Efecto de la consanguinidad y selección sobre los componentes de un índice productivo, en ratones bajo apareamiento estrecho

In order to examine the influence of inbreeding depression on some productive characteristics of the laboratory mouse, 871 records were reanalyzed, which were from 20 generations in a line with narrow inbred crossing with selection for a productive index (WOFW) comparing with a line without selection, with inbred crossing (n= 135). Inbreeding coefficients (F) were calculated for each generation. In all the components of the index (reproductive life, fertile postpartum estruses and litter size), the two lines were compared, in the 15 available generations of the non-selected one, by the least squares method, grouping every five generations. The selected one was analyzed in the 20 generations for intergenerational differences with the same method. Inbreeding depression was estimated in all generations with a linear regression of consanguinity (expressed in 10 %) in all components. A significant difference (P<0.01) was observed between lines in the variables analyzed. The fertile postpartum estruses of the selected line remained constant, there was a decrease of 0.331 in the non-selected one (P<0.01). The productive index remained stable (increased 0.071) in the selected one, in the non-selected one it decreased (0.39) until disappearing (G15). Inbreeding depression impacted the reproductive life of both, decreased 4.741 d in the selected one vs 7.718 d in the non-selected one (P<0.01). In the non-selected one, it affected mortality at weaning and estrous cycle, the selection to the index counteracted that impact, probably due to the selection of genes that favor the gonadal development of mice.Con objeto de examinar la influencia de la depresión endogámica en algunas características productivas del ratón de laboratorio, se reanalizaron 871 registros provenientes de 20 generaciones en una línea con cruza consanguínea estrecha con selección a un índice productivo (CNHS) comparando con una línea sin selección, con cruzamiento endogámico (n= 135). Se calcularon los coeficientes de endogamia (F) para cada generación. En todos los componentes del índice (vida reproductiva, estros postparto fértiles y tamaño de camada), se compararon las dos líneas, en las 15 generaciones disponibles de la no seleccionada, por método de mínimos cuadrados, agrupando cada cinco generaciones. La seleccionada, se analizó en las 20 generaciones, para diferencias intergeneracionales con el mismo método. La depresión endogámica se estimó en todas las generaciones con una regresión lineal de consanguinidad (expresada en 10 %) en todos los componentes. Se observó diferencia significativa (P<0.01) entre líneas en las variables analizadas. Los estros post parto fértiles de la línea seleccionada se mantuvieron constantes, hubo un decremento de 0.331 en la no seleccionada (P<0.01). El índice productivo se mantuvo estable (aumentó 0.071) en la seleccionada, en la no seleccionada disminuyó (0.39) hasta desaparecer (G15). La depresión endogámica impactó en la vida reproductiva de ambas, decreció 4.741 días en la seleccionada vs. 7.718 días en la no seleccionada (P<0.01). En la no seleccionada afectó en mortalidad al destete y ciclo estral, la selección al índice contrarrestó ese impacto, probablemente debido a la selección de genes que favorecen el desarrollo gonadal de los ratones.

Parámetros genéticos para producción de leche de ganado Holstein en dos modalidades de control de producción

Variance components and genetic parameters were estimated for total milk production at first lactation (MP1), milkyield adjusted to 305 d and adult equivalent at the first lactation (MP1std), total milk production of the first fivelactations (MP5) and milk yield adjusted to 305 d and mature equivalent of the first five lactations (MP5std). Thedatabases of the Mexican Holstein Association (MHA, n= 43,668) and of the National Bank of Dairy Information(NBDI, n= 120,217) were used. Variances were estimated by REML, using a simple animal model for MP1 and MP1stdand a repeatability animal model for MP5 and MP5std. Heritability estimates ranged from low to moderate for thefirst lactation (0.17 ± 0.009 to 0.49 ± 0.019) and for the first five lactations (0.16 ± 0.006 to 0.41 ± 0.004). Therepeatabilities for MP5 and MP5std ranged from 0.32 ± 0.002 to 0.41 ± 0.004. The inclusion of information of theNBDI on the national evaluations made possible the incorporation of production data that had not been taken intoconsideration before. This inclusion not only improved the accuracy of sire breeding values   for milk production, butalso allowed the prediction of breeding values of more foreign and domestic animals with progeny in Mexico.Se estimaron componentes de varianza y parámetros genéticos para producción de leche total a la primera lactancia (PL1), producción de leche ajustada a 305 días y a equivalente adulto de la primera lactancia (PL1std), producción de leche total de las cinco primeras lactancias (PL5) y producción de leche ajustada a 305 días y a equivalente adulto de las primeras 5 lactancias (PL5std). Se utilizaron las bases de datos de la Asociación Holstein de México (AHM; n= 43,668) y del Banco Nacional de Información Lechera (BNIL; n= 120,217). Las varianzas fueron estimadas mediante REML, utilizando un modelo animal simple para PL1 y PL1std y un modelo animal de repetibilidad para PL5 y PL5std. Las heredabilidades estimadas fueron desde bajas a moderadas para la primera lactancia (0.17 ± 0.009 a 0.49 ± 0.019) y para las primeras cinco lactancias (0.16 ± 0.006 a 0.41 ± 0.004). Las repetibilidades para PL5 y PL5std tuvieron un rango de 0.32 ± 0.002 a 0.41 ± 0.004. La inclusión de la información del BNIL en las evaluaciones genéticas permitió incorporar datos de producción que no se estaban tomando en cuenta. Esto no solamente mejoró la precisión de los valores genéticos de los sementales para producción de leche, sino que también permitió la predicción de los valores genéticos de animales nacionales y extranjeros con progenies en México

Parámetros genéticos para producción de leche de ganado Holstein en dos modalidades de control de producción

Variance components and genetic parameters were estimated for total milk production at first lactation (MP1), milkyield adjusted to 305 d and adult equivalent at the first lactation (MP1std), total milk production of the first fivelactations (MP5) and milk yield adjusted to 305 d and mature equivalent of the first five lactations (MP5std). Thedatabases of the Mexican Holstein Association (MHA, n= 43,668) and of the National Bank of Dairy Information(NBDI, n= 120,217) were used. Variances were estimated by REML, using a simple animal model for MP1 and MP1stdand a repeatability animal model for MP5 and MP5std. Heritability estimates ranged from low to moderate for thefirst lactation (0.17 ± 0.009 to 0.49 ± 0.019) and for the first five lactations (0.16 ± 0.006 to 0.41 ± 0.004). Therepeatabilities for MP5 and MP5std ranged from 0.32 ± 0.002 to 0.41 ± 0.004. The inclusion of information of theNBDI on the national evaluations made possible the incorporation of production data that had not been taken intoconsideration before. This inclusion not only improved the accuracy of sire breeding values   for milk production, butalso allowed the prediction of breeding values of more foreign and domestic animals with progeny in Mexico.Se estimaron componentes de varianza y parámetros genéticos para producción de leche total a la primera lactancia (PL1), producción de leche ajustada a 305 días y a equivalente adulto de la primera lactancia (PL1std), producción de leche total de las cinco primeras lactancias (PL5) y producción de leche ajustada a 305 días y a equivalente adulto de las primeras 5 lactancias (PL5std). Se utilizaron las bases de datos de la Asociación Holstein de México (AHM; n= 43,668) y del Banco Nacional de Información Lechera (BNIL; n= 120,217). Las varianzas fueron estimadas mediante REML, utilizando un modelo animal simple para PL1 y PL1std y un modelo animal de repetibilidad para PL5 y PL5std. Las heredabilidades estimadas fueron desde bajas a moderadas para la primera lactancia (0.17 ± 0.009 a 0.49 ± 0.019) y para las primeras cinco lactancias (0.16 ± 0.006 a 0.41 ± 0.004). Las repetibilidades para PL5 y PL5std tuvieron un rango de 0.32 ± 0.002 a 0.41 ± 0.004. La inclusión de la información del BNIL en las evaluaciones genéticas permitió incorporar datos de producción que no se estaban tomando en cuenta. Esto no solamente mejoró la precisión de los valores genéticos de los sementales para producción de leche, sino que también permitió la predicción de los valores genéticos de animales nacionales y extranjeros con progenies en México

Aptitud de producción probable en vacas brangus y charolais bajo condiciones de agostadero en Sonora

Con la información de registros de produce ion de 15 años (1970-1984) de dos hatos de ganado Brangus y Charolais, bajo condiciones de agostadero en Sonora

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial.

Abstract Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs. Keywords: NGS; circulating free DNA; epidermal growth factor receptor; non-small-cell lung cancer; osimertinib; tyrosine kinase inhibitor

Contribution of cardio-vascular risk factors to depressive status in the PREDIMED-PLUS Trial. A cross-sectional and a 2-year longitudinal study

Background Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial. Methods and findings Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol <160 mg/mL showed higher odds of depression than LR [OR (95% CI) = 1.77 (1.13, 2.77) and 2.83 (1.25, 6.42) respectively)] but those with total cholesterol ¿280 mg/mL showed lower odds of depression than LR [OR (95% CI) = 0.26 (0.07, 0.98) and 0.23 (0.05, 0.95), respectively]. All participants decreased their BDI-II score after 2 years, being the decrease smaller in MR and HR diabetic compared to LR [adjusted mean±SE = -0.52±0.20, -0.41 ±0.27 and -1.25±0.31 respectively). MR and HR participants with total cholesterol between 240-279 mg/mL showed greater decreases in the BDI-II score compared to LR (adjusted mean±SE = -0.83±0.37, -0.77±0.64 and 0.97±0.52 respectively). Conclusions Improving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response.The PREDIMED-Plus trial was supported by the European Research Council through a grant to MAM (Advanced Research Grant 2013-2018; 340918). The project was also supported by the official funding agency for biomedical research of the Spanish Government (ISCIII) through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects), who awarded grants to JS and JV (PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732 and PI17/00926). The International Nut&Dried Fruit Council-FESNAD also provided funding through a grant to MAM (201302), and Recercaixa also awarded a grant to JS (2013ACUP00194). The Department of Health, Generalitat de Cataluña by the calls 'Acció instrumental de programes de recerca orientats en lámbit de la recercaila innovació en salut' and 'Pla estrategic de recerca i innovació en salut (PERIS),' also awarded a grant to FF (SLT006/17/00246). This research was also partially funded by: Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); Generalitat Valenciana (PROMETEO/2017/017); SEMERGEN, CIBEROBN, FEDER and ISCIII (CB06/03); EU-H2020 Grants (Eat2beNICE/h2020-sfs-2016-2, ref.728018; PRIME/h2020-SC1-BHC-2018-2020, ref: 847879)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Best Practice Guide for Positive Parenting. A resource for practitioners working with families

[spa] El modo en que se concibe el ejercicio de la parentalidad ha cambiado sustancialmente en nuestra sociedad. Ello no sólo se debe a la gran variedad de formas familiares y diversidad de culturas que conviven actualmente en su seno, sino también a un cambio conceptual que afecta al núcleo básico de la tarea parental. Nos referimos a la necesidad de sustituir el concepto de autoridad parental, centrado únicamente en la necesidad de lograr metas de obediencia y disciplina en los hijos e hijas, por otro más complejo y demandante como es el concepto de responsabilidad parental. Según este concepto, la cuestión clave no es si las figuras parentales deben ejercer la autoridad para que sus hijos/as les obedezcan, sino cómo ejercerla de modo responsable para que se preserven los derechos de los mismos, sin menoscabar los de padres y madres, y se fomenten sus capacidades críticas y de participación en el proceso de socialización, al mismo tiempo que se promueve progresivamente su autonomía y contribución a la vida comunitaria. Ante este cambio cualitativo en la manera de entender las responsabilidades parentales, se alzan muchas voces de desánimo entre los propios padres y madres, quienes en ocasiones se ven impotentes en su tarea al no saber cómo actuar para lograr metas educativas tan complejas y sentir, al mismo tiempo, que están perdiendo capacidades de control sobre sus hijos e hijas. En otras ocasiones, el desánimo y el estrés ante la tarea parental no surge por no saber llevarla a cabo sino por no poder hacerlo adecuadamente debido a la situación de la persona que educa en solitario o en pareja sin contar con redes de apoyo apropiadas. Esto crea situaciones límite que repercuten negativamente en todos y cada uno de los miembros de la familia, especialmente en los más vulnerables.[eng] Our conception of what parenting should look like has changed considerably in our society. This is due not only to the large variety of family structures and the diversity of cultures that currently co-exist in our society, but also to a shift in mindset that touches the very heart of the parenting task. This can be expressed as the need to replace the concept of parental authority, which focuses solely on meeting aims related to the child’s obedience and discipline, with the much more complex and demanding concept of parental responsibility. Here, the key question is not whether the parent figure should exert the necessary authority to ensure a child’s obedience. Rather, it is about how this authority can be exerted responsibly in a way that protects the child’s rights - without of course neglecting the mother’s and father’s rights - and that fosters the child’s skills in critical thinking and participation in the socialisation process, while at the same time progressively fostering the child’s autonomy and contribution to community life. There has been much concern expressed in response to this qualitative shift in how a parent’s responsibilities are viewed, including amongst mothers and fathers themselves. Parents often feel powerless to act, as they do not know how to achieve such complex parenting goals, and feel like they are losing control over their children. Other times, feelings of discouragement and stress arise not because parents do not how to go about the task of parenting, but rather because they find themselves unable to do so, as may be the case for single parents or couples raising children without the necessary support networks. This can lead to extreme situations which can have a negative impact on the entire family, and especially its most vulnerable members

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

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio