Abstract: Methods, processes, and systems for predicting a subject's disease complications and/or response to therapy are described herein. The methods generally comprise genotyping or receiving genotyping information from the subject at a plurality of risk alleles associated with the disease and at a plurality of ancestry-informative markers. The genotyping information is used to generate a polygenic risk score (PRS) by weighting the number of risk alleles by the effect size of their association (weighted genetic risk score or wGRS), combined with a geo-ethnic principal component (PC) determined from the subject's genotype at said ancestry-informative markers. The PRS enables better prediction of the subject's disease complications and/or response to therapy, as compared to a corresponding PRS generated lacking the geo-ethnic principal component. Computer-implemented methods and processes are also described herein.

Abstract: The invention provides with means to predict, in subjects affected by type-2-diabetes (T2D), the probability of developing complications related to the disease. The invention involves (1) identification of genetic features such as single nucleotide polymorphisms (SNPs) for the establishment of a patient profile that can be used for prediction of complications associated with T2D. Signature profiles comprising a combination of SNPs which have greater predictive value for prognosticating particular types of complications, such as, stroke, myocardial infarction and kidney complications associated with T2D are further described. Compositions and kits that can be used with a set of complementary phenotypic markers to evaluate the risk for an individual affected by T2D to develop complications related to the disease and to evaluate the likelihood that an individual affected by type 2 diabetes type will benefit from treatments that collectively aim to reduce the risk of developing such complications.

Abstract: The invention provides means and methods to predict, in subjects affected by type II diabetes (T2D), the probability of developing complications which include, but are not limited to, micro/macrovascular disorder, hypertension, neuropathy, atrial fibrillation, nephropathy and other major adverse cardiovascular events (MACE) that are associated with the disease, by detecting one or more genetic features. The genetic features that are useful in prediction include, but are not limited to, genes, single nucleotide polymorphisms (SNPs) and other genomic markers. The invention further involves characterizing individuals based on the probability of developing complications related to T2D, such as, micro/macrovascular disorder, hypertension, neuropathy, atrial fibrillation, nephropathy or MACE, based on the identification of one or more aforementioned genetic features. Also described are combinations and kits for carrying out the above-described methods.

Abstract: The present invention concerns a method of determining a predisposition to atrial fibrillation (AF) in a subject comprising: determining the presence of at least one copy of a risk allele from at least one polymorphic marker in a sample from the subject, wherein the presence of at least one copy of the risk allele is indicative of a predisposition to AF, and wherein said at least one polymorphic marker is: a) rs4674485; b) rs1466560; c) rs1880039; d) rs3849387; e) rs7039; f) rs2952860; g) rs9312515; h) rs1897527; i) rs2299277; j) rs2418828; k) rs2385833; l) rs6717960; m) rs10510266; or n) a substitute polymorphic marker in linkage disequilibrium with any one of the polymorphic markers of a) to m). Also described are kits for determining a predisposition to atrial fibrillation (AF).

Abstract: The invention provides with means to predict, in subjects affected by type 2 diabetes (T2D), the probability of developing complications related to the disease. The invention involves 1) use of genetic features (SNPs, STRs, or other genomic markers) together with other chromosomal features and phenotypic information to establish a patient profile specifically developed for prediction of complications of T2D 2) use of a set of SNPs allowing to discriminate between individuals according to their descent. The invention also provides with methods for characterizing and selecting, within a population of subjects with type-2 diabetes, subjects that are suited for clinical trials based on the identification of one or more genetic features. Also described are combinations and kits for carrying out the above-described methods.

Abstract: The invention provides with methods for characterizing and selecting, within a population of subjects with type-2 diabetes, subjects that are suited for clinical trials based on the identification of one or more genetic features, which are single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), and/or other genomic markers. The invention further involves characterizing these subjects based on the probability of developing complications related to type-2 diabetes, such as, myocardial infarction, stroke and albuminuria. Also described are combinations and kits for carrying out the above-described methods.

Abstract: The invention provides with means to predict, in subjects affected by type 2 diabetes (T2D), the probability of developing complications related to the disease. The invention involves 1) use of genetic features (SNPs, STRs, or other genomic markers) together with other chromosomal features and phenotypic information to establish a patient profile specifically developed for prediction of complications of T2D 2) use of a set of SNPs allowing to discriminate between individuals according to their descent. A preferred set of genomic markers selected for their association with complications of T2D is provided that can be used with a set of complementary phenotypic markers to evaluate the risk for an individual affected by T2D to develop complications related to the disease and to evaluate the likelihood that an individual affected by T2D type will benefit from treatments reducing the risk of developing such complications.

Abstract: Novel nucleic acids and corresponding encoded proteins are described. Also described are corresponding recombinant vectors and host cells, as well as methods of producing the proteins. Also described are mimetics and antibodies to the proteins as well as compositions comprising the nucleic acid or proteins or a portion thereof. Methods and kits for the detection of a disease, disorder or abnormal physical state caused by abnormal modulation of calcium levels in a patient are also described. Methods for treating a patient having a disease, disorder or abnormal physical state caused by abnormal calcium levels are also described. Methods for assaying abnormal calcium levels are also described, as are methods for screening the efficacy of products for modulating abnormal calcium levels.

Abstract: Apoptosis and/or necrosis related disorders in the mammalian body, namely radiation exposure disorders, chemical exposure and ingestion disorders, neurological disorders and physical trauma disorders, are treated, and their onset is counteracted by preconditioning, by extracting from the mammalian body an aliquot of blood, subjecting the extracted aliquot, ex vivo, to an oxidative stressor such as exposure to ozone gas, a temperature stressor, i.e. temperatures above or below body temperatures, and ultraviolet light, and re-injecting the treated blood aliquot into the mammalian body. The treatment ha the effect of decreasing apoptosis/necrosis in the body, and of pre-conditioning the body better to withstand subsequently encountered apoptosis-inducing events.

Abstract: Apoptosis and/or necrosis related disorders in the mammalian body, namely radiation exposure disorders, chemical exposure and ingestion disorders, neurological disorders and physical trauma disorders, are treated, and their onset is counteracted by preconditioning, by extracting from the mammalian body an aliquot of blood, subjecting the extracted aliquot, ex vivo, to an oxidative stressor such as exposure to ozone gas, a temperature stressor, i.e. temperatures above or below body temperatures, and ultraviolet light, and re-injecting the treated blood aliquot into the mammalian body. The treatment ha the effect of decreasing apoptosis/necrosis in the body, and of pre-conditioning the body better to withstand subsequently encountered apoptosis-inducing events.

Abstract: This invention relates to a novel gene that shows tissue specific expression and increased expression in a low calcium concentration medium. Low renin hypertension is characterized by decreased levels of serum ionized calcium in the presence of increased levels of parathyroid hormone. It is hypothesized that hypertensive factor(s) are co-secreted with PTH in SHR, a model of low renin hypertension, the parathyroid hypertensive factor being one of them. As a negative calcium balance is present in spontaneously hypertensive rats (SHR), we searched for gene(s) involved in this dysregulation. A cDNA library was constructed from the SHR parathyroid gland which is a key regulator of serum ionized calcium. From 7 overlapping DNA fragments, a 1100-bp novel cDNA containing an open reading frame of 224 codons was reconstituted.

Abstract: Longterm elevation of the intracellular Na+/K+ ratio inhibits macromolecule synthesis and proliferation in the majority of cell types studied so far, including vascular smooth muscle cells (VSMC). We report here that inhibition of the Na+,K+ pump in VSMC by ouabain or 1 hour preincubation in K+-depleted medium attenuated apoptosis triggered by serum withdrawal, staurosporine or okadaic acid. In the absence of ouabain, both DNA degradation and caspase-3 activation in VSMC undergoing apoptosis were insensitive to modification of the extracellular Na+/K+ ratio as well as to hyperosmotic cell shrinkage. In contrast, protection of VSMC from apoptosis by ouabain was abolished under equimolar substitution of Na+o with K+o, showing that the anti apoptotic action of Na+,K+ pump inhibition was caused by inversion of the intracellular Na+/K+ ratio.

Abstract: This invention relates to a novel gene that shows tissue specific expression and increased expression in a low calcium concentration medium. Low renin hypertension is characterized by decreased levels of serum ionized calcium in the presence of increased levels of parathyroid hormone. It is hypothesized that hypertensive factor(s) are co-secreted with PTH in SHR, a model of low renin hypertension, the parathyroid hypertensive factor being one of them. As a negative calcium balance is present in spontaneously hypertensive rats (SHR), we searched for gene(s) involved in this dysregulation. A cDNA library was constructed from the SHR parathyroid gland which is a key regulator of serum ionized calcium. From 7 overlapping DNA fragments, a 1100-bp novel cDNA containing an open reading frame of 224 codons was reconstituted.

Abstract: Symptoms of stress such as elevated blood pressure in mammals are treated, and mammalian bodies are preconditioned to manifest reduced adverse reactions to subsequently encountered stresses, by injecting into the mammalian patient a small quantity of the patient's own blood which has been previously extracted and subjected extracorporeally to at least one stressor, such as ultraviolet radiation, an oxidative environment, ozone-oxygen and mild heating, especially infra-red radiation causing mild heating. Particularly beneficial combinations of stressors are simultaneous applications of UV radiation and an ozone-oxygen gas mixture bubbled through the blood sample to provide the oxidative environment, or simultaneous application of UV radiation, ozone-oxygen gas mixtures and mild heating. One specific use of the invention is in preconditioning against ischemic-reperfusion injury e.g. prior to surgery.

Abstract: Symptoms of stress such as elevated blood pressure in mammals are treated, and mammalian bodies are preconditioned to manifest reduced adverse reactions to subsequently encountered stresses, by injecting into the mammalian patient a small quantity of the patient's own blood which has been previously extracted and subjected extracorporeally to at least one stressor, such as ultraviolet radiation, an oxidative environment, ozone-oxygen and mild heating, especially infra-red radiation causing mild heating. Particularly beneficial combinations of stressors are simultaneous applications of UV radiation and an ozone-oxygen gas mixture bubbled through the blood sample to provide the oxidative environment, or simultaneous application of UV radiation, ozone-oxygen gas mixtures and mild heating. One specific use of the invention is in preconditioning against ischemic-reperfusion injury, e.g. prior to surgery.

Abstract: Uptake, binding, and/or displacement of atrial natriuretic factor in a target organ of a mammal can be quantified by nuclear imaging. A diagnostically effective amount of a radio-labelled mammalian atrial natriuretic factor, active fragment or analog thereof is administered to a live mammal, and the live mammal or a portion thereof is subsequently imaged at one or more time intervals using a suitable radio-detecting device to quantify the uptake, binding and/or displacement of the radio-labelled atrial natriuretic factor, fragment or analog in one or more target organs.