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Numerous studies evaluating the effects of the incorporation of microalgae in feeds have reported favourable impacts on different physiological aspects of aquacultured fish. Although productivity is the major goal in terms of profitability in fish farming, however, qualitative aspects are gaining the attention of producers, given the relevance of quality attributes related to organoleptic parameters, proximal composition, and shelf life on the commercial value of fish. Indeed, microalgae are acknowledged for their richness in substances with potential positive effects on all those quality attributes. In this context, this study assesses the effects of finishing diets enriched with the microalga Nannochloropsis gaditana, either crude or enzymatically hydrolysed, on several quality parameters of gilthead seabream (Sparus aurata) fillets. Two inclusion levels (2.5 and 5%) of raw and enzymatically hydrolysed microalgal biomass were incorporated into diets, plus a microalgae-free control diet, and a 42-d feeding trial was carried out on fish of commercial size (approx. 500 g body weight). The influence of the experimental diets on fish biometry, fillet quality parameters, and shelf life was evaluated. The results indicate, overall, that microalgae-enriched diets yielded favourable, dose-dependent effects on several objective quality parameters of fillets, namely, improved fatty acid profile, reduced microbial counts, enhanced lipid oxidative status, and improved textural and skin colour attributes. Although the enzymatic pre-treatment of the microalgal biomass was expected to impact positively its functional effects on all quality parameters, however, no general trend was observed.

Today, the emergence of increasingly restrictive treatment and reuse policies make the implementation of full-scale tertiary treatment, capable of improving the quality of water, a priority. Full-scale TiO2 photocatalysis systems are resulting in a promising option, since TiO2 is commercially available. However, questions such as how to work continuously during day/night irradiation cycle, or the removing of TiO2 in outlet flow are still unresolved. In this work, a full-scale system integrating a solar CPC/UV-LED step combined with commercial microfiltration membranes was installed in a conventional WWTP for agricultural reuse purposes. After optimization, 0.5 g/L of catalyst and combined SOLAR + UV-LED showing the highest pharmaceutical removal percentages, while a self-designed UV-LED included in the own reaction tank resulting in higher efficiencies compared with commercial lamps. Longer membrane surface area decreased fouling problems in the system. However, 60 min of irradiation time was necessary to reach the most restrictive water quality values according with (EU 2020/741). After optimization step, total costs were reduced by 45%. However, it was shown that a reduction in operating and maintenance costs, along with the development of more effective and economical commercial filtration membranes is a key factor; therefore, working on these aspects is essential in the treated water cost reduction. Graphical abstract

Background Neratinib has efficacy in central nervous system (CNS) metastases from HER2‐positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods NALA was a randomized, active‐controlled trial in patients who received two or more previous HER2‐directed regimens for HER2‐positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression‐free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS‐directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2‐positive MBC. Implications for Practice In a subgroup of patients with central nervous system (CNS) metastases from HER2‐positive breast cancer after two or more previous HER2‐directed regimens, the combination of neratinib plus capecitabine was associated with improved progression‐free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2‐positive brain metastases following antibody‐based HER2‐directed therapies., This article reports outcomes among HER2‐positive breast cancer patients with central nervous system metastases at baseline from the phase III NALA trial of neratinib plus capecitabine versus lapatinib plus capecitabine.

In this paper a 3D numerical model using a software based on the Finite Element Method (FEM), was developed and validated using the results obtained in a geotechnical centrifuge model of a piled raft system founded in soft soils undergoing regional subsidence. The piled raft configuration had nine piles distributed in the center of the raft. The kaolin parameters were obtained, calibrated, and validated for the Hardening Soil Model (HSM), based on laboratory triaxial and oedometer test results. Also, a single pile load test was carried out in the centrifuge to get the resistance parameters used in the FEM. The developed numerical model reproduced satisfactorily soil and foundation consolidation displacements due, not only by the structural service load but also by the pore pressure drawdown. For load distribution on piles and raft, the model reproduces with good agreement the foundation behavior only for the structural service load, for pore pressure drawdown some adjustments on the embedded piles elements shaft and base resistance had to be done. The developed model allowed to identify the most sensitive parameters for this type of simulation, to define the types and stages of analysis that had the best fit for the physical model, and to obtain additional results to those measured in the physical model, e.g., the axial load distribution developed along the piles and therefore the magnitude of the negative skin friction, that is an important load that should be considered for the structural safety review of piled foundations subjected to this complex conditions.

Background Tuberculosis (TB) is a communicable, preventable and curable disease caused by the bacterium Mycobacterium tuberculosis (MTB). Peru is amongst the 30 countries with the highest burden of multidrug-resistant tuberculosis (MDR-TB) worldwide. In the fight against drug-resistant tuberculosis, the UKMYC6 microdilution plate was developed and validated by the CRyPTIC project. The objective of the study was to evaluate the use of the broth microdilution (BMD) plate methodology for susceptibility testing of drug-resistant MTB strains in Peru. Methods MTB strains isolated between 2015 and 2018 in Peru were used. 496 nationally-representative strains determined as drug-resistant by the routine 7H10 Agar Proportion Method (APM) were included in the present study. The Minimum Inhibitory Concentration (MIC) of 13 antituberculosis drugs were determined for each strain using the UKMYC6 microdilution plates. Diagnostic agreement between APM and BMD plate methodology was determined for rifampicin, isoniazid, ethambutol, ethionamide, kanamycin and levofloxacin. Phenotypes were set using binary (or ternary) classification based on Epidemiological cut-off values (ECOFF/ECV) proposed by the CRyPTIC project. Whole Genome Sequencing (WGS) was performed on strains with discrepant results between both methods. Results MIC distributions were determined for 13 first- and second-line anti-TB drugs, including new (bedaquiline, delamanid) and repurposed (clofazimine, linezolid) agents. MIC results were available for 80% (397/496) of the strains at 14 days and the remainder at 21 days. The comparative analysis determined a good agreement (0.64 ≤ k ≤ 0.79) for the drugs rifampicin, ethambutol, ethionamide and kanamycin, and the best agreement (k > 0.8) for isoniazid and levofloxacin. Overall, 12% of MIC values were above the UKMYC6 plate dilution ranges, most notably for the drugs rifampicin and rifabutin. No strain presented MICs higher than the ECOFF/ECV values for the new or repurposed drugs. Discrepant analysis using genotypic susceptibility testing by WGS supported half of the results obtained by APM (52%, 93/179) and half of those obtained by BMD plate methodology (48%, 86/179). Conclusions The BMD methodology using the UKMYC6 plate allows the complete susceptibility characterization, through the determination of MICs, of drug-resistant MTB strains in Peru. This methodology shows good diagnostic performances for rifampicin, isoniazid, ethambutol, ethionamide, kanamycin and levofloxacin. It also allows for the characterization of MICs for other drugs used in previous years against tuberculosis, as well as for new and repurposed drugs recently introduced worldwide.

Peru is amongst the 30 countries with the highest burden of multidrug-resistant tuberculosis worldwide. In the fight against drug-resistant tuberculosis, the UKMYC6 microtiter plate was developed and validated by the CRyPTIC project. Our objective was to evaluate the use of the broth microdilution UKMYC6 plate for susceptibility testing of drug-resistant Mycobacterium tuberculosis (MTB) strains in Peru. 496 nationally-representative MTB strains determined drug-resistant by the routine agar proportion method (APM) were selected. MICs of 13 anti-tuberculosis drugs were determined for each strain using the microdilution UKMYC6 plates and compared with the APM result. MIC distributions for APM-susceptible and APM-resistant strains were demonstrated for rifampicin, isoniazid, kanamycin, and levofloxacin, with reasonable agreement (0.64≤k≤0.79) for rifampicin, ethambutol, ethionamide and kanamycin and the best agreement for isoniazid and levofloxacin (k>0.8). No strain presented MICs higher than the CRyPTIC Epidemiological cut-off values for the new (bedaquiline, delamanid) or repurposed (clofazimine, linezolid) drugs. The microbroth dilution method using the UKMYC6 microtiter plate allowed the complete susceptibility characterization, through the determination of MICs, of drug-resistant Mycobacterium tuberculosis strains in Peru. This methodology showed a good diagnostic performance for the drugs rifampicin, isoniazid, kanamycin and levofloxacin drugs.

Introducción: Reconstruir historias contribuye a forjar identidades sólidas. El ejercicio interdisciplinario desde la metodología histórica, permite vincular la disciplina de enfermería con las prácticas tradicionales de la partería del México Antiguo enfocada en la actividad del cuidado de la mujer embarazada. Objetivo: Interpretar el cuidado de las parteras nahuas prehispánicas de México en las crónicas de fray Bernardino de Sahagún. Desarrollo: Se analiza el papel de las parteras nahuas prehispánicas tomando como fuente primaria el facsímil del Códice Florentino o Historia General de las Cosas de Nueva España de fray Bernardino de Sahagún, disponible en la Biblioteca Central de la Universidad Nacional Autónoma de México (UNAM), en conjunto con fuentes secundarias de investigadores especialistas de la cultura náhuatl. Con base en la hermenéutica para la historiografía de la Colonia, la investigación se organiza en dos dimensiones, de lo general a lo particular. Mientras que la primera muestra los aspectos generales, geográficos, la cosmogonía y cosmovisión de la población estudiada; la segunda corresponde a las características sociales, culturales, políticas y fenomenológicas como son símbolos, cualidades, divinidades, además de significaciones en torno a la partera. Conclusiones: El estudio de la historicidad de la partería devela prácticas tradicionales permeadas de la cosmovisión mesoamericana, de las cuales subyace un cuidado multidimensional que ve a la mujer como un reflejo del cosmos, la tierra y el origen de lo sagrado. Asimismo, desde la cosmovisión de la partera se identifica un ejercicio de prácticas tradicionales, de las cuales subyacen premisas clasificadas como supuestos epistemológicos a partir de la acción.

Inflammatory diseases remain critical health problems worldwide. The search for anti-inflammatory drugs is a primary activity in the pharmaceutical industry. Cacalol is a sesquiterpene with anti-inflammatory potential that is isolated from Psacalium decompositum, a medicinal plant with several scientific reports supporting its anti-inflammatory activity. Cacalol acetate (CA) is the most stable form. Nevertheless, the participation of CA in the main signaling pathway associated with inflammation is unknown. Our aim was to study the anti-inflammatory effect of CA and to determine its participation in NF-κB signaling. In TPA-induced edema in mice, CA produced 70.3% inhibition. To elucidate the influence of CA on the NF-κB pathway, RAW 264.7 macrophages were pretreated with CA and then stimulated with LPS, evaluating NF-ΚB activation, IKK phosphorylation, IΚB-α, p65, cytokine expression, and COX-2 release and activity. CA inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKB-α and p65 levels. CA also reduced expression and secretion of TNF-α, IL-1β, and IL-6. Additionally, it decreased the activity and expression of COX-2 mRNA. These data support that CA regulates the NF-κB signaling pathway, which might explain, at least in part, its anti-inflammatory effect. CA is a bioactive molecule useful for the development of anti-inflammatory agents with innovative mechanisms of action.

The antihyperglycemic activity of ethanolic extract from

Two photon interference in transverse momentum variables is presented via spatially resolved correlation measurements. Interest is devoted to study theoretically and experimentally the interference when the input photons are distinguishable in their spatial variables.

BACKGROUND: The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. PATIENTS AND METHODS: In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. RESULTS: In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36-0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37-0.64, P = 0.001). The most frequent grade 3-4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3-4 adverse event was fatigue (4.3% vs. 0%). CONCLUSIONS: Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients.

La rica tradición artesanal de México, e indudablemente de muchos otros países, ha sido utilizada por marcas de “prestigio” a nivel internacional sin darle reconocimiento a sus creadores. Esas imágenes autóctonas forman parte de una cosmología y una forma de ver el mundo y que en algunos casos son imágenes “sagradas” o bien, forman parte de rituales ancestrales. Cuando una marca internacional hace uso de diseños creados por miembros de comunidades autóctonas sin que medie permiso o contrato de uso de su iconografía o diseño de prendas ¿Estamos hablando de “INSPIRACIÓN” o de PLAGIO?

Health-related quality of life; Metastatic breast cancer; Neratinib Calidad de vida relacionada con la salud; Cáncer de mama metastásico; Neratinib Qualitat de vida relacionada amb la salut; Càncer de mama metastàtic; Neratinib Purpose To characterize health-related quality of life (HRQoL) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) from the NALA phase 3 study. Methods In NALA (NCT01808573), patients were randomized 1:1 to neratinib + capecitabine (N + C) or lapatinib + capecitabine (L + C). HRQoL was assessed using seven prespecified scores from the European Organisation for Research and Treatment of Cancer Quality Of Life Questionnaire core module (QLQ-C30) and breast cancer-specific questionnaire (QLQ-BR23) at baseline and every 6 weeks. Descriptive statistics summarized scores over time, mixed models evaluated differences between treatment arms, and Kaplan–Meier methods were used to assess time to deterioration in HRQoL scores of ≥ 10 points. Results Of the 621 patients randomized in NALA, patients were included in the HRQoL analysis if they completed baseline and at least one follow-up questionnaire. The summary, global health status, physical functioning, fatigue, constipation, and systemic therapy side effects scores were stable over time with no persistent differences between treatment groups. There were no differences in time to deterioration (TTD) for the QLQ-C30 summary score between treatment arms; the hazard ratio (HR) for N + C vs. L + C was 0.94 (95% CI 0.63–1.40). Only the diarrhea score worsened significantly more in the N + C arm as compared to the L + C arm, and this remained over time (HR for TTD for N + C vs. L + C was 1.71 [95% CI 1.32–2.23]). Conclusion In NALA, patients treated with N + C maintained their global HRQoL over time, despite a worsening of the diarrhea-related scores. These results may help guide optimal treatment selection for HER2-positive MBC. This work was supported by Puma Biotechnology Inc., Los Angeles, CA, USA [no grant number is applicable]. Puma Biotechnology Inc. funded the provision of editorial support provided by CMD Consulting and Miller Medical Communications.

In this paper a 3D numerical model using a software based on the Finite Element Method (FEM), was developed and validated using the results obtained in a geotechnical centrifuge model of a piled raft system founded in soft soils undergoing regional subsidence. The piled raft configuration had nine piles distributed in the center of the raft. The kaolin parameters were obtained, calibrated, and validated for the Hardening Soil Model (HSM), based on laboratory triaxial and oedometer test results. Also, a single pile load test was carried out in the centrifuge to get the resistance parameters used in the FEM. The developed numerical model reproduced satisfactorily soil and foundation consolidation displacements due, not only by the structural service load but also by the pore pressure drawdown. For load distribution on piles and raft, the model reproduces with good agreement the foundation behavior only for the structural service load, for pore pressure drawdown some adjustments on the embedded piles elements shaft and base resistance had to be done. The developed model allowed to identify the most sensitive parameters for this type of simulation, to define the types and stages of analysis that had the best fit for the physical model, and to obtain additional results to those measured in the physical model, e.g., the axial load distribution developed along the piles and therefore the magnitude of the negative skin friction, that is an important load that should be considered for the structural safety review of piled foundations subjected to this complex conditions.

A study of temporal variations of particulate matter in different size fractions (TSP, PM10, PM2.5) was undertaken in the city of San Francisco de Campeche (SFC), in southeast Mexico, in the years 2014 and 2015 in order to assess the contribution of the chemical components. The samples were analyzed using X-ray fluorescence (XRF) and ion exchange chromatography (IC) for PM10. XRF identified the presence of Al, Si, P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, and Zn. The results of a cluster analysis (CA) indicates a strong correlation of S and P in the three fractions due to agricultural land use and this may be related to the burning of biomass during the dry season. Also the CA also suggests that the elements Al, Si, K, Ca, Ti, Mn, and Fe can be associated with a geological origin. The results of the IC analysis show high levels of Na+, Cl−, and SO4−2 and the latter must be related to anthropogenic sources. The application of principal components analysis (PCA) suggests that Na+, Cl− and Mg+2 are associated with marine aerosols; NO3− and SO4−2 are from emissions related to fuel combustion due to increase in the number of motor vehicles in the city.

Evaluación de las mejores prácticas para seleccionar sustitutos y métodos para establecer metas de conservación en un país megadiverso La planificación sistemática de la conservación proporciona un marco para identificar áreas representativas de la biodiversidad, pero su eficacia depende de la elección de sustitutos y de las metas de conservación. México ha realizado análisis integrales y participativos de vacíos y omisiones en conservación. En este trabajo presentamos los resultados de dos evaluaciones independientes sobre sustitutos de la biodiversidad a fin de poner a prueba los criterios utilizados en México para identificar las prioridades espaciales de conservación. Se probó el efecto sombrilla de los mamíferos restringidos, endémicos y amenazados, y la influencia del establecimiento de las metas en la configuración espacial de la red de áreas de conservación, así como el desempeño de sustitutos taxonómicos. Los resultados muestran que el establecimiento de metas influye mucho en la configuración espacial y en los valores de unicidad de la red. La eficacia de la representación y la cobertura de las áreas de distribución de las especies variaron con la selección de los sustitutos, pero no con el establecimiento de las metas. Las especies amenazadas y las raras no estuvieron suficientemente representadas cuando se usaron otras especies como sustitutos, mientras que los mamíferos amenazados representaron el 90% de todas las especies. La eficacia de las redes diseñadas para un solo taxón de vertebrados varió mucho; los reptiles y anfibios obtuvieron mejores resultados que los obtenidos al azar, y lograron una alta representación de otros grupos taxonómicos en la red diseñada para dichos taxones., Systematic conservation planning provides a framework to identify representative areas of biodiversity, but its effectiveness depends on the choice of surrogates and targets. Mexico has conducted participatory and comprehensive gap analyses. We present the results of two independent surrogate assessments to test the criteria used in Mexico’s spatial conservation prioritization. We tested the surrogate efficiency of range restricted, endemic, and threatened mammals and the influence of target–setting on the spatial configuration of the conservation network, as well as the performance of taxonomic–based surrogates. Results show that target–setting heavily influences the spatial configuration and irreplaceability values of the conservation area network. Representation effectiveness and coverage of species distribution was sensitive to surrogate selection but not to target–setting. Threatened and rare species were poorly represented when other surrogate species were used, while threatened mammals represented 90 % of all species. The effectiveness of networks designed for a single vertebrate taxon varied greatly; reptiles and amphibians performed better than random achieving high species representation.

Background: TILs in HER2+ breast cancer (BC) predict 1) prognosis in early setting, 2) complete pathological response (pCR) following neoadjuvant antiHER2-based therapy and 3) response to trastuzumab and pembrolizumab in the metastatic setting. However, less is known regarding changes in TILs during antiHER2-based treatment. Methods: Stromal TILs where evaluated centrally using H/E slides in tumor samples from the PAMELA (NCT01973660) neoadjuvant phase II trial. Briefly, 151 women with HER2+ BC were treated with lapatinib and trastuzumab, and hormonal therapy if HR positive, for 18 weeks. TIL levels were determined at baseline (n=148), after 2 weeks of treatment (n=134) and at surgery (n=137). Expression of 560 genes, including immune-related genes (e.g. CD8A, CD4, PD1 and PDL1) was measured at the same timepoints (baseline n=151, 2-weeks n=144, surgery n=144) using the nCounter platform. Intrinsic subtyping at baseline was determined using the PAM50 gene expression predictor. Changes in TILs between 2 time-points were determined by paired t-tests. Correlation of TILs with gene expression was assessed by quantitative SAM analysis using a False Discovery Rate Results: Compared to baseline, a significant increase in TILs was observed at week 2 in HR- (p Conclusions: In early HER2+ BC, a general increase in TILs is observed following 2 weeks of dual HER2 blockade. This observation is mostly observed in HR- and HER2-E subtype, but regardless of pathological response at surgery. After 2 weeks of treatment, TILs consistently decrease in patients achieving a pCR, whereas two main patterns of TILs expression are observed in patients with residual disease at surgery. Nonetheless, most residual tumors at surgery are inflamed (i.e. TILs ≥5%) and might be good candidates for clinical trials evaluating adjuvant immune checkpoint inhibitors. Citation Format: Griguolo G, Holgado E, Cortés J, Fasani R, Pascual T, Paré L, Bermejo B, Oliveira M, Morales S, Martinez N, Vidal M, Pernas S, Lopez R, Muñoz M, Galvan P, Garau I, Manso L, Alarcón J, Martínez E, Villagrasa P, LLombart-Cussac A, Prat A, Nuciforo P. Dynamics of tumor-infiltrating lymphocytes (TILs) during neoadjuvant dual HER2 blockade in HER2-positive (HER2+) breast cancer in the absence of chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-08.

Background: HER2-positive (HER2+) breast cancer (BC) is composed of 4 molecular subtypes: Luminal A and B, HER2-enriched (HER2-E) and Basal-like. Among them, the HER2-E is highly sensitive to anti-HER2 treatment. However, ˜60% of HER2-E tumors do not achieve a pathological complete response (pCR) following neoadjuvant dual HER2 blockade without chemotherapy. Here, we aimed to better understand the molecular changes of the HER2-E subtype during anti-HER2 treatment. Methods: Gene expression was evaluated in 101 patients with HER2-E tumors from the PAMELA neoadjuvant phase II trial (Lancet Oncol 2017). Briefly, women with HER2+ BC were treated with lapatinib and trastuzumab (and hormonal therapy if hormone receptor [HR]-positive) for 18 weeks. The median time between the last dose of treatment and surgery was 35 days (range=213; interquartile range=16). Expression of the PAM50 genes and 6 PAM50 signatures (Luminal A, Luminal B, HER2-E, Basal-like, normal-like and the PAM50 proliferation score) were determined using the nCounter platform at baseline (n=101), after 2 weeks of treatment (n=96) and in residual tumors (non-pCR) at surgery (n=57). Same analyses were done in 2 HER2+/HER2-E cell line models (BT474 [HR+] and SKBR3 [HR-]) following in vitro treatment with trastuzumab in combination with lapatinib. Biological changes between 2 time-points were determined by paired t-tests with a false discovery rate (FDR) Results: After 2 weeks of treatment, 85.7% and 94.6% of the 56 genes/signatures were found differentially expressed (FDR Conclusions: Dual HER2 blockade in the HER2-E subtype induces large biological changes that lead to a more low-proliferative Luminal A phenotype both in tumors and in vitro models, especially in HER2-E/HR+ disease. These phenotypic changes are reversible upon stopping anti-HER2 treatment. This finding supports the use of maintenance anti-HER2 treatment +/- endocrine therapy (if HR+) in advanced HER2+ BC. Citation Format: Brasó-Maristany F, Griguolo G, Llombart-Cussac A, Pascual T, Paré L, Bermejo B, Oliveira M, Morales S, Martinez N, Vidal M, Pernas S, Lopez R, Muñoz M, Galvan P, Garau I, Manso L, Alarcón J, Martínez E, Villagrasa P, Cortés J, Prat A. Gene signatures and subtype changes during HER2 dual blockade in PAM50 HER2-enriched HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-07.

We experimentally compare the optical and electrical characteristics of Light Emitting Capacitors (LECs) using textured and polished silicon surface. The goal of this work is focused to investigate the influence of the roughening of the surface of the silicon substrates in the electro-optical properties of LECs fabricated with off-stoichiometric silicon oxide (SiOx). The textured surface is produced by reactive ion etching using Ar and SF6 as ion sources. It exhibits an average roughness of 4.0 ± 0.2 nm, with a spike density of 3.7 ± 1.8 × 1010 cm−2. The SiOx is deposited by low-pressure chemical vapor deposition on polished and textured substrates. The turn-on electric field of LECs using textured substrate is reduced from 8.5 MV/cm to 7.0 MV/cm, and the power conversion is improved 4.1 times compared with LECs with polished substrate. Furthermore, in LECs fabricated over textured substrates, the electrical current value increases at low voltages and once it reaches the high current regime, this value remains constant. Then, the spikes on the silicon substrate improve carrier injection towards the SiOx at low electric fields, causing more trapping of electrons in the SiOx and enhancing the electroluminescence response at high electric fields. An explanation of the enhanced electro-emission mechanisms is given. Also, a figure of merit that allows the comparison with LECs with different technological characteristics is proposed.

Taca de plasma sec; Hepatitis C; Targeta de separació de plasma Mancha de plasma seco; Hepatitis C; Tarjeta de separación de plasma Dried plasma spot; Hepatitis C; Plasma separation card Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC. We thank all the patients and family members for participating in the PAMELA study. This study was supported, in part, by Instituto de Salud Carlos III—PI16/00904, The Breast Cancer Research Foundation and Fundación Científica Asociación Española Contra el Cáncer (Ayuda Postdoctoral AECC 2017), Fundación Merck—Immunología and Comprehensive Programme of Cancer Immunotherapy & Immunology (CAIMI) BBVA Foundation (grant number 89/2017). Acknowledgements to the Cellex Foundation for providing research facilities and equipment. G.G. acknowledges funding from a 2019 Conquer Cancer Foundation YIA in Breast Cancer. This work has been realised in the Surgery and Morphological Sciences Doctorate framework of Univ Autonoma de Barcelona.

This study evaluates the potential of different algae extracts (Crassiphycus corneus, Cc; Ulva ohnoi, Uo; Arthrospira platensis, Ap; Haematococcus pluvialis, Hp) as additives for the preservation of rainbow trout fillets. The extracts were prepared with different water to ethanol ratios from the four algae species. The highest ferric reducing antioxidant power (FRAP) was observed in Uo extracted in 80% ethanol. Ap aqueous extract also had considerable FRAP activity, in agreement with a high total phenolic content. Radical scavenging activity (DPPH) was higher in Cc 80% ethanol extract, in agreement with a high total carotenoid content. In fact, when the algae aqueous extracts were assayed on the fish fillets, their antioxidant activity exceeded that of ascorbic acid (ASC). All algae extracts delayed microbial growth and lipid oxidation processes in trout fillets throughout the cold storage period compared to controls, and also improved textural parameters, these effects being more evident for Ap and Hp. With respect to the color parameters, the Hp extract prevented the a* values (redness) from decreasing throughout cold storage, a key point when it comes to colored species, not least salmonids. On the other hand, the Ap extract was not as effective as the rest of treatments in avoiding a* and b* decrease throughout the storage period, and thereby the color parameters were impaired. The results obtained, together with the natural origin and the viability for large-scale cultivation, make algae extracts interesting fish preservative agents for the food industry.

Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells.RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Transfected cells were treated with glycine (10 mM). The expressions of TNF-α and IL-6 mRNA were measured by qRT-PCR, while concentrations were quantified by ELISA.Glycine decreased the expression and concentration of TNF-α and IL-6; this effect did not occur in the absence of TNF-α receptor due to siRNA. In contrast, glycine produced only slight changes in the expression of TNF-α and IL-6 in the absence of the glycine receptor due to siRNA. A docking analysis confirmed the possibility of binding glycine to the TNF-α1a receptor.These findings support the idea that glycine could partially inhibit the binding of TNF-α to its receptor and provide clues about the mechanisms by which glycine inhibits the secretion of pro-inflammatory adipokines in adipocytes through the TNF-α receptor.

The antihyperglycemic activity of ethanolic extract from Salvia polystachya (EESpS) and its products was evaluated using in vivo, ex vivo and in silico assays; additionally, an acute toxicity assay was evaluated. EESpS was classified as a nontoxic class 5 drug. EESpS, ethyl acetate fraction (EtOAcFr), secondary-6-fraction (SeFr6), ursolic acid (UA), and oleanolic acid (OA) reduced the hyperglycemia in DM2 mice. α-glucosidase inhibition was evaluated with oral sucrose and starch tolerance tests (OSuTT and OStTT), an intestinal sucrose hydrolysis (ISH) assay and molecular docking studies using acarbose as control. SGLT1 inhibition was evaluated with oral glucose and galactose tolerance tests (OGTT and OGaTT), an intestinal glucose absorption (IGA) assay and molecular docking studies using canagliflozin as the control. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak, similar to the control drugs. During the ISH, IC50 values of 739.9 and 726.3 µM for UA and OA, respectively, were calculated. During the IGA, IC50 values of 966.6 and 849.3 for UA, OA respectively, were calculated. Finally, during the molecular docking studies, UA and OA showed ∆G values of −6.41 and −5.48 kcal/mol−1, respectively, on α-glucosidase enzymes. During SGLT1, UA and OA showed ∆G values of −10.55 and −9.65, respectively.

The main aim of FE model updating is to iteratively correct the inaccurate parameters in a structural model so that the agreement between numerical predictions and modal test results is improved. Modeling the boundary conditions and contact interfaces between the different components is a challenge that needs to be taken into account in regards to the computational cost of the model for the iterative stage of the study. For instance, an extremely detailed model is of no use if each iteration takes hours to solve.

Resumen La mayor parte de los pacientes que superan la infeccion por SARS-CoV-2 no presentan complicaciones ni requieren un seguimiento especifico, pero una proporcion significativa (especialmente aquellos con formas clinicas moderadas/graves de la enfermedad) necesitan un seguimiento clinico-radiologico. Aunque apenas existen referencias o guias clinicas sobre el seguimiento a largo plazo de estos pacientes post-COVID-19, se estan realizando pruebas radiologicas y constituyendo consultas monograficas de vigilancia en la mayor parte de los centros hospitalarios para atender sus necesidades. El proposito de este trabajo es compartir nuestra experiencia en el manejo del paciente post-COVID-19 en dos instituciones que han tenido una elevada incidencia de la COVID-19 y proponer unas recomendaciones generales de seguimiento desde una perspectiva clinica y radiologica.

Inflammatory diseases remain critical health problems worldwide. The search for anti-inflammatory drugs is a primary activity in the pharmaceutical industry. Cacalol is a sesquiterpene with anti-inflammatory potential that is isolated from