Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

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ObjectivesTo identify and critically appraise published clinical practice guidelines (CPGs) regarding healthcare of gender minority/trans people.DesignSystematic review and quality appraisal using AGREE II (Appraisal of Guidelines for Research and Evaluation tool), including stakeholder domain prioritisation.SettingSix databases and six CPG websites were searched, and international key opinion leaders approached.ParticipantsCPGs relating to adults and/or children who are gender minority/trans with no exclusions due to comorbidities, except differences in sex development.InterventionAny health-related intervention connected to the care of gender minority/trans people.Main outcome measuresNumber and quality of international CPGs addressing the health of gender minority/trans people, information on estimated changes in mortality or quality of life (QoL), consistency of recommended interventions across CPGs, and appraisal of key messages for patients.ResultsTwelve international CPGs address gender minority/trans people’s healthcare as complete (n=5), partial (n=4) or marginal (n=3) focus of guidance. The quality scores have a wide range and heterogeneity whichever AGREE II domain is prioritised. Five higher-quality CPGs focus on HIV and other blood-borne infections (overall assessment scores 69%–94%). Six lower-quality CPGs concern transition-specific interventions (overall assessment scores 11%–56%). None deal with primary care, mental health or longer-term medical issues. Sparse information on estimated changes in mortality and QoL is conflicting. Consistency between CPGs could not be examined due to unclear recommendations within the World Professional Association for Transgender Health Standards of Care Version 7 and a lack of overlap between other CPGs. None provide key messages for patients.ConclusionsA paucity of high-quality guidance for gender minority/trans people exists, largely limited to HIV and transition, but not wider aspects of healthcare, mortality or QoL. Reference to AGREE II, use of systematic reviews, independent external review, stakeholder participation and patient facing material might improve future CPG quality.PROSPERO registration numberCRD42019154361.

Summary Background Erosive pustular dermatosis of the scalp (EPDS) is a chronic condition characterized by erosive plaques and subsequent scarring alopecia as a result of local trauma or inflammation. A number of therapeutic approaches have been described in the literature but there is no consensus of opinion on optimal treatment of the disease. Objectives To provide evidence‐based recommendations for topical and systemic treatment of adult patients with EPDS by performing a systematic review. Methods The MEDLINE, MEDLINE In‐Process, Embase and Cochrane databases were searched from inception to 26 June 2019 in accordance with the PRISMA guidelines for studies involving adult patients treated for EPDS with at least one reported response to treatment. The study was registered on PROSPERO. Texts were reviewed independently by two authors. The risk of bias and quality of the studies were assessed using the Quality Appraisal Checklist for Case Series Studies. Results In total 75 studies were included, involving 168 patients. Many treatments have been reported in the literature, with varying degrees of therapeutic success. The results were highly heterogeneous and methodological quality was very low. We were unable to perform a meta‐analysis on the data. Conclusions The limited available evidence supports use of topical corticosteroids, with or without oral zinc, followed by maintenance therapy with topical calcineurin inhibitors as being effective in managing this condition. Topical photodynamic therapy is also potentially beneficial in the management of EPDS. Prospective, comparative, randomized controlled trials are required in order to provide further evidence to guide treatment.