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Δευτέρα 20 Νοεμβρίου 2017

New insights into pemphigoid diseases

Abstract

Pemphigus and pemphigoid diseases are organ-specific autoimmune blistering diseases (AIBD), characterized and caused by autoantibodies to structural components of the skin (1). The autoantigens targeted in pemphigus are desmoglein 1 and 3, two proteins of the desmosomal structure, while the autoantigens in pemphigoid diseases (PD) are components of the basal membrane. For example, bullous pemphigoid (BP), the most frequent PD is characterized by autoantibodies against type XVII collagen (COL17, BP180) and BP230, and epidermolysis bullosa acquisita (EBA) is caused by autoantibodies against type VII collagen (COL7).

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Laryngeal candidiasis: our experience from sixty biopsy specimens

Persistent throat symptoms, such as dysphonia, globus and throat pain, are highly prevalent and are a significant cause of morbidity1. In a number of cases a clear cause of these symptoms is not identified and many patients are treated empirically with lifestyle advice and/or anti-reflux medication2.

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Melanoma in Patients with GATA2 Deficiency

Summary

GATA2 deficiency is a recently described genetic disorder affecting hematopoietic stem cells and is associated with immunodeficiency, cutaneous findings, and hematologic malignancy. The risk of non-hematologic malignancies is unclear. To explore the incidence and clinical course of melanoma in GATA2 deficient patients we conducted a retrospective chart review of 71 patients with GATA2 deficiency. We identified two patients with melanoma, including an invasive melanoma presenting as a graft-versus-tumor effect following bone marrow transplantation. Our observations and published studies of melanoma biology suggest an association between decreased GATA2 expression and melanoma progression. These findings suggest that GATA2 deficient patients may have an increased risk of melanoma and should be observed closely for new or changing skin lesions.

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Association of PD-L1 expression with treatment outcomes in patients with BRAF mutation–positive melanoma treated with vemurafenib or cobimetinib combined with vemurafenib

Summary

The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD-L1 expression with progression-free survival (PFS) and overall survival (OS) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD-L1+ melanoma, with hazard ratios (HRs) (PD-L1+ versus PD-L1) of 0.70 (95% CI, 0.46–1.07) and 0.69 (95% CI, 0.42–1.13) for PFS and OS, respectively. However, in patients treated with cobimetinib plus vemurafenib, a similar trend was not observed with HRs (PD-L1+ versus PD-L1) of 1.04 (95% CI, 0.66–1.68) and 0.94 (95% CI, 0.57–1.57) for PFS and OS, respectively. The combination cobimetinib plus vemurafenib appears to overcome the poor prognosis associated with low PD-L1 expression.

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Identifying and assessing human activity impacts on groundwater quality through hydrogeochemical anomalies and NO 3 − , NH 4 + , and COD contamination: a case study of the Liujiang River Basin, Hebei Province, P.R. China

Abstract

In the face of rapid economic development and increasing human activity, the deterioration of groundwater quality has seriously affected the safety of the groundwater supply in eastern China. Identifying and assessing the impact of human activities is key to finding solutions to this problem. This study is an effort to scientifically and systematically identify and assess the influence of human activities on groundwater based on irregularities in hydrochemical properties and water contamination, which are considered to directly result from anthropogenic activity. The combination of the hydrochemical anomaly identification (HAI) and the contaminant identification (CI) was proposed to identify the influence of human activities on groundwater quality. And the degree of abnormality was quantified by the background threshold value. The principal component analysis (PCA) and land use map were used to verify the reliability of the identification result. The final result show that the strong influence areas mainly distributed in the south of the basin and the affected indicators contained the major elements and NO3, NH4+, COD. Impacts from anthropogenic activities can be divided into two types: mine drainage that disrupts natural water–rock interaction processes, agricultural cultivation, and sewage emissions that contribute to nitrate pollution.



Isolation of lead-resistant Arthrobactor strain GQ-9 and its biosorption mechanism

Abstract

In this study, lead-resistant bacterium Arthrobacter sp. GQ-9 with a resistant capability to cadmium, zinc, and copper was isolated from a heavy metal polluted soil. Microcalorimetry analysis was applied to assess the strain's microbial activity under Pb(II) stress and suggested that GQ-9's microbial activities under Pb(II) stress were stronger than a non-resistant strain. Biosorption batch experiments revealed that the optimal condition for adsorption of Pb(II) by GQ-9 was pH 5.5, a biomass dosage of 1.2 g L−1, and an initial Pb(II) concentration of 100 mg L−1 with a maximum biosorption capacity of 17.56 mg g−1.Adsorption-desorption experiments and Fourier transform infrared spectroscopy (FTIR) analysis were applied to elucidate the biosorption mechanisms. Adsorption-desorption analysis showed that GQ-9 cells could sequester 56.60% of the adsorbed Pb(II) ions on the cell wall. FTIR analysis suggested that hydroxyl, carboxyl, amino, nitrile, and sulfhydryl groups and amide I, amide II bands on the GQ-9 cell wall participated in the complexation of Pb(II) ions. The present study illustrates that the lead-resistant bacteria GQ-9 has the potential for further development of an effective and ecofriendly adsorbent for heavy metal bioremediation.



Correction

Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: Tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72(5):840-50.

The mechanism of skin lipids influencing skin status

Skin lipids, compose of sebocyte-, keratinocyte-, and microbe- derived lipids, dramatically influence skin status by different mechanisms. (I) Physical chemistry function: They are "mortar" to establish the physico-chemical barrier function of skin; (II) Biochemistry function: They function as signals in the complex signaling network originating at the epidermal level; (III) Microecology function: Sebocyte- and keratinocyte-derived lipids vary the composition of microbial skin flora, and microorganisms metabolize them to produce lipids as signal starting signaling transduction.

Exploring the potential relationship between indoor air quality and the concentration of airborne culturable fungi: a combined experimental and neural network modeling study

Abstract

Indoor airborne culturable fungi exposure has been closely linked to occupants' health. However, conventional measurement of indoor airborne fungal concentration is complicated and usually requires around one week for fungi incubation in laboratory. To provide an ultra-fast solution, here, for the first time, a knowledge-based machine learning model is developed with the inputs of indoor air quality data for estimating the concentration of indoor airborne culturable fungi. To construct a database for statistical analysis and model training, 249 data groups of air quality indicators (concentration of indoor airborne culturable fungi, indoor/outdoor PM2.5 and PM10 concentrations, indoor temperature, indoor relative humidity, and indoor CO2 concentration) were measured from 85 residential buildings of Baoding (China) during the period of 2016.11.15–2017.03.15. Our results show that artificial neural network (ANN) with one hidden layer has good prediction performances, compared to a support vector machine (SVM). With the tolerance of ± 30%, the prediction accuracy of the ANN model with ten hidden nodes can at highest reach 83.33% in the testing set. Most importantly, we here provide a quick method for estimating the concentration of indoor airborne fungi that can be applied to real-time evaluation.



Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs in human serum from Shanghai, China: a study on their presence and correlations

Abstract

Polybrominated diphenyl ethers (PBDEs) are becoming a public health concern because of their potential toxicity, from endocrine disruption system to neurodevelopmental impairments. Nonetheless, information on their levels in human blood is scarce. In this study, human serum samples collected in Shanghai, China, were analyzed for the concentrations of PBDEs and their hydroxylated metabolites (OH-PBDEs). Eight PBDE congeners and six OH-PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC-MS) and high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). As a result, total PBDE concentration ranged from 0.280 to 12.330 ng g−1 on a lipid weight basis lw (median: 1.100 ng g−1 lw) and the total OH-PBDE level ranged from 0.045 to 0.363 ng g−1 (lw) (median: 0.187 ng g−1 lw). Among them, BDE-47 and 6-OH-BDE-47 were the predominant PBDEs and OH-PBDEs, respectively. In addition, based on the results of the Bartelett X 2 test, BDE-47 significantly (p < 0.05) correlated with BDE-28, BDE-100, BDE-85, and BDE-154, whereas 3′-OH-BDE-7 significantly (p < 0.01) correlated with 3-OH-BDE-47, 2-OH-BDE-68, and 6′-OH-BDE-99. Among all donors, no significant association between age and PBDEs (or OH-PBDEs) was found. Further research on the exposure routes in the environment and metabolic processing of PBDEs in human blood is necessary.



Comparison of bioaccumulation and elimination of Escherichia coli and male-specific bacteriophages by ascidians and bivalves

Abstract

Levels of Escherichia coli and male-specific bacteriophages (MSBs) were determined in the filter feeders obtained from retail markets, commercial farms, and wild beds in Korea. The accumulation and elimination of E. coli and MSBs were compared between ascidians and bivalves (oysters and mussels) during relaying and depuration. E. coli concentrations in ascidians from retail markets ranged between < 20 and 460 most probable number/100 g while MSBs were not detected. E. coli levels in bivalves from commercial farms and wild beds were not significantly different but bacterial levels in ascidians were consistently lower. Ascidians exhibited much lower ability than bivalves to accumulate E. coli and MSBs during relaying in a polluted coastal area. This study also shows that an equilibrium was developed between levels of microbes in water and ascidians and shellfish during relaying. E. coli and MSBs in ascidians decreased quickly during depuration in a clean seawater tank. However, after 1 day, E. coli in bivalves decreased by only 1.1–1.6 logs, and the elimination of MSBs was negligible. Therefore, depuration is an effective means to reduce the health risk of contaminated ascidians.



Modeling clinical efficacy of the S1P receptor modulator ponesimod in psoriasis

Psoriasis is a chronic inflammatory disorder with substantial impact on quality of life [1,2]. The most common form is plaque psoriasis. The disease is mediated by T cells [3] and manifests itself as inflammation of the skin with plaque formation and rapid growth of skin cells [4,5].

Sweat Mechanisms and Dysfunctions in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory dermatosis that involves a complex interplay between genetic, immunologic and environmental factors [1]. Barrier abnormalities play an important role in the pathogenesis of AD, as mutations in the gene for the structural protein filaggrin (FLG) result in increased epidermal permeability, decreased SC hydration and increased pH [2,3]. SC pH provides an acidic environment for optimal antimicrobial enzyme activity and surface microbiome diversity [4].

A novel anti-melanogenic agent, KDZ-001, inhibits tyrosinase enzymatic activity

Skin primarily consists of three different cell types: keratinocytes, fibroblasts, and melanocytes. Melanocytes are specialized cells that synthesize pigment, which is also known as melanin. Melanin is a heterogeneous biopolymer that is produced in melanosomes, which are organelles that synthesize, store, and transport melanin through a series of enzymatic reactions known as melanogenesis. Melanogenesis involves the catalysis of tyrosine by TYR-family proteins, including TYR and TYR-related protein 1/2 (TRP-1/2) [1,2].

Determination of selected elements in canned food sold in Jordan markets

Abstract

In this study, the concentrations of seven heavy metals including As, Cd, Cr, Cu, Ni, Pb, and Zn in imported canned food samples of different brands including tuna, beef, sardines, and mushroom were determined. Samples were collected from popular Jordanian market, Irbid city, Northern Jordan (44 samples of each type). The metal concentrations in canned food samples were found to be in the range of 1.85–4.50 μg/g for As, 0.42–0.58 μg/g for Cd, 0.47–1.67 μg/g for Cr, 0.73–0.90 μg/g for Cu, 1.08–2.77 μg/g for Ni, 2.5–3.0 μg/g for Pb, and 0.43–2.25 μg/g for Zn. Results revealed that As and Pb have the highest concentrations in all samples analyzed, whereas, the lowest concentrations obtained were in Cd. For example, in canned sardine, the mean concentrations of heavy metals are 0.43 μg/g for Zn, 2.50 μg/g for Pb, 1.74 μg/g for Ni, 0.80 μg/g for Cu, 0.47 μg/g for Cr, 0.42 μg/g for Cd, and 1.85 μg/g for As. Whereas, the mean concentrations in canned tuna were 3.48 μg/g for As, 0.47 μg/g for Cd, 0.53 μg/g for Cr, 0.73 μg/g for Cu, 2.77 μg/g for Ni, 2.80 μg/g for Pb, and 1.63 μg/g for Zn. The results of this study indicated that the concentration of the tested elements including As, Cd, Cr, Ni, and Pb in canned food samples sold in Jordanian markets exceeded the permissible limits set by health organizations such as FAO/WHO. The results were compared with the literature values.



Social networks as a tool for science communication and public engagement: focus on Twitter

Abstract
Social networks have been used to teach and engage people about the importance of science. The integration of social networks in the daily routines of Faculty and Scientists is strongly recommended to increase their personal brand, improve their skills, enhance their visibility, share and communicate science to society, promote scientific culture, and even as a tool for teaching and learning. Here we review the use of Twitter in Science and comment our previous experience on using this social network as a platform for a Massive Online Open Course (MOOC) in Spain and Latin America. We propose to extend this strategy to a pan-European Microbiology MOOC in the near future.

Multiple Imputation for Incomplete Data in Epidemiologic Studies

Abstract
Epidemiologic studies are frequently susceptible to missing information. Omitting observations with missing variables remains a common strategy in epidemiologic studies, yet this simple approach can often severely bias parameter estimates of interest if the values are not missing completely at random. Even when missingness is completely random, complete case analysis can reduce efficiency of estimated parameters, because large amounts of available data are simply tossed out with the incomplete observations. Alternative methods to mitigate missing information, such as multiple imputation, are becoming an increasing popular strategy to retain all available information, reduce potential bias, and improve efficiency in parameter estimation. In this paper, we describe the theoretical underpinnings of multiple imputation, and we illustrate application of this method in a collaborative challenge to assess the performance of various techniques to dealing with missing data. We detail the steps necessary to perform multiple imputation on a subset of the Collaborative Perinatal Project, where the goal is to estimate the odds of spontaneous abortion associated with smoking during pregnancy.

Inverse Probability Weighted Estimation for Monotone and Nonmonotone Missing Data

Abstract
Missing data is of common occurrence in epidemiologic research. In this paper, three data sets with induced missing values from the Collaborative Perinatal Project, a multisite United States study conducted from 1959 to 1974, are provided as examples of prototypical epidemiologic studies with missing data. Our goal is to estimate the effect of maternal smoking behavior on spontaneous abortion while adjusting for numerous confounders. At the same time, we do not necessarily wish to evaluate the joint distribution among potentially unobserved covariates, which is seldom the subject of substantive scientific interest. The inverse probability weighting approach preserves the semiparametric structure of the underlying model of substantive interest, and clearly separates the model of substantive interest from the model used to account for the missing data. However, inverse probability weighting often will not result in valid inference if the missing data pattern is nonmonotone, even if the data are missing at random. We describe a recently proposed approach to model nonmonotone missing data mechanisms under missing at random for use to construct the weights in inverse probability weighted complete-case estimation, and we illustrate the approach in the three data sets described in the companion manuscript (Am J Epidemiol. 2017;000(0):000-000) of this issue of the journal.

Principled Approaches to Missing Data in Epidemiologic Studies

Abstract
Principled methods to appropriately analyze missing data have long existed; however, broad implementation of these methods remains challenging. In this and companion papers, we discuss issues of missing data in the epidemiologic literature. We provide details regarding missing data mechanisms and nomenclature and motivate principled analyses through a detailed comparison of multiple imputation and inverse probability weighting. We do so in the setting of a masked data-analytic challenge with missing data induced by known mechanisms to data from the Collaborative Perinatal Project, a multisite US study conducted from 1959 to 1974. We illustrate the deleterious effects of missing data with naïve methods and show how principled methods can sometimes mitigate such effects. For example when data were missing at random, naïve methods showed a spurious protective effect of smoking on spontaneous abortion, odds ratio (OR) of 0.43 (95% confidence interval, CI: 0.19, 0.93) while implementing principled methods multiple imputation (OR = 1.30, CI: 0.95, 1.77) or augmented inverse probability weighting (OR = 1.40, CI: 1.00, 1.97) provided estimates closer to the "true" full data effect (OR = 1.31, CI: 1.05, 1.64). We call for greater acknowledgement of and attention to missing data and for the broad use of principled missing data methods in epidemiologic research.

Editorial



Male Breast Cancer: Pink Ribbon Blues



Will liquid biopsies become our fluid transition to personalized immunotherapy?

ImmunotherapyPD-L1 expressionLiquid biopsyCirculating tumour cellsNon-small cell lung cancer

Secondary erythromelalgia: a tryptophan dietary supplement-induced case associated with elevated 5-hydroxyindoleacetic acid (5HIAA) urinary levels



An extension of a multicenter, randomized, split-face clinical trial evaluating the efficacy and safety of chromophore gel-assisted blue light phototherapy for the treatment of acne

Abstract

A variety of laser/light-based devices have been reported to be effective for the treatment of acne, yet no long-term data on efficacy and safety have been published. A first 12-week clinical trial ("Main trial") recently demonstrated that the KLOX BioPhotonic System, an LED blue light device using photo-converter chromophores, can significantly improve moderate and severe facial acne vulgaris with an excellent safety profile. This Extension trial followed the Main trial, using the same BioPhotonic System, with the same dose and instructions for use, on patients having already completed treatment in the Main trial. Main objectives of this open-label long-term extension 12-week study were to evaluate the efficacy of the KLOX BioPhotonic System on the untreated hemiface during the Main trial, as well as the duration of response on the hemiface treated during the first 12-week Main trial. Despite their young age (mean age: 21.6 years) and their 12-week participation in the Main trial, 49 (54.4%) of the total number of patients who participated in the Main trial enrolled in this additional 12-week Extension trial. Baseline grading of acne was performed with the Investigator's Global Assessment (IGA) scale. For each patient, the hemiface randomly selected as a control during the Main trial received 6 weeks of treatment (twice weekly) and was then followed up for an additional 6 weeks. The first hemiface treated in the Main trial was consequently observed throughout the Extension trial, allowing for a further 12-week assessment of outcomes (total 24 weeks). In light of an additional 12 weeks of treatment on the contralateral face, the patient compliance rate was excellent, with 91.9% of the total number of patients receiving at least 80% of the treatments. Patients with a baseline IGA grade of 2 (mild) on the treated hemiface demonstrated a success rate of 58.3 and 66.7% at weeks 6 and 12, respectively. At these same time points, subjects with a baseline IGA grade of 3 (moderate) demonstrated a success rate of 81.8 and 90.0%. Patients with a baseline IGA grade of 4 (severe) demonstrated a success rate of 100% at both week 6 and week 12. When evaluating the originally treated hemifaces from the Main trial, the rate of return to baseline at 24 weeks was calculated to be 15.5%. This latter outcome confirmed the long duration of effect following treatment. The patient safety profile was also excellent, with very few related adverse events. The BioPhotonic System, which is comprised of LED blue light phototherapy and photo-converter chromophores, provides long-term efficacy and safety in the treatment of acne vulgaris, with a rate of compliance above what is generally observed in a young population of patients suffering from acne vulgaris, especially in light of sequential enrollment in a study treating one hemiface.



Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade

Abstract

Background

Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy.

Case reports

We report two patients with melanocytic nevi that regressed with pembrolizumab therapy. The first patient had stage IV BRAF K601E/L584F mutant melanoma that developed a regressed melanocytic nevus while being treated with pembrolizumab. The second patient had stage III BRAF V600R mutant melanoma that was treated with pembrolizumab and dabrafenib, and also developed a regressed melanocytic nevus. Both patients had good response to therapy and stable disease at 8 and 12 months of treatment, respectively.

Results

Regressed melanocytic nevi were observed in both patients treated with pembrolizumab for advance-stage melanoma. Immunohistochemical analysis of a regressed melanocytic nevus was associated with an inflammatory infiltrate rich in CD8+ T cells and CD163+, CD11c+ histiocytes.

Conclusion

Regressed melanocytic nevi are an emerging dermatologic effect from pembrolizumab therapy.



Syringe lubricant and adverse reactions



Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America

Abstract

Background

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF).

Methods

Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre-EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens.

Results

Overall, 57/57 patients affected by El Bagre-EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non-Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01).

Conclusions

Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients.



Anti-desmogleins autoantibodies detected by ELISA and blotting in bullous pemphigoid: what do they mean?



The “Duvic regimen” for erythrodermic flares secondary to Staphylococcus aureus in mycosis fungoides and Sézary syndrome



Polymorphous presentation of subcutaneous phaeohyphomycosis: a rare occurrence



Changing practices of hair relaxer use among black women in the United States



Human papillomavirus-associated cutaneous disease burden in human immunodeficiency virus (HIV)-positive patients: the role of human papillomavirus vaccination and a review of the literature

Abstract

Human papillomavirus (HPV) infection is related to the development of cutaneous squamous cell carcinoma, oropharyngeal carcinoma, and anogenital malignancies. Patients infected with human immunodeficiency virus (HIV) have impaired cell-mediated immunity, placing them at risk for more prolonged infection with a greater likelihood of disease expression. This presents important implications for screening and treatment of HPV in the HIV patient population. The use of prophylactic vaccines directed against HPV has been a promising clinical development, though the immunogenicity of these vaccines in the immunocompromised host and in patients with previously established HPV infections has not been well established. In this review, we describe the pathogenesis and epidemiology of HPV-related cutaneous malignancies in patients with HIV. We outline the current guidelines and recent advances in the field of HPV vaccination. It is our hope that increasing awareness of the HPV-related HIV comorbidities will lead to developments in preventative medicine capable of reducing the burden of these diseases. We recognize the importance of prevention as a primary defense against disease and hope that this article organizes and disseminates recent findings in the field of HPV-associated comorbidities in the HIV population.



Naturalizing the content of desire

Abstract

Desires, or directive representations, are central components of human and animal minds. Nevertheless, desires are largely neglected in current debates about the naturalization of representational content. Most naturalists seem to assume that some version of the standard teleological approach, which identifies the content of a desire with a specific kind of effect that the desire has the function of producing, will turn out to be correct. In this paper I argue, first, that this common assumption is unjustified, since the standard approach is in fact deeply problematic. Secondly, I propose an alternative account of the content of (basic) desires which, while generating plausible and determinate content ascriptions, avoids the main problem that plagues the standard approach, and is also preferable on other grounds.



Atomic force microscopy for biomechanical and structural analysis of human dermis: a complementary tool for medical diagnosis and therapy monitoring

Abstract

Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behavior of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify nanoscale changes in the biomechanical properties and ultrastructure of human papillary dermis exposed to different mechanical and physical stimuli. Samples from three human skin biopsies were studied: one stretched by obesity, one subjected to a high level of sun-exposure, and normal skin as control. Slices of the papillary dermis layer were harvested at controlled depths from each skin biopsy and 25 μm2 areas of each slice were imaged and D-periodicity of collagen fibers measured by AFM, together with their stiffness. Standard histological analysis was also carried out in order to correlate biochemical properties and their distribution with stiffness and topography. We obtained similar stiffness values between the sample affected by obesity and the control sample at any depth level into the dermis, while the sun-exposed sample presented a significant lower stiffness. Additionally, all samples presented an increase in the stiffness at higher depths into the papillary dermis layer. Collagen fibers close to the epidermis of sample affected either by obesity and sun-exposure– the former even more than the latter – are thicker and present a larger D-period than those in the control sample. Our results open the possibility to use structural and mechanical analysis based on AFM as a complementary tool for medical diagnosis and therapy monitoring.

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Interleukin-17 Alters the Biology of Many Cell Types Involved in the Genesis of Psoriasis, Systemic Inflammation, and Associated Comorbidities

Abstract

Psoriasis is a chronic, immune-mediated, systemic inflammatory disease that is defined by a characteristic skin reaction produced when elevated levels of inflammatory cytokines such as interleukin (IL)-17 alter the growth and differentiation of skin cells. The pathogenesis of comorbid conditions associated with psoriasis, including psoriatic arthritis, cardiovascular disease, obesity, metabolic syndrome, liver disorders, renal disease, and depression are also largely affected by inflammation. In this review, we examine the effect of IL-17 on the inflammatory pathways in a variety of different cell types, including keratinocytes, as well as epithelial cells of the colon, kidney, gut, and liver. Additionally, we investigate the role of IL-17 in mediating the psoriasis-associated comorbidities detailed above.

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Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin

Summary

Background

Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.

Objective

To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.

Methods

Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter.

Results

Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration.

Conclusions

Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin.



Effects of rainfall intensity and slope gradient on runoff and sediment yield characteristics of bare loess soil

Abstract

Soil erosion is a universal phenomenon on the Loess Plateau but it exhibits complex and typical mechanism which makes it difficult to understand soil loss laws on slopes. We design artificial simulated rainfall experiments including six rainfall intensities (45, 60, 75, 90, 105, 120 mm/h) and five slopes (5°, 10°, 15°, 20°, 25°) to reveal the fundamental changing trends of runoff and sediment yield on bare loess soil. Here, we show that the runoff yield within the initial 15 min increased rapidly and its trend gradually became stable. Trends of sediment yield under different rainfall intensities are various. The linear correlation between runoff and rainfall intensity is obvious for different slopes, but the correlations between sediment yield and rainfall intensity are weak. Runoff and sediment yield on the slope surface both presents an increasing trend when the rainfall intensity increases from 45 mm/h to 120 mm/h, but the increasing trend of runoff yield is higher than that of sediment yield. The sediment yield also has an overall increasing trend when the slope changes from 5° to 25°, but the trend of runoff yield is not obvious. Our results may provide data support and underlying insights needed to guide the management of soil conservation planning on the Loess Plateau.



Mineralogical and geochemical characterization of waste rocks from a gold mine in northeastern Thailand: application for environmental impact protection

Abstract

Waste rocks from gold mining in northeastern Thailand are classified as sandstone, siltstone, gossan, skarn, skarn-sulfide, massive sulfide, diorite, and limestone/marble. Among these rocks, skarn-sulfide and massive sulfide rocks have the potential to generate acid mine drainage (AMD) because they contain significant amounts of sulfide minerals, i.e., pyrrhotite, pyrite, arsenopyrite, and chalcopyrite. Moreover, both sulfide rocks present high contents of As and Cu, which are caused by the occurrence of arsenopyrite and chalcopyrite, respectively. Another main concern is gossan contents, which are composed of goethite, hydrous ferric oxide (HFO), quartz, gypsum, and oxidized pyroxene. X-ray maps using electron probe micro-analysis (EPMA) indicate distribution of some toxic elements in Fe-oxyhydroxide minerals in the gossan waste rock. Arsenic (up to 1.37 wt.%) and copper (up to 0.60 wt.%) are found in goethite, HFO, and along the oxidized rim of pyroxene. Therefore, the gossan rock appears to be a source of As, Cu, and Mn. As a result, massive sulfide, skarn-sulfide, and gossan have the potential to cause environmental impacts, particularly AMD and toxic element contamination. Consequently, the massive sulfide and skarn-sulfide waste rocks should be protected from oxygen and water to avoid an oxidizing environment, whereas the gossan waste rocks should be protected from the formation of AMD to prevent heavy metal contamination.



The Genetic Basis of Seborrheic Dermatitis: A Review

Abstract

Seborrheic Dermatitis (SD) is a common inflammatory skin disease that presents as itchy, flaking skin in the seborrheic areas. Various environmental and intrinsic factors have been identified as predisposing factors for SD, but its etiology remains poorly understood. Although it was recognized that genetic factors play a role in SD etiology, there have not been studies that systematically review the literature specifically for causal mutations or protein deficiencies in SD. In this review, we searched various databases for gene mutations and protein deficiencies that cause SD or SD-like phenotype in humans and experimental animals, and summarize 11 gene mutations or protein deficiencies that were described in the literature. Most of the encoded proteins play a role either in the immune response (ACT1, C5, IKBKG/NEMO, STK4, 2C TCR) or epidermal differentiation (ZNF750, MPZL3). Understanding the genetic basis of SD can impart knowledge of the pathobiology of the disease and help identify novel therapeutic targets.

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Long-term effect of the insoluble thread-lifting technique