Check out “What’s New in Research” to find out about discoveries and advancements from Brigham researchers. This month, we feature new research from Brigham researchers on microfinance interventions to reduce intimate partner violence, a new platform to probe cell-cell crosstalk PSA level at time of salvage therapy and risk of death, an ingestible microdevice and more.
Microfinance Interventions Found to Reduce Rates of Intimate Partner Violence
Approximately 27 percent of women between 15 and 49 years old who have ever been sexually active have experienced intimate partner violence (IPV). A new study led by researchers at Brigham and Women’s Hospital analyzed the use of microfinance interventions as a way of reducing rates of IPV, as poverty has been associated with higher prevalence of IPV. The types of violence measured were defined by the World Health Organization (WHO), which recognizes four IPV domains: physical, psychological and emotional, sexual, and controlling behaviors. The study evaluated results from 10 randomized clinical trials, each of which used different permutations of subjects and microfinance interventions. Microfinance interventions included cash and asset transfers, as well as microloan programs targeting poverty. Some trials included lifestyle trainings such as health and nutrition or gender and HIV, and one trial provided health services. The subjects were women considered at risk for IPV, with three trials focusing on mothers and one with an emphasis on young women enrolled in high school. Overall, the researchers found that microfinance interventions play a role in the reduction of psychological and emotional IPV, as well as controlling behaviors. There was also low-certainty evidence to suggest these interventions reduce sexual violence; however, no association was found regarding physical violence.
“Poverty is a key driver associated with IPV, and is associated with several indirect drivers of IPV, including worse educational outcomes and higher exposure to childhood abuse and neglect,” said Lao-Tzu Allan-Blitz, MD and Rose Olson, MD, the studies two lead authors from the Brigham’s Division of Global Health Equity. “The observed reductions were persistent and significant despite heterogeneity in microfinance interventions.”
Read more in JAMA Open Network.
New Platform Allows Researchers to Listen in on Cell-Cell Crosstalk
Inflammatory neurological diseases, such as multiple sclerosis (MS), can arise when cell-to-cell communication between cells in the central nervous system (CNS) goes awry. But exactly how this cellular crosstalk leads to the molecular changes that drive disease remain unknown. To address this, researchers from Brigham and Women’s Hospital developed a platform that allows them to perform genetic screens of cell-cell interactions to identify genes that control biologic processes. The new tool, known as systematic perturbation of encapsulated associated cells followed by sequencing, or SPEAC-seq, combines CRISPR-Cas9 and droplet microfluidics. Using this platform, the team studied interactions between two types of CNS cells—microglia and astrocytes—and identified a potential suppressor of disease-promoting astrocytes in preclinical models of MS and in clinical samples.
“SPEAC-Seq allows the high-throughput and systematic identification of cell-cell communication mechanisms,” said corresponding author Francisco Quintana, PhD, of the Brigham’s Ann Romney Center for Neurologic Diseases. “There are many potential applications for this platform, such as combining it with epigenome or transcriptome analyses to identify therapeutics that could change cell-cell interactions. We look forward to exploring these possibilities in the future.”
Read more in Science.
Researchers Discover Link Between PSA Level at Time of Salvage Therapy Following Surgery and Risk of Death
The performance characteristics of prostate-specific membrane antigen positron emission tomography improves with increasing prostate-specific antigen (PSA) level. This, coupled with insurance approval concerns if applied for too early, causes some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) until well after PSA failure, typically at PSA levels exceeding 0.30 ng/ml.
To determine whether such a delay increases mortality risk, a multinational group led by researchers from Dana-Farber Brigham Cancer Center studied radical prostatectomy and lymph node specimens from 25,551 patients with no more than one high-risk factor (prostatectomy Gleason score of 8–10 or evidence at surgery of extension of the cancer outside the prostate). They sought to identify a PSA level above which initiating sRT is associated with increased mortality risk.
The research team used multivariable Cox regression analysis beginning at a PSA level of 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of surgery, established prostate cancer prognostic factors, institution, and time-dependent use of androgen deprivation therapy.
The study found that after a median follow-up of six years, patients who received sRT at a PSA level higher than 0.25 ng/mL had approximately a 50 percent higher risk of death compared with those who received sRT when the PSA was at or below 0.25 ng/ML.
“At Dana-Farber Brigham, we tend to be more medically conservative and not allow these restraints to drive patients to a lower cure rate,” said principal investigator Anthony Victor D’Amico, MD, PhD, chief of Genitourinary Radiation Oncology, Dana-Farber Brigham Cancer Center. “Normally, we would want to start sRT at a PSA level of 0.2, or even 0.1 ng/ml in most cases, to decrease the risk of the cancer metastasizing or becoming resistant to existing salvage treatments such as radiation and androgen deprivation therapy and to maximize curability.”
Read more in the Journal of Clinical Oncology.
Location-aware Ingestible Microdevices Monitor Gastrointestinal Environment
Gastrointestinal (GI) tract motility disorders such as gastroparesis, incontinence and constipation affect more than one-third of the population globally. Currently, techniques like nuclear studies, endoscopy, manometry, and radiologic studies are the gold standard to understand, monitor and treat such disorders. However, these procedures are invasive, often involve potentially harmful X-ray radiation, and require repeated evaluations in a hospital setting. Alternatives like video capsule endoscopy are less invasive but lack direct measurement of the capsule’s location in the GI tract.
Researchers from Brigham and Women’s Hospital, in collaboration with engineers at MIT and Caltech, developed a platform for localizing and tracking wireless microdevices with millimeter-scale spatial resolution inside the GI tract in real time and in non-clinical settings, without any X-ray radiation. They were able to achieve this by generating three-dimensional magnetic field gradients in the gastrointestinal field using high-efficiency planar electromagnetic coils that each encoded a point in space with a distinct magnetic field. They tested the coils in an in vitro saline tank to confirm the theoretical localization resolution. Then they tracked the coils in swine models and found the system was a highly accurate indicator of defecation.
“Here we report the three-dimensional localization and tracking of wireless ingestible microdevices in the gastrointestinal tract of large animals in real time and with millimeter-scale resolution,” said corresponding author Giovanni Traverso, MD, PhD, MBBCH, Division of Gastroenterology, Hepatology and Endoscopy at the Brigham. “Such a portable and non-invasive procedure holds the potential for significant clinical benefit without causing patients discomfort.”
Read more in Nature Electronics.