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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