Vitiligo-like lesions located over In-transit metastases of malignant melanoma as a clinical marker of complete response to pembrolizumab.

Anti-programmed cell death (PD)-1 therapies in metastatic tumors have a high incidence of immune adverse events, including cutaneous manifestations such as vitiligo-like lesions. This side effect is associated with increased survival and it is a clinical marker of response to treatment. This case report is a graphic representation of the appearance of vitiligo-like lesions over in-transit metastases of malignant melanoma linked to a complete response to treatment with pembrolizumab

New developments in sunscreens

Topical sunscreen application is one of the most important photoprotection tool to prevent sun damaging effects in human skin at the short and long term. Although its efficacy and cosmeticity have significantly improved in recent years, a better understanding of the biological and clinical effects of longer wavelength radiation, such as long ultraviolet A (UVA I) and blue light, has driven scientists and companies to search for effective and safe filters and substances to protect against these newly identified forms of radiation. New technologies have sought to imbue sunscreen with novel properties, such as the reduction of calorific radiation. Cutaneous penetration by sunscreens can also be reduced using hydrogels or nanocrystals that envelop the filters, or by binding filters to nanocarriers such as alginate microparticles, cyclodextrins, and methacrylate polymers. Finally, researchers have looked to nature as a source of healthier products, such as plant products (e.g., mycosporines, scytonemin, and various flavonoids) and even fungal and bacterial melanin, which could potentially be used as substitutes or enhancers of current filters

Evolución de la prescripción antibiótica en un servicio de urgencias pediátricas hospitalarias

Introducción: El incremento de las resistencias a los antibióticos constituye una de las principales amenazas para la salud pública a nivel global, siendo la prescripción antibiótica inadecuada el principal determinante de este incremento. Esta problemática ha obligado a tomar medidas como la creación del Plan Nacional frente a las Resistencias a los Antibióticos en España. Desde el servicio de pediatría del Hospital Universitario de San Juan de Alicante (HUSJA), se planteó una intervención de mejora basada en la realización de una charla formativa presencial sobre antibioterapia empírica, la difusión de los documentos de consenso de la Asociación Española de Pediatría y la guía ABE y la revisión a posteriori de las prescripciones realizadas en urgencias pediátricas. Objetivo: El objetivo del estudio fue evaluar si esta intervención mejoraba el porcentaje de adecuación en la prescripción de antibioterapia oral al alta en urgencias pediátricas del HUSJA, respecto a un estudio realizado pre-intervención. Material y métodos: Estudio prospectivo observacional realizado tras la intervención formativa. Del total de urgencias atendidas entre el 22/11/2021 y el 22/12/2021 en urgencias pediátricas del HUSJA, se incluyeron en el análisis aquellas en las que se prescribió antibioterapia oral al alta, evaluando el grado de adecuación de la prescripción según documentos de consenso nacionales. Estos resultados se compararon con un estudio previo a la intervención, en enero de 2021. Resultados: En el periodo de estudio se atendieron 987 urgencias, 690 de etiología infecciosa, prescribiéndose antibióticos orales en 71 niños (7.19% del total). Dicha prescripción se consideró inadecuada en el 53.52% de los casos (n=38), lo que supuso 4 una ligera reducción respecto al estudio previo a la intervención, donde la inadecuación fue del 57.70%. Esta diferencia no fue estadísticamente significativa. Discusión: Los resultados muestran que la intervención planteada no fue suficiente para mejorar la adecuación de la prescripción antibiótica, existiendo diversos aspectos que limitaron su impacto. Sin embargo, existe margen de mejora y, con la experiencia de este estudio, se deben plantear nuevas intervenciones que optimicen la prescripción antibiótica en los servicios de urgencias de pediatría.Introduction: The increase in antibiotics resistance is one of the main threats to global public health, being the inadequate antibiotic prescription the main determinant of this increase. This problem has forced to make measures, such us the creation of the National Plan against Antibotic Resistance in Spain. From the pediatric service of the Universitary Hospital of San Juan de Alicante (HUSJA), an improvement intervention was proposed based on a presencial formative talk on empirical antibiotic therapy, Spanish Pediatric Association consensus documents’s and ABE guide difusión and posteriori review of prescriptions done in pediatric emergencies. Objective: The objective was to evaluate if the intervention improves the adequation percentage of oral antibiotics prescriptions in pediatrics emergencies of HUSJA, respect to a pre-intervention studie's. Methods: Observational prospective study realized after formative intervention. Of total emergencies attended between 11/22/2021 and 12/22/2021 in pediatric emergencies at HUSJA, those which oral antibiotic therapy was prescribed at hospital discharge were included in the análisis, evaluating adequacy degree according to national consensus guideline. These results were compared with a pre-intervention study realized in January 2021. Results: During study period, 987 emergencies were attended, 690 of infectious etiology, being prescribing oral antibiotics in 71 children (7.19% of total). This prescription was inadequate in 53.52% of cases (n=38), which represented a slight reduction compared to pre-intervention studie's, in which inadequation was 57.70%. This difference was not statistically significant. Discussion: The results show that the proposed intervention was not enough to improve the antibiotic prescription adequacy, with several aspects that limited its impact. However, there is improvement’s margin and, bases on this study experiences, new interventions should be proposed to optimize antibiotic prescriptions in pediatrics emergency services

In situ generation of COx-free H2 by catalytic ammonia decomposition over Ru-Al-monoliths

Ru catalysts supported on alumina coated monoliths has been prepared employing three different precursor, which are ruthenium chloride, ruthenium nitrosyl nitrate and ruthenium acetyl acetonate, by an equilibrium adsorption method. The Ru particle sizes could be controlled varying the metal precursor salt. Among the prepared catalysts, Ru catalyst prepared from nytrosyl nitrate exhibited the highest activity which is concomitant to the largest mean Ru particle size of 3.5 nm. The values of the apparent activation energy calculated from the Arrhenius equation are according to the Temkin-Phyzev model, indicating that the recombinative desorption of N ad-atoms is the rate-determining step of the reaction. However, the ratio between the kinetic orders with respect to ammonia and hydrogen (-a/ß), is not in agreement to the valued predict by Temkin formalism. This fact could be related to the different operational conditions used during the reaction, and/or catalyst nature, but not to any change on the controlling step of the reaction

Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Caracterización y evaluación de un modelo in vitro de células musculares lisas de aorta humana para el estudio de la calcificación vascular asociada a la uremia

La elevada morbi-mortalidad cardiovascular de los pacientes urémicos se ha relacionado con las alteraciones en el metabolismo mineral, y más concretamente con la presencia de calcificaciones vasculares, que contribuyen a las alteraciones estructurales del vaso. El fenómeno incluye la transdiferenciación de las células del músculo liso vascular (VSMC) hacia a un fenotipo con características osteogénicas como respuesta a la hiperfosfatemia y/o a la presencia de toxinas urémicas. Los mecanismos por los que la uremia promueve la calcificación vascular y su relación con la patología cardiovascular, acelerada, precoz y severa, plantean aún múltiples interrogantes, parte de los cuales se derivan de la utilización de modelos de estudio poco adecuados. En este trabajo, nos planteamos el desarrollo de un nuevo modelo de estudio in vitro de calcificación en células musculares lisas de aorta humana (HASMC) expuestas a suero urémico humano e hipotetizamos que el cambio fenotípico producido en HASMC podría está asociado a alteraciones en la expresión y función de canales iónicos presentes en estas células. Los resultados obtenidos en este trabajo demuestran no solo que el uso de este modelo in vitro reproduce de manera global y con una aproximación más fisiopatológica la transformación fenotípica de las células musculares lisas en respuesta a la uremia, bajo condiciones normofosfatémicas. Sino también, que la remodelación en el perfil de expresión de canales iónicos ocasionada por el suero urémico en las HASMC deja al descubierto nuevos mecanismos subyacentes a dicha modulación fenotípica

Process water recirculation during hydrothermal carbonization as a promising process step towards the production of nitrogen-doped carbonaceous materials

Hydrothermal Carbonization (HTC) refers to the conversion of biogenic wastes into char-like solids with promising perspectives for application, but a process water (PW) results which is difficult to dispose untreated. Thus, a biorefinery approach including one or two recirculation steps with the additional objective of improving the physico-chemical characteristics of the solid was performed in this study. During HTC, constitutive molecules such as saccharides, proteins and lignin of Brewer''s Spent Grains decompose into hundreds of organic compounds, following complex reactions. To get deeper insights a combination of proximate, ultimate and structural analysis for solid products as well as liquid chromatography for liquid products were the choice. The main reactions could be identified by key compounds of low and high molecular weight resulting from hydrolysis, dehydration, decarboxylation, deamination as well as amide formation and condensation reactions. Their intensity was influenced by the feedwater pH and reaction temperature. Via reactions of Maillard character up to around 90% of the dissolved nitrogen of the recirculated process water at 200, 220 and 240 degrees C result in the formation of nitrogen containing heterocycles or rather Quartnernary nitrogen incorporated into the hydrochar (HC). Thus, already one recirculation step during HTC at 240 degrees C promises the fabrication of high added-value materials, i.e. nitrogen doped carbonaceous materials

Synthesis of graphenic nanomaterials by decomposition of methane on a Ni-Cu/biomorphic carbon catalyst. Kinetic and characterization results

This work addresses the preparation and application of the synthesis of graphene in Ni-Cu catalysts supported on carbonaceous materials. The catalysts have been prepared by a biomorphic mineralization technique which involves the thermal decomposition, under reductive atmosphere, of commercial cellulose previously impregnated with the metallic precursors. The characterization results indicate that the preparation method leads to the formation of carbonaceous supports with a moderate microporosity (ca. 33% pore volume) and adequate surface area (343 m2/g), maintaining the original external texture. The catalytic performance of these materials was previously tested in liquid phase reactions (Zampieri et al., 2007 [7]). In order to extend the use of these catalysts, in this work we present a study corresponding to a gas phase reaction: the synthesis of graphenic nanomaterials by catalytic decomposition of methane (CDM). The influence of the reaction temperature and of the feed composition (i.e.%CH4 and%H2) has been studied. The graphenic nanomaterials obtained after reaction were characterized by nitrogen adsorption-desorption isotherms, Raman spectroscopy and transmission electron microscopy (TEM). The results indicate that the carbonaceous nanomaterial with the highest quality is obtained operating at 950 °C and feeding 28.6% of CH4 and 14.3% of H2. The evolution of the carbon mass during the reaction time was analysed using a phenomenological kinetic model that takes into account the main stages involved during the formation of carbonaceous nanomaterials (NCMs). The results obtained from the kinetic model along with the characterization results enable the influence of the operating variables on each stage of the carbonaceous nanomaterial formation to be discerned

PROSTAGLANDIN E2 stimulates cancer-related phenotypes in prostate cancer PC3 cells through cyclooxygenase-2

Cyclooxygenase (COX)?derived prostaglandin E2 (PGE2) affects many mechanisms that have been shown to play roles in carcinogenesis. Recently, we found that, in androgenindependent prostate cancer PC3 cells, PGE2 acts through an intracrine mechanism by which its uptake by the prostaglandin transporter (PGT) results in increased intracellular PGE2 (iPGE2), leading to enhanced cell proliferation, migration, invasion, angiogenesis, and loss of cell adhesion to collagen I. These iPGE2?mediated effects were dependent on hypoxia?inducible factor 1?? (HIF?1?), whose expression increased upon epidermal growth factor receptor (EGFR) transactivation by a subset of intracellular PGE2 receptors. Here, we aimed to study the role of COX in PGE2 protumoral effects in PC3 cells and found that the effects were prevented by inhibition of COX?2, which highlights its crucial role amplifying the levels of iPGE2. Treatment with exogenous PGE2 determined a transcriptional increase in COX?2 expression, which was abolished by genetic or pharmacologic inhibition of PGT. PGE2?induced increase in COX?2 expression and, thereby, in transcriptional increase in HIF?1? expression was due to EGFR activation, leading to the activation of Phosphoinositide 3-kinase/Akt, Extracellular signal -regulated kinases 1/2, p38 and Mitogen- and stress-activated protein kinase-1 (PI3K/Akt, Erk1/2, p38 and MSK?1). Collectively, the data suggest that EGFR?dependent COX?2 upregulation by a novel positive feedback loop triggered by iPGE2 underlies the intracrine pro?tumoral effects of PGE2 in PC3 cells. Therefore, this feedback loop may be relevant in prostate cancer for the maintenance of PGE2?dependent cancer cell growth through amplifying the activity of the COX?2 pathway.Ministerio de Ciencia e Innovació