Skin microbiota and human 3D skin models

Abstract

Although the role of the microbiota in skin homeostasis is still emerging there is growing evidence that an intact microbiota supports the skin barrier. The increasing number of research efforts that are trying to shed more light on the human skin-microbiota interaction require the use of suitable experimental models. Three-dimensional (3D) skin equivalents have been established as a valuable tool in dermatological research because they contain a fully differentiated epidermal barrier that reflects the morphological and molecular characteristics of normal human epidermis. In this review we provide an overview of current 3D skin models and illustrate the potential of 3D skin models to study the human skin-microbiota interplay.

This article is protected by copyright. All rights reserved.

p.Glu477Lys mutation in keratin 5 is not necessarily mortal in generalized severe epidermolysis bullosa simplex

Lack of correlation of desiccation and radiation tolerance in microorganisms from diverse extreme environments tested under anoxic conditions

Abstract

Four facultative anaerobic and two obligate anaerobic bacteria were isolated from extreme environments (deep subsurface halite mine, sulfidic anoxic spring, mineral-rich river) in the frame MASE (Mars Analogues for Space Exploration) project. The isolates were investigated under anoxic conditions for their survivability after desiccation up to six months and their tolerance to ionizing radiation up to 3000 Gy. The results indicated that tolerances to both stresses are strain-specific features. Yersinia intermedia MASE-LG-1 showed a high desiccation tolerance but its radiation tolerance was very low. The most radiation tolerant strains were Buttiauxella sp. MASE-IM-9 and Halanaerobium sp. MASE-BB-1. In both cases, cultivable cells were detectable after an exposure to 3 kGy of ionizing radiation, but cells only survived desiccation for 90 and 30 days, respectively.Although a correlation between desiccation and ionizing radiation resistance has been hypothesized for some aerobic microorganisms, our data showed that there was no correlation between tolerance to desiccation and ionizing radiation, suggesting that the physiological basis of both forms of tolerances is not necessarily linked. In addition, these results indicated that facultative and obligate anaerobic organisms living in extreme environments possess varied species-specific tolerances to extremes.

Sorption of benzene derivatives onto a humic acid-zeolitic tuff adduct

Abstract

The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT-ImHA) was analysed by batch technique at 25 °C and neutral pH. PCT-ImHA was prepared by binding leonardite-extracted humic acids (HA) to a zeolitic tuff sample rich in phillipsite and chabazite and enriched with Ca²⁺ by cation exchange (Ca-PCT). The HA calcium salts were gently mixed with wet Ca-PCT; then, the mixture was heated at 330 °C for 1.5 h. An adduct with almost 2% of HA was obtained. The experimental data were well fitted by the Langmuir adsorption isotherm and showed that saturation capacity (q_Max) increased with the octanol-water repartition coefficient (K_O-W). The comparison with previous data on sorption onto immobilised HA highlights that q_Max values for PCT-ImHA are far higher than the sum of the contributions of the two separate components.

Promising therapeutic option for cutaneous plasmacytosis: 308-nm excimer lamp

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss

Abstract

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid-frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α-reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset

The efficacy of botulinum neurotoxin A in the treatment of plaque psoriasis

Desmoplastic transformation of a nodular melanoma arising from a speckled lentiginous nevus

Monitoring of immunoglobulin A antibodies to epidermal and tissue transglutaminases over an 18-month period in a Japanese patient with dermatitis herpetiformis

Comparison of stratum corneum thickness between two proposed methods of calculation using Raman spectroscopic depth profiling of skin water content

Abstract

Background/purpose

The stratum corneum (SC) is the most important layer for the barrier function of skin, so investigation of the SC is very important in cosmetic and medical research. Here, we calculated the SC thickness using the depth profile of the skin's water concentration based on previously described methods, and then compared the results.

Methods

Seven Korean women in their 30s participated in this study. Raman spectroscopy was used to measure the in vivo depth profile of skin water concentration. A total of 21 areas were measured at forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the slope and intersection methods.

Results

The slope method and the intersection method gave a forearm SC thickness calculated at 21.3 ± 2.6 μm and 17.6 ± 2.8 μm, respectively. There was a significant difference between the two calculation methods but the two methods showed strong correlation of SC thickness results (r = .899).

Conclusion

Although there was a difference in calculated SC thickness of about 20% between the two methods, these results reveal that the two SC thickness calculation methods using Raman spectroscopy were suitable for measuring SC thickness, a finding consistent with other published results.

The shaded side of the UHC cube: a systematic review of human resources for health management and administration in social health protection schemes

Managers and administrators in charge of social protection and health financing, service purchasing and provision play a crucial role in harnessing the potential advantage of prudent organization, management a...

Novel splice site mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis: Case report and published work review

Abstract

Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a frame-shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.

Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance

Abstract

A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for Japanese patients with malignant melanoma and accumulate data on all adverse events (AE) and efficacy. In this interim analysis, we evaluated data from approximately 100 Japanese medical institutions obtained from the nivolumab approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored during the first 12 months of treatment. Nivolumab was administrated by i.v. infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated for safety and efficacy, respectively. The incidences of adverse drug reactions (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%), alkaline phosphatase (6.18%) and γ-glutamyltransferase (5.44%). Grade 3 or higher ADR of special interest with an incidence of 1% or higher were hepatic function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special interest, were observed. The estimated median overall survival was 379 days (95% confidence interval [CI], 290–not reached [NR]) in the overall population, NR (95% CI, 305–NR) for cutaneous melanoma and 340 days (95% CI, 275–NR) for mucosal melanoma. The improvement rate based on the antitumor response at the last evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and serious ADR of special interest were infrequent. Nivolumab showed equivalent efficacy in patients with mucosal melanoma and those with cutaneous melanoma.

Kinetics, isotherms, and thermodynamic studies of lead, chromium, and cadmium bio-adsorption from aqueous solution onto Picea smithiana sawdust

Abstract

Lead (Pb), chromium (Cr), and cadmium (Cd) removal capacity of sawdust (Picea smithiana) from aqueous solution was investigated by conducting batch experiments. Thermodynamic parameters, like change in standard free energy (ΔG^Θ), enthalpy (ΔH^Θ) and entropy (ΔS^Θ) during bio-adsorption process were estimated using the Van't Hoff equation. The maximum metals adsorption was observed at pH 8, 20 g L⁻¹ bio-adsorbent and at 60 min of contact time. The metal adsorption kinetics was examined by fitting the pseudo-first-order as well as four forms of pseudo-second-order kinetic models. Type 1 pseudo-second-order equation described adsorption kinetics better than others. Langmuir model and Freundlich equations were used for calculation of sorption parameters. The Langmuir maximum adsorption capacity of Pb, Cr, and Cd was 6.35, 3.37, and 2.87 mg g⁻¹ at room temperature, respectively. The values of the separation factor (RL) were in between 0 and 1, indicating that bio-adsorption was favorable. Thermodynamics study revealed that the Pb, Cr, and Cd uptake reactions were endothermic and spontaneous. Results of the study asserted that the removal of heavy metal ions from aqueous solution is viable and the sawdust could be used in the treatment of effluents from industries, thereby reducing the level of water pollution.

Glyoxal-induced exacerbation of pruritus and dermatitis is associated with staphylococcus aureus colonization in the skin of a rat model of atopic dermatitis.

Atopic dermatitis (AD) is a chronically relapsing inflammatory disease resulting from complex interactions between immunological and environmental factors [1]. Immunological features, including barrier dysfunction and type 2 T-helper cell (Th2) immune reactions, form the basis for initiation of AD pathology. Accordingly, acute lesions in the skin of patients with AD are characterized by profound increment of Th2 cytokines such as interleukin (IL)-4 and IL-5 [2], whereas in chronic AD lesions, type 1 T-helper cell (Th1) immune reaction coexists with Th2 immune reaction rather than a switch to Th1-dominant inflammation [3–5].

A heterozygous mutation in the SAM domain of p63 underlies a mild form of ectodermal dysplasia

p63 is a major transcription factor which plays crucial roles in development of various epithelial tissues including skin [1]. In humans, p63 is encoded by TP63 gene and mutations in the TP63 gene are known to underlie at least five distinct ectodermal dysplasia (ED) syndromes: Rapp-Hodgkin syndrome (OMIM 129400), ankyloblepharon, ectodermal defects and cleft lip/palate (AEC) syndrome (OMIM 106260), ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285), and limb mammary syndrome (OMIM 603543) [1,2].

The UVA-induced long non-coding RNA GS1-600G8.5 regulates the expression of IL-8

Exposure of the skin to ultraviolet radiation (UVR) has many detrimental effects, including sunburning/inflammation, photocarcinogenesis, and photoaging. Longwave ultraviolet radiation (UVA) has long been considered less damaging than shortwave ultraviolet radiation (UVB), but has since been recognized to be a complete carcinogen itself [1], to be a particular cause of photoaging, and to elicit a number of inflammatory photodermatoses. Cells are equipped to counteract the damaging effects of UVR and respond to UVR by altering the expression of thousands of genes [2].

Title Page

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1

Table of Contents

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1

Editorial Board

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1

CME Overview

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1

The future is finally here: Advances in the treatment of atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Matthew J. Zirwas

Dupilumab: A review of its use in the treatment of atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Melinda J. Gooderham, H. Chih-ho Hong, Panteha Eshtiaghi, Kim A. Papp
Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD. Clinical trials have shown that adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient-reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant use of topical corticosteroids along with dupilumab results in a greater improvement in signs and symptoms of AD than with use of dupilumab alone. Biomarker analyses show that dupilumab modulates the AD molecular signature and other Th2-associated biomarkers. Common adverse events reported in the clinical trials were nasopharyngitis, upper respiratory tract infection, injection site reactions, skin infections, and conjunctivitis. These were mild-to-moderate in nature, and overall rates of adverse events occurred with similar frequency between the treatment and placebo groups. There were no significant serious safety concerns identified in phase III clinical trials. Dupilumab, as monotherapy or with concomitant use of topical corticosteroids, can significantly improve clinical outcomes and quality of life in patients suffering from moderate-to-severe AD. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use.

New therapies for atopic dermatitis: Additional treatment classes

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Paras P. Vakharia, Jonathan I. Silverberg
BackgroundA wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic, and biologic agents.ObjectiveTo review the known efficacy and safety to date for such agents being studied for the treatment of AD.MethodsA nonsystematic review of the literature was performed. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described previously for the treatment of AD. Randomized controlled trials were primarily sought, but other study types were also included if they contained pertinent data. Agents are presented by mechanism of action, with analysis of mechanism of action and data regarding efficacy and safety in patients with AD.ResultsData regarding the following agents are presented: omiganan (an antimicrobial peptide), tapinarof (a nonsteroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (a κ-opioid agonist), DS107 (dihomo-γ-linolenic acid), ZPL-389 (a histamine H4 receptor antagonist), secukinumab (an interleukin 17A inhibitor), and fezakinumab (interleukin 22 inhibitor).LimitationsLimited clinical data exist for many of the described agents.ConclusionsAs recent research has improved our understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD. Many of these hold great therapeutic promise for AD, and continued research and development is warranted.

Monoclonal antibodies against interleukin 13 and interleukin 31RA in development for atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Carsten R. Hamann, Jacob P. Thyssen
The interleukin 13 (IL-13) and IL-31 cytokines and inflammatory pathways have been identified as important for the pathophysiology of atopic dermatitis (AD). Monoclonal antibodies against IL-13 have been studied for the treatment of asthma since 2011. More recently, 2 phase 2 trials have been completed with these antibodies in AD treatment. In both trials, significant reductions of Eczema Area and Severity Index scores were seen. IL-31 is thought to play a role transmitting itch sensation to the central nervous system, and blocking IL-31 activity reduces itch in patients with AD. One phase 2 trial has been completed for a humanized antibody against IL-31 receptor alpha, which is 1 subunit of the IL-31 receptor complex. This study showed significant dose-dependent reductions in pruritus, Eczema Area and Severity Index scores, and markers of sleep quality. Initial clinical trials for monoclonal antibodies against IL-13 and IL-31 receptor A all show promise, although long-term safety and efficacy data are lacking. Nevertheless, these medications will likely play a role in the treatment of moderate-to-severe AD.

Phosphodiesterase 4 inhibitors

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Rema Zebda, Amy S. Paller
Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration–approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety.

Emerging therapies for atopic dermatitis: JAK inhibitors

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): David G. Cotter, David Schairer, Lawrence Eichenfield
The Janus kinase–signal transducer and activator of transcription pathway is a conserved master regulator of immunity and myeloproliferation. Advanced understanding of this pathway has led to development of targeted inhibitors of Janus kinases (Jakinibs). As a class, JAK inhibitors effectively treat a multitude of hematologic and inflammatory diseases. Given such success, use of JAK inhibitors for mitigation of atopic dermatitis is under active investigation. Herein, we review the evolving data on the safety and efficacy of JAK inhibitors in treatment of atopic dermatitis. Although it is still early in the study of JAK inhibitors for atopic dermatitis, evidence identifies JAK inhibitors as effective alternatives to conventional therapies. Nonetheless, multiple large safety and efficacy trials are needed before widespread use of JAK inhibitors can be advocated for atopic dermatitis.

Emerging therapies for atopic dermatitis: TRPV1 antagonists

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Jonathan G. Bonchak, Robert A. Swerlick
Transient receptor potential (TRP) ion channels are important mediators of somatosensory signaling throughout the body. Our understanding of the contribution of TRPs to a multitude of cutaneous physiologic processes has grown substantially in the past decade. TRP cation channel subfamily V member 1 (TRPV1), one of the better-understood members of this large family of ion channels, affects multiple pathways involved in pruritus. Further, TRPV1 appears to play a role in maintaining skin barrier function. Together, these properties make TRPV1 a ripe target for new therapies in atopic dermatitis. Neurokinin antagonists may affect similar pathways and have been studied to this effect. Early trials data suggest that these therapies are safe, but assessment of their efficacy in atopic dermatitis is pending as we await publication of phase II and III clinical trials data.

T-cell inhibitors for atopic dermatitis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): W. James Tidwell, Joseph F. Fowler
The management of atopic dermatitis is changing with the development of novel biologic agents to target specific molecules in the inflammatory cascade. Following the ability of dupilumab has proved its ability to act on the interleukin 4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin monoclonal antibody (AMG157/MEDI9929) and OX40 blocking antibody (GBR 830) were developed by targeting the same pathway as dupilumab further upstream. The clinical data on the efficacy for these drugs are not yet known. There is some early evidence that AMG157/MEDI9929 attenuates most measures of allergen-induced asthmatic responses. However, there are no public data on its ability to treat atopic dermatitis. In a phase 2a study, GBR 830 showed at least a 50% reduction in the Eczema Area and Severity Index scores of 17 of 23 patients, but it was not sufficiently powered for identification of statistical differences between GBR 830 versus placebo. Although there is potential for these 2 drugs to greatly improve the management of severe atopic dermatitis, significant clinical trials have not yet been completed to prove efficacy, and there are not yet any available phase 3 clinical trials, which are needed to truly evaluate their efficacy in affecting T-cells.

Emerging therapies for atopic dermatitis: The prostaglandin/leukotriene pathway

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3, Supplement 1
Author(s): Daniel A. Yanes, Joy L. Mosser-Goldfarb
The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, whereas small pilots using zileuton did have some clinically significant improvement. There are several agents in development that target leukotrienes and/or prostaglandins as well, including OC000459, Q301, and ZPL-521. In atopic dermatitis, OC000459 did not demonstrate efficacy in clinical trials, and the efficacy of the other 2 agents remains to be seen. Should these medications prove promising, these topical agents may play a future role in chronic maintenance therapy and flare prophylaxis in atopic dermatitis, as antileukotriene therapy does in asthma.

Antioxidant biomarkers in Gammarus pulex to evaluate the efficiency of electrocoagulation process in landfill leachate treatment

Abstract

The discharge of landfill leachate into the environment without effective treatment poses a serious threat for the aquatic ecosystems. This present study was undertaken to evaluate whether electrocoagulation process is efficient for treatment landfill leachate (LL) or not by using antioxidant biomarkers in Gammarus pulex. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities and malondialdehyde (MDA) and glutathione (GSH) levels in G. pulex exposed to untreated, treated, and diluted rates 1/10 and 1/20 in both LL during 24 and 96 h were tested. Physiochemical characteristics of leachate (chemical oxygen demand, electrical conductivity, pH, phosphate, turbidity, NH₃, Cl⁻, and color) were determined pre and post treatment. All physiochemical characteristics of LL decreased after treatment process. GSH-Px and CAT activities and GSH and MDA levels were increased in untreated groups when compared to control (p < 0.05). After treatment by electrocoagulation, MDA and GSH levels and CAT activities were returned to control values. In conclusion, the abilities of LL to stimulate oxidative stress in G. pulex have been proven. The results revealed that antioxidant parameters are useful biomarkers for determining the treatment efficiency of the electrocoagulation process.

Quantifying particulate matter accumulated on leaves by 17 species of urban trees in Beijing, China

Abstract

Airborne particulate matter (PM) has become a serious environmental problem and harms human health worldwide. Trees can effectively remove particles from the atmosphere and improve the air quality. In this study, a washing and weighing method was used to quantify accumulation of water-soluble ions and insoluble PM on the leaf surfaces and within the wax of the leaves for 17 urban plant species (including 4 shrubs and 13 trees). The deposited PM was determined in three size fractions: fine (0.2–2.5 μm), coarse (2.5–10 μm), and large (> 10 μm). Significant differences in the accumulation of PM were detected among various species. The leaves of Platycladus orientalis and Pinus armandi were the most effective in capturing PM. Across the species, 65 and 35% of PM, on average, deposited on the leaf surface and in the wax, respectively. The greatest PM accumulation by mass on leaves was in the largest PM size fraction, while the accumulation of coarse and fine particle size fractions was smaller. Water-soluble ions accumulated on the leaf surfaces contributed 28% to the total PM mass, on average. This study demonstrated that leaves of woody plants accumulate PM differently, and the most effective plant species should be selected in urban areas for attenuating ambient PM.

Exploring the effects of earthworms on bacterial profiles during vermicomposting process of sewage sludge and cattle dung with high-throughput sequencing

Abstract

This study aims to reveal the effects of earthworms (Eisenia fetida) on bacterial profiles during the vermicomposting process of sewage sludge and cattle dung with the high-throughput sequencing technology. The earthworms could accelerate organic degradation and improve the stabilization process. Moreover, the addition of earthworms not only affected the bacterial numbers, but also increased the bacterial community diversity. The activity of earthworms had significant effects on the bacterial community structure as the bacterial community was clearly different between the vermicomposting and the control treatment. Furthermore, the earthworms affected the physical and chemical properties of substrates, thus promoting the growth of some microorganisms, such as Flavobacteria, Acidbacteria, and Planctomycetes. Earthworms largely inhibited the growth of various human pathogenic bacteria. In summary, earthworms significantly affected the bacterial community in vermicomposting and it could be applied as an authentically effective technique for the stabilization of organic wastes.

Polycyclic aromatic hydrocarbons (PAHs) in multi-phases from the drinking water source area of the Pearl River Delta (PRD) in South China: Distribution, source apportionment, and risk assessment

Abstract

Sixteen priority polycyclic aromatic hydrocarbons (PAHs) were investigated in the water dissolved phase (DP), suspended particulate matter (SPM), and sediment collected from the water source zone of the Pearl River Delta region. The sum of 16 PAH concentrations ranged from 92.8 to 324 ng/L in the water DP, from 28.8 to 205 ng/L in the SPM, and from 55.7 to 381 ng/g (d.w.) in the sediment. Compared with other areas globally, the PAH levels were considerably moderate in the DP and SPM and relatively low in the sediment. Spatial distribution of PAHs was site-specific, and relatively higher PAH levels were found in the areas with dense population and heavy traffic. The PAH profile was dominated by two- and three-ring PAHs, and PAH pollution was identified of pyrolytic origins. Based on risk quotient, the ecological risk in water was ranked as moderate, but the adverse health risk associated with water ingestion was minimal. Naphthalene and fluorene of the sediment samples showed potential biological impairment in some locations; nevertheless, the mean effects range median quotient suggested that the ecological risk of multiple PAHs was quite low (less than 10% incidence of adverse effects).

Time-lapse imaging points towards a non-toxic, mainly immune-driven mode of action of ingenol mebutate in the treatment of anogenital warts

Abstract

Recently, it has been reported that ingenol mebutate (IM) is an effective treatment option for anogenital warts (AGW), inducing fast wart necrosis within 24 hours in vivo. With regard to its mode of action, IM is thought to act both by direct cytotoxic effects and as an inducer of immunologic mechanisms. To distinguish, whether the wart necrosis is mainly caused by cytotoxic effects, or whether immune mechanisms are leading, we used time-lapse imaging to analyze IM-treated warts ex vivo over 24 hours. Ex vivo IM-treated warts, which have been detached from the immune system, did not show destructive necrosis, pointing towards a primarily immune-driven mode of action of IM in the treatment of AGW.

This article is protected by copyright. All rights reserved.

PACAP and its receptors in cranial arteries and mast cells

In migraineurs pituitary adenylate cyclase activating peptide1–38 (PACAP1–38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion ...

On Carolina Sartorio’s Causation and Free Will

Abstract

In this article I review the core elements of Carolina Sartorio's actual causal sequence account of free will and moral responsibility, and propose two revisions. First, I suggest replacing the contested notion of absence causation by the relatively uncontroversial notion of causal explanation by absences. Second, I propose retaining explanation by unreduced dispositions, of which Sartorio appears to be wary. I then set out a response to her critical treatment of manipulation arguments against compatibilism. Lastly, I point out that Sartorio's reasons-sensitivity condition on moral responsibility is amenable to a conception of moral responsibility that, unlike the one she endorses, dispenses with basic desert.

Cover Image

The cover image, by Uwe Wollina et al., is based on the Review Article Deep facial mycosis due to Trichophyton verrucosum—molecular genetic identification of the dermatophyte in paraffin-embedded tissue—case report and review of the literature, DOI: 10.1111/myc.12719.

Management of naevus sebaceous: a national survey of UK dermatologists and plastic surgeons

Summary

Naevus sebaceous (NS) is a congenital cutaneous hamartoma, which typically occurs on the head and neck. Historically, the treatment of choice was excision in infancy because of the potential for malignant transformation; however, recent studies suggest that this risk is < 1% and unlikely in childhood. We sent a questionnaire to UK dermatologists and plastic surgeons to investigate current management practice of NS. We found that almost a third of dermatologists still recommend excision for malignancy prevention, while over 90% of plastic surgeons consider excision, with 64% citing malignancy prevention as the reason. Plastic surgeons most commonly recommended excision in childhood, whereas dermatologists waited until adulthood. We have shown there is significant variation in practice across the UK in the management of naevus NS. It is important that patients across the UK receive the same standard of care, and therefore we advocate the development of evidence-based guidance for treatment of naevus NS.

Use of Tisseel fibrin glue for a recurrent cheek haematoma after Mohs micrographic surgery

Effects of fermentation on the hemolytic activity and degradation of Camellia oleifera saponins by Lactobacillus crustorum and Bacillus subtilis

Abstract

The saponins, as components of tea seed meal (TSM), are undesirable hemolytic components, and should be degraded for reducing their hemolytic activity in order to be used in animal feed. In this study, β-glucuronidase was verified to be a potent hydrolase of tea seed saponins to reduce their hemolytic activity, and a β-glucuronidase-producing Lactobacillus crustorum (L. crustorum) strain was screened from raw bovine milk. Next, solid-state fermentation with the isolated L. crustorum and a Bacillus subtilis natto strain, which can produce cellulase and hence improve the fermentation performance of tea seed meal, was processed for detoxification of tea seed meal. The 50% hemolytic dosage (HD₅₀) value of tea seed saponins was increased from 6.69 to 27.43 μg mL⁻¹. The results of LC-MS analysis showed that the percentage of saponin aglycones increased from 30.95 to 84.25% after the fermentation. According to the roles of sugar moieties in hemolytic activity, and the enzymatic hydrolysis characteristics of β-glucuronidase, the degradation of tea seed saponins from glucosides to aglycones may contribute to the reduction of hemolytic activity. Therefore, TSM may be used as feed after fermentation with the tested saponin degrading microbial strains.

Leukocytoclastic vasculitis associated with rivaroxaban

Subacute thyroiditis in a patient with psoriasis treated with a tumor necrosis factor-α inhibitor

Tumescent contravenom: murine model for prehospital treatment of Naja naja neurotoxic snake envenomation

Abstract

Background

Snake envenomation is a neglected global health problem. There is a need for a prehospital treatment of neurotoxic snakebite that prolongs survival and allows time for a victim to reach a hospital for antivenom therapy. Tumescent epinephrine consists of a large volume of dilute epinephrine (2 mg/l) injected subcutaneously. It functions as "contravenom" by causing capillary vasoconstriction and delaying venom absorption.

Methods

A murine model of neurotoxic envenomation using lidocaine as a surrogate for neurotoxic snake venom was first developed in a pilot study. A lethal dose of lidocaine was injected subcutaneously into control and treatment groups. Mice in the treatment group were then treated with a tumescent infiltration of dilute epinephrine in saline, while control mice either received no treatment or tumescent infiltration with saline alone. The experiment was repeated using lethal doses of neurotoxic Naja naja cobra venom. The main end-points were survival rate and survival time.

Results

None of the control mice survived a lethal (LD₁₀₀) dosage of subcutaneous lidocaine. Mice given an LD₁₀₀ of subcutaneous lidocaine and treated immediately with tumescent epinephrine had 80% survival. Following LD₅₀ doses of Naja naja venom, 50% of control mice survived, while 94% survived when treated immediately with tumescent epinephrine (P < 0.01). All animals died following LD₁₀₀ doses of Naja naja venom, but survival was significantly prolonged (P < 0.0001) by immediate tumescent epinephrine.

Conclusions

Tumescent epinephrine, when given immediately after toxin injection, improves survival rates in mice following neurotoxic doses of lidocaine or Naja naja cobra venom.

Appreciation Through Use: How Industrial Technology Articulates an Ecology of Values Around Norwegian Seaweed

Abstract

This paper offers a moral history of the industrialisation of seaweed harvesting in Norway. Industrialisation is often seen as degrading natural resources. Ironically, we argue, it is precisely the scale and scope of industrial utilisation that may enable non-instrumental valuations of natural resources. We use the history of the Norwegian seaweed industry to make this point. Seaweed became increasingly interesting to harvest as a fruit and then as a crop of the sea in the early twentieth century following biochemical applications for alginates derived from seaweed. When harvesting was mechanised, however, attention turned to the environmental and aesthetic value of kelp forests. Further, the sale of the industry to the American FMC corporation flagged the national value of these plants. In sum epistemic, aesthetic and moral appreciations of natural resources are tangled up and co-evolve with their industrial utilisation, in an ecology of values. Our account uses interview and ethnographic material from key sites in Norway.

Photochemical inhibition of Trichophyton rubrum by different compoundings of curcumin

Summary

Background

Recently we had shown that conidia-derived growth of many dermatophytes can be inhibited by curcumin plus exposure to visible light.

Objectives

This method of photo inactivation should be developed further aiming for an option to stop mycelial growth in superficial tinea.

Methods

Wells of microtiter plates were inoculated with either mycelial or conidial elements collected from 5 strains of T. rubrum. Then either micellar curcumin or curcumin dissolved with DMSO was added and after 20 min the wells were filled up with Sabouraud broth.

Thereafter the assays were irradiated once with visible light (wave length 420 nm, 20 J/cm²) and fungal growth was monitored photometrically.

Results

Identical effects were measured with conidia and mycelial elements of all 5 T. rubrum strains. Curcumin dissolved with DMSO plus irradiation had a marked dose-dependent inhibitory effect on fungal growth that was almost complete with 5.0 mg/l (p<0.01) over a period of 9 days. In contrast, the same procedure with micellar curcumin had no inhibitory effect on growth obtained from conidia or mycelial elements.

Conclusions

Mycelial elements of T.rubrum and its conidia are equally sensitive to photochemical inactivation with curcumin and the galenic compounding of curcumin is essential to achieve this photochemical effect.

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Evaluation of the new AspID polymerase chain reaction assay for detection of Aspergillus species: a pilot study

Abstract

The newly developed AspID PCR assay for detection of Aspergillus spp. was evaluated with an interlaboratory quality control program panel and human bronchoalveolar lavage fluid (BALF) samples. With the quality control program, eight out of nine panel members were correctly identified. With the clinical study, 36 BALF samples that had been obtained from 18 patients with invasive pulmonary aspergillosis (IPA) and 18 without IPA were investigated. Sensitivity, specificity, positive and negative likelihood ratio for the AspID assay were 94.1% (95%CI 73.3 – 99.9), 76.5% (95% CI 50.1 – 93.2), 4 (95% CI 1.7 – 9.5), and 0.1 (95% CI 0.01 – 0.5) respectively.

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Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines†

Anaemia and iron deficiency (ID) are frequent complications in patients with solid tumours or haematological malignancies, particularly in patients treated with chemotherapeutic agents [1–3]. Frequently, anaemia is associated with fatigue, impaired physical function and reduced quality of life (QoL) [4–7]. Consequences of anaemia may include impaired response to cancer treatment and reduced overall survival (OS), even though a causal direct relationship has not yet been established [8, 9].

Using a multi-method approach based on soil radon deficit, resistivity, and induced polarization measurements to monitor non-aqueous phase liquid contamination in two study areas in Italy and India

Abstract

Geochemical and geophysical surveys employing radon deficit, resistivity, and induced polarization (IP) measurements were undertaken on soil contaminated with non-aqueous phase liquids (NAPLs) in two different sites in India and in Italy. Radon deficit, validated through the comparison with average soil radon in reference unpolluted areas, shows the extension of contamination in the upper part of the unsaturated aquifers. In site 1 (Italy), the spill is not recent. A residual film of kerosene covers soil grains, inhibiting their chargeability and reducing electrical resistivity difference with background unpolluted areas. No correlation between the two parameters is observed. Soil volatile organic compounds (VOCs) concentration is not linked with radon deficit, supporting the old age of the spillage. NAPL pollution in sites 2a and 2b (India) is more recent and probably still active, as demonstrated by higher values of electrical resistivity. A good correlation with IP values suggests that NAPL is still distributed as droplets or as a continuous phase in the pores, strengthening the scenario of a fresh spill or leakage. Residual fraction of gasoline in the pore space of sites 2a and 2b is respectively 1.5 and 11.8 kg per cubic meter of terrain. This estimation is referred to the shallower portion of the unsaturated aquifer. Electrical resistivity is still very high indicating that the gasoline has not been strongly degraded yet. Temperature and soil water content influence differently radon deficit in the three areas, reducing soil radon concentration and partly masking the deficit in sites 2a and 2b.

Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for decolorization of azo dye

Abstract

Activated carbon fiber (ACF) has become an emerging activator for peroxydisulfate (PDS) to generate sulfate radical (SO₄^•−). However, the relative low activation efficiency and poor contaminant mineralization limited its widespread application. Herein, ultrasound (US) was introduced to the ACF activated PDS system, and the synergistic effect of US and ACF in PDS activation and the enhancement of contaminant mineralization were investigated. The synergistic effect of US and ACF was observed in the PDS activation to decolorize orange G (OG). The decolorization efficiency increased with increasing ACF loading and US power, and PDS/OG ratio from 1 to 40. The activation energy was determined to be 24.065 kJ/mol. The radical-induced decolorization of OG took place on the surface of ACF, and both SO₄^•− and hydroxyl radical (^•OH) contributed to OG decolorization. The azo bond and naphthalene ring on OG were destructed to other aromatic intermediates and finally mineralized to CO₂ and H₂O. The introduction of US in the ACF/PDS system significantly enhanced the mineralization of OG. The combination of US and PDS was highly efficient to activate PDS to decolorize azo dyes. Moreover, the introduction of US remarkably improved the contaminant mineralization.

Comparisons of cadmium bioaccumulation potentials and resistance physiology of Microsorum pteropus and Echinodorus grisebachii

Abstract

To better monitor and remediate environments contaminated by cadmium (Cd), plants are used as hyperaccumulators or biomonitors; however, few have been identified for aquatic Cd pollution. In our study, two aquatic ornamental plants, Microsorum pteropus (Blume) Copel. and Echinodorus grisebachii Small, were studied for their Cd accumulation capacity, morphological characteristics, and leaf physiological indexes. Microsorum pteropus (Blume) Copel. leaf has the potential to hyperaccumulate Cd (166 mg/kg dry weight for 1 mg/L exposure), with no significant physiological difference under exposure. Echinodorus grisebachii Small had sensitive diagnostic responses to Cd toxicity, such as significant decreases in Chl (a + b) and Chl-a/b, increased peroxidase (POD) activity, greater malondialdehyde (MDA) content, and increased soluble sugar content. These results suggest that Microsorum pteropus (Blume) Copel. could have the potential to be a Cd hyperaccumulator, while Echinodorus grisebachii Small could serve as a biomonitor for Cd-contaminated water bodies.

Comparative study of calcium alginate, ball-milled biochar, and their composites on aqueous methylene blue adsorption

Abstract

In this work, a novel composite, ball-milled biochar (BMB) encapsulated in calcium-alginate (CA) beads (CA-BMB), was synthesized as an alternative adsorbent for the removal of methylene blue (MB) from an aqueous solution. Sorption performance was compared among CA, BMB, and CA-BMB composite with batch adsorption experiments. With 25% BMB and 75% alginate, the new composite resembled CA in MB adsorption. With an initial MB concentration of 50 mg L⁻¹, kinetics studies showed that 74% MB removal by CA-BMB was achieved within 8 h, followed by slow kinetics reaching 91% removal in 16 h. The adsorption kinetics was well explained by the Ritchie's kinetic model, indicative of energetically heterogeneous solid surface of the composite. Adsorption isotherms of BMB, CA, and CA-BMB can all be fitted with the Langmuir models; the adsorption capacity of CA-BMB (1210.7 mg g⁻¹) was close to that of CA (1282.2 mg g⁻¹) and much higher than that of BMB alone (184.1 mg g⁻¹). The outstanding adsorption performance suggested that CA-BMB can serve as a low-cost and eco-friendly adsorbent for MB removal from an aqueous solution.

Topical pimecrolimus for paediatric cutaneous mastocytosis

Summary

Background

Most cases of paediatric cutaneous mastocytosis (CM) occur before the age of 2 years, and regression occurs in only 67% of children. Given the absence of any specific therapy, CM is usually treated symptomatically. A few publications have reported the beneficial effect of calcineurin inhibitors for CM.

Aim

We sought to evaluate the clinical effectiveness and safety profile of topical pimecrolimus cream for the treatment of CM.

Methods

We performed a retrospective study of all diagnosed cases of CM treated with topical pimecrolimus 1% cream between 2013 and 2015. All patients were evaluated in a paediatric dermatology unit of a tertiary medical centre. Epidemiological, clinical and treatment data, including effectiveness and safety, were reviewed.

Results

In total, 18 children (11 male, 7 female; age range 3–42 months) with CM were evaluated. Of the 146 treated lesions, 39 (26.7%) disappeared and 98 (67%) faded or developed postinflammatory hyperpigmentation. Of the 119 papular lesions, 24 (16.4%) showed partial flattening and 56 (47%) became macular. Darier sign became negative in 14 (82%) of 17 patients. No topical or systemic complications were observed.

Conclusions

Topical therapy with pimecrolimus 1% cream should be considered in the treatment of CM.

Emollient product design: objective measurements of formulation structure, texture and performance, and subjective assessments of user acceptability

Abstract

Background

The choice of prescribed emollients is usually based on cost and patient preference. Differences in formulations can affect user acceptability.

Aim

To compare the physical performance, user acceptability and various product design features of two emollient gels that are prescribed in the UK and alleged to be therapeutically interchangeable because their formulations are described as having the same contents of oily ingredients.

Results

We found that here are in fact significant measurable differences between the structure and performance of the two formulations, which materially affect their user acceptability. These differences are attributed to the use of different types of gelling agents and other ingredients of differing grades/quality and concentrations, and probably due to the formulations being made by different manufacturing processes. We also identified other product design features that are important to user appeal, including the type of container in which the formulations are presented, the type of dispensing devices provided, and the nature and form of the supplied user instructions.

Conclusion

Patients and prescribers should be aware that there can be important differences in performance and user appeal between emollients, even between products that, superficially, may appear to be very similar. These important performance aspects should be characterized for new emollient introductions to encourage better informed product selection.