Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm, Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, consequently promoting longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids whose abundance was increased in worms constitutively over-expressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans.

Background: Intracellular lipid-binding proteins stimulate lipid-induced gene expression. Results: Fatty acid-binding protein 5 (FABP5) uses a molecular switch that controls nuclear import when complexed with activating fatty acids. Conclusion: FABP5 is tuned to selectively stimulate peroxisome proliferation-activated receptor ␤/␦ transactivation in response to specific fatty acids based on their structural features. Significance: FABPs provide a second level of regulatory control of nuclear receptor-mediated lipid signaling.

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procedure (SOP) for the management of patients with a CIED undergoing radiation therapy treatment. The team recognized the importance of nursing in this process and determined that the process to manage this patient population should be nurse driven. A cardiac device carepath and cardiac device checklist were created within the electronic health record (ARIA). The SOP, care path and checklist were reviewed and approved by the multidisciplinary team to include cardiology. Results: Optimized workflow for CIED patients includes identification of these patients at the time of consultation by nursing. The radiation oncology nurse then launches the ARIA care path and encounter to initiate CIED workflow which facilitates communication and care coordination. An alert is placed in the patient's ARIA record and a copy of the CIED card is scanned into ARIA. A consult is then placed with cardiology for recommendations regarding risk level and interrogations schedule. Simulation therapist measures the proximity of the treatment field to the device and documents in ARIA. If CIED is within 3 CM of the field or 5% isodose line the dosimetrist will contour the CIED as a structure and determine DVH/point dose. Physics performs in vivo measurements per TG203 guidelines and documents in ARIA record. Patients are followed throughout treatment to verify interrogation time points are completed. All documentation of this process is performed using ARIA carepaths and checklists as outlined above. Conclusion: By implementing the AAPM TG-203 guidelines, this multidisciplinary team has been able to create a workflow to enhance patient safety. It has standardized the CIED management across our six campuses and ensures that all key stakeholders are involved in the workflow. Use of ARIA based documentation creates a stream-lined, transparent process that could be easily duplicated within other radiation oncology clinics.