A minimally invasive clinical model to test sunscreen toxicity based on oxidative stress levels using microbiopsy and confocal microscopy - a proof of concept study.

OBJECTIVE: This proof-of-concept study demonstrated that using minimally invasive skin microsampling could enable significantly higher throughput of cosmetic testing in volunteers than conventional biopsy. Nanoparticle sunscreen was used as a model to test toxicity based on oxidative stress using microbiopsy and confocal imaging. METHODS: Six volunteers were recruited for this study (3 males and 3 females). Zinc oxide nanoparticle containing topical formulation was prepared at 10% w/v. Each volunteer had 3 areas of 4 cm2 each mapped on each inner forearm for a total of 6 treatment areas (intact/ tape-stripped and with/without treatment). The topical zinc-nanoparticle formulation was applied directly to volunteer skin (2mg/cm2 ) for 2 hrs. Microbiopsied tissue from each treatment group was stained for reactive oxygen and nitrogen species in addition to mitochondrial superoxide. The stained samples were then imaged using confocal microscopy prior to image analysis. RESULTS: Skin exposed to zinc oxide nanoparticles did not show any significant increases in oxidative stress. Zinc oxide nanoparticle tape-stripped skin resulted in signal significantly lower (P < 0.001) oxidative stress levels than t-butylated hydroxytoluene treated tape-stripped skin for oxidative stress markers. Topically applied zinc oxide nanoparticles had no detectable effect on the oxidative status in volunteer skin. No adverse reactions or effects were observed after all treatments including microbiopsy. CONCLUSION: The data support the hypothesis that microbiopsy is a viable approach to study cosmeceutical- skin interactions in volunteers with capacity for molecular assays and high throughput with very low risk to the volunteer.

OBJECTIFS: Cette étude de validation de concept a démontré que le microprélèvement cutané minimalement invasif pouvait augmenter considérablement la cadence des essais de produits cosmétiques sur des volontaires par rapport à une biopsie conventionnelle. Un écran solaire contenant des nanoparticules a été utilisé comme modèle pour tester la toxicité liée au stress oxydatif à l'aide de la microbiopsie et de l'imagerie confocale. MÉTHODES: Six volontaires ont été recrutés pour cette étude (3 hommes et 3 femmes). Une formulation topique contenant des nanoparticules d'oxyde de zinc a été préparée à 10 % p/v. Chaque volontaire disposait de 3 zones de 4 cm2 situées sur chaque pliure de coude pour un total de 6 zones de traitement (intactes / strippée et avec / sans traitement). La formulation topique contenant des nanoparticules d'oxyde de zinc a été appliquée directement sur la peau des volontaires (2 mg/cm2 ) pendant 2 heures. Les tissus microbiopsiés de chaque groupe de traitement ont été colorés pour détecter des espèces réactives de l'oxygène et de l'azote en plus de la superoxyde mitochondriale. Les échantillons colorés ont ensuite été examinés par microscopie confocale avant l'analyse des images. RÉSULTATS: La peau exposée aux nanoparticules d'oxyde de zinc n'a pas montré de hausse significative de stress oxydatif. La peau strippée traitée aux nanoparticules d'oxyde de zinc a entraîné des niveaux de stress oxydatif nettement inférieurs (p<0,001) comparés à ceux de la peau strippée traitée à l'hydroxytoluène t-butylé en ce que concerne les marqueurs de stress oxydatif. Les nanoparticules d'oxyde de zinc appliquées par voie topique n'ont eu aucun effet détectable sur l'état oxydatif de la peau des volontaires. Aucune réaction ou effet indésirable n'a été observé(e) après tous les traitements, y compris la microbiopsie. CONCLUSION: Les données obtenues étayent l'hypothèse selon laquelle la microbiopsie est une approche viable pour étudier les interactions des produits cosmétiques sur la peau des volontaires, avec la possibilité de réaliser des dosages moléculaires et à haut débit, avec un risque très faible pour les volontaires.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

Evaluating healthcare practitioners' views on store-and-forward teledermoscopy services for the diagnosis of skin cancer.

OBJECTIVE: The aim of the study is to evaluate healthcare practitioners' views on and satisfaction with (i) digital image acquisition and storage and (ii) store-and-forward teledermoscopy services for the diagnosis of skin cancer in their clinical practice. METHODS: An online survey was conducted among 59 healthcare practitioners (GPs (n=17), dermatologists (n=22), dermatology registrars (n=18), a dermatology research fellow (n=1) and a plastic surgeon (n=1)) to assess usability of digital image acquisition and storage for when the imaging process is conducted by the healthcare practitioners themselves, or by their patients. The study identifies the enablers and barriers of this emerging mode of medical practice. A thematic analysis was used to extract key themes from open-ended responses, which involved identifying themes and patterns within and across participants. RESULTS: Thirty-four healthcare practitioners (58%) had previously used a mobile dermatoscope within their practice. Participants most appreciated its use in their practice for lesion monitoring (59%) and record keeping (39%). Challenges reported were the increased time to support the additional workload (45%), technical issues (33%) and cost of equipment (27%). Practitioners were unsure (36%) or did not advocate teledermoscopy for direct-to-consumer use (41%). Only 23% supported the use of direct-to-consumer teledermoscopy. CONCLUSION: While most practitioners are receptive to mobile teledermoscopy, there was less support for patient-initiated use, whereby the patient controls the imaging process. As technology improves rapidly it is important to evaluate practitioners' acceptance and satisfaction of evolving telehealth services, moving forward with models of practice where healthcare practitioners and other healthcare providers will feel comfortable engaging in telehealth services.

Multiple primary cancers associated with Merkel cell carcinoma in Queensland, Australia, 1982-2011.

The relatively high incidence of Merkel cell carcinoma (MCC) in Queensland provides a valuable opportunity to examine links with other cancers. A retrospective cohort study was performed using data from the Queensland Cancer Registry. Standardized incidence ratios (SIRs) were used to approximate the relative risk of being diagnosed with another primary cancer either following or prior to MCC. Patients with an eligible first primary MCC (n = 787) had more than double the expected number of subsequent primary cancers (SIR = 2.19, 95% confidence interval (CI) = 1.84-2.60; P<0.001). Conversely, people who were initially diagnosed with cancers other than MCC were about two and a half times more likely to have a subsequent primary MCC (n=244) compared with the general population (SIR = 2.69, 95% CI = 2.36-3.05; P<0.001). Significantly increased bi-directional relative risks were found for melanoma, lip cancer, head and neck cancer, lung cancer, myelodysplastic diseases, and cancer with unknown primary site. In addition, risks were elevated for female breast cancer and kidney cancer following a first primary MCC, and for subsequent MCCs following first primary colorectal cancer, prostate cancer, non-Hodgkin lymphoma, or lymphoid leukemia. These results suggest that several shared pathways are likely for MCC and other cancers, including immunosuppression, UV radiation, and genetics.

Phenotypic characterization of nevus and tumor patterns in MITF E318K mutation carrier melanoma patients.

A germline polymorphism of the microphthalmia transcription factor (MITF) gene encoding a SUMOylation-deficient E318K-mutated protein has recently been described as a medium-penetrance melanoma gene. In a clinical assessment of nevi from 301 volunteers taken from Queensland, we identified six individuals as MITF E318K mutation carriers. The phenotype for 5 of these individuals showed a commonality of fair skin, body freckling that varied over a wide range, and total nevus count between 46 and 430; in addition, all were multiple primary melanoma patients. The predominant dermoscopic signature pattern of nevi was reticular, and the frequency of globular nevi in carriers varied, which does not suggest that the MITF E318K mutation acts to force the continuous growth of nevi. Excised melanocytic lesions were available for four MITF E318K carrier patients and were compared with a matched range of wild-type (WT) melanocytic lesions. The MITF staining pattern showed a predominant nuclear signal in all sections, with no significant difference in the nuclear/cytoplasmic ratio between mutation-positive or -negative samples. A high incidence of amelanotic melanomas was found within the group, with three of the five melanomas from one patient suggesting a genetic interaction between the MITF E318K allele and an MC1R homozygous red hair color (RHC) variant genotype.

High-contrast coherent terahertz imaging of porcine tissue via swept-frequency feedback interferometry.

There is considerable interest in the interrogation of biological tissue at terahertz (THz) frequencies, largely due to the contrast in the optical properties of different biological tissues which occur in this electro-magnetic radiation band. Of particular interest are THz biomedical images, which have the potential to highlight different information than those acquired in other frequency bands, thereby providing an augmented picture of biological structures. In this work, we demonstrate the feasibility of an interferometric biological imaging technique using a THz quantum cascade laser (QCL) operating at 2.59 THz to perform coherent imaging of porcine tissue samples. We show the potential of this new THz biomedical imaging technique for in vivo studies, by virtue of its reflection geometry and useful tissue penetration depth enabled by the large THz powers emitted by the quantum cascade laser used in this work. The observed clustering of interferometric tissue signatures opens a pathway towards automatic techniques for the discrimination of healthy tissue types for the study of normal physiology and possible therapeutic approaches.