of biocompatible polymer of the present invention is fabricated for surgical implantation into the site of the spinal cord injury.