Mine water as a source of energy: an application in a coalfield in Laciana Valley (León, NW Spain).

Mine water can be a renewable and economical source of geothermal and hydraulic energy. Nine discharges from closed and flooded coal mines in the Laciana Valley (León, NW Spain) have been studied. Various technologies for the energy use of mine water, as well as the influence of factors such as temperature, the need for water treatment, investment, potential customers and expansion capacity, have been evaluated by means of a decision-making tool. It is concluded that the most advantageous option is an open-loop geothermal system using the waters of a mountain mine, the temperature of which exceeds 14 °C and whose distance to customers is less than 2 km. A technical-economic viability study for a district heating network designed to supply heating and hot water to six public buildings in the nearby town of Villablino is presented. The proposed use of mine water might help areas that have been greatly affected socioeconomically by the closure of the mines and has other advantages compared to conventional energy systems, such as the reduction of CO2 emissions. Graphical Abstract: It showing the advantages of using mine water as an energy source for district heating and a simplified layout. Supplementary Information: The online version contains supplementary material available at 10.1007/s10098-023-02526-y.

Generation of a novel three-dimensional scaffold-based model of the bovine endometrium.

Bovine in vitro endometrial models that resemble tissue function in vivo are needed to study infertility, long-term uterine alterations induced by pathogens and impact of endocrine disruptor chemicals on reproductive function and other reproductive system complications that cause high economic losses in livestock species. The present study aimed to generate an innovative, reproducible, and functional 3D scaffold-based model of the bovine endometrium structurally robust for long term-culture. We developed a multicellular model containing both endometrial epithelial and stromal cells. Epithelial cells organized to form a luminal-like epithelial layer on the surface of the scaffold. Stromal cells produced their own extracellular matrix forming a stable subepithelial compartment that physiologically resembles the normal endometrium. Both cell types released prostaglandin E2 and prostaglandin F2α following a treatment with oxytocin and arachidonic acid. Additionally signal pathways mediating oxytocin and arachidonic acid stimulation of prostaglandin synthesis were analyzed by real time PCR (RT-PCR). Oxytocin receptor (OXTR), prostaglandin E2 receptor 2 (EP2), prostaglandin E2 receptor 4 (EP4), prostaglandin F receptor (PTGFR), prostaglandin E synthase (PTGES), PGF-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (COX-2) expression was detected in both control and treatment groups, however, only significant changes in abundance of OXTR mRNA transcripts were found. The results obtained by this study are a step forward in bovine in vitro culture technology. This 3D scaffold-based model provides a platform to study regulatory mechanisms involved in endometrial physiology and can set the basis for a broader tool for designing and testing novel therapeutic strategies for recurrent uterine pathologies.

A finely tuned interplay between calcium binding, ionic strength and pH modulates conformational and oligomerization equilibria in the Respiratory Syncytial Virus Matrix (M) protein.

As in most enveloped RNA viruses, the Respiratory Syncytial Virus Matrix (RSV-M) protein plays key roles in viral assembly and uncoating. It also plays non-structural roles related to transcription modulation through nucleo-cytoplasmic shuttling and nucleic acid binding ability. We dissected the structural and conformational changes underlying the switch between multiple functionalities, identifying Ca2+ binding as a key factor. To this end, we tackled the analysis of M's conformational stability and equilibria. While in silico calculations predict two potential calcium binding sites per protomer, purified RSV-M dimer contains only one strongly bound calcium ion per protomer. Incubation of RSV-M in the presence of excess Ca2+ leads to an increase in the thermal stability, confirming additional Ca2+ binding sites. Moreover, mild denaturant concentrations trigger the formation of higher order oligomers which are otherwise prevented under Ca2+ saturation conditions, in line with the stabilizing effect of the additional low affinity binding site. On the other hand, Ca2+ removal by chelation at pH 7.0 causes a substantial decrease in the thermal stability leading to the formation of amorphous, spherical-like aggregates, as assessed by TEM. Even though the Ca2+ content modulates RSV-M oligomerization propensity, it does affect its weak RNA binding ability. RSV-M undergoes a substantial conformational change at pHs 4.0 to 5.0 that results in the exposure of hydrophobic surfaces, an increase beta sheet content but burial of tryptophan residues. While low ionic strength promotes dimer dissociation at pH 4.0, physiological concentrations of NaCl lead to the formation of soluble oligomers smaller than 400 kDa at pH 4.0 or insoluble aggregates with tubular morphology at pH 5.0, supporting a fine tuning by pH. Furthermore, the dissociation constants estimated for the low- and high affinity calcium binding sites are 13 µM and 58 nM, respectively, suggesting an intracellular calcium sensing mechanism of RSV-M upon infection. We uncover a finely tuned interplay between calcium binding, ionic strength, and pH changes compatible with the different cellular compartments where M plays key roles, revealing diverse conformational equilibria, oligomerization, and high order structures, required to stabilize the virion particle by a layer of molecules positioned between the membrane and the nucleocapsid.

Tecnologías de la información y la comunicación al servicio de la atención farmacéutica: “Tu farmacéutico de guardia”, una web por y para los pacientes / Information and communication technologies at the service of pharmaceutical care: «Your pharmacist on duty», a website by and for patients

Objetivo: Alineado con la recomendación de la OMS de incorporar a la atención sanitaria diferentes estrategias de salud digital, el objetivo es doble: describir las funcionalidades y recursos de una página web creada para formar e informar a los pacientes y analizar la actividad de la herramienta tras un periodo de funcionamiento de seis años.Material y métodos: Los pasos que se siguieron en la creación de la web fueron: 1) desarrollo del logotipo y sistema de marca; 2) creación de contenidos tanto escritos como audiovisuales y 3) campaña de lanzamiento. Para evaluar su uso se realizó un estudio descriptivo retrospectivo (septiembre 2015 – noviembre 2021) en el que se recogieron los indicadores clave de rendimiento.Resultados: La web se estructuró en 11 grupos de patologías disponiendo de información escrita (179 fichas) y audiovisual (61 videos) sobre medicamentos y un repositorio de temas actuales sobre la salud a modo de noticias (515 reseñas publicadas). Desde su lanzamiento se han registrado un total de 176.530 visitas por 150.004 usuarios diferentes. En noviembre de 2020 se rediseñó la web, optimizándola para móviles con un diseño de marca renovado; hecho que reportó un importante crecimiento de las visitas, siendo el móvil (74,9%) el dispositivo de visualización más utilizado en este último periodo. (AU)

Objectives: To write the functionalities and resources of a web page created to train and inform patients and to analyze the activity of the tool after a six-year operating period. These two objectives are aligned with the WHO recommendation to incorporate different digital health strategies into health care.Material and methods: To create the web page we followed the next steps: 1) development of the logo and brand system; 2) creation of written and audiovisual content and 3) launch campaign. To evaluate the use of the web page, a retrospective descriptive study was carried out (September 2015 – November 2021) and key performance indicators were collected.Results: The website was structured into 11 groups of pathologies, including written information (179 files) and audiovisual information (61 videos) about drugs and a repository of current health topics shown as news (515 published reviews). Since its launch, a total of 176,530 visits have been registered by 150,004 different users. In November 2020 the web was redesigned, optimizing it for mobile devices and with a renewed brand design. This update reported a significant growth in visits, with mobile phones being the most used display (74.9%) in this last period. (AU)

Estimating personal solar ultraviolet radiation exposure through time spent outdoors, ambient levels and modelling approaches.

BACKGROUND: Evidence on validation of surrogates applied to evaluate the personal exposure levels of solar ultraviolet radiation (UVR) in epidemiological studies is scarce. OBJECTIVES: To determine and compare the validity of three approaches, including (i) ambient UVR levels, (ii) time spent outdoors and (iii) a modelling approach integrating the aforementioned parameters, to estimate personal UVR exposure over a period of 6 months among indoor and outdoor workers and in different seasons (summer/winter). METHODS: This validation study was part of the European Commission-funded ICEPURE project and was performed between July 2010 and January 2011 in a convenience sample of indoor and outdoor workers in Catalunya, Spain. We developed linear regression models to quantify the variation in the objectively measured personal UVR exposure that could be explained, separately, by the ambient UVR, time spent outdoors and modelled UVR levels. RESULTS: Our 39 participants - mostly male and with a median age of 35 years - presented a median daily objectively measured UVR of 0·37 standard erythemal doses. The UVR dose was statistically significantly higher in summer and for outdoor workers. The modelled personal UVR exposure and self-reported time spent outdoors could reasonably predict the variation in the objectively measured personal UVR levels (R2 range 0·75-0·79), whereas ambient UVR was a poor predictor (R2 = 0·21). No notable differences were found between seasons or occupation. CONCLUSIONS: Time outdoors and our modelling approach were reliable predictors and of value to be applied in epidemiological studies of the health effects of current exposure to UVR.

Efficacy of a topical gel containing chitosan, chlorhexidine, allantoin and dexpanthenol for pain and inflammation control after third molar surgery: A randomized and placebo-controlled clinical trial.

BACKGROUND: The aim of this study was to evaluate and compare the postoperative effect of a topic gel containing chlorhexidine, chitosan, allantoine and dexpanthenol versus a placebo for pain and inflammation control after third molar surgery. MATERIAL AND METHODS: A gel combining 0.2% chlorhexdine, 0.5% chitosan, 5% dexpanthenol, 0.15% allantoin and 0.01% sodium saccharin was selected for this split mouth randomized controlled and double-blind trial including 36 patients with bilaterally and symmetrically impacted lower third molars. The teeth (n=72) were randomly divided into two groups before surgical removal: control group (CG; in which a placebo was given) and experimental group (EG). Swelling, trismus, postoperative pain, wound healing and complications were measured and recorded in order to evaluate differences between the placebo and experimental product. RESULTS: Five patients suffered from an alveolitis in the CG (13.9%), and none in the study group (0%), but no statistically significant difference was found (p=0.063). From day 0 to day 7, trismus and swelling were significantly less pronounced in the EG, and wound healing was considered 'good' in 22.2% for the CG and 97.2% for the EG (p<0.001). Mean VAS scores during the seven postoperative days were statistically lower in the study (2.56±1,19) compared to the placebo group (3.25±1.6) (p=0.002). The mean consumption of analgesic pills during the first 92 hours was also statistically lower in the EG (0.26±0.51) in comparison to the CG (0.56±0.67) (p=0.003). CONCLUSIONS: The use of an experimental gel containing chlorhexidine, chitosan, allantoine and dexpanthenol seems to significantly reduce postoperative pain, trismus and signs of inflammation. Future studies should further evaluate, if the gel is effective in dry socket preventing after third molar removal.

Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer.

BACKGROUND: Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival. PATIENTS AND METHODS: A total of 254 samples from 143 patients with rectal adenocarcinomas were analyzed for the presence and abundance of F. nucleatum using RNA in situ hybridization and digital image analysis. Assay accuracy was determined using infected cell lines and tumor samples with available quantitative PCR data. We studied the impact of F. nucleatum load on pathologic complete response and relapse-free survival. Treatment-induced changes were evaluated in paired pre- and post-nCRT samples (n = 71). Finally, tumor microenvironment changes during nCRT were assessed in paired samples (n = 45) by immune contexture analysis. RESULTS: F. nucleatum tissue levels by RNA in situ hybridization strongly correlated with quantitative PCR (r = 0.804, P < 0.001). F. nucleatum abundance was higher in untreated [median, 7.4; 95% confidence interval (3.7-16.2)] compared with treated [median, 1.6; 95% confidence interval (1.3-2.4)] tumors (P <0.001) with 58% (73/126) and 26% (22/85) positive tumors, respectively (P < 0.001). Baseline F. nucleatum levels were not associated with pathologic complete response. F. nucleatum positivity after nCRT, but not baseline status, significantly increased risk of relapse [hazard ratio = 7.5, 95% confidence interval (3.0-19.0); P < 0.001]. Tumors that turned F. nucleatum-negative after nCRT had a strong increase in CD8+ T cells post-nCRT (P < 0.001), while those that persisted F. nucleatum-positive after nCRT lacked CD8+ T cells induction in post-nCRT samples compared with baseline (P = 0.69). CONCLUSION: F. nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity.

The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype.

In addition to their detection in typical X-linked severe combined immunodeficiency, hypomorphic mutations in the interleukin (IL)-2 receptor common gamma chain gene (IL2RG) have been described in patients with atypical clinical and immunological phenotypes. In this leaky clinical phenotype the diagnosis is often delayed, limiting prompt therapy in these patients. Here, we report the biochemical and functional characterization of a nonsense mutation in exon 8 (p.R328X) of IL2RG in two siblings: a 4-year-old boy with lethal Epstein-Barr virus-related lymphoma and his asymptomatic 8-month-old brother with a Tlow B+ natural killer (NK)+ immunophenotype, dysgammaglobulinemia, abnormal lymphocyte proliferation and reduced levels of T cell receptor excision circles. After confirming normal IL-2RG expression (CD132) on T lymphocytes, signal transducer and activator of transcription-1 (STAT-5) phosphorylation was examined to evaluate the functionality of the common gamma chain (γc ), which showed partially preserved function. Co-immunoprecipitation experiments were performed to assess the interaction capacity of the R328X mutant with Janus kinase (JAK)3, concluding that R328X impairs JAK3 binding to γc . Here, we describe how the R328X mutation in IL-2RG may allow partial phosphorylation of STAT-5 through a JAK3-independent pathway. We identified a region of three amino acids in the γc intracellular domain that may be critical for receptor stabilization and allow this alternative signaling. Identification of the functional consequences of pathogenic IL2RG variants at the cellular level is important to enable clearer understanding of partial defects leading to leaky phenotypes.

Abordaje nutricional en pacientes críticos diagnosticados de neumonía por COVID-19 / Nutritional approach in critical patients diagnosed with pneumonia by COVID-19

OBJETIVO: Evaluar las actuaciones nutricionales en pacientes con diagnóstico de neumonía COVID-19 en una Unidad de Cuidados Intensivos (UCI) y su ajuste a las guías de las sociedades Europea y Americana de Nutrición Clínica. METODOLOGÍA: Estudio retrospectivo observacional de 2 meses de duración en pacientes con diagnóstico de neumonía COVID-19 con ingreso en UCI. Se utilizaron los programas ICCA(R), OrionClinic(R) y Kabisoft(R) para obtener las variables de los pacientes. RESULTADOS: Ingresaron 27 pacientes, de los cuales 20 precisaron soporte nutricional. Un 65% eran hombres y la media de edad fue 62 ± 13,2 años. Los requerimientos energéticos teóricos fueron entre 1.535-1.800 Kcal/día. Permanecieron 2,5 ± 4,5 días en planta previo a su estancia en UCI, que fue de 17 ± 6,9 días. Al término del estudio, el 15% de pacientes fueron alta, el 35% seguían hospitalizados y el 50% fueron éxitus. La variación de los datos analíticos al ingreso y alta fue: proteínas +1,3 g/dl, albúmina +1,2 g/dl, linfocitos +0,5*103/mm3, PCR -114,5 mg/l y triglicéridos +19,4 mg/dl. Un 10% recibieron remdesivir y un 30% tocilizumab como tratamientos de segunda línea. Todos fueron intubados y tratados con propofol; el 75% requirió posición decúbito prono. Todos los pacientes requirieron nutrición enteral, siendo la fórmula hiperproteica-hipercalórica con fibra la más utilizada. Un 70% necesitó nutrición parenteral total, utilizándose formulaciones hiperproteicas-hipocalóricas de forma prioritaria y suplementadas con vitaminas y oligoelementos. CONCLUSIÓN: Dentro del complicado manejo de este tipo de pacientes, las intervenciones nutricionales han sido necesarias en un 75% de ellos y la adherencia a las guías actuales se ha dado en todos los casos, con resultados favorables

PURPOSE: Evaluate nutritional performance in patients with COVID-19 pneumonia admitted to the Intensive Care Unit (ICU). Adjustment done following the guidelines of the European and American societies for Clinical Nutrition. METHODOLOGY: Retrospective observational during 2 months study of some patients with pneumonia by COVID-19 in ICU. Informatic programs ICCA(R), OrionClinic(R) and Kabisoft(R) were used to obtain variables of patients. RESULTS: 27 patients were admitted in ICU, while 20 of them required nutritional support. There were 65% of men with average age about 62 ± 13.2. Their theoretical nutritional requirements were between 1,535-1,800 kcal/day. They stayed 2.5 ± 4.5 days in the hospital before their ICU admission. They were 17 ± 6.9 days on average in ICU. At the end of this study, 15% of patients were discharged, 35% were hospitalized, and 50% were dead. The variation of the analytical data at admission and discharge was: proteins +1.3 g/dl, albumin +1.2 g/dl, lymphocytes +0.5*103/mm3, PCR -114.5 mg/l and triglycerides +19.4 mg/dl. 10% took remdesivir and 30% tocilizumab. All of them were intubated and treated with propofol and 75% required prone position. All of patients required enteral nutrition being the hyperprotein-hypercaloric with fiber formula the most used. 70% required central total parenteral nutrition being mostly hyperprotein-hypocaloric and supplemented with vitamins and trace elements. CONCLUSION: Within the complicated management of this type of patients, nutritional interventions have been necessary in 75% of them and adherence to current guidelines has occurred in all cases, with favorable results

Geometrical and spectral study of ß-skeleton graphs.

We perform an extensive numerical analysis of ß-skeleton graphs, a particular type of proximity graphs. In a ß-skeleton graph (BSG) two vertices are connected if a proximity rule, that depends of the parameter ß∈(0,∞), is satisfied. Moreover, for ß>1 there exist two different proximity rules, leading to lune-based and circle-based BSGs. First, by computing the average degree of large ensembles of BSGs we detect differences, which increase with the increase of ß, between lune-based and circle-based BSGs. Then, within a random matrix theory (RMT) approach, we explore spectral and eigenvector properties of random BSGs by the use of the nearest-neighbor energy-level spacing distribution and the entropic eigenvector localization length, respectively. The RMT analysis allows us to conclude that a localization transition occurs at ß=1.

Análisis de la relación solicitud-implante de injerto para trasplante osteomuscular / Analysis of the order-implantation relationship for musculoskeletal tissue transplantation

Objetivo: Analizar los pedidos solicitados a un banco musculoesquelético y evaluar el porcentaje de utilización de los tejidos. Material y métodos: Se analizaron 265 pedidos de tejido osteomuscular en el transcurso de un año. Exclusiones: 5 duplicaciones y 5 pedidos en los cuales no hubo disponibilidad para cubrir la necesidad. Se analizó la cantidad de cirugías en las que finalmente se utilizó el injerto. Resultados: De 255 pedidos solicitados, en 178 (70%) el injerto fue utilizado, mientras que en 77 (30%) el injerto no fue utilizado. De los 178 utilizados, en 23 (10%) hubo una devolución parcial. De los 77 pedidos de injerto no utilizado, en 32 (13%) la cirugía fue realizada sin necesidad de utilizar tejido de banco, mientras que en los 45 (17%) restantes la cirugía fue suspendida. Discusión: Un 30% de los injertos solicitados no fueron utilizados; un 17% debido a que la cirugía fue suspendida y un 13% porque el tejido fue devuelto, ya que la cirugía no lo requirió. En otro 10% hubo una devolución parcial del tejido. Con base en este análisis, consideramos que es importante tener una confirmación directa de la realización de la cirugía para evitar enviar tejido a cirugías suspendidas, ya que además del impacto económico, el banco debe asegurar un adecuado mantenimiento de la temperatura durante el transporte y almacenamiento en el centro trasplantológico, para evitar el descarte de dicho tejido, en caso de ser devuelto

Objective: To analyze orders requested from a musculoskeletal tissue bank and to evaluate the percentage of tissue implantation. Material and methods: Two hundred and sixty-five orders for musculoskeletal tissue were analyzed over the course of a year. Exclusions: 5 duplications and 5 orders for which there was no availability to cover the need. We analyzed the number of surgeries in which the graft was finally used. Results: Of a total of 255 orders, the graft was used in 178 (70%), and the graft was not used in 77 (30%). Of the 178 used, there was a partial refund in 23 (10%). Of the 77 orders not used, surgery was performed in 32 (13%) without the use of bank tissue, while surgery was discontinued in the remaining 45 (17%). Discussion: A non-utilization rate of 30% was identified, of which 17% was from surgery that was not performed and 13% from surgery that was performed, but the tissue was returned to the tissue bank, because it was not required. In a further 10% there was partial return of the tissue. Based on this analysis, we consider that it is important to have direct confirmation of the surgery to avoid sending tissue for discontinued surgeries, since in addition to the economic impact, the bank must ensure adequate temperature maintenance during transportation and storage in the transplantation centre, to avoid discarding said tissue if it is returned

Analysis of the order-implantation relationship for musculoskeletal tissue transplantation. / Análisis de la relación solicitud-implante de injerto para trasplante osteomuscular.

OBJECTIVE: To analyze orders requested from a musculoskeletal tissue bank and to evaluate the percentage of tissue implantation. MATERIAL AND METHODS: Two hundred and sixty-five orders for musculoskeletal tissue were analyzed over the course of a year. EXCLUSIONS: 5 duplications and 5 orders for which there was no availability to cover the need. We analyzed the number of surgeries in which the graft was finally used. RESULTS: Of a total of 255 orders, the graft was used in 178 (70%), and the graft was not used in 77 (30%). Of the 178 used, there was a partial refund in 23 (10%). Of the 77 orders not used, surgery was performed in 32 (13%) without the use of bank tissue, while surgery was discontinued in the remaining 45 (17%). DISCUSSION: A non-utilization rate of 30% was identified, of which 17% was from surgery that was not performed and 13% from surgery that was performed, but the tissue was returned to the tissue bank, because it was not required. In a further 10% there was partial return of the tissue. Based on this analysis, we consider that it is important to have direct confirmation of the surgery to avoid sending tissue for discontinued surgeries, since in addition to the economic impact, the bank must ensure adequate temperature maintenance during transportation and storage in the transplantation centre, to avoid discarding said tissue if it is returned.

Exceso de bases, un marcador útil en el pronóstico del traumatismo torácico en la población geriátrica / Base excess, a useful marker in the prognosis of chest trauma in the geriatric population

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Prenatal Therapy with Magnesium Sulfate and Its Correlation with Neonatal Serum Magnesium Concentration.

INTRODUCTION: Antenatal magnesium sulfate (MgSO4) administration has shown to be effective in minimizing cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIALS AND METHODS: A prospective cohort study was conducted on neonates of less than 32 weeks' gestation admitted to the neonatal intensive care unit of University Hospital Complex of Vigo from December 2012 to July 2015. Comparative analysis of magnesium levels between the groups of neonates exposed to MgSO4 and the control group. RESULTS: A total of 118 neonates were included in the study. The mothers of 62 of them had received MgSO4 as a neuroprotective agent. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24 hours of life (r2 = 0.397; p < 0.001). CONCLUSION: The MgSO4 dose received by the mother has a linear relationship with the magnesium levels obtained in neonates.

Identifying network structure similarity using spectral graph theory.

Most real networks are too large or they are not available for real time analysis. Therefore, in practice, decisions are made based on partial information about the ground truth network. It is of great interest to have metrics to determine if an inferred network (the partial information network) is similar to the ground truth. In this paper we develop a test for similarity between the inferred and the true network. Our research utilizes a network visualization tool, which systematically discovers a network, producing a sequence of snapshots of the network. We introduce and test our metric on the consecutive snapshots of a network, and against the ground truth. To test the scalability of our metric we use a random matrix theory approach while discovering Erdös-Rényi graphs. This scaling analysis allows us to make predictions about the performance of the discovery process.

Bioactive compounds and antioxidant activity in scalded Jalapeño pepper industrial byproduct (Capsicum annuum).

Bioactive compounds and antioxidant activity were evaluated from industrial Jalapeño pepper byproducts and simulated non processed byproducts from two Mexican states (Chihuahua and Sinaloa) to determine their value added potential as commercial food ingredients. Aqueous 80% ethanol produced about 13% of dry extract of polar compounds. Total phenolic content increased and capsaicin and dihydrocapsaicin decreased on scalding samples (80 °C, 2 min) without affecting ascorbic acid. The major phenolic compounds, rutin, epicatechin and catechin comprised 90% of the total compounds detected by HPLC of each Jalapeño pepper byproducts. ORAC analysis showed that the origin and scalding process affected the antioxidant activity which correlated strongly with capsaicin content. Although scalding decreased capsaicinoids (up to 42%), phenolic content by (up to 16%), and the antioxidant activity (variable). Jalapeño pepper byproduct is a good source of compounds with antioxidant activity, and still an attractive ingredient to develop useful innovative products with potential food/non-food applications simultaneously reducing food loss and waste.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program

Background. The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. Methods. Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. Results. Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. Conclusion. Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases (AU)

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