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Archive - Nov 11, 2019


Biomarker Blood Test Could Reveal High-Risk Heart Patients in Need of Treatment

Without occasionally looking under the hood, it’s difficult topredict whether expensive car repairs lie ahead. In a similar way, preventive cardiologists are looking for ways to detect early-stage heart disease in people who aren’t currently in treatment. Preventive cardiology researchers at the University of Texas (UT) Southwestern Medical Center believe that a new blood test for protein biomarkers could identify these individuals. Their new study, published online on November 11, 2019 in Circulation, pooled patient data from three major patient populations including multiple ethnicities and totaling nearly 13,000 people. The team asked whether measuring levels of two biomarkers – proteins in the blood – would identify people in need of treatment. The researchers found that approximately one-third of adults with mild hypertension who are not currently recommended for treatment have slight elevations of one of these two biomarkers; these individuals were more likely to have heart attacks, strokes, or congestive heart failure over the next 10 years. In other words, these patients are “flying under the radar” and do not know that they are at greater risk of cardiovascular events. The Circulation article is titled “Incorporation of Biomarkers Into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA High Blood Pressure Guideline: A Pooled Cohort Analysis.” Dr. Ambarish Pandey (left in photo) and Dr. Parag Joshi (right in photo) believe some patients at risk of heart disease could be helped by a biomarker blood test.“We think this type of test can help in the shared decision-making process for patients who need more information about their risk,” said preventive cardiologist Dr. Parag Joshi, Assistant Professor of Internal Medicine.

Study Reveals How Two Strains of One Bacterium Combine to Cause Flesh-Eating Infection

In recent years, scientists have found that serious infections that progress rapidly and resist treatment are often caused by multiple microbes interacting with one another. Very little is known about these so-called “polymicrobial infections,” but traditional diagnostic methods often misidentify them as monomicrobial, or single-microbe, infections. A new study by a team of scientists that included researchers from the University of Maryland, the University of Texas Medical Branch, and CosmosID, Inc., used genetic analysis to reveal how two different strains of a single species of flesh-eating bacteria worked in concert to become more dangerous than either one strain alone. The study was published online in the Proceedings of the National Academy of Sciences on November 11, 2019. The article is titled “T6SS and ExoA of Flesh-Eating Aeromonas Hydrophila In Peritonitis And Necrotizing Fasciitis During Mono- And Polymicrobial Infections.” "This research provides clear evidence that a very severe infection considered to be caused by a single species of a naturally occurring bacterium actually had two strains," said Rita Colwell (photo), PhD, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies and a co-author of the study. "One of the strains produces a toxin that breaks down muscle tissue and allows the other strain to migrate into the blood system and infect the organs." The original infection--cultured from a patient who developed the severe flesh-eating disease known as necrotizing fasciitis--was diagnosed as a monomicrobial disease. Traditional diagnostics could only determine that the infection was caused by a single species of bacteria called Aeromonas hydrophila.

Penn Scientists Uncover Dose of Medication More Likely to Put Patients with Pemphigus (Chronic, Sometimes Fatal Skin Disease) into Remission; Findings May Inform Use of Recent FDA Approved Drug Rituximab to Better Treat Patients with Pemphigus

Pemphigus, an autoimmune disease mediated by B cells and which causes painful blisters and sores on the skin and mucous membranes, is a rare chronic autoimmune condition that can be fatal if not treated. Treatment for pemphigus, most commonly through an oral medication, was often slow and would not result in complete remission. Now, new research from a team in the Perelman School of Medicine at the University of Pennsylvania shows that a lymphoma-dose regimen of rituximab, a medication regularly used to treat lymphoma and rheumatoid arthritis, is more likely to put patients with pemphigus into complete remission as compared to a rheumatoid arthritis (RA) regimen of the same medication. The findings--which were published online on October 23, 2019 in JAMA Dermatology -- have direct implications for patient care. The article is titled " Factors Associated with Complete Remission After Rituximab Therapy for Pemphigus.” When rituximab, an antibody which was first used to treat B cell lymphoma, became a treatment for pemphigus vulgaris, clinicians could choose to prescribe either a "lymphoma dose" or an "RA dose." A lymphoma-dose regimen of rituximab is a more aggressive approach to treatment compared to the dosing method for patients with rheumatoid arthritis. What's more, the U.S. Food and Drug Administration (FDA) now has an approved dosing regimen for pemphigus vulgaris, but it closely resembles the often less-effective RA dose. While both lymphoma and RA dosing approaches deplete B cells that cause disease, the lymphoma regimen takes into account a person's height and weight to determine a dose and is given weekly for four weeks. A rheumatoid arthritis dose is a fixed dose of two 1000 mg infusions given two weeks apart.

Computer Analysis Reveals Over 1 Million Nucleic Acid Polymer Molecules That Are Possible Alternatives to DNA & RNA

Biology encodes information in DNA and RNA, which are complex molecules finely tuned to their functions. But are they the only way to store hereditary molecular information? Some scientists believe life as we know it could not have existed before there were nucleic acids, thus understanding how they came to exist on the primitive Earth is a fundamental goal of basic research. The central role of nucleic acids in biological information flow also makes them key targets for pharmaceutical research, and synthetic molecules mimicking nucleic acids form the basis of many treatments for viral diseases, including HIV. Other nucleic acid-like polymers are known, yet much remains unknown regarding possible alternatives for hereditary information storage. Using sophisticated computational methods, scientists from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, the German Aerospace Center (DLR), and Emory University explored the "chemical neighborhood" of nucleic acid analogues. Surprisingly, they found well over a million variants, suggesting a vast unexplored universe of chemistry relevant to pharmacology, biochemistry and efforts to understand the origins of life. The molecules revealed by this study could be further modified to gives hundreds of millions of potential pharmaceutical drug leads. The study results were published on September 9, 2019, in the Journal of Chemical Information and Modeling.

Genetic Diversity Facilitates Effectiveness of Cancer Therapy; Cancer Patients with Broader Diversity of HLA Genes Respond Better to Treatment with Checkpoint Inhibitors

The constant battle against infectious pathogens has had a decisive influence on the human immune system over the course of our evolution. A key role in our adaptation to pathogens is played by HLA molecules. These proteins activate the immune system by presenting it with fragments of pathogens that have entered the body. People with a wide variety of different HLA proteins are thus better armed against a large number of pathogens. Researchers at the Max Planck Institute for Evolutionary Biology in Plön, Germany, together with colleagues in New York, have been investigating the diversity of HLA genes in cancer patients being treated with immune checkpoint inhibitors. This form of immunotherapy activates the body's own immune cells to enable them to identify and eliminate tumor cells. The researchers discovered that patients with a wide variety of HLA molecules derive more benefit from this type of therapy. This means that in future, doctors may be able to offer improved individual treatment based on a patient's HLA gene profile. In the evolution of an organism, the characteristics which often prevail are those which increase the chances of survival and reproduction of their carrier. In contrast, for a robust immune system it could be advantageous for it to be variable, keeping as many options open as possible - a hypothesis which has been tested and confirmed in an early study carried out specifically on HLA molecules by Fr. Federica Pierini and Dr. Tobias Lenz at the Max Planck Institute for Evolutionary Biology. It is therefore essential for the effectiveness of an immune system to have many different variants of HLA molecules, Because each variant can bind to several different pathogen or cancer cell protein fragments.