Saint Louis University

About: Saint Louis University is a education organization based out in St Louis, Missouri, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 18927 authors who have published 34895 publications receiving 1267475 citations. The organization is also known as: SLU & St. Louis University.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Hepcidin in Human Iron Disorders: Diagnostic Implications

Abstract: BACKGROUND: The peptide hormone hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. Many human diseases are associated with alterations in hepcidin concentrations. The measurement of hepcidin in biological fluids is therefore a promising tool in the diagnosis and management of medical conditions in which iron metabolism is affected. CONTENT: We describe hepcidin structure, kinetics, function, and regulation. We moreover explore the therapeutic potential for modulating hepcidin expression and the diagnostic potential for hepcidin measurements in clinical practice. SUMMARY: Cell-culture, animal, and human studies have shown that hepcidin is predominantly synthesized by hepatocytes, where its expression is regulated by body iron status, erythropoietic activity, oxygen tension, and inflammatory cytokines. Hepcidin lowers serum iron concentrations by counteracting the function of ferroportin, a major cellular iron exporter present in the membrane of macrophages, hepatocytes, and the basolateral site of enterocytes. Hepcidin is detected in biologic fluids as a 25 amino acid isoform, hepcidin-25, and 2 smaller forms, i.e., hepcidin-22 and −20; however, only hepcidin-25 has been shown to participate in the regulation of iron metabolism. Reliable assays to measure hepcidin in blood and urine by use of immunochemical and mass spectrometry methods have been developed. Results of proof-of-principle studies have highlighted hepcidin as a promising diagnostic tool and therapeutic target for iron disorders. However, before hepcidin measurements can be used in routine clinical practice, efforts will be required to assess the relevance of hepcidin isoform measurements, to harmonize the different assays, to define clinical decision limits, and to increase assay availability for clinical laboratories.

Some aspects of band-pass filtering of surface waves

Abstract: Narrow band-pass filtering of multi-mode surface-wave signals can be used to extract information concerning the group velocities and spectral amplitudes of each mode. A detailed examination of narrow band-pass filtering shows the effect of epicentral distance and the shape of the group-velocity curve upon the filtered signal. With this knowledge, the filtered signal can be used to make accurate estimates of the spectral amplitudes of each mode. A rectangular and a Gaussian filter are considered in detail. A numerical example is provided to indicate the values and limitations of the technique for determining the spectral amplitudes of each mode.

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

Abstract: Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia. A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as "nonclassical" cannabinoid analgetics that conform to this agonist-receptor three-point interaction model. At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor. A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro. Enantio- and stereoselectivity were exhibited by the nonclassical cannabinoid compounds for both the analgetic response and the ability to inhibit adenylate cyclase. The magnitude of the enantioselective response was equal for both the biochemical and physiological endpoints. Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo. A conceptualization of the cannabinoid analgetic receptor is presented.

Use Your Words Carefully: What Is a Chronic Disease?

Abstract: One important element of effective communication is having a shared language or at least a shared understanding of the meaning of the central words used in a conversation. One term that is often used in discussions between patients and medical providers, in the academic literature, and in policy discussions, is “chronic disease.” There is not only tremendous variation in the diseases that are included under the umbrella term “chronic disease” but also variation in the time a disease must be present for something to be referred to as chronic. Furthermore, there is a move to include chronic conditions that are not indicators of disease, but long-standing functional disabilities, including developmental disorders and visual impairment (1–4). Within professional communities (i.e., medical, public health, academic, and policy), there is a large degree of variation in the use of the term chronic disease. For example, the Centers for Disease Control (CDC) classify the following as chronic diseases: heart disease, stroke, cancer, type 2 diabetes, obesity, and arthritis (5). The Centers for Medicare and Medicaid Services have a more extensive list of 19 chronic conditions that includes Alzheimer’s disease, depression, and HIV, to name a few. This difference, within the Department of Health and Human Services alone, although not surprising to those in the field, has the potential to create confusion and misunderstanding when speaking in generalities about the impact of chronic disease, the cost of chronic disease, and overall measures to reduce chronic disease. The academic literature is not immune to the same kind of terminology variation. Differences in how “chronic disease” is used are largely dependent on the data used for the research and the discipline of the lead authors (i.e., public health and sociology). For example, one study, authored by individuals from Harvard Medical School, explored the prevalence of chronic disease using NHANES data (1999–2004). The study classifies the following as chronic diseases: cardiovascular disease, hypertension, diabetes mellitus, hypercholesterolemia, asthma, COPD, and previous cancer (6). Another academic study on chronic disease, authored by a geriatrician, classifies chronic illness as “conditions that last a year or more and require ongoing medical attention and/or limit activities of daily living” (7). The implication of a non-uniform use of the term is that a detailed read of each study is necessary to avoid erroneous conclusions regarding interventions necessary to reduce chronic disease burden for the individual and society. Popular Internet sources used by the general public to gather medical information use the terms “chronic disease” or “chronic condition” to mean slightly different things. For example, MedicineNet describes a chronic disease as,