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Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers. Using a linear mixed model adjusting for age and skin phototype, we compared biomarkers between both skin sites in indoor and outdoor workers. We measured markers of the immune response and skin barrier, including cytokines, GFs, 15-hydroxyeicosatetraenoic acid, cis- and trans-urocanic acid, and corneocyte topography, indicated by circular nano objects. Differences between the 2 skin sites were found for cis-urocanic acid, total urocanic acid, IL-1α, IL-1RA, IL-1RA/IL-1α, IL-18, 15-hydroxyeicosatetraenoic acid, CCL4, and circular nano objects. The levels of cis-urocanic acid and CCL4 also differed between indoor and outdoor workers. These findings underscore changes in both immune response and skin barrier induced by UVR. They indicate the potential utility of stratum corneum biomarkers in detecting both chronic UVR exposure in occupational setting and aiding in the development of preventive measures.

Abstract Backgrounds The detection of biomarkers of a stress response in the stratum corneum (SC) could be used as objective assessment of early stress symptoms and monitoring of stress reduction interventions in health care workers (HCWs). Aim The aim of this study is to explore SC biomarkers of immune and hormonal response and skin barrier for assessment of psychological distress (PD) in HCWs. Methods Twenty‐five female HCWs and 25 non‐HCWs participated. SC samples were collected using adhesive tapes at baseline and 3−5 days later (T1). We analyzed 24 biomarkers (immunological, vascular, hormones, and natural moisturizing factors). Stress symptoms were assessed using three scales of Copenhagen Psychosocial Questionnaire. The study involved: identifying SC biomarkers, correlating stress symptoms and biomarkers at baseline and T1, examining stress symptoms between the groups with a Mann‐Whitney test, comparing stress symptoms and biomarkers between groups using Ordinary Least Regression and investigating temporal variability of SC biomarkers at baseline and T1 using a Wilcoxon‐signed rank. Results Fourteen SC biomarkers were identified. We found correlations between general stress and “IL18” (r = 0.55) physical stress and “IL1b” (r = 0.36) and cognitive stress and “MIP3a” (r = 0.38) at baseline and general stress and cortisol (r = −0.49), physical stress and cortisol (r = −0.60) and cortisone (r = −0.67) at T1. We found no differences in stress symptoms and biomarkers between the groups, except for “MIP3a” at baseline. Differences in the biomarker levels between two time points were found for “TARC,” “VEGFA,” “ILRA,” “IL1RA/IL1a,” “NMF,” and “DHEA.” Conclusion The SC can be suitable biological material to assess biomarkers related to immune response, hormonal response, and skin barrier function. The SC biomarkers, showed strong, moderate and weak correlations with stress symptoms. Notably, these associations include cytokines of innate immunity and well‐known stress hormones, cortisol and cortisone.

Abstract Background Outdoor work is associated with high and chronic exposure to solar ultraviolet radiation which might lead to an increased risk of developing skin (pre)malignancies. Prevalence of actinic keratosis (AK), basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous melanoma (cM) in Dutch outdoor workers (OW) has not previously been investigated. Objective This study compares the prevalence of premalignant lesions and skin tumours in OW and matched controls (non‐OW). Methods In a population‐based cohort study, prevalence of premalignant lesions and skin tumours was investigated in a group of OW (n = 841) and controls matched 1:1 by age, sex, skin colour and tendency for sunburn. Skin examinations were conducted by physicians and skin cancer history was derived from the nationwide Dutch Pathology Registry. Information on OW was obtained through interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between OW and BCC, cSCC, cM and (number of) AK. Results AK was found in 22.7% of OW and 22.9% of non‐OW, BCC in 14% of OW and 15.7% of non‐OW, cSCC in 4.9% of OW and 3.4% of non‐OW, and cM in 1.9% of OW and 2% of non‐OW. There was no significant association between OW and premalignant lesions and skin tumours, with exception for developing ≥4 AKs (OR 1.3 [95% CI 1.0–1.78]). Conclusions This study reveals high prevalence of premalignant lesions and skin tumours in a Dutch population. No association between OW and the occurrence of premalignant lesions and skin tumours was found, however, multiple AKs were more prevalent in OW.

Contact dermatitis because of use of diabetes devices is frequent in individuals with type 1 diabetes (TD1), especially in the pediatric age group, but the putative role of a constitutional impaired skin barrier in persons with TD1 is unclear. This study examined the skin barrier function by the measurement of natural moisturizing factor and free cytokines collected through skin tape strips, as well as biophysical markers and the skin microbiome, in persons with TD1 than to age- and sex-matched healthy controls. All measurements were done in nonlesional skin. We found that the skin barrier function was similar in children and adolescents with TD1 than to controls but found that the beta-diversity of skin microbiome at the buttock differed between the two groups. We conclude that individuals with TD1 have normal skin barrier function, and that the increased occurrence of contact dermatitis following pump and sensor use is explained by exogenous factors.

Solar ultraviolet radiation (UVR) is the most significant occupational carcinogenic exposure in terms of the number of workers exposed (i.e., outdoor workers). Consequently, solar UVR-induced skin cancers are among the most common forms of occupational malignancies that are potentially expected globally. This systematic review is registered in PROSPERO (CRD42021295221) and aims to assess the risk of cutaneous squamous cell carcinoma (cSCC) associated to occupational solar UVR exposure. Systematic searches will be performed in three electronic literature databases (PubMed/Medline, EMBASE, and Scopus). Further references will be retrieved by a manual search (e.g., in grey literature databases, internet search engines, and organizational websites). We will include cohort studies and case-control studies. Risk of Bias assessment will be conducted separately for case-control and cohort studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used for the certainty of assessment. In case quantitative pooling is not feasible, a narrative synthesis of results will be performed.

This prospective birth cohort followed 150 preterm and 300 term newborns during the first year of life to assess possible differences in risk factors, age at onset, anatomical location, and severity of atopic dermatitis. Atopic dermatitis was diagnosed clinically, and severity was assessed using Eczema Area Severity Index (EASI). DNA was analysed for filaggrin gene mutations. Parents were asked about environmental exposures and emollient use. Atopic dermatitis during the first year of life was observed in 21.2% of children and was more common in term children compared with preterm children (26.7% vs 11.7%, p

BackgroundOutdoor workers (OW) receive a higher dose of ultraviolet radiation (UVR) compared to indoor workers (IW) which increases the risk of non-melanoma skin cancer (NMSC). Regular sunscreen use reduces the NMSC risk, however, adequate sun-safety behavior among OW is poor. The main objective was to conduct method- and intervention-related elements of a future intervention trial among OW, based on providing sunscreen and assessing sunscreen use on group- and individual level.MethodsThis pilot study was conducted at a construction site in the Netherlands from May-August 2021. Nine dispensers with sunscreen (SPF 50+) were installed at the worksite. OW (n = 67) were invited to complete two (cross-sectional) questionnaires on sun-safety behavior, before and after providing sunscreen. Stratum corneum (SC) samples for the assessment of UV-biomarkers were collected from the forehead and behind the ear from 15 OW and 15 IW. The feasibility of the following elements was investigated: recruitment, (loss to) follow-up, outcome measures, data collection, and acceptability of the intervention.ResultsThe first questionnaire was completed by 27 OW, the second by 17 OW. More than 75 percent of the OW were aware of the risks of sun exposure, and 63% (n = 17) found sunscreen use during worktime important. The proportion of OW never applying sunscreen in the past month was 44.4% (n = 12) before, and 35.3% (n = 6) after providing sunscreen. A majority of OW (59.3%, n = 16) found sunscreen provision encouraging for sunscreen use, the dispensers easy to use (64.7%, n = 17) and placed in practical spots (58.8%, n = 18). Collecting SC-samples was fast and easy, and several UV-biomarkers showed higher levels for sun-exposed compared to less exposed body parts. There was no significant difference in UV-biomarker levels between OW and IW.ConclusionsThis pilot study revealed low sunscreen use among OW despite providing sunscreen, overall satisfaction with the sunscreen, and the sufficient awareness of the risks of UVR-exposure. Collecting SC-samples at the workplace is feasible and several UV-biomarkers showed to be promising in assessing UVR-exposure. The low participation rate and high loss to follow-up poses a challenge for future intervention studies.

Introduction Hairdressers constitute a major subgroup in the service sector. They are exposed to various substances hazardous for skin, airways or systemically. Accordingly, skin and other occupational diseases are common. The present systematic review will compile and appraise evidence regarding skin, systemic and airways toxicity of an indicative set of specific, important product ingredients. Additionally, evidence concerning hand eczema morbidity among hairdressers will be reviewed.Methods and analysis Systematic searches will be performed in two electronic literature databases (Medline, Web of Science–Core Collection), the Cochrane register and two collections of toxicological dossiers (Scientific Committee on Consumer Safety of the European Commission and the MAK Commission of the German Research Council). Additional literature sources will be retrieved using hand search of reference lists of included studies and snowballing methods. We will include studies with all types of quantitative study designs, including results from in vitro and in vivo experiments, chemical analysis, epidemiological findings and clinical results. We will assess the risk of bias within studies amalgamating an abbreviated version of the Mixed Methods Appraisal Tool, basic Cochrane criteria and US Environmental Protection Agency assessment factors for scientific information. As we expect large heterogeneity in methods and outcomes, we will conduct a narrative synthesis of results instead of a meta-analysis, except where quantitative pooling is feasible.Ethics and dissemination Ethical approval and patient consent are not required as this is a systematic review based on published studies. The results of this study will be published in international peer-reviewed journals.PROSPERO registration number CRD42021238118

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from melanoma and non-melanoma skin cancer (or keratinocyte carcinoma) from occupational exposure to solar ultraviolet radiation, to inform the development of the WHO/ILO joint methodology. Objectives: We aim to systematically review studies on occupational exposure to solar ultraviolet radiation (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to solar ultraviolet radiation on melanoma and non-melanoma skin cancer (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework and conducting both systematic reviews in tandem and in a harmonized way. Data sources: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and Web of Science. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records and consult additional experts. Study eligibility and criteria: We will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (

Introduction: Non-melanoma skin cancer (NMSC) incidence is increasing, and occupational solar exposure contributes greatly to the overall lifetime ultraviolet radiation (UVR) dose. This is reflected in an excess risk of NMSC showing up to three-fold increase in outdoor workers. Risk of NMSC can be reduced if appropriate measures to reduce UVR-exposure are taken. Regular use of sunscreens showed reduced risk of NMSC. However, sun-safety behavior in outdoor workers is poor. The objective of this study is to investigate the effectiveness of an intervention aiming at increasing sunscreen use by construction workers.Methods: This non-randomized controlled intervention study is comprised of two intervention and two control groups recruited at four different construction sites in the Netherlands. The study population comprises ~200 construction workers, aged 18 years or older, followed during 12 weeks. The intervention consists of providing dispensers with sunscreens (SPF 50+) at construction sites and regular feedback on the application achieved by continuous electronic monitoring. All groups will receive basic information on UV-exposure and skin protection. Stratum corneum (SC) samples will be collected for measurement of biomarkers to assess internal UV-dose. External UV-dose will be assessed by personal UV-sensors worn by the workers during work-shifts in both groups. To detect presence of actinic keratosis (AK) or NMSC, a skin check of body parts exposed to the sun will be performed at the end of the study. The effect of the intervention will be assessed from data on self-reported sunscreen use by means of questionnaires collected on baseline and after 12 weeks of intervention (primary outcome). Levels of SC biomarkers of internal UV-dose, external UV-dose, number of sunburn episodes, and prevalence of NMSC including AK will be assessed as secondary outcomes. The electronically monitored sunscreen consumption will be assessed as process outcome.Discussion: This study is intended to provide evidence of the effectiveness of a technology-driven intervention to increase sunscreen use in outdoor construction workers. Furthermore, it will increase insight in the UV-protective behavior, external and internal UV-exposure, and the prevalence of NMSC, including AK, in construction workers.Trial Registration: The Netherlands Trial Register (NTR): NL8462 Registered on March 19, 2020.

Background: Impaired skin barrier is an important etiological factor in atopic dermatitis (AD). The structural protein filaggrin (FLG) plays a major role in maintenance of the competent skin barrier and its deficiency is associated with enhanced susceptibility to mechanical injury. Here we examined biomechanical characteristics of the corneocytes in children with AD and healthy controls. Methods: We recruited 20 children with AD and 7 healthy children. They were genotyped for filaggrin gene (FLG) loss-of-function mutations. Stratum corneum was collected from clinically unaffected skin by adhesive tapes. Cell stiffness (apparent elastic modulus, Ea) was determined by atomic force microscopy and filaggrin degradation products (NMF) by liquid chromatography. Skin barrier function was assessed through trans-epidermal water loss (TEWL) and disease severity by the SCORing Atopic Dermatitis (SCORAD) tool. Results: Corneocytes collected from AD patients showed a decreased elastic modulus which was strongly correlated with NMF and TEWL, but not with SCORAD. As compared with healthy controls, AD patients had reduced TEWL and NMF levels regardless of FLG mutations. NMF was strongly correlated with TEWL. Conclusion: Our findings demonstrate that AD patients have decreased corneocyte stiffness which correlates with reduced levels of filaggrin degradation products, NMF and skin barrier function. Altered mechanical properties of the corneocytes likely contribute to the loss of mechanical integrity of the SC and to reduced skin barrier function in AD.

Introduction Skin barrier development and dysfunction in premature and mature newborns is important for the risk of atopic dermatitis (AD).Methods and analysis The Barrier dysfunction in Atopic newBorns studY (BABY) Cohort is a prospective birth cohort study of 150 preterm children (gestational age (GA) below 37+0) and 300 term children (GA 37+0 to 41+6). Skin barrier is assessed through transepidermal water loss, tape stripping, Raman-spectroscopy and microbiome sampling. Clinical examinations are done and DNA from buccal swabs is collected for genetic analyses. Thymus size is assessed by ultrasound examination. Information on pregnancy, delivery, parental exposures and diseases are collected, and structured telephone interviews are conducted at 18 and 24 months to assess exogenous exposures in the child and onset of AD. Hanifin and Rajka criteria as well as The UK Working Party's Diagnostic Criteria for Atopic Dermatitis are used to diagnose AD. Severity of AD is assessed using the Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM).Ethics and dissemination The study is approved by the scientific Ethical Committee of the Capital Region (H-16042289 and H-16042294).Outcomes will be presented at national and international conferences and in peer-reviewed publications.

Abstract Background The Healthy Hands Project (HHP) is a randomised clinical trial aiming to determine the effectiveness of an intervention program in the prevention of hand dermatitis in healthcare workers (HCWs). The intervention is comprised of placing dispensers with hand creams on wards combined with continuous electronic monitoring of cream consumption and regular feedback to HCWs. The clinical severity (HECSI score) was used as the primary outcome and natural moisturising factor (NMF) levels as the secondary outcome. The study protocol for the cluster-randomised controlled trial of HHP was published in Trials in 2017. This article describes the detailed statistical analysis plan for the HHP trial. Methods/design The HHP is a single-centre, cluster-randomised controlled trial with two parallel groups and blinded outcome assessment. This update article presents (1) the descriptive statistics of the primary and secondary outcomes, (2) the statistical models used for the analysis of the main outcomes, (3) sensitivity analyses on the effect of observed exposure to wet work, (4) handling of missing data including sensitivity analysis and (5) an updated power calculation. This statistical analysis plan was written prior to unblinding of the study. Discussion This paper presents a comprehensive statistical analysis plan for the data resulting from the HHP trial. It supports transparency in reporting by clarifying differences between the previously published protocol and the proposed actual statistical analyses. Trial registration Netherlands Trial Register (NTR), identification number NTR5564. Registered on 2 November 2015.

Epidermal filaggrin level is affected by ultraviolet B irradiation in animal and experimental models. This study examined the effect of ultraviolet B irradiation on epidermal filaggrin and natural moisturizing factors in vivo in healthy adults (n = 22). Participants were irradiated with 2 minimal erythema doses of ultraviolet B on the skin. Biopsies and tape strips were collected from skin irradiated 24 and 72 h earlier and from non-irradiated skin (control). Real-time quantitative PCR on skin biopsies showed significantly reduced profilaggrin mRNA expression 24 h after irradiation (mean relative mRNA expression ± standard deviation: control, 3.86 ± 2.06 vs. 24 h, 1.52 ± 0.640; p = 0.02; n = 8). Immunohistochemistry showed aberrant spatial distribution of filaggrin protein 72 h after irradiation (n = 3). High-pressure liquid chromatography of tape extracts showed no change in mean total natural moisturizing factor levels after irradiation, but mean trans-urocanic acid was significantly reduced, as expected (n = 8). In conclusion, erythemal doses of ultraviolet B exert acute effects on profilaggrin mRNA and filaggrin protein in human skin in vivo.

Abstract Background Health care workers (HCW) are at high risk for developing occupational hand dermatitis (HD) due to frequent exposure to ‘wet work’. Amongst HCWs, nurses are at highest risk, with an estimated point prevalence of HD ranging between 12 and 30%. The burden of disease is high with chronicity, sick leave, risk of unemployment and impaired quality of life. Despite evidence from the medical literature on the risk factors and the importance of skin care in the prevention of HD, in practice, compliance to skin care protocols are below 30%. New preventive strategies are obviously needed. Methods/design This is a cluster randomized controlled trial, focusing on nurses performing wet work. In total, 20 wards are recruited to include 504 participating nurses in the study at baseline. The wards will be randomized to an intervention or a control group and followed up for 18 months. The intervention consists of the facilitation of creams being available at the wards combined with the continuous electronic monitoring of their consumption with regular feedback on skin care performance in teams of HCWs. Both the intervention and the control group receive basic education on skin protection (as ‘care as usual’). Every 6 months, participants of both groups will fill in the questionnaires regarding exposure to wet work and skin protective behavior. Furthermore, skin condition will be assessed and samples of the stratum corneum collected. The effect of the intervention will be measured by comparing the change in Hand Eczema Severity Index (HECSI score) from baseline to 12 months. The Natural Moisturizing Factor (NMF) levels, measured in the stratum corneum as an early biomarker of skin barrier damage, and the total consumption of creams per ward will be assessed as a secondary outcome. Discussion This trial will assess the clinical effectiveness of an intervention program to prevent hand dermatitis among health care workers Trial registration Netherlands Trial Register (NTR), identification number NTR5564. Registered on 2 November 2015.

Introduction Atopic eczema affects 20% of UK children, and environmental factors are important in its aetiology. Several observational studies suggest an increased risk of atopic eczema in children living in hard water areas. The Softened Water for Eczema Prevention pilot trial tests the feasibility of installing domestic ion-exchange water softeners around the time of birth to reduce the risk of atopic eczema in children with a family history of atopy. A further aim is to explore the pathophysiological mechanisms for this in an embedded mechanistic study.Methods and analysis Multicentre parallel group assessor-blinded randomised controlled pilot trial. Participants are newborn babies (n=80) living in a hard water (>250 mg/L calcium carbonate) area at risk of developing atopic eczema because of a family history of atopy. Participants will be randomised prior to birth in a 1:1 ratio. The intervention group will have an ion-exchange water softener installed prior to birth. The control group will receive their usual domestic hard water supply. Follow-up will be until 6 months of age. Data will be collected at birth (baseline), 1, 3 and 6 months of age. The main outcome is the proportion of eligible families screened who are willing and able to be randomised. Several secondary feasibility and clinical endpoints will also be evaluated, alongside mechanistic outcomes. Data will be analysed on an intention-to-treat basis. There will be no hypothesis testing for the clinical outcomes. Study acceptability will be evaluated through semistructured interviews.Ethics and dissemination This study has been reviewed and given a favourable opinion by the North West–Liverpool East Research Ethics Committee (Ref: 17/NW/0661). The results of the study will be reported at international conferences and in peer-reviewed scientific journals. We will send participating families a summary of the pilot trial results.Trial registration number NCT03270566.

ABSTRACT The bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments. IMPORTANCE Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. In this study, we decipher the molecular forces at play during adhesion of Staphylococcus aureus to skin corneocytes in the clinically important context of atopic dermatitis (AD), also known as eczema. We identify a unique relationship between the level of natural moisturizing factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion. Bacterial adhesion is primarily mediated by the surface protein clumping factor B (ClfB) and is enhanced by physical stress, highlighting the role of protein mechanobiology in skin colonization. Similar to a catch bond behavior, this mechanism represents a promising target for the development of novel antistaphylococcal agents.

A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. We demonstrate for the first time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.