Sex-specific mechanisms of cerebral microvascular BK dysfunction in a mouse model of Alzheimer's disease.

Introduction: Cerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca-activated K channels (BK) regulate cerebrovascular reactivity and are impaired in AD. BK activity depends on intracellular Ca (Ca sparks) and nitro-oxidative post-translational modifications.

A Framework for the Use and Likelihood of Regulatory Acceptance of Single-Arm Trials.

Background: Single-arm clinical trials (SAT) are common in drug and biologic submissions for rare or life-threatening conditions, especially when no therapeutic options exist. External control arms (ECAs) improve interpretation of SATs but pose methodological and regulatory challenges.

Objective: Through narrative reviews and expert input, we developed a framework for considerations that might influence regulatory use and likelihood of regulatory acceptance of an SAT, identifying non-oncology first indication approvals as an area of interest.

Effects of multi-walled carbon nanotubes on message and Micro-RNA in human lung BEAS-2B cells.

Multi-walled Carbon nanotubes (MWCNTs) lack sufficient quality cytotoxicity, toxicity, genotoxicity and genomic data on which to make environmental and regulatory decisions. Therefore, we did a multidisciplinary study of 3 MWCNTs in human lung cells (BEAS-2B) with the following endpoints: cytotoxicity, DNA damage, reactive oxygen and nitrogen species, lipid peroxidation and mRNA and microRNA expression analyses. The MWCNTs were either unfunctionalized or functionalized with either -OH or -COOH.

Effects of multi-walled carbon nanotubes on gene and microRNA expression in human hepatocarcinoma HepG2 cells.

The usage of multi-walled carbon nanotubes (MWCNT) has increased exponentially in the past years, but, potential toxicity mechanisms are not clear. We studied the transcriptomic alterations induced by one multi-walled carbon nanotube (MWCNT) and its -OH and -COOH functionalized derivatives in human HepG2 cells. We showed that all three MWCNT treatments induced alterations in stress-related signaling pathways, inflammation-related signaling pathways, cholesterol synthesis pathways, proliferation-related pathways, senescence-related pathways and cancer-related pathways.

Skeletal muscle density performance for screening frailty in older adults with cancer and the impact of diabetes: The CARE Registry.

Introduction: Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status.

Materials And Methods: We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry.