Dr. Hurwitz[/caption]
Lauren Hurwitz, PhD
Postdoctoral Fellow
Division of Cancer Epidemiology & Genetics
National Cancer Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prior studies have demonstrated that frequent (i.e., daily or near daily) use of aspirin is associated with a lower risk of developing ovarian cancer. We sought to determine if this risk reduction is also observed for individuals with greater genetic susceptibility to ovarian cancer, who may benefit more from preventive interventions.
Our study found that individuals who took aspirin frequently had a lower risk of ovarian cancer, regardless of whether they had higher or lower genetic susceptibility to ovarian cancer.
Response: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery.
IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases.
Larissa K. Samuelson, PhD
Professor
Developmental Dynamics Lab
School of Psychology; UK 14th for Research Quality
Psychology, Psychiatry, and Neuroscience
University of East Anglia, United Kingdom
MedicalResearch.com: What is the background for this study?
Response: Words direct the attention of infants, children and adults to mentioned objects in the environment. When someone says “Can you find the candy,” you look to the candy sitting on the counter. This fact is the basis of many tests of infant cognition in laboratories. To find out if a child knows the word “bike” we put a picture of a bike and a truck on a TV screen, say the word “bike” and see if they look at the correct object.
There is also evidence that words can direct attention even if you don’t know what they mean yet. For example, in studies of learning in the lab novel made up words like “modi” can direct children’s attention to specific features of objects. One particular example of this is the “shape bias”. If a two-year-old is shown a novel object and told a novel name, for example “This is my blicket,” and then asked, “Can you get your blicket” and shown one object that matches the named one in shape and another that is made from the same material, they will attend to the one that matches in shape. Researchers think the naming event “This is my…” cues children to look at things that are the same shape because they already know many names for things in sets that are similar in shape; cups are all cup-shaped, keys are all key-shaped, spoons are all spoon-shaped, etc.
Prior research suggests there may be differences in the way children who struggle with language decide what a new word means. For example, children with Developmental Language Disorder do not pay attention to the same things when learning new words as children with typical language development. These children do not look to an object that matches a named exemplar in shape when asked to “get your blicket”. But you can’t diagnose children with DLD until they are 3 or 4. We want to see if we can identify these children earlier, so they can get early support.
Dr. Taylor[/caption]
Matthew H. Taylor, MD
Earle A. Chiles Research Institute
Providence Cancer Institute
Portland, OR
MedicalResearch.com: What is the background for this study? What is the importance of ILT4 or LILRB2 in tumor growth?
MedicalResearch.com Interview with: [caption id="attachment_60303" align="alignleft" width="150"] Dr. Zafar Janjua[/caption] Naveed Zafar Janjua, MBBS, MSc, DrPH Executive Director, Data and Analytic Services BC Centre for Disease Control Provincial Health Services Authority Clinical Professor, School of Population and Public Health University of British Columbia Vancouver, BC MedicalResearch.com: What is the background for this study? Response: Ongoing research suggests that COVID-19 may...
Dr. Esteban McCabe[/caption]
Sean Esteban McCabe, PhD
Director, Center for the Study of Drugs, Alcohol, Smoking and Health
Department of Health Behavior and Biological Sciences
University of Michigan School of Nursing
Ann Arbor, MI
MedicalResearch.com: What is the background for this study?
Response: Prescription stimulant therapy for ADHD helps millions of people, including in my own family, and students, friends and colleagues. It's critical to balance the need for access to these medications while reducing the risk for misuse. This is more important than ever now because there have been recent increases in the prescribing of stimulant therapy for ADHD. There is a need to understand the prevalence of stimulant therapy for ADHD and prescription stimulant misuse in U.S. middle and high schools.
Edward Liu[/caption]
Edward Liu, BA
Second year medical student
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, PA
Medicalresearch.com: What is the background for this study?
Response: The United States’ opioid epidemic continues to rise because of increasing opioid use and availability, contributing to prescription opioid misuse, mortality, and rising cost.1 The worsening health and economic impact of opioid use disorder in the US warrants further attention on the adverse effects and distribution pattern of commonly prescribed opioids like oxycodone (OxyContin), fentanyl (Duragesic), and morphine (MS-Contin). Using the Automated Reports and Consolidated Ordering System (ARCOS) database,2 a comprehensive data collection system of pharmacies and hospitals distribution of Schedule II and III controlled substances in the US with the FDA Adverse Event Reporting System (FAERS)3 has never been done before. This approach may provide a more complete picture of the risks of prescription opioids which can include drowsiness, nausea, and potentially fatal respiratory depression.
Dr. Sundström[/caption]
Johan Sundström, MD, PhD
Professor of Epidemiology at Uppsala University
Professorial Fellow at The George Institute for Global Health
Cardiologist at Uppsala University Hospital
MedicalResearch.com: What is the background for this study?
Response: High blood pressure, hypertension, is a growing global health challenge. Over the last 30 years, the number of people with hypertension has doubled, and it is estimated that around a third of adults aged 30-79 have the condition - a total of 1.28 billion people worldwide. Untreated hypertension can lead to kidney disease, heart disease, and stroke, accounting for 11.3 million deaths in 2021 alone. A small minority get their blood pressure under control with drug therapy, and some studies indicate that as little as half are taking their blood pressure medications as intended. Is this because the drugs' effectiveness and side effects differ between different individuals? If so, there would be a substantial risk that patients will not get their optimal medication on the first try, with poor blood pressure lowering and unnecessary side effects as a result.
In a new clinical trial in Sweden, it was studied whether there is an optimal blood pressure medication for each person, and thus a potential for personalized blood pressure treatment. In the study, 280 people with high blood pressure tried out four different blood pressure drugs on several different occasions over a total of one year.
Prof. Hamdy[/caption]
Freddie C. Hamdy FRCS, FMedSci
Nuffield Professor of Surgery, University of Oxford
[caption id="attachment_60283" align="alignleft" width="100"]
Prof. Donovan[/caption]
Jenny L. Donovan PhD, FMedSci
Professor of Social Medicine, University of Bristol
MedicalResearch.com: What is the background for this study?
Response: Prostate cancer is a common malignancy in men. Prostate cancer diagnosis is made largely through opportunistic screening with a PSA (Prostate Specific Antigen) blood test, followed by prostate biopsies. The ProtecT study, funded by the National Institute for Health and Care Research in the UK, is the largest randomised trial of treatment in screen-detected localised prostate cancer. The study began by testing 82,429 men between the ages of 50 and 69 years, across nine UK centres with a PSA blood test, followed by biopsies of the prostate if the PSA level was elevated. 2,664 men with clinically localised prostate cancer were found. From these, 1,643 (62%) agreed to be randomised to Surgery (radical prostatectomy to remove the prostate gland), Radiotherapy (external beam with a period of hormone treatment beforehand), or Active Monitoring (where men received regular checks and further investigations, with change to radical treatment as necessary). The men were carefully followed up for an average of 15 years. In parallel, the side-effects of treatments and quality of life of these men was investigated using patient-reported outcomes included in an annual study questionnaire completed for at least 12 years.
Dr. Buckley[/caption]
Rachel Buckley, PhD
Assistant Professor
Department of Neurology
Massachusetts General Hospital/Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: While a fair amount of studies have focused on the effects of menopause and hormone therapy on risk of dementia, far fewer studies have tested their association with the biology of Alzheimer’s disease, namely amyloid and tau. This is critical to know given that it still remains unclear what might be the driving mechanism of the menopause transition on risk for dementia. This is what our study set out to investigate.
This study is one of the first to report a link between women’s age at menopause and tau in the brain, which we measured with positron emission tomography neuroimaging. We found that in multiple areas of the brain that tend to be most likely to show higher tau in women than men, women with earlier age at menopause and elevated levels of amyloid showed higher levels of tau than those who reported an average age at menopause (~50 years in the United States). Women who reported premature menopause (<40 years at menopause onset) exhibited a much higher risk of tau in the brain. This supports the notion that longer exposure to estrogen throughout life might be protective against Alzheimer’s disease.
The hectic nature of modern living, especially if you’re very much immersed in the changing world of business, can result in the accidental neglect of both your physical health and emotional well-being. Naturally, your health is the topmost priority and as such, making the switch to ensuring you’re taking care of...
Dr. Tauscher-Wisniewski,[/caption]
Sitra Tauscher-Wisniewski, MD
Vice President Clinical Development & Analytics
Novartis Gene Therapies
MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of Spinal muscular atrophy (SMA)?
Response: At the 2023 Muscular Dystrophy Association Conference, we presented new data from two of our Long-Term Follow-Up (LTFU) studies, LT001 and LT002, which show the continued efficacy and durability of Zolgensma across a range of patient populations, with an overall benefit-risk profile that remains favorable. LT001 is a 15-year ongoing observational LTFU study following the Phase 1 START patients, who were the very first patients to receive our gene replacement therapy. LT-002 is a voluntary Phase 4 15-year ongoing follow-up safety and efficacy study of Zolgensma IV and investigational intrathecal (IT) OAV101 in patients previously treated in the Phase 3 IV studies (STR1VE-US, STR1VE-EU, STR1VE-AP, SPR1NT) and the Phase 1 IT study (STRONG).
Spinal muscular atrophy (SMA) is a rare, devastating genetic disease that leads to progressive muscle weakness, paralysis, and when left untreated in one of its most severe forms (SMA Type 1), permanent ventilation or death in 90% of cases by age 2. It is caused by a lack of a functional survival motor neuron 1 (SMN1) gene, and in the most severe forms results in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement.
Dr. Hatoum[/caption]
Alexander S. Hatoum, PhD
Research Assistant Professor
Institute for Behavioral Genetics
Washington University in St. Louis
MedicalResearch.com: What is the background for this study?
Response: It is well known that someone with one substance use disorder will have another sometime in their lifetime or concurrently. Further, individuals that do manifest two or more substance use disorders in their lifetime have the most morbid conditions. However, research often ignores the comorbidity and focuses on diagnosis of one substance use disorder at a time (i.e. opioid use disorder or alcohol use disorder). We set out to identify the biology behind the cross-substance liability.
Dr. Potter[/caption]
MedicalResearch.com Interview with:
Kelly Potter, PhD, RN, CNE
T32 Postdoctoral Scholar
CRISMA Center, Department of Critical Care Medicine
University of Pittsburgh
MedicalResearch.com: What is the background for this study?
Response: While it is well-recognized that survivors of critical illness often experience persistent problems with mental, cognitive, and physical health, very little is known about how these problems (collectively known as post-intensive care syndrome (PICS)) affect resumption of meaningful activities, such as driving.
Dr. Lillegraven[/caption]
Siri Lillegraven MD MPH PhD
Dr. Le Calvez-Kelm[/caption]
Florence Le Calvez-Kelm, Ph.D.
Genomic Epidemiology Branch
International Agency for Research on Cancer
Lyon, France and
[caption id="attachment_60206" align="alignleft" width="150"]
Dr. Levin[/caption]
Trevor Levin Ph.D.
Founder and CEO of Convergent Genomics that produces the Uroamp assay
San Francisco, CA
MedicalResearch.com: What is the background for this study?
Response: Bladder cancer is one of the most expensive and challenging to diagnose and treat. Therefore, identifying cost-effective urine bladder cancer biomarkers to complement or replace the gold-standard invasive and costly cystoscopy for the early detection and monitoring of this highly recurrent disease is crucial. At the international Agency for research on Cancer (IARC-WHO), we have developed a simple urine-based assay TERT promoter mutations, the most common mutations in bladder cancer, and showed that the urine biomarker could detect bladder cancer patients at diagnosis but many years prior to clinical diagnosis. However, in this study, we wanted to see whether a more comprehensive genomic profiling of urine samples collected years prior to clinical diagnosis of bladder cancer could identify even more patients before they develop any symptoms.
The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by the Oregon Health Science University spin out company, Convergent Genomics. Drawing on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test down to focus on mutations within just ten genes.
Working with colleagues from the Tehran University of Medical Sciences in Iran, they trialled the potential new test using samples from the Golestan Cohort Study, which has tracked the health of more than 50,000 participants over ten years, all of whom provided urine samples at recruitment. Forty people within the study developed bladder cancer during that decade, and the team were able to test urine samples from twenty-nine of them, along with samples from 98 other similar participants as controls.
This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis or treatment. Contact a qualified medical professional before engaging in any physical activity, or making any changes to your diet, medication or lifestyle, Alcohol abuse is a serious problem that can have devastating...
Dr. Jonathan Silverberg[/caption]
Jonathan Silverberg, MD, PHD, MPH
Professor
Director of Clinical Research
Director of Patch Testing
George Washington University School of Medicine and Health Sciences
Washington, DC
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Lebrikizumab was previously shown to be safe and effective as a treatment for moderate-severe atopic dermatitis in a phase 2 study. These Phase 3 randomized placebo-controlled trials are the largest studies to date of lebrikizumab in AD. They showed that lebrikizumab was safe and highly effective for the treatment of moderate-severe atopic dermatitis. These studies will hopefully support the approval of lebrikizumab in the United States later this year.
Dr. D'Orsogna[/caption]
Maria-Rita D'Orsogna Ph.D.
Professor, Mathematics
California State University, Northridge
Adjunct Associate Professor
Department of Computational Medicine at UCLA
MedicalResearch.com: What is the background for this study?
Response: Drug overdose deaths have been increasing in the USA for the past two decades. A ‘third wave’ of overdose fatalities started in 2013, with a shift from prescription opioids towards synthetic ones, in particular illicit fentanyl.
To examine trends in drug overdose deaths by gender, race and geography in the United States during the period 2013-2020, we used an epidemiological database provided by the Centers for Disease Control and Prevention, extracting rates by race and gender in all 50 states plus the District of Columbia. We considered the impact of four main drug categories psychostimulants with addiction potential such as methamphetamines; heroin; prescription opioids and synthetic opioids such as fentanyl and its derivatives.
Dr. Koh[/caption]
Andrew Y. Koh, M.D.
Associate Professor, Pediatrics and Microbiology
University of Texas Southwestern Medical Center
Director of Pediatric Cellular and ImmunoTherapeutics Program
University of Texas Southwestern Medical Center and Children's Health
MedicalResearch.com: What is the background for this study?
Response: We asked the basic question how does a bacteria in your gut help your immune system fight a cancer outside the gut (extraintestinal tumor). Based on work that our group and others have published in the infectious diseases, microbiology, and inflammation fields, we knew that certain conditions (e.g. inflammation, infection) promote gut microbiota to move from the gut to the mesenteric lymph nodes. So we hypothesized that immune checkpoint therapy (which essentially induces inflammation to promote tumor killing) might induce gut microbiota translocation to the mesenteric lymph nodes and that this might be the first step by which gut bacteria can engage with host immune cells.
Prof. Rahimi[/caption]
Kazem Rahimi FRCP, DM, MSc, FESC
Professor of Cardiovascular Medicine and Population Health
University of Oxford
Consultant cardiologist
Oxford University Hospitals NHS Trust
MedicalResearch.com: What is the background for this study?
Response: The prevalence of hypertension has been rising worldwide. To mitigate the burden, identifying the modifiable environmental risk factors of hypertension and developing preventive interventions constitute important public health priorities. Despite the biological plausibility of the link between road traffic noise and the risk of hypertension, the quality of relevant evidence has been low, and the role of air pollution has been uncertain.
Dr. Turro[/caption]
Ernest Turro, PhD
Associate Professor Genetics and Genomics Sciences
The Turro group runs a research program on statistical genomics,
with a dual focus on rare diseases and blood-related traits at the Icahn School of Medicine
Mount Sinai Health System
MedicalResearch.com: What is the background for this study? Would you describe the Rareservoir database?
Response: The main motivation for our work is that only half of the approximately 10,000 catalogued rare diseases have a resolved genetic cause (or aetiology). Patients with these diseases are unable to obtain a genetic diagnosis which could otherwise inform prognosis, treatment for themselves and affected relatives.
One route towards resolving the remaining aetiologies is to enroll large numbers of rare disease patients into research studies so that statistical analyses can be performed comparing the genetic with the clinical characteristics of the study participants. One major endeavour, the 100,000 Genomes Project (100KGP), sequenced the genomes and collected clinical phenotype data for 34,523 UK patients and 43,016 unaffected relatives across 29,741 families.
The scale of this study is unprecedented, partly thanks to the ever-decreasing cost of DNA sequencing (25 years ago, it cost $1bn to sequence a whole genome, while now it costs only a few hundred dollars). Working with such large datasets is notoriously cumbersome. To overcome this, we developed a computational approach (the Rareservoir) that distills the most important information into a relatively small database, allowing us to apply our statistical methods nimbly.
We noted that the "genetic variants" that cause rare diseases are typically kept rare in the human population by natural selection because affected individuals tend to have few children, if any. This meant that we could discard the genetic information corresponding to variants that are common in the human population without throwing away the key disease-causing variants. By focussing on these "rare variants", we were able to perform our analyses using a small database (a `Rareservoir’), only 5.5GB in size, hastening our progress significantly.
Dr. Keyes[/caption]
Dr Helen Keyes PhD, AFBPsS, SFHEA
Head of School Psychology & Sport Science
Anglia Ruskin University
Cambridge
MedicalResearch.com: What is the background for this study? What types of sporting events?
Response: The data were collected as part of a large government study looking at a range of measures on health and activities across the UK population. Our study honed in on aspects of wellbeing – life satisfaction, loneliness, happiness, anxiety, a sense that life is worthwhile – as well as whether participants had attended a live sporting event in the last year. The data collected did not differentiate between different types of sport – the positive effects that we report for wellbeing are population-wide across a whole range of sports, from attending a local football match all the way up to elite sporting events.
Dr. Mosley[/caption]
Jonathan Mosley, MD, PhD
Associate Professor
Division of Clinical Pharmacology
Departments of Internal Medicine and Biomedical Informatics
Vanderbilt University Medical Center
MedicalResearch.com: What is the background for this study?
Response: Prostate cancer is an important source of morbidity and mortality among men. Earlier detection of disease is essential to reduce these adverse outcomes. Prostate cancer is heritable, and many single nucleotide polymorphisms (SNPs) associated with disease risk have been identified. Thus, there is considerable interest in using tools such as polygenic risk scores, which measure the burden of genetic risk variants an individual carries, to identify men at elevated risk of disease.
Dr. Moses, D.O., J.D.[/caption]
Richard E. Moses, D.O., J.D.
Gastroenterologist, Associate Vice President, Mirikizumab Indication Lead
Global Medical Affairs, Eli Lilly and Company
MedicalResearch.com: What is the background for this study? Would you briefly describe how mirikizumab works in UC?
Response: First, this study specifically evaluated mirikizumab, a humanized IgG4 monoclonal antibody that selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of UC.
Regulatory decisions for mirikizumab as a potential treatment for adults with moderately to severely active UC in the U.S., E.U and other countries around the world are expected in 2023. If approved, mirikizumab has the potential to be the only UC treatment that selectively targets the p19 subunit of IL-23.
Gastroenterologists today benefit from having data from a range of endpoints, which can help them determine appropriate treatment options depending on their specific patients' needs and symptoms. In addition to clinical response and clinical remission – which are often used to determine the effectiveness of a treatment – we can also use combined endpoints like histologic-endoscopic mucosal improvement (which gauges remission and treatment effectiveness), histologic-endoscopic mucosal remission (the reduction of underlying inflammation visible endoscopically) and inflammatory biomarkers faecal calprotectin (fCal) and C-reactive protein (CRP) to inform our treatment strategies.
This analysis focused on patients treated with mirikizumab from the induction study who received intravenous mirikizumab every 4 weeks until Week 12 (LUCENT-1), and patients who responded to mirikizumab during 12-week induction period who were re-randomized for the maintenance period, receiving subcutaneous mirikizumab every four weeks up to Week 40 (LUCENT-2) for 52 weeks of continuous treatment.
This study explored the relationship between achieving histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR) and improvement of biomarkers fCal and CRP levels at Weeks 12 and 52.