Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin.

BACKGROUND: An increasing number of studies have investigated the adverse effect profile of oral cannabinoids; however, few studies have provided sufficient data on the tolerability of topical cannabinoids in human participants. AIM: To assess the tolerability profile of several commercial topical formulations containing cannabidiol (CBD) and palmitoylethanolamide (PEA) on the skin of healthy human participants. METHODS: Three human clinical trials and one in vitro study were conducted. The potential for skin irritation, sensitization and phototoxicity of several products, were assessed via patch testing on healthy human skin. The products assessed included two formulations containing CBD and PEA, one containing hemp seed oil and four concentrations of CBD alone. Ocular toxicity was tested using a traditional hen\u27s egg chorioallantoic membrane model with three CBD, PEA and hemp seed oil formulations. RESULTS: There was no irritation or sensitization of the products evident via patch testing on healthy participants. Additionally, mild phototoxicity of a hemp seed oil product was found at the 48-h time point compared with the negative control. The in vitro experiment demonstrated comparable effects of cannabinoid products with historically nonirritating products. CONCLUSION: These specific formulations of CBD- and PEA-containing products are nonirritating and nonsensitizing in healthy adults, and further encourage similar research assessing their long-term safety and efficacy in human participants with dermatological diseases. There are some limitations to the study: (i) external validity may be limited as formulations from a single manufacturer were used for this study, while vast heterogeneity exists across unregulated, commercial CBD products on the market; and (ii) products were assessed only on normal, nondiseased human skin, and therefore extrapolation to those with dermatological diseases cannot be assumed

All-codon scanning identifies p53 cancer rescue mutations

In vitro scanning mutagenesis strategies are valuable tools to identify critical residues in proteins and to generate proteins with modified properties. We describe the fast and simple All-Codon Scanning (ACS) strategy that creates a defined gene library wherein each individual codon within a specific target region is changed into all possible codons with only a single codon change per mutagenesis product. ACS is based on a multiplexed overlapping mutagenesis primer design that saturates only the targeted gene region with single codon changes. We have used ACS to produce single amino-acid changes in small and large regions of the human tumor suppressor protein p53 to identify single amino-acid substitutions that can restore activity to inactive p53 found in human cancers. Single-tube reactions were used to saturate defined 30-nt regions with all possible codon changes. The same technique was used in 20 parallel reactions to scan the 600-bp fragment encoding the entire p53 core domain. Identification of several novel p53 cancer rescue mutations demonstrated the utility of the ACS approach. ACS is a fast, simple and versatile method, which is useful for protein structure–function analyses and protein design or evolution problems

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function

Color Atlas and Synopsis Of Pediatric Dermatology

xv.483 hal;23 c

Topical corticosteroid withdrawal (‘steroid addiction’): an update of a systematic review

Background Topical corticosteroid withdrawal is an entity associated with chronic steroid use and misuse that has not been fully described. Objective To further characterize this entity, elucidate relevant clinical features, and investigate possible treatments we provided an update to a systematic review done in 2015. Methods We searched Ovid Medline, Pubmed, and Cochrane library for terms related to topical corticosteroid withdrawal from April 2014 to September 2020. Results This entity usually occurs after prolonged use of moderate- to high-intensity topical steroid usage usually on the face. It is most common in women and many patients present due to improper use such as for cosmetic reasons. Symptoms include erythema, itchiness, and burning; secondary lesions are common scales. Limitations Due to the paucity of available study, we elected to include all articles found which led to limitations being lack of heterogeneity, diversity of outcome measures reported, and a higher risk of bias in some included studies. Conclusion Topical corticosteroid withdrawal should be suspected in patients presenting with prolonged usage, erythema, and burning or itch. Patient education and follow up is important to address improper usage. Future studies should focus on comparison group studies to investigate treatment and risk factors

Alternative, Complementary, and Forgotten Remedies for Atopic Dermatitis

Atopic dermatitis, perhaps more than other dermatologic diseases, has garnered much attention in the realm of alternative medicine. This may be because its etiopathogenesis is incompletely understood, it is increasingly common, and it waxes and wanes often without clear precipitants, opening up many opportunities for misinterpretation. Herein we explore the evidence for a number of different alternative and complementary therapies, from textiles to vitamin supplements. By definition, none have enough data to be deemed “effective” in a conventional sense, but it is hopeful that some show promising evidence that may one day lead to mainstream acceptance with further research

Algorithm-based readability assessment of online patient educational material for erythropoietic protoporphyria

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173089/1/ijd15825.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173089/2/ijd15825_am.pd

Color Atlas dan Synopsis of Pediatric Dermatology

xiv. 497 hln.; ill.; 23 c

The Role of Polyphenols in Rosacea Treatment: A Systematic Review

Objectives: Various treatment options are available for the management of rosacea symptoms such as facial erythema, telangiectasia, papules and pustules, burning, stinging, and itching. Botanical therapies are commonly used to treat the symptoms. The objective of this review is to evaluate the use of polyphenols in rosacea treatment. Design: PubMed, Embase, Biosis, Web of Knowledge, and Scopus databases were systematically searched for clinical studies evaluating polyphenols in the management of rosacea. Results: Of 814 citations, 6 met the inclusion criteria. The studies evaluated licochalcone ( n  = 2), silymarin ( n  = 2), Crysanthellum indicum extract ( n  = 1), and quassia extract ( n  = 1). The studies only evaluated topical formations of stated polyphenols. Main results were summarized. Conclusions: There is evidence that polyphenols may be beneficial for the treatment of rosacea symptoms. Polyphenols appear to be most effective at reducing facial erythema and papule and pustule counts. However, studies included have significant methodological limitations and therefore large-scale, randomized, placebo-controlled trials are warranted to further assess the efficacy and safety of polyphenols in the treatment of rosacea