Transient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration-approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium-dependent effects on myocyte contractility.

Rates of STIs continue to rise worldwide, and novel evidence-based interventions such as text messaging aimed at improving client services are needed. We conducted a meta-analysis to evaluate text messaging to support STI/HIV prevention and treatment interventions.

Body image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT).

Mutations effects on p53 isoforms' activities remain largely unknown, although they are mutated in 92% of TP53 mutant cancers. Therefore, exploring the effect of mutations on p53 isoforms activities is a critical, albeit unexplored area in the p53 field. In this article, we report for the first time a mutant Δ133p53α-specific pathway which increases IL4I1 and IDO1 expression and activates AHR, a tumor-promoting mechanism. Accordingly, mutant Δ133p53α R273H increases glioblastoma cancer cells proliferation and invasion while the WT does not. Furthermore, while WT Δ133p53α reduces apoptosis to promote DNA repair, the mutant also reduces apoptosis but fails to maintain genomic stability.Furthermore, both WT and mutant Δ133p53α reduce cellular senescence in a senescence inducer-dependent manner (temozolomide or radiation) because they regulate different senescence-associated target genes. Hence, WT Δ133p53α rescues temozolomide-induced but not radiation-induced senescence, while mutant Δ133p53α R273H rescues radiation-induced but not temozolomide-induced senescence. Lastly, using TCGA data, we determined that IL4I1, IDO1 and AHR are significantly higher in GBMs compared to LGGs. IL4I1 expression is increased in mutant TP53 LGGs and GBMs, although only significantly in LGG. Importantly, high expression of all three genes in LGG and IL4I1 in GBM is significantly associated with poorer patients' survival. These data show that, compared to WT Δ133p53α, R273H mutation reorientates its activities toward carcinogenesis and activates the oncogenic IL4I1/IDO1/AHR pathway, a potential prognostic marker and therapeutic target in GBM by combining drugs specifically modulating Δ133p53α expression and IDO1/Il4I1/AHR inhibitors.

Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue.