A molecular probe includes a detector molecule specific to a target molecule, and at least one label linked covalently or non-covalently to the detector molecule. The label includes a catalyst for generating electrons and/or mediators from a solution. The catalyst includes a nanomaterial, an enzyme, a metal, and/or a metal complex. The mediators can accumulate in the solution for a period of time. The detector molecule and the target molecule interact with each other by a protein based or nucleotide sequence based interaction. The mediators participate in a chemical reaction that generates a signal that may be a change in optical, electromagnetic, thermodynamic or mechanical properties. Generation efficiency of the mediators is enhanced by providing an energy to the solution. The molecular probe may be used with a molecular detection assay performed on a surface. A method for assaying the target molecule using the molecular probe is also provided.

Provided herein are methods for assessing risk of infection or cardiovascular disease (CVD) in a subject with an inflammatory disease, e.g., rheumatoid arthritis. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers with or without additional clinical variables to assess infection and CVD risk. Also provided are uses of inflammatory biomarkers for guiding treatment decisions.

The present disclosure is directed to microneedle patches for direct sampling and ultrasensitive detection of protein biomarkers in dermal interstitial fluids. The microneedle patches are comprised of polymers with high protein absorption capability (e.g. polystyrene) and are modified with capture biorecognition elements that are specific to target analytes in the interstitial fluid (ISF). Systems and methods are further provided for detection of a target ISF analyte obtained by in vivo sampling of the ISF using a microneedle patch.

The present disclosure relates to the use of an anti-IL6 receptor antibody for treating rheumatoid arthritis in subjects with serum concentrations of certain biomarkers.

Methods and kits for evaluating a clinical outcome of an autoimmune disease, specifically disease flare e.g. if the subject stops taking the biologic disease modifying anti-rheumatic drug (DMARD), by comparing biomarkers of CD45RA, TNF-alpha and/or CXCR5 from CD3.sup.+CD4.sup.+ T cell population are disclosed. In a specific embodiment, the ratio of first subset of CD3.sup.+CD4.sup.+CD45RATNFA.sup.+ (memory) T cells to a second subset comprising CD3.sup.+CD4.sup.+CD45RA.sup.+TNFA.sup.+ (nave) T cell is determined, wherein an increase in the ratio indicates a disease flare state of juvenile idiopathic arthritis (JIA). In another embodiment, enrichment of CD45RACR5.sup.+ subset among the T cell population indicates likelihood of flare state in JIA via memory persistence enhancement through B cell interaction. In other embodiments, additional markers including IL-6, CCR6, CD152 and PD1 are also determined, and the enrichment of CD45RA-TNFA.sup.+IL-6.sup.+ subset among the T cell population indicates a likelihood of amplification of the autoimmune disease.

Biomarkers useful for diagnosing and assessing inflammatory disease are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. The biomarkers include at least two biomarkers selected from the DAIMRK group and the score is a disease activity index (DAI).

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that have one or more of the following effects in an injured subject: interact with splenocytes, preserve splenic mass, increase proliferation of CD4.sup.+ and CD8.sup.+ T-cells, increase IL-4 and IL-10, decrease IL-6 and IL-1, and increase M2:M1 macrophage ratio at the site of injury. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to have these effects. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for achieving these effects.

The present invention relates to methods for detecting, diagnosing and/or treating ulcerative interstitial cystitis (UIC) by detecting in a urine sample from a patient the levels of each of the proteins IL-6, IL-8 and GRO [also known as CXCL 1 (chemokine C-X-C motif ligand 1]. In some embodiments, the method also includes diagnosing the patient with UIC when each of the proteins IL-6, IL-8 and GRO in the urine sample is at a different level than a statistically validated threshold for the respective proteins. In some embodiments a companion diagnostic, e.g., a cystoscopy, is used in conjunction with the protein biomarker diagnostic. In some embodiments, once UIC is diagnosed, the patient is treated for the UIC.

The invention relates to a method for the diagnosis and/or risk stratification of invasive fungal infections (IFI)/invasive fungal diseases (IFD) and in particular associated with sepsis or septic shock, wherein a determination of the marker proadrenomedullin (proADM) or a partial peptide or fragment thereof, in particular midregional proadrenomedullin (MR-proADM), or contained in a marker combination (panel, cluster), is carried out from a patient to be examined. Furthermore, the invention relates to a diagnostic assay and a kit for carrying out the method.

This invention provides devices and methods for self-administered noninvasive retrieval of biological materials of the uterus and cervix, and preimplantation stage embryos. The procedure uses a Uterine Device, with a receptacle of variable volume, a controller configured to change the volume of the receptacle cavity, a flexible pouch for generation of suction to facilitate their retrieval, and an Absorption Capsule, which is a surface for collection of the above biological materials. The biological materials retrieved include cells and secretions, directly from the site of pathology, not metabolized or diluted in the body fluids, allow comprehensive analysis of various biomarkers of diseases and disorders of reproduction. Information generated by analyzing these biological materials permits early diagnosis and assessment of prognosis of diseases and disorders of the female reproductive organs, irregularities of pregnancy, anomalies of the fetus in utero, and microbial infections. The preimplantation stage embryos are recovered from normal subjects or those received treatment of gonadotrophins and/or other methods for induction of ovulation or superovulation to improve the yield of ovulated oocytes (ova). Multiple ova released from the ovaries travel through the fallopian tubes, which may be fertilized with sperms made available by artificial or normal insemination (copulation). The fertilized embryos divide and differentiate further into free preimplantation stage embryos at morula- and blastocyst-stages are deposited on the Absorption Capsule. These embryos, retrieved from the Absorption Capsule and may be processed by a variety of methods routinely utilized in the Assisted Reproductive procedures, including, screening for various genomic diseases, karyotype errors of trisomy and other chromosomal anomalies, and deleterious mutations. The screening procedures may involve Preimplantation Genetic Diagnosis (PGD) and Trophectoderm biopsy methods. Normal embryos free of disease potential are transferred to the mothers or surrogates for further in utero development. These procedures allow prevention of human birth defects and pre- and post-natal genomic diseases by selection of disease-free normal embryos for further in utero development, and possible cure of genomic diseases at this stage, in the future.