On average, about 100,000 people in the U.S. experience severe fractures that fail to heal each year. The current standard of care for these injuries often involves long hospital stays, repeated surgeries, and still result in long-term disability.

While bones are usually able to repair themselves in the case of small cracks and fractures, severe breaks and fractures can result in gaps that are too large for the bones to fill on their own. In these cases, missing bone may be replaced by bone from another place in the patient’s body, which is painful and may cause infection at the donor site, or by a piece of bone from a cadaver, which does not always integrate well with the patient’s bone because it is dead tissue.

A new fracture-healing method, developed by University researchers and colleagues at Cedars-Sinai and successfully demonstrated in laboratory animals, combines ultrasound, stem cell, and gene therapies to help cue bones to regenerate across large gaps, Susanne Pallo reports at the Research@URMC blog. Their findings are published in the journal Science Translational Medicine.

Hani Awad, professor of biomedical engineering and orthopaedics, tested the healed fractures in the Center for Musculoskeletal Research’s state-of-the-art Biomechanics Lab with the help of Jayne Gavrity, a biomechanical and imaging engineer in the center. According to Awad, the newly formed bone was as strong as the patient’s own bone grafts, suggesting the new procedure could replace the painful grafting procedure.

To heal the fractures, the team filled the fracture gaps with a scaffold of collagen, a structural protein the body normally uses to make bone. Over two weeks, stem cells were recruited to the scaffold in the fracture site. Then the team delivered a gene to the stem cells that would turn them into bone-creating cells. The gene was delivered with the aid of microbubbles that create tiny holes in the stem cell membrane and enable entry of the gene into the cells when they are hit with pulses of ultrasound.

This technique improves upon other investigational therapies that are costly, painful, and increase risk of infection and tissue damage near the fracture site. And it was able to completely heal leg fractures in the laboratory animals in just eight weeks.

Co-senior authors Dan Gazit, co-director of the Skeletal Regeneration and Stem Cell Therapy Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Gadi Pelled, assistant professor of surgery at Cedars-Sinai, hope this technique will be useful in humans, but more studies are needed to determine this.

The study was featured in Science magazine, a publication of the American Association for the Advancement of Science.

The ubiquitous human herpesvirus 6 (HHV-6) may play a critical role in impeding the brain’s ability to repair itself in diseases like multiple sclerosis.  The findings, which appear in the journal Scientific Reports, may help explain the differences in severity in symptoms that many people with the disease experience.

“While latent HHV-6 – which can be found in cells throughout the brain – has been associated with demyelinating disorders like multiple sclerosis it has not been clear what role, if any, it plays in these diseases,” said Margot Mayer-Proschel, an associate professor of biomedical genetics and co-author of the study. “These findings show that, while in the process of hiding from the immune system, the virus produces a protein that has the potential to impair the normal ability of cells in the brain to repair damaged myelin.”

It is estimated that more than 80 percent of people have been exposed to HHV6 at some point during their early childhood. HHV-6 is the most common human herpesvirus. Infections that occur during childhood often go unnoticed.  A much smaller number – one percent of people – have congenital HHV6 in which a single copy of the virus is acquired through either the father’s sperm or mother’s egg and is passed on to the developing child.

While the immune system fights off the most active forms of the infection, the virus never truly leaves our bodies and can reactivate later in life. The herpesvirus 6 accomplishes this form of latency by integrating itself into our genetic code and thus hiding in cells and evading the immune system.

One of the ways the virus does this is by expressing a protein called U94. The researchers discovered that when U94 is expressed in oligodendrocyte progenitor cells (OPCs) — which play an important role in maintaining the brain’s supply of myelin– the cells stop migrating to where they are needed.

Read more here.

A pathology researcher at the Medical Center believes she’s discovered an important phenomenon in normal-looking breast tissue that could foreshadow an aggressive tumor known as triple-negative breast cancer.

Xi Wang, who recently reported her findings in Human Pathology,  analyzes hundreds of breast tissue samples each month, and based on her observations came up with the hypothesis that an alteration in the p53 gene might be the beginning of a cell’s cascade toward becoming fully cancerous.

P53 is a well-known tumor-suppressor gene. When it’s acting as it should, p53 keeps cancer at bay. But when it is mutated, it no longer suppresses cancer cells. It is frequently mutated in lung cancer and also commonly mutated in a type of high-grade ovarian cancer. In breast cancer, the p53 mutation is detected in less than 25 percent of cases, Wang said, but the frequency is much higher in triple-negative breast cancer, which is much harder to treat.

Her latest research looked at normal/benign tissue samples from women who also carried the BRCA1 or BRCA2 genetic mutations, which increase the chances of getting breast cancer by more than 50 percent and significantly boost the likelihood that breast cancer will be the triple-negative subtype. Results showed that p53 is more frequently altered in the seemingly “normal” breast tissue in BRCA carriers, compared with the general population. This may help to explain why BRCA carriers are at much higher risk for aggressive cancer.

Read more here.

LaRon E. Nelson, assistant professor at the School of Nursing and the Dean’s Endowed Fellow in Health Disparities, who has been selected for induction as a fellow in the American Academy of Nursing (AAN). Nelson is among a class of 173 nurse leaders who will be honored at the academy’s annual policy conference in Washington, D.C., in October. Read more here.

(This is part of a monthly series to help principal investigators understand their role in ensuring that human subject protection requirements are met in their studies.)

Insufficient documentation of the regulatory file is the most common deficiency found by Office for Human Subject Protection Quality Improvement (OHSP-QI) reviewers.

And yet, of all the possible errors to be identified, this is the easiest to prevent.

All studies, regardless of the nature of study procedures or the risks involved in participating, are required to maintain documentation that demonstrates compliance with regulatory requirements pertaining to Institutional Review Board (IRB) review and approval. This is often referred to as the ‘regulatory file.’

Minimally, for research deemed exempt, this means maintaining a copy of the finalized study protocol, IRB application, notification regarding the exemption determination, and watermarked information letters or recruitment materials, if applicable. For all other research, this includes copies of all IRB approval letters (including amendment and continuing review approval letters), all IRB-approved protocols, watermarked versions of all IRB-approved consent documents/recruitment materials, and any other IRB-approved documents or communications, at a minimum. See the OHSP-QI website for a full description of Regulatory File Contents.

The first major hurdle in meeting this responsibility is knowing exactly what types of documentation must be maintained. If you are unsure, OHSP-QI provides a free Study Start-Up Consultation service aimed at assisting study teams in identifying and evaluating planned study documentation.

The second major hurdle in meeting this responsibility is maintaining the file throughout the conduct of the study. Do not rely on the RSRB Online Submission System (ROSS) to maintain this regulation; ROSS is not meant to act as your regulatory file.  Best practices for maintaining your regulatory file include:

• Organizing regulatory files in a systematic manner (an example of how to organize an electronic regulatory file is available here)
• Saving regulatory file items in “real time” (e.g., as soon as items are approved/re-approved)
• If you have delegated this responsibility to other study team members, monitoring progress of this expectation (e.g., randomly spot checking the regulatory file bi-annually)

Have questions about your study documentation? Contact the OHSP-QI team.

The Rochester Aging Research Center invites applications for pilot funding for projects in basic or geriatric aging research. Applications are due September 1. Contact Dirk Bohmann or Anne Reed for more information.

The Clinical and Translational Science Institute (CTSI) offers a Research Team Builder service that can connect faculty members with established researchers who have obtained funding in their field.

The report is built from data available through the NIH Reporter Matchmaker application, which analyzes large amounts of text and gives ranked results of projects that most closely resemble the concept and terms in the provided text.

Researchers can supply a conference abstract, research statement, or other scientific text up to 15,000 characters, and the CTSI will do the rest. See an example and learn more in the CTSI Stories Blog.

To obtain a report, contact the Research Help Desk.

Mobile technology can be used in clinical trials to provide new types of information that were previously difficult or impossible to access.

For example, continuous measurement by a mobile device such as an accelerometer worn by persons with Parkinsons disease might capture more details about fluctuations in functionality, responses to medication, and important information about symptoms triggered by stress or other episodic disturbances that are hard to observe in clinic evaluations.

The Clinical Trials Transformation Initiative, a public-private partnership of over 80 members that strives to identify and drive adoption of practices that will increase the quality and efficiency of clinical trials, has released new endpoint recommendations focused on the use of mobile technology. Recommendations for selecting novel endpoints and practical approaches to developing endpoints are provided. Read the report here.

CTTI was established in 2007 through a partnership between the FDA and Duke, and is administered through the Duke Translational Medicine Institute.

Sara Nowacki, Biomedical Engineering, “Short-term parathyroid hormone treatment aids in early cartilage repair, but cannot rescue matrix-assisted repair.” 9:30 a.m., July 18, 2017. K-307 (SMD). Advisor: Hani Awad.

Miles Wilklow-Marnell, Chemistry, “Manipulation of Carbon-Element Bonds by Pincer Ligated Iridium Complexes.” 11 a.m. July 18, 2017. 209 Computer Studies Building. Advisor: William Jones.

Ashley Cannaday, Optics, “Improved Time-Lapsed Angular Scattering Microscopy of Single Cells.” 9 a.m. July 20, 2017. Goergen 109. Advisor: Andrew Berger.

Pengcheng Li, Computer Science, “Optimizing Memory Management Using Timescale Theories.” 10 a.m. July 20, 2017. Wegmans Hall 2506. Advisor: Chen Ding.

Bradley Smith, Political Science, “Essays on Military Conflict and Cooperation.” 1 p.m. July 21, 2017. Harkness 329. Advisor: Mark Fey.

Jared Kneebone, Chemistry, “Electronic Structure and Reactivity in Iron-Catalyzed Carbon-Carbon Cross-Coupling Reactions and Dioxygen Reduction.” Noon, July 21, 2017. 109 Bausch & Lomb Hall. Advisor: Michael Neidig.

Today: UNYTE scientific session, “Collaborate to Innovate Maternal & Child Health Translational Research.” 10 a.m. to 3:30 p.m. Helen Wood Hall. Panel presentations, a poster session, interactive break-out groups, and a keynote address by Michele Caggana, deputy director of genetics and director of newborn screening at the Wadsworth School of Laboratory Sciences. For additional information, go to UNYTE Scientific Session.

July 18: Clinical and Translational Science Institute Town Hall Meeting.  Updates on new initiatives and funding opportunities; open forum question and answer period. Refreshments served. 4 to 5 p.m. Evarts Lounge, Helen Wood Hall.

July 19: Science, Technology, and Culture – a multidisciplinary reading group examining how science is shaped by the culture that surrounds it and how technological innovations change society. Join us for snacks and good conversation about Archangel, by Andrea Barrett. 5 p.m., Humanities Center Lobby (Rush Rhees Library). August book is Hidden Figures by Margot Lee Shetterly (meeting date tba). Please contact Emma_Grygotis@urmc.rochester.edu with any questions.

July 21:  Pangaea Discussion Series: “From Imaginationland to the Realm of Reality:  How Science Fiction Transforms Us.” 4:30 to 5:30 p.m., Medical Center Specialty Room 2-7536. Discussion Leader: Jeffrey Tucker, associate professor in the Department of English.  Snacks, coffee and tea provided. Hosted by the SMD Graduate Student Society and AS&E Graduate Student Association. Pangaea is a free-flowing group discussion that brings together perspectives from multiple academic disciplines to help participants discover creative new ideas and opportunities. Visit the GSS Facebook page for more student event updates.

Sept. 1: Deadline to apply for pilot funding from The Rochester Aging Research Center for projects in basic or geriatric aging research. Contact Dirk Bohmann or Anne Reed for more information.

Sept. 25 to 29: Early Stage Faculty Boot Camp to help senior instructors and assistant professors identify the skills they need for successful career advancement. 9 a.m. to 5 p.m. Visit the CTSI website for more details. Registration deadline is September 1.