An investigation of the skin barrier restoring effects of a cream and lotion containing ceramides in a multi-vesicular emulsion in people with dry, eczema-prone, skin: The RESTORE study phase 1

Introduction The replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids. Methods A double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 μl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application). Results The test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h. Conclusion The sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3–4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis

The effect of an emollient containing urea, ceramide NP, and lactate on skin barrier structure and function in older people with dry skin

Xerosis affects up to 75% of older people and develops as a result of a skin barrier defect. Emollients are widely used to treat xerosis; however, there is limited understanding of the differences between them and their effects on the skin barrier in older people. This study aimed to compare the effect of a commercially available emollient containing 5% urea, ceramide NP and lactate (test emollient) to an alternative emollient without these additives (control emollient) on the properties of the skin barrier in older people. Two cohorts of 21 volunteers aged 60+ years with dry skin were recruited. The first applied the test emollient to one forearm and no treatment to the other for 28-days. The second compared the test emollient to the control emollient observing the same parameters. Effects on the skin barrier were determined by measuring skin barrier function, hydration, skin surface pH and by analyzing FTIR spectra before and after treatment. A third cohort of 6 young adults was recruited to investigate the effect of a single treatment with the test emollient on the molecular structure of the skin barrier at greater depths by employing the tape-stripping technique. The test emollient hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient, an effect associated with a significant elevation of carboxylate groups (a marker of NMF content) within the stratum corneum. Furthermore, the test emollient imparted additional benefits to the structure and function of the skin barrier not exhibited by the control emollient. In conclusion the test emollient addressed the pathological features of xerotic aged skin, supporting its use as first-line therapy for xerotic skin conditions in this population

Quantification of natural moisturizing factors at the skin surface using a portable infrared spectrometer device: a pilot, calibration model

Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR) is a useful technique for the molecular analysis of surfaces, including the skin, with promising translational clinical potential. Skin‐surface levels of natural moisturizing factor (NMF) are a biomarker of filaggrin (FLG) status (both inherited and acquired) and skin dryness. FLG‐related atopic dermatitis (AD) is associated with more severe and persistent disease. The objective of this study was to combine FTIR with chemometric analysis to generate a pilot calibration model for the in vivo quantification of NMF at the skin surface using a portable FTIR device. This study was performed in a climate‐controlled, skin barrier suite located at the University of Sheffield, U.K. patients with either healthy skin or AD were recruited from the local Sheffield community, and informed consent was obtained prior to enrolment in the study. A diagnosis of AD was made using the U.K. working party criteria, and disease severity was classified by the Eczema Area and Severity Index score. Genotyping for the five most common European loss‐of‐function FLG mutations was performed from buccal swabs. FTIR spectra of 4‐cm−1 resolution were collected from the volar forearm and antecubital fossa in conjunction with tape strips for the quantification of NMF components by high‐performance liquid chromatography (HPLC) and o‐phthaldialdehyde derivatization. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) measurements were collected as an assessment of barrier function. Ethical permission for this study was granted by the National Health Service Trent research ethics committee. Partial least‐squares regression modelling of absorbance in the mid infrared spectral region (1710–1185 cm−1) with skin‐surface NMF components determined by HPLC generated a predictive r2 value of 0.90. Modelling was superior on the antecubital fossa compared with the forearm, presumably due to the increased FTIR signal obtained from this site. Predicted NMF values correlated with FLG status, TEWL and SCH. FTIR combined with chemometric analysis is a suitable technique for the instantaneous in vivo quantification of NMF at the skin surface. The use of a portable FTIR device makes this methodology suitable for any clinical setting, with the potential to inform long‐term treatment strategies in AD

Isotropic atomic layer etching of GaN using SF₆ plasma and Al(CH₃)₃

GaN is an enabling material for light emitting diodes, advanced radio frequency, and power semiconductor devices. However, fabrication of GaN devices often relies on harsh etch processes, which can leave an etch damage layer, limiting final device performance. In this work, an isotropic atomic layer etching (ALE) process involving SF6 plasma and trimethylaluminium [Al(CH3)3] is presented for the controlled etching of GaN, which reduces oxygen and carbon contamination while smoothing the surface. The ALE chemistry was first examined with density functional theory. A comparison between proposed thermal and plasma-driven reactions is made by implementing Natarajan-Elliott analysis, highlighting that the plasma process is a good candidate for GaN ALE. Saturation was experimentally confirmed for both ALE half-cycles at 150 and 300 °C, with etch rates of 0.31 ± 0.01 and 0.40 ± 0.02 nm/cycle, respectively. Analysis of the films post-ALE shows that the RMS roughness of the films decreases from 2.6 ± 0.1 to 1.9 ± 0.1 nm after 25 nm of etching at 300 °C, in agreement with a previously developed curvature-dependent smoothing model. Taken together, this ALE process enables accurate GaN thickness tuning, surface cleaning, and surface smoothing, allowing for further development of GaN devices.</p

ASSOCIATION BETWEEN SKIN BARRIER DEVELOPMENT AND EARLY-ONSET ATOPIC DERMATITIS: A LONGITUDINAL BIRTH COHORT STUDY

A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals. A longitudinal observational cohort study (NCT03143504) assessed the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by 12-months of age. Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and Natural Moisturising factor (NMF) analysis. The four common European Filaggrin (FLG) risk alleles were screened. A total of 128 infants completed the study with 20% developing mild disease. Significant changes in permeability barrier function, desquamatory protease activity and molecular composition assessed spectroscopically were observed longitudinally, but only subtle evidence of differential skin barrier development was noted between infant subgroups. Common FLG risk alleles were strongly associated with early onset disease and conferred a significant reduction in NMF and water content by four weeks of age. Accounting for a family history of atopy, these parameters alongside a greater lipid/protein ratio and reduced chymotrypsin-like activity at birth were associated with AD. Measured in ambient conditions, transepidermal water loss did not signal disease risk at any stage. Skin barrier dysfunction lacked an acquired modality but was considered proportional to cohort severity and suggests that a portfolio of tests used in a community setting, has the potential to improve current AD risk evaluations from birth

Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis

Background Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). Objectives To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. Methods We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. Results Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm–1 (full width half maximum) and 1340 cm–1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = –0.59, carboxylate peak area r = –0.50). Conclusions ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies

Maintenance of an acidic skin surface with a novel zinc lactobionate emollient preparation improves skin barrier function in patients with atopic dermatitis

INTRODUCTION: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH. METHODS: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests. RESULTS: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m2/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control. CONCLUSION: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens

Vitamin D and antimicrobial peptide levels in patients with atopic dermatitis and atopic dermatitis complicated by eczema herpeticum: A pilot study.

In this study, Vitamin D supplementation results in improved clinical severity of atopic dermatitis and increased skin surface LL-37 levels, analyzed by a novel, non-invasive method. Vitamin D supplementation could be a therapeutic option in AD