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International audience; BackgroundReflectance confocal microscopy (RCM) allows for real-time in vivo visualization of the epidermis at the cellular level noninvasively. Parameters relating to tissue architecture can be extracted from RCM images, however, analysis of such images requires manual identification of cells to derive these parameters, which can be time-consuming and subject to human error, highlighting the need for an automated cell identification method.MethodsFirst, the region-of-interest (ROI) containing cells needs to be identified, followed by the identification of individual cells within the ROI. To perform this task, we use successive applications of Sato and Gabor filters. The final step is post-processing improvement of cell detection and removal of size outliers. The proposed algorithm is evaluated on manually annotated real data. It is then applied to 5345 images to study the evolution of epidermal architecture in children and adults. The images were acquired on the volar forearm of healthy children (3 months to 10 years) and women (25–80 years), and on the volar forearm and cheek of women (40–80 years). Following the identification of cell locations, parameters such as cell area, cell perimeter, and cell density are calculated, as well as the probability distribution of the number of nearest neighbors per cell. The thicknesses of the Stratum Corneum and supra-papillary epidermis are also calculated using a hybrid deep-learning method.ResultsEpidermal keratinocytes are significantly larger (area and perimeter) in the granular layer than in the spinous layer and they get progressively larger with a child's age. Skin continues to mature dynamically during adulthood, as keratinocyte size continues to increase with age on both the cheeks and volar forearm, but the topology and cell aspect ratio remain unchanged across different epidermal layers, body sites, and age. Stratum Corneum and supra-papillary epidermis thicknesses increase with age, at a faster rate in children than in adults.ConclusionsThe proposed methodology can be applied to large datasets to automate image analysis and the calculation of parameters relevant to skin physiology. These data validate the dynamic nature of skin maturation during childhood and skin aging in adulthood.

Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer, and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.

Skin surface pH has been identified as a key regulator of the epidermal homeostasis through its action on serine protease activity. These enzymes, like kallikreins (KLK), are responsible for the degradation of corneodesmosomes, the protein structures linking together corneocytes, and are regulated by Lympho-Epithelial Kazal-Type-related Inhibitor (LEKTI). KLK activity increases at pH levels higher than physiological. An increase in skin surface pH has been observed in patients suffering from skin diseases characterized by impaired barrier function, like atopic dermatitis. In this work, we introduce an agent-based model of the epidermis to study the impact of a change in skin surface pH on the structural and physiological properties of the epidermis, through the LEKTI-KLK mechanism. We demonstrate that a less acidic pH, compared to the slightly acidic pH observed in healthy skin, is sufficient to significantly affect the water loss at the surface and the amount of irritant permeating through the epidermis. This weakening of the skin barrier function eventually results in a more intense skin inflammation following exposure to an external irritant. This work provides additional evidence that skin surface pH and serine proteases can be therapeutic targets to improve skin barrier integrity.

Background The study objective was to examine if age and chronic environmental exposure affect the water content and the composition of the natural moisturizing factors (NMFs) of the stratum corneum (SC). Methods Forty healthy Caucasian women 18-70 years of age were recruited. Measurements were done on the cheek and on two skin sites on the arm (one relatively protected and one exposed to environmental factors). SC water content and NMF composition were measured by Raman confocal microspectroscopy. Results The SC water content was gradually reduced with age, reaching statistically significant levels only on the exposed arm site. The SC water content remained higher on the face than on the two arm sites throughout the ages tested. The age-dependent concentration changes of various amino acids were species-specific, potentially indicating different protein sources. Interestingly, on the arm sites, the sum of decreasing amino acid concentrations is compensated by the sum of those increasing, resulting in constant total amino acid content. However, on the face, the total amino acid content statistically increased with age potentially relating to the declining cell turnover rates. The lactate content was higher on the face for all ages and statistically decreased on both arm sites. Conclusion Both chronological aging and chronic exposure to environmental factors mildly affect SC hydration, while they have variable effects in the concentrations of NMF components. The dynamics of NMF composition may at least partially explain the age-related changes in SC hydration.

International audience; Reflectance confocal microscopy (RCM) allows real-time in vivo visualization of the skin at cellular level. The study of RCM images provides information on the topological and geometrical properties of the epidermis. These may change in each layer of the epidermis, depending on the subject's age and the presence of certain dermatological conditions. Studying RCM images requires manual identification of cells to derive these properties which is timeconsuming and subject to human error, highlighting the need for an automated cell identification method. We propose an automated pipeline to analyze the structure of the skin in RCM images. The first step is to identify the region of interest (ROI) containing the epidermal cells. The second step is to identify individual cells in the segmented tissue area using an image filter. We then use prior biological knowledge to process the resulting detected cells, removing cells that are too small and reapplying the used filter locally on detected regions that are too big to be considered as a single cell. The results are evaluated both on simulated data and on manually annotated real RCM data. This study shows that automatic cell identification can be achieved, with an accuracy (precision and recall) that matches the interexpert variability.

The advent of 16S RNA profiling and shotgun metagenomics has enabled a holistic approach to the study of the skin microbiome composition. Despite the interesting findings in this rapidly developing scientific area, the big question remains: What role does the microbiome play in skin physiology? To begin answering this question, we employed an integrative methodology for microbiome and metabolome analysis of skin surface samples collected from the volar forearm of healthy infants aged 3–6-months. Whereas the infant skin metabolome was dominated by amino acids, lipids, and xenobiotics, the primary phyla of the microbiome were Firmicutes, Actinobacteria, and Proteobacteria. Zooming in on the species level revealed a large contribution of commensals belonging to the Cutibacterium and Staphylococcus genera, including Cutibacterium acnes, Staphylococcus epidermidis, and S. aureus. This heterogeneity was further highlighted when combining the microbiome with metabolome data. Integrative analyses delineated the coexistence of three distinct metabolite‒microbe clusters: one dominated by Cutibacterium linked to hydrophobic elements of the skin barrier, one associating Staphylococcus genus with amino acids relevant to the water holding capacity and pH regulation of the skin surface, and one characterized by Streptococcus and independent of any particular metabolomic profile.

EGFR inhibitors used in oncology therapy modify the keratinocyte differentiation processes, impairing proper skin barrier formation and leading to cutaneous adverse drug reactions. To uncover the molecular signatures associated with cutaneous adverse drug reactions, we applied phosphoproteomic and transcriptomic assays on reconstructed human epidermis tissues exposed to a therapeutically relevant concentration of afatinib, a second-generation EGFR inhibitor. After drug exposure, we observed activation of the phosphatidylinositol 3-kinase/protein kinase B pathway associated with an increased expression of gene families involved in keratinocyte differentiation, senescence, oxidative stress, and alterations in the epidermal immune-related markers. Furthermore, our results show that afatinib may interfere with vitamin D3 metabolism, acting via CYP27A1 and CYP24A1 to regulate calcium concentration through the phosphatidylinositol 3-kinase/protein kinase B pathway. Consequently, basal layer keratinocytes switch from a pro-proliferating to a prodifferentiative program, characterized by upregulation of biomarkers associated with increased keratinization, cornification, T helper type 2 response, and decreased innate immunity. Such effects may increase skin susceptibility to cutaneous penetration of irritants and pathogens. Taken together, these findings demonstrate a molecular mechanism of EGFR inhibitor–induced cutaneous adverse drug reactions.

Computational models of skin permeability are typically based on assumptions of fixed geometry and homogeneity of the whole epidermis or of epidermal strata and are often limited to adult skin. Infant skin differs quantitatively from that of the adult in its structure and its functional properties, including its barrier function to permeation. To address this problem, we developed a self-organizing multicellular epidermis model of barrier formation with realistic cell morphology. By modulating the parameters relating to cell turnover reflecting those in adult or infant epidermis, we were able to generate accordingly two distinct models. Emerging properties of these models reflect the corresponding experimentally measured values of epidermal and stratum corneum thickness. Diffusion of an externally applied substance (e.g., caffeine) was simulated by a molecular exchange between the model agents, defined by the individual cells and their surrounding extracellular space. By adjusting the surface concentration and the intercellular exchange rate, the model can recapitulate experimental permeability data after topical exposure. By applying these parameters to an infant model, we were able to predict the caffeine concentration profile in infant skin, closely matching experimental results. This work paves the way for a better understanding of skin physiology and function during the first years of life.

Background Cutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45–100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient’s quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function. Methods To test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model. Results EGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype. Conclusions This study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

Background/Objectives Infant skin undergoes a maturation process during the early years of life. Little is known about the skin's innate immunity. We investigated the dynamics of innate immunity markers collected from the surface of infant skin during the first 36 months of life. Methods A total of 117 healthy infants aged 3‐36 months participated in the study. We extracted human beta defensin‐1 and interleukin 1 alpha and its receptor antagonist using transdermal analysis patches from the skin surface of the posterior lower leg area. The extracts were analyzed using a spot enzyme‐linked immunosorbent assay. Results Skin surface human beta defensin‐1 levels were higher early in life and decreased with infant age. The ratio of interleukin 1 alpha receptor antagonist to interleukin 1 alpha did not change significantly with age but showed a distinct difference between sexes, with female infants having higher values than male infants. Conclusion As is the case with skin structure and functional properties, cutaneous innate immunity also appears to undergo a maturation period during infancy, with innate immunity slowly declining as adaptive immunity takes over. Sex differences in immune markers may explain sex‐dependent susceptibilities to infection.

BACKGROUND/OBJECTIVES The establishment of newborn skin flora depends on the ongoing skin maturation and the existence of potential microbial colonizers within the environment of the infant during a period of intense mother-infant physical interaction. This longitudinal study assessed culturable skin bacteria in the mother-infant dyad during the first year of life. METHODS A total of 17 mother-infant dyads were swabbed within 24 hours postpartum and at 3, 6, 9, and 12 months. Skin swabbing was performed on two anatomical areas per individual (mothers: chest-abdomen; infants: forehead-buttocks) and were incubated in five different solid culture media to optimize yield. Isolated bacterial species were identified to genus or species level using the API system (BioMerieux, Marcy l'Etoile, France). RESULTS A total of 444 microbial strains were isolated belonging to 22 genera: 6 "frequent" (isolated from > 5% samples: S aureus, Proteus, Klebsiella, Pseudomonas, Enterobacter, and Enterococcus) and 16 "infrequent." Isolated genera per individual peaked at 6 months postpartum for mothers and infants (P

Background/Objective Epidermal structure, function, and composition are different in white infants and adults. We investigated whether ethnicity and location contribute to differences in functional and clinical measurements of skin barrier function during the first years of life and in adults. Methods Children (n = 397, ages 3–49 mos) and women (n = 117, mean age 31 yrs) were enrolled at independent centers in Beijing, China (ethnic Chinese), Skillman, New Jersey (white, African American), and Mumbai, India (ethnic South Asian). Water barrier properties of the stratum corneum were assessed using high-frequency conductance and transepidermal water loss (TEWL) on the dorsal forearm and upper inner arm. Digital imaging was used to evaluate facial erythema and scaling. Results Despite differences in local climate, TEWL was similar in adults. In children, conductance and TEWL decreased monotonically from age 3 months to 4 years. In children from Beijing, TEWL values were higher in both arm locations than in children in Mumbai and Skillman. No significant differences were observed in TEWL or conductance between the white and African American groups. Conclusion In general, TEWL and conductance were greater on the upper inner arm than the dorsal forearm. Erythema and scaling were observed most often in subjects from Beijing and most infrequently in subjects from Mumbai. Stratum corneum water barrier properties were different in children and adults. Although there may be differences in these properties between ethnic groups in childhood, TEWL values were similar in adults across the three geographic locations and four ethnicities.

In a paper published at the J Invest Dermatol in 1998 Nik Kollias and coworkers described distinct changes in skin native fluorescence associated with skin aging and photoaging, using in vivo fluorescence excitation spectroscopy. The assignment of the 295 nm band to tryptophan fluorescence had a profound significance influencing many later studies from multiple groups. The reproducible changes in skin native fluorescence suggested that aging causes predictable alterations in both the epidermis and the dermis, whereas chronic UV exposure induces the appearance of new fluorophores. This seminal, but insufficiently widely appreciated work deserves re-examination as it points to important horizons in future experimental dermatology, such as cancer diagnostics, diabetes, wound healing, and understanding skin aging and photoaging mechanisms.

Keratinocyte organization and biochemistry are important in forming the skin’s protective barrier. Intrinsic and extrinsic factors can affect skin barrier function at the cellular and molecular levels. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging, a technique which combines both molecular aspects and histological details, has proven to be a valuable method in various disciplines including pharmacology, dermatology and cosmetology. It typically requires ex vivo samples, prepared following frozen tissue sectioning. This paper demonstrates the feasibility of performing MALDI analysis on tape strips collected non-invasively on skin. The aim is to obtain molecular imaging of corneocytes on tapes towards novel biological insights. Tapes were collected from two skin sites (volar forearm and cheek) of human volunteers. Ten molecules relating to skin barrier function were detected with a single mode of acquisition at high spatial resolution with a 7 T MALDI-Fourier transform ion cyclotron resonance (FTICR) instrument. The method sensitivity was adequate to create molecular maps which could be overlaid on transmission microscopy images of the same area of the tape. Analysis of the molecular distributions from tapes at the two skin sites was consistent with the known skin properties of the two sites, confirming the validity of the observations. Hierarchical clustering analysis was used to differentiate corneocyte populations based on their molecular profiles. Furthermore, morphological analysis provided a new way of considering statistical populations of corneocytes on the same tape, rather than measuring a single averaged value, providing additional useful information relating to their structure-function relationship.

A cross-sectional observational study of 43 infants and 60 adult women was performed in South Africa to assess skin barrier (SB) function through noninvasive quantification of transepidermal water loss (TEWL) and skin surface hydration (SSH). TEWL and SSH improved with age and in anatomic locations with chronic environmental exposure in keeping with reported trends in other ethnicities.

Skin physiology is dynamically changing over the frst years of postnatal life; however, ethnic variations are still unclear. Te aim\ud of this study was to characterize infant skin barrier function, epidermal structure, and desquamation-related enzymatic activity\ud as compared to that of adult skin in an East Asian population. Te skin properties of 52 infants (3-24 months) and 27 adults (20-\ud 40 years) were assessed by noninvasive methods at the dorsal forearm and upper inner arm. Transepidermal water loss and skin\ud surface conductance values were higher and more dispersed for infants compared to adults. Infant skin surface pH was slightly\ud lower than adult on the dorsal forearm. Te infant SC and viable epidermis were thinner compared to adults with diferences that\ud were site-specifc. Although the chymotrypsin-like activity for infant skin was comparable to adult level, the caseinolytic specifc\ud activity was signifcantly higher for the infant cohort. Tese observations indicate a diferently controlled pattern of corneocyte\ud desquamation in infants. In conclusion, structural and functional diferences exist between infant and adult skin in the East Asian\ud population pointing to dynamic maturation of the epidermal barrier early in life.\ud

Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy provide direct visualization of the skin dermal fibers in vivo. A typical method for analyzing TPF/SHG images involves averaging the image intensity and therefore disregarding the spatial distribution information. The goal of this study is to develop an algorithm to document age-related effects of the dermal matrix. TPF and SHG images were acquired from the upper inner arm, volar forearm, and cheek of female volunteers of two age groups: 20 to 30 and 60 to 80 years of age. The acquired images were analyzed for parameters relating to collagen and elastin fiber features, such as orientation and density. Both collagen and elastin fibers showed higher anisotropy in fiber orientation for the older group. The greatest difference in elastin fiber anisotropy between the two groups was found for the upper inner arm site. Elastin fiber density increased with age, whereas collagen fiber density decreased with age. The proposed analysis considers the spatial information inherent to the TPF and SHG images and provides additional insights into how the dermal fiber structure is affected by the aging process.

Androgenetic alopecia is the most common form of hair loss. Minoxidil has been approved for the treatment of hair loss, however its mechanism of action is still not fully clarified. In this study, we aimed to elucidate the effects of 5% minoxidil topical foam on gene expression and activation of signaling pathways in vertex and frontal scalp of men with androgenetic alopecia. We identified regional variations in gene expression and perturbed signaling pathways using in silico Pathway Activation Network Decomposition Analysis (iPANDA) before and after treatment with minoxidil. Vertex and frontal scalp of patients showed a generally similar response to minoxidil. Both scalp regions showed upregulation of genes that encode keratin associated proteins and downregulation of ILK, Akt, and MAPK signaling pathways after minoxidil treatment. Our results provide new insights into the mechanism of action of minoxidil topical foam in men with androgenetic alopecia.

The epidermis and the stratum corneum (SC) as its outermost layer have evolved to protect the body from evaporative water loss to the environment. To morphologically represent the extremely flattened cells of the SC - and thereby the epidermal barrier - in a multicellular computational model, we developed a 3D biomechanical model (BM) based on ellipsoid cell shapes. We integrated the BM in the multicellular modelling and simulation platform EPISIM. We created a cell behavioural model (CBM) with EPISIM encompassing regulatory feedback loops between the epidermal barrier, water loss to the environment, and water and calcium flow within the tissue. This CBM allows a small number of stem cells to initiate self-organizing epidermal stratification, yielding the spontaneous emergence of water and calcium gradients comparable to experimental data. We find that the 3D in silico epidermis attains homeostasis most quickly at high ambient humidity, and once in homeostasis the epidermal barrier robustly buffers changes in humidity. Our model yields an in silico epidermis with a previously unattained realistic morphology, whose cell neighbour topology is validated with experimental data obtained from in vivo images. This work paves the way to computationally investigate how an impaired SC barrier precipitates disease.

Background Striae Distensae (SD) or stretch marks are manifestations of epidermal atrophy that occurs after tissue tearing due to rapid growth or over-stretching and are characterized by distinct microstructural features. The objective of this in vivo study was to investigate the biophysical properties of SD lesions, including skin barrier function, skin surface hydration, mechanical properties, and chromophore concentrations, compared to normal adjacent skin. Methods Non-invasive methods were used on 29 volunteers with SD to characterize: (i) visual appearance (visual assessment and clinical imaging), (ii) skin barrier function by measuring transepidermal water loss, (iii) skin surface hydration using corneometry (skin capacitance), (iv) mechanical properties measuring skin elasticity under vacuum and surface propagation of a sonic wave, (v) the presence of erythema and pigmentation using diffuse reflectance spectroscopy, and (vi) the levels of interleukin-1α on the skin surface. Results No difference was observed in skin barrier function and a slight difference in skin hydration between the striae and adjacent uninvolved skin. Viscoelasticity measurements showed that SD lesions were significantly less firm, less elastic, and less deformable than normal skin (P

Diaper dermatitis (DD) is one of the most common skin conditions in neonates and infants, with a peak between the ages of 9 and 12 months. Appropriate skin care practices that support skin barrier function and protect the buttocks skin from urine and feces are supposed to be effective in the prevention of DD. Despite many recommendations for parents and caregivers on proper diaper skin care, there is no up-to-date synthesis of the available evidence to develop recommendations for DD prevention practice. Therefore we performed a systematic literature review on the efficacy of nonmedical skin care practices on the diapered area of healthy, full-term infants ages 0 to 24 months. We identified 13 studies covering skin care practices such as cleansing, bathing, and application of topical products. DD prevalence and incidence and physiologic skin parameters were used as efficacy parameters. The results of this review indicate that cleansing of the diaper area using baby wipes or water and a washcloth have comparable effects on diapered skin. Bathing with a liquid baby cleanser twice weekly seems comparable with water alone. The application of ointments containing zinc oxide or petrolatum with or without vitamin A seems to have comparable effects on DD severity. There seems to be no information on whether single skin care practices such as cleansing, bathing, and application of topical preparations can prevent DD. High-quality randomized clinical trials are needed to show the effectiveness of skin care practices for controlling and preventing DD.

Pediatricians and parents report diaper dermatitis (DD) to be one of the most common skin diseases that affects almost every child at some point during the early months and years of life. Diapered skin is exposed to friction and excessive hydration, has a higher pH than nondiapered skin, and is repeatedly soiled with feces that contains enzymes with high irritation potential for the skin. The combination of these factors frequently results in skin damage, leading to visible erythematous lesions that can be irritating and painful to the child. Behavioral changes such as increased crying and agitation and changes in eating and sleeping patterns indicate emotional distress. Appropriate skin care can help to prevent the occurrence of DD and to speed up the healing of affected skin. This includes frequent diaper changes and aeration, gentle cleansing, and the use of a barrier cream. Mild to moderate cases usually resolve after a few days of following this routine, but the use of harsh cleaning products can exacerbate DD.

Background Stretch marks or striae distensae (SD) are characterized by epidermal atrophy following repeated over-stretching of the skin tissue. The objective of this study was to investigate the skin texture and microstructure of SD lesions compared to those of normal adjacent skin in vivo using non-invasive methods. Methods A population of 26 women and 3 men with SD were examined after giving written informed consent. Following clinical grading, skin replicas were collected, confocal microscopy was performed on SD lesions and healthy neighboring skin. Skin surface texture parameters were calculated using 3D image analysis of the skin replicas and epidermal and dermal microstructure were evaluated by analysis of the confocal images. In a parallel study, histological analysis was performed on 6 skin biopsies taken from abdominal reduction surgeries in areas where skin exhibited SD. Results Analysis of the skin surface texture showed that the SD area was more anisotropic and with higher skin roughness than the adjacent skin in terms of directions of skin microglyphics. Confocal microscopy demonstrated that SD were characterized by shallower dermal papillae (P

Linked Article: Franco, et al. Br J Dermatol 2016; 174:499–504.

The stratum corneum (SC) is the main barrier of the skin, offering a first line of defence against external pathogens and insults. The SC of patients with atopic dermatitis (AD) has underlying barrier deficiencies, even in non-lesional sites. A defective SC barrier is more vulnerable to environmental insults, which trigger immune reactions, further deteriorating the barrier. [...]

In recent years, there have been continuing efforts to understand the effects of baby skin care routines and products on the healthy development of baby skin. Such efforts aim ultimately to determine the best infant skin care practices. The pediatric and dermatologic communities have not reached consensus on what constitutes an appropriate cleansing practice. In the United States, guidelines for neonatal skin care have been developed, propagated, and implemented. The accumulated knowledge has promoted evidence-based clinical practices and, therefore, may help to improve clinical outcomes, although these guidelines primarily cover the care of preterm newborns and the treatment of those with other health problems. High-level, long-term clinical evidence of the effective and safe cleansing of healthy, full-term newborns and infants is scarce. This review presents a comprehensive analysis of the scientific literature on baby skin development, cleansing practices, and related products (for healthy newborns and babies) since 1970. The evidence drawn from the reviewed literature can be summarized as follows: Bathing immersed in water seems generally superior to washing alone. Bathing or washing with synthetic detergents (syndets) or mild liquid baby cleansers seems comparable with or even superior to water alone. Nevertheless, larger randomized clinical trials with age-defined cohorts of babies as well as more-defined parameters are required to identify optimal practices and products for skin cleansing of healthy infants. These parameters may include standardized skin function parameters such as transepidermal water loss, stratum corneum hydration, skin surface pH, and sebum production. Clinical skin scores such as the Neonatal Skin Condition Score may be employed as outcome measures.

The presence of irritants from feces and urine with the concurrent mechanical friction and occlusion creates an environment in the diapered area that renders the skin prone to diaper dermatitis. Besides being a source of discomfort to the infant, these skin irritations pose a risk of secondary infections. In this study, we used noninvasive in vivo techniques to define measurable parameters that correlate with diaper dermatitis pathophysiology. In 35 infants (16 with mild or moderate and 19 without diaper dermatitis) we compared skin of diapered areas afflicted with diaper dermatitis to lesion-free diapered sites and to skin outside the diapered area (thigh). Our findings show significantly elevated cutaneous erythema, pH, and hydration, with significantly compromised water barrier function in involved areas compared to nonlesional sites both within and outside the diapered area. Furthermore, skin pH in nonlesional diapered skin for the diaper dermatitis cohort was significantly higher compared to the nondiapered sites. These observations are consistent with the current understanding of pathological skin changes in diaper dermatitis. In this study, we demonstrate that noninvasive methods can document relevant parameters to diaper dermatitis in vivo.

Background Currently, there is the need of a validated grading scale for assessing lip volume/thickness. Objective The aim of this study was to assist clinicians in managing individuals seeking lip rejuvenation and to provide an objective method for evaluating the efficacy and longevity of such treatments. Methods Using accepted criteria for the development of dermatological grading scales, we have developed and validated a photographic grading scale for assessing lip volume and thickness based on digital parallel-polarized light imaging. Results The photographic grading scale was shown to be a valid and reliable instrument for assessing lip volume and thickness, with good inter- and intra-grader consistency. The validity of the scale was demonstrated by its correlation with clinical evaluation and 3-dimensional measurements. Conclusions This validated lip-volume/thickness grading scale should prove helpful in clinical trial settings to standardize clinical evaluations and to quantify results and measure the longevity of dermal fillers and other procedures for lip rejuvenation.

Infant skin is often presented as the cosmetic ideal for adults. However, compared to adult skin it seems to be more prone to develop certain pathological conditions, such as atopic dermatitis and irritant contact dermatitis. Therefore, understanding the physiology of healthy infant skin as a point of reference is of interest both from the cosmetic as well as from the clinical point of view. Clinical research on healthy infants is, however, limited because of ethical considerations of using invasive methods and therefore until recently data has been scarce. Technical innovations and the availability of non-invasive in vivo techniques, such as evaporimetry, electrical impedance measurement, in vivo video and confocal microscopy, and in vivo fibre-optic based spectroscopy, opened up the field of in vivo infant skin physiology research. Studies incorporating such methods have demonstrated that compared to adult, infant skin continues to develop during the first years of life. Specifically, infant skin appears to have thinner epidermis and stratum corneum (SC) as well as smaller corneocytes at least until the second year of life. The water-handling properties are not fully developed before the end of the first year and infant SC contains more water and less amounts of natural moisturizing factors. Such findings re-evaluate the old notions that skin is fully matured at birth. Armed with this knowledge, we are in a position not only to better understand infant dermatological conditions but also to design better skin care products respecting the distinct qualities of infant skin.

Functional differences between infant and adult skin may be attributed to putative differences in skin microstructure. The purpose of this study was to examine infant skin microstructure in vivo and to compare it with that of adult skin. The lower thigh area of 20 healthy mothers (ages 25-43) and their biological children (ages 3-24 months) was examined using in vivo noninvasive methods including fluorescence spectroscopy, video microscopy, and confocal laser scanning microscopy. Stratum corneum and supra-papillary epidermal thickness as well as cell size in the granular layer were assessed from the confocal images. Adhesive tapes were used to remove corneocytes from the outer-most layer of stratum corneum and their size was computed using image analysis. Surface features showed differences in glyph density and surface area. Infant stratum corneum was found to be 30% and infant epidermis 20% thinner than in adults. Infant corneocytes were found to be 20% and granular cells 10% smaller than adult corneocytes indicating a more rapid cell turnover in infants. This observation was confirmed by fluorescence spectroscopy. Dermal papillae density and size distribution also differed. Surprisingly, a distinct direct structural relationship between the stratum corneum morphology and the dermal papillae was observed exclusively in infant skin. A change in reflected signal intensity at approximately 100 mum indicating the transition between papillary and reticular dermis was evident only in adult skin. We demonstrate in vivo qualitative and quantitative differences in morphology between infant and adult skin. These differences in skin microstructure may help explain some of the reported functional differences.

Background: When the skin is exposed to solar irradiation, UVA photons interact with skin tissues and induce excessive reactive oxygen species, resulting in oxidative stress. We have shown in a previous study that in vivo chemiluminescence's measurement can be used to evaluate the overall level of UVA-induced oxidative stress in human skin. However, the origin of the observed chemiluminescence signals remains unclear. Methods: UVA-induced chemiluminescence measurements were conducted: (a) in vitro on collagen solutions and solid collagen sheet preparations, (b) ex vivo on human and mouse skin biopsies, and (c) in vivo on human skin of various constitutive pigmentation levels. Fluorescence was measured on collagen in vitro as well as on skin for the in vivo experiments. Results: We found in the in vitro experiments that UVA-induced chemiluminescence increases with the presence of collagen cross-links. When dermal sides were exposed to UVA irradiation, both mouse and human skin biopsies demonstrated significantly higher chemiluminescence levels than when epidermal sides were exposed to UVA. The amount of collagen cross-links decreases slightly following UVA exposure, as shown both by in vivo fluorescence and by UVA-induced chemiluminescence. Finally, there was less measurable UVA-induced chemiluminescence in dark skin compared with light pigmented skin in vivo. Conclusions: The dermis is very sensitive to UVA photons. Dermal cross-links are potential UVA sensitizers. The oxidative stress induced by UVA and measured by chemiluminescence may largely be attributed to the breakdown of dermal collagen cross-links.

Skin water barrier development begins in utero and is believed to be complete by week 34 of gestational age. The goal of this investigation was to assess the dynamic transport and distribution of water of the stratum corneum of infants and compare it to those of adults. The interaction of water with the stratum corneum was assessed by measuring capacitance, transepidermal water loss (TEWL), rates of absorption-desorption as well as Raman spectra as a function of depth (a total of 124 infants (3-12 months) and 104 adults (14-73 years)). The results show that capacitance, TEWL, and absorption-desorption rates had larger values consistently for infant stratum corneum throughout the first year of life and showed greater variation than those of adults. The Raman spectra analyzed for water and for the components of natural moisturizing factor (NMF) showed the distribution of water to be higher and have a steeper gradient in infants than in adults; the concentration of NMF was significantly lower in infants. The results suggest that although the stratum corneum of infants may appear intact shortly after birth (