Author Interviews / 28.08.2020
Icahn Mt.Sinai Study Identifies Two Switches That Regulate RNA Transcription in Cancer Cells
MedicalResearch.com Interview with:
[caption id="attachment_55231" align="alignleft" width="130"] Dr. Fisher[/caption]
Robert Fisher, MD, PhD
Professor of Oncological Sciences
Icahn School of Medicine at Mount Sinai
Member of The Tisch Cancer Institute
MedicalResearch.com: What is the background for this study?
Response: Gene transcription by RNA polymerase II underlies cellular identity, and cell fate decisions such as proliferation or death, and is regulated by enzymes that add phosphates (kinases) or remove them (phosphatases) from components of the transcription machinery. Here we define two kinase-phosphatase switches that regulate different steps of the transcription cycle in human cancer cells.
We raised antibodies specific for different phosphorylated states of a key elongation factor, Spt5, and used genomic analyses such as chromatin immunoprecipitation and sequencing (ChIP-seq) to monitor when these phosphorylations were added and removed, and by which kinases and phosphatases, respectively, as RNA polymerase II traversed genes in human cancer cells.
Dr. Fisher[/caption]
Robert Fisher, MD, PhD
Professor of Oncological Sciences
Icahn School of Medicine at Mount Sinai
Member of The Tisch Cancer Institute
MedicalResearch.com: What is the background for this study?
Response: Gene transcription by RNA polymerase II underlies cellular identity, and cell fate decisions such as proliferation or death, and is regulated by enzymes that add phosphates (kinases) or remove them (phosphatases) from components of the transcription machinery. Here we define two kinase-phosphatase switches that regulate different steps of the transcription cycle in human cancer cells.
We raised antibodies specific for different phosphorylated states of a key elongation factor, Spt5, and used genomic analyses such as chromatin immunoprecipitation and sequencing (ChIP-seq) to monitor when these phosphorylations were added and removed, and by which kinases and phosphatases, respectively, as RNA polymerase II traversed genes in human cancer cells.
Dr. Wick[/caption]
Cameron C. Wick, MD
Assistant Professor, Otology/Neurotology
Washington University School of Medicine
St. Louis, MO
MedicalResearch.com: What do you see as the primary message of your findings for the general public?
Response: Older adults not satisfied with their hearing aids achieved clinically meaningful improvement in both hearing and quality of life with a cochlear implant compared to an optimized bilateral hearing aid condition.
MedicalResearch.com: Do you see your findings as changing the way older adults with hearing loss are managed?
Response: Yes and partially because this study is unique in its design and the outcomes that were measured. Specifically the study is a prospective, multicenter clinical trial conducted at 13 locations across the United States. All patients were setup with a 30-day optimized hearing aid experience before cochlear implantation (context: sometimes hearing aids are not appropriately optimized so baseline testing may not reflect the "best" that hearing aids can do). This study assesses both hearing data as well as quality of life data before and 6-months after cochlear implantation. After implantation patients were tested in both the unilateral (cochlear implant alone) and bimodal (cochlear implant plus hearing aid in the opposite ear) conditions. My paper is a subanalysis of adults 65 years and older (range 65 - 91 years) enrolled in the clinical trial. The principal investigator of the clinical trial is Dr. Craig Buchman. Dr. Buchman and myself are at Washington University in St. Louis which was the lead center for the clinical trial.
The findings of the study are meaningful because they demonstrate clear superiority of cochlear implants over hearing aids in many key areas, such as understanding speech, hearing in background noise, and ability to communicate. Hearing loss, which becomes more prevalent as we age, can negatively impact communication leading to social isolation, depression, frustration, and possibly cognitive decline. This study highlights that if patients are not satisfied with their hearing aid performance then they should be referred to a center that can evaluate for cochlear implantation. Cochlear implant indications have evolved considerably since they were first FDA approved in 1984. This study emphasizes that patients do not have to be profoundly deaf to experience significant hearing and social benefits from cochlear implants. Also, it demonstrates that cochlear implant surgery is well tolerated even as adults age and acquire other health ailments. 
Salim S. Virani, MD, PhD, FACC, FAHA, FASPC
Professor, Section of Cardiovascular Research
Director, Cardiology Fellowship Training Program
Baylor College of Medicine
Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center
Co-Director, VA Advanced Fellowship in Health Services Research & Development at the Michael E. DeBakey VA Medical Center, Houston, TX
Investigator, Health Policy, Quality and Informatics Program
Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation
Houston, TX @virani_md
MedicalResearch.com: What is the background for this study? What are the main findings? What do you think accounts for the gender differences?
Response: We know that women with ischemic heart disease (IHD) have lower prescription rates for statin and high-intensity statin therapy. In this study, we assessed whether the same trends hold true for women with other forms of atherosclerotic cardiovascular disease (ASCVD) i.e. women with peripheral artery disease (PAD) or ischemic cerebrovascular disease (ICVD). Maximally tolerated statin therapy is a Class-I indication in patients with clinical ASCVD which includes PAD and ICVD.
We also assessed statin adherence among men and women with PAD and ICVD.
Lastly, we performed exploratory analyses to assess whether statin therapy, statin intensity, and statin adherence in women with PAD and ICVD were associated with cardiovascular outcomes and/or mortality. 
Ruth Fernandez-Ruiz, MD
Post-Doctoral Fellow
Department of Rheumatology
NYU Langone Heath
MedicalResearch.com: What is the background for this study?
Response: Patients with systemic lupus erythematosus (SLE) represent a unique population in considering risk for COVID-19 with biologic, genetic, demographic, clinical and treatment issues at play. By the nature of their chronic inflammatory autoimmune condition, the presence of comorbidities, and regular use of immunosuppressants, these individuals would traditionally be considered at high risk of contracting SARS-CoV-2 and possibly having worse outcomes from the viral infection.
However, it might be speculated that inherently elevated type I Interferon, characteristic of the majority of patients with SLE, confers a protective effect as a first line anti-viral defense. Additionally, hydroxychloroquine, which was suggested as a potential therapeutic agent for COVID-19 early on, is used in most patients with SLE. Accordingly, we initiated this study to provide critical data needed to address the frequency and severity of COVID-19 in patients with SLE.
Dr. Yonker[/caption]
Lael Yonker, MD
Pediatric Pulmonology
Director, MGH Cystic Fibrosis Center
Principal Investigator, Pediatric COVID biorepository
Mucosal Immunology and Biology Research Center
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Children were initially felt to be spared from the COVID-19 pandemic. Here, we show that children can become sick from SARS-CoV-2 infection, and even if the initial illness is mild, some go on to develop a severe inflammatory illness after the initial illness. We also show that children can carry very high levels of virus early in the course of infection, suggesting they may play a larger role in spreading the virus than previously thought.
Dr. Trudo[/caption]
Frank Trudo, MD MBA
Vice President, US Medical Affairs
Respiratory & Immunology
AstraZeneca
MedicalResearch.com: What is the background for this study?
Response: ETHOS was a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of PT010 in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. A subset of patients participated in the 4-hour pulmonary function test (PFT) sub-study, with the following primary endpoints: change from baseline in morning pre-dose trough FEV1 at Week 24 at (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI versus glycopyrrolate/formoterol fumarate MDI), and FEV1 area under the curve from 0-4 hours at Week 24 (both doses of budesonide/glycopyrrolate/formoterol fumarate MDI vs budesonide/formoterol fumarate MDI). 
Dr. Jimenez[/caption]
Monik Carmen Jimenez, Sc.D
Assistant Professor of Medicine
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Response: We wanted to get a comprehensive picture of the epidemiology of COVID-19 in carceral facilities that included jails and was not restricted solely to prisons. We utilized publicly available data collected in Massachusetts, pursuant to a court order. These data included prison and jail systems and were used to calculate rates of confirmed cases of COVID-19 and testing rates among incarcerated individuals. We were also able to compare those to changes in the population size within each system.
Dr. Ratnasiri[/caption]
Anura Ratnasiri PhD
Senior Research Scientist
(Epidemiology and Biostatistics) Benefits Division
Department of Health Care Services
Sacramento, CA 95899-7417
MedicalResearch.com: What is the background for this study?
Response: Infant mortality rate (IMR) is a widely-reported indicator of population health and is used as a standardized measurement of deaths in the first year of life per thousand live births. While IMR has been steadily declining in the United States, it remains relatively high compared with other developed countries.
Even though significant improvements have been made in the quality and access to neonatal and infant care during the past decade, large educational, socioeconomic, racial, ethnic, geographic and behavioral disparities persist, and appear to be responsible for significant differences in IMR among different subgroups. Certain maternal and infant characteristics have important associations with IMR, and this study attempted to quantify major maternal and infant predictors, and trace associated mortality trends during the study period.
There were no recent studies on infant mortality using a large data set such as California State. Moreover, gestational age based on obstetric estimates from fetal ultrasound, prepregnancy obesity, and smoking during pregnancy were not available in prior population-based studies in California.
Dr. Reyes Gil[/caption]