Investigating causal relationships between Body Mass Index and risk of atopic dermatitis : a Mendelian randomization analysis

Population studies suggest that atopic dermatitis (AD) is associated with an increased risk of obesity, however a causal relationship between these two conditions remains to be established. We therefore use Mendelian randomization (MR) to evaluate whether obesity and AD are causally interlinked. We used summary statistics extracted from genome wide association studies of Body Mass Index (BMI) and AD. MR analysis was performed in both directions to establish the direction of causality between BMI and AD. We find that genetically determined increase in adiposity is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI). Conversely, genetically determined increased risk of AD is not associated with a higher BMI (change in BMI attributable to AD based on genetic information: 0.00; 95% CI - 0.02 to 0.02; p = 0.862). There was no evidence for confounding of these genetic analyses by horizontal pleiotropy. Our results indicate that the association of AD with obesity is likely to reflect a causal role for adiposity in the development of AD. Our findings enhance understanding of the etiology of AD, and the basis for experimental studies to evaluate the mechanistic pathways by which adiposity promotes AD.Published versio

Melanogenesis Inhibitors

Abnormally high production of melanin or melanogenesis in skin melanocytes results in hyperpigmentation disorders, such as melasma, senile lentigines or freckles. These hyperpigmentary skin disorders can significantly impact an individual’s appearance, and may cause emotional and psychological distress and reduced quality of life. A large number of melanogenesis inhibitors have been developed, but most have unwanted side-effects. Further research is needed to better understand the mechanisms of hyperpigmentary skin disorders and to develop potent and safe inhibitors of melanogenesis. This review summarizes the current understanding of melanogenesis regulatory pathways, the potential involvement of the immune system, various drugs in current use, and emerging treatment strategies to suppress melanogenesis

A silk-microneedle patch to detect glucose in the interstitial fluid of skin or plant tissue

Glucose is critical to all organisms. Herein, we developed a wire electrode embedded microneedle patch (WEMNP) for in situ real-time detection of glucose in the interstitial fluid (ISF) of skin or plant tissues with minimal invasiveness. WEMNP is made of proline treated silk fibroin proteins, which provide good mechanical strength (0.75 N/microneedle) for tissue penetration and desirable bioelectronic interface for fast and high-fidelity detection. WEMNP shows specific and linear response to glucose between 3 and 18 mM for detection in skin ISF with a sensitivity of 21.21 nA/mM and between 30 and 180 mM for detection in plant ISF with a sensitivity of 1.22 nA/mM. Such self-administrable WEMNP could be instrumental to long-term home-based management for chronic diseases and to smart agriculturing.Ministry of Education (MOE)Submitted/Accepted versionThis research was financially supported by AcRF Tier-1 Grants (RG110/20 and RT02/20) and AcRF Tier-2 grant (MOE2019-T2-2-004) from Singapore Ministry of Education

Creating a smartphone app for caregivers of children with atopic dermatitis with caregivers, health care professionals, and digital health experts : participatory co-design

Background: Smartphone apps could support patients and caregivers in disease self-management. However, as patients’ experiences and needs might not always align with clinical judgments, the eliciting and engaging of perspectives of all stakeholders in the smartphone app design process is of paramount importance. Objective: The aims of this study are to better understand the needs of and challenges facing caregivers and health care professionals (HCPs) who care for children with atopic dermatitis (AD) and to explore the desirable features and content of a smartphone app that would support AD self-management. Methods: This study adopted a qualitative participatory co-design methodology involving 3 focus group discussions: workshop one focused on caregivers; workshop two engaged with HCPs; and in the last workshop, caregivers and digital health experts were asked to design the wireframe prototype. The participants completed a sociodemographic questionnaire, a technology acceptance questionnaire, and a workshop evaluation form. Results: Twelve caregivers participated in the first workshop, and 10 HCPs participated in the second workshop. Eight caregivers and 4 digital health experts attended the third workshop. Three superordinate themes that reflected caregivers’ and HCPs’ challenges and needs were identified: empowerment by education, confusion over treatment, and emotional impact. Workshop participants also raised a series of suggestions on the features and contents of the AD self-management app, which informed the last co-design workshop, and described their needs and challenges. In the last workshop, the participants developed a wireframe prototype of the app following the identified requirements and recommendations. Conclusions: The co-design approach was found to be a successful way of engaging with the participants, as it allowed them to express their creativity and helped us to articulate the root of the clinical problems. The co-design workshop was successful in creating and generating new ideas and solutions for smartphone app development.Nanyang Technological UniversityPublished versionThis research was funded by a principal investigator start-up grant (Lee Kong Chian School of Medicine, Nanyang Technological University). JC’s post at Imperial College London is supported by the National Institute for Health Research NW London Applied Research Collaboration

Classification of non-tumorous skin pigmentation disorders using voting based probabilistic linear discriminant analysis

Non-tumorous skin pigmentation disorders can have a huge negative emotional impact on patients. The correct diagnosis of these disorders is essential for proper treatments to be instituted. In this paper, we present a computerized method for classifying five non-tumorous skin pigmentation disorders (i.e., freckles, lentigines, Hori's nevus, melasma and nevus of Ota) based on probabilistic linear discriminant analysis (PLDA). To address the large within-class variance problem with pigmentation images, a voting based PLDA (V-PLDA) approach is proposed. The proposed V-PLDA method is tested on a dataset that contains 150 real-world images taken from patients. It is shown that the proposed V-PLDA method obtains significantly higher classification accuracy (4% or more with p< 0.001 in the analysis of variance (ANOVA) test) than the original PLDA method, as well as several state-of-the-art image classification methods. To the authors' best knowledge, this is the first study that focuses on the non-tumorous skin pigmentation image classification problem. Therefore, this paper could provide a benchmark for subsequent research on this topic. Additionally, the proposed V-PLDA method demonstrates promising performance in clinical applications related to skin pigmentation disorders.Accepted versio

The cost of childhood atopic dermatitis in a multi-ethnic Asian population : a cost-of-illness study

Background: Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. Objectives: The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. Methods: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. Results: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. Conclusions: Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The costs related to atopic dermatitis are also strongly related to disease severity. This information is important for policy makers and other health planners when considering how to better support affected families.Agency for Science, Technology and Research (A*STAR)Nanyang Technological UniversityThis research was supported through the Skin Research Grant by the Skin Research Institute of Singapore, a tripartite partnership between the Agency for Science, Technology and Research, the National Healthcare Group through its National Skin Centre and Nanyang Technological University, Singapore

Concordance between physician-rated and caregiver-perceived disease severity in children with atopic dermatitis : a cross-sectional study

This study examined concordance between caregiver-reported and physician-rated estimates of severity of atopic dermatitis (AD) in paediatric patients and explored potential explanatory factors. Physician-reported severity of AD was retrieved from medical records, while caregiver-reported disease severity and sociodemographic data were obtained through a survey that also collected information on out-of-pocket expenses due to AD. There was 38.5% (95% confidence interval (95% CI) 30.1, 43.5) disagreement between physician and caregivers with regards to both underestimating and overestimating the condition. A duration since AD diagnosis shorter than 6 months showed higher concordance (kappa: 44.4%; 95% CI 30.6, 58.2) between caregiver and physician estimates of AD severity compared with a duration of 6 months or longer. Caregivers underestimating their child’s AD accounted for 27.7% among all participants, while 10.8% overestimated the severity of AD compared with physicians. Factors significantly associated with caregiver’s underestimation of disease severity were age of the child and time since disease diagnosis. Comparison of concordance between caregiver-reported and physician-rated estimates of severity of AD in paediatric patients revealed a tendency amongst caregivers to underestimate severity of AD. This information may have clinical implications for treatment outcomes if caregivers fail to adhere to medical advice.Agency for Science, Technology and Research (A*STAR)Nanyang Technological UniversitySkin Research Institute of Singapore (SRIS)Published versionThe authors would like to thank all children and caregivers that responded to the questionnaire and made this study possible. This research was supported through the Skin Research Grant by the Skin Research Institute of Singapore (SRIS), a tripartite partnership between the Agency for Science, Technology, and Research (A*STAR), National Healthcare Group through its National Skin Centre (NHG) and the Nanyang Technological University (NTU). Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the legally authorized representative (LAR) of the child prior to enrolment in the study

Microneedle-assisted topical delivery of photodynamically active mesoporous formulation for combination therapy of deep-seated melanoma

Topical treatment using photodynamic therapy (PDT) for many types of skin cancers has largely been limited by the inability of existing photosensitizers to penetrate into the deep skin tissue. To overcome these problems, we developed a mesoporous nanovehicle with dual loading of photosensitizers and clinically relevant drugs for combination therapy, while utilizing microneedle technology to facilitate their penetration into deep skin tissue. Sub-50 nm photodynamically active mesoporous organosilica nanoparticles were synthesized with photosensitizers covalently bonded to the silica matrix, which dramatically increased the quantum yield and photostability of these photosensitizers. The mesopores of the nanoparticles were further loaded with small-molecule inhibitors, i. e., dabrafenib and trametinib, that target the hyperactive mitogen-activated protein kinase (MAPK) pathway for melanoma treatment. As-prepared empty nanovehicle was cytocompatible with normal skin cells in the dark, while NIR-irradiated drug-loaded nanovehicle showed a synergistic killing effect on skin cancer cells mainly through reactive oxygen species and caspase-activated apoptosis. The nanovehicle could significantly inhibit the proliferation of tumor cells in a 3D spheroid model in vitro. Porcine skin fluorescence imaging demonstrated that microneedles could facilitate the penetration of nanovehicle across the epidermis layer of skin to reach deep-seated melanoma sites. Tumor regression studies in a xenografted melanoma mouse model confirmed superior therapeutic efficacy of the nanovehicle through combinational PDT and targeted therapy.Nanyang Technological UniversityNational Research Foundation (NRF)This research is supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03) and the NTU-Northwestern Institute for Nanomedicine