ABSTRACT
Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics.
Subject(s)
Adipogenesis , Bone Marrow , Fluorocarbons , Mice, Inbred C57BL , PPAR gamma , Sulfonic Acids , Adipogenesis/drug effects , Animals , Fluorocarbons/toxicity , Mice , Bone Marrow/drug effects , Bone Marrow/metabolism , PPAR gamma/metabolism , Sulfonic Acids/toxicity , Male , Signal Transduction/drug effects , Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Adipose Tissue/drug effects , Adipose Tissue/metabolismABSTRACT
Multiplex PCR combined with a pharmacist-driven reporting protocol was compared to the standard of care within a community hospital to evaluate initial changes after notification of a positive blood culture. The intervention group demonstrated decreased times to changes in antimicrobial therapy (P = 0.0081), increased changes to optimal antimicrobial therapy (P = 0.013), and decreased vancomycin use for coagulase-negative staphylococcus contaminants (P < 0.01) with multiplex PCR implementation and pharmacist intervention.