Objective: To assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau. Methods: From the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly aged >=65 years with both AV-1451 tau-PET and PiB-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the...

Intrapleural pressure during a forced vital capacity (VC) manoeuvre is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression; TGC), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across...

Objective Localization of seizure onset zone in focal epilepsy patients is a crucial step prior to surgical planning. Noninvasively achieving this goal would have a tremendous impact on clinical management of intractable seizure. Methods In a total of 39 focal epilepsy patients, we recorded and extracted 138 seizures and 1,325 interictal epileptic discharges using high-density EEG. We have investigated a novel approach for directly imaging sources of seizures and interictal spikes from high density EEG...

The role of our gut microbiota in health and disease is largely attributed to the collective metabolic activities of the inhabitant microbes. A system-level framework of the microbial community structure, mediated through metabolite transport, would provide important insights into the complex microbe-microbe and host-microbe chemical interactions. This framework, if adaptable to both mouse and human systems, would be useful for mechanistic interpretations of the vast amounts of experimental data from gut microbiomes in murine animal...

Adipose tissue is recognized as a major source of systemic inflammation with age, driving age-related tissue dysfunction and pathogenesis. Macrophages (Mϕ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA-seq analysis of ATMs from young (10-week old) and healthy aged (80-week old) mice. One of the genes identified, V-set immunoglobulin-domain-containing 4 (VSIG4/CRIg), encodes a...

Objective. Identify preferred neurofilament assays, and clinically validate serum NfL and pNfH as prognostic and potential pharmacodynamic biomarkers relevant to ALS therapy development. Methods. Prospective, multi-center, longitudinal observational study of patients with ALS (n=229), primary lateral sclerosis (PLS, n=20) and progressive muscular atrophy (PMA, n=11). Biological specimens were collected, processed and stored according to strict standard operating procedures (SOPs) 1. Neurofilament assays were performed in a blinded manner by independent contract research organizations (CROs). Results....

Background: Somatic CDKN2A and TP53 mutations are recurrent events in melanoma, occurring in 13.3% and 15.1% of cases respectively and are associated with poorer outcomes. It is unclear what effect somatic CDKN2A and TP53 mutations have on the clinical outcomes of patients treated with checkpoint inhibitors. Methods: All patients with cutaneous melanoma or melanoma of unknown primary who received checkpoint inhibitor therapy and underwent genomic profiling with the 50-gene Mayo Clinic solid tumor targeted cancer...