Obtención de barras nutritivas a base de centeno (Secale cereale L), amaranto (Amaranthus hipochondriacus) y stevia (Stevia rebaudiana ertoni) como fuentes de proteínas, vitaminas y calorías

The increase in health problems related to poor nutrition has pushed many investigations to focus on the use of whole foods, especially cereals and pseudocereals. In this sense, the objective of this work was to develop nutritional bars based on Rye (factor A), Amaranth (factor B) and Stevia (factor C) as sources of protein, vitamins and calories. For this purpose, analyzes were carried out on the raw material such as: moisture content, fat or ethereal extract, protein content, fiber and determination of vitamin D or calciferol, in the process I re-blanched, roasted, then the bars. In the finished product, organoleptic analysis and nutritional determination such as proteins, fiber, vitamins and calories, carbohydrates, fat, humidity, ashes, sugars were carried out. According to the sensory analysis, it was determined that treatment 1 presented better acceptance by the tasters. In addition, after the physical-chemical and nutritional analysis of the bars, the results were 10.2% protein, 2.16% fat; dietary fiber 8.71%; total carbohydrates 52.4%; ashes 1.01%; 25.5% moisture, providing 49 kcal and 3 kcal of fat per unit consumed, values that have been calculated based on a diet of 2000 calories per day. Finally, it was found that 18 g of rye; 4 g of amaranth and 1 mL of Stevia meets the sensory and nutritional characteristics within the parameters established in Ecuadorian standards, providing a minimum number of calories, making it ideal for people with diabetes, overweight, obesity, and malnutrition.El incremento de problemas de salud relacionado a la mala nutrición ha empujado a que muchas investigaciones se centren en el aprovechamiento de alimentos integrales, especialmente cereales y pseudocereales. En tal sentido, el objetivo del presente trabajo fue Elaborar barras nutritivas a base de Centeno (factor A), Amaranto (factor B) y Stevia (factor C) como fuentes de proteínas, vitaminas y calorías. Para el efecto, se realizaron análisis organolépticos a las barras obtenidas mediante la participación de un panel de catadores semi entrenados. También, se efectuaron análisis físico químicos tanto a las materias primas como al producto terminado, y análisis de composición nutricional del mejor tratamiento obtenido. De acuerdo con los análisis sensoriales se determinó que el tratamiento 1 presentó mejor aceptación por parte de los catadores. Además, tras los análisis físico-químicos y nutricional de las barras, los resultados fueron, en proteína 10,2%, grasa 2,16%; fibra dietética 8,71%; carbohidratos totales 52,4%; cenizas 1,01%; humedad 25,5%, aportando un 49 kcal y 3 kcal de la grasa por unidad consumida, valores que han sido calculados en base a una dieta de 2000 calorías al día. Finalmente se comprobó que 18 g de centeno; 4 g de amaranto y 1 mL de Stevia cumple con las características sensoriales y nutricionales dentro de los parámetros establecidos en las normas ecuatorianas, aportando una mínima cantidad de calorías siendo ideal para personas con diabetes, sobrepeso, obesidad y desnutrición

Preclinical assessment of CAR-NK cell-mediated killing efficacy and pharmacokinetics in a rapid zebrafish xenograft model of metastatic breast cancer

Natural killer (NK) cells are attractive effectors for adoptive immunotherapy of cancer. Results from first-in-human studies using chimeric antigen receptor (CAR)-engineered primary NK cells and NK-92 cells are encouraging in terms of efficacy and safety. In order to further improve treatment strategies and to test the efficacy of CAR-NK cells in a personalized manner, preclinical screening assays using patient-derived tumor samples are needed. Zebrafish (Danio rerio) embryos and larvae represent an attractive xenograft model to study growth and dissemination of patient-derived tumor cells because of their superb live cell imaging properties. Injection into the organism’s circulation allows investigation of metastasis, cancer cell-to-immune cell-interactions and studies of the tumor cell response to anti-cancer drugs. Here, we established a zebrafish larval xenograft model to test the efficacy of CAR-NK cells against metastatic breast cancer in vivo by injecting metastatic breast cancer cells followed by CAR-NK cell injection into the Duct of Cuvier (DoC). We validated the functionality of the system with two different CAR-NK cell lines specific for PD-L1 and ErbB2 (PD-L1.CAR NK-92 and ErbB2.CAR NK-92 cells) against the PD-L1-expressing MDA-MB-231 and ErbB2-expressing MDA-MB-453 breast cancer cell lines. Injected cancer cells were viable and populated peripheral regions of the larvae, including the caudal hematopoietic tissue (CHT), simulating homing of cancer cells to blood forming sites. CAR-NK cells injected 2.5 hours later migrated to the CHT and rapidly eliminated individual cancer cells throughout the organism. Unmodified NK-92 also demonstrated minor in vivo cytotoxicity. Confocal live-cell imaging demonstrated intravascular migration and real-time interaction of CAR-NK cells with MDA-MB-231 cells, explaining the rapid and effective in vivo cytotoxicity. Thus, our data suggest that zebrafish larvae can be used for rapid and cost-effective in vivo assessment of CAR-NK cell potency and to predict patient response to therapy

Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect in vivo

IntroductionNatural killer 92 (NK-92) cells are an attractive therapeutic approach as alternative chimeric antigen receptor (CAR) carriers, different from T cells, once they can be used in the allogeneic setting. The modest in vivo outcomes observed with NK-92 cells continue to present hurdles in successfully translating NK-92 cell therapies into clinical applications. Adoptive transfer of CAR-NK-92 cells holds out the promise of therapeutic benefit at a lower rate of adverse events due to the absence of GvHD and cytokine release syndrome. However, it has not achieved breakthrough clinical results yet, and further improvement of CAR-NK-92 cells is necessary.MethodsIn this study, we conducted a comparative analysis between CD19-targeted CAR (CAR.19) co-expressing IL-15 (CAR.19-IL15) with IL-15/IL-15Rα (CAR.19-IL15/IL15Rα) to promote NK cell proliferation, activation, and cytotoxic activity against B-cell leukemia. CAR constructs were cloned into lentiviral vector and transduced into NK-92 cell line. Potency of CAR-NK cells were assessed against CD19-expressing cell lines NALM-6 or Raji in vitro and in vivo in a murine model. Tumor burden was measured by bioluminescence.ResultsWe demonstrated that a fourth- generation CD19-targeted CAR (CAR.19) co-expressing IL-15 linked to its receptor IL-15/IL-15Rα (CAR.19-IL-15/IL-15Rα) significantly enhanced NK-92 cell proliferation, proinflammatory cytokine secretion, and cytotoxic activity against B-cell cancer cell lines in vitro and in a xenograft mouse model.ConclusionTogether with the results of the systematic analysis of the transcriptome of activated NK-92 CAR variants, this supports the notion that IL-15/IL-15Rα comprising fourth-generation CARs may overcome the limitations of NK-92 cell-based targeted tumor therapies in vivo by providing the necessary growth and activation signals

Relación del covid – 19 y la dermatomiositis asociada al anticuerpo anti – MDA-5

Anti-melanoma with gene 5 (MDA-5) is an antibody associated with the rheumatologic pathology dermatomyositis, and this antibody has been demonstrated in complications in rheumatologic and pulmonary diseases, which can be fatal. Objective: To determine the relationship between COVID-19 and dermatomyositis associated with anti-MDA-5 antibody. Methodology: A bibliographic review of the last 5 years was carried out. A total of 21 articles were identified including original and review articles. Results: Both MDA-5-DM and COVID-19 appear to share activation of the Interferon type I signaling pathway. COVID-19 infection activates cytoplasmic viral RNA sensors such as RIG-I and MDA-5. The recent description of new cohorts of patients with a broader range of clinical features of presentation has broadened the spectrum of anti-MDA-5 MD disease associated with COVID-19. Knowledge of the condition and its possible manifestations is key to early detection and improved survival. Anti-MDA-5 has a prevalence in 2019 coronavirus patients, and increases when mRNA vaccine is administered causing increased clinical and mortality in patients. further studies are needed to improve the relationship.El Anti-melanoma con el gen 5(MDA-5) es un anticuerpo asociado a la patología reumatológica dermatomiositis, y este anticuerpo ha sido demostrado en complicaciones en la enfermedades reumatológicas y pulmonares, las cuales pueden llegar a ser mortales. Objetivo: Determinar la relación del COVID – 19 y la dermatomiositis asociada al anticuerpo anti – MDA-5. Metodología: se realizó una revisión bibliográfica de los últimos 5 años. Se identificaron un total de 21 artículos entre ellos artículos originales y de revisión. Resultados: Tanto MDA-5-DM como COVID-19 parecen compartir activación de la vía de señalización Interferón tipo I. La infección por COVID-19 activa sensores virales citoplasmáticos de ARN como el RIG-I y MDA-5. La descripción reciente de nuevas cohortes de pacientes con una gama más amplia de características clínicas de presentación ha ampliado el espectro de la enfermedad de la DM anti-MDA-5 asociada con el Covis-19. El conocimiento de la afección y sus posibles manifestaciones es clave para la detección temprana y una mejor supervivencia. El Anti-MDA-5 tiene una prevalencia en los pacientes con coronavirus del 2019, y aumenta cuando se administra la vacuna ARNm provocando un incremento de la clínica y de la mortalidad de los pacientes. se necesitan más estudios para mejorar la relación

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

K0S and Λ production in Pb-Pb collisions at sNN−−−−√=2.76 TeV

The ALICE measurement of K0S and Λ production at midrapidity in Pb-Pb collisions at sNN−−−√=2.76  TeV is presented. The transverse momentum (pT) spectra are shown for several collision centrality intervals and in the pT range from 0.4  GeV/c (0.6  GeV/c for Λ) to 12  GeV/c. The pT dependence of the Λ/K0S ratios exhibits maxima in the vicinity of 3  GeV/c, and the positions of the maxima shift towards higher pT with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate pT is not observed in pp interactions at s√=0.9  TeV and at s√=7  TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured pT spectra above 2  GeV/c progressively decouple from hydrodynamical-model calculations. For higher values of pT, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the pT dependence of the Λ/K0S ratio

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe