Expanded Genetic DNA More Susceptible To Ultraviolet Light Damage

MedicalResearch.com Interview with:

Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio

Dr. Carlos E. Crespo-Hernández

Carlos E. Crespo-Hernández PhD
Associate Professor and Co-director of the Center for Chemical Dynamics
Department of Chemistry
Case Western Reserve University
Cleveland, Ohio

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival.

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Computer Bests Neuroradiologists in Distinguishing Tumor Recurrence From Radiation Necrosis

MedicalResearch.com Interview with:

Dr. Pallavi Tiwari PhD Assistant Professor biomedical engineering Case Western Reserve University

Dr. Pallavi Tiwari

Dr. Pallavi Tiwari PhD
Assistant Professor biomedical engineering
Case Western Reserve University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One of the biggest challenges in neuro-oncology currently is distinguishing radionecrosis, a side-effect of aggressive radiation, from tumor recurrence on imaging. Surgical intervention is the only means of definitive diagnosis, but suffers from considerable morbidity and mortality. The treatments for radionecrosis and cancer recurrence are very different. Early identification of the two conditions can help speed prognosis, therapy, and improve patient outcomes.

The purpose of this feasibility study was to evaluate the role of machine learning algorithms along with computer extracted texture features, also known as radiomic features, in distinguishing radionecrosis and tumor recurrence on routine MRI scans (T1w, T2w, FLAIR). The radiomic algorithms were trained on 43 studies from our local collaborating institution – University Hospitals Case Medical Center, and tested on 15 studies at a collaborating institution, University of Texas Southwest Medical Center. We further compared the performance of the radiomic techniques with two expert readers.

Our results demonstrated that radiomic features can identify subtle differences in quantitative measurements of tumor heterogeneity on routine MRIs, that are not visually appreciable to human readers. Of the 15 test studies, the radiomics algorithm could identify 12 of 15 correctly, while expert 1 could identify 7 of 15, and expert 2, 8 of 15.

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Health Care Personnel Can Easily Contaminate Themselves When Removing Gowns and Gloves

Curtis J. Donskey, MD Professor of Medicine Case Western Reserve University Staff Physician, Infectious Diseases Section, Louis Stokes Cleveland VA Medical Center

Dr. Curtis Donskey

MedicalResearch.com Interview with:
Curtis J. Donskey, MD
Professor of Medicine
Case Western Reserve University
Staff Physician, Infectious Diseases Section,
Louis Stokes Cleveland VA Medical Center

Medical Research: What is the background for this study?

Dr. Donskey: Personal protective equipment (PPE) is intended to protect healthcare personnel by preventing them from acquiring an infection and to protect patients by preventing pathogen transmission. This study focused on gloves and gowns which are designed to reduce contamination of the skin and clothing of personnel. There are several concerns about the effectiveness of gloves and gowns.

  • First, several studies have demonstrated that personnel may acquire pathogens such as Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) on their hands and clothing during patient care activities despite wearing gloves and gowns.
  • Second, some studies involving simulations have suggested that contamination of the skin and clothing occurs frequently during removal of gloves and gowns.
  • Finally, lapses in technique for PPE removal may contribute to acquisition of potentially fatal pathogens such as Ebola virus. These concerns highlight the urgent need for improved strategies to prevent contamination of personnel during PPE removal.

We had 3 goals in the study.

  • First, we wanted to determine if contamination with a fluorescent lotion during glove and gown removal would correlate well with contamination with a benign virus. We did this because the fluorescent lotion method could potentially be very useful for training personnel because you can easily visualize contamination with a black light and provide immediate feedback.
  • Second, we used the fluorescent lotion method to evaluate contamination of the skin and clothing of personnel from 4 hospitals during removal of contaminated gloves or gowns.
  • Finally, we tested whether an intervention would reduce contamination in one of the 4 hospitals. The intervention included practice in removal of contaminated gloves and gowns with immediate visual feedback based on fluorescent lotion contamination of skin and clothing.

Medical Research: What are the main findings?

Dr. Donskey: Our first key finding was that contamination with the fluorescent lotion correlated well with contamination with the benign virus. This was an important finding because it suggests that the fluorescent lotion method is a useful surrogate method to assess pathogen contamination during Personal protective equipment removal.

Our second key finding was that contamination of the skin and clothing of personnel occurred frequently during removal of contaminated gloves or gowns. For 435 total simulations, contamination occurred 46% of the time, with similar results for each the 4 study hospitals (43%-50%). Incorrect donning or doffing technique was common and was associated with an increase in contamination (70% of the time with incorrect technique versus 30% with correct technique).

Our final key finding was that the intervention was very effective in reducing contamination during PPE removal. Immediately after the training session, the frequency of contamination decreased from 60% to 20% and then was 12% at 1 and 3 months after the intervention.

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RNA Can Promote Colon Cancer Progression

Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955

MedicalResearch.com Interview with:
Ahmad M. Khalil, PhD

Department of Genetics
School of Medicine
Case Western Reserve University
Cleveland, Ohio 44106-4955

Medical Research: What is the background for this study? What are the main findings?

Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression.  In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known.  In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation – the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells.

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Twin Study Shows Rosacea Has 50:50 Genetic and Environmental Influences

Nely Aldrich, MD Department of Dermatology University Hospitals Case Medical CenterMedicalResearch.com Interview with:
Nely Aldrich, MD
Department of Dermatology
University Hospitals Case Medical Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Aldrich:   To our knowledge, no formal studies have been performed on the genetic vs. environmental factors that lead to the development of rosacea. Our department has the unique opportunity to attend the Twins Days festival in Twinsburg, Ohio. This is a yearly festival where thousands of twin pairs come from all over the world. This was the perfect setting to ask our research question. Our main finding was that there is an approximately 50% contribution of genetics to rosacea and the other 50% can be attributed to environmental factors. Sun exposure, smoking, alcohol use, skin cancer history, and heart disease were also found to be correlated with a higher rosacea severity.

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Compromised Antimicrobial Response Tied to Infections in Diabetes

Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental MedicineMedicalResearch.com Interview with:
Wesley M. Williams, PhD

Cell molecular biologist
Department of Biological Sciences
Case Western Reserve University School of Dental Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Williams: Individuals with uncontrolled blood sugar levels frequently present with higher than normal rates of infection and protracted wound healing. The beta-defensin family of antimicrobial peptides responds to bacterial, fungal and viral invasion. As part of the innate immune system, these cationic peptides normally expressed by epithelial cells are important early responders that, together with other components of the innate immune response, act to inhibit microbial infection. Our initial observations led us to question whether glucose or a metabolite of glucose could contribute to antimicrobial peptide dysfunction, and thus compromise control of infection. Elevated levels of glucose result in increased production of dicarbonyls, a class of molecule that can selectively react with proteins having an unusually high content of cationic amino acids, such as arginine and lysine. We first investigated the effects of two well-characterized dicarbonyls, methylglyoxal (MGO) and glyoxal (GO) on recombinant beta-defensin 2 (rHBD-2) structure using MALDI TOF and LC/MS/MS mass spectral analysis of the recombinant peptide. We found MGO to be particularly reactive with the rHBD-2 peptide as it readily and irreversibly adducted to two arginine residues and the N-terminal glycine. Next we tested in vitro for the effects of adducted rHBD-2 on antimicrobial and chemotactic functions, both essential to an effective innate and adaptive immune response in vivo. Through radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, we found that both antimicrobial and chemotactic functions of rHBD-2 were significantly compromised by MGO.

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Genes Identified That May Be New Drug Targets In HER2 Breast Cancer

Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with:
Ahmad M. Khalil, PhD

Assistant professor, Department of Genetics and Genome Sciences
Case Western Reserve University School of Medicine

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don’t work at all in some patients.

Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes.

Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis.

There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely.

Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor. Continue reading

Service To Others May Help Addicted Adolescents Overcome Fear Of Social Humiliation

Maria Pagano, PhD Case Western Reserve University School of Medicine Department of Psychiatry, Division of Child Psychiatry Cleveland, OHMedicalResearch.com Interview with:
Maria Pagano, PhD
Case Western Reserve University School of Medicine
Department of Psychiatry, Division of Child Psychiatry
Cleveland, OH

MedicalResearch: What is the background for this study?

Dr. Pagano: Socially anxious adolescents quickly figure out that alcohol and drugs can provide ease and comfort in social situations that are anxiety provoking.  Reaching for a substance to change how you feel can quickly become a knee-jerk reaction, can develop into an addiction, and robs youths of learning how to tolerate interpersonal differences and uncomfortable feelings, developing emotional maturity, and cultivating self acceptance.

Adolescents who fear being criticized by their peers are likely to not speak up in group therapies during treatment, which can limit their benefit from treatment.  There is a lot of healing that comes sharing your insides with others. Socially anxious patients may not get this healing nor let others really get to know who they are and give input to their lives

Higher peer helping in AA during treatment means getting active in low intensity tasks like putting away chairs, or making coffee at a 12-step meeting.  It is less about needing peer assistance or expecting praise or recognition from giving service.  It is more about adopting the attitude of “how can I be helpful?”

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Physical Activity Including Housework Linked To Better Physical and Emotional Aging

kathy-wrightMedicalResearch.com Interview with:
Kathy Wright, PhD, RN, GCNS-BC, PMHCNS-BC
KL2 Postdoc, Clinical Instructor 2011-13 SAMHSA Scholar
2010-12 National Hartford Center of Gerontological Nursing Excellence
Patricia G. Archbold Scholar
Frances Payne Bolton School of Nursing
Case Western Reserve University Cleveland, Ohio

MedicalResearch: What is the background for this study?

Dr. Wright: This study was a secondary analysis of baseline data from the After Discharge Care Management of Low Income Frail Elderly (Agency for Healthcare Research and Quality grant #1 R01 HS014539-01A1). The participants were aged 65 and older enrolled during an acute care hospitalization. Each participant had at least one deficit in activities of daily living (e.g., bathing, dressing) or two deficits in instrumental activities of daily living (e.g., transportation, paying bills). The purpose of the study was to test House’s Conceptual Framework for Understanding Social Inequalities in Health and Aging in Medicare-Medicaid enrollees in a group of low-income older adults to determine the relationships between socio-demographic factors (i.e., race, education, age, gender, income, and neighborhood poverty), health behaviors, and physical function and emotional well-being. As a part of the health behavior component, participants were interviewed and asked questions regarding the amount of physical activity they engaged in during the week.

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Rate At Which Genetic Code Read May Offer New Drug Targets

Jeff Coller, PhD  Associate professor Division of General Medical Science Associate director, The Center for RNA Molecular Biology, Case Western Reserve University School of MedicineMedicalResearch.com Interview with:
Jeff Coller, PhD
  Associate professor
Division of General Medical Science
Associate director, The Center for RNA Molecular Biology,
Case Western Reserve University School of Medicine

MedicalResearch: What is the background of this study?

Dr. Coller: There are a diverse number of half-lives for any individual messenger RNA (mRNA). The range of those half-lives is from seconds to hours. What the field has wanted to know for 30 years is how those rates are regulated, and there has been considerable anecdotal and real evidence that sequences in untranslated regions (UTRs) could regulate decay, but it doesn’t explain all of the half-lives that are observed for all messages. In addition, we have known mRNAs that are translated better are more stable than mRNAs that are translated poorly, so those pieces together led to the discovery.

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Y Chromosome Mutation Can Lead To Sex Reversal and Cancer

Michael A. Weiss, MD, PhD The Cowan-Blum Professor and Chairman of the Department of Biochemistry Distinguished Research Professor andMedicalResearch.com Interview with:
Michael A. Weiss, MD, PhD

The Cowan-Blum Professor and Chairman of the Department of Biochemistry Distinguished Research Professor and Professor of Medicine in the Endocrine Division at the Case Western Reserve School of Medicine in Cleveland, Ohio.

Joseph Racca Researcher and graduate student Department of BiochemistryJoseph Racca
Researcher and graduate student
Department of Biochemistry

Case Western Reserve School of Medicine in Cleveland, Ohio.

Medical Research: What is the background for this study? What are the main findings?

Response: The function of the gene responsible for male differentiation, sex-determining region of the Y chromosome (SRY), was first demonstrated in transgenic mouse models by P. Koopman, R. Lovell-Badge and colleagues in the early 1990s. These findings were corroborated by identification of mutations in human SRY that are associated with human sex reversal: XY, 46 gonadal dysgenesis leading to somatic sex reversal (Swyer’s Syndrome). Such mutations may occur spontaneously in spermatogenesis or be inherited. The characterization of the molecular defects associated with these mutations has unmasked novel biological and biochemical activities of SRY. More broadly, such studies have also increased our understanding of an entire family of related transcription factors (Sry-box related; SOX), which broadly function in metazoan development (from worms, fish and flies to mammals). Within human SRY, the majority of clinical mutations occur in the region of the protein responsible for specific DNA binding and DNA bending, the primary molecular actions of SRY at target genes. Our study bridges structure (i.e., protein folding and stability) and function (i.e., transcriptional activation of target genes and related cell-biological processes such as trafficking and proteosomal degradation).

In our current study, we highlighted the importance of a structural scaffold in human SRY, specifically a key single amino acid that buttresses the unique L-shape structure of this domain. The mutation of interest represents a “perfect storm” leading to deleterious effects on multiple activities, including specific DNA binding, cellular localization, and both protein and cellular stability (lifetime), among other properties, together leading to sex reversal and cancer (gonadoblastoma) in the proband patient. Our integrated multi-disciplinary approach allowed us to characterize these various facets of SRY in the context of its biological site of action: the pre-Sertoli cell in an embryonic gonadal ridge just prior to its morphological differentiation into a testis. We are grateful to Prof. Patricia K. Donahoe (Harvard Medical School and the Massachusetts General Hospital), who generously provided this micro-dissected pre-Sertoli cell line.

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Childhood Atopic Dermatitis Linked To Obesity And Hypertension

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, IllinoisMedicalResearch.com Interview with:
Dr. Jonathan L. Silverberg MD PhD MPH

Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine
Northwestern University, Chicago, Illinois

Medical Research: What is the background for this study?

Dr. Silverberg: Previous studies found associations between obesity and atopic dermatitis (AD). However, little was known about the association between AD and metabolic risk factors, such as central obesity and high blood pressure.
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Stepping Closer To Nerve Regeneration After Spinal Cord Injury

Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with:
Bradley T. Lang, PhD
Researcher, Jerry Silver Lab
Department of Neurosciences
Case Western Reserve University School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Lang: In the late 1980’s, Jerry Silver, PhD, discovered the presence of chondroitin sulfate proteoglycans in the developing nervous system, which form barriers to prevent aberrant growth. He has been building on this finding for more than 30 years, attempting to understand why the adult spinal cord is incapable of regenerating, or why axons don’t grow where they don’t. He has found that the glial scar, which surrounds the site of neural trauma, is incredibly rich in proteoglycans, which prevent regeneration in the spinal cord. In 2009 we collaborated with a group at Harvard to discover the very first receptor for chondroitin sulfate proteoglycans, protein tyrosine phosphatase-sigma, or PTPsigma.

Medical Research: What are the main findings?

Dr. Lang: The findings in this paper are twofold. We first describe a novel mechanism of regeneration failure, where regenerating axons become stabilized within a gradient of chondroitin sulfate proteoglycan, completely preventing motility. This finding helps explain why axons persist in the vicinity of the glial scar after injury indefinitely, with little to no regeneration potential—they are simply embedded within the scar. We were able to model this interaction in a petri dish to screen for drugs that were capable of promoting motility.

The second finding in the manuscript is the discovery and characterization of a novel peptide therapeutic that binds to the receptor for chondroitin sulfate proteoglycans and releases inhibition. Most importantly, this drug was given systemically, similar to a daily insulin injection, avoiding complications due to direct nervous system infusion/injection. After several weeks of treatment (which began 1 day after injury), rats with severe spinal cord injury regained coordinated locomotion, bladder control, and/or balance. In total, 21/26 treated animals regained some function. Continue reading

Reduction of Surgical Resident Duty Hours Resulted In No Change In Outcomes

Ravi Rajaram MD Division of Research and Optimal Patient Care, American College of Surgeons Surgical Outcomes and Quality Improvement Center (SOQIC), Department of Surgery and Center for Healthcare Studies in the Institute for Public Health and Medicine Feinberg School of Medicine, Northwestern University, Chicago, IllinoisMedicalResearch.com Interview with:
Ravi Rajaram MD

Division of Research and Optimal Patient Care, American College of Surgeons Surgical Outcomes and Quality Improvement Center (SOQIC), Department of Surgery and Center for Healthcare Studies in the Institute for Public Health and Medicine
Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Medical Research: What is the background for this study? What are the main findings?

Dr. Rajaram: The Accreditation Council for Graduate Medication Education (ACGME) first implemented restrictions to resident duty hours in 2003. In surgical populations, these reforms have not been associated with a change in patient outcomes.

However, in 2011, the ACGME further restricted resident duty hours to include: a maximum of 16 hours of continuous duty for first-year residents (interns), direct supervision of interns at all times, a maximum of 4 hours for transitions in care activities for residents in-house for 24 hours, and that these residents be given 14 hours off prior to returning to work. The association between the 2011 ACGME resident duty hour reform with surgical patient outcomes and resident education has not previously been reported.

The 2011 resident duty hour reform was not associated with a change in death or serious morbidity in the two years after the reform was implemented. Additionally, the 2011 duty hour reform was not associated with a change in any of the secondary outcomes examined, including any morbidity, failure to rescue, surgical site infection, and sepsis.

Furthermore, common measures of surgical resident education, such as in-training examination scores and board certification pass rates, were unchanged after the implementation of the 2011 duty hour reform when compared to scores prior to the reform. Continue reading

Breast Cancer: Overcoming Tumor Resistance With Combinatinon Therapy

Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center  Case Western Reserve UniversityMedicalResearch.com Interview with:
Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology

Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center  Case Western Reserve University

Medical Research: What is the background for this study?

Dr. Keri: Over the last several decades, the discovery of targeted therapies for certain types of breast cancer, and their use in the clinic, have greatly improved the long-term outcome of patients. Yet some breast cancers don’t respond to these therapies, and ones that do often become resistant over time, resulting in patient relapse and metastatic disease. Why does resistance occur? There are many tricks a tumor employs to evade death. When a drug targets a certain protein or pathway the cancer cell relies on for survival, one potential route of resistance is the cancer cell’s ability to adapt and find another pathway to maintain growth. We reasoned that targeting two separate proteins or pathways important for cancer cell growth may be more effective at preventing or delaying this adaptation.

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Does Dental Trauma Play A Role in Oral Cavity Cancer?

MedicalResearch.com Interview with:
Brendan J. Perry, BSc, MBBS
Princess Alexandra Hospital
Brisbane, Queensland, Australia

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Brendan J. Perry: Oral cavity cancer is usually attributed to the “Five S’s” – smoking, spirits (alcohol), spices, syphillis and sharp (or septic) teeth. Cigarettes and alcohol are the most important recognised factors. Spices, such as betel nut, and syphillis are known carcinogens but are not commonly seen in western practice. The role of chronic dental trauma on the mucosa of the mouth to cause cancer has only been examined in a limited number of studies previously and its importance has not been elucidated and has never really affected clinical practice.

This retrospective review examined the position in the oral cavity where cancers occurred with respects to smoking status and other variables over a 10 year period in a major Australian hospital. The edge of the tongue, a site of potential dental trauma, was the most common site affected, accounting for 35% of oral cavity cancers in smokers. However, in lifelong non-smokers without other significant risk factors, 65% of cancers occurred on the edge of the tongue. A significant number also occurred on the buccal mucosa (inner lining of cheek) which is also exposed to dental trauma, but to a much lesser degree than the more mobile tongue. The floor of the mouth and the alveolar ridge (gums) were also common sites of cancer, but tended to occur in an older age group. This is possibly due to irritation caused by the movement of dentures in this age group against these areas of the mouth.

We also found that males had an equal chance of developing oral cavity versus oropharyngeal cancer (255 cases vs 265). However, females are almost twice as likely to develop an oral cavity cancer than an oropharyngeal cancer (135 cases vs 69), and this ratio jumps to 4 times the risk for lifelong non-smoking females (53 vs 12). Although a lot of attention has been given to HPV in causing oropharyngeal cancer, for non-smokers, especially females, it appears that oral cavity cancer is a more common disease, and also that chronic dental trauma may be a significant contributing factor.
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Reliability of East German Pharmaceutical Investigations Questioned

MedicalResearch.com Interview with: Dr. med. Rainer Erices Institut für Geschichte und Ethik der MedizinMedicalResearch.com Interview with:
Dr. med. Rainer Erices
Institut für Geschichte und Ethik der Medizin

Medical Research: What are the main findings of the study?

Dr. Erices: The study presents the results of a first systematic investigation of clinical drug trials carried out by Western pharmaceutical firms in Eastern Germany in the 1980s. The scientific investigation of the East German Health system has only just started. The study shows that in that period of time, around 220 clinical trials were carried out. We now know how many patients took part and what remuneration the GDR received. It continues to be difficult to evaluate these tests. Despite intensive research efforts in different archives, we have been unable to find documentation on how detailed (and systematically) patients were informed about the trial they were taking part in. The responsible institutions repeatedly advised testers to stick to the law during the clinical trials. The law required that these trials should only be carried out on patients which had given their informed consent and had decided to participate voluntarily. However, so far there is no convincing proof that these legal requests were met.

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Researchers Discuss Atrial Fibrillation and ZIO Service For Detection and Management

MedicalResearch.com Interview with:
Philip Gorelick, M.D., M.P.H, F.A.C.P. Medical Director of the Hauenstein Neuroscience Center Saint Mary’s Health Care, Grand Rapids, MI; Professor, Translational Science and Molecular Medicine Michigan State University College of Human Medicine; Board member of the National Stroke AssociationPhilip Gorelick, M.D., M.P.H, F.A.C.P.
Medical Director of the Hauenstein Neuroscience Center
Saint Mary’s Health Care, Grand Rapids, MI;
Professor, Translational Science and Molecular Medicine
Michigan State University College of Human Medicine;
Board member of the National Stroke Association
and
Judy Lenane, R.N., M.H.A. Chief Clinical Officer of iRhythm Technologies, Inc.

Judy Lenane, R.N., M.H.A.
Chief Clinical Officer of iRhythm Technologies, Inc.

 

Medical Research: What is atrial fibrillation and how common a problem is it among US adults?

Dr. Gorelick: Nearly 3 million people in the US suffer from Atrial Fibrillation or “Afib,” an abnormal heart rhythm that causes the heart to beat rapidly and irregularly. While Afib can occur at any age, the incidence increases with age and the number of cases is expected to increase significantly in the coming years as the population ages. Approximately 5 percent of people 65 years and older and one in every 10 people over 80 years of age have Afib. It is more common in those with high blood pressure, heart disease or lung disease. Continue reading

Females Neglected In Basic Medical Research Studies

Melina Kibbe, MD, FACS, FAHA Professor and Vice Chair of Research Edward G. Elcock Professor of Surgical Research Department of Surgery Northwestern University Institute for BioNanotechnology in Medicine Deputy DirectorMedicalResearch.com Interview with:
Melina Kibbe, MD, FACS, FAHA
Professor and Vice Chair of Research
Edward G. Elcock Professor of Surgical Research
Department of Surgery,Northwestern University
Institute for BioNanotechnology in Medicine Deputy Director

Medical Research: What are the main findings of the study?

Dr. Kibbe: We found that approximately 1/3 of all peer-reviewed published manuscripts in 5 top surgery journals did not state the sex of the animal or cell used for research. Of those that did state the sex, 80% used only males.
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Lyme Disease A Year Round Threat in Northern California

Daniel Salkeld, PhD Lecturer & Research Associate Stanford Woods Institute for the Environment Professor Colorado State UniversityMedicalResearch.com Interview with:
Daniel Salkeld, PhD
Lecturer & Research Associate
Stanford Woods Institute for the Environment Professor
Colorado State University


Medical Research: What are the main findings of the study that were just published in Ticks and Tick-borne Diseases?

Dr. Salkeld: The primary findings of this new study show that western black-legged ticks, which can transmit Lyme disease, are active throughout the year in Northwest California, making the threat of Lyme disease year-round phenomenon.

More specifically, my colleagues from California Department of Public Health Vector-borne Disease Section and University of California, Berkeley and I found that the activity of Western Black-legged ticks (Ixodes pacificus), which are the ticks most commonly known to carry Lyme disease (caused by Borrelia burgdorferi) in Northwest California, is largely predictable and year-round. In general, tick larvae (newly hatched immature ticks) are active April to June, and sometimes activity extends into October, while adult ticks are active from October to May. Nymphal ticks (the tick stage following larvae and preceding adults) are active from January to October but peak from April-June. This is important because nymphs are responsible for most Lyme disease infections.
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Acid Reflux More Frequent During Naps than Nighttime Sleep

Ronnie Fass, M.D., FACG, Professor of Medicine Case Western Reserve University Director, Division of Gastroenterology and Hepatology, Head, Esophageal and Swallowing Center, Metro Health Medical Center Cleveland, OHMedicalResearch.com Interview with:
Ronnie Fass, M.D., FACG, Professor of Medicine
Case Western Reserve University
Director, Division of Gastroenterology and Hepatology, Head, Esophageal and Swallowing Center, Metro Health Medical Center
Cleveland, OH

MedicalResearch: What are the main findings of the study?

Dr. Fass: This is the first study to compare the extent of acid reflux between nighttime sleep and daytime naps in patients with Gastroesophageal reflux disease. The results of our study show that naps are associated with significantly greater esophageal acid exposure compared to sleep. Acid reflux events were more frequent and their total duration was longer during naps when compared with acid reflux events during nighttime sleep. Additionally, the fraction of time that the subjects were experiencing acid reflux with pH < 4 was significantly higher during naps than nighttime sleep and subjects experienced more symptoms due to acid reflux during their nap than their sleep.

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Lung Cancer: Germline Mutation Predisposes Women Who Never Smoked

Dr. Azi  Gazdar, MD UT Southwestern Medical Center W. Ray Wallace Distinguished Chair in Molecular Oncology Research Hamon Center for Therapeutic Oncology, PathologyMedicalResearch.com Interview with:
Dr. Azi  Gazdar, MD
UT Southwestern Medical Center
W. Ray Wallace Distinguished Chair in Molecular Oncology Research
Hamon Center for Therapeutic Oncology, Pathology


MedicalResearch.com: What are the main findings of the study?

Dr. Gazdar: We describe the characteristics of lung cancers arising in subjects who inherited a germline mutation that predisposes to lung cancer.  The mutation is rare in the general populations, and is inherited equally by both sexes.  However it is a potent predisposing gene, and one third of the never smoking carriers will develop lung cancer.  Thus, about 1% of patients who develop lung cancer carry the germline mutation.  This figure may rise as awareness of the condition and its link to lung cancer is raised among doctors diagnosing lung cancer. However, lung cancers mainly develop in women who are lifetime never smokers.  Lung cancer development is much less common among smokers and men, although accurate figures are not yet available. So the risk among carriers is somewhat similar to the BRCA genes predisposing to breast cancer, where a female carrier has about a 50% lifetime chance of developing breast cancer.

The specific germline mutation (known as T790M) occurs in a gene known as epidermal growth factor receptor (EGFR) gene.  Sporadic mutations in this gene usually predict for effective responses to a class of drugs known as tyrosine kinase inhibitors (TKIs), which are widely used in the treatment of lung cancer.  However, the T790M mutation, when it occurs in sporadic tumors not associated with germline inheritance are resistant to TKI therapy.  Thus the prediction is that lung cancers arising in carriers with the germline mutation would also be resistant to TKI therapy.
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Autism: Autistic Brains Create More Information at Rest

Roberto Fernández Galán, PhD Department of Neurosciences, School of Medicine Case Western Reserve University Cleveland, OH, USAMedicalResearch.com Interview with:
Roberto Fernández Galán, PhD
Department of Neurosciences, School of Medicine
Case Western Reserve University
Cleveland, OH, USA
MedicalResearch.com: What are the main findings of the study?

Dr. Galán: The main finding is that autistic brains create more information at rest than non-autistic brains. This is consistent with the classical view on autism as withdrawal into self. It is also consistent with a recent theory on autism, the “Intense World Theory”, which claims that autism results from hyper-functioning neural circuitry, leading to a state of excessive arousal. From both perspectives, the classical and the IWT, communication and social deficits associated with autism result from having a more intense inner life and a higher level of introspection.
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Dabigatran: Comparison Mini-Sentinel Clinical Trials and GI Bleeding

Ilke Sipahi, MD Department of Cardiology Acibadem University Medical School, Istanbul, Turkey Harrington Heart and Vascular Institute, University Hospitals Case Medical Cente  Case Western Reserve University School of Medicine, Cleveland, OhioMedicalResearch.com Interview with:
Ilke Sipahi, MD
Department of Cardiology
Acibadem University Medical School, Istanbul, Turkey
Harrington Heart and Vascular Institute, University Hospitals Case Medical Cente, Case Western Reserve University School of Medicine, Cleveland, Ohio

MedicalResearch.com: Were you surprised at the extreme difference between these 2 analyses?

Answer: I was surprised. However, it is not unusual to find completely
contradictory results in medical studies. I was more surprised at the
fact that FDA paid more attention to it administrative observational
dataset rather than the huge large randomized clinical trials, all
showing excess GI bleeds with dabigatran (Pradaxa). Anyone who is even
slightly familiar with the medical literature knows that randomized trials are the gold standard in medical studies.
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Myocardial Fat Content : Effects of Age and Aerobic Fitness

Dr. Satyam Sarma MD Assistant Instructor, Cardiology University of Texas, Southwestern Medical Center Inst. for Exercise and Environmental Medicine 7232 Greenville Ave. Dallas TX 75231MedicalResearch.com Interview with:
Dr. Satyam Sarma MD
Assistant Instructor, Cardiology
University of Texas, Southwestern Medical Center
Inst. for Exercise and Environmental Medicine
7232 Greenville Ave. Dallas TX 75231


MedicalResearch.com: What are the main findings of the study?

Dr. Sarma: The main findings of our study were that as we age or live a sedentary lifestyle, fat tends to accumulate in the muscle of the heart. The accumulation of myocardial lipids were linked to abnormalities in diastolic function. With increasing levels of fat, the left ventricle became less distensible and had impaired tissue relaxation.
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URI: Safety and Effectiveness of an Oral CPC Spray

Pranab K. Mukherjee, Ph.D. Assistant Professor Center for Medical Mycology Department of Dermatology University Hospitals Case Medical Center Case Western Reserve University Cleveland, OH 44106-5028MedicalResearch.com Interview with:
Pranab K. Mukherjee, Ph.D.
Assistant Professor
Center for Medical Mycology
Department of Dermatology
University Hospitals Case Medical Center
Case Western Reserve University
Cleveland, OH 44106-5028

MedicalResearch.com: What are the main findings of the study?

Answer: We performed a randomized double-blinded placebo-controlled pilot clinical trial to assess the safety, tolerability and effectiveness of a cetylpyridinium chloride (CPC)-based oral spray in the prevention of acute upper respiratory tract infections (URIs).

  • The tested CPC spray (ARMS-I, developed by Arms Pharmaceutical LLC, Cleveland, OH) was safe and exhibited high tolerability and acceptability among study participants
  • The product exhibited a trend to protect against URIs (55% relative reduction compared to the placebo), based on confirmed URIs, post-medication exit interviews, and daily electronic diaries completed by study participants
  • There was statistically significant reduction in frequency of cough and sore throat in the active group
  • The number of days (duration) of cough was significantly reduced in the active group compared to placebo arm
  • URI-associated viruses (influenza, rhinovirus and coronavirus) were detected in three individuals, all in the placebo arm. No virus was detected in the active arm/
  • No drug-related adverse events or oral lesions were observed
  • Previous vaccination status of the study participants did not affect the study outcome.

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Barrett’s Esophagus, Erosive Esophagitis, GI Symptoms and H. Pylori

Joel H. Rubenstein, MD, MSc, FACG, FASGE Research Scientist, Veterans Affairs Center for Clinical Management Research Assistant Professor, Division of Gastroenterology, University of Michigan Medical School VA Medical Center 111-D 2215 Fuller Rd. Ann Arbor, MI 48105MedicalResearch.com Interview with:
Joel H. Rubenstein, MD, MSc, FACG, FASGE
Research Scientist, Veterans Affairs Center for Clinical Management Research
Assistant Professor, Division of Gastroenterology, University of Michigan Medical School
VA Medical Center Ann Arbor, MI 48105
MedicalResearch.com: What are the main findings of the study?

Dr. Rubenstein: In a set of case-control studies within the same population, we found that H. pylori was inversely associated with erosive esophagitis, and with Barrett’s esophagus, but we did not find such a relation with symptoms of gastroesophageal reflux disease (GERD).
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Nerve Block after Surgery Reduced Narcotic Usage, Shortened Hospital Stays

MedicalResearch.com Interview with:

Conor P. Delaney, MD MCh PhD FRCSI FACS FASCRS

The Jeffrey L. Ponsky Professor of Surgical Education | Chief, Division of Colorectal Surgery | Vice-Chair, Department of Surgery | Director, CWRU Center for Skills and Simulation | Surgical Director, Digestive Health Institute | University Hospitals Case Medical Center | Case Western Reserve University | 11100 Euclid Avenue Cleveland, OH 44106-5047

MedicalResearch.com: What are the main findings of the study?

Answer: Our goal was to see whether the transversus abdominis plane (TAP) block reduced complications and shortened the hospital stay of patients undergoing colorectal operations.  The TAP block is a nerve block injection given at the conclusion of the operation which reduces pain in the operative area.  Results showed that the mean hospital stay dropped to less than 2.5 days after the surgical procedure, significantly lower than the 3.7 days which the University Hospitals Case Medical Center Care pathway had already described for more than 1,000 consecutive patients. In our new study, we employed the TAP block and the Enhanced Recovery Pathway (ERP) on 100 patients.  We found that 27 patients went home the next day and another 35 went home 48 hours after their operations. That is considerably better than the five or six days patients usually stay in the hospital after laparoscopic colorectal procedures, and certainly better than nine days often seen after an open operation.  With a third of patients leaving the day after colorectal resection, we feel these results are significant.
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Rheumatoid Arthritis: Are Two Drugs Better than One?

Dr Janet E Pope Division of Rheumatology, Department of Medicine The University of Western Ontario, St Joseph's Health Centre 268 Grosvenor Street, London, ON, Canada N6A 4V2MedicalResearch.com Interview with:
Dr. Janet E Pope
Division of Rheumatology, Department of Medicine
The University of Western Ontario, St Joseph’s Health Centre
268 Grosvenor Street, London, ON, Canada N6A 4V2

 

MedicalResearch.com: What are the main findings of the study?

 Dr. Pope: We performed a RCT of patients who were stable for 6 months of etanercept added to methotrexate (inadequate responders to Mtx) who were randomized to stopping Mtx or continuing Mtx to determine if in the next 6 months (and later as the trial continues) the response rate would be the same if Mtx was discontinued. Overall, Mtx + etanercept was not statistically equivalent to etanercept alone (ie non-inferiority did not occur); implying 6 months after stopping Mtx, the etanercept patients on monotherapy performed slightly less well than those on combination therapy.
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Analyzing excess mortality from cancer among individuals with mental illness

MedicalResearch.com: eInterview with Siran M. Koroukian, Ph.D.
Population Health and Outcomes Research Core,
Clinical & Translational Science Collaborative
Associate Professor Department of Epidemiology and Biostatistics
School of Medicine Case Western Reserve University
Cleveland, OH 44106-7281

MedicalResearch.com: What are the main findings of the study?

Dr. Koroukian: Among individuals who died of cancer, those with mental illness (MI) died an average of 10 years earlier than those without MI.

Overall, there was excess mortality from cancer associated with having mental illness in all the race/sex strata: SMR, 2.16 (95% CI, 1.85-2.50) for black men; 2.63 (2.31-2.98) for black women; 3.89 (3.61-4.19) for nonblack men; and 3.34 (3.13-3.57) for nonblack women.

We note statistically significant higher SMRs for every anatomic cancer site in nonblack men and women and for most cancer sites in black men and women.
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