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.

Endotaxial stabilization of 2D charge density waves with long-range order.

Charge density waves are emergent quantum states that spontaneously reduce crystal symmetry, drive metal-insulator transitions, and precede superconductivity. In low-dimensions, distinct quantum states arise, however, thermal fluctuations and external disorder destroy long-range order. Here we stabilize ordered two-dimensional (2D) charge density waves through endotaxial synthesis of confined monolayers of 1T-TaS2. Specifically, an ordered incommensurate charge density wave (oIC-CDW) is realized in 2D with dramatically enhanced amplitude and resistivity. By enhancing CDW order, the hexatic nature of charge density waves becomes observable. Upon heating via in-situ TEM, the CDW continuously melts in a reversible hexatic process wherein topological defects form in the charge density wave. From these results, new regimes of the CDW phase diagram for 1T-TaS2 are derived and consistent with the predicted emergence of vestigial quantum order.

Clinically identified postpartum depression in Asian American mothers.

OBJECTIVE: To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. DESIGN: Cross-sectional study using electronic health records (EHR). SETTING: A large, outpatient, multiservice clinic in Northern California. PARTICIPANTS: A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. METHODS: Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. RESULTS: The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. CONCLUSION: In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting.