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.
We sought to study (NCT03143504) and assess the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by age 12 months.
Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and natural moisturizing factor analysis. The 4 common European filaggrin 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 filaggrin risk alleles were strongly associated with early-onset disease and conferred a significant reduction in natural moisturizing factor and water content by age 4 weeks. 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.
The skin barrier, formed by the stratum corneum, envelops our bodies and provides an essential protective function. However, this barrier function differs between individuals due to biological ...variation. This variation arises as a result of inherited genetic variants, negative environmental or extrinsic factors, and age. A multitude of genetic changes determine a person's predisposition to a skin barrier defect and consequently their risk of developing a dry skin condition, such as atopic dermatitis. Extrinsic factors, including the weather and detrimental skin care practices, interact with these genetic changes to determine the severity of the defect and additively increase the risk of developing dry skin conditions. How these dry skin conditions present clinically, and how they persist and progress depends very much on a person's age. Understanding how the skin barrier varies between individuals, how it differs based on clinical presentation, and how it alters with age is important in developing optimum therapies to maintain healthy skin that provides the best protection.
Enzymatic prenyl and glycosyl transfer are seemingly unrelated reactions that yield molecules and protein modifications with disparate biological functions. However, both reactions employ ...diphosphate-activated donors and each proceed via cationic species: allylic cations and oxocarbenium ions, respectively. In this study, we explore the relationship between these processes by preparing valienyl ethers to serve as glycoside mimics that are capable of allylic rather than oxocarbenium cation stabilization. Rate constants for spontaneous hydrolysis of aryl glycosides and their analogous valienyl ethers were found to be almost identical, as were the corresponding activation enthalpies and entropies. This close similarity extended to the associated secondary kinetic isotope effects (KIEs), indicating very similar transition state stabilities and structures. Screening a library of over 100 β-glucosidases identified a number of enzymes that catalyze hydrolysis of these valienyl ethers with k cat values up to 20 s–1. Detailed analysis of one such enzyme showed that ether hydrolysis occurs via the analogous mechanisms found for glycosides, and through a very similar transition state. This suggests that the generally lower rates of enzymatic cleavage of the cyclitol ethers reflects evolutionary specialization of these enzymes toward glycosides rather than inherent reactivity differences.
The climate of high midlatitude mountains appears to be warming faster than the global average, but evidence for such elevation-dependent warming (EDW) at higher latitudes is presently scarce. Here, ...we use a comprehensive network of remote meteorological stations, proximal radiosonde measurements, downscaled temperature reanalysis, ice cores, and climate indices to investigate the manifestation and possible drivers of EDW in the St. Elias Mountains in subarctic Yukon, Canada. Linear trend analysis of comprehensively validated annual downscaled North American Regional Reanalysis (NARR) gridded surface air temperatures for the years 1979–2016 indicates a warming rate of 0.028°C a−1 between 5500 and 6000 m above mean sea level (MSL), which is ∼1.6 times larger than the global-average warming rate between 1970 and 2015. The warming rate between 5500 and 6000 m MSL was ∼1.5 times greater than the rate at the 2000–2500 m MSL bin (0.019°C a−1), which is similar to the majority of warming rates estimated worldwide over similar elevation gradients. Accelerated warming since 1979, measured by radiosondes, indicates a maximum rate at 400 hPa (~7010 m MSL). EDW in the St. Elias region therefore appears to be driven by recent warming of the free troposphere. MODIS satellite data show no evidence for an enhanced snow albedo feedback above 2500 m MSL, and declining trends in sulfate aerosols deposited in high-elevation ice cores suggest a modest increase in radiative forcing at these elevations. In contrast, increasing trends in water vapor mixing ratio at the 500-hPa level measured by radiosonde suggest that a longwave radiation vapor feedback is contributing to EDW.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atopic dermatitis (AD) is a multifactorial, heterogenous disease that arises as a result of the interaction between both environmental and genetic factors. Changes in at least three groups of genes ...encoding structural proteins, epidermal proteases, and protease inhibitors predispose to a defective epidermal barrier and increase the risk of developing AD. Loss-of-function mutations found within the FLG gene encoding the structural protein, filaggrin, represent the most significant genetic factor predisposing to AD identified to date. Enhanced protease activity and decreased synthesis of the lipid lamellae lead to exacerbated breakdown of the epidermal barrier. Environmental factors, including the use of soap and detergents, exacerbate epidermal barrier breakdown, attributed to the elevation of stratum corneum pH. A sustained increase in pH enhances the activity of degradatory proteases and decreases the activity of the lipid synthesis enzymes. The strong association between both genetic barrier defects and environmental insults to the barrier with AD suggests that epidermal barrier dysfunction is a primary event in the development of this disease. Our understanding of gene-environment interactions should lead to a better use of some topical products, avoidance of others, and the increased use and development of products that can repair the skin barrier.
Summary
Background The emollient aqueous cream BP is frequently used for the treatment of atopic dermatitis (AD), yet it is associated with a high rate of adverse cutaneous reactions. It contains ...the harsh anionic surfactant sodium lauryl sulphate, a known negative environmental factor associated with the exacerbation of AD.
Objectives To investigate the effect of aqueous cream BP on stratum corneum (SC) integrity and skin barrier function in volunteers with a predisposition to a defective skin barrier.
Methods Thirteen volunteers with a previous history of AD (no symptoms for 6 months) applied aqueous cream BP twice daily to the volar side of one forearm for 4 weeks. The other forearm was left untreated as a control. Permeability barrier function and SC integrity were determined before and after treatment by measuring transepidermal water loss (TEWL) in conjunction with tape‐stripping. For comparison, 13 volunteers with current AD were recruited for assessment, without treatment, of SC integrity and skin barrier function at unaffected sites.
Results Topical application of aqueous cream BP resulted in significant elevation of baseline TEWL and a concomitant decrease in SC integrity. Measurements made after no treatment in volunteers with current AD, at unaffected sites, suggest that application of aqueous cream BP negatively affects the skin barrier towards the damaged state associated with onset of flares of the disease.
Conclusions Aqueous cream BP used as a leave‐on emollient caused severe damage to the skin barrier in volunteers with a previous history of AD. Aqueous cream BP should not be used as a leave‐on emollient in patients with AD.
Crisaborole 2% ointment is a non-steroidal treatment for mild-moderate atopic dermatitis (AD) and may produce fewer adverse effects than topical corticosteroids (TCS). We used PS-OCT to quantify ...dermal collagen at baseline and after 29 days of treatment with crisaborole and betamethasone valerate (BMV), in 32 subjects. PS-OCT detected a mean increase 1 × 10-6, 95% CI (6.3, 1.37) × 10-6 in dermal birefringence following TCS use (p < 0.0001, ad-hoc, not powered), whereas a change of -4 × 10-6, 95% CI (-32, 24) × 10-6 was detected for crisaborole (p = 0.77, ad-hoc, not powered). These results could suggest a differential effect on dermal collagen between the two compounds. PS-OCT may thus find an important role in safety assessment of novel AD treatment’ and larger trials are warranted.
Changes in body posture cause changes in morphological properties at different skin sites. Although previous studies have reported the thickness of the skin, the details of the postures are not ...generally given. This paper presents the effect of a change in posture on parameters such as thickness and surface roughness in 21 load-bearing and non-load-bearing sites.
A total of 12 volunteers (8 males and 4 females) were selected in an age group of 18–35 years and of Fitzpatrick skin type I-III. Images were captured using a clinically-approved VivoSight® optical coherence tomography system and analysed using an algorithm provided by Michelson Diagnostics.
Overextension (extending joints to full capacity) resulted in changes to thickness, roughness and undulation of the skin around the body.
The load-bearing regions have thicker skin compared to non-load-bearing sites. This is the first time that undulation topography of the stratum corneum–stratum lucidum and the dermal–epidermal junction layers have been measured and reported using statistical values such as Ra. The data presented could help to define new skin layer models and to determine the variability of the skin around the body and between participants.
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•Morphological parameters such as thickness, roughness and undulation topography are reported for sites around the body.•Undulation of the stratum corneum–stratum lucidum and the dermal–epidermal junction layers are reported for the first time.•Extending joints to full capacity resulted in changes to thickness, roughness and undulation of the skin around the body.•The load-bearing regions have thicker skin compared to non load-bearing sites.•These data are useful for design and development of new skin layer models.
Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain ...the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm‐controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin‐surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research.
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