Retinol and alpha-Tocopherol Contents, Fat Color, and Lipid Oxidation as Traceability Tools of the Feeding System in Suckling Payoya Kids

Simple Summary In Spain, goat farms are mainly oriented to milk production, although kid meat contributes to their sustainability, particularly in autochthonous breeds such as Payoya. Usually, kids are fed artificial milk until slaughter, allowing the use of goat milk for the commercialization of cheese, but several studies indicate that feeding kids natural milk improve the quality of their meat. The aim of the present study was to find traceability markers to discriminate between kids that are fed natural milk (with different goat management systems) and those fed a milk replacer. For this purpose, we proposed the quantification of retinol and alpha-tocopherol contents in plasma and fat, the amount of kidney fat, lipid oxidation, and some fat color parameters as potential markers. The results showed that plasma retinol concentrations were higher in kids fed feeding systems with synthetic vitamins. The plasma alpha-tocopherol concentrations were higher in kids fed grass-based feeding systems (which contain the natural forms of these vitamins). A dilution effect was shown for the retinol concentration in fat. Collectively, the analyzed variables allowed a discriminant analysis to correctly classify kids according to their feeding system and could ensure traceability to consumers. The effects of Payoya kid feeding systems on the fat-soluble vitamin (retinol/alpha-tocopherol) contents, fat content, fat color, and the oxidation index were evaluated to determine their potential for use as feeding system traceability tools. Four groups of Payoya kids (55 animals in total) fed milk exclusively were studied: a group fed a milk replacer (MR) and three groups fed natural milk from dams reared with different management systems (mountain grazing (MG), cultivated meadow (CM) and total mixed ration (TMR)). Kids were slaughtered around one month of age and 8 kg of live weight. Kids from the MG and CM groups presented lower retinol (5.56 and 3.72 mu g/mL) and higher alpha-tocopherol plasma (11.43 and 8.85 mu g/mL) concentrations than those from the TMR and MR groups (14.98 and 22.47 mu g/mL of retinol; 2.49 and 0.52 mu g/mL of alpha-tocopherol, respectively) (p < 0.001). With respect to fat, kids with a higher intramuscular fat percentage (CM and TMR groups) had lower retinol contents (16.52 and 15.99 mu g/mL, respectively) than kids from the MG and MR groups (26.81 and 22.63 mu g/mL, respectively) (p < 0.001). A dilution effect of vitamins on fat was shown: the higher the amount of fat, the lower the vitamin concentrations, the higher the lipid oxidation index (MDA), and the lower the SUM (absolute value of the integral of the translated spectra between 450 and 510 nm). A discriminant analysis that included all studied variables showed that 94.4% of the kids were classified correctly according to their feeding system and could allow traceability to the consumer

Src kinase activity and SH2 domain regulate the dynamics of Src association with lipid and protein targets

Src functions depend on its association with the plasma membrane and with specific membrane-associated assemblies. Many aspects of these interactions are unclear. We investigated the functions of kinase, SH2, and SH3 domains in Src membrane interactions. We used FRAP beam-size analysis in live cells expressing a series of c-Src–GFP proteins with targeted mutations in specific domains together with biochemical experiments to determine whether the mutants can generate and bind to phosphotyrosyl proteins. Wild-type Src displays lipid-like membrane association, whereas constitutively active Src-Y527F interacts transiently with slower-diffusing membrane-associated proteins. These interactions require Src kinase activity and SH2 binding, but not SH3 binding. Furthermore, overexpression of paxillin, an Src substrate with a high cytoplasmic population, competes with membrane phosphotyrosyl protein targets for binding to activated Src. Our observations indicate that the interactions of Src with lipid and protein targets are dynamic and that the kinase and SH2 domain cooperate in the membrane targeting of Src

Simulación dinámica para el dimensionado de una instalación basada en energías renovables que abastece energéticamente a una construcción Pasivhaus de emisiones cero

Dimensionamiento energético de una construcción en tres escenarios climáticos por medio del software HOMER ENERGY.<br /

A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Background: pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods: epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K array) from Illumina. The epigenetic silencing of those methylated genes in the discovery cohort were validated by bisulfite pyrosequencing (PyroMark Q96 System version 2.0.6, Qiagen) and qRT-PCR in an independent cohort of TN patients and in TN cell lines. Results: twenty-four and 30 patients were included in the discovery and validation cohorts, respectively. In the discovery cohort, nine genes were differentially methylated: six presented higher methylation in non-responder patients (LOC641519, LEF1, HOXA5, EVC2, TLX3, CDKL2) and three greater methylation in responder patients (FERD3L, CHL1, and TRIP10). After validation, a two-gene (FER3L and TRIP10) epigenetic score predicted RCB = 0 with an area under the ROC curve (AUC) = 0.905 (95% CI = 0.805-1.000). Patients with a positive epigenetic two-gene score showed 78.6% RCB = 0 versus only 10.7% RCB = 0 if signature were negative. Conclusions: these results suggest that pCR in TNBC could be accurately predicted with an epigenetic signature of FERD3L and TRIP10 genes. Further prospective validation of these findings is warranted

Evaluación de la experiencia asistencial en pacientes con Enfermedad Renal Crónica Avanzada

Introducción: Los resultados clínicos están más condicionados al papel activo del paciente en su autocuidado que por la cualificación profesional, por ello es importante capturar la experiencia del paciente para mejorar la calidad asistencial. Objetivo: Evaluar la experiencia del paciente renal en la atención recibida por los profesionales. Material y Método: Estudio descriptivo transversal en pacientes de Hemodiálisis y consulta de Enfermedad Renal Crónica Avanzada. Se administró el Instrumento de Evaluación de la eXperiencia del PAciente Crónico, 15 ítems que puntuaron de 0 (peor) a 10 (mejor experiencia) y que, midió 3 factores: interacciones productivas, autogestión del paciente y nuevo modelo relacional. Los datos se analizaron con el software R. Resultados: Se incluyeron 76 pacientes. La puntuación de la experiencia del paciente (ítems 1-11) fue de 6,68±1,41 puntos, siendo para cada factor: “interacciones productivas” (9,00±1,37 puntos), “autogestión del paciente” (7,80±1,78 puntos) y “nuevo modelo relacional” (1,86±2,01 puntos). Los ítems 12-15 obtuvieron bajas puntuaciones con valores medios entre 2-4 puntos. Al comparar los pacientes de consulta y hemodiálisis, el grupo hemodiálisis puntuó menos en los factores: “autogestión del paciente” (p=0,01) y “nuevo modelo relacional” (p=0,03); y con respecto a los ítems 12-15, también se obtuvo menor puntuación en el ítem “atención continuada tras un ingreso/urgencia (p=0,04). Conclusiones: La experiencia del paciente renal es positiva en la interacción con los profesionales y en la gestión del autocuidado, pero surgen áreas de mejora como el uso de tecnología digital, compartir experiencias con iguales y, el seguimiento de la salud tras un episodio agudo

How Frequently Benign Uterine Myomas Appear Suspicious for Sarcoma as Assessed by Transvaginal Ultrasound?

Uterine myomas may resemble uterine sarcomas in some cases. However, the rate of benign myomas appearing as sarcomas at an ultrasound examination is not known. The objective of this study is to determine the percentage of benign myomas that appear suspicious for uterine sarcoma on ultrasound examination. This is a prospective observational multicenter study (June 2019-December 2021) comprising a consecutive series of patients with histologically proven uterine myoma after hysterectomy or myomectomy who underwent transvaginal and/or transabdominal ultrasound prior to surgery. All ultrasound examinations were performed by expert examiners. MUSA criteria were used to describe the lesions (1). Suspicion of sarcoma was established when three or more sonographic features, described by Ludovisi et al. as "frequently seen in uterine sarcoma", were present (2). These features are no visible myometrium, irregular cystic areas, non-uniform echogenicity, irregular contour, "cooked" appearance, and a Doppler color score of 3-4. In addition, the examiners had to classify the lesion as suspicious based on her/his impression, independent of the number of features present. Eight hundred and ten women were included. The median maximum diameter of the myomas was 58.7 mm (range: 10.0-263.0 mm). Three hundred and forty-nine (43.1%) of the patients had more than one myoma. Using the criterion of &gt;3 suspicious features, 40 (4.9%) of the myomas had suspicious appearance. By subjective impression, the examiners considered 40 (4.9%) cases suspicious. The cases were not exactly the same. We conclude that approximately 5% of benign uterine myomas may exhibit sonographic suspicion of sarcoma. Although it is a small percentage, it is not negligible

Endozoochory by native and exotic herbivores in dry areas: consequences for germination and survival of Prosopis seeds

Mammalian herbivores can play a role in the endozoochorous dispersal of Prosopis seeds in the arid zones of Argentina, and the introduction of exotic mammals can change relevant parameters of the plant's reproductive ecology. Our specific goals were to quantify the seeds of Prosopis flexuosa, P. chilensis and P. torquata contained in the faeces of native [mara (Dolichotis patagonum), guanaco (Lama guanicoe)] and exotic [donkey (Equus asinus) and hare (Lepus europaeus)] mammals, and to determine the mortality, germination percentage and germination speed of seeds borne in faeces, compared with those collected from trees. In 2006, seeds were collected directly from trees or removed from mammal faeces. Seeds were counted and classified as apparently healthy or damaged. P. torquata and P. flexuosa seeds were found in the dung of guanaco, hare and mara, whereas only P. flexuosa seeds appeared in donkey faeces. P. chilensis seeds were only found in guanaco faeces. There was a notable relative abundance of seeds contained in small herbivore faeces in comparison to the large herbivores. The passage through the digestive tract of animals modified seed germination capacity and speed, with great variability between animal species. Guanacos had greater effects than donkeys on mortality, germination percentage and germination speed. Differences between the effects of both smaller-sized herbivores on seeds were much smaller.Fil: Campos, Claudia Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Peco, Begoña. Universidad Autónoma de Madrid; EspañaFil: Campos Valeria. Universidad Nacional de San Juan; ArgentinaFil: Malo Arrázola, Juan Esteban. Universidad Autónoma de Madrid; EspañaFil: Giannoni, Stella Maris. Universidad Nacional de San Juan; ArgentinaFil: Suarez Francisco. Universidad Autónoma de Madrid; Españ

Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma?

Introduction: Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC. Methods: In this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry. Results: One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001). Discussion: The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).This work was supported by the Instituto de Salud Carlos III (grants PI17/01304 to J.C and M.C; grant PI16/00766 to F.B., and a Miguel Servet grant to J.C, cofunded by the European Regional Development Fund (ERDF) (CPII18/00026), through the Plan Estatal de Investigacion Científica y Tecnica y de Innovación, and Agencia de Gestiò d’Ajuts Universitaris i de Recerca (2017SGR653 and 2017SGR1035). CIBERehd is funded by the Instituto de Salud Carlos III. We also acknowledge the support of the CERCA Programme/Generalitat de Catalunya, and the Xarxa de Bancs de Tumors de Catalunya (XBTC)

Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice

Chronic kidney disease; Diabetic nephropathy; Endothelin receptor antagonistsEnfermedad renal crónica; Nefropatía diabética; Antagonistas de los receptores de endotelinaMalaltia renal crònica; Nefropatia diabètica; Antagonistes dels receptors d'endotelinaTreatments with sodium–glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin–angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model.The following study was funded with Spanish government grants (FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII (PI17/00257 and RICORS RD21/0005/0016)) and with financial support from Boehringer Ingelheim Pharma GmbH. The funders had no role in study design, analyses, interpretation of the data, drafting of the manuscript, or decision to submit the manuscript for publication. The funders were allowed to comment on the manuscript prior to publication; however, the final wording was at the full discretion of the investigators