Abstract: The present invention provides for compounds of formula (I) wherein Y1, Y2, R1, R2, R3, A1, A2, A3, and A4, have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

Abstract: The present disclosure identifies a novel subtype of follicular lymphoma (FL) characterized by dysregulation of the cyclin/CDK/RB proliferative pathway. This subtype of FL is associated with increased malignancy and mortality, relative to FL which is not associated with cell cycle dysregulation. Accordingly, this disclosure presents novel methods to subtype FL and stratify patient risk by detection of biomarkers associated with RB inactivation. This disclosure further presents novel therapies for the treatment of FL subtyped by inactivation of RB.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A risperidone sustained release microsphere formulation is provided. The microsphere formulation includes risperidone or 9-hydroxy risperidone or salts thereof, and a polymer blend having a first uncapped lactide-glycolide copolymer and a second uncapped lactide-glycolide copolymer, in which the first uncapped lactide-glycolide copolymer is a copolymer with a high intrinsic viscosity and the second uncapped lactide-glycolide copolymer is a copolymer with a low intrinsic viscosity. The sustained release micro sphere formulation according to an embodiment of the present disclosure is suitable for large-scale industrialized production with improved stability, the in vivo release behavior of which will not change after long-term storage.

Abstract: The present disclosure is related to heteroaryl compounds as MEK inhibitors. These compounds include heteroaryl compounds of formula I, their pharmaceutically acceptable salts, combinations with suitable medicament and pharmaceutical compositions thereof. The present disclosure also includes processes of preparation of the compounds and their use in methods of treatment.

Abstract: Provided herein are methods, compositions, and kits for treating myeloproliferative disorders or neoplasms, including polycythemia vera, primary myelofibrosis, thrombocythemia, and essential thrombocythemia. Also provided herein are methods for treating cancers. Such methods may include the use of a JAK inhibitor and a PI3K inhibitor. Such methods may include the use of an anti-CD20 antibody and a PI3K inhibitor. Provided herein are also compositions, articles of manufacture and kits related thereto.

Abstract: A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof and (b) a gonadorelin agonist and, optionally, (c) an antiestrogen agent, particularly for use in the treatment or prevention of a cancer; uses of such a combination in the preparation of a medicament for the treatment or prevention of a cancer; pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a cancer in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

Abstract: The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.

Abstract: The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA ?5) and act as GABAA ?5 negative allosteric modulators (GABAA ?5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA ?5 such as Alzheimer's disease.

Abstract: The present invention is directed generally to stable formulations of a TLR agonist preferably a TLR7 or a TLR8 agonist, for use in the treatment of cancer, preferably solid tumors and lymphomas. Specifically, the present invention is directed to stable formulations of up to 50 mg/ml of a TLR agonist which comprise a cyclodextrin.

Abstract: A medicinal composition is administered orally twice a day to a patient to ameliorate the symptoms related to Parkinson's disease. The medicinal composition includes mixing a quantity of ibogaine, a quantity of vitamin supplements and a quantity of manufacturing additives into a heterogeneous medicinal mixture. The quantity of ibogaine, formulated as ibogaine HCl, other non-toxic salts of ibogaine (an alkaloid of the family apocynaceae), or noribogaine, its active metabolite, is an active ingredient to regulate endogenous glial cell line-derived neurotrophic factor (GDNF). The quantity of vitamin supplements promotes the general health and neurological functions. The quantity of manufacturing additives bonds the quantity of ibogaine and the quantity of vitamin supplements together, as well as, provides anti-adherent properties to prevent the medicinal mixture from adhering to manufacturing equipment.

Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that reduces the biological activity of one or more bromodomain and extra-terminal family member (BET) proteins (e.g., a bromodomain inhibitor), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell.

Abstract: In various embodiments, methods and compositions for treating Raynaud's disease and Raynaud's phenomenon are provided. Topical administration of a semisolid composition comprising a prostaglandin E1 compound provides the desired relief of the Raynaud's disease or Raynaud's phenomenon without the possible complications of systemic administration. The semisolid composition can be administered as needed, or in a regimen of several doses per day.

Abstract: Described are transdermal drug delivery systems for the transdermal administration of testosterone, comprising a polymer matrix and testosterone. Methods of making and using such systems also are described.

Abstract: The present disclosure relates to pharmaceutically acceptable complex formulae comprising complexes of Abiraterone acetate and pharmaceutically acceptable excipients, process for the preparation thereof and pharmaceutical compositions containing them. The complex formulae of the present disclosure have improved physicochemical properties which results in reduced food effect which allows significant dose reduction and the abandoning of the requirement of taking the drug on an empty stomach.

Abstract: A composition for delivering cholecalciferol to skin and/or mucous membranes via topical application. The composition comprises xylitol and cholecalciferol in emulsion. Optionally, the composition may include additional components such as glycerol, polyethylene glycol, propylene glycol, pharmaceutical agents, stabilizers, acids, bases, buffers, antioxidants, emulsifiers, suspending agents, and preservatives. Methods of preparation of the composition and of using it as a topical treatment for delivery of cholecalciferol to the skin and/or mucous membranes are also disclosed.

Abstract: The method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient's normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient's normal historical physiological range between doses of Vitamin D hormone replacement therapies.

Abstract: Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, can be used to treat or alleviate pain or related conditions.

Abstract: Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, can be used to treat or alleviate pain or related conditions.

Abstract: Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions.

Abstract: The present invention provides a therapeutic drug for diabetes containing 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE) as an active ingredient, particularly a therapeutic drug for diabetes that exhibits a GLUT4 endocytosis suppressive action by suppressing activation of PKC? and the like.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

Abstract: Provided are methods and compositions for treating and preventing hyperproliferative disorders such as psoriasis by administration of a cardiac glycoside alone or in combination locally or systemically with a calciotropic agents and/or a diffusion-limiting component, such a vasoconstrictor or collagen barrier.

Abstract: Composition comprising a uridine source, an omega-3 PUFA for improving coordination, balance, grip strength or fine motor skills. The invention is directed to a combination of a uridine source and an omega-3-polyunsaturated fatty acid having 18-24 carbon atoms for use in •—the prevention or treatment of a disturbance in coordination of limbs in a mammal •—the prevention or treatment of a disturbance in equilibrium in a mammal •—for use in the prevention or treatment of a disturbance in limb strength •—or use in the prevention or treatment of a disturbance in a motor skill in a mammal.

Abstract: The present invention relates to the use of a combination of an anti-retroviral agent such as zidovudine and anti-microbial agents for killing clinically latent microorganisms associated with microbial infections and to novel combinations comprising an anti-retroviral agent such as zidovudine and anti-microbial agents for the treatment of microbial infections.

Abstract: This invention is directed to ?-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The ?-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.

Abstract: The present disclosure provides compositions and methods for treating and preventing thrombosis. In particular, the present disclosure provides methods and compositions for treating and preventing thrombosis utilizing E-selectin inhibition in combination with heparin.

Abstract: The present invention relates to a pharmaceutical composition for use as a medicament in the prophylactic or therapeutic topical treatment of viral eye infections caused by adenovirus of subtype D or influenza A virus of subtype H7. The composition in its ready-for-use formulation comprises iota carrageenan as an active antiviral ingredient and is substantially free of a metal halide salt or contains no more than 0.5% w/v of a metal halide salt.

Abstract: The disclosure relates to an alginate oligomer of 2 to 75 monomer residues, wherein said monomer residues do not carry a sulphate group, for use as a blood anticoagulant in clinical and non-clinical applications, including in vivo, ex vivo and in vitro contexts. The invention further provides for the use of such an alginate oligomer in preparing a product or device having a reduced capacity to promote blood coagulation, wherein said alginate oligomer is provided at or on a surface of said product or device. Such products and devices form a further aspect of the invention.

Abstract: A liposomal rehydration salt formulation comprising phosphatidylcholine liposomes, salts, water, and a percentage inclusion ratio of salts (salts retained within said liposomes/total salts) of at least 40%; and a process for preparing said formulation using tangential ultrafiltration.

Abstract: Toxins produced by bacteria promote infection and disease by directly damaging host tissues and by disabling the immune system. In one embodiment, the present application provides methods of treating and prevention further inflammation by inactivating toxins through use positive chlorinated ionic solution and or their derivatives.

Abstract: The invention relates to an edible product containing a decontaminant. Particularly, the invention relates to an edible product, for instance, a food-like product, containing an effective amount of activated charcoal to mitigate, substantially reduce or cause the cessation of at least one adverse effect associated with the ingestion of a toxic substance. The invention also relates to methods for manufacturing such a decontaminant edible product and uses thereof.

Abstract: Various embodiments of the invention relate to compositions comprising marrow infiltrating lymphocytes (“MILs”). The MILs may be activated MILs. Some embodiments relate to methods for activating MILs, comprising incubating MILs in an environment comprising less than 21% oxygen. Some embodiments relate to methods for treating cancer in a subject, comprising administering to the subject a composition comprising activated MILs.

Abstract: This invention relates to compounds of Formula I: (Formula I), and pharmaceutically acceptable salt thereof, which are allosteric effectors that increase the oxygen-being affinity of hemoglobin, which are useful in the treatment of sickle cell disease, high altitude tissue hypoxia, and other conditions.

Abstract: This invention relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are allosteric effectors that reduce the oxygen-binding affinity of hemoglobin, which can enhance the efficacy of radiation therapy for cancer and which are useful for the treatment of ischemia and other conditions.

Abstract: Described are compositions and methods for treating liver disease, e.g., acute liver disease, using bone marrow-derived stem cells and bone marrow-derived stem cell conditioned media.

Abstract: A population of cells possesses enhanced selectin binding based upon a fucosylated selectin ligand present on a surface thereof. Methods of producing the population of cells, along with therapeutic methods of using the cells, are also disclosed.

Abstract: The present disclosure provides methods and compositions for making and using pluripotent stem cell-derived oligodendrocyte progenitor cells.

Abstract: Compositions and methods for darkening skin and treating vitiligo are provided.

Abstract: The disclosure provides a composition for inhibiting thrombosis. The composition includes 5 to 25% by weight of Fish Oil, 15 to 55% by weight of Willow Bark Extract, and 0.2 to 5% by weight of Vitamin E.

Abstract: Methods are provided for isolating and using a whole-saliva leech extract. The methods can include feeding a phagostimulatory agent to a leech; inducing a regurgitation in the leech, the inducing including placing the leech in an environment having a temperature of less than about 0° C.; and, collecting an unrefined, whole saliva in the regurgitation of the cooled leech. The methods can include revitalizing the leech by warming it at a temperature ranging from about 5° C. to about 40° C. Stable, lyophilized, whole-saliva extracts of a leech are also provided, the extract having a stable activity when stored for use at a temperature below about ?20° C., the extract maintaining at least 70% of the activity for at least 6 months. The extracts can be used to treat solid tumors, treat liquid tumors, treat diabetes, treat a viral disease, treat a parasitic disease, treat an antibacterial disease, or serve as an anti-oxidant.

Abstract: Methods are also provided for isolating and using a whole-saliva leech extract in the treatment of a bacterial skin infection. The methods can include feeding a phagostimulatory agent to a leech; inducing a regurgitation in the leech, the inducing including placing the leech in an environment having a temperature of less than about 0° C.; and, collecting an unrefined, whole saliva in the regurgitation of the cooled leech. The methods can include revitalizing the leech by warming it at a temperature ranging from about 5° C. to about 40° C. Stable, lyophilized, whole-saliva extracts of a leech are also provided, the extract having a stable activity when stored for use at a temperature below about ?20° C., the extract maintaining at least 70% of the activity for at least 6 months. The extracts can be used to treat solid tumors, treat liquid tumors, treat diabetes, treat a viral disease, treat a parasitic disease, treat an antibacterial disease, or serve as an anti-oxidant.

Abstract: This application provides compositions, e.g., formulations, used for gastric, gastrointestinal and/or colonic treatments, and methods for making, storing and using them, including storage, including long term storage, at ambient temperature. Compositions provided herein are useful for treating various diseases or conditions such as autism spectrum disorder, Crohn's Disease, ulcerative colitis, irritable bowel syndrome, and recurrent or primary C. difficile infection.

Abstract: The invention relates to methods and compositions for restoring normal microbiota in pre-term newborns or newborns delivered by Cesarean section and methods for preventing or ameliorating diseases associated with delivery by Cesarean section or pre-term birth comprising administering to said newborns at the time of birth or shortly thereafter an effective amount of a vaginal microbiota inoculum obtained from the newborn's mother or a donor or an effective amount of a probiotic composition.

Abstract: The present disclosure relates to a group B adenovirus comprising a sequence of formula (I): 5?ITR-B1-BAB2-BX-BB-BY-B3-3?ITR wherein: B1 is bond or comprises: E1A, E1B or E1AE1B; BA comprises: E2B-L1-L2-L3-E2A-L4; B2 is a bond or comprises: E3; BX is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both; BB comprises L5; BY is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both; B3 is a bond or comprises: E4; wherein at least one of BX or BY is not a bond, pharmaceutical compositions comprising the same and use of the viruses and compositions in treatment, particularly in the treatment of cancer. The disclosure also extends to plasmids and processes employed to prepare the said viruses.

Abstract: The present application relates to a composition for the treatment of persistent cough, suitable also for pediatric use, processes for the preparation of said composition, and a method for the treatment of persistent cough in adult individuals or in individuals of pediatric age by means of the administration of pharmaceutically effective doses of the above-mentioned composition.

Abstract: Composition comprising (optionally processed) edible parts of an okra plant species for use in reducing dietary fat absorption in a subject or for use in treating or preventing obesity and/or for use in treating or preventing a metabolic disease such as metabolic syndrome, or for managing the weight of a subject, by binding dietary fat in the subject's stomach.

Abstract: Embodiments of the inventions described herein provide, among other things, enriched Amaranthus blitoides compositions, such as those enriched with Vitamin D and to the use thereof to alleviate symptoms or discomforts associated with inflammation, inflammatory disorders, Benign Prostatic Hyperplasia (BPH), other inflammation related problems, infections of the genitourinary tract, hemorrhoidal diseases and the same, and to use of the same to treat these and other disorders and diseases.

Abstract: The invention provides a dermatological composition comprising materials of algae origin (e.g. Arthrospira platensis) and olive leaf origin, the composition at least comprising a polypeptide and hydroxytyrosol. The composition is for use in the treatment and/or prevention of a dermatological microbial infection, e.g. nail fungus, Athlete's foot, wound, chickenpox, acne. The invention also provides an applicator device comprising such composition. Further, the invention provides a method for preparing such dermatological composition. Especially, the composition at least comprises a polypetide and hydroxytyrosol.

Abstract: Compositions are disclosed which have as a component thereof an inhibitor of the enzymatic production of 3-deoxyglucosone (3DG) from fructoselysine and/or an inactivator of 3DG, and which are useful for the treatment or prophylaxis of a condition or disease state that is alleviated by inhibiting such 3DG production. Methods of using such compositions, e.g., for improving the appearance, texture and/or elasticity of aging skin, are also disclosed.