Topical application of retinyl propionate, 4 hexyl resorcinol, and niacinamide reverses molecular and clinical features of ageing.

OBJECTIVE: Topical tretinoin is the mainstay of treatment for photoageing, despite the risk of skin irritation. Cosmetic combination anti-ageing formulations may offer similar efficacy to tretinoin, while improving on tolerability. We aim to demonstrate facial appearance benefits of a novel triple-active cosmetic formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide and to identify transcriptomic biomarkers underpinning these benefits. METHODS: A cosmetic prototype formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide was evaluated ex vivo and in a clinical study. For ex vivo experiments, the cosmetic formulation was applied for 3 days to healthy surgical discard skin from female donors aged 31-51 years, with tissues harvested for gene expression and histologic analyses. In the clinical study, females aged 47-66 years with moderate-to-severe overall visual photodamage on the face applied either topical 0.02% tretinoin or the cosmetic formulation to the face for 16 weeks and to forearms for 1 week, with forearm biopsies taken for gene expression analyses. Visual grading for facial photodamage and VISIA-CR images was taken throughout the clinical study. Safety was visually assessed during site visits, and adverse event monitoring was conducted throughout. RESULTS: Gene expression analyses in both studies revealed modulation of pathways associated with skin rejuvenation, with several genes of interest identified due to being implicated in ageing and differentially expressed following the application of the cosmetic formulation. Reversal of a consensus skin ageing gene signature was observed with the cosmetic formulation and tretinoin in the ex vivo and clinical studies. Both the cosmetic formulation and tretinoin clinically improved the overall appearance of photoageing, crow's feet, lines, wrinkles, and pores. Adverse event reporting showed that the cosmetic formulation caused less skin irritation than tretinoin. CONCLUSION: In a double-blind clinical study, the novel triple-active cosmetic combination formulation improved the visual appearance of photoageing similarly to prescription tretinoin. The cosmetic formulation and tretinoin reversed a consensus gene signature associated with ageing. Together with adverse event reporting, these results suggest that the cosmetic formulation may be a well-tolerated and efficacious alternative to tretinoin for improving the visual features of photoageing.

OBJECTIF: Le trétinoine topique est le pilier du traitement du photovieillissement, malgré le risque d'irritation cutanée. Les formulations cosmétiques combinés anti­âge peuvent offrir une efficacité similaire à la trétinoine, tout en améliorant la tolérance. Notre objectif est de démontrer les avantages esthétiques pour l'apparence du visage d'une nouvelle formulation cosmétique triple active contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide, et d'identifier les biomarqueurs transcriptomiques sous­jacents à ces avantages. MÉTHODES: Une formulation cosmétique prototype contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide a été évaluée ex vivo et lors d'une étude clinique. Pour les expériences ex vivo, la formulation cosmétique a été appliquée pendant 3 jours sur des peaux saines issues de donatrices âgées de 31 à 51 ans, avec prélèvement de tissus pour l'analyse de l'expression génique et l'histologie. Dans l'étude clinique, des femmes âgées de 47 à 66 ans présentant un photovieillissement visuel global modéré a sévère sur le visage ont appliqué soit du trétinoine topique à 0.02%, soit la formulation cosmétique sur le visage pendant 16 semaines et sur les avant­bras pendant 1 semaine, avec des biopsies d'avant­bras prélevées pour l'analyse de l'expression génique. L'évaluation visuelle du photovieillissement facial et les images VISIA­CR ont été réalisées tout au long de l'étude clinique. La sécurité a été évaluée visuellement lors des visites sur site, et une surveillance des événements indésirables a été effectuée. RÉSULTATS: Les analyses de l'expression génique dans les deux études ont révélé une modulation des voies associées au rajeunissement cutané, avec plusieurs gènes d'intérêts identifiés en raison de leur implication dans le vieillissement et de leur expression différentielle suite à l'application de la formulation cosmétique. Une inversion de la signature génique du vieillissement cutané consensuelle a été observée avec la formulation cosmétique et la trétinoine dans les études ex vivo et cliniques. La formulation cosmétique et la trétinoine ont toutes deux amélioré cliniquement l'apparence globale du photovieillissement, des pattes d'oie, des ridules, des rides et des pores. Les rapports sur les événements indésirables ont montré que la formulation cosmétique provoquait moins d'irritation cutanée que la trétinoine. CONCLUSION: Dans une étude clinique en double aveugle, la nouvelle formulation cosmétique triple active a amélioré l'apparence visuelle du photovieillissement de manière similaire à la trétinoine sur ordonnance. La formulation cosmétique et la trétinoine ont inversé une signature génique consensuelle associée au vieillissement. En tenant compte des rapports sur les événements indésirables, ces résultats suggèrent que la formulation cosmétique pourrait constituer une alternative bien tolérée et efficace à la trétinoine pour améliorer les caractéristiques visuelles du photovieillissement.

Technical aspects and evaluation methodology for the application of two automated brain MRI tumor segmentation methods in radiation therapy planning.

The purpose of this study was to design the steps necessary to create a tumor volume outline from the results of two automated multispectral magnetic resonance imaging segmentation methods and integrate these contours into radiation therapy treatment planning. Algorithms were developed to create a closed, smooth contour that encompassed the tumor pixels resulting from two automated segmentation methods: k-nearest neighbors and knowledge guided. These included an automatic three-dimensional (3D) expansion of the results to compensate for their undersegmentation and match the extended contouring technique used in practice by radiation oncologists. Each resulting radiation treatment plan generated from the automated segmentation and from the outlining by two radiation oncologists for 11 brain tumor patients was compared against the volume and treatment plan from an expert radiation oncologist who served as the control. As part of this analysis, a quantitative and qualitative evaluation mechanism was developed to aid in this comparison. It was found that the expert physician reference volume was irradiated within the same level of conformity when using the plans generated from the contours of the segmentation methods. In addition, any uncertainty in the identification of the actual gross tumor volume by the segmentation methods, as identified by previous research into this area, had small effects when used to generate 3D radiation therapy treatment planning due to the averaging process in the generation of margins used in defining a planning target volume.

Brain tumor target volume determination for radiation treatment planning through automated MRI segmentation.

PURPOSE: To assess the effectiveness of two automated magnetic resonance imaging (MRI) segmentation methods in determining the gross tumor volume (GTV) of brain tumors for use in radiation therapy treatment planning. METHODS AND MATERIALS: Two automated MRI tumor segmentation methods (supervised k-nearest neighbors [kNN] and automatic knowledge-guided [KG]) were evaluated for their potential as "cyber colleagues." This required an initial determination of the accuracy and variability of radiation oncologists engaged in the manual definition of the GTV in MRI registered with computed tomography images for 11 glioma patients. Three sets of contours were defined for each of these patients by three radiation oncologists. These outlines were compared directly to establish inter- and intraoperator variability among the radiation oncologists. A novel, probabilistic measurement of accuracy was introduced to compare the level of agreement among the automated MRI segmentations. The accuracy was determined by comparing the volumes obtained by the automated segmentation methods with the weighted average volumes prepared by the radiation oncologists. RESULTS: Intra- and inter-operator variability in outlining was found to be an average of 20% +/- 15% and 28% +/- 12%, respectively. Lowest intraoperator variability was found for the physician who spent the most time producing the contours. The average accuracy of the kNN segmentation method was 56% +/- 6% for all 11 cases, whereas that of the KG method was 52% +/- 7% for 7 of the 11 cases when compared with the physician contours. For the areas of the contours where the oncologists were in substantial agreement (i.e., the center of the tumor volume), the accuracy of kNN and KG was 75% and 72%, respectively. The automated segmentation methods were found to be least accurate in outlining at the edges of the tumor volume. CONCLUSIONS: The kNN method was able to segment all cases, whereas the KG method was limited to enhancing tumors and gliomas with clear enhancing edges and no cystic formation. Both methods undersegment the tumor volume when compared with the radiation oncologists and performed within the variability of the contouring performed by experienced radiation oncologists based on the same data.

Spectral analysis of full field digital mammography data.

The spectral content of mammograms acquired from using a full field digital mammography (FFDM) system are analyzed. Fourier methods are used to show that the FFDM image power spectra obey an inverse power law; in an average sense, the images may be considered as 1/f fields. Two data representations are analyzed and compared (1) the raw data, and (2) the logarithm of the raw data. Two methods are employed to analyze the power spectra (1) a technique based on integrating the Fourier plane with octave ring sectioning developed previously, and (2) an approach based on integrating the Fourier plane using rings of constant width developed for this work. Both methods allow theoretical modeling. Numerical analysis indicates that the effects due to the transformation influence the power spectra measurements in a statistically significant manner in the high frequency range. However, this effect has little influence on the inverse power law estimation for a given image regardless of the data representation or the theoretical analysis approach. The analysis is presented from two points of view (1) each image is treated independently with the results presented as distributions, and (2) for a given representation, the entire image collection is treated as an ensemble with the results presented as expected values. In general, the constant ring width analysis forms the foundation for a spectral comparison method for finding spectral differences, from an image distribution sense, after applying a nonlinear transformation to the data. The work also shows that power law estimation may be influenced due to the presence of noise in the higher frequency range, which is consistent with the known attributes of the detector efficiency. The spectral modeling and inverse power law determinations obtained here are in agreement with that obtained from the analysis of digitized film-screen images presented previously. The form of the power spectrum for a given image is approximately l/f2beta with beta approximately 1.4-1.5.