All posts by Toni Baker

Rawson selected to design, lead new Commission on Patient Experience for American College of Radiology

Dr. James V. Rawson, chairman of the Department of Radiology and Imaging at the Medical College of Georgia at Georgia Regents University, will design and lead a new Commission on the Patient Experience for the American College of Radiology.

Rawson, who also holds the P.L., J. Luther, Ada Warren Chair of Radiology at MCG, was recently elected to a three-year term on the 33-member Board of Chancellors of the American College of Radiology.

He has lectured and consulted nationally on bringing the patient centered focus to radiology. Leading this new commission, he will help his big machinery, high-tech specialty shift its focus even more toward patients.

“We have to put the patient in the center of health care,” said Rawson, an advocate for doing just that during his 15-year tenure as MCG’s Radiology chairman. “Everything has to be about the patient,” from how appointments are scheduled to parking to care delivery to timely receipt of study results, he said.

Rawson had sick family members throughout his medical school years at Tufts University in Boston and while completing a diagnostic radiology residency at New York Medical College, and a Body Magnetic Resonance Imaging Fellowship at Mallinckrodt Institute of Radiology at Washington University. He believes those experiences made him a better doctor and encouraged him early on to build care around the patient.

“I never was very far from the experiences patients and families were having in health systems because I was always on both sides of the table,” said Rawson. He serves on the Patient Experience Operations Committee of Georgia Regents Medical Center and works closely with the GRHealth Center for Patient and Family Centered Care to ensure patient advisors are involved in every facility and service decision made in radiology, from the patient-friendly Breast Health Center to extensive changes still underway in the Children’s Hospital of Georgia.

“The challenge was and is to think about how you can improve a child’s experience coming to a strange place that is potentially scary,” Rawson said of changes being made at the children’s hospital that will include color, lighting, and child-friendly technology. Even large imaging machines, such as MRIs, for adults already have lighted overhead boxes with soothing scenes for patients to focus on as they prepare for their exam. Adult waiting rooms also now have the look and feel of a coffee shop. Review of patient satisfaction surveys are part of regular radiology faculty meetings.

Mounting evidence indicates that a patient and family focus also yields shorter hospital stays and better outcomes; in fact, hospital reimbursement from federal health insurance programs are now tied to patient satisfaction. “Patient satisfaction surveys are part of the culture of medicine now,” said Rawson, who is excited and honored to help further incorporate this approach into his chosen specialty. He plans to populate the new American College of Radiology commission with a strong cross section of radiologists, related administrators, as well as patients with experience and/or interest in enhancing the philosophy and practice.

Rawson’s other leadership roles with the American College of Radiology include serving as Chair of the Committee on Governmental and Regulatory Issues in Academic Radiology, and the Committee on Economic Issues in Academic Radiology. He is on the editorial board of the Journal of the American College of Radiology and just completed an 11-year term as Chair of Hospital Outpatient Prospective Payment System/Ambulatory Payment Categories for the college.

High blood levels of growth factor correlate with smaller brain areas in patients with schizophrenia

High blood levels of a growth factor known to enable new blood vessel development and brain cell protection correlate with a smaller size of brain areas key to complex thought, emotion and behavior in patients with schizophrenia, researchers report in the journal Molecular Psychiatry.

Higher blood levels of vascular endothelial growth factor, or VEGF, also correlate with high blood levels of interleukin 6, a cytokine that can cross the protective blood-brain barrier and typically promotes inflammation, said Dr. Anilkumar Pillai, neuroscientist in the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Georgia Regents University. As with many disease types, inflammation is increasingly associated with schizophrenia, and high blood levels of IL-6 already have been found in these patients.

The new findings appear to point toward a blood test as an easier way to confirm the diagnosis of schizophrenia, rather than complicated and expensive imaging studies of the brain, and, ultimately, better disease understanding and treatment, said Pillai, the study’s corresponding author. “We are talking about a molecule where you can just draw blood and look at the lab profile,” he said.

A smaller prefrontal cortex is one of the brain abnormalities identified through brain scans of living patients as well as autopsies. Pillai’s lab had earlier shown low brain levels of VEGF, which could help explain lower blood flow and brain volumes in these patients. “Decreased blood flow leads to decreased brain tissue volume,” he said. Inflammation also can reduce brain size.

While findings of higher blood levels may sound counterintuitive to low VEGF levels in the brain, they likely indicate a “feedback inhibition” with the brain recognizing high circulating levels and deciding to produce less VEGF itself, Pillai said. In fact, high blood levels of VEGF may contribute to the disease process, the researchers write.

More patients need to be studied to see if the correlations hold up, Pillai said, and work also is needed to determine which comes first: high blood levels or low brain levels of VEGF.

The study, in collaboration with scientists at the School of Psychiatry at the University of New South Wales in Australia, looked at 96 people with schizophrenia as well as 83 healthy individuals. Brain scans were available on 59 of the patients and 65 healthy controls. Patients were recruited to Neuroscience Research Australia, a not-for-profit research institution based in Sydney that focuses on the brain and nervous system, as well as Lyell McEwin Hospital, a teaching hospital in South Australia affiliated with the University of Adelaide and the University of South Australia.

While likely best known for its role in making new blood vessels, VEGF also is key to the brain’s ability to adapt to change, such as respond to an injury, and protect against brain cell loss.

Kidney, bladder stones do not increase postmenopausal women’s risk of osteoporosis

Postmenopausal women with kidney or bladder stones are not at increased risk for osteoporosis, but they do have about a 15 percent increased risk of another painful stone, physician-scientists report.

Researchers looked at data on approximately 150,000 postmenopausal women and found, despite the two conditions being clearly associated in men, the same did not hold true for women, said Dr. Laura D. Carbone, chief of the Section of Rheumatology at the Medical College of Georgia at Georgia Regents University.

“We know in men that if you have a kidney stone, you are more likely to have osteoporosis,” said Carbone, corresponding author of the study in the Journal of Bone and Mineral Research. “We were trying to find out if that is also the case for women. We found that, unlike what has been reported in men, a woman having a kidney stone is not a risk factor for osteoporosis. However, having one urinary tract stone does put women at increased risk for a second stone.”

“We wanted women and their physicians to have this information,” said Dr. Monique Bethel, a research resident in the MCG Department of Medicine and study co-author. “If the two relate, and a patient who has not been screened for osteoporosis comes to the office with a kidney stone, her physician might have been concerned she also has a higher risk for osteoporosis. Our studies indicate she likely does not.”

However, women with a stone likely should work with their physician to reduce their increased risk of a subsequent stone, the physicians said, noting that low water/fluid intake and a high-salt, high-calorie diet are common stone risks. Having a stone also was known to put people at risk for subsequent stones, but the new study helps clarify the risk, Carbone said.

Their data came from participants in the National Institutes of Health Women’s Health Initiative, a major study to address common health problems, such as osteoporosis and cancer, in postmenopausal women. Out of more than 150,000 women followed in the WHI, 9,856 women reported urinary tract stones at the start of or over the course of the study. They were followed about eight years, on average. MCG researchers believe theirs is the largest, most comprehensive study of the association of the two conditions in postmenopausal women. They looked at the data several different ways, adjusting for factors that could also influence outcome, such as physical inactivity, a known risk factor for both osteoporosis and kidney stones. They only looked at whether urinary tract stones increased the risk of osteoporosis, not the reverse.

The incidence of urinary tract stones is on the rise generally, particularly in women, with a 70 percent increase in the last 15 years. Osteoporosis already affects about 1 in 3 postmenopausal women and 1 in 5 older men, although the incidence of hip fractures is trending downward, Bethel said.

The Osteoporotic Fractures in Men, or MrOS, study, which looked at nearly 6,000 men with a mean age of 73.7 to determine risk factors for osteoporosis, identified urinary tract stones are a risk factor.

One link between the seemingly disparate conditions of stones and weak bones is an excess of calcium in the urine, which tends to be more common in men, Carbone said. Sodium and calcium share a common transport mechanism at the kidney, and sodium affects reabsorption of calcium by that organ. When sodium levels are high, from eating too much processed or fast food, for example, more calcium is eliminated in the urine. Also, overactivity of the parathyroid glands, which regulate levels of calcium in the blood, is associated with both urinary tract stones and fractures of the vertebra in the spine, a sign of the typically silent osteoporosis.

Interestingly some treatments for osteoporosis, including calcium supplements, can increase the risk of stones. Conversely, individuals who’ve already experienced a urinary tract stone might avoid calcium to help avoid a subsequent stone and inadvertently increase their osteoporosis risk, the researchers write.

Higher vitamin D doses may be needed to restore healthy levels in overweight blacks

The current recommended minimum daily dose of vitamin D is not sufficient to restore healthy vitamin D levels in overweight or obese blacks, researchers report.

Rather, daily intake of more than three times the recommended minimum is needed to restore what is generally considered a healthy blood level of vitamin D, said Dr. Yanbin Dong, geneticist and cardiologist at the Georgia Prevention Institute at the Medical College of Georgia at Georgia Regents University.

Overweight blacks are at increased risk for vitamin D deficiency because darker skin absorbs less sunlight – the skin makes vitamin D in response to sun exposure – and fat tends to sequester vitamin D for no apparent purpose.

The study, published in the journal BioMed Central Obesity, looked at the effects of three levels of vitamin D supplementation in 70 overweight-to-obese blacks under age 50 living in the Southeastern United States who appeared healthy, although their circulating level of vitamin D was considered low.

The Institute of Medicine recommends a daily intake of 600 international units of vitamin D for most children and adults; 800 IUs for those age 70 and older. For adolescents and adults, they recommend 4,000 IUs as the upper daily limit; 2,000 was the previous upper limit.

In what appears to be the first randomized controlled study in this cohort, researchers found that 600 IUs did not restore what many experts consider the optimal blood level of vitamin D within 16 weeks.

However, both 2,000 and 4,000 IUs restored the desirable levels of 30 nanograms per milliliter to individuals with previous levels of less than 20 ng/mL, levels which put them at high risk for bone-weakening rickets and potentially other maladies.

The 4,000 upper-limit dose restored the healthy blood level quicker – by eight weeks – and was also better at suppressing parathyroid hormone, which works against vitamin D’s efforts to improve bone health by absorbing calcium, said Dong, the study’s corresponding author.

“We hope these studies will give physicians better guidelines for some of their patients,” said Dong.  “As with many therapies in medicine today, evidence is emerging that a more personalized approach is likely the best approach when determining how much vitamin D is optimal for an individual. Dose definitely matters.”

As an example, participants in the group he studied who had high parathyroid hormone levels likely should take 4,000 IUs daily while the remainder appear to achieve desired results with 2,000 IUs.

Although long known as a way to build strong bones and teeth, there is increasing evidence of vitamin D’s role in the cardiovascular and immune systems, kidneys, mental health, and more. It’s likely, as with high parathyroid hormone levels, patients at high risk for cardiovascular disease might benefit from higher doses, said Dong, noting that much work is needed to identify optimal dosing for specific conditions.

Although wide ranges of daily doses already have been studied and there are no known serious side effects, there is no point in people taking more than they should, even if it’s only to save money, Dong said. Also, correlations are emerging –  but no hard science yet – that at too-high doses, for example, vitamin D can go from being a cancer preventer to a cause, he said.

For the study, researchers gave all doses of vitamin D monthly rather than daily to help ensure that all participants were getting the correct doses. Giving this once-monthly version of even the maximum recommended daily dose was equivalent to spending an afternoon at the beach in a bathing suit, Dong said.

Dr. Jigar Bhagatwala, a research resident in the MCG Department of Medicine, is the study’s first author.  The research was funded by the National Institutes of Health and the American Heart Association.

Rawson elected to American College of Radiology leadership

Dr. James V. Rawson, Chairman of the Department of Radiology and Imaging at the Medical College of Georgia at Georgia Regents University, has been elected to a three-year term on the 33-member Board of Chancellors of the American College of Radiology.

Rawson, who holds the P.L., J. Luther, Ada Warren Endowed Chair of Radiology at MCG, also was recently named President of the Georgia Radiological Society, the Georgia chapter of the national group.

His leadership roles with the American College of Radiology include serving as Chair of the Committee on Governmental and Regulatory Issues in Academic Radiology, the Committee on Economic Issues in Academic Radiology, and the Committee on Hospital Outpatient Prospective Payment System and Ambulatory Patient Classification.

He is on the editorial board of the Journal of the American College of Radiology and just completed an 11-year term as Chair of Hospital Outpatient Prospective Payment System/Ambulatory Payment Categories for the college.

Rawson has served on the Georgia Radiological Society’s Executive Committee since 1999.  His other national leadership roles in radiology include serving on the Association of University Radiologists Board of Directors, as a Councilor for the Board of the Society of Chairs of Academic Radiology Departments, and a one-year term on the Society of Health Systems Content and Connections Committee.

Lokeshwar named Chairwoman of MCG Department of Biochemistry and Molecular Biology

VinataLokeshwarwebDr. Vinata B. Lokeshwar, Professor and Co-Director of Urology Research in the Departments of Urology and Cell Biology at the University of Miami-Miller School of Medicine, is the new Chairwoman of the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Georgia Regents University.

Lokeshwar also is one of two Directors of the Pilot and Collaborative Translational and Clinical Studies component of the Miami Clinical And Translational Science Institute, one of 61 translational centers in the nation funded by the National Institutes of Health’s National Center for Advancing Translational Sciences.

The cancer researcher, who studies the metastasis of prostate, bladder, and kidney cancer with the goal of better diagnosis and treatment, assumes her new duties at MCG in September.

“We are very pleased that Dr. Lokeshwar, an accomplished scientist, educator, and leader, will be joining the MCG team,” said Dr. Peter F. Buckley, Dean of the state’s public medical school; Interim Executive Vice President for Health Affairs, Georgia Regents University; and Interim CEO, Georgia Regents Medical Center & Medical Associates.

“One of her many great strengths is that she is strongly committed to the tenet that great science, great education, really any great accomplishments require a great team and hard work and that the best leaders are ones who nurture and practice both. Her scientific expertise also is a terrific addition to our collaborative efforts to grow cancer research in our state where the cancer incidence exceeds the national rate and to our already strong urology program. Those attributes and many more make her a great fit for our medical school,” Buckley said.

The Dean thanked Dr. Shuang Huang for his service as interim Chair and Drs. Clinton Webb and Nita Maihle for co-chairing the national search.

Lokeshwar’s research has had continuous external funding for 18 years. She is currently Principal Investigator on three National Institutes of Health grants as well as two additional grants from the Women’s Cancer Association of the University of Miami to help develop a urine test for bladder cancer and pursue early diagnosis and new treatment for kidney cancer.

She is a past President of the Society for Basic Urologic Research; an ad hoc member of the Research Advocacy and NIH Relations workgroup of the American Urological Association Office of Research; and recently chaired the Bladder Cancer – Basic Research Session at the American Urological Association Annual Meeting two years in a row.

She is Senior Editor of the textbook, “Bladder Tumors: Molecular Aspects and Clinical Management,” Associate Editor of the journal Bladder, Consulting Editor of the journal Urologic Oncology, and a member of the editorial board of World Journal of Urology and Bladder Cancer.

She has mentored more than 30 graduate students, residents, fellows, and junior faculty. Recent educational honors include the 2015 Sylvester Comprehensive Cancer Center Outstanding Mentor of the Year for Trainees. Urology residents at the Miller School of Medicine honored her with the 2011 Urology Teacher of the Year Award, and the American Urological Association honored her as a Female Leader in Urology that same year.

Lokeshwar earned a PhD from St. Louis University in Missouri and completed postdoctoral studies in the Department of Cell Biology and Anatomy at the University of Miami Miller School of Medicine. During her postdoctoral work, she completed American Heart Association and National Cancer Institute fellowships. She joined the university’s faculty in 1994.

When inflammation occurs, kidneys work to protect themselves, researchers find

In an apparent effort to help themselves, inflamed kidney cells produce one of the same inflammation-suppressing enzymes fetuses use to survive, researchers report.

Inflammation is a major culprit in most kidney disease – from rare conditions, such as Goodpasture syndrome, where the immune system starts producing antibodies against kidney collagen to an infection with hepatitis C to the slow, persistent pounding of hypertension, said Dr. Tracy L. McGaha, immunologist in the Department of Medicine at the Medical College of Georgia at Georgia Regents University.

Prolonged inflammation can reduce or eliminate the kidneys’ ability to daily filter 150-180 liters of blood and enable resorption of most of that valuable volume, said Dr. Michael P. Madaio, nephrologist and MCG Medicine Department Chairman. Lost function means dialysis or a transplant.

In an animal model of inflammatory kidney disease, the researchers found kidney cells respond to potentially destructive inflammation by producing the enzyme indoleamine 2,3-dioxygenase, or IDO. IDO’s appearance sets in motion a chain of events that can eliminate the damaged protein produced during inflammation, allowing cells to better recover, said McGaha, corresponding author of the study featured on the cover of the Journal of Immunology.

They also found evidence of the same protective scenario in kidney tissue from humans with a variety of inflammation-related conditions.

When MCG researchers blocked IDO in an animal model then gave a fatal dose of an antibody to collagen found only in the kidney, it accelerated the already-rapid process whereby the normal structure of the kidney is replaced with dysfunctional scar tissue, suggesting IDO is part of the body’s natural protection against inflammation. “When the kidney cells couldn’t make IDO, the inflammation that was induced by the antibody caused those kidney cells to die,” McGaha said.

Even when they gave just enough antibody to induce mild inflammation in mice lacking IDO, it instead resulted in rapidly progressive and deadly kidney destruction. “If you inhibit the mechanism, the disease is worse,” McGaha said.

Once they saw IDO’s natural protective role in the kidney, they looked and found it was coming from the podocytes, a type of kidney cell with foot-like appendages that literally wrap around the capillaries of the filtering units, enabling the kidney to recirculate needed substances, such as sodium and protein, and excrete toxins in the urine that can cause damage. In humans and animal models alike, loss of podocytes, which have a limited ability to replicate, is directly linked to the kidneys’ lost ability to filter.

McGaha likens podocytes to gatekeepersn and when filtering fails, high levels of substances such as protein start showing up in the urine, which is why protein levels are one of the things measured in a urinalysis, Madaio said.

However, it wasn’t known that the kidney cells were providing another layer of protection by making IDO. The scenario goes something like this: podocytes make IDO, which consumes tryptophan, an amino acid that is essential for metabolism. Another enzyme, GCN2, is activated by the dearth of amino acids, initiating a stress response in the now-hungry kidney cells, which induces another natural cell process called autophagy.

While part of what autophagy does is enable the cell to consume itself, the goal is actually to enable the cell to survive and/or replicate. Autophagy slows production of the damaged protein made by the inflamed cells and eats up the damaged protein already made, McGaha said. If it’s early enough in the process, autophagy essentially clears out the damage, and the kidney cells recover. If autophagy goes on too long, because inflammation goes on too long, it triggers another natural cell process, called apoptosis, or cell suicide. It was already known that disrupting autophagy in mice leads to chronic, progressive kidney disease.

The researchers found that activation of the IDO-GCN2 pathway was essential to ensuring autophagy.

“The process of autophagy didn’t happen in the podocytes without those two,” McGaha said. “The podocytes went ahead and died.”

When they looked at kidney tissue from humans with a wide range of kidney disease, they also found levels of IDO and stress genes were way above baseline for healthy individuals, Madaio said, further indicating that the IDO-GCN2 pathway is functional in many types of kidney disease and identifying it as a potential new treatment target.

Early evidence suggests it may be a good one. When they gave DNA nanoparticles known to induce IDO, they found healthy mice kidneys produced IDO. When they gave mice a lethal dose of the collagen-injuring antibodies and the DNA nanoparticles at the same time, the IDO-GCN2 pathway was protective.  The researchers also directly activated GCN2, and that worked as well, reinforcing the theory that it takes the enzyme pair to provide protection.

“What we are realizing is that most diseases have common pathways to either inflammation, fibrosis, or recovery,” said Madaio, a study coauthor. “What Dr. McGaha is doing is discovering those pathways or identifying new pathways in inflammation and protection.”

Next steps include learning more about how autophagy protects podocytes. Researchers also want to confirm their observation that activation of the IDO-GCN2 pathway is common in kidney inflammation.

The research was funded by the National Institutes of Health. Longtime MCG research colleagues, Drs. David Munn and Andrew Mellor, reported in 1998 that the fetus expresses IDO as a way to protect itself from being targeted by the mother’s immune response. Later studies found tumors use it as well.  Mellor, an immunologist, developed the nanoparticles used in the new studies.

Buckley receives international recognition as a top achiever in life sciences

Dr. Peter F. Buckley, Dean of the Medical College of Georgia at Georgia Regents University, Interim Executive Vice President for Health Affairs at GRU, and Interim CEO, Georgia Regents Medical Center & Medical Associates, is among Irish America magazine’s 2015 list of the best and brightest Irish-American and Irish-born trailblazers in the life sciences.

The 30-year-old magazine covers political, economic, social, and cultural matters of interest to Irishmen living in the United States. This annual issue focuses on the top 50 leaders in the fields of medical care, pharmaceuticals and biotechnology, medical devices, research and development, as well as life sciences venture capital. The August/September issue of the magazine will be out next month and an award reception will be held in October in Manhattan.

Buckley, who became the 26th Dean of Georgia’s public medical school in 2011, was born in Dublin, emigrated to the U.S. in 1992, and maintains dual citizenship. The son of two physicians earned his medical degree from the University College Dublin School of Medicine in 1986, and completed a psychiatry residency and research fellowship at St. John of God Psychiatric Services.

He came to the U.S. to serve as Clinical Director of the Psychobiology Evaluation and Treatment Programs at University Hospitals of Cleveland and Assistant Professor at Case Western Reserve University. Buckley became Medical Director of Western Reserve Psychiatric Hospital in 1994; Medical Director and Vice President for Clinical Affairs at Ohio’s Northcoast Behavioral Healthcare System, which included three inpatient facilities, in 1995; Associate Professor of Psychiatry at Case Western in 1996; Vice Chairman for State Services at Case Western’s Department of Psychiatry in 1999; and Professor at Case Western in 2000.

Buckley came to MCG in 2000 as Chairman of the Department of Psychiatry and Health Behavior, was named the inaugural Associate Dean for Leadership Development of the medical school in 2007, Senior Associate Dean for Leadership Development in 2010, and Interim Dean later that same year. He assumed interim leadership over GRU health affairs in 2014.

His international leadership roles include serving on the Administrative Board of the Council of Deans of the Association of the American Medical Colleges and as Chair of the Council’s Fellowship Committee.  Earlier this month, he chaired the National Institute of Mental Health Special Emphasis Panel on Early Psychosis Intervention and he has been a member of the institute’s Data and Safety Monitoring Board Committee since 2006. Buckley also is a member of the Psychiatry Maintenance of Certification Committee of the American Board of Psychiatry and Neurology and the American Psychiatric Association Committee on Research Awards and Membership Committee. He recently served on the association’s Workgroup on the Role of Psychiatry in Healthcare Reform, and he co-chairs the Georgia Mental Health and Physical Integrations Task Force for the Atlanta-based Carter Center. Buckley is a Past President of the Pan American Division of the Royal College of Psychiatrists and is immediate Past President of the Richmond County Medical Society.

Buckley, an expert in schizophrenia, is a member of the Executive Committee of the International Congress on Schizophrenia, which is planning the future of the premier global schizophrenia research conference. He is also a member of the Election Committee of the Schizophrenia International Research Society. Buckley, along with Dr. David J. Castle, Chairman of Psychiatry at Australia’s St. Vincent’s Health and The University of Melbourne, recently co-edited the second edition of a reference book for mental health professionals on schizophrenia. He also is editor of a similar, new reference textbook on the intersection of mental and physical health and is editor/author of 15 other books. He continues an active, federally funded research program with national, multicenter collaborations.

This year he received the inaugural Spirit of MCG Award for Excellence in Leadership from the MCG Faculty Senate. The American Psychiatric Association honored him with the Kempf Fund Award for Psychobiological Research and Mentorship in Schizophrenia in 2014 and the Presidential Commendation for Leadership Accomplishments in 2013.

Linder named Chairman of MCG Department of Pediatrics

16596700910_a489b6b37f_zDr. Charles W. Linder, a 1963 graduate of the Medical College of Georgia at Georgia Regents University who directed the Division of General Pediatrics and Adolescent Medicine for nearly 30 years, has been named Chairman of the MCG Department of Pediatrics.

Linder has served as Interim Chairman and Pediatrician-in-Chief of the Children’s Hospital of Georgia since last June. He will continue to serve as the top medical officer for the children’s hospital.

“Dr. Linder is an exceptional individual and leader with an absolute commitment to the well-being of children and his medical school,” said Dr. Peter F. Buckley, MCG Dean, GRU Interim Executive Vice President for Health Affairs, and Interim CEO, Georgia Regents Medical Center & Medical Associates.

“He has never truly ‘retired,’ rather has continued to contribute to his alma mater by serving as a volunteer faculty member,” Buckley said. “When asked to serve as Interim Chairman last summer, Dr. Linder stepped up again, and watching the department rally around his leadership has been most impressive. Now, his extensive knowledge, experience, and commitment will continue to drive the betterment of our pediatrics department and our children’s hospital.”

Linder was named Director of the Division of General Pediatrics and Adolescent Medicine in 1972, Professor in 1981, Associate Dean of Medicine in 1985, and Associate Dean Emeritus in 2001. He has served as an Assistant Hospital Administrator, Chief of Staff, and Chief Medical Officer for the university’s teaching hospitals. He served on the MCG Admissions Committee for seven years.

His memberships include the Child Health Finance Committee of the Georgia Chapter of the American Academy of Pediatrics and the Provisional Committee on Development of the American Academy of Pediatrics. He is a past President of the Georgia Chapter of the Academy and recipient of the chapter’s Lifetime Achievement Award. Linder has served in numerous leadership roles in the American Academy of Pediatrics, including a six-year term on the Board of Directors and Chairman of the Southeastern District.

Linder helped bring the Ronald McDonald House to Augusta in the early 1980s. The Charles W. Linder MD Endowed Chair in Pediatrics was established in his honor in 2009.

He completed a pediatrics residency at Fitzsimmons Army Hospital (now Fitzsimmons Army Medical Center) and Colorado General Hospital in Denver and a pediatric allergy and respiratory disease fellowship at MCG. He served as a major in the U.S. Army Medical Corps before joining the faculty of the MCG Department of Pediatrics. Linder’s clinical specialties include primary care and prevention and fluid and electrolyte therapy in children.

Mouse with weaker bones, stronger metabolism points toward new diabetes therapies

One mouse with weak bones appears to have a strong metabolism, even on a high-fat diet, scientists report.

While weaker bones are clearly not a good thing, scientists suspect that, somewhere in the conversation between the genetically engineered mouse’s skeleton and the rest of its body, there may be an answer that helps obese individuals avoid some of the worst ravages of this health epidemic.

“We know that bone is great for biomechanical motion; we know that it’s great at protecting internal organs; and we know that it’s great at serving as a bank for calcium,” said Dr. Meghan E. McGee-Lawrence.

“But within the last 10 years or so, people have really started to understand that there is more to the skeleton than that and, in fact, it has a really important endocrine role in the body as well,” said McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Georgia Regents University.

She calls bone’s metabolic impact a “new frontier” and its exploration important for getting a total picture of what bone does. Mounting evidence of its function as an endocrine organ also may point toward new ways to intervene in obesity-related type 2 diabetes.

“If we can understand, not only the role of fat and the pancreas, but the role the skeleton plays in this process, we can come up with new avenues for treatment,” said McGee-Lawrence, a corresponding author of the study in the journal Molecular and Cellular Endocrinology.

McGee-Lawrence’s bone studies had her looking at the molecule Hdac3, an important regulator of gene expression found throughout the body that can turn gene expression up or down. When her research team deleted Hdac3 specifically from the skeleton, they were not surprised to find the mice had weaker bones, but they were surprised to find the mice had major metabolic adjustments.

“We were not really sure what to make of the phenotype when we first saw it,” she said. The mice got more interesting as they looked further and found that although the knockout mice ate a normal amount of food compared to controls, they had less body fat and a low fasting-glucose level, an indicator that their body is using glucose, its key energy source, efficiently. The mice also are efficient users of insulin, a hormone produced by the pancreas that is essential to cells using glucose as energy.

One of the first signs of type 2 diabetes in mice and humans is reduced insulin sensitivity in the liver and their Hdac3 knockout’s liver was very sensitive to insulin.

They started with a logical suspect, osteocalcin, which is made by bone-making osteoblasts and is the most recognized bone-derived molecule known to affect insulin secretion and sensitivity. Their mice surprised them again because osteocalcin levels actually trended low in the Hdac3 knockout.

So they looked to the liver, which has a major role in digestion, managing metabolism, and storing energy reserves. “The knockout mice are making something that is good for their metabolic rate,” McGee-Lawrence said. “What’s coming from the bone and talking to these other organs?  If we can figure out what that molecule is, then that is your starting point for coming up with a new therapy,” McGee-Lawrence said.

They suspect part of the magic may be a molecule that helps the liver maintain healthy insulin sensitivity, and that molecule could be osteoprotegerin, or OPG. OPG is also made by osteoblasts to help decrease the amount of bone broken down in the skeleton. “It’s a good molecule,” she says, whose function in the skeleton is mimicked by the drug denosumab, one of the newer generation osteoporosis drugs.

The Hdac3 knockout mice have high levels of OPG, another surprise the mice provided scientists. Others have shown that, in addition to its role in the skeleton, OPG can travel in the blood to the liver where it reduces inflammation, and that reduced liver inflammation means improved insulin sensitivity, which made OPG a good suspect.

“Is this OPG molecule our missing piece of the puzzle to explain why the Hdac3 knockout with weak bones has a great metabolism?” she said of their ongoing studies. If the answer turns out to be “yes,” that could mean an existing drug has a new usage in directly addressing obesity’s high profile role as a leading cause of preventable diseases, including type 2 diabetes and the cardiovascular and other problems that typically follow.

McGee-Lawrence notes the irony that her knockout mice have weaker bones but higher levels of a molecule that aids bone strength. But these mice don’t have weaker bone because of higher resorption, which OPG addresses, rather they are not building enough bone, the other side of the healthy bone equation, she said.

The jury is still out on whether denosumab could affect metabolism; nothing has jumped out from retrospective analyses of osteoporosis patients taking the drug, but this question would have to be addressed in a specific patient population, such as individuals with pre-diabetes, McGee-Lawrence said.

The research was supported by the National Institutes of Health, The Minnesota Obesity Center, and the Mayo Clinic Center for Regenerative Medicine. Collaborators include Drs. Thomas A. White, Nathan K. LeBrasseur, and Jennifer J. Westendorf at the Mayo Clinic. McGee-Lawrence came to MCG from the Mayo Clinic in August 2014.