Gain-of-function mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most prevalent in low-grade gliomas and secondary glioblastoma. They lead to intracellular accumulation of the oncometabolite 2-hydroxyglutarate, represent an early pathogenic event, and are considered a therapeutic target. In this proof-of-concept study, we show that [1-13C] α-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Using 13C magnetic resonance spectroscopy in combination with dissolution Dynamic Nuclear Polarization, the metabolic fate of hyperpolarized [1-13C] α-ketoglutarate is studied in isogenic glioblastoma cells that differ only in their IDH1 status. In lysates and tumors that express wild-type IDH1, only hyperpolarized [1-13C] α-ketoglutarate can be detected. In contrast, in cells that express mutant IDH1, hyperpolarized [1-13C] 2-hydroxyglutarate is also observed, both in cell lysates and in vivo in orthotopic tumors.

There are over 1 million transgender people living in the United States, and 33% report negative experiences with a healthcare provider, many of which are connected to data representation in electronic health records (EHRs). We present recommendations and common pitfalls involving sex- and gender-related data collection in EHRs. Our recommendations leverage the needs of patients, medical providers, and researchers to optimize both individual patient experiences and the efficacy and reproducibility of EHR population-based studies. We also briefly discuss adequate additions to the EHR considering name and pronoun usage. We add the disclaimer that these questions are more complex than commonly assumed. We conclude that collaborations between local transgender and gender-diverse persons and medical providers as well as open inclusion of transgender and gender-diverse individuals on terminology and standards boards is crucial to shifting the paradigm in transgender and gender-diverse health.

Background--Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction.

BackgroundCirculating angiogenic cells (CACs) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease (CAD) impairs the therapeutic potential of CACs for myocardial infarction (MI) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (NO) synthase (eNOS) overcomes these defects.Methods and ResultsWe recruited 40 volunteers varying by sex, age (< or ≥45 years), and CAD and subjected their CACs to well‐established functional tests. Age and CAD were associated with reduced CAC intrinsic migration (but not specific response to vascular endothelial growth factor, adherence of CACs to endothelial tubes, eNOS mRNA and protein levels, and NO production. To determine how CAC function influences therapeutic potential, we injected the 2 most functional and the 2 least functional CAC isolates into mouse hearts post MI. The high‐function isolates substantially improved cardiac function, whereas the low‐function isolates led to cardiac function only slightly better than vehicle control. Transduction of the worst isolate with eNOS cDNA adenovirus increased NO production, migration, and cardiac function of post‐MI mice implanted with the CACs. Transduction of the best isolate with eNOS small interfering RNA adenovirus reduced all of these capabilities.ConclusionsAge and CAD impair multiple functions of CACs and limit therapeutic potential for the treatment of MI. eNOS gene therapy in CACs from older donors or those with CAD has the potential to improve autologous cell therapy outcomes.