Human breast milk exosomes accelerate mouse wound healing

P543 The healing of cutaneous wounds is a very efficient process despite being very complex. Under certain pathological conditions healing may be impaired, prolonging the healing process and eventually leading to medical intervention and the chronicity of the wound. Exosomes are secreted extracellular vesicles present in biological fluids where they play a key role in intercellular communication at the tissue, organ and organismal levels. Given that human breast milk contains abundant maternal extracellular vesicles (MEVs) with pro-regenerative and immunomodulatory properties, the aim of the present study was to evaluate if topical application ofMEVs into open wounds would be beneficial for healing. Full-thickness excision wounds of 4-mm diameter were created in the dorsal skin of C57BL/6 mice and topical application of 20 micrograms of human MEV isolated at weeks 9, 11, 12 and 15 postpartum of breastfeeding were placed onto the open wounds. Control wounds were vehicle-treated. Macroscopic measurements up to 7 days postwounding revealed that the area of the wound treated with MEV significantly decreased compared with controls. Histological analyses at day 7 post-wounding showed no differences in the granulation tissue area between groups. ..

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients withelanoma

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma. © 2000 Cancer Research Campaig

Melanoma and nevi subtype histopathological characterization with optical coherence tomography

Background: Melanoma incidence has continued to rise in the latest decades, and the forecast is not optimistic. Non-invasive diagnostic imaging techniques such as optical coherence tomography (OCT) are largely studied; however, there is still no agreement on its use for the diagnosis of melanoma. For dermatologists, the differentiation of non-invasive (junctional nevus, compound nevus, intradermal nevus, and melanoma in-situ) versus invasive (superficial spreading melanoma and nodular melanoma) lesions is the key issue in their daily routine. Methods: This work performs a comparative analysis of OCT images using haematoxylin-eosin (HE) and anatomopathological features identified by a pathologist. Then, optical and textural properties are extracted from OCT images with the aim to identify subtle features that could potentially maximize the usefulness of the imaging technique in the identification of the lesion?s potential invasiveness. Results: Preliminary features reveal differences discriminating melanoma in-situ from superficial spreading melanoma and also between melanoma and nevus subtypes that pose a promising baseline for further research. Conclusions: Answering the final goal of diagnosing non-invasive versus invasive lesions with OCT does not seem feasible in the short term, but the obtained results demonstrate a step forward to achieve this.This work has been funded by the Department of Economic Development, Sustainability and the Environment of the Basque Government (Spain) ELKARTEK projects ONKOTOOLS with grant numbers KK-2020/00069, the Spanish Ministry of Science and Education CERVERA project AI4ES with grant numbers CER-20211030, and by the ECSEL JU European project ASTONISH with the grant number 692470, UC Industrial Doctorate DI14

AgroTutor: A Mobile Phone Application Supporting Agricultural Sustainable Intensification

Traditional agricultural extension services rely on extension workers, especially in countries with large agricultural areas. In order to increase adoption of sustainable agriculture, the recommendations given by such services must be adapted to local conditions and be provided in a timely manner. The AgroTutor mobile application was built to provide highly specific and timely agricultural recommendations to farmers across Mexico and complement the work of extension agents. At the same time, AgroTutor provides direct contributions to the United Nations Sustainable Development Goals, either by advancing their implementation or providing local data systems to measure and monitor specific indicators such as the proportion of agricultural area under productive and sustainable agriculture. The application is freely available and allows farmers to geo-locate and register plots and the crops grown there, using the phone’s in-built GPS, or alternatively, on top of very high-resolution imagery. Once a crop and some basic data such as planting date and cultivar type have been registered, the app provides targeted information such as weather, potential and historical yield, financial benchmarking information, data-driven recommendations as well as commodity price forecasts. Farmers are also encouraged to contribute in-situ information, e.g., soils, management, and yield data. The information can then be used by crop models, which, in turn, would send tailored results back to the farmers. Initial feedback from farmers and extension agents has already improved some of the app’s characteristics. More enhancements are planned for inclusion in the future to increase the app’s function as a decision support tool

AgroTutor: A Mobile Phone Application Supporting Sustainable Agricultural Intensification

Traditional agricultural extension services rely on extension workers, especially in countries with large agricultural areas. In order to increase adoption of sustainable agriculture, the recommendations given by such services must be adapted to local conditions and be provided in a timely manner. The AgroTutor mobile application was built to provide highly specific and timely agricultural recommendations to farmers across Mexico and complement the work of extension agents. At the same time, AgroTutor provides direct contributions to the United Nations Sustainable Development Goals, either by advancing their implementation or providing local data systems to measure and monitor specific indicators such as the proportion of agricultural area under productive and sustainable agriculture. The application is freely available and allows farmers to geo-locate and register plots and the crops grown there, using the phone&rsquo;s built-in GPS, or alternatively, on top of very high-resolution imagery. Once a crop and some basic data such as planting date and cultivar type have been registered, the application provides targeted information such as weather, potential and historical yield, financial benchmarking information, data-driven recommendations, and commodity price forecasts. Farmers are also encouraged to contribute in-situ information, e.g., soils, management, and yield data. The information can then be used by crop models, which, in turn, send tailored results back to the farmers. Initial feedback from farmers and extension agents has already improved some of the application&rsquo;s characteristics. More enhancements are planned for inclusion in the future to increase the application&rsquo;s function as a decision support tool

Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms

Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfenadine induced autophagy, that can promote apoptosis. These findings demonstrate the great potential of terfenadine to kill melanoma cells through different cellular signaling pathways and could contribute to define new therapeutic strategies in melanoma

Beyond the mean gender wage gap : decomposition of differences in wage distributions using quantile regression

Using linked employer-employee data, this study measures and decomposes the differences in the earnings distribution between male and female employees in Germany. I extend the traditional decomposition to disentangle the effect of human capital characteristics and the effect of firm characteristics in explaining the gender wage gap. Furthermore, I implement the decomposition across the whole wage distribution with the method proposed by Machado and Mata (2005). Thereby, I take into account the dependence between the human capital endowment of individuals and workplace characteristics. The selection of women into less successful and productive firms explains a sizeable part of the gap. This selection is more pronounced in the lower part of the wage distribution than in the upper tail. In addition, women also benefit from the success of firms by rent-sharing to a lesser extent than their male colleagues. This is the source of the largest part of the pay gap. Gender differences in human capital endowment as well s differences in returns to human capital are less responsible for the wage differential

A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date