Seminar Recap: Cognition in the Menopausal Transition

Labeled “The Seven Dwarves of Menopause,” they grinned out at the audience from the projector screen in Helen Wood Hall Auditorium: Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and Psycho.

“So, I’m interested in numbers 2, 6, 7, and a little bit of 4,” quipped Miriam Weber, Ph.D., assistant professor of neurology and obstetrics and gynecology, at URMC.

Miriam Weber, Ph.D.

Miriam Weber, Ph.D.

For the past decade, Weber has been studying cognition in women in the menopausal transition. While the symptoms embodied by the Seven Dwarves have long been accepted as common experiences for women in the menopausal transition, there hasn’t been a particularly robust array of science to support the cognitive symptoms until recently.

On Sept. 23 at the CTSI Seminar Series, Weber shared her past work in the field and discussed how her current study is expanding on her previous findings.

What we know

In creating her original study, Weber had a little background from two prior studies. The first, published in 2000 (SWMHS-Mitchell), found that 62 percent of middle-aged women reported an undesirable change in memory. Meanwhile, the longitudinal SWAN study had also found that 40 percent of peri- and post-menopausal women listed “forgetfulness” among a self-reported inventory of their symptoms.

With this data as a backdrop, Weber launched her Rochester Investigation of Cognition Across Menopause (RICAM) study, hoping to expand on the findings. The first study took place in 2005-2006, and a second took place from 2007-2009. Weber is now in the midst of her most comprehensive study yet, which began in 2010 and runs through 2015.

“Memory complaints really do reflect objective performance, maybe not in retentive memory, but in working memory,” said Weber.

Since publishing her initial results, other groups have reported similar findings — other researchers found that memory complaints were associated with loss of verbal memory and attention, that subjectively recorded memory problems were associated with objective measures, and that the brains of post-menopausal women with cognitive complaints were working harder in order to perform to previous levels.

“These are high-functioning women, and they’re not impaired, but they’re noticing subtle differences,” said Weber.

Weber’s study also looked which women were struggling the most with memory symptoms, and found that women in early post-menopause — the first year after the post-menstrual period — were performing worse with verbal learning, verbal memory, and fine motor and dexterity, than women in the late-reproductive stage.

Future directions

In confirming that women are indeed good at self-reporting their memory symptoms during the menopausal transition, Weber offered a few directions for future studies.

Among other suggestions, Weber said that researchers need better measures of symptoms known to impact cognition.

“With that in mind, we just received funding to add to RICAM objective measures of hot flashes and sleep monitors,” said Weber. “That way, we can get subjectively reported symptoms as well as objective measures.”

She’s also hoping to expand the study to multiple sites and make it more representative, which may allow for more parsing of the data.

“Ideally, we need to identify who is at risk for cognitive declines. Clearly, some women are doing better and some who are taking a more significant hit,” said Weber. “So I’m interested in describing in general what the experience is during this time period for all women, but also whether there are certain factors that put some women at increased risk.”

First SRB Data Blitz! Is a Success

The new SRB Data Blitz! Series aims to give a broad and entertaining overview of research programs in the Saunders Research Building. The inaugural session was held on September 24th, 2014 in the Saunders Research Building and featurPictureed both poster and live presentations from members of the Heart Research Follow-up Program. Dr. Wojciech Zareba, Director of the Heart Research Follow-up program, welcomed approximately 40 attendees and offered opening remarks for the event.

Eight posters were setup for attendees to peruse as their own leisure and a slide presentation ran throughout the event, highlighting recent research projects and findings. PDFs of the posters and the presentations are available on the CTSI Website. Additionally, there was a Long QT measurement station where attendees could have their levels assessed in 30 seconds. This technology aids Doctors in identifying patients at risk for heart disease and prescription side Pictureeffects.

Make sure to join us for the next session of the SRB Data Blitz! Series which will be held on October 29th and will feature research from the Developmental Disabilities group. See you then!

Checking in at the CRC: Fall 2014

Welcome to our new quarterly feature: Checking in at the CRC! Every few months, we’ll chat with Ann Miller, nurse manager at the Clinical Research Center, to learn more about all the ways that the CRC supports researchers and their human subjects.

In this kickoff edition, Miller gives an overview of the center.

SRB Data Blitz! kicks off Wednesday

If you want to learn a whole lot about cardiology research in just a little bit of time, there’s no better place to do so than the Saunders Research Building atrium this Wednesday afternoon.

The CTSI is launching a new series called the SRB Data Blitz!, whereby a team of researchers gives a series of rapid-fire presentations on their work.

Wojciech Zareba, M.D., Ph.D.

Wojciech Zareba, M.D., Ph.D.

This month, researchers from the Heart Research Follow-up Program headed by Wojciech Zareba, M.D., Ph.D., are presenting. Eight research posters will be on display, and researchers will give 2-3 minute talks on each poster. Topics that could be covered include, but are not limited to:

-Long QT syndrome
-Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D)
-Risk Stratification in Postinfarction Patients with Implantable Cardiac Defibrillators
-Repolarization Abnormalities as Indicator of Increased Risk of Cardiac Arrhythmias
-Telemetric and Holter Electrocardiology Warehouse (THEW)
-Thrombogenic and Lipid Factors in Postinfarction Patients (THROMBO)
-Cardiovascular Effects of Air Pollution

Coffee and cookies will be served. Be there, and get Blitzed!

What: SRB Data Blitz! featuring the Heart Research Follow-up Program.
Where: Saunders Research Building atrium.
When: Noon on Wednesday, Sept. 24.

CTSI Welcomes Margaret Demment to Informatics Team

Whether it’s coming from Upstate New York or Antarctica, Margaret Demment can help you make sense of that data.

“My training is in community nutrition, which is the public health side of nutrition, so I’ve studied health disparities and how to improve health in vulnerable populations. I’ve done qualitative work, quantitative work, large epidemiological studies, and smaller stuff,” said Demment. “So here, I’ll get to be a utility player and help with lots of different things.”

Margaret Demment, Ph.D.

Margaret Demment, Ph.D.

Previously a postdoctoral associate at Cornell University, Demment is one of the newest additions to the rapidly-growing CTSI Biomedical Informatics team, and she’s already begun work on a variety of projects.

Alongside Tim Dye, Ph.D., the director of the CTSI’s Biomedical Informatics team, she’s currently helping to create and study a massive data set called the Perinatal Data Network. The data, collected from more than 1 million women in Rochester, Syracuse, Albany, and Buffalo over the past decade, gives a snapshot of the women’s health just after giving birth.

Demment and Dye would eventually like to make this data set accessible to researchers, but for now, Demment is studying the implications of an unwanted pregnancy on the health outcomes for the mother and child. Unwanted pregnancies are relatively rare, but the large dataset is allows her to perform the analysis previously impossible in other datasets.

A second project she’s involved in involves a qualitative analysis of a series of interviews conducted with researchers and workers in Antarctica.

“Many people go there because they think it’s going to be an adventure, but they end up working 6-day weeks, often long days, often in the dark depending on the time of year,” said Demment. “So people start seeking that adventure and often get injured, so we’re trying to pull out some themes that emerge from these interviews and provide information that would help with injury education and prevention.”

That Demment is capable of working on such wildly different projects is among the reasons that she joined the CTSI Biomedical Informatics team.

“Meg is perfectly suited to work in our research group — she’s got substantial qualitative and quantitative expertise, and importantly, has serious community engagement experience locally and internationally,” said Dye. “Her field is nutrition, which is inherently team-science oriented, so she’s used to working with a range of disciplines, which complements our team’s multidisciplinary orientation.”

Demment is currently working at the university part time. She’s also still finishing up some work at Cornell, while maintaining a side business that performs data analysis and program evaluation for community health organizations in Rochester.

Her office is within the CTSI Director’s Suite; stop by and say hello.

Seminar Recap: Environmental Exposures and Antinuclear Antibodies (ANAs)

When it comes to autoimmune diseases — conditions such as lupus, rheumatoid arthritis, and multiple sclerosis that cause a body to attack itself — women are at a higher risk than men.

But the reasons why aren’t completely clear.

Todd Jusko, Ph.D.

Todd Jusko, Ph.D.

Antinuclear antibodies (ANAs) are present in patients with autoimmune conditions, but the vast majority of ANAs haven’t been tied to certain diseases. Without good biomarkers to use when testing patients, diagnosis can be challenging, and prevention becomes nearly impossible.

So researchers at URMC are working to understand more. On Sept. 9, at the CTSI Seminar Series, Todd Jusko, Ph.D., assistant professor in the Department of Public Health Sciences and Department of Environmental Medicine, shared his past work and his search for an easy-to-identify biomarker.

What we know

Jusko was part of a group that looked at ANA prevalence in 4,340 individuals from the National Health and Nutrition Examination Survey, or NHANES between 1999 and 2003. Among those participants — 14 percent tested positive for ANAs in their blood. The proportion was slightly higher for African Americans, and, interestingly, slightly lower for individuals who were obese or overweight.

Women were also much more likely than men to test positive for ANA prevalence, particularly in their reproductive years, or just beyond. Overall, 18 percent of women tested positive for ANA, while 10 percent of men did. Women aged 30-39 were 2.5 times as likely to have ANAs in their blood as men. Women aged 40-49 were four times as likely. Nulliparous women — women who have not carried a pregnancy past 20 weeks — were also found to be much less likely to have ANAs present in their blood.

“Certainly, it’s related to some sort of hormonal difference,” said Jusko.


For a more recent study with the NHANES database, Jusko began searching for environmental causes of ANA. Dioxins and dioxin-like compounds have been documented to alter immune function, so it seemed logical that their presence may play a role in ANAs.

Jusko did find that one compound, triclosan, was biologically plausible as a potential cause of ANAs in men only, but his research revealed a variety of limitations with the data available. Jusko stressed the need for further studies measuring incident, or newly arising ANA and linking it to environmental chemicals.

“We were underpowered for some analyses. I know we had 4,300 people, which sounds like a lot, but some of the cycles didn’t measure the ANA or the chemical concentration,” he said. “So this was exploratory and this is far from the final word.”

CTSI Pilot Program: Improving mitochondrial function to help patients with osteoporosis

Sometimes, as Albert Einstein once famously opined, scientific breakthroughs come from looking at an old problem from a new angle.

“In the cardiovascular field, it’s all about mitochondria, and most of the cardiovascular literature has been about protecting mitochondrial function and boosting it during aging,” said Roman Eliseev, M.D., Ph.D., assistant professor of orthopaedics. “But very little has really been studied about the role of mitochondria in bone biology.”

Roman Eliseev, M.D., Ph.D.

Roman Eliseev, M.D., Ph.D.

Now, Eliseev thinks that techniques being applied to aging patients with cardiovascular disease might also apply to aging patients with osteoporosis.

His research, supported by a 1-year Pilot Grant from the CTSI, began on July 1.

For several years, researchers have been studying mesenchymal stem cells that can transform into other cells, such as bone, cartilage, muscle or fat, when necessary. These cells are also responsible for bone repair.

But if the energy-producing mitochondria within those cells lose their effectiveness, then the cell won’t have the energy to differentiate into the various cells the body needs. This energy loss often occurs in aging patients, putting them at higher risk for various degenerative diseases.

Eliseev has seen this disruption occur in the bones of aging mice and believes that the same disruption likely occurs in humans.

“People with osteoporosis have an increased risk of fracture, and when it occurs, the fracture doesn’t heal well. It can take months,” said Eliseev. “But by boosting mitochondrial function in mesenchymal stem cells, maybe we can accelerate that fracture healing in aged osteoporotic individuals.”

Eddie Schwarz, Ph.D., who was on the committee that selected Eliseev’s project from a variety of Pilot proposals, said that the project’s originality — and the fact that Eliseev is one of the only researchers studying the topic — were among the reasons that it was chosen for a CTSI Pilot Grant.

“It ties together a triad of basic sciences — metabolomics, stem cells, and osteoporosis,” said Schwarz, associate director for funding programs at the CTSI. “It was the basic science connection of these things that enabled it to do very well.”

With data generated from the Pilot study, Eliseev is hoping to seek an R01 grant to further illustrate the role of the mitochondria in mesenchymal stem cells, and run a small clinical trial in humans.

Eliseev’s findings may be quickly translatable to human care, as several drugs that protect mitochondrial function are already in clinical trials and could be repurposed for the necessary treatments. Bone marrow biopsies could also be used to extract mesenchymal stem cells from a patient, which could then be manipulated them to enhance mitochondrial function, and reinserted into the patient to accelerate fracture healing.

The CTSI recently released requests for applications for both the CTSI Incubator Program and the CTSI Pilot Awards Program.

Get your study approved! Tips for researchers from the IRB directors

The ubiquity of social media is such that, when Facebook does a study that angers its users, many begin voicing their outrage… on Facebook.

The recent study, which manipulated users’ timelines to gauge whether it would affect their own posts, showed both the remarkable research potential inherent in social media (their study involved a stunning 689,000 users), as well as the tremendous backlash that can result when people believe they’ve been involved in a study that they didn’t explicitly sign up for.ResearchersStock

While much of the ire has been directed at the social media giant, the scientific world has expressed some curiosity regarding the Institutional Review Board at Cornell University, where researchers performed some data analysis for Facebook’s study.

In late June, Cornell issued a statement, which said that the university’s IRB did not review the study because its researchers were not the ones collecting the information, nor did they have access to any individual, identifiable data.

But regardless of whether Cornell should share any blame — and some believe they should not — the publicity is likely to change how IRBs operate.

“Even though what was done at Cornell may not have been technically incorrect, IRBs, including ourselves, tend to be conservative,” said Kelly O’Donoghue, director of UR’s Office of Human Subject Protection. “So it’s going to change practice. Nobody wants to be on the front page of the newspaper.”

“Social media is evolving so quickly,” said Tiffany Gommel, director of UR’s Research Subject Review Board. “Each institution has to take it as it comes and figure out how they want to handle it, because there’s no guidance from the government right now. So it’s definitely been on a case by case basis.”

When it comes to IRBs, social media policies aren’t the only things that researchers can struggle with. In a recent chat with the CTSI Stories Blog, O’Donoghue and Gommel shared the three most common problems they encounter when reviewing research study submissions.

  1. Consistency

“Be consistent across all documents,” said Gommel. “Protocol, consent forms, recruitment materials, study measures, etc. That’s definitely one of the biggest issues we see is that people don’t pay close enough attention. Maybe they’ll have a protocol from earlier that was similar, and they’ll cut and paste it, but they won’t edit it, or update things on every page. This leads to errors and we have to send it back to the study team requesting changes.”

  1. Comprehensiveness

“One problem we run into is that researchers have been working in their field for a long time, and they know what they’re going to do, and what order they’re going to do it in,” said O’Donoghue. “But when they translate it to paper, sometimes they leave big holes in the study. They’re inside it and they know it so well that they assume other people will, too. But they are the experts, and we’re not. So using our protocol templates can really help with making sure your submission is comprehensive.”

  1. Inadequate Amendments

“Researchers are required by federal regulations to submit all changes to their study to the RSRB before implementing them,” said O’Donoghue. “But sometimes researchers don’t give enough information within their amendment form, or enough rationale for the change, or they won’t make the requested changes in their application. This will slow down the review process for amendments and require the RSRB to send it back to the study team.”

Director’s Update – September 2014

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, Karl Kieburtz discusses the CTSI’s growing biomedical informatics team and how it can support university researchers.

Karl Kieburtz, director of the CTSI

Karl Kieburtz, director of the CTSI

On the growing need for biomedical informatics:

One thing we focus on in the CTSI is population health, meaning the overall health of a city, a county, a region, and so on. And we want to know, when we do something — when we educate people, when we develop new programs, when we open Strong West — does it make any difference? Does the population do any better?

Nana Bennett talked a little bit about this last month, but right now, there are a lot of agencies that collect health information on the population, and could potentially answer that question. We do it, the other health agencies in town do it, Rochester RHIO (Regional Health Information Organization) does it, the Finger Lakes Health Systems Agency does it. We all have databases. But it’s almost like they’re different bank accounts: The information is structured in different ways and lives in different places, and the data collected is everything from how much people are using hospitals, to vaccination rates, to transmission of infectious diseases, to obesity rates.

So we have a lot of different numbers, a lot of data, but we don’t always have a ton of usable information from that data. The only way to truly understand it is to establish some common rules around it, so people are comfortable with others going into the databases and pulling data out.

This takes a tremendous amount of effort. The business section of the New York Times recently had a piece on big data, and it talked about how 50 to 80 percent of the time spent with big data is just spent getting the data together — reconciling different data sets. And when I read that I said, “Of course! That’s what we’re doing here!”

On how we’re doing it:

Bioinformatics isn’t one of our pillars — it’s actually part of the foundation of the CTSI, and we think it’s important enough that we’re creating a faculty position in the CTSI around it. We’ve hired Dongmei Li, who will join us shortly, and she will be the first faculty member who is actually based in the CTSI.

Dr. Li will join Tim Dye, who got here in January; Jack Chang, who got here in June; Meg Demment who started in August; as well as Kathleen Holt, who is joining shortly; and Adam Tatro, who has been our EMR (Electronic Medical Record) expert for a while. Carrie Irvine and Amanda Davin in Academic IT are also part of the team.

So we’re going to be a robust resource for people who are looking to sort through nearly any kind of big data. Whether it’s small, in-house research projects that use the EMR, or a project that looks at patient information across populations and across datasets, or something as big as national utilization data of Medicare — we can help with all of that. And that’s what we want people to know.

Previous director’s updates:

August 2014 – Nana Bennett talks about the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.