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Δευτέρα 5 Μαρτίου 2018

An enlarging nodule on the shin



Skin cancer prevention messages on Facebook: Likes, shares, and comments

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Adi Nosrati, Matthew A. Pimentel, Ashley Falzone, Roshini Hegde, Shilpa Goel, Mary-Margaret Chren, Rachel Eye, Eleni Linos, Sherry Pagoto, Barbara J. Walkosz




Patient quality of life fluctuates before and after Mohs micrographic surgery: A longitudinal assessment of the patient experience

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Junqian Zhang, Christopher J. Miller, Victoria O'Malley, Jeremy R. Etzkorn, Thuzar M. Shin, Joseph F. Sobanko
BackgroundChanges in patient perceptions of quality of life (QOL) after Mohs micrographic surgery (MMS) may benefit from different counseling or treatment.ObjectiveTo measure QOL before and after MMS and to identify risk factors associated with impaired QOL.MethodsProspective observational study of 727 skin cancer patients who self-reported QOL via the Skin Cancer Index immediately before and at 1-2 weeks and 3 months after MMS.ResultsQOL fluctuated after MMS. At 1-2 weeks after surgery, overall QOL remained unchanged compared to before MMS. Patients reported reduced anxiety about skin cancer, but had increased distress about social interactions and physical appearance. At three months after surgery, patients reported an overall improvement in QOL compared to before MMS, (p = 0.0007). Age under 65 years (p = 0.0001), female gender (p = 0.0001), and tobacco use (p = 0.03) were associated with lower QOL scores at all assessment points.LimitationsSingle-site observational study. Significant loss to follow-up at both time points after MMS.ConclusionSkin cancer patients had persistent concerns about social interactions and physical appearance 1-2 weeks after MMS, but all aspects of QOL improved by three months after surgery. MMS patients who were less than 65 years old, female, or smoked were at increased risk for longitudinally impaired QOL.

Teaser

Patient QOL is initially impaired from restricted social interactions and appearance concerns after Mohs micrographic surgery (MMS), but QOL improves from baseline by three months after MMS. Patients younger than 65, women, and smokers report worse QOL before and after MMS, Characterizing the evolution of and risk factors for impaired QOL may allow targeted management to improve the experience of MMS patients.


Type I pityriasis rubra pilaris treated with tumor necrosis factor inhibitors, ustekinumab, or secukinumab: a systematic review

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Nolan J. Maloney, Lisa D. Hisaw, Scott Worswick




An Effective Game-Based Learning Intervention for Improving Melanoma Recognition

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Amit Sharma, Muneeb Ilyas, Nishita Maganty, Nan Zhang, Mark R. Pittelkow




Assessing the Safety of Superficial Chemical Peels in Darker Skin: A Retrospective Study

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Shalini Vemula, Mayra B.C. Maymone, Eric A. Secemsky, Raphael Widjajahakim, Nicole M. Patzelt, Dana Saade, Neelam A. Vashi
BackgroundChemical peels have shown efficacy in the treatment of acne, photoaging, and pigmentary dyschromias; however, studies evaluating side effects, particularly in patients with skin of color, are limited.ObjectiveWe sought to determine the frequency of side effects and complications associated with superficial chemical peels in patients with skin types III-VI.MethodsA 5-year single center retrospective analysis was performed.ResultsOf 473 chemical peel treatments included in this study, 18 (3.8%) were associated with short-term (≤2 weeks) or long-term (>2 weeks) complications. The most frequent complications were crusting (2.3%), post-inflammatory hyperpigmentation (PIH) (1.9%) and erythema (1.9%). All side effects resolved within 8 months of treatment and were located on the face. When stratified by season, side effects were noted to be less common during the winter. In the adjusted model, Fitzpatrick skin type VI was associated with a higher odds of side effects (OR, 5.14; 95% [CI], 1.21-21.8; P=0.0118).LimitationsSingle center retrospective design.ConclusionIn this study, superficial chemical peels performed in patients with skin types III-VI had a relatively low complication rate, and skin type VI had higher odds of experiencing an adverse event. Side effects were noted to be less frequent during the winter months.

Teaser

There is limited data about the side effects and complications of chemical peels in darker skin types. Side effects are infrequent and include post-inflammatory erythema, crust, and post-inflammatory hyperpigmentation with no permanent sequelae. When performed in an appropriate manner, superficial chemical peels have a relatively low complication rate in darker skin types.


Somatic and psychiatric comorbidities of hidradenitis suppurativa in children and adolescents.

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Hannu Tiri, Jari Jokelainen, Markku Timonen, Kaisa Tasanen, Laura Huilaja
BackgroundHidradenitis suppurativa (HS) is associated with various somatic and psychiatric comorbidities. Data regarding comorbidities in young HS patients are sparse.ObjectiveWe analyzed both somatic and psychiatric comorbidities in young patients in a nationwide HS cohort.MethodsIn this retrospective case-control study, data from cases of HS in young (aged ≥5 and <18 years) patients and age-matched controls with benign melanocytic nevi were collected from the Finnish Care Registry of Health Care. The prevalence of preselected comorbidities was compared between HS and control groups.ResultsA total of 153 HS cases were found in the specified age group. Of these, 34.0% had one or more somatic comorbidity compared with 4.9% of controls. At least one of the preselected psychiatric diagnoses was present before the age of 18 years in 15.7% of HS cases compared with 5.6% of controls. By the age of 23 years, at least one psychiatric comorbidity was identified in 23.5% of HS patients and 8.7% of controls.LimitationsDespite being one of the largest HS cohorts ever studied, the number of young HS patients was relatively low. Since this was a registry-based study, it was not possible to verify the accuracy of International Classification of Diseases codes.ConclusionPhysicians should monitor young patients with HS for both somatic and psychiatric comorbidities.

Teaser

- Epidemiologic data on hidradenitis suppurativa in childhood and adolescence are sparse; - This study demonstrates the psychiatric and somatic comorbidities of hidradenitis suppurativa in young patients; - Young patients with hidradenitis suppurativa need care for the comorbidities of HS, which may accumulate over time.


The Prognostic Significance of Tumor-Infiltrating Lymphocytes for Primary Melanoma Varies by Sex

Publication date: Available online 5 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Andrew J. Sinnamon, Cimarron E. Sharon, Yun Song, Madalyn G. Neuwirth, David E. Elder, Xiaowei Xu, Emily Y. Chu, Michael E. Ming, Douglas L. Fraker, Phyllis A. Gimotty, Giorgos C. Karakousis
BackgroundThe immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored.MethodsPatients with clinically localized primary melanoma ≥0.76mm in Breslow thickness who underwent sentinel lymph node (SLN) biopsy at our institution were identified. Association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated using logistic regression. Overall survival (OS) was evaluated by TILs status and sex.ResultsAmong 1,367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (p=0.71). SLN positivity was associated with TILs among men (brisk 3.8%, nonbrisk 16.9%, absent 26.6%, p<0.001). In contrast, there was no association between SLN positivity and TILs among women (p=0.49). Interaction between brisk TILs and sex on SLN positivity was significant (p=0.029). Among men, presence of brisk TILs was associated with prolonged OS (p=0.038) but not after adjustment for SLN status (p=0.42). There was no association between TILs status and OS among women.LimitationsFindings from this single-institution study have yet to be validated by other research groups.ConclusionsThe implications of TILs in predicting SLN positivity appear to be more relevant for men than women.

Teaser

Some studies suggest tumor-infiltrating lymphocytes in primary melanoma are associated with a lower likelihood of sentinel lymph node mestastases. In this institutional cohort study, TILs were found to be predictive of SLN status in men but not among women. TILs status may be more useful for clinical decision-making among men than women


Characterizing the environmental impact of metals in construction and demolition waste

Abstract

Large quantities of construction and demolition (C&D) waste are generated in China every year, but their potential environmental impacts on the surrounding areas are rarely assessed. This study focuses on metals contained in C&D waste, characterizing the metal concentrations and their related environmental risks. C&D waste samples were collected in Shenzhen City, China, from building demolition sites, renovation areas undergoing refurbishment, landfill sites, and recycling companies (all located in Shenzhen city) that produce recycled aggregate, in order to identify pollution levels of the metals As, Cd, Cr, Cu, Pb, Ni, and Zn. The results showed that (1) the metal concentrations in most demolition and renovation waste samples were below the soil environmental quality standard for agricultural purposes (SQ-Agr.) in China; (2) Cd, Cu, and Zn led to relatively higher environmental risks than other metals, especially for Zn (DM5 tile sample, 360 mg/kg; R4 tile sample, 281 mg/kg); (3) non-inert C&D waste such as wall insulation and foamed plastic had high concentrations of As and Cd, so that these materials required special attention for sound waste management; and (4) C&D waste collected from landfill sites had higher concentrations of Cd and Cu than did waste collected from demolition and refurbishment sites.



Rapid and high-capacity adsorption of PFOS and PFOA by regenerable ammoniated magnetic particle

Abstract

Adsorption is well accepted as an effective method for perfluorinated compounds' (PFCs) removal from water among various conventional methods. However, development of adsorbents that combine good performance of PFC removal and regenerability has not yet been realized. This work demonstrated the fabrication and application of an ammoniated magnetic adsorbent for efficient and economical PFOS and PFOA removal. Functional ammonium groups and γ-Fe2O3 were effectively incorporated in the particle with the proposed method. These fabricated magnetic particles presented superior adsorption performance for PFOS and PFOA with short equilibrium time of 120 min and high adsorption capacity. The isotherms revealed that the adsorption process belonged to multilayer sorption with their intricate interactions including anion exchange and hydrophobic interaction. The magnetic particle maintained its removal efficacy over a wide pH range of 3–9 or with coexisting substances. Moreover, the regeneration and reuse of the magnetic particle were successfully carried out with PFOS and PFOA removal efficiency sustained higher than 80% in 15 consecutive treatment cycles. Along with the efficient adsorption and easy separation of adsorbents, we expect that this ammoniated magnetic particle can serve as an excellent alternative for PFOS and PFOA removal from water.



Enhanced sterilization and healing of cutaneous pseudomonas infection using 5-aminolevulinic acid as a photosensitizer with 410-nm LED light

After the discovery of penicillin by Fleming in 1929, various antibiotics have been discovered and developed, making it one of the most important medical interventions to reduce morbidity and mortality [1,2]. However, multi-resistant bacteria have emerged due to the misuse of antibiotics [3], and we are challenged by this new threat. Thus, new means for treating infections that do not rely on antibiotics are needed.

Skin cancer prevention messages on Facebook: Likes, shares, and comments



Assessing the Safety of Superficial Chemical Peels in Darker Skin: A Retrospective Study

There is limited data about the side effects and complications of chemical peels in darker skin types. Side effects are infrequent and include post-inflammatory erythema, crust, and post-inflammatory hyperpigmentation with no permanent sequelae. When performed in an appropriate manner, superficial chemical peels have a relatively low complication rate in darker skin types.

Somatic and psychiatric comorbidities of hidradenitis suppurativa in children and adolescents.

- Epidemiologic data on hidradenitis suppurativa in childhood and adolescence are sparse; - This study demonstrates the psychiatric and somatic comorbidities of hidradenitis suppurativa in young patients; - Young patients with hidradenitis suppurativa need care for the comorbidities of HS, which may accumulate over time.

Patient quality of life fluctuates before and after Mohs micrographic surgery: A longitudinal assessment of the patient experience

Patient QOL is initially impaired from restricted social interactions and appearance concerns after Mohs micrographic surgery (MMS), but QOL improves from baseline by three months after MMS. Patients younger than 65, women, and smokers report worse QOL before and after MMS, Characterizing the evolution of and risk factors for impaired QOL may allow targeted management to improve the experience of MMS patients.

The Prognostic Significance of Tumor-Infiltrating Lymphocytes for Primary Melanoma Varies by Sex

Some studies suggest tumor-infiltrating lymphocytes in primary melanoma are associated with a lower likelihood of sentinel lymph node mestastases. In this institutional cohort study, TILs were found to be predictive of SLN status in men but not among women. TILs status may be more useful for clinical decision-making among men than women

An Effective Game-Based Learning Intervention for Improving Melanoma Recognition



Type I pityriasis rubra pilaris treated with tumor necrosis factor inhibitors, ustekinumab, or secukinumab: a systematic review



Have reducing tonsillectomy rates in England led to increasing incidence of invasive Group A Streptococcus infections in children?

Abstract

Objectives

To determine if there is a correlation between falling tonsillectomy numbers and increasing numbers of tonsillitis admissions and invasive Group A β-haemolytic streptococcus (iGAS) infection in children aged 14 and under in England.

Design

An observational cross-sectional study was performed.

Setting

The data extracted covered the period from 1991 until 2014.

Participants

Hospital admissions for tonsillectomies, tonsillitis/pharyngitis, and and all diagnoses of iGAS in children aged 14 and under who had a tonsillectomy.

Main outcome measures

Correlation between trends in tonsillectomies, tonsillitis/pharyngitis and iGAS.

Results

Across all age groups there was a dramatic reduction in the total number of tonsillectomies performed in England from 28,309 in 1990/1991, down to 6327 in 2013/2014 (77.7% reduction). The numbers of hospital admissions for management of acute tonsillitis and pharyngitis has risen dramatically. iGAS numbers have increased steadily over this time period and more than doubled in children aged 14 and under. There are significant negative correlations between the trend in iGAS infections and numbers of tonsillectomies in all ages. There are also strong positive correlations between the trend in numbers of tonsillitis episodes and the number of iGAS infections in all under14 year groups; the strongest correlation was seen in the 1-4 years age group (+0.92 Pearson correlation coefficient).

Conclusions

There appears to be a correlation between falling tonsillectomy numbers, increasing hospital admissions with tonsillitis and rising iGAS infection in England. Further studies are required to assess the aetiological role of tonsillitis in predisposing to iGAS infection and the potential societal benefit of tonsillectomies.

This article is protected by copyright. All rights reserved.



Assessment of n -pentanol/ Calophyllum inophyllum /diesel blends on the performance, emission, and combustion characteristics of a constant-speed variable compression ratio direct injection diesel engine

Abstract

Alcohol is used as an additive for a long time with the petroleum-based fuels. In this study, the higher alcohol, n-pentanol, was used as an additive to Calophyllum inophyllum (CI) biodiesel/diesel blends at 10, 15, and 20% by volume. In all blends, the ratio of CI was maintained at 20% by volume. The engine characteristics of the pentanol fuel blends were compared with the diesel and CI20 (Calophyllum inophyllum 20% and diesel 80%) biodiesel blend. The nitrogen oxide (NO) emission of the pentanol fuel blends showed an increased value than CI20 and neat diesel fuel. The carbon dioxide (CO2) also increased with increase in pentanol addition with the fuel blends than CI20 fuel blend and diesel. The carbon monoxide (CO) and hydrocarbon (HC) emissions were decreased with increase in pentanol proportion in the blend than the CI20 fuel and diesel. The smoke emission was reduced and the combustion characteristics of the engine were also improved by using pentanol blended fuels. From this investigation, it is suggested that 20% pentanol addition with the biodiesel/diesel fuel is suitable for improved performance and combustion characteristics of a diesel engine without any engine modifications, whereas CO2 and NO emissions increased with addition of pentanol due to effective combustion.



Contamination and Ecological Hazard Assessment of Heavy Metals in Freshwater Sediments and Oreochromis niloticus (Linnaeus, 1758) Fish Muscles in a Nile River Canal in Egypt

Abstract

Heavy metal residues in sediment and Oreochromis niloticus fish muscles, collected from a Nile River Canal (Bahr Shebeen Canal), Egypt, were investigated from September 2014 to December 2015. The spatial and seasonal distributions of Cd, Cu, Fe, Pb, and Zn are described and discussed. Relative abundance of these metals in sediment was found as follows: Fe > Zn > Cu > Pb > Cd. Indices of pollution were used to detect the degree of sediment contamination and indicated elevated concentrations likely to adversely affect benthic and benthic-associated organisms. Anthropogenic activities strongly influenced metal occurrence in sediments. Accumulation of heavy metals in fish muscular tissue was found to be nearly comparable to the sediment. Relative abundance of metals in fish tissue followed the trend of Fe > Zn > Pb > Cu > Cd. Fish can be used as a surrogate for heavy metals pollution. The bioaccumulation factor (BAF) in fish muscle showed the following trend: Pb > Zn > Cu > Fe > Cd. Levels of most selected heavy metals detected in muscular tissue of fish were below admissible limits set by different organizations. However, HI (hazard index) showed that the cumulative risk effects are of considerable concern, especially where fish consumption is high. Consequently, it is recommended that discharged water containing pollutants should be prioritized to include continuous monitoring, and adequate public awareness.



Investigation on the origin of sperm morphological defects: oxidative attacks, chromatin immaturity, and DNA fragmentation

Abstract

DNA fragmentation can be deleterious on spermatozoon morphology but the pathogenesis of teratozoospermia associated with DNA breaks is not fully understood, even if oxidative attacks and defects in chromatin maturation are hypothesized. Therefore, this study is one of the first to clarify on the underlying hypothesizes behind such observations. The objectives of our study were to assess the role of oxidative attacks in DNA damage pathogenesis in ejaculated spermatozoa from patients with isolated teratozoospermia. We aimed to assess the correlation of DNA breaks with morphologically abnormal spermatozoa, as well as ROS level and impairment chromatin condensation. A total of 90 patients were divided into two groups, men with isolated teratozoospermia (n = 60) and men with normal semen parameters (n = 30) as controls. DNA fragmentation was evaluated by TUNEL assay; chromatin immaturity was studied using acridine orange and toluidine blue staining. We evaluated the ability of spermatozoa to produce reactive oxygen species with nitro blue tetrazolium staining. Patient with teratozoospermia when compared to fertile men showed significantly higher rates of semen ROS production, sperm hypocondensated chromatin, denaturated DNA, and fragmented DNA. All these parameters were positively correlated with abnormal sperm morphology. The studied DNA integrity markers were also correlated with ROS production. Fragmented DNA is the main pathway leading to morphology defects in the sperm. In fact, impaired chromatin compaction may induce DNA breaks and free radicals, which can break the DNA backbone indirectly, by reducing protamination and disulphide bond formation, as oxidative attack appears to be the major cause of poor semen morphology.



Spatial econometric analysis of factors influencing regional energy efficiency in China

Abstract

Increased environmental pollution and energy consumption caused by the country's rapid development has raised considerable public concern, and has become the focus of the government and public. This study employs the super-efficiency slack-based model–data envelopment analysis (SBM–DEA) to measure the total factor energy efficiency of 30 provinces in China. The estimation model for the spatial interaction intensity of regional total factor energy efficiency is based on Wilson's maximum entropy model. The model is used to analyze the factors that affect the potential value of total factor energy efficiency using spatial dynamic panel data for 30 provinces during 2000–2014. The study found that there are differences and spatial correlations of energy efficiency among provinces and regions in China. The energy efficiency in the eastern, central, and western regions fluctuated significantly, and was mainly because of significant energy efficiency impacts on influences of industrial structure, energy intensity, and technological progress. This research is of great significance to China's energy efficiency and regional coordinated development.



Sulfur removal from model fuel by Zn impregnated retorted shale and with assistance of design of experiments

Abstract

There is global concern about acid rain and other pollution which is caused by the consumption of oil. By decreasing sulfur content in the oil, we can reduce unwanted emissions and acid rain. Shale was used which is a solid waste generated in the pyrolysis of shale, impregnated with Zn as an adsorbent which removes sulfur present in fuels from the hexane/toluene model solution. An influence of the agitation time (60–180 min), temperature (25–35 °C), adsorbent mass (0.1–0.25 g), and initial sulfur concentration (100–250 ppm) factorial 24 with three central points totaling 19 experiments was applied to investigate the effect of the variables on the efficiency of sulfur removal in fuels. The values of the parameters tested for maximum sulfur removal were obtained as follows: contact time = 180 min, temperature = 35 °C, adsorbent mass = 0.25 g, and initial sulfur concentration = 100 ppm. The mathematical model proposed with R2 99.97% satisfied the experimental data. This may provide a theoretical basis for new research and alternative uses for tailings of schist industrialization in order to evaluate its potential.



Spatiotemporal distribution and risk assessment of organophosphate esters in sediment from Taihu Lake, China

Abstract

The occurrence and spatiotemporal distribution of 12 organophosphate esters (OPEs) were investigated in the sediments collected from Taihu Lake. Compared to the same lake in 2012 (3.4–14 ng/g dw), the concentrations of ∑12 OPEs in sediments ranged from 10.76 to 335.37 ng/g dw and from 8.06 to 425.39 ng/g dw in 2015 and in 2016, respectively, indicating that the OPEs levels in Taihu Lake have aggravated, recently. TEHP was the most abundant compound of the OPEs, which suggested that TEHP was the most widely used around Taihu Lake recently. The positive correlations between some of individual OPEs and the principal components analysis suggested the same potential sources for them. The strong positive correlation between ∑BPs and TOC content indicated that TOC content was one of the factors affected the distribution of ∑OPEs in the sediment. Risk quotient (RQ) for OPEs showed no high eco-toxicity risk in sediment for aquatic organisms.



Lipid Nanoparticles (SLN & NLC) for delivery of vitamin E: A Comprehensive Review

Abstract

The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability, and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium, and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE, and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E.

This article is protected by copyright. All rights reserved.



PD-L1 expression by tumor cell-lines: a predictive marker in melanoma

Abstract

Prognostic biomarkers for melanoma patients after lymph node resection are of clinical relevance and could thus enable the identification of patients who therefore would most benefit from adjuvant treatment. The aim of this work was to determine, using an in vitro model, whether immune-related biomarkers such as MHC-class I and II, melanoma associated antigens, IDO1 and PD-L1, could also be relevant to predict the risk of relapse of stage III melanoma patients after lymph node resection.

We established tumor cell lines from metastatic lymph nodes of 50 melanoma patients. The expression of investigated biomarkers was determined on untreated and IFN-γ treated melanoma cell lines using flow cytometry. Among the selected biomarkers, the IFN-γ induced expression of PD-L1 and IDO1 was associated with an increased risk of relapse (p=0.0001 and p=0.013, respectively) and was also associated with death for IDO1 (p=0.0005). In the future, this immunologic signature could permit the identification of patients at higher risk of relapse, and justifying an adjuvant treatment using immunotherapy.

This article is protected by copyright. All rights reserved.



Reinhard Kahle and Michael Rathjen (eds.): Gentzen’s Centenary. The Quest for Consistency



Macrophage-derived GPNMB accelerates skin healing

Abstract

Healing is a vital response important for the re-establishment of the skin integrity following injury. Delayed or aberrant dermal wound healing leads to morbidity in patients.The development of therapies to improve dermal healing would be useful. Currently, the design of efficient treatments is stalled by the lack of detailed knowledge about the cellular and molecular mechanisms involved in wound healing. Recently, by using state-of-art technologies, it was revealed that macrophages signal via GPNMB to mesenchymal stem cells, accelerating skin healing. Strikingly, transplantation of macrophages expressing GPNMB improves skin healing in GPNMB-mutant mice. Additionally, topical treatment with recombinant GPNMB restored mesenchymal stem cells recruitment and accelerated wound closure in the diabetic skin. From a drug development perspective, this GPNMB is a new candidate for skin healing.

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Malassezia species retrieved from skin with pityriasis versicolor, seborrheic dermatitis and skin free of lesions: a comparison of two sampling methods

Abstract

Malassezia are involved in the pathogenesis of different skin diseases including pityriasis versicolor (PV) and seborrheic dermatitis (SD), but these yeasts are also important inhabitants of the skin microbiome. Culture is not performed routinely, although it may be of value in doubtful cases to support the diagnosis; culture is crucial for identification tools such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Culture is also critical to assess the number of organisms and viability and, eventually, to perform antifungal susceptibility tests.

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Potential impacts of climate change and adaptation strategies for sunflower in Pakistan

Abstract

Growth, development, and economic yield of agricultural crops rely on moisture, temperature, light, and carbon dioxide concentration. However, the amount of these parameters is varying with time due to climate change. Climate change is factual and ongoing so, first principle of agronomy should be to identify climate change potential impacts and adaptation measures to manage the susceptibilities of agricultural sector. Crop models have ability to predict the crop's yield under changing climatic conditions. We used OILCROP-SUN model to simulate the influence of elevated temperature and CO2 on crop growth duration, maximum leaf area index (LAI), total dry matter (TDM), and achene yield of sunflower under semi-arid conditions of Pakistan (Faisalabad, Punjab). The model was calibrated and validated with the experimental data of 2012 and 2013, respectively. The simulation results showed that phenological events of sunflower were not changed at higher concentration of CO2 (430 and 550 ppm). However LAI, achene yield, and TDM increased by 0.24, 2.41, and 4.67% at 430 ppm and by 0.48, 3.09, and 9.87% at 550 ppm, respectively. Increased temperature (1 and 2 °C) reduced the sunflower duration to remain green that finally led to less LAI, achene yield, and TDM as compared to present conditions. However, the drastic effects of increased temperature on sunflower were reduced to some extent at 550 ppm CO2 concentration. Evaluation of different adaptation options revealed that 21 days earlier (as compared to current sowing date) planting of sunflower crop with increased plant population (83,333 plants ha−1) could reduce the yield losses due to climate change. Flowering is the most critical stage of sunflower to water scarcity. We recommended skipping second irrigation or 10% (337.5 mm) less irrigation water application to conserve moisture under possible water scarce conditions of 2025 and 2050.



Enoxaparin does not affect network formation of adipose tissue-derived microvascular fragments

Abstract

Dermal substitutes are frequently used for the initial coverage of extensive skin defects. The seeding of these implants with adipose tissue-derived microvascular fragments (ad-MVF) has recently been shown to accelerate their vascularization and incorporation. In the present study we analyzed whether these processes are affected by a thromboprophylactic therapy with the low molecular weight heparin (LMWH) enoxaparin (enox). Green fluorescent protein (GFP)+ ad-MVF were isolated from enox- (8 mg/kg s.c.) and vehicle-treated (0.9% NaCl s.c.) (C57BL/6-Tg(CAG-EGFP)1Osb/J mice and seeded onto Integra® matrices. Subsequently, these were implanted into full-thickness skin defects within dorsal skinfold chambers of enox- and vehicle-treated C57BL/6 wild-type mice. Repetitive stereomicroscopy and intravital fluorescence microscopy over 2 weeks as well as histological and immunohistochemical analyses on day 14 revealed that enox does not inhibit the reassembly of ad-MVF into new microvascular networks. In addition, treatment with the anti-coagulative compound did not promote implant-induced hemorrhage formation. Accordingly, Integra® matrices in enox- and vehicle-treated animals exhibited a comparable final microvessel density, fraction of GFP+ blood vessels originating from seeded ad-MVF, collagen fiber content, and epithelialization. These novel findings demonstrate that the seeding of dermal substitutes with ad-MVF may be applied also during thromboprophylactic therapy without affecting implant vascularization and bleeding risk. This article is protected by copyright. All rights reserved.



Hospitality and Embodied Encounters in Educational Spaces

Abstract

This short paper responds to the essays by Shilpi Sinha, Shaireen Rasheed, and Lyudmila Bryzzheva. It considers how racial inequality between teachers and students affects the possibilities of educational hospitality, both in cases of white teachers teaching racialized students and in cases of racialized teachers teaching white students. The response takes a phenomenological turn, considering the relative vulnerability of bodies that encounter each other in educational spaces which, themselves, are not neutral.



100PAntitumor effect of dendritic cells loaded with Fe2O3 magnetic nanocomplex in mice with sarcoma 37

Background: Increasing the target delivery of generated dendritic cells (DCs) to the lymphoid tissue of the recipient can significantly improve the efficiency of immunotherapy. This can be achieved by using iron oxide nanoparticles under the action of a magnetic field – a magnetic nanocomplex (MNC).

101PDelivery of E-cadherin (CDH1) gene and epidermal growth factor receptor (EGFR) siRNA, using carbonate apatite as a promising vehicle in treatment of breast cancer

Background: E-cadherin (CDH1), a cell adhesion glycoprotein is widely associated with breast cancer where it is involved in tumor growth, invasion and metastasis. Down regulation of its gene is hall mark for epithelial-mesenchymal transition, which is an essential process for tumor metastasis. While various pathways are associated with E-cadherin, one of the prominent signaling pathways is via epidermal growth factor reception (EGFR), which is found to be over expressed. Silencing the over expressed EGFR gene by using a specific short-interfering RNA (siRNA), or inducing the expression of CDH1 gene with the help of a plasmid could improve management of malignant cancers by disturbing cancer cell interactions with adjacent cells and extracellular matrix; however, tumor-targeted delivery of these complexes is a major challenge in cancer therapy. This could be overcome by using pH-sensitive carbonate apatite nanoparticles that can enhance the intracellular delivery and release of the bound DNA or siRNA from endosomes to cytosol, after being transported to the tumor.

70PmTORC1 and its downstream effectors predict poor outcome in primary epithelial ovarian cancer

Background: Ovarian cancer is associated with the highest mortality rate among gynaecologic malignancies. There is a need to refine classification of ovarian cancer and identify novel targets. The mammalian target of rapamycin (mTOR) pathway has a crucial role in the regulation of translation of specific proteins associated with ovarian cancer progression. The major downstream effectors of mTOR are eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (p70S6K). We aimed to investigate the biological significance of this pathway in ovarian cancer.

102PFunctional characterization of mammagliobin-1 isoform in breast cancer

Background: Since 2007, oncologists have been using the GeneSearchTM Breast Lymph Node (BLN) Assay for the detection of metastatic breast cancer. This test detects the presence of Mammaglobin-1 (MGB1) expression in lymph nodes of breast cancer patients. Although MGB1 is overexpressed in 90% of breast cancers, its aberrant expression and function in breast cancer tissue is still misunderstood. We have recently reported the first evidence for MGB1 as potent induction of breast cancer malignancy and disease progression. More precisely, loss of MGB1 expression correlates with a decrease of cell proliferation, spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also show that MGB1 expression activates pro-malignant signaling cascades leading to epithelial to mesenchymal transitioning (EMT). More interestingly, we have also discovered new MGB1 gene products that result from transcript editing. The objective of this research is to elucidate the role of MGB1 gene products in breast cancer, we set out to investigate and characterize MGB1 isoforms in breast cancer cell processes.

54PIdentifying the oncogenic role of USP10 as the regulator of PTEN function in breast cancer

Background: The PI3K pathway is the most commonly activated signaling pathway in human cancer. The loss of PTEN further contributes to the tumorigenic impact of the active PI3K pathway, and have direct effect on prognosis of breast cancer. Although many small molecules are used in clinic to target the PI3K pathway, only minority of breast cancer patients respond to these drugs. This study identified the role of a deubiquitinating enzyme, USP10 in the regulation of PI3K pathway in breast cancer.

103PAfatinib is active in osteosarcoma in vitro models

Background: Osteosarcoma is the most common bone tumour and affects younger patients. The combination of chemotherapy with aggressive surgical resection results in survival rates achieving 60%-70% in patients with localized disease. Unfortunately, 30% of osteosarcoma patients present metastatic disease at diagnosis and only 20-30% will become long-term survivors. Therefore, finding new drugs to treat these patients is a research priority. Preclinical and clinical studies suggest involvement of ErbB network aberrations in the aetiology of osteosarcomas. The present study assessed the effect of Afatinib, an irreversible ErbB family blocker, in osteosarcoma cell lines.

86PPim1 promotes ovarian cancer growth and the Warburg effect via c-Myc-glycolysis signaling axis

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy, but its mortality ranks the highest in the world. Pim1, belongs to a group of constitutively activated serine/threonine kinases, has been reported in many types of cancer. Little is known about Pim1 in OC.

104PAugmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiomyopathy

Background: Adriamycin (ADR) is a potent anticancer drug widely used to treat a variety of human neoplasms. However, its clinical use is hampered because of severe side effects such as cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidative stress, DNA damage, and inflammatory responses. Nevertheless, the remedy for ADR cardiomyopathy is still not developed. We describe the effect of NAD+/NADH modulation by NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action on AIC.

46OA Phase 1a/2a trial of AVID100, an anti-EGFR antibody-drug conjugate

Background: AVID100, an anti-EGFR-DM1 conjugate, showed potent activity in preclinical models in vitro and in vivo including in cell lines resistant to approved anti-EGFR mAbs.

105PTargeted delivery of albumin-binding caspase-3 cleavable docetaxel prodrug to radiation exposed local tumor

Background: Targeted delivery of therapeutic agent meets with hurdle of finding target ligand or receptor those are expressed tumor cells in homogenous patterns but not on normal cells. Apoptosis is an event that is programmed in all cells exposed to specific stimuli and this phenotypic event does not vary in patient to patient. In attempt to overcome limitations of conventional targeted therapy, radiation-induced apoptosis-targeted chemotherapy (RIATC) was suggested in our previous study. Caspase-3 cleavable docetaxel prodrug is treated following local administration of low dose radiation in tumor site which induces apoptosis. After initial activation of the prodrug, in-situ amplification of prodrug from expressed caspase-3 boost further activation of the prodrug.

62PTargeting Wnt pathway reduces primary tumor and metastasis in breast cancer models

Background: Biomarkers CD44 and CD24 are routinely used to identify breast cancer stem cells (BCSCs). BCSCs are chemotherapy resistant and bear high tumorigenesis and metastatic capabilities. Wnt/β-catenin signaling is involved in maintaining CSCs and thus is responsible for recurrence and poor prognosis. Role of Wnt receptor LRP6 in breast cancer promotion and progression is well known. We hypothesized that interactions between cancer cells, macrophages, and endothelial cells induce cancer stemness via activation of Wnt/-β catenin pathway, and blocking that pathway will reduce primary and metastatic tumors.

106PAntiproliferative effect of trastuzumab and nimotuzumab with EGF on breast cancer cells MCF-7

Background: In this study, we addressed antiproliferative effects of trastuzumab (Herceptin®) and nimotuzumab (Theraloc®) in a combined application with EGF on MCF-7 cells. The epidermal growth factor (EGF) receptors have been found to be implicated in the ontology and maintenance of tumor tissues, which has fostered the discovery and development of molecularly targeted anti-EGF-receptor therapies. However, the accessibility of chemotherapeutic preparations and humanized antibodies to tumor cells in the G0 phase of the cell cycle is lower than to the cells of theproliferative pool. Given this, antitumor efficiency can potentially be enhanced by synchronizing cells in the proliferative pool. To explore this opportunity, we added EGF to tumor cells in combination with nimotuzumab and trastuzumab (antibodies against EGF-R typeI and II, respectively).

79PRole of DNA methylation in early detection of gastric cancer in patient with chronic atrophied gastritis

Background: Chronic atrophied gastritis is the most important and independent risk factor for gastric adenocarcinoma, i.e., precancerous condition, especially in cases of intestinal metaplasia development.

108PThe role of citrus peel extract in inhibiting progression and recurrence of prostate cancer

Background: Prostate cancer (PC) is one of the leading cause of cancer related deaths in men. PC progression and recurrence following initial treatments possesses mortality threat amongst these patients. Cell cycle re-entry of quiescent cancer cells has been suggested for cancer progression and recurrence. The slow progression of PC allows a window of opportunity for intervention through diet. An inverse association of flavonoids intake and PC development has been demonstrated in epidemiological studies. We hypothesized that citrus peel that is rich in various bioactive compounds including flavonoids may impede cell cycle re-entry by quiescent PC cells.

95PEnergy restriction as a novel approach targeting breast cancer stem cells multi-drug resistance

Background: Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide. The progression, metastasis and drug resistance of breast cancer cells were suggested to be driven by a special population within the tumor called cancer stem cells (CSC). Targeting CSC is extremely challenging due to the high expression levels of ATP-binding cassette (ABC) transporters which facilitates the multi drug resistance (MDR) capacity of CSC. The aim of this work was to test whether Energy restriction mimetic agents (ERMAs) as OSU-CG5 can counteract cancer multidrug resistance by limiting the availability of energy in CSC. In addition to exploit the mechanistic synergy between OSU-CG5 and a conventional chemotherapeutic agent as Doxorubicin.

109PMultiphysics modelling of alpha-immuno-conjugate delivery and background dose

Background: Radiotherapy is one of the commonly used approaches to treat cancer. The research trend and breakthroughs in radiotherapy is focusing on the high linear energy transfer (LET) radiation like the alpha particles. Thus, the alpha particles based method is an important option of radiotherapy development, and Targeted Alpha Therapy (TAT) is the most important application of using alpha particles in the past decade. This paper highlights the research work done on computational modelling of TAT at Canadian Nuclear Laboratories (CNL).

41OA phase I study of CPI-0610, a bromodomain and extra terminal protein (BET) inhibitor in patients with relapsed or refractory lymphoma

Background: NF-kB has been found to be constitutively activated in many lymphomas, such as diffuse large B-cell lymphomas (DLBCL), particularly the ABC subgroup. In preclinical studies, CPI-0610, a BET specific small molecule inhibitor, results in downregulation of NF-κB signaling activity, accompanied by loss of viability of ABC-DLBCL cell lines. Here we report the results from the first-in human Phase 1 study of CPI-0610 in patients with relapsed or refractory lymphomas (NCT01949883).

110PCellMiner and CellMiner cross-database (CDB): Resources for the exploration of pharmacogenomics using cancerous cell-lines

Background: Determining the influence of molecular alterations on pharmacological responses in cancer cell lines from the omic perspective is the logical first step towards making oncology treatment for patients more effective, specific, and targeted. Our established CellMiner (and in development CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-applications provide high-quality, clean, and numerically extensive molecular and pharmacological data for these purposes.

50OA first-in-human first-in-class (FIC) trial of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in patients with advanced solid tumours

Background: A key metabolic alteration in tumour cells is increased dependency on glycolysis, resulting in the production of lactate which is transported out of cells by MCTs. Inhibition of MCT-1 can constrain cancer cell growth in preclinical models. We report results on the phase I study of AZD3965, a FIC inhibitor of MCT-1.

111PEffect of IFNα-2b on migrational ability of tumor cells on early stages of breast cancer development

Background: Inflammatory reactions play an important role in all stages of tumor development. A shift to the mesenchymal phenotype causes an increase of migratory capacity of tumor cells. Epithelial-mesenchymal transition (EMT) can also be caused by local inflammation. Searching for factors that can inhibit the transition of the cell population from the epithelial to the mesenchymal phenotype is very important for antitumor therapy. Interferon alfa (IFNα-2b) can be such a factor that has a direct effect on proliferation, differentiation and migration of tumor cells. The aim of this study was to compare the effect of IFNα-2b on the expression of EMT markers and on the basic cellular processes on 2D and 3D growth models.

Treating the tear trough: A new classification system, a 6-step evaluation procedure, hyaluronic acid injection algorithm, and treatment sequences

Summary

Introduction

The tear trough deformity is commonly requested for correction, most often by filler injections. However, the tear trough remains difficult to treat due to its complex anatomy, a variety of other concurrent deformities, and the high risk of complications.

Objectives

To create a standardized categorization, evaluation, and treatment protocol for the management of tear troughs with fillers.

Methods

(1) Patient deformity profiles are determined using three categories of traits: A (Atrophy), B (Bulging), L (Laxity). (2) A 6-step evaluation process (Tilt, Snap, Smile, Squint, Pull, Push) aids in ABL determination. (3) Treatment is simplified into a comprehensive protocol for each category (with 6 major injection points and a variety of injection depths and volumes).

Results

The author has achieved satisfactory results using the presented protocols, with photographic examples.

Conclusion

The author proposes a comprehensive categorization system that takes into account both the tear trough and other concurrent deformities. The author also presents 6 tests to aid in categorization, and simple protocols with injection sequences, amounts, and depth.



Ethics, Subjectivity, and Sociomaterial Assemblages: Two Important Directions and Methodological Tensions

Abstract

Research that explores ethics can help educational communities engage twenty-first century crises and work toward ecologically and socially just forms of life. Integral to this research is an engagement with social theory, which helps educators imagine our shared worlds differently. In this paper I present two theoretical-methodological directions for educational research that centres ethics: Ethics and (human) subjectivity; and Ethics-in-assemblage. While both approaches might be seen as commensurable, they can also be seen as quite divergent. Using Michel Foucault's later work on subjectivity and ethics, as well as recent work in Anthropology, I present a methodological direction for research into ethical subjectivity, how students come to see themselves as self-reflective ethical actors. Relevant here is the tension between ethics and politics, individual and collective modes of being, as both are crucial to both struggles for justice on a damaged planet. The second direction involves a sociomaterialist approach that employs Deleuze and Guattari's concept of 'assemblage' as well as Karen Barad's notion 'entangled responsibility' to show that ethics can also be seen to co-emerge with/in phenomena that exceed human relations. In short, exploring ethics through educational research means simultaneously examining ethics as subjectivity and ethics as co-emergent larger assemblages/phenomena.



Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical-pathological features and intra-tumor heterogeneity over time.

Abstract
Background
Tumor immune microenvironment (TME) plays a key role in malignant pleural mesothelioma (MPM) pathogenesis and treatment outcome, supporting a role of immune checkpoint inhibitors as anticancer approach. This study retrospectively investigated TME and PD-L1 expression in naïve MPM cases and their change under chemotherapy.
Patients and methods
Diagnostic biopsies of MPM patients were collected from four Italian and one Slovenian cancer centers. Pathological assessment of necrosis, inflammation, grading, and mitosis was performed. Ki-67, PD-L1 expression, and tumor infiltrating lymphocytes were detected by immunohistochemistry. When available, the same paired sample after chemotherapy was analyzed. Pathological features and clinical characteristics were correlated to overall survival (OS).
Results
TME and PD-L1 expression were assessed in 93 and 65 chemonaive MPM samples, respectively. 28 samples have not sufficient tumor tissue for PD-L1 expression. Sarcomatoid/biphasic samples were characterized by higher CD8+ T-lymphocytes and PD-L1 expression on tumor cells, while epithelioid showed higher peritumoral CD4+ T and CD20+ B-lymphocytes. Higher CD8+ T-lymphocytes, CD68+ macrophages and PD-L1 expression were associated with pathological features of aggressiveness (necrosis, grading, Ki67). MPM cases characterized by higher CD8+ T- infiltrate showed lower response to chemotherapy and worse survival at univariate analysis. Patients stratification according to a combined score (CS) including CD8+T-lymphocytes, necrosis, mitosis and proliferation index showed median OS of 11.3 months compared with 16.4 months in cases with high versus low CS (p<0.003). Subgroup exploratory analysis of 15 paired samples before and after chemotherapy showed a significant increase of cytotoxic T lymphocytes in MPM samples and PD-L1 expression in immune cells.
Conclusions
TME enriched with cytotoxic T-lymphocytes is associated with higher levels of macrophages and PD-L1 expression on tumor cells and with aggressive histopatological features, lower response to chemotherapy and shorter survival. The role of chemotherapy as a tumor immunogenicity inducer should be confirmed in a larger validation set.