Excess dietary salt and salt-sensitivity contribute to cardiovascular disease. Distinct T cell phenotypic responses to high salt and hypertension as well as influences from environmental cues are not well understood. The aryl hydrocarbon receptor (AhR) is activated by dietary ligands, promoting T cell and systemic homeostasis.
View Article and Find Full Text PDFGenetic disruption of the RAS binding domain (RBD) of PI 3-kinase (PI3K) prevents the growth of mutant RAS driven tumors in mice and does not impact PI3K's role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3K interaction may represent an attractive strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3K lipid kinase activity such as alpelisib. Here we report compounds that bind covalently to cysteine 242 in the RBD of PI3K p110α and block the ability of RAS to activate PI3K activity.
View Article and Find Full Text PDFCurrent NICE guidelines state that in high-risk melanoma patients, imaging should not be offered before SLNB unless lymph node or distant metastases are suspected. Our experience has been that in patients with pT3b, pT4a and pT4b melanomas, the rate of management-changing findings on axial imaging prior to SLNB was high and that 'stage before operating' is a better approach. We now offer full axial imaging as staging to all high-risk melanoma patients prior to SLNB and advise other skin cancer MDTs to follow this approach.
View Article and Find Full Text PDFPhase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases such as cystic fibrosis (CF), particularly with increasing rates of multi-drug-resistant infections.
View Article and Find Full Text PDFBackground: Posterior fossa tumors (PFTs) comprise 15%-20% of adult brain tumors, with the reported frequency of hydrocephalus (HCP) ranging between 3.7% and 58%. Most HCP resolves after resection of PFTs, but studies report persistent or new-onset HCP occurring in between 2% and 7% of cases.
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