The impact of airborne pollution on atopic dermatitis: a literature review.

The increasing prevalence of atopic dermatitis (AD) parallels a global rise in industrialization and urban living over recent decades. This shift in lifestyle is accompanied by greater cutaneous exposure to environmental pollutants during the course of daily activities. The objectives of this review are to highlight the effects of airborne pollution on epidermal barrier function, examine evidence on the relationship between pollutants and AD, synthesize a proposed mechanism for pollution-induced exacerbation of AD, and identify potential methods for the reduction and prevention of pollutant-induced skin damage. The literature review was done by searching the PubMed, Embase and Google Scholar databases. Inclusion criteria were in vitro and animal studies, clinical trials and case series. Non-English-language publications, review articles and case reports were excluded. Pollutants induce cutaneous oxidative stress and have been shown to damage skin barrier integrity by altering transepidermal water loss, inflammatory signalling, stratum corneum pH and the skin microbiome. AD represents a state of inherent barrier dysfunction, and both long- and short-term pollutant exposure have been linked to exacerbation of AD symptoms and increased AD rates in population studies. Airborne pollutants have a detrimental effect on skin barrier integrity and AD symptoms, and appear to pose a multifaceted threat in AD through several parallel mechanisms, including oxidative damage, barrier dysfunction, immune stimulation and propagation of the itch-scratch cycle. Future research is needed to elucidate specific mechanisms of pollution-induced epidermal barrier dysfunction and to identify efficacious methods of skin barrier repair and protection against pollutant-driven damage.

Recent advances in hidradenitis suppurativa in pediatrics.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HS in the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children.

The impact of stress on epidermal barrier function: an evidence-based review.

BACKGROUND: The epidermal barrier functions to limit skin infection and inflammation by inhibiting irritant and immunogen invasion. Abundant evidence suggests that psychological stress stemming from crowding, isolation, nicotine smoking, insomnia, mental arithmetic tasks, physical pain, real-life stressors (examinations and marital strain) and lack of positive personality traits may impart both acute and chronic epidermal dysfunction. OBJECTIVES: To review the relationship between stress and epidermal barrier dysfunction. METHODS: A review of the PubMed and Embase databases was conducted to identify all English-language case-control, cross-sectional and randomized control trials that have reported the effect of stress on epidermal barrier function. The authors' conclusions are based on the available evidence from 21 studies that met the inclusion and exclusion criteria. RESULTS: Psychological stressors upregulate the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. This ultimately leads to aberrant barrier dysfunction, characterized by decreased epidermal lipid and structural protein production, decreased stratum corneum hydration and increased transepidermal water loss. CONCLUSIONS: This evidence-based review explores the adverse effects of psychological stressors on epidermal barrier function. Future investigations using more real-life stressors are needed to elucidate further their impact on skin physiology and identify practical stress-relieving therapies that minimize and restore epidermal barrier dysfunction, particularly in at-risk populations. What's already known about this topic? The literature reports the negative effect of stress on prolonged wound healing. Less is known about the relationship between stress and epidermal barrier dysfunction, a chronic, superficial wound involving the upper epidermal layers. What does this study add? Psychological stressors impact epidermal barrier function by activating the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. Stress hormones negatively affect the epidermal barrier by decreasing epidermal lipids and structural proteins, decreasing stratum corneum hydration and increasing transepidermal water loss. Identification of such stressors can promote stress-avoidance and stress-reduction behaviours that protect epidermal barrier function and prevent certain dermatological conditions.

Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation.

BACKGROUND: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. OBJECTIVES: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. METHODS: A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. RESULTS: Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin-mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. CONCLUSIONS: As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long-term outcomes and reduce allergen sensitization in the airway and gut.

Topical micronutrients in atopic dermatitis-An evidence-based review.

The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti-inflammatory and anti-microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis.

Diffusion tensor invasive phenotypes can predict progression-free survival in glioblastomas.

INTRODUCTION: Glioblastomas multiformes (GBM) remain incurable in most cases. Their invasion into normal brain makes current therapies ineffective. Post-mortem studies suggest about a 25% of GBMs invade less than 1 cm from the tumour bulk and 20% invade more than 3 cm. AIM OF STUDY: The study aims to use DTI to assess tumour extension and determine how previously reported patterns relate to the progression-free survival (PFS). MATERIALS AND METHODS: Twenty-five patients with GBM treated according to the EORTC/NCIC protocol were retrospectively analysed. Patients were imaged post-operatively at 1.5 T. The sequences were composed of standard anatomical and a standard DTI sequence. As described earlier p and q maps were constructed. For each of the p and q maps, regions of interest were drawn around the visible abnormality. Patients were assigned a diffuse, localised or minimally invasive pattern. Progression was defined according to the RANO criteria (4) and PFS determined in days. Kaplan-Meier plots of survival for the three groups were plotted as were the proportion of patients who had not progressed at 24 months. RESULTS: The median PFS for the diffuse group was 278 days, for the localised group 605 days and 820 days for the minimally invasive group. Three-fourth of the minimally invasive group were progression-free at 24 months (LOG RANK 9.25; p = 0.010). CONCLUSION: It is possible to identify three invasive phenotypes in GBMs using Diffusion tensor imaging , and these three phenotypes have different progression free survival. A minimal phenotype (20% of patients) predicts a greater delay to progression.

Down-modulation of cancer targets using locked nucleic acid (LNA)-based antisense oligonucleotides without transfection.

Usually, small interfering RNAs and most antisense molecules need mechanical or chemical delivery methods to down-modulate the targeted mRNA. However, these delivery approaches complicate the interpretations of biological consequences. We show that locked nucleic acid (LNA)-based antisense oligonucleotides (LNA-ONs) readily down-modulate genes of interest in multiple cell lines without any delivery means. The down-modulation of genes was quick, robust, long-lasting and specific followed by potent down-modulation of protein. The efficiency of the effect varied among the 30 tumor cell lines investigated. The most robust effects were found in those cells where nuclear localization of the LNA-ON was clearly observed. Importantly, without using any delivery agent, we demonstrated that HER3 mRNA and protein could be efficiently down-modulated in cells and a tumor xenograft model. These data provide a simple and efficient approach to identify potential drug targets and animal models. Further elucidation of the mechanism of cellular uptake and trafficking of LNA-ONs may enhance not only the therapeutic values of this platform but also antisense molecules in general.

Potential Factors Influencing Repeated SARS Outbreaks in China.

Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor-angiotensin-converting enzyme 2 (ACE2)-for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.

Enhancing life cycle chemical exposure assessment through ontology modeling.

In its 2014 report, A Framework Guide for the Selection of Chemical Alternatives, the National Academy of Sciences placed increased emphasis on comparative exposure assessment throughout the life cycle (i.e., from manufacturing to end-of-life) of a chemical. The inclusion of the full life cycle greatly increases the data demands for exposure assessments, including both the quantity and type of data. High throughput tools for exposure estimation add to this challenge by requiring rapid accessibility to data. In this work, ontology modeling was used to bridge the domains of exposure modeling and life cycle inventory modeling to facilitate data sharing and integration. The exposure ontology, ExO, is extended to describe human exposure to consumer products, while an inventory modeling ontology, LciO, is formulated to support automated data mining. The core ontology pieces are connected using a bridging ontology and discussed through a theoretical example to demonstrate how data from LCA can be leveraged to support rapid exposure modeling within a life cycle context.

In Vivo Reflectance Confocal Microscopy: Emerging Role in Noninvasive Diagnosis and Monitoring of Eczematous Dermatoses. / Microscopia confocal de reflectancia in vivo: papel emergente en el diagnóstico no invasivo, así como en el seguimiento de las dermatosis eccematosas.

Dermatologic diagnosis and monitoring have been dependent largely on visual grading. A skin biopsy is performed in case of diagnostic uncertainty, but can be traumatic, and results are delayed due to time for specimen transport and processing. Biopsies also destroy specimens, prohibiting lesion evolution monitoring. In vivo reflectance confocal microscopy (RCM) offers a diagnostic alternative to skin biopsy. RCM captures real-time, high-resolution images, and has been piloted for the evaluation of various dermatologic conditions. Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies. Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are diagnosed by patch testing that currently uses a subjective scoring system. RCM has increasingly been studied for early detection and severity grading of CD. Common RCM features shared by ACD and ICD are stratum corneum disruption, vesicle formation, exocytosis, spongiosis, and parakeratosis. Features unique to ACD are vasodilation, increased epidermal thickness, intercellular edema, and acanthosis. Features unique to ICD are detached corneocytes and targetoid keratinocytes. This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool.

A meta-analysis of selected near-road air pollutants based on concentration decay rates.

Traffic-related air pollution has been associated with various health risks for human populations living near roadways. Understanding the relationship between traffic density and dispersion of vehicle-released air pollutants is important for assessing human exposure to near-road air pollutants. We performed a literature survey targeting publications containing measurement data of traffic-related air pollutants near roads with distance information on their concentration distribution. Concentration decay rates over down-wind distance away from major roads were calculated for black carbon (BC), carbon monoxide (CO) and nitrogen oxides (NO2 or NOx) and meta-data analysis on these rates was performed. These analyses showed metadata-based exponential decay rates of 0.0026, 0.0019, 0.0004, and 0.0027 m-1 for BC, CO, NO2 and NOx, respectively. Using these measurement data-based decay rates, concentrations for BC, CO, NO2 and NOx over various near-road distances were predicted. These results are useful for enhancing exposure modeling and thus more reliably assessing the health risk of exposure to near road air pollution.