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Rugby Study Identifies New Method Using MicroRNAs in Saliva to Diagnose Concussion; Results Pave Way for First Non-Invasive Clinical Test for Concussion for Use in Sport and Other Settings

A University of Birmingham-led study of top-flight UK rugby players--carried out in collaboration with the Rugby Football Union, Premiership Rugby, and Marker Diagnostics--has identified a method of accurately diagnosing concussion using saliva, paving the way for the first non-invasive clinical test for concussion for use in sport and other settings. Following the scientific team’s previous research (https://pubmed.ncbi.nlm.nih.gov/28279125/), which identified that the concentration of specific molecules (microRNAS) in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these “biomarkers” could be used as a diagnostic test for sport-related concussion. Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues--the Premiership and the Championship. The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs), published online in March 2021 in the British Journal of Sports Medicine, has for the first time shown that specific salivary biomarkers can be used to indicate if a player has been concussed. Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later. The open-access article is titled “Unique Diagnostic Signatures of Concussion in the Saliva of Male Athletes: The Study of Concussion In Rugby Union Through MicroRNAs (SCRUM)” (https://Bjsm.Bmj.Com/Content/Early/2021/02/09/Bjsports-2020-103274).

Coming Off Antipsychotics May Take Years: New Review Outlines How Antipsychotics Should Be Reduced to Minimize Withdrawal Effects and Risk of Relapse

Withdrawing from antipsychotics may require months or even years, and patients need to gradually reduce to very low doses, according to a new analysis led by University College London (UCL) and King’s College London academics. The review, published online on March 23, 2021 in Schizophrenia Bulletin, is believed to be the first-ever scientific paper outlining how exactly antipsychotic medication should be reduced in order to minimize both withdrawal effects and the risk of relapse. The open-access article is titled “A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse” (https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.10...). Withdrawal symptoms can be severe, and may include psychotic symptoms similar to the underlying condition, which can result in patients being advised to remain on the medication indefinitely, even though the new symptoms might have been avoidable with a carefully-managed withdrawal. The review’s lead author Dr. Mark Horowitz (UCL Psychiatry) said: “Surprisingly, there are no published guidelines on how to come off antipsychotics. From my own experience I know how hard it can be to wean off psychiatric medications--so we set out to write guidance on how to withdraw safely from antipsychotics. Stopping medications is an important part of the job of a psychiatrist, yet it has received relatively little attention.” Antipsychotics are one of the fastest growing classes of drugs being prescribed in England (https://nhsbsa-opendata.s3-eu-west-2.amazonaws.com/mh-annual-narrative-f...), growing from 660,000 people (9.4 million prescriptions) in 2015/2016 to 750,000 people in 2019/2020.

Coming Off Antipsychotics May Take Years: New Review Outlines How Antipsychotics Should Be Reduced to Minimize Withdrawal Effects and Risk of Relapse

Withdrawing from antipsychotics may require months or even years, and patients need to gradually reduce to very low doses, according to a new analysis led by University College London (UCL) and King’s College London academics. The review, published online on March 23, 2021 in Schizophrenia Bulletin, is believed to be the first-ever scientific paper outlining how exactly antipsychotic medication should be reduced in order to minimize both withdrawal effects and the risk of relapse. The article is titled “A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse” (https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.10...). Withdrawal symptoms can be severe, and may include psychotic symptoms similar to the underlying condition, which can result in patients being advised to remain on the medication indefinitely, even though the new symptoms might have been avoidable with a carefully-managed withdrawal. The review’s lead author Dr. Mark Horowitz (UCL Psychiatry) said: “Surprisingly, there are no published guidelines on how to come off antipsychotics. From my own experience I know how hard it can be to wean off psychiatric medications--so we set out to write guidance on how to withdraw safely from antipsychotics. Stopping medications is an important part of the job of a psychiatrist, yet it has received relatively little attention.” Antipsychotics are one of the fastest growing classes of drugs being prescribed in England (https://nhsbsa-opendata.s3-eu-west-2.amazonaws.com/mh-annual-narrative-f...), growing from 660,000 people (9.4 million prescriptions) in 2015/2016 to 750,000 people in 2019/2020.

Researchers Identify DNA Elements That Affect MECP2 Expression; New Results from Huda Zoghbi Lab Have Bearing on Rett Syndrome and MECP2 Duplication Syndrome

Researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital (NRI) have identified and characterized two regions of DNA required for the proper expression of Mecp2/MECP2 in mice and humans. These findings, published online on March 18, 2021 in Genes & Development, are helping to shed light on the function of these DNA regions and how they could be potential targets for diagnostic and therapeutic interventions for intellectual disabilities such as Rett syndrome and MECP2 duplication syndrome. Both of these intellectual disabilities are examples of the importance of precise MECP2 protein levels for proper brain function. A decrease in this protein leads to Rett Syndrome, while an increase in this protein causes MECP2 Duplication Syndrome. Both are severe neurological disorders characterized by learning disabilities, features of autism and motor difficulties. Huda Zoghbi (photo), MD, Professor at Baylor, Director of the NRI, and a Howard Hughes Medical Institute Investigator, underscored the importance of understanding how the levels of RNA encoding this protein are regulated. Researchers in her lab identified two DNA regions that, when mutated, lead to either a decrease or an increase in MECP2 RNA and protein levels, resulting in partial behavioral deficits seen in Rett Syndrome and MECP2 Duplication Syndrome, respectively. The new article is titled “Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions” (http://genesdev.cshlp.org/content/early/2021/03/17/gad.345397.120.abstract).

March 2021 Virtual Issue of Genome Biology and Evolution Features Collection of Recent High-Impact Articles Focusing on Viral Evolution

Despite the fact that viruses are among the simplest biological entities--consisting only of DNA or RNA encapsulated in a protein shell--they can have devastating consequences, with viruses such as influenza, human immunodeficiency virus (HIV), and Ebola having dramatically affected the course of human history. Because viruses generally lack the cellular machinery necessary to reproduce, they propagate by hijacking host cells, often to the host's detriment. While their status as a "living" organism may be in question, there is no doubt that viruses are shaped by evolutionary forces that influence their genomes, as well as their replication, host range, virulence, and other features. With the emergence of SARS-CoV-2, a virus that has intimately affected virtually all aspects of human life for the past year, the study of viral evolution may seem more profound and relevant than ever before. Genome Biology and Evolution's latest virtual issue (Volume 13, Issue 13, March 2021) (https://academic.oup.com/gbe/pages/viral-evolution) is a collection of thought-provoking papers in the field of viral evolution from the past two years, providing new insight into the evolutionary mechanisms that influence viruses, their genomes, and their hosts, as well as showcasing their use in the study of evolution.The rapid and variable mutation rates observed among viruses create challenges for studies of viral genome evolution. A study by González et al. (2019) sought to investigate the balance between beneficial and deleterious mutations by creating a mutant library of the tobacco etch potyvirus containing every possible single-nucleotide substitution of the 6K2 gene and then infecting tobacco plants with the library.

Anti-Tuberculosis Drug Rifampicin Can Be Safely Dosed Even Higher, New Study Shows; May Lead to Shorter Treatment Time and Reduced Antibiotic Resistance

A considerably higher dose of the anti-tuberculosis drug rifampicin is safe and can also lead to a shorter treatment for tuberculosis (TB) and less resistance. This is what researchers from Radboud University Medical Center in Nijmegen, the Netherlands, write in a February 4, 2021 publication European Respiratory Journal. The article is titled“Increased bactericidal activity but dose-limiting intolerability at 50 mg·kg−1 rifampicin” https://erj.ersjournals.com/content/early/2020/12/10/13993003.00955-2020. With this study, the researchers complete a year-long search for the right dosing of an old drug against tuberculosis that appears to be the key drug. Tuberculosis is a deadly, pertinacious bacterial infectious disease that affects nine million people worldwide each year, mainly in countries in low- and middle-income countries. For over a million of these people, the disease has a fatal outcome. Although drug manufacturers have been developing tuberculosis drugs for forty years, supplemented by research on the BCG vaccine, which appears to strengthen the immune system against respiratory infections, the number of people affected by tuberculosis remains fairly stable. This is partly due to patients being treated for too short a time or with inadequate medication. Due to TB treatment being inadequately dosed or for too short a time, many drugs do not touch, or barely reach, all TB bacilli in the body. This can lead to resistance: the pathogens that survive the treatment multiply, after which the disease returns in a new form that is even more difficult to treat. Effective treatments for drug-resistant tuberculosis are therefore tough and last a long time, sometimes up to eighteen months.

Further Collaborations Underway to Demonstrate Potential of ReNeuron’s Proprietary Exosome Platform; Emerging Data Shows Platform’s Application to a Range of Novel Therapeutics Targeting Brain & Other Tissues

On March 19, 2021, ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, provided an update on the positive progress being made by third-party commercial collaborators with its exosome technology platform and the signing of new collaboration agreements with a major pharmaceutical company and leading academic institutions in the UK and mainland Europe. ReNeuron’s exosome technology is being explored by pharmaceutical, biotechnology, and academic collaboration partners as a novel delivery vehicle for third-party therapeutic agents targeting the brain and other parts of the body. The company is developing its lead exosome candidate from its proprietary CTX neural stem cell line. These exosomes can be manufactured according to GMP standards through a fully qualified, xeno-free, scalable process and loaded with a diverse range of therapeutic agents, including siRNA/mRNA/miRNA, CRISPR/Cas9, antibodies, peptides, and small molecules. The exosomes have been shown to exhibit a natural ability to cross the blood-brain barrier. ReNeuron is also developing further exosome candidates derived from a panel of additional producer cell lines owned by the company. These exosome candidates have the potential to broaden the repertoire of tissues and indications that the company is able to target. ReNeuron is exploring multiple methods of loading exosomes, both internally and on the exosome surface, and is collaborating with major pharmaceutical/biotechnology companies on these projects. Since the last update in the company’s interim results statement on 24 November 24, 2020, the company has signed a further commercial collaboration agreement with a major pharmaceutical company, focusing on the potential of the ReNeuron’s exosomes to deliver DNA cargoes for expression of therapeutic genes in the brain.

Birds Breathe Differently & More Efficiently Than Humans; One-Directional Air Flow Through Looped Lung Airways Allows Birds “To Perform the Most Difficult & Energetically Costly Activity of Any Animal: They Can Fly”--Findings May Aid Flow Engineering

Birds breathe with greater efficiency than humans due to the structure of their lungs--looped airways that facilitate air flows that go in one direction--a team of researchers has found through a series of lab experiments and simulations. The findings were published online on March 19, 2021 in Physical Review Letters. The article is titled “Flow Rectification in Loopy Network Models of Bird Lungs” (https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.126.114501). The study, conducted by researchers at New York University (NYU) and the New Jersey Institute of Technology(NJIT), also points to smarter ways to pump fluids and control flows in applications such as respiratory ventilators. "Unlike the air flows deep in the branches of our lungs, which oscillate back and forth as we breathe in and out, the flow moves in a single direction in bird lungs, even as they inhale and exhale," explains Leif Ristroph, PhD, an Associate Professor at NYU's Courant Institute of Mathematical Sciences and the senior author of the paper. "This allows them to perform the most difficult and energetically costly activity of any animal: they can fly, and they can do so across whole oceans and entire continents and at elevations as high as Mount Everest, where the oxygen is extremely thin. The key is that bird lungs are made of looped airways--not just the branches and tree-like structure of our lungs--and we found that this leads to one-way or directed flows around the loops," adds Dr. Ristroph. "This wind ventilates even the deep recesses of the lungs and brings in fresh air." The one-way flow of air in birds' breathing systems was discovered a century ago. But what had remained a mystery was an explanation of the aerodynamics behind this efficient breathing system.

Medical Cannabis Can Reduce Essential Tremor: It Turns On Overlooked Cells (Astrocytes) in Central Nervous System in Mouse Model

Medical cannabis is a subject of much debate. There is still a lot we do not know about cannabis, but researchers from the University of Copenhagen’s Department of Neuroscience at the Faculty of Health and Medical Sciences have made a new discovery that may prove vital to future research into, and treatment with, medical cannabis. The discovery was reported online on March 18, 2021 in Nature Neuroscience. The article is titled “Spinal Astroglial Cannabinoid Receptors Control Pathological Tremor” (https://www.nature.com/articles/s41593-021-00818-4). Cannabinoids are compounds found in cannabis and in the central nervous system. Using a mouse model, the researchers have demonstrated that a specific synthetic cannabinoid (cannabinoid WIN55,212-2) reduces essential tremor by activating the support cells of the spinal cord and brain, known as astrocytes. Previous research into medical cannabis has focused on the nerve cells themselves, the so-called neurons. “We have focused on the disease essential tremor. It causes involuntary shaking, which can be extremely inhibitory and seriously reduce the patient's quality of life. However, the cannabinoid might also have a beneficial effect on sclerosis and spinal cord injuries, for example, which also cause involuntary shaking,” says Associate Professor Jean-François Perrier, PhD, from the Department of Neuroscience, who has headed the research project.

Therapy for Most Common Cause of Cystic Fibrosis Found Safe and Effective in 6-11-Year-Olds

An international, open-label Phase 3 study, co-led by Susanna McColley, MD, from Ann & Robert H. Lurie Children's Hospital of Chicago, found that a regimen of three drugs (elexacaftor/tezacaftor/ivacaftor) that targets the genetic cause of cystic fibrosis was safe and effective in 6-11-year-olds with at least one copy of the F508del mutation in the CFTR gene, which is estimated to represent almost 90 percent of the cystic fibrosis population in the United States. For children in this age group who have only one copy of F508del mutation--or about 40 percent of patients with cystic fibrosis in the United States--this would be the first treatment that addresses the underlying genetic defect in cystic fibrosis. This three-drug cystic fibrosis treatment was approved by the FDA in October 2019 for people 12 years and older with at least one copy of the F508del mutation. Based on the positive results of this study, the FDA has accepted the application to expand treatment indication to younger children, with a decision expected by June 2021. "The most exciting aspect of our findings is that this population of children had normal lung function at the start of the study and still had a significant improvement," said Susanna McColley (photo), MD, Co-Global Principal Investigator on the study and senior author, who is the Scientific Director for Interdisciplinary Research Partnerships at Stanley Manne Children's Research Institute at Lurie Children's and Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Coupled with what we saw in studies and in practice with the older population, starting treatment earlier may avert serious long-term complications and really change the trajectory of health for children with cystic fibrosis."

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