Prolonged exposure of the skin to UV radiation causes previtamin D3, the initial photoproduct formed by opening of the B ring of 7-dehydrocholesterol, to undergo a second photochemical reaction where the B-ring is reformed giving lumisterol3 (L3), a stereoisomer of 7-dehydrocholesterol. L3 was believed to be an inactive photoproduct of excessive UV radiation whose formation prevents excessive vitamin D production. Recently, we reported that L3 is present in serum and that CYP11A1 can act on L3 producing monohydroxy- and dihydroxy-metabolites which inhibit skin cell proliferation similarly to 1α,25-dihydroxyvitamin D3. In this study we tested the ability of human CYP27A1 to hydroxylate L3. L3 was metabolized by purified CYP27A1 to 3 major products identified as 25-hydroxyL3, (25R)-27-hydroxyL3 and (25S)-27-hydroxyL3, by NMR. These three products were also seen when mouse liver mitochondria containing CYP27A1 were incubated with L3. The requirement for CYP27A1 for their formation by mitochondria was confirmed by the inhibition of their synthesis by 5β-cholestane-3α,7α,12α-triol, an intermediate in bile acid synthesis which serves as an efficient competitive substrate for CYP27A1. CYP27A1 displayed a high k for the metabolism of L3 (76 mol product/min/mol CYP27A1) and a catalytic efficiency (k/K) that was 260-fold higher than that for vitamin D3. The CYP27A1-derived hydroxy-derivatives inhibited the proliferation of cultured human melanoma cells and colony formation with IC values in the nM range. Thus, L3 is metabolized efficiently by CYP27A1 with hydroxylation at C25 or C27 producing metabolites potent in their ability to inhibit melanoma cell proliferation, supporting that L3 is a prohormone which can be activated by CYP-dependent hydroxylations.

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Background The COVID‐19 pandemic led to a global shortage of iodinated contrast media (ICM) in early 2022. ICM is used in more than half of the computed tomography of the abdomen and pelvis (CTAP) performed to diagnose an acute abdomen (AA). In response to the shortage, the RANZCR published contrast‐conserving recommendations. This study aimed to compare AA diagnostic outcomes of non‐contrast CTs performed before and during the shortage. Methods A single‐centre retrospective observational cohort study of all adult patients presenting with an AA who underwent a CTAP was conducted during the contrast shortage period from May to July 2022. The pre‐shortage control comparison group was from January to March 2022; key demographics, imaging modality indication and diagnostic outcomes were collected and analysed using SPSS v27. Results Nine hundred and sixty‐two cases met the inclusion criteria, of which n = 502, 52.2% were in the shortage period group. There was a significant increase of 464% in the number of non‐contrast CTAPs performed during the shortage period (P < 0.001). For the six AA pathologies, only n = 3, 1.8% of non‐contrast CTAPs had equivocal findings requiring further imaging with a contrast CTAP. Of the total CTs performed, n = 464, 48.2% were negative. Conclusion This study showed that when non‐contrast CTs are selected appropriately, they appear to be non‐inferior to contrast‐enhanced CTAPs in diagnosing acute appendicitis, colitis, diverticulitis, hernia, collection, and obstruction. This study highlights the need for further research into utilizing non‐contrast scans for assessing the AA to minimize contrast‐associated complications.

Skin and wound blotting are non‐invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or broken cutaneous surface to detect biomarkers. However, there has been no comprehensive review of the evidence for the techniques used and data obtained to date. The primary aim of this study was to review the utilities of surface blotting for the diagnosis and prognosis of physiological, pre‐disease, and pathological states. The secondary aim was to summarise the procedural steps. A systematic literature search was conducted on 9 July 2021 using Medline, Embase, and Google Scholar databases. Investigators used McMaster's Critical Review Form for Quantitative Studies to assess quality, then performed a narrative synthesis reporting according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Twenty‐five studies were reviewed. Eighteen studies were of good quality, and seven were of moderate quality. These studies conducted skin and wound blotting on 176 animals and 1546 humans. Studies reported physiological and pathological states for diagnosis and prediction of conditions, including skin tears, wound healing, biofilm detection, and skin barrier function. The four steps for blotting are surface preparation, blot preparation, application and removal of blot, and analysis. This review demonstrates that blotting can determine the skin and wound surface chemistry using a versatile and reproducible technique. However, future research is needed to validate the technique and skin biomarkers identified.