Phosphodiesterase inhibition restoreshypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study.

To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).

Combinatorial therapies for epigenetic, immunotherapeutic, and genetic targeting of chordoma.

Purpose: Chordoma, a rare malignancy of the axial skeleton and skull base, presents significant therapeutic challenges due to the high rates of tumor recurrence and resistance. While surgical resection and radiation therapy remain the gold standard of treatment, the lack of additional treatment options necessitates the exploration of novel therapies. Combinatorial therapies hold significant potential in shaping patient prognosis.

Policy and perceptions of pregnancy during training among residents of various subspecialties.

Purpose Of The Study: Increased risk for adverse birth outcomes, long work hours, limited control over one's own schedule, and concern for making up time may color resident perceptions of their pregnancy during residency. We aimed to survey residents across four different specialties about their personal experiences with pregnancy during training.

Study Design: Using a novel, validated, anonymous web-based survey instrument, we assessed experiences around pregnancy during residency training nation-wide.

Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.