Linoleic acid-derived diol 12,13-DiHOME enhances NLRP3 inflammasome activation in macrophages.

12,13-dihydroxy-9z-octadecenoic acid (12,13-DiHOME) is a linoleic acid diol derived from cytochrome P-450 (CYP) epoxygenase and epoxide hydrolase (EH) metabolism. 12,13-DiHOME is associated with inflammation and mitochondrial damage in the innate immune response, but how 12,13-DiHOME contributes to these effects is unclear. We hypothesized that 12,13-DiHOME enhances macrophage inflammation through effects on NOD-like receptor protein 3 (NLRP3) inflammasome activation. To test this hypothesis, we utilized human monocytic THP1 cells differentiated into macrophage-like cells with phorbol myristate acetate (PMA). 12,13-DiHOME present during lipopolysaccharide (LPS)-priming of THP1 macrophages exacerbated nigericin-induced NLRP3 inflammasome activation. Using high-resolution respirometry, we observed that priming with LPS+12,13-DiHOME altered mitochondrial respiratory function. Mitophagy, measured using mito-Keima, was also modulated by 12,13-DiHOME present during priming. These mitochondrial effects were associated with increased sensitivity to nigericin-induced mitochondrial depolarization and reactive oxygen species production in LPS+12,13-DiHOME-primed macrophages. Nigericin-induced mitochondrial damage and NLRP3 inflammasome activation in LPS+12,13-DiHOME-primed macrophages were ablated by the mitochondrial calcium uniporter (MCU) inhibitor, Ru265. 12,13-DiHOME present during LPS-priming also enhanced nigericin-induced NLRP3 inflammasome activation in primary murine bone marrow-derived macrophages. In summary, these data demonstrate a pro-inflammatory role for 12,13-DiHOME by enhancing NLRP3 inflammasome activation in macrophages.

Implementation of Teledermatology in Alberta, Canada: A Report of One Thousand Cases.

BACKGROUND: Teledermatology utilizes photoimaging and background information to allow dermatologists to remotely provide a diagnosis to practitioners. ConsultDerm is an asynchronous, web-based teledermatology software that allows practitioners to submit their electronic referrals for assessment by board-certified dermatologists. OBJECTIVE: Our study aimed to retrospectively analyze teledermatology's utilization in Canada by using the teledermatology platform ConsultDerm. METHODS: After implementing inclusion criteria, 1000 patients were selected, and relevant demographic and clinical information were extracted for data analysis. In addition, an online survey with pre-formulated questions was distributed to 7 dermatologists currently using the ConsultDerm platform to determine their experience in utilizing teledermatology. RESULTS: Of the 1000 patients, 66.5% had not received treatment prior to their teledermatology referral, and on average, patients experienced symptoms for 489.5 days prior to their referral. Diagnoses made were categorized by conditions, most common being dermatitis (37.1%), followed by acneiform conditions (10.6%), benign lesions/neoplasms (12.1%), infections (9.4%), and dyspigmentation (3.1%). Most consults originated from small population centers, and the referring practitioners were predominantly family physicians. Dermatologists utilizing the platform expressed ease of use, however, areas of improvement were identified such as increasing the quality of imaging and more detailed patient history. CONCLUSION: Through our analysis of 1000 cases, we identified how a teledermatology consultation could be used to assess a wide variety of cutaneous conditions, improving access for patients who may face barriers to seeing a dermatologist.