Author Interviews, Biomarkers, Brigham & Women's - Harvard, Diabetes, Endocrinology / 26.06.2023
ENDO23: Study Correlates Dietary Sugar End Products with Skin Autofluorescence Findings
MedicalResearch.com Interview with:
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Dr. Zahedi[/caption]
Dr. Bita Zahedi MD MA
Endocrinologist
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study?
Response: The purpose of this study was to develop and validate a measure of dietary advanced glycation end-products (AGEs) to investigate the role of dietary AGEs in diabetic disease processes. AGEs are a group of highly reactive compounds involved in the pathophysiology of diabetic complications, such as microvascular disease, cardiomyopathy, and possibly bone health. AGEs form through a nonenzymatic reaction between reducing sugars and free amino groups of proteins, lipids, and nucleic acids, also known as a Maillard or browning reaction.
Endogenous AGE formation and accumulation is a normal part of metabolism and aging, however the process of glycation can be enhanced by hyperglycemia, hyperlipidemia, and increased oxidative stress. Additionally, AGEs can be absorbed from exogenous sources via consumption of various food items. Prior studies demonstrate that skin AGEs are predictive of Dietary AGEs (dAGEs) which are naturally present in certain uncooked foods, mainly animal-derived products, furthermore the method of food preparation can result in significant AGE formation. Considering the ubiquitous intake of dAGEs, it is possible that the consumption of exogenous AGEs contribute to AGE-induced oxidative stress, inflammation, and its subsequent detrimental sequalae.
Dr. Zahedi[/caption]
Dr. Bita Zahedi MD MA
Endocrinologist
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study?
Response: The purpose of this study was to develop and validate a measure of dietary advanced glycation end-products (AGEs) to investigate the role of dietary AGEs in diabetic disease processes. AGEs are a group of highly reactive compounds involved in the pathophysiology of diabetic complications, such as microvascular disease, cardiomyopathy, and possibly bone health. AGEs form through a nonenzymatic reaction between reducing sugars and free amino groups of proteins, lipids, and nucleic acids, also known as a Maillard or browning reaction.
Endogenous AGE formation and accumulation is a normal part of metabolism and aging, however the process of glycation can be enhanced by hyperglycemia, hyperlipidemia, and increased oxidative stress. Additionally, AGEs can be absorbed from exogenous sources via consumption of various food items. Prior studies demonstrate that skin AGEs are predictive of Dietary AGEs (dAGEs) which are naturally present in certain uncooked foods, mainly animal-derived products, furthermore the method of food preparation can result in significant AGE formation. Considering the ubiquitous intake of dAGEs, it is possible that the consumption of exogenous AGEs contribute to AGE-induced oxidative stress, inflammation, and its subsequent detrimental sequalae.
Dr. Miller[/caption]
Alex P. Miller, PhD
TranSTAR T32 Postdoctoral Fellow
Department of Psychiatry
Washington University School of Medicine
St. Louis, MO
MedicalResearch.com: What is the background for this study?
Response: Adolescent cannabis use is increasing in the United States. Prior research suggests that people who start using cannabis earlier are more likely to engage in problematic use and also experience greater mental health challenges and socioeconomic disadvantages overall. For example, children who begin using cannabis early are more likely to have behavioral problems and disorders and are more less likely to complete school.
In our study, we used data from the Adolescent Brain Cognitive Development (ABCD) Study, which is following nearly 12,000 kids across the nation to track behavior and brain development as well as health from middle childhood to young adulthood. We looked at what factors are associated with the initiation of cannabis use by age 12-14.
Dr. Hafezi-Moghadam[/caption]
Ali Hafezi-Moghadam, Ph.D., M.D
Director, Molecular Biomarkers Nano-Imaging Laboratory (MBNI)
Associate Professor of Radiology, Harvard Medical School
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: “It is very easy to answer many fundamental biological questions” said Richard Feynman in his 1959 address, where he also offered his simple and ingenious solution: “you just look at the thing!”
Dr. GALBIATI[/caption]
Francesca Galbiati, MD
Clinical/Research fellow in Endocrinology
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study?
Response: Arginine-vasopressin (AVP) is a neurohormone well known for its role in water balance regulation. It promotes renal water absorption in the kidney, to maintain normal sodium levels in the blood via a tightly controlled osmotic regulation. Besides AVP classical role, data have shown that AVP effects extend beyond water balance regulation. Animal studies have shown that AVP has metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice.
Furthermore, AVP is regulated differently in males and females, and affects cognition differently across sexes, a phenomenon called sexual dimorphism. However, it is unknown whether its dimorphism translates to metabolism. Also, findings on AVP metabolic role are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, which regulation is still largely unknown. We performed this study to better investigate AVP metabolic role, and explore sex differences. We hypothesized that AVP would be positively associated with BMI, adiposity, and lean mass (acting as a signal of energy availability). We also predicted that relationships between AVP and body composition measures would differ by sex. We used the AVP area under the curve around a standardized meal to better capture repeated measures in response to food intake (that directly impacts energy availability). This also allowed to avoid the possible risk of fluctuating AVP levels due to possible pulsatile secretion.
Dr. Thomas[/caption]
Dr. Daniel Thomas MD PhD FRACP FRCPA
Program Leader, Blood Cancer
Precision Medicine Theme at the South Australia Health Medical Research Institute
Clinical Hematologist, Royal Adelaide Hospital
Associate Professor, Adelaide Medical School, The University of Adelaide
MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of CMML?
Response: Chronic myelomonocytic leukemia (CMML) is a rare, but increasingly frequent, clonal stem cell disorder that results in hyperproliferation of inflammatory monocytes, a form of white blood cells. It features both myelodysplasia and myeloproliferation. CMML is most often found in older adults and leads to anemia, decreased quality of life, and an increased risk of acute myeloid leukemia (AML).
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates production, growth, differentiation, activation, and function of myeloid cells (monocytes, neutrophils, and eosinophils). In the presence of RAS-pathway mutations, a greater sensitivity to GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML). In CMML, greater sensitivity to GM-CSF stimulates excessive monocytic precursor proliferation.
The PREACH-M Trial, which stands for PREcision Approach to CHronic Myelomonocytic Leukemia, assesses the efficacy of lenzilumab in addition to azacitidine in treatment-naïve CMML participants with RAS-pathway mutations (KRAS, NRAS, CBL) and separately high dose ascorbate in participants with TET2 mutations who do not have RAS-pathway mutations. The study is currently underway and actively enrolling. It is being conducted and funded by the South Australian Health and Medical Research Institute (SAHMRI).
Dr. Kamath[/caption]
Dr. Suneel Kamath MD
Gastrointestinal Oncologist
Cleveland Clinic
Senior Author on this research
MedicalResearch.com: What is the background for this study?
Response: Colorectal cancer rates in young people under age 50 are skyrocketing and have been for the last 3-4 decades. We really don’t understand why because most cases (probably around 70%) are not genetic or hereditary, just random, unfortunate events. We suspect that it is some exposure(s) like excess consumption of red meat, processed foods, sugar-sweetened beverages, excess antibiotic use altering the microbiome, rising incidence of obesity or some other factors. We really don’t know why yet.
Our study used a technology called metabolomics, the study of breakdown products and production building blocks for our bodies, to look for differences in colorectal cancer in young people versus people that are older that developed colorectal cancer. Because metabolomics measures how each individual interacts with the exposures in our environment like diet, air quality, etc., it is a way to bridge the gap between our nature (determined by genetics) and nurture (determined by our exposures).
Dr. Nowell[/caption]
W. Benjamin Nowell PhD
Director of Patient-Centered Research at Global Healthy Living Foundation
Columbia University in the City of New York
Dr. Lova Sun[/caption]
Lova L. Sun, MD, MSCE
Medical Oncology
Assistant Professor of Medicine
Hospital of the University of Pennsylvania
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: An common clinical question for patients with metastatic non-small cell lung cancer with long-term response to immunotherapy-based treatment is how long to continue treatment. The major clinical trials stopped immunotherapy at a maximum of 2 years, but in clinical practice many patients and clinicians continue treatment beyond this time point.
We conducted a retrospective study of lung cancer patients across the US with long-term response to immunotherapy, to compare survival between those who stopped treatment at 2 years vs those who continued beyond 2 years. We found that there was no statistically significant difference in survival between the two groups.
Joanna Gorgol[/caption]
Joanna Gorgol
PhD Student
University of Warsaw
MedicalResearch.com: What is the background for this study?
Response: People differ in the time when they prefer to wake up and fall asleep: some people prefer going to bed and waking up early, while others prefer later hours. Most of the population is somewhere between them. Research indicates that being a morning person is related to reporting higher satisfaction with life and conscientiousness. Studies also show the associations between being religious and having higher life satisfaction and conscientiousness. It seems that religiosity might mediate the relationship between morningness and higher life satisfaction. To better understand these associations we conducted two questionnaire-based studies of Polish adults, one with 500 participants and the other with 728 participants. All participants completed questionnaires measuring their chronotype, satisfaction with life, personality traits, and religiosity
Prof. Hiddo Lambers Heerspink, PhD PHARMD
Department of Clinical Pharmacy and Pharmacology
University Medical Center Groningen
Groningen
Dr. Manson[/caption]
JoAnn E. Manson, MD, DrPH, MACP
Dr. Lovestead[/caption]
Tara M Lovestead, PhD, (She/her/hers)
Dr. Finn[/caption]
Aloke V. Finn MD
Medical Director/Chief Scientific Officer
CVPath Institute Inc.
Gaithersburg, MD 20878
MedicalResearch.com: What is the background for this study?
Response:Transcatheter left atrial appendageal closure (LAAC) has become an established therapeutic approach for prevention of stroke in subjects with non-valvular atrial fibrillation who are ineligible for long-term oral anticoagulation. Device-related thrombus (DRT), developing after LAAO procedures occurs in a small proportion but patients receiving these devices but is associated with critical embolic events such as ischemic stroke. Thrombogenicity and delayed endothelialization of fabric play a role in the development of DRT. Fluorinated polymers are known to have thromboresistant properties which may favorably modify blood biomaterial interactions of a LAAO device.
In this study we compared the thrombogenicity and endothelial coverage (EC) after left atrial appendage occlusion (LAAO) between a novel fluoropolymer-coated Watchman (FP-WM (Watchman FLX PRO) and the conventional uncoated Watchman FLX (WM).
Julia Cave Arbanas[/caption]
Julia Cave Arbanas
Project Manager and
Prof. Dubinsky[/caption]
Marla Dubinsky, M.D.
Professor of Pediatrics and Medicine
Co-director of the Susan and Leonard Feinstein IBD Clinical Center
Chief of the Division of Pediatric Gastroenterology and Nutrition
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? How does MIRIKIZUMAB differ from other medications for UC?
Response: This is a phase 2 study to assess the PK (pharamcokinetics), safety and efficacy of mirikizumab in pediatric ulcerative colitis (UC).
Dr. Zirwas[/caption]
Matthew Zirwas, MD
Founder, Bexley Dermatology Research Clinic
Bexley, OH 43209
MedicalResearch.com: What is the background for this study? How does Roflumilast differ from other treatments for seb derm?
Response: Seborrheic dermatitis affects up to 5% of the population globally and can have major impacts on quality of life. Treatment regimens are often complicated given the association of seborrheic dermatitis to hair bearing areas of the body, requiring multiple treatments for different parts of the body. Our phase 2 study aimed to understand the efficacy and safety of once-daily roflumilast foam 0.3% in adults with seborrheic dermatitis on their scalp, face and trunk. Roflumilast foam is a selective and highly potent phosphodiesterase (PDE) 4 inhibition that is being studied for a range of inflammatory skin conditions.
Dr. Greenhawt[/caption]
Matthew Greenhawt, MD, MBA, MSc
Professor of Pediatrics
Section of Allergy and Immunology
Director, Food Challenge and Research Unit
Children’s Hospital Colorado
University of Colorado School of Medicine
Anschutz Medical Campus