Studies look at measuring blood flow velocity, a treatment strategy for non-small cell lung cancer, and the body’s response to airborne pathogens
Cerebrovascular Dynamics Index could help diagnose Alzheimer’s
The buildup of two pathological proteins, amyloid beta and phosphorylated tau, have long been considered hallmarks of Alzheimer’s disease. However, efforts to diagnose Alzheimer’s by searching for these proteins in spinal taps, PET imaging, and blood samples have drawbacks, including high cost and relatively low accuracy.
Research has shown that Alzheimer’s impairs vasomotor reactivity, in which the brain’s blood vessels dilate when carbon dioxide builds up in the blood. To determine whether this effect could be used to diagnose Alzheimer’s, two researchers from UT Southwestern Medical Center joined colleagues to develop the Cerebrovascular Dynamics Index (CDI). This noninvasive test uses Doppler ultrasound to measure blood flow velocity in some main arteries of the brain and near-infrared spectroscopy to measure oxygenation in the brain’s cortex.
Results from nearly 200 participants, published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, showed that the CDI distinguished among mild cognitive impairment, Alzheimer’s, and healthy individuals with better accuracy than existing methods. The authors say this test has significant promise to improve Alzheimer’s disease diagnosis and staging.
The study authors from UT Southwestern are Rong Zhang, Ph.D., Professor of Neurology, Biomedical Engineering, and Internal Medicine, an Investigator in the Peter O’Donnell Jr. Brain Institute, and Director of the Cerebrovascular Laboratory in the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Dallas; and Danilo Cardim, Ph.D., Instructor of Neurology.
Timed radiation extends survival for some non-small cell lung cancers
A subset of non-small cell lung cancer (NSCLC), the most common lung cancer type, has mutations in a molecule known as epidermal growth factor receptor (EGFR). Although EGFR-targeting drugs often work well initially to fight these cancers, most cases develop resistance and progress within two years. A study led by UT Southwestern researchers and published in eClinicalMedicine suggests that precisely timed radiation could be a useful additional treatment.
Results from a clinical trial involving 42 patients showed that highly targeted radiation therapy delivered eight weeks after drug initiation extended progression-free survival more than one year compared to outcomes seen with the drug alone. Patients on the new protocol also lived longer, with few additional side effects.
The study was led by Sawsan Rashdan, M.D., Associate Professor of Internal Medicine in the Division of Hematology and Oncology, and David Gerber, M.D., Professor of Internal Medicine and in the Peter O’Donnell Jr. School of Public Health. Dr. Rashdan is Director of Thoracic Medical Oncology Clinical Operations and a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW. Dr. Gerber serves as Co-Director of Education and Training in the Simmons Cancer Center.
Investigating how airway cells respond to pathogens
Airway epithelial surfaces are the primary contact point for numerous infectious bacteria and viruses, including those that cause tuberculosis, measles, COVID-19, the common cold, and influenza. Rare epithelial microfold cells (M cells) can serve as an entry site and initiate early immune responses to these pathogens. Although M cells have been extensively studied in the intestines, little is known about their development and function in the airway.
To better understand these cells and how the body responds to airborne pathogens, UT Southwestern researchers and colleagues analyzed single cell gene expression to identify cell types in the adenoid – an airway immune organ where M cells are found – and defined their developmental trajectories and relationships. Their study in Mucosal Immunology identified 26 unique cell types and determined that airway M cells arise from progenitor club cells and have a distinct gene expression signature consistent with their ability to shuttle particles and pathogens from the airway surface to waiting immune cells.
The researchers also found a previously unknown cell type that appears to be primed by the immune molecule interferon to prevent early infection. This research could eventually lead to new treatments and vaccines for airway infections.
UTSW contributors to this study are first author Samuel Alvarez-Arguedas, Ph.D., Assistant Instructor of Internal Medicine in the Division of Infectious Diseases and Geographic Medicine; senior author Michael Shiloh, M.D., Ph.D., Professor of Internal Medicine in the Division of Infectious Diseases and Geographic Medicine and of Microbiology; Ron Mitchell, M.D., Professor of Otolaryngology-Head & Neck Surgery and Pediatrics; and John Lafin, Ph.D., Computational Biologist.