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UC researchers say early puberty in girls may be the new big bang theory for migraine

CINCINNATI—Adolescent girls who reach puberty at an earlier age may also have a greater chance of developing migraine headaches, according to new research from investigators at the University of Cincinnati (UC) College of Medicine. “We know that the percentage of girls and boys who have migraine is pretty much the same until menstruation begins,” says Vincent Martin, MD, professor in the Division of General Internal Medicine and director of the Headache and Facial Pain Center at the UC Gardner Neuroscience Institute. “When the menstrual period starts in girls, the prevalence goes way up, but what our data suggests is that it occurs even before that.” The findings will be presented by Martin at the American Headache Society 61st Annual Scientific Meeting Saturday, July 13, in Philadelphia. Nationally, about 10 percent of school age children suffer from migraine, according to the Migraine Research Foundation (MRF). As adolescence approaches, the incidence of migraine increases rapidly in girls, and by age 17, about 8 percent of boys and 23 percent of girls have experienced migraine, the MRF reports. Martin and a team of researchers were part of a longitudinal study looking at 761 adolescent girls from sites in Cincinnati, New York and the San Francisco Bay area. The girls ranged in age from 8 to 20 and study took place over a 10-year period beginning in 2004. Girls enrolled in the study at age 8-10 were examined during study visit every six to 12 months. Researchers determined when they showed initial signs of thelarche (breast development), pubarche (pubic hair growth) and menarche (start of menstrual periods). Girls answered a headache questionnaire to find out if they suffered from migraine headache, no migraine or probable migraine—the latter is defined as meeting all the diagnostic criteria for migraine except one. The average age at which they completed the survey was 16. Of those surveyed, 85 girls (11 percent) were diagnosed with migraine headache while 53 (7 percent) had probable migraine and 623 (82 percent) had no migraine, according to Martin, also a UC Health physician specializing in migraine. Researchers found that girls with migraine had an earlier age of thelarche (breast development) and the onset of menarche (menstrual periods) than those with no migraine. On average breast development occurred four months earlier in those with migraine while menstruation started five months earlier. There was no difference in the age of pubarche (pubic hair development) between those with migraine and no migraine. “There was a 25 percent increase in the chance of having migraine for each year earlier that a girl experienced either thelarche or menarche,” says Susan Pinney, PhD, professor in the UC Department of Environmental Health and lead investigator on the study. “This suggests a strong relationship between early puberty and the development of migraine in adolescent girls.” The age of onset of thelarche, pubarche or menarche did not differ between those with probable migraine and no migraine, says Pinney. Previous research suggests that migraine often starts with the onset of menstrual cycles during menarche in adolescent girls. But this study looks at earlier stages of puberty such as thelarche and pubarche, explains Martin. “To suggest the origins of migraine may occur actually before menstrual periods begin is pretty novel,” says Martin. “At each of these stages, different hormones are starting to appear in girls. During pubarche, testosterone and androgens are present, and during thelarche, there is the very first exposure to estrogen. Menarche is when a more mature hormonal pattern emerges. Our study implies that the very first exposure to estrogen could be the starting point for migraine in some adolescent girls. It may be the Big Bang Theory of migraine.” So is there anything that one can do to prevent an early puberty? “Studies suggest that childhood obesity is associated with early puberty,” says Martin, who is also president of the National Headache Foundation. “Keeping your weight down might prevent the early onset of puberty. Future studies will need to be done to determine if strategy will decrease also the likelihood of developing migraine.” Other co-investigators in the study include Frank Biro, MD, UC professor in the Department of Pediatrics and Cincinnati Children’s pediatrician, Jun Ying, PhD, professor in the UC Department of Environmental Health, and Hao Yu, biostatistician, UC Department of Environmental Health. Funding for this research came grant U01ES026119 from the National Institute of Environmental Health Sciences and grant 1R03HD094236 of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. UC researchers say early puberty in girls may be the new big bang theory for migraine Full Story

UC researcher examines impact opioids and HIV have on each other

A University of Cincinnati (UC) College of Medicine researcher is trying to determine how opioids interact with HIV and the medications used to manage it in the search for new therapies to better assist individuals battling addiction and living with HIV. Jason Blackard, PhD, associate professor in the UC Department of Internal Medicine’s Division of Digestive Diseases, has secured a $1.7 million National Institute of Drug Abuse (NIDA) grant awarded over a three-year period to conduct an omics analysis of synthetic opioids and HIV. “This is a complex issue. We have a very poor understanding of how HIV impacts opioids or how opioids impact HIV. We don’t know if current therapies will work as well as they normally do,” says Blackard, whose translational research laboratory studies virus-virus and virus-host interactions. “What is the interaction between these synthetic opioids that are commonly found in high-risk individuals and some of the infections that might be associated with drugs of abuse like HIV or Hepatitis C virus?” In 2017, an estimated 1.7 million people in the United States suffered from substance use disorders related to prescription opioid pain relievers and 652,000 suffered from a heroin use disorder, according to NIDA. About 47,000 Americans that same year died as a result of opioid overdose—a statistic that includes the use of prescription opioids, heroin and illegally manufactured synthetic opioids such as fentanyl, per NIDA. Drug users often share needles when using injectable opioids, an action that increases the risk of contracting HIV and Hepatitis C virus. A key advantage of this project is its multi-disciplinary approach. Co-investigators involved in the study include UC faculty and UC Health clinicians: Michael Lyons, MD, associate professor of emergency medicine, and Jennifer Brown, PhD, associate professor of psychiatry. They will help Blackard in bridging the divide between basic and clinical science that this translational research project is designed to address. Blackard says the research project will include an observational study in humans as well as ex vivo experiments using blood samples manipulated and exposed to HIV and/or synthetic opioids in the laboratory. As part of the clinical trial, Blackard will work closely with clinicians and health professionals to enroll 25 patients annually over the grant period who come to UC Medical Center’s emergency room as a result of drug overdose. When patients presenting with opioid-related overdose are seen by an emergency physician, blood is drawn to determine what substance is present in their bodies. Many of these individuals may already know their HIV status, while others may require additional testing for HIV, explains Blackard. Blackard says the observational study focuses on individuals with HIV so he is looking for patients who are HIV positive and battling addiction. “What we will do is measure their viral load; it is the measure of how much virus is in the body. It also tells us how well HIV treatments are working and provides important information about disease progression,” he explains. “There are a whole bunch of markers of HIV disease we can measure. What is it doing to the cells that are infected in the first place? We know that people with opioid use disorders relapse quite frequently. We know that people who are relapsing may not adhere to their HIV medications or they may chose not to take them or they may not work,” says Blackard. “So, we have to take this relatively holistic approach to saying, you know what we probably need is new medications or additional medications to treat opioid use disorder in the context of HIV or some other chronic infection because these two things are synergetic, but they are helping each other along in a bad way.” Ex vivo experiments also yield important information for the research study, says Blackard. “In my lab we grow HIV, Hepatitis C, Hepatitis B and we take something we grow in a petri dish and add it to blood sample that we took from a patient,” says Blackard. “We do the same measure of replication; how well does HIV grow in the presence of an opioid? “It helps us determine what medications we should use or how we intervene,” says Blackard. “If we know the drugs of abuse promote HIV replication then maybe we need to have a discussion about pre-exposure prophylaxis.” Pre-exposure prophylaxis (PrEP) involves using antiviral drugs in people not yet exposed to HIV/AIDS to prevent infection. PrEP is sometimes offered to subpopulations deemed at high risk of HIV infection. “Maybe we need to look at what specific combinations of drugs work the best for reducing HIV replication for people that are injecting versus those that don’t,” says Blackard. “Perhaps a certain recognition there are certain types of drugs that may not be appropriate for injection drug users, but they might be appropriate for other subpopulations at risk for HIV.” “At the end of the day, we are really limited in what we have to treat substance abuse in people that have something else,” says Blackard. “Even though we talk about how we treat the HIV, which we do reasonably well, we do a poor job of also treating the substance abuse.” This research was supported by National Institutes of Health NIDA grant 1R61DA048439-01. UC researcher examines impact opioids and HIV have on each other Full Story

UC Hosts 8th Annual Internal Medicine Research Symposium

The University of Cincinnati (UC) Department of Internal Medicine in the College of Medicine hosted its eighth annual research symposium Friday, April 5, 2019, in the CARE/Crawley Atrium. Trainees submitted 38 posters and each trainee had an identified mentor. The theme for the event was “Building and Fostering Research for Discovery, Innovation and Impact.” “This year’s symposium attracted overwhelming support from faculty and staff,” explains Gregory Rouan, MD, chair of the Department of Internal Medicine. “Forty-five faculty volunteered to judge trainee research posters while staff submitted seven posters in the basic and clinical research categories. Our keynote speaker offered a thought-provoking address that was well attended.” Rouan also offered thanks to all symposium participants and attendees and to Carl Fichtenbaum, MD, associate chair for translational research, and Sakthivel Sadayappan, PhD, associate chair for basic research, both in the Department of Internal Medicine, for their roles in organizing the event. The keynote speaker was Robert Siliciano, MD, PhD, professor of medicine at John Hopkins Medicine in Baltimore, Maryland. Siliciano’s address was titled “Curing HIV Infection: Going Beyond N=1.” The Department of Internal Medicine has long served as an incubator for discovery and scientific advancement at the university and comprises nine divisions with more than 280 faculty as clinicians, scientists and investigators. The department is responsible for $86.9 million in research funding, including $10.3 million in new awards during the 2018 fiscal year. Winning presentations in the basic research, clinical research and clinical case report categories for the poster competition during the symposium are listed below: Trainee Basic Research Poster Awards: 1st place tie - $500 award given Name and Division: Hannah M Russell, Division of Cardiovascular Health and Disease Mentor: A. Phillip Owens, III, PhD Poster Title: Fibrinogen Depletion Attenuates Angiotensin II-induced Abdominal Aortic Aneurysm 1st place tie - $500 award given Name and Division: Mohit Kumar, PhD, Department of Pharmacology and System Physiology Mentor: Sakthivel Sadayappan, PhD Poster Title: Cardiac myosin binding protein c phosphorylation regulates calcium homeostasis Honorable Mention Award - $150 award given Name and Division: Yiyang Lu, Department of Pathobiology and Molecular Medicine Mentor: Jane Yu, PhD Poster Title: Rapamycin associated pro-survival pathways that contribute to treatment refractory in Tuberous sclerosis complex (TSC) Trainee Clinical Research Poster Awards: 1st place - $500 award given Name and Division: Masaaki Yamada, MD, Division of Nephrology, Kidney C.A.R.E. Program Mentor: Charuhas V. Thakar, MD Poster Title: Incidence and Consequence of Hyperkalemia in Solid Organ Transplant: An analysis of over 14,000 organ transplant recipients 2nd place - $250 award given Name and Division: Nicole Wilson, PharmD, Division of Nephrology, Kidney C.A.R.E. Program Mentor: Rita Alloway, PharmD Poster Title: Early And Late Borderline Lesions Exhibit Differential Outcomes In Renal Transplant Recipients Honorable Mention Award - $150 award given Winner: Malik Khurram Khan, MD, Pulmonary, Critical Care and Sleep Medicine Mentor: Muhammad Ahsan Zafar, MD, MS-CTR Poster Title: Reducing Delirium in the Medical ICU - Implementation of a sleep hygiene bundle and standardizing sedation in the Medical ICU Trainee Clinical Case Report Poster Awards: 1st place - $500 award given Winner: Yufei Dai, MD, Division of Endocrinology, Diabetes and Metabolism Mentor: Robert Cohen, MD Poster Title: Prolonged glycosuria after Canagliflozin discontinuation in a patient with euglycemic diabetic ketoacidosis 2nd place - $250 award given Winner: Yazan Vwich, MD and Andrew Welch, DO, Division of Endocrinology, Diabetes and Metabolism Mentor: Abid Yaqub, MD Poster Title: Subclinical Cushing's Syndrome with Bilateral Adrenal Adenomas in MEN1 Honorable Mention Award - $150 award given Winner: Jillian Thompson, DO, Cardiovascular Health and Disease Mentor: Tehmina Naz, MD Poster Title: A Case of Isolated Cardiac Sarcoidosis 2019 Research Symposium Poster Competition Awardees: Staff Staff Awards: 1st place - $150 award given Winner: Caterina Bartolacci, PhD, Division of Hematology Oncology Mentor/PI: Pier Paolo Scaglioni, MD Poster Title: FASN as a novel Therapeutic Target in Mutant KRAS Lung Cancer 2nd place - $100 award given Winner: Begoña Campos-Naciff, PhD, Nephrology, Kidney C.A.R.E. Program Mentor/PI: Charuhas Thakar, MD Poster Title: Kidney injury under oxidative stress release CD36 and CD47 microparticles Honorable Mention Award - $50 award given Winner: Ameet Chimote, PhD, Division of Nephrology, Kidney C.A.R.E. Program Mentor/PI: Laura Conforti, PhD Poster Title: Failure to upregulate calmodulin underlies the suppressed KCa3.1 function and enhanced sensitivity to adenosine in CD8+ T cells of head and neck cancer patients 2019 Research Symposium Image Gallery Awardees Basic Research Images: 1st place - $100 award given Winner: Kristen Engevik, Department of Pharmacology and Systems Physiology Image Title: Mouse Gastric Glands 2nd place - $50 award given Winner: Andrew Dunn, PhD, Division of Digestive Diseases Image Title: A Hole New World Clinical Research Images: 1st place - $100 award given Winner: Humna Abid Memon, MD, Division of Pulmonary Critical Care Medicine Image Title: Piercing of the Aorta 2nd place - $50 award given Winner: Ameet Chimote, PhD, Division of Nephrology, Kidney CARE Program Image Title: The Soldiers of the Immune System Images in Medicine: 1st place - $100 award given Name and Department/Division: Ameet Chimote, PhD, Division of Nephrology, Kidney CARE Program Image Title: Reflections 2nd place - $50 award given Name and Department/Division: Eric P. Smith, MD, Academic Research Services Image Title: On top of old twister People’s Choice: Name and Department/Division: Ameet Chimote, PhD, Division of Nephrology, Kidney CARE Program Image Title: Fiery Sunset UC Hosts 8th Annual Internal Medicine Research Symposium Full Story

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CARE/Crawley atrium

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