Among participants with optimum health, the risk of blood clots was 44 percent lower than those with inadequate health. Those with average health had a 38 percent lower risk.

Maintaining ideal levels of physical activity and body mass index were the most significant lifestyle changes related to lower risk of blood clots.

(This article is based on a news tip created by Darcy Spitz of the American Heart Association.)

Learn more about the IFFGD.

(This article was adapted from a news release produced by the International Foundation for Functional Gastrointestinal Disorders.)

The award is named in honor of the work of the late Roger R. Williams, M.D., who founded the division of cardiovascular genetics at the University of Utah School of Medicine and was a pioneer in the field of the genetics of inherited lipid disorders and the prevention of atherosclerosis.

To be eligible for this award, a candidate must be a member of the AHA, the first and presenting author of the abstract, and their work may not have been previously presented or published in any form. The winning abstract is the one achieving the highest average score of all applicants who submit abstracts to the category of genetic epidemiology. The Roger R. Williams Award recipient receives a cash prize of $1,500 and a plaque.

Olson’s winning abstract, titled “Common Single Nucleotide Polymorphisms in the Coagulation Factor XII Gene (F12) are Associated With Endogenous Thrombin Potential via In Situ Activation of the Intrinsic System of Coagulation: the Cardiovascular Health Study,” is coauthored by several UVM colleagues, including Tracy; Saulius Butenas, Ph.D., associate professor of biochemistry; Nancy Swords Jenny, Ph.D., associate professor of pathology; and Mary Cushman, M.D., M.Sc., professor of medicine. Olson and his colleagues’ work received support from a National Heart, Lung and Blood Institute (NHLBI) grant titled “Thrombosis Genetics, MI and Stroke in Older Adults,” led by Alex Reiner, M.D., M.Sc., at the University of Washington, of which Tracy is a co-investigator.

Olson and colleagues’ work utilized a recently developed laboratory test, called the endogenous thrombin potential (ETP) assay in samples from approximately 5,400 people participating in the Cardiovascular Health Study (CHS), an NIH-funded observational study of risk factors for cardiovascular disease in older adults. The ETP test measures the generation of thrombin, an enzyme critically important in blood coagulation. Increased generation of thrombin can result in blood clots, which are the hallmark of such diseases as venous thrombosis (clots in the deep veins of the leg or in the arteries of the lungs), heart attack, and stroke.

The researchers sought to understand the contributions of genetic factors to an individual’s capacity to generate thrombin. For their study, the group analyzed genetic variation, called single nucleotide polymorphisms (SNPs), with the goal of identifying variation in genes associated with variation in thrombin generation. Results from their work identified variation in one gene, the gene for Coagulation Factor XII (FXII), as being significantly associated with higher or lower thrombin generation, depending on which allele, or copy, of the gene participants carried.

“This was a particularly exciting finding because FXII is the initiating component of what is referred to as the contact, or intrinsic, pathway of blood coagulation,” says Olson. “This pathway has long been considered unimportant in blood clotting experiments in humans. Our results suggest a previously unsuspected importance of intrinsic pathway-dependent coagulation in vivo, and may have important implications in diseases such as arterial and venous thrombosis.”

According to Olson, the laboratory group is currently investigating the ETP assay for prediction of future cardiovascular disease events in the Cardiovascular Health Study, and examining the mechanism for how genetic variation in FXII affects thrombin generation, as well as other components of the coagulation system.

Olson received his Ph.D. from UVM in 2011 and was mentored by Albert van der Vliet, Ph.D., professor of pathology. He is currently supported by the NHLBI-funded Hemostasis and Thrombosis Training Grant directed by Kenneth Mann, Ph.D., professor emeritus of biochemistry.

The study appears in the March 2013 issue of The FASEB Journal.

In addition to kidney and cardiovascular damage, preeclampsia can lead to seizures (called eclampsia). According to Cipolla and her co-authors, neurological complications occur more often in EPE, in which delivery of the fetus occurs prior to 34 weeks of gestation and is viewed as more severe, than in late-onset preeclampsia (LPE). The only current “cure” for preeclampsia is delivery, which can be detrimental to the fetus if delivery is preterm.

Cipolla specializes in the blood-brain barrier (BBB) – a unique form of cells that line the many small blood vessels of the brain that is a selective barrier between the blood into the brain. She and former postdoctoral fellow Malou Schreurs, M.D., the first author on the study, were specifically interested in brain injury associated with preeclampsia and determining why this state could result in seizure.

To examine whether or not EPE plasma increases BBB permeability that could lead to seizure, the team used human blood plasma samples from normal pregnant, early-onset preeclamptic, and late-onset preeclamptic women to perfuse the cerebral vessels of nonpregnant rats.

While conducting this research, Schreurs described the EPE plasma as “gooey” to Cipolla, which provided the team with a clue to examine lipids, which are fats.

“Pregnancy is a physiologic state of hyperlipidemia,” says Cipolla. “When you add oxidative stress that occurs during preeclampsia, you get another form of low-density lipoprotein or oxidized LDL.” In the FASEB Journal article, she and her coauthors report that “BBB disruption in response to the EPE plasma was due to a 260 percent increase of circulating oxidized LDL binding to its receptor, LOX-1, and subsequent generation of peroxynitrite.”

Cipolla, who also has appointments in obstetrics, gynecology and reproductive sciences, as well as pharmacology, says the activation of LOX-1 is what causes the BBB permeability in response to high circulating oxLDL. In the future, she says, this process could be blocked at the early-onset stage, thus preventing an increase in permeability and the risk of seizure. Cipolla adds that having a biomarker for those at risk for brain injury could impact treatment and prevention options as well as delivery decisions in women with preeclampsia.

“Marilyn Cipolla’s identification of oxLDL as a diagnostic for the neurological form of preeclampsia has potential commercial uses as a diagnostic,” says Kerry Swift, M.S., technology licensing officer in the UVM Office of Technology Commercialization. “In addition, compounds that target LOX-1 could be potential therapeutics.”

In addition to Schreurs and Cipolla, coauthors on the study include Carl Hubel, Ph.D., and Arun Jeyabalan, M.D., of the Magee-Womens Research Institute at the University of Pittsburgh, and Ira Bernstein, M.D., professor and chair of obstetrics, gynecology and reproductive sciences at UVM.

Cipolla presented on the study’s findings at the Society for Gynecologic Investigation 2013 Annual Scientific Meeting March 20 to 23 in Orlando, Fla.

“Our project has had a major effect on what were once the most common skiing related injuries – fractures and sprains of the lower leg and ankle,” says Ettlinger, an engineer who has played a major role in the development of safety related equipment and training programs for ski areas and ski shops and the skiing public. “These injuries declined by 86 percent in the first 17 years of the study in response to improvements in ski equipment design and equipment service practices.”

According to Shealy, the team’s findings, published in numerous peer reviewed journals, became the scientific basis for U.S. and international standards down to the level of ski shop practices. To date, the reduction in the incidence of these lower leg injuries amounts to a savings of billions of dollars in medical expenses in the U.S. alone. 

“However, our greatest success,” Ettlinger points out, “ has been the determination that the risk of serious knee injury involving the ACL is not related to the release system.” Ettlinger runs Vermont Ski Safety, which provides safety related products and services to the snow sports industry.

He and the research team developed a free pamphlet – distributed online and at ski shops – titled “Tips for Knee-Friendly Skiing,” which is currently the only proven means to help skiers reduce the risk of ACL sprains. The video based research recorded a 55% reduction in the incidence of ACL injuries among ski area employees overall at 20 U.S. resorts, with a 75% reduction noted among ski patrollers.

The value of the team’s contributions has been recognized nationally and internationally, with dozens of interviews and articles in the lay media, including a recent Reuters News article and a December 2008 article in the New York Times.

Over the last 40 years the team, and their orthopaedics colleagues, have published more than 50 peer reviewed papers and books using data from the Sugarbush project.  Additionally, 16 volumes of the text Skiing Trauma and Safety (ASTM International), have been co-edited by Johnson, Shealy, and others since the 1980s. Johnson is the recipient of many honors, including the 2011 Distinguished American Award from the Vermont Chapter of the National Football Foundation, 2007 American Orthopaedic Society of Sports Medicine Hall of Fame, 2006 Hughston Award from the American Orthopaedic Society for Sports Medicine, and three O’Donoghue Research Awards from the American Orthopaedic Society for Sports Medicine (1983, 1996 and 2005).

The study appears in the March 15, 2013 issue of the Journal of Infectious Diseases.

Transmitted to humans by Aedes mosquitoes and prevalent in many tropical and subtropical regions of the world, dengue infection is caused by any of four related viruses: Dengue viruses (DENV) 1 through 4. Classically described dengue fever includes fever, headache, severe joint and muscle pain, and rash. Severe dengue infections, dengue hemorrhagic fever, and dengue shock syndrome include a higher risk of complications and death and are more commonly seen after a second infection with dengue viruses. The World Health Organization estimates that 500,000 patients, many of them children, are hospitalized every year with severe dengue-related disease.

Launched in July 2010 and led by principle investigators Beth Kirkpatrick, M.D., UVM associate professor of medicine, and Anna Durbin, M.D., of Johns Hopkins Bloomberg School of Public Health in Baltimore, Md., the Phase I clinical trial tested a single dose of each of four versions of the investigational dengue vaccine TetraVax-DV. The vaccine was developed by scientists in the National Institute of Allergy and Infectious Diseases’ Laboratory of Infectious Diseases. It is a live-attenuated vaccine, which means that the viruses it contains are weakened enough such that they do not cause illness, but still can induce an immune response. Each of the four vaccines tested included different mixtures of components designed to protect against all four dengue viruses.

The Phase I study was conducted in Baltimore, Md., Burlington, Vt., and Washington, D.C. The final study analysis included 112 healthy men and women ages 18 to 50 years who had not previously been exposed to dengue or related viruses such as West Nile virus and yellow fever virus.

Participants were randomized into four groups. In each group, 20 volunteers received a single 0.5-milliliter subcutaneous (under the skin) injection of one of the tetravalent candidate vaccine combinations, and eight others received placebo. All were monitored for immediate adverse reactions for at least 30 minutes after vaccination, and subsequently took their body temperatures three times daily for 16 days to check for possible adverse reactions. Participants also received a physical exam every other day up to Study Day 16, and then again on study days 21, 28, 42 and 180, when blood tests were also performed.

The researchers found that all four candidate vaccine combinations induced antibody responses against each of the dengue viruses. However, one vaccine combination, TV003, appeared to induce the most balanced antibody response against the dengue viruses. A single dose of TV003 resulted in an antibody response to all four dengue viruses in 45 percent of participants and against three of the four viruses in an additional 45 percent. Overall, an immune response to at least three viruses was seen in 90 percent of vaccinees given TV003.

Kristen Pierce, M.D., assistant professor of medicine and investigator at UVM, says that she and her collaborators found that a single dose of the NIH vaccine induced an immune response comparable to three doses of the leading candidate vaccine, which was developed by Sanofi Pasteur. Pierce adds that the trial had another plus – low production cost, and thereby, greater potential for better accessibility.

“The safety of the vaccine has now been clearly demonstrated after many vaccine trials at both UVM and Johns Hopkins,” says Pierce. “Over the last year, the focus has really been to determine which of the formulations, or combinations, of the four vaccines will provide vaccine recipients with the best antibody response to all four serotypes of dengue.”

Infection with one dengue virus results in immunity to that specific virus, but not to the other three. Research shows that the likelihood of severe disease increases when a person is subsequently infected with a different dengue virus. This observation suggests that the ideal dengue vaccine would be tetravalent – that is, protective against all four dengue viruses.

“What is promising about TV003 is that it elicited solid antibody responses after just one dose,” explained Stephen Whitehead, Ph.D., of NIAID’s Laboratory of Infectious Diseases, who led the development of the vaccine candidates. “Other vaccines in development require two or three injections at higher doses to achieve similar results.”

All four candidate tetravalent vaccines were found to be safe, and no participants experienced fever or dengue-like illness after vaccination.

“The results of this Phase I dengue vaccine study look very promising, and the NIAID is pursuing further development of TV003,” says Kirkpatrick., director of UVM’s Vaccine Testing Center. The NIAID, in conjunction with the site investigators, are conducting studies to further evaluate the vaccine's safety and ability to stimulate an immune response in healthy volunteers  and in people who have been infected previously by dengue or related viruses.

TV003's inexpensive production cost – less than $1 per dose – is critical to its potential use in developing countries, Kirkpatrick says. Manufacturers in Brazil, India and Vietnam – countries where dengue is prevalent – have licensed the vaccine technology for production and further evaluation. Phase II trials to evaluate the safety of TV003 and its capacity to create an immune response will begin soon in Brazil and Thailand.

To date, UVM Vaccine Testing Center researchers have tested the experimental vaccine on approximately 200 healthy volunteers.

“The next phase is to ensure that this antibody response will be adequate to provide protection against natural dengue infection, and whether a booster of the vaccine would provide better protection,” explains Pierce.

UVM’s Vaccine Testing Center has made significant contributions to the development and testing of a variety of vaccines of global importance since 2002. For the NIH dengue vaccine, UVM’s role in the future will focus on defining a precise dose and timing, as well as benefit of a second dose. In addition, says Pierce, the UVM researchers may also engage in vaccine trials on West Nile infection.

Learn more about NIAID’s dengue research and the UVM Vaccine Testing Center.

(This article was adapted from a news release produced by the National Institutes of Health.)

The study was published online January 31, 2013 in The FASEB Journal.

Estrogens are female sex hormones that are involved in a variety of physiological processes, including growth and development of the uterus and mammary gland. According to Wall, a postdoctoral associate in immunobiology, the response of reproductive tissues to the estrogen known as 17β-estradiol (E₂) is genetically regulated, but the mechanisms underlying the genetic control, and the pathways involved, are unknown.

In previous rodent model studies, Teuscher, a professor of medicine who has been studying the genetic control of uterine responsiveness to E₂ for 20 years, has identified several key genetic pathways underlying differential responsiveness to E₂. For this study, he, Wall and colleagues used two strains of inbred mice – one with high and one with low responses to E₂ – in order to examine E₂-regulated genetically controlled pathways. Their aim was to identify the genes and pathways associated with the differences in the uterine response to E₂ in each strain and, when comparing the strains at baseline, determine which of the genes and pathways that were expressed differently might regulate the uterotropic response. They also measured E₂-induced cellular changes that could be linked to the strain differences in tissue architecture after treatment with E₂.

Their findings revealed that the uterine response to E₂ is associated with at least 80 genes that are differentially expressed between the strains at baseline and are also located within the boundaries of previously identified regions of the genome influencing the uterotropic response to E₂.

“One of these genes, Runx1, has been recognized as being able to intensify E₂-signaling and might underlie the heightened uterine response to E₂ in the more sensitive mice,” says Wall. The research also showed that there are marked differences in E₂-induced uterine epithelial (surface) cell death, which Wall says could explain genetically-controlled differences in uterine weight.

Because the key factors involved in the regulation of uterine and mammary function are consistent across species, the team’s findings, though performed in mice, have direct application to other animals, including humans.

Elizabeth Bonney, M.D., UVM professor and director of research in obstetrics, gynecology and reproductive sciences, says “This is important work that provides a better understanding of the normal reproductive biology of women, and has implications for the treatment of infertility and evaluation of risk for endometrial cancer.”

“These results provide a potential explanation for differential responses to exposure to environmental estrogens noted in both mammalian and human studies and should enhance our understanding of potential vulnerable populations and help inform environmental health policy,” says Frances Carr, Ph.D., professor of pharmacology, whose research includes the study of the impact of environmental estrogens on thyroid cancer and development.

According to Teuscher, the current finding underscores comments by Jeffrey W. Pollard, Ph.D., director of the Center for Study of Reproductive Biology and Women’s Health at Albert Einstein College of Medicine, featured in an editorial review of his team’s article in Endocrinology (40:556-61, 1999): “A Holy Grail of the pharmaceutical industry is to find estrogens that are effective in one tissue but not others so that preventative treatments can be employed for bone loss, or in the prevention of cardiovascular disease, without increasing the risk of endometrial or breast cancer.”

The current findings delineating the gene pathways that affect estrogen responsiveness pave the way for the development of alternative therapeutic approaches.

In addition to increasing funded research focused on aging, Center on Aging Program Manager Jeanne Hutchins, M.A., says the goal of this $50,000 annual award is to support projects that seek to explore new questions or avenues of investigation, including basic, translational, clinical, and behavioral investigation.

Grams came to UVM in 1970 to establish the Human Development and Family Studies Program. During the earlier portion of his career, his work focused on parent-child relationships, but later transitioned to human relationships and sexuality. Following his retirement from UVM in 1990, he remained professionally active, developing and teaching several courses on gerontology, and playing an integral role in the establishment of both the former UVM Center for the Study of Aging and a Gerontology Certificate program. He also served in many national and international aging-related organizations, including as president of the Association of Gerontology in Higher Education (AGHE). Grams passed away at the age of 78 in 2002.

Fukagawa and Kolodinsky are co-chairs of the UVM Food Systems Spire. Their pilot project aims to investigate the effectiveness of community-based nutrition education tools as a means to improve nutrition literacy of older residents and staff in affordable housing sites and to determine whether or not these tools can impact food intake, biomarkers of nutritional status and health, and indices of frailty. Among the tools they will be assessing are computer-based applications. Fukagawa and Kolodinsky are interested in learning whether these applications are useful in monitoring adherence to dietary recommendations and general health status, and could thereby assist staff in targeting individuals for earlier intervention. Their work will capitalize on a program developed by affordable housing provider Cathedral Square Corporation and will seek to determine whether the intervention contributes to positive outcomes associated with the Support And Services at Home (SASH) model: reduced hospitalizations or falls; control of chronic diseases; medication compliance; and identification of cognitive issues.

Learn more about the Center on Aging at UVM.

(Jeanne Hutchins, M.A., contributed to this report.)

Among the UVM College of Medicine faculty members highlighted in the researcher banners on display at the event was Professor of Medicine and Surgery Harold Dauerman, M.D., whom with his co-investigators, is celebrating the first anniversary of UVM/Fletcher Allen’s participation in the Medtronic CoreValve^® U.S. Pivotal Trial, a study on a treatment called Transcatheter Aortic Valve Replacement (TAVR) for patients with severe aortic stenosis who are at high risk to receive surgical valve therapy.

One of 45 U.S. sites participating in this clinical trial, UVM/Fletcher Allen has treated dozens of critically ill patients with this new investigational TAVR technology, says Dauerman, who collaborates with Joseph Smoker, M.D., associate professor of surgery, to perform the procedure. The trial aims to determine whether TAVR is a safe and effective treatment option for certain patients with severe aortic stenosis.

When blood leaves the heart, it flows through the aortic valve into the aorta and returns to the body. But if this valve is narrow, or does not fully open, the flow decreases and the heart must work harder, which can lead to chest pain and ultimately, heart failure. The experimental TAVR procedure involves attaching an artificial aortic heart valve to a wire frame, which is guided by thin, flexible tube – a catheter – to the heart. When it gets to the appropriate location in the heart, the wire frame expands, allowing the new aortic valve to open and begin to pump blood.

“During our first year of clinical experience and trial participation, the Heart Team has reached a number of significant milestones,” says Dauerman. “First, we anticipate having treated 30 critically ill patients with this new CoreValve® TAVR technology in the context of our cutting-edge clinical research program. This makes us the highest volume TAVR program in Vermont, New Hampshire or Maine, even though we were not the first program to initiate this new approach to these high-risk patients.”

Another advance has been the expansion of this treatment option using a non-femoral arterial access approach. With leadership from Schmoker, a cardiovascular surgeon, the research team is now using a mini-sternotomy approach for selected patients. This method delivers the aortic valve implant percutaneously – through the skin, beneath the sternum – via a small puncture into the ascending aorta.

“We are also offering some patients a fully percutaneous option now,” Dauerman says. “We are able to use less than a one-centimeter incision in the groin area to do the entire procedure, allowing patients to be out of bed, sitting in a chair, as early as four hours after the aortic valve is replaced.”

The procedure has been extended to the most critically ill patients – including those who are on dialysis or have several diseased valves or suffer from a very weakened heart function.

The team anticipates reaching several new milestones in its second year participating in the CoreValve® trial. Dauerman and Schmoker plan to enroll patients who have received prior aortic valve replacements that are failing, which occurs about ten years following the initial bioprosthetic valve replacement surgery. Dauerman believes these TAVR “valve in valve” procedures can help patients in this high-risk group from undergoing a second surgery. Non-high-risk patients will also be invited to enroll, beginning in spring 2013.

“By randomizing patients at intermediate risk for surgical aortic valve replacement to either standard surgery or TAVR, we’ll be able to understand whether or not TAVR should be expanded clinically as a realistic option for many more patients with severe aortic valve disease,” says Dauerman.

“I suspect that we will also be able to distinguish between bacterial, viral and fungal infections of the lung,” says Hill, who is among the junior faculty receiving support from the College of Medicine’s Center for Immunology and Infectious Diseases IDeA grant.

The World Health Organization estimates that one-third of the world’s population carries tuberculosis and that this lung disease causes more than a million deaths each year.

“TB takes about six weeks to diagnose,” says Hill, allowing an infected person to spread it unwittingly. “Faster diagnosis of the disease would allow for faster treatment decisions and would also decrease disease transmission.”

She anticipates a time when patients could visit a physician, breathe into an instrument and know within minutes, “what you’re infected with,” she says, and, perhaps, “whether your antibiotic regime is effective, whether you need different antibiotics, and whether you have more then one bug causing your problem.”

The new research has drawn the attention of international media including the BBC and Scientific American.

This research was supported by the UVM College of Medicine’s Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (grant 8 P20 GM103496-07) within the National Institutes of Health; the Cystic Fibrosis Foundation; and NASA EPSCoR.

(Portions of this story were written by Michael Bishop, Institute of Physics.)

“The Forum is designed to promote cross‐disciplinary research and collaboration in investigating behavior and its underlying neurobiology as a major factor affecting human health, disease, and disability by providing avenue for disseminating new research findings and discussion,” says Rae Nishi, Ph.D., UVM professor of neurological sciences, director of the Neuroscience Graduate Program and director of the NBH Initiative.

The research forum began with a poster session at 4 p.m. on Friday, January 18, followed by a keynote lecture, titled “Rethinking Stress Biology,” at 5 p.m. James Herman, Ph.D., professor of psychiatry and behavioral neuroscience and director of the Laboratory of Stress Neurobiology at the University of Cincinnati, delivered the keynote. His laboratory studies how brain circuits get modified by stress and how this leads to disorders such as depression and hypertension.

On Saturday, January 19 from 8:30 a.m. to 4 p.m., faculty members and graduate students delivered scientific poster presentations and short talks on current research in neuroscience and behavior. More than170 people attended the forum, including faculty members, graduate students, and undergraduate students. Participants came from Dartmouth College, McGill University and HEC Montreal, in addition to UVM. To promote public outreach, students from area high schools served as judges at the event, evaluating graduate students’ ability to explain their research clearly to a non‐neuroscientist.

Information and registration information.

About the Neuroscience, Behavior and Health Initiative
The Neuroscience, Behavior and Health (NBH) Initiative focuses on understanding the development and fundamental basis of human behaviors that are linked to health and disease — a research challenge that spans fields from molecular biology and genetics to behavior, rehabilitation, and education. Research in NBH is directed towards studying preventable diseases and disabilities, informing policies, and strategic investments that create healthier communities and decrease costs of treatment and mitigation. UVM NBH director is Rae Nishi, PhD, professor of neurological sciences and Steering Committee members include: vice-chair: Stephen Higgins, Ph.D., professor of psychiatry and psychology; vice-chair: Mark Bouton, Ph.D., professor of psychology; Timothy Stickle. Ph.D., associate professor of psychology; Brian Flynn, Ph.D., professor emeritus of family medicine and professor of psychiatry; Sharon Henry, Ph.D., professor of rehabilitation and movement science; tech transfer liaison: Kerry Swift, M.S., interim director of the Office of Technology Commercialization; central administration liaison: Cindy Forehand, Ph.D., associate dean, Graduate College, and professor of neurological sciences.

To determine the long-term trends of HRT use, Sprague and colleagues used data from National Health and Nutrition Examination Survey (NHANES) surveys – a nationally representative sample – conducted between 1999 and 2010. The group generated prevalence estimates for the entire country and found that postmenopausal HRT use in the U.S. has declined continuously to low levels across a wide variety of patient subgroups.

“From 1999 to 2002, one in five women older than age 40 was a current user of oral postmenopausal hormones,” explains Sprague. “By 2009–2010, the prevalence was fewer than one in 20; only 1.7 percent of women aged 40 and older report current use of estrogen plus progestin formulations.”

The sharpest decline – almost 50 percent – occurred during the first two years following the halt of the estrogen plus progestin arm of WHI study, when overall HRT use went from 22.4 percent in 1999-2000 to 11.9 percent in 2003-04. While the earliest observed decline was found predominantly in non-Hispanic whites, Sprague’s study showed that the use of both estrogen alone and estrogen plus progestin continued to decrease between 2005 and 2010 and was observed in women of all ages, races or ethnicities, education, income groups, and those with and without hysterectomy. 

“There are still differences in the prevalence of hormone use according to socioeconomic indicators such as income and race,” says Sprague, who works in UVM’s Office of Health Promotion Research. “However, the differences in use according to these characteristics are much smaller than they used to be.”

According to Sprague, criticisms and concerns about the WHI trial have continued to crop up over the past decade. In surveys on the subject, physicians have reported being skeptical about the results and how they apply to their patients.

“Our findings suggest that these concerns about the Women’s Health Initiative have not led to a rebound in the use of postmenopausal hormones,” says Sprague. He and his coauthors note that, since 2001-2002, “the prevalence of hormone use among women aged 40 and older had declined by . . . 79 percent in 2009–2010.”

The researchers recommend continued monitoring of treatments for menopausal symptoms in order to keep track of the therapies’ impact on women’s health.

Designed to encourage developing young scientists to pursue careers in various aspects of tropical disease research, the award is presented to outstanding young researchers during the ASTMH Annual Meeting. Bessoff discussed his research on “Improving Therapeutics for the Treatment of Cryptosporidiosis using High Throughput Methods” as part of the Young Investigator Award program at the conference.

“We study a parasite called Cryptosporidium parvum, which, along with another closely related parasite, causes a diarrheal disease known as cryptosporidiosis,” says Bessoff. “The disease is a leading cause of diarrhea in the developing world, and is particularly devastating to AIDS patients and little children. Currently, there are no vaccines or effective treatments available.”

Bessoff has been working with mentor Christopher Huston, M.D., associate professor of medicine, since 2010. According to Huston, there is little incentive for the pharmaceutical industry to develop treatments for the developing world and methods to work on Cryptosporidium parasites are severely lacking.

“To address both of these issues, Kovi took a ‘drug repurposing approach’ – focusing on identification of drugs already approved for other uses that can possibly be used to treat cryptosporidiosis,” explains Huston.

The approach paid off. Bessoff developed the first high-throughput cell-based screening assay to identify drugs that inhibit growth of Cryptosporidium parvum within intestinal epithelial cells. Then, using his unique method to screen a library of drugs, he was able to identify 16 drugs that inhibit Cryptosporidium growth.

“We discovered that the cholesterol-lowering drug pitavastatin has good activity against the parasite,” Bessoff says. “We believe that it inhibits Cryptosporidium parvum growth by the same mechanism that it employs to reduce cholesterol levels and think this provides sufficient evidence to conduct human clinical trials of pitavastatin for the treatment of cryptosporidiosis.”

Proud mentor Huston is excited about the potential of these candidate drugs for treatment of cryptosporidiosis.

“A great deal is known about the mechanism of action for many of the drugs, because of the compound libraries that we chose to screen, and this enabled us to formulate hypotheses about how they affect Cryptosporidium parasites,” he says. “Kovi followed-up on one of the most interesting drug leads, which is an inhibitor of the host cell enzyme HMG-CoA reductase.”

In collaboration with Adam Sateriale, another Cellular, Molecular and Biomedical Sciences graduate student also working in Huston’s lab, Bessoff used the drug and a bioinformatics analysis of the Cryptosporidium genome to prove that Cryptosporidium parvum is dependent on host cell synthesis of isoprenoid precursors. The team determined that the parasite appears to require isoprenoids for many biochemical processes, but cannot synthesize them itself.

Huston credits Bessoff with not only identifying potential treatments for Cryptosporidiosis, but also elucidating critical information about Cryptosporidium biology that can be shared with scientists in the field. 

A new study, led by Daniel Weiss, M.D., Ph.D., professor of medicine at the University of Vermont College of Medicine and a pulmonologist at Fletcher Allen Health Care, was the first-ever clinical trial examining the potential of mesenchymal stem cell (MSC) therapy to reduce chronic pulmonary and systemic inflammation in patients with moderate to severe COPD. The results were published online November 22, 2012 in CHEST, the journal of the American College of Chest Physicians.

“MSCs are stem cells isolated from adult bone marrow, adipose, and other tissues, that in addition to having the ability to differentiate into several specific tissue types can potently regulate inflammation,” says Weiss.

Isolated MSCs, adds Weiss, are not associated with immune system rejection, which allows for safe administration of MSCs obtained from un-related donors. Although the full range of mechanisms of MSC actions on inflammatory processes in different diseases has not yet been fully clarified, there are a growing number of clinical investigations using MSCs in inflammatory and immune-mediated diseases, including multiple sclerosis, type 1 diabetes, and others. Based on the results of these and animal model-based lung disease studies, Weiss and colleagues hypothesized that MSCs would reduce chronic pulmonary and systemic inflammation in COPD patients with corresponding improvement in lung function and in quality of life.

The study was conducted at six sites in the United States including UVM, with Weiss serving as the lead investigator. Participants in the trial received four separate administrations of MSCs or a placebo control and were subsequently followed for two years. A total of 62 patients at the six sites were randomized to double-blinded intravenous infusions of either allogeneic MSCs (Prochymal®, Osiris Therapeutics, Inc.) or placebo control. Patients received four monthly infusions and were subsequently followed for two years after the first infusion. Endpoints included comprehensive safety evaluation, pulmonary function testing, quality of life indicators, including questionnaires, six minute walk evaluation, and assessments of systemic inflammation. According to Weiss, most of the patients enrolled in the study were elderly, had significant lung disease, and also had a number of other medical conditions.

“The study clearly demonstrated safety both during the actual administration of the MSCs, as well as over the two-year follow-up period,” Weiss says. “While there was no obvious efficacy of the MSCs in improving either lung function or quality of life, there were too few patients to accurately assess this. However, the trial’s clear demonstration of safety opens the door to larger trials of MSCs in patients with COPD and also opens the door to investigation of MSCs in other lung diseases.”

Those most at risk for COPD are current and former cigarette smokers. Despite its rising incidence, awareness of COPD has recently dropped to 2008 levels, according to a 2012 report issued by the National Institutes of Health, underscoring a need for improved educational efforts about the disease.

In addition to Weiss, coauthors on the CHEST study include Richard Casaburi, M.D., Ph.D., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif.; Robin Flannery, Osiris Therapeutics Incorporated, Columbia, Md.; Michelle LeRoux-Williams, Ph.D., Osiris Therapeutics Incorporated, Columbia, Md.; and Donald Tashkin, M.D., David Geffen School of Medicine at UCLA, Los Angeles, Calif.

Several University of Vermont and Fletcher Allen Health Care staff and faculty joined Weiss in playing important roles in the trial, including Vermont Blood Bank members Nella Bartolai-Drexler, Sharon Bushor, Audrey Chafetz, Mark Fung, M.D., Paulette Hammond, and Shelly Hitchcox; Vermont Lung Center staff Stephanie Burns, R.N., Laurianne Griffiths, R.N., and Joan Lippmann, R.N.; and University of Vermont Clinical Research Center members Richard Galbraith, M.D., Ph.D., Joan Bertolet, R.N., Delana Braves, R.N., Betsy Cutler, R.N., Susanna Knoop, R.N., Nanse Nathan, R.N., and Rachel Stringer, R.N.

Designed to support international early-career development, the fellowship provides a three-year, $300,000 grant to fund scientific research into important questions about the causes, diagnosis and treatment of Alzheimer‘s disease, as well as help promising scientists establish their careers within Alzheimer‘s research internationally. The program also aims to enhance international research output by supporting meaningful scientific collaboration between scientists in the United States and the United Kingdom. Reese’s U.K. mentor is Karen Horsburgh, Ph.D., senior research fellow and deputy director of the Centre for Neuroscience Research in the School of Biomedical Sciences at the University of Edinburgh in Scotland.

In Alzheimer's disease, a toxic protein called beta-amyloid is over-produced and accumulates into “plaques” that deposit on the brain. In many people with Alzheimer’s disease, these plaques also occur in the blood vessels that supply the brain.

“The blood-brain barrier separates cells in the brain from the blood circulation and controls what molecules enter and leave the brain,” says Reese. “Some evidence suggests that the blood-brain barrier is damaged in Alzheimer's disease, possibly as a result of amyloid deposition or impaired blood flow.”

For her project, Reese will examine the role of impaired blood flow and amyloid deposition in blood-brain barrier damage. Specifically, she will use brain tissue samples from people who died of Alzheimer’s disease collected by Randall Woltjer, M.D., Ph.D., director of the Oregon Brain Bank at Oregon Health & Science University, and examine cerebrovascular proteins to determine whether or not they are affected by the disease. In addition, she and colleagues will seek to determine if any markers of damage to the blood-brain barrier exist in blood samples. The goal of this work will be to provide new insights into how the blood-brain barrier is affected by amyloid deposition and impaired blood flow and may suggest targets for drugs to prevent damage.

Cipolla, who is a blood-brain barrier expert, is serving as Reese’s primary supervisor for the fellowship. In addition, Reese plans to spend three months during the summer of 2014 working in Horsburgh’s laboratory at the University of Edinburgh.

Prior to coming to UVM, Reese completed her Ph.D. in neuroscience and cell biology at The University of Texas Medical Branch at Galveston and a postdoctoral fellowship in the National Institute on Aging-funded Neuroscience of Aging program at Oregon Health & Science University.

Co-chaired by Susan Lakoski, M.D., UVM assistant professor of medicine and director of cardiovascular prevention, and Kim Dittus, M.D., Ph.D., assistant professor of medicine and oncologist, the symposium's presentations focused on clinical and translational research at the VCC and other cancer research institutions with a particular emphasis on exercise, nutrition, and their overall effect on cancer risks and outcomes. This conference was designed to encourage the collaborations and development of effective processes to foster clinical and translational research pipelines.

Jones’ research focuses on a translational approach to evaluating the cardiovascular/functional impact of cancer therapy, and efficacy of defined exercise training to prevent and/or treat dysfunction, and elucidating the effects, and underlying systemic and molecular mechanisms, of defined aerobic training on tumor progression and metastatic dissemination. A native of Stoke-on-Trent, England, he received a Bachelor of Science degree, with honors, in sport and exercise science from the University of Brighton, then moved to Canada to complete a Master of Science degree in kinesiology at Lakehead University in Thunder Bay, Ontario, and a Ph.D. in exercise oncology research at the University of Alberta. After completing a postdoctoral fellowship at the University of Alberta, Jones joined the Program of Cancer Prevention, Detection, and Control at Duke in 2005. He was named director of Cancer Survivorship Research and the Duke Exercise-Oncology Program within the Duke University Health System and Duke Cancer Institute in 2009. The author of numerous scientific articles and book chapters, he is also a member of the International Editorial Board for Lancet Oncology. His research is supported by the National Institutes of Health, American Cancer Society, and U.S. Department of Defense Breast Cancer Research Program.

In addition to a welcome provided by VCC co-director and director of hematology/oncology Claire Verschraegen, M.D., UVM presenters at the symposium included: Michael Toth, Ph.D., associate professor of medicine; Jean Harvey-Berino, Ph.D., R.D., professor and chair of nutrition and food sciences and associate professor of medicine; Lakoski; and Dittus.

The Lake Champlain Cancer Research Organization has provided support for the Juckett Lecture and the symposium. For more information about the event, including a full agenda and list of speakers, visit the Vermont Cancer Center website or call (802) 656-2176.

Both of the group’s studies included study participants undergoing bariatric (weight loss) surgery. In the latest study article, the authors write that their objective was to determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity.

The 2012 study included 15 obese control women and 11 women with asthma. All of the participants with asthma had adult-onset asthma, and tended to be older and significantly heavier than the control subjects. The researchers followed the study participants for twelve months following bariatric surgery, comparing markers in adipose tissue and the airways from the participants with asthma and control subjects, and noted any changes experienced by the participants with asthma over time. After 12 months, the authors report, the subjects with asthma had an average weight loss of 28.4 +/- 16.5 kilos (62.6 +/- 36.4 pounds), and asthma control and airway hyper-responsiveness (AHR) improved significantly.  What was not anticipated by the investigators was the fact that these asthmatics had little in the way of airway inflammation typically seen in asthma.  Their airway cells expressed receptors for factors produced by adipose tissue, and this was closely related to their airway reactivity.  This suggests that proteins excreted by adipose tissue that affect metabolism and other processes may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing the type of airway inflammation that is usually seen in asthma.

“Our group has really helped develop the idea that there are two distinct forms of asthma occurring in the setting of obesity,” explains Dixon, who serves as chief of pulmonary and critical care medicine at the UVM College of Medicine and Fletcher Allen Health Care. “There are people with early onset allergic asthma that develop obesity as they grow older and another group that develops late-onset asthma as a consequence of obesity. The two groups are quite different in terms of their disease, and the abdominal fat may be particularly important in those developing asthma later in life.”

In addition to Dixon, who serves as senior author on the American Journal of Respiratory and Critical Care Medicine study, coauthors include first author Olga Sideleva, Ph.D., UVM post-doctoral associate in pulmonary disease and critical care medicine; Benjamin Suratt, M.D., UVM associate professor of medicine; Kendall Black, UVM senior lab/research technician in pulmonary and critical care medicine; W. Gabriel Tharp, UVM M.D.-Ph.D student; Patrick Forgione, M.D., UVM associate professor of surgery; Oliver Dienz, Ph.D., UVM assistant professor of medicine; Charles Irvin, Ph.D., professor of medicine and director, Vermont Lung Center; and Richard Pratley, M.D., professor at Florida Hospital/Sanford-Burnham Transitional Research Institute., and former UVM faculty member.

The team is sharing their research expertise across the globe. In October, Dixon was invited to deliver the keynote presentation at the Newcastle Asthma meeting, an annual meeting held in Newcastle, Australia. In addition, Dixon co-edited a new book, titled Obesity and Lung Disease: A Guide to Management (Humana Press; 2013 edition, released September 10, 2012), which features multiple contributors from the UVM College of Medicine.

Titled “Secondary Sexual Characteristics in Boys: Data from the Pediatric Research in Office Settings Network,” the study was published online October 20 to coincide with the AAP National Conference & Exhibition in New Orleans, La., and will appear in the November 2012 issue of the AAP’s journal Pediatrics.

The trend toward earlier onset of puberty in girls is now generally accepted and supported by extensive research. Until now, little research was available on the age of onset of puberty in boys in contemporary times.

The AAP PROS network is a system of hundreds of pediatricians nationwide who contribute data to AAP-led scientific studies on children’s health. A 1997 PROS study was the first large study to document earlier pubertal onset in U.S. girls. For the study of pubertal characteristics in boys, 212 practitioners in 144 pediatric offices in 41 states recorded information on more than 4,100 boys.

This new research found that the observed mean ages of stage 2 genital and pubic hair growth and early testicular enlargement – standard indications of pubertal onset – were occurring six months to two years earlier than documented by data several decades earlier. Pediatricians recorded the earliest stage of puberty as occurring in non-Hispanic white boys at age 10.14 years; in non-Hispanic African-American boys at age 9.14 years; and in Hispanic boys at age 10.4 years.

Overall, African-American boys were more likely to start puberty earlier than white or Hispanic boys. Study authors say the causes and public health implications of an apparent shift toward a lower age of puberty onset for boys is unclear and warrants further research.

“Contemporary data on the ages of pubertal characteristics in U.S. boys from onset to maturity, lacking until now, are needed by pediatricians, public health scientists, and parents,” says lead study author Marcia E. Herman-Giddens, P.A., M.P.H., Dr.PH., of the University of North Carolina and a member of PROS. “Following changes in growth and development is an important part of assessing the health of the nation’s children. I am grateful to the pediatricians and the boys who participated in this exciting study.”

“All parents need to know whether their sons are maturing within the contemporary age range, but, until now, this has not been known for U.S. boys,” says Wasserman. “The PROS study provides 21^st century standards.“

“The landmark PROS study of the 1990s provided contemporary data for girls’ puberty,” Wasserman explains. “A study on boys’ puberty was a logical follow-up. Our pediatric endocrinologist colleagues now use the PROS puberty assessment training materials in their own studies and fellowship training.”

Link to a Wall Street Journal article and CBS News online article about the study.

(This article has been adapted from a news release produced by the American Academy of Pediatrics Division of Media Relations.)

The ATS unrestricted grant, which provides $80,000 in research funding over two years (October 1, 2012 to September 30, 2014), is awarded to a researcher whose program has a high likelihood of advancing the understanding of lung disease. Applications are encouraged from new faculty members who have a strong link with one or more senior investigators. According to the ATS, Anathy was the best ranked applicant in the unrestricted category. The unrestricted grant’s review process included 54 letters of intent, a review of 16 full applications, and finally, four acceptances for funding.

“Repeated lung exposure to allergens, toxins, particulates, and pathogens can initiate a vicious cycle of repair and remodeling of the lung that ultimately leads to stiffness and respiratory failure,” explains Anathy. “Our research team has discovered that repeated exposure to allergens results in endoplasmic reticulum stress response, and this response mediates the progression from allergen exposure to airway remodeling.”

For this project, Anathy and his collaborators Matthew Poynter, Ph.D., UVM associate professor of medicine, and Anne Dixon, M.D., UVM associate professor of medicine and director of pulmonary and critical care medicine, will use genetically modified mice to improve understanding of the disease mechanism and to identify pharmacological inhibitors that interrupt airway remodeling.

A 2010 recipient of an ATS Travel Award, Anathy received his Ph.D. in biological sciences from Madurai Kamaraj University in Madurai, India. He joined the UVM faculty in 2004.

Now in its fifth season, “Emerging Science” airs on VPT Wednesdays at 7:30 p.m. The series features Vermont scientists who expand human knowledge and help solve problems around the world. A collaboration between Vermont EPSCoR (Experimental Program to Stimulate Competitive Research) at UVM and VPT, “Emerging Science” is a multi-award-winning program that utilizes broadcast programs, web resources, community events, and educational outreach to spark high school students’ interest in scientific careers. Designed to fulfill the National Science Foundation’s mandate to promote scientific progress nationwide, Vermont EPSCoR supports Vermont scientists and business leaders through funding, outreach and technology development.

The October 24 “Acupuncture: A Connective Tale” program featuring Langevin explores the role of connective tissue in acupuncture and the importance of connective tissue to overall health. The episode profiles Vicky Dubois of Burlington, Vt., who suffers from the connective tissue disorder scleroderma. The episode also includes interviews with Brian Erickson, M.D., UVM clinical assistant of psychiatry, and pain medicine psychiatrist at Fletcher Allen Health Care, and Janet Kahn, Ph.D., UVM assistant professor of psychiatry and Program in Integrative Health member, and massage therapist.

The October 31 “Traumatic Brain Injury in Sports” program featuring Freeman’s research profiles young Kacy Chicoine of Huntington, Vt., whose life has been altered by a series of concussions while playing hockey. An interview with Magdalena Naylor, M.D., Ph.D., UVM professor of psychiatry and a co-investigator with Freeman on this concussion research, will also be included in this program.

The November 7 program, titled “Traumatic Brain Injury at War,” focuses on studies by Matthew Friedman, M.D., Ph.D., of the National Center for PTSD (post-traumatic stress disorder) and Thomas McAllister, M.D., of the Geisel School of Medicine at Dartmouth that explore the association between PTSD and Traumatic Brain Injury (TBI). The segment will feature comments by Jom Hammack, Ph.D., UVM associate professor of psychology, who studies PTSD at a molecular level with colleagues Victor May, Ph.D., professor of neurological sciences, Karen Braas, Ph.D., associate professor of neurological sciences, and Donna Toufexis, Ph.D., assistant professor of psychology. An interview with Sgt. Andrew Reeves, a veteran of the Iraq war who was injured by an improvised explosive device in 2004 and has been diagnosed with TBI and PTSD, will also be featured in the program.

Each program will be rebroadcast the following Saturday at 10:30 a.m. and the following Sunday at 1:00 p.m. Program videos will also be available on demand on the "Emerging Science" website.

“Emerging Science” was created and is produced in partnership with Vermont EPSCoR and VPT with funding provided by NSF EPS #1101317. VPT’s Anya Huneke serves as producer, and Dorothy Dickie as executive producer, of “Emerging Science.”