Targeted Electromyographic Biofeedback With Endoanal Electrostimulation for Anal Incontinence.

Purpose. Anal incontinence (AI) is a disabling condition with a variable response to conservative physical therapies. We assess the utility of combining electromyographic biofeedback with endoanal electrostimulation targeted to the weakest areas of the pelvic floor using the MAPLe® probe (Multiple Array Probe Leiden Novuqare). Methods. Patients with AI unresponsive to conservative measures were assessed before and after treatment with anorectal manometry (ARM), electromyography (EMG), Wexner Continence Scoring, Visual Analog Scoring (VAS), FIQL and SF-12 quality of life determination. Results. Of 29 patients in the final analysis, there was an improvement in the mean Wexner continence score from 13.59 to 8.03 and a concomitant improvement in the reported VAS from 3.45 to 6.72. Both Wexner continence and VAS scores were maintained during follow-up. Maximum voluntary manometric contraction significantly improved from 91.76 mmHg to 110.33 mmHg with no changes in resting pressure. The EMG values ​​(µV) that significantly improved included the average and peak resistance, the average general voluntary contraction, and the average and peak voluntary contraction for both the external anal sphincter and the puborectalis. In the FIQL, behavior, depression and shame domains improved after treatment and during follow-up with lifestyle improvements detected at 6 and 12 months. Physical and mental components of the SF-12 improved at 6 and 12 months. Conclusions. Targeted electromyographic biofeedback and endoanal electrostimulation using MAPLe® probe in AI patients sustainably improves objective ARM and EMG parameters along with subjective reporting of continence severity, VAS, and quality of life.

Mitigation of greenhouse gases in dairy cattle via genetic selection: 2. Incorporating methane emissions into the breeding goal.

The objective of this study was to analyze the impact of incorporating enteric methane into the breeding objective of dairy cattle in Spain, and to evaluate both genetic and economic response of traits in the selection index under 4 scenarios: (1) the current ICO (Spanish total merit index), used as benchmark; (2) a hypothetical penalization of methane emissions through a carbon tax; (3) considering methane as a net energy loss for the animal; and (4) desired genetic response to reduce methane production by 20% in 10 yr. A bio-economic model was developed to derive the economic values for production and methane traits in each scenario. The estimated economic values for methane were estimated at -€1.21/kg and -€0.32/kg for scenarios 2 and 3, respectively. When merged with other traits in the selection index, methane had less economic importance (1-5%) than milk protein yield (39-42%) or milk fat yield (27-28%). Under these scenarios, selection resulted in an unfavorable response in methane emissions when it was included with an economic weight, with an increase in methane estimated from 0.52 to 0.60 kg/cow per year. Small differences in total profit per cow per year were observed between indices. The incorporation of methane production into the breeding objective had a negligible effect on production, with minor reductions in the expected genetic gain for fat and protein yields and in total economic benefits. However, total methane emissions in the dairy industry in Spain were estimated to decrease between 2 and 5% in the next 10 yr due to positive genetic trends for milk yield and an expected decrease in the total number of dairy cows. Additionally, methane intensity per 1 billion liters of milk would decrease in all scenarios. The uncertainty in the genetic parameters of methane and in carbon prices were tested in a sensitivity analysis, resulting in small deviations from the benchmark scenario. A major effect was observed only under the desired genetic response scenario. In this case, it was possible to achieve a 20% reduction of methane production in 10 yr via selective breeding but at the expense of a larger ad hoc weight (33%) of methane in the selection index and decelerating the genetic gain for production traits from 6 to 18%. This study shows the potential of including environmental traits in the selection indices while retaining populations profitable for producers.

Mitigation of greenhouse gases in dairy cattle via genetic selection: 1. Genetic parameters of direct methane using noninvasive methods and proxies of methane.

Records of methane emissions from 1,501 cows on 14 commercial farms in 4 regions of Spain were collected from May 2018 to June 2019. Methane concentrations (MeC) were measured using a nondispersive infrared methane detector installed within the feed bin of the automatic milking system during 14- to 21-d periods. Rumination time (RT; min/d) was collected using collars with a tag that registered time (minutes) spent eating and ruminating. The means of MeC and methane production (MeP) were 1,254.28 ppm and 182.49 g/d, respectively; mean RT was 473.38 min/d. Variance components for MeC, MeP, and RT were estimated with REML using pedigree and genomic information in a single-step model. Heritabilities for MeC and MeP were 0.11 and 0.12, respectively. Rumination time showed a slightly larger heritability estimate (0.17). The genetic correlation between MeP and MeC was high (>0.95), suggesting that selection on either trait would lead to a positive correlated response on the other. Negative correlations were estimated between RT and MeC (-0.24 ± 0.38) and MeP (-0.43 ± 0.35). Methane concentration and MeP had slightly positive correlations with milk yield (0.17 ± 0.39 and 0.21 ± 0.36), protein percentage (0.08 ± 0.32 and 0.30 ± 0.45), protein yield (0.22 ± 0.41 and 0.31 ± 0.35), fat percentage (0.02 ± 0.40 and 0.27 ± 0.36), and fat yield (0.27 ± 0.28 and 0.29 ± 0.28) from bivariate analyses. Rumination time had positive correlations with milk yield (0.41 ± 0.75) and protein yield (0.26 ± 0.57) and negative correlations with fat yield (-0.45 ± 0.32), protein percentage (-0.15 ± 0.38), and fat percentage (-0.40 ± 0.47). A positive approximated genetic correlation was estimated between fertility and MeC (0.10 ± 0.05) and MeP (0.18 ± 0.05), resulting in slightly higher CH4 production when selecting for better fertility [days open estimated breeding values (EBV) are expressed with mean 100 and SD 10, inversely related to days from calving to conception; that is, greater days open EBV implies better fertility]. Positive correlations were also estimated for stature with MeC and MeP (0.30 ± 0.04 and 0.43 ± 0.04, respectively). Other type traits (chest width, udder depth, angularity, and capacity) were positively correlated with methane traits, possibly because of higher milk yield and higher feed intake from these animals. Rumination time showed positive EBV correlations with production traits and type traits, and negative correlations with somatic cell count and body condition score. Based on the genetic correlations and heritabilities estimated in this study, methane is measurable and heritable, and estimates of genetic correlations suggest no strong opposition to current breeding objectives in Spanish Holsteins.

[Primary tumours and pseudotumors of the hand in adults. Epidemiological analysis of cases, management and evolution]. / Tumores y seudotumores primarios de la mano en adultos. Análisis epidemiológico de casos, manejo y evolución.

INTRODUCTION: Tumors in the hand are rare, and malignant tumors in the hand are peculiar; However, primary pseudotumoral lesions of the hand, such as ganglion, are very frequent. Most of the tumors found in the bone and soft tissue can be presented in the same way in the hand but their frequency and distribution is different. Despite the low incidence of benign and malignant tumors in the hand, these can be locally invasive or compromise the hand function. The main objective of this study is to determine the epidemiology, types, location and management of tumors and pseudotumors of the hand in adults in the Mexican population. MATERIAL AND METHODS: We designed a retrospective study by review of clinical records of patients in our institution with diagnosis of tumors or pseudotumors in hand from January 2007 to December 2016 evaluating variables such as age, gender, laterality, Diagnosis, histological lineage, localization and treatment. RESULTS: Our study comprises 215 patients with an average age of 44.23 years, predominantly women. Pseudotumors are the most frequently encountered (synovial cyst), followed by benign soft tissue tumors, benign bone tumors, and, finally, malignant tumors. DISCUSSION: After all we suggests a possible new classification for the hand that is simple, reproducible and give guidance for treatment. The need for a classification system is imminent to standardize diagnostics, guide future research, focus treatments and preserve hand function.

INTRODUCCIÓN: Los tumores en la mano son poco frecuentes y los tumores malignos son particularmente raros; sin embargo, las lesiones seudotumorales primarias de la mano, como gangliones, son muy frecuentes. La mayoría de los tumores que se encontraron en el hueso y tejido blando pueden presentarse de igual manera en la mano, pero su frecuencia y distribución es distinta. A pesar de la baja incidencia de los tumores benignos y malignos en la mano, éstos pueden ser localmente invasivos o comprometer su función. El objetivo principal de este estudio es determinar la epidemiología, tipos, localización y manejo de los tumores y seudotumores de la mano en adultos en población mexicana. MATERIAL Y MÉTODOS: Se diseñó un estudio retrospectivo mediante revisión de expedientes clínicos de pacientes de nuestra institución con diagnóstico de tumores o seudotumores en la mano de Enero de 2007 a Diciembre de 2016 evaluando variables como edad, género, lateralidad, abordaje diagnóstico, estirpe histológica, localización y tratamiento. RESULTADOS: Nuestro estudio comprende 215 pacientes con una edad promedio de 44.23 años, predominantemente mujeres. Los seudotumores son los que con más frecuencia se detectan (quiste sinovial), seguidos de los tumores benignos de tejido blando, tumores óseos benignos y, por último, los tumores malignos. DISCUSIÓN: Después de todo, sólo sugerimos una clasificación para la mano que es sencilla y reproducible y dar orientación para el tratamiento. La necesidad de un sistema de clasificación es inminente para estandarizar los diagnósticos, guiar futuras investigaciones, enfocar tratamientos y preservar la función de la mano, independientemente de la epidemiología que se observe.

[Strength and function of hand before and after release of carpal tunnel in patients with type 2 diabetes mellitus by open and endoscopic approach. Case-control study]. / Fuerza y función de mano antes y después de liberación de túnel del carpo en pacientes con diabetes mellitus tipo 2 por abordaje abierto y endoscópico. Estudio de casos y controles.

BACKGROUND: Carpal tunnel syndrome (CTS) is the upper extremity neuropathy more frequent. Treatments led to the entrapment of the median nerve in the carpal tunnel are more complicated and the results less promising and unsatisfactory in diabetic patients. The objective of this study is to compare the results of strength and hand function in healthy patients against patients with diabetes mellitus type 2 (DM2) with a diagnosis of CTS before and after the open and endoscopic release of the carpal tunnel. MATERIAL AND METHODS: This is an observational, retrospective and descriptive study for a period of five years where we evaluated the results in healthy patients and with DM2, with diagnosis of CTS who underwent surgical treatment by open or endoscopic approach; we applied the DASH questionnaire, force grip and clamp fine measurements, presence of infection, pain and complications. RESULTS: The results of 86 patients evaluated, showed a statistical association in the decrease in scores on the functional scale DASH with both approaches, association between remission of hypoesthesias in healthy patients with either of the two approaches as opposed to diabetic patients and association between developing DM2 and complications in the short term. CONCLUSION: Both approaches improve symptoms and function of the hand in healthy and diabetic patients, but the fi rst group will present cases of complete remission in contrast to the group of diabetic patients.

ANTECEDENTES: El síndrome del túnel del carpo (STC) es la neuropatía más frecuente de la extremidad superior a nivel mundial. Los tratamientos dirigidos para el atrapamiento del nervio mediano en el túnel del carpo son más complicados y los resultados menos prometedores e insatisfactorios en pacientes diabéticos. El objetivo de este estudio es comparar los resultados de fuerza y función de la mano en pacientes sanos contra pacientes con diabetes mellitus tipo 2 (DM2) con diagnóstico de STC antes y después de la liberación abierta y endoscópica del túnel del carpo. MATERIAL Y MÉTODOS: Se diseñó un estudio observacional, retrospectivo y descriptivo durante un período de cinco años en el que se evaluaron pacientes sanos y con DM2 con diagnóstico de STC que fueron sometidos a tratamiento quirúrgico por abordaje abierto o endoscópico y a quienes se les aplicó el cuestionario DASH, mediciones de fuerza de prensión y pinza fi na, presencia de hipoestesias, dolor y complicaciones. RESULTADOS: Los resultados de los 86 pacientes evaluados mostraron una asociación estadística en la disminución de los puntajes de la escala funcional DASH con ambos abordajes, asociación entre la remisión de hipoestesias en pacientes sanos con cualquiera de los dos abordajes a diferencia de los pacientes diabéticos y asociación entre padecer DM2 y tener complicaciones a corto plazo. CONCLUSIÓN: Ambos abordajes mejoran los síntomas y función de la mano en pacientes sanos y diabéticos, pero el primer grupo presentará casos de remisión completa a diferencia del grupo de pacientes diabéticos.

Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective tissues of developing digits and regulates fibrogenic differentiation of limb mesodermal progenitors.

Four and a half LIM domain 2 (FHL2) is a multifunctional scaffolding protein of well-known function regulating cell signalling cascades and gene transcription in cancer tissues. However, its function in embryonic systems is poorly characterized. Here, we show that Fhl2 is involved in the differentiation of connective tissues of developing limb autopod. We show that Fhl2 exhibits spatially restricted and temporally dynamic expression around the tendons of developing digits, interphalangeal joint capsules, and fibrous peridigital tissue. Immunolabelling analysis of the skeletal progenitors identified a predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated with focal adhesions and actin cytoskeleton. In the course of chondrogenic differentiation of cultures of limb skeletal progenitors, the expression of Fhl2 is down-regulated. Furthermore, cultures of skeletal progenitors overexpressing Fhl2 take on a predominant fibrogenic appearance. Both gain-of-function and loss-of-function experiments in the micromass culture assays revealed a positive transcriptional influence of Fhl2 in the expression of fibrogenic markers including Scleraxis, Tenomodulin, Tenascin C, ßig-h3, and Tgif1. We further show that the expression of Fhl2 is positively regulated by profibrogenic signals including Tgfß2, all-trans-retinoic acid, and canonical Wnt signalling molecules and negatively regulated by prochondrogenic factors of the bone morphogenetic protein family. Expression of Fhl2 is also regulated negatively in immobilized limbs, but this influence appears to be mediated by other connective tissue markers, such as Tgfßs and Scleraxis.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.

[Intercarpal fusion as a salvage procedure in Kienböck disease]. / Artrodesis intercarpiana como tratamiento de salvamento en pacientes con enfermedad de Kienböck.

INTRODUCTION: Functional results of four surgical techniques to resolve the IIIB-IV Litchman's stage of the Kienböck disease were analyzed. We observed the evolution from 2000 to 2015. MATERIAL AND METHODS: Transversal retrospective study of 33 patients treated with different surgical techniques and evaluated with Quick-DASH scale, dynamometer and EVA. RESULTS: Less functional limitation was found in the patients who underwent the intercarpal fusion with or without neurotomy of the posterior interosseous. DISCUSSION: It was shown that the fact of making a less aggressive surgery is enough to evolve into an increase in symptoms and a decrease in function and strength; therefore, the intercarpal fusion performed at the right time of the natural history of the disease can achieve better results than other methods used previously and endorsed by international associations. CONCLUSIONS: The surgical technique of choice in our series to prevent disease progression was the intercarpal fusion and neurotomy of the posterior interosseous nerve.

INTRODUCCIÓN: Se analizaron los resultados funcionales de cuatro técnicas quirúrgicas de salvamento para resolver la etapa IIIB-IV de Litchman de la enfermedad de Kienböck. Observamos la evolución de los procedimientos quirúrgicos de salvamento realizados del 2000 al 2015. MATERIAL Y MÉTODOS: Estudio retrospectivo transversal de 33 pacientes tratados con cuatro técnicas quirúrgicas distintas a quienes se les realizó la escala Quick-DASH, dinamometría y EVA. RESULTADOS: Se encontró menor limitación funcional al año postquirúrgico en los individuos a los cuales se les realizó la artrodesis intercarpiana con o sin neurotomía del nervio interóseo posterior, con una media de 16.4, una mediana de 16.35, una moda de 15.3 y una p 0.05. DISCUSIÓN: Se demostró que una cirugía poco agresiva es suficiente para evolucionar a un aumento sintomatológico y un descenso de la función y fuerza, por lo que la artrodesis intercarpiana logra mejores resultados que otros procedimientos usados con anterioridad y avalados por las grandes asociaciones internacionales. CONCLUSIONES: La técnica quirúrgica de salvamento de elección en nuestra serie, que sugiere evitar la progresión de la enfermedad de Kienböck, es la artrodesis intercarpiana más neurotomía del nervio interóseo posterior, ya que presenta menor número de complicaciones.

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix.

Interdigital cell death is a physiological regression process responsible for sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity of this degenerative process account for the different patterns of interdigital webbing among vertebrate species. Here, we show that Reelin is present in the extracellular matrix of the interdigital mesoderm of chick and mouse embryos during the developmental stages of digit formation. Reelin is a large extracellular glycoprotein which has important functions in the developing nervous system, including neuronal survival; however, the significance of Reelin in other systems has received very little attention. We show that reelin expression becomes intensely downregulated in both the chick and mouse interdigits preceding the establishment of the areas of interdigital cell death. Furthermore, fibroblast growth factors, which are cell survival signals for the interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which are proapototic signals, downregulate its expression in the interdigit. Gene silencing experiments of reelin gene or its intracellular effector Dab-1 confirmed the implication of Reelin signaling as a survival factor for the limb undifferentiated mesoderm. We found that Reelin activates canonical survival pathways in the limb mesoderm involving protein kinase B and focal adhesion kinase. Our findings support that Reelin plays a role in interdigital cell death, and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be involved in this process.

Assets of imputation to ultra-high density for productive and functional traits.

The aim of this study was to evaluate different-density genotyping panels for genotype imputation and genomic prediction. Genotypes from customized Golden Gate Bovine3K BeadChip [LD3K; low-density (LD) 3,000-marker (3K); Illumina Inc., San Diego, CA] and BovineLD BeadChip [LD6K; 6,000-marker (6K); Illumina Inc.] panels were imputed to the BovineSNP50v2 BeadChip [50K; 50,000-marker; Illumina Inc.]. In addition, LD3K, LD6K, and 50K genotypes were imputed to a BovineHD BeadChip [HD; high-density 800,000-marker (800K) panel], and with predictive ability evaluated and compared subsequently. Comparisons of prediction accuracy were carried out using Random boosting and genomic BLUP. Four traits under selection in the Spanish Holstein population were used: milk yield, fat percentage (FP), somatic cell count, and days open (DO). Training sets at 50K density for imputation and prediction included 1,632 genotypes. Testing sets for imputation from LD to 50K contained 834 genotypes and testing sets for genomic evaluation included 383 bulls. The reference population genotyped at HD included 192 bulls. Imputation using BEAGLE software (http://faculty.washington.edu/browning/beagle/beagle.html) was effective for reconstruction of dense 50K and HD genotypes, even when a small reference population was used, with 98.3% of SNP correctly imputed. Random boosting outperformed genomic BLUP in terms of prediction reliability, mean squared error, and selection effectiveness of top animals in the case of FP. For other traits, however, no clear differences existed between methods. No differences were found between imputed LD and 50K genotypes, whereas evaluation of genotypes imputed to HD was on average across data set, method, and trait, 4% more accurate than 50K prediction, and showed smaller (2%) mean squared error of predictions. Similar bias in regression coefficients was found across data sets but regressions were 0.32 units closer to unity for DO when genotypes were imputed to HD density. Imputation to HD genotypes might produce higher stability in the genomic proofs of young candidates. Regarding selection effectiveness of top animals, more (2%) top bulls were classified correctly with imputed LD6K genotypes than with LD3K. When the original 50K genotypes were used, correct classification of top bulls increased by 1%, and when those genotypes were imputed to HD, 3% more top bulls were detected. Selection effectiveness could be slightly enhanced for certain traits such as FP, somatic cell count, or DO when genotypes are imputed to HD. Genetic evaluation units may consider a trait-dependent strategy in terms of method and genotype density for use in the genome-enhanced evaluations.

Cardiac cell therapy: boosting mesenchymal stem cells effects.

Acute myocardial infarction is a major problem of world public health and available treatments have limited efficacy. Cardiac cell therapy is a new therapeutic strategy focused on regeneration and repair of the injured cardiac muscle. Among different cell types used, mesenchymal stem cells (MSC) have been widely tested in preclinical studies and several clinical trials have evaluated their clinical efficacy in myocardial infarction. However, the beneficial effects of MSC in humans are limited due to poor engraftment and survival of these cells, therefore ways to overcome these obstacles should improve efficacy. Different strategies have been used, such as genetically modifying MSC, or preconditioning the cells with factors that potentiate their survival and therapeutic mechanisms. In this review we compile the most relevant approaches used to improve MSC therapeutic capacity and to understand the molecular mechanisms involved in MSC mediated cardiac repair.

The gradient boosting algorithm and random boosting for genome-assisted evaluation in large data sets.

In the next few years, with the advent of high-density single nucleotide polymorphism (SNP) arrays and genome sequencing, genomic evaluation methods will need to deal with a large number of genetic variants and an increasing sample size. The boosting algorithm is a machine-learning technique that may alleviate the drawbacks of dealing with such large data sets. This algorithm combines different predictors in a sequential manner with some shrinkage on them; each predictor is applied consecutively to the residuals from the committee formed by the previous ones to form a final prediction based on a subset of covariates. Here, a detailed description is provided and examples using a toy data set are included. A modification of the algorithm called "random boosting" was proposed to increase predictive ability and decrease computation time of genome-assisted evaluation in large data sets. Random boosting uses a random selection of markers to add a subsequent weak learner to the predictive model. These modifications were applied to a real data set composed of 1,797 bulls genotyped for 39,714 SNP. Deregressed proofs of 4 yield traits and 1 type trait from January 2009 routine evaluations were used as dependent variables. A 2-fold cross-validation scenario was implemented. Sires born before 2005 were used as a training sample (1,576 and 1,562 for production and type traits, respectively), whereas younger sires were used as a testing sample to evaluate predictive ability of the algorithm on yet-to-be-observed phenotypes. Comparison with the original algorithm was provided. The predictive ability of the algorithm was measured as Pearson correlations between observed and predicted responses. Further, estimated bias was computed as the average difference between observed and predicted phenotypes. The results showed that the modification of the original boosting algorithm could be run in 1% of the time used with the original algorithm and with negligible differences in accuracy and bias. This modification may be used to speed the calculus of genome-assisted evaluation in large data sets such us those obtained from consortiums.

Comparison of methods for the implementation of genome-assisted evaluation of Spanish dairy cattle.

The aim of this study was to evaluate methods for genomic evaluation of the Spanish Holstein population as an initial step toward the implementation of routine genomic evaluations. This study provides a description of the population structure of progeny tested bulls in Spain at the genomic level and compares different genomic evaluation methods with regard to accuracy and bias. Two bayesian linear regression models, Bayes-A and Bayesian-LASSO (B-LASSO), as well as a machine learning algorithm, Random-Boosting (R-Boost), and BLUP using a realized genomic relationship matrix (G-BLUP), were compared. Five traits that are currently under selection in the Spanish Holstein population were used: milk yield, fat yield, protein yield, fat percentage, and udder depth. In total, genotypes from 1859 progeny tested bulls were used. The training sets were composed of bulls born before 2005; including 1601 bulls for production and 1574 bulls for type, whereas the testing sets contained 258 and 235 bulls born in 2005 or later for production and type, respectively. Deregressed proofs (DRP) from January 2009 Interbull (Uppsala, Sweden) evaluation were used as the dependent variables for bulls in the training sets, whereas DRP from the December 2011 DRPs Interbull evaluation were used to compare genomic predictions with progeny test results for bulls in the testing set. Genomic predictions were more accurate than traditional pedigree indices for predicting future progeny test results of young bulls. The gain in accuracy, due to inclusion of genomic data varied by trait and ranged from 0.04 to 0.42 Pearson correlation units. Results averaged across traits showed that B-LASSO had the highest accuracy with an advantage of 0.01, 0.03 and 0.03 points in Pearson correlation compared with R-Boost, Bayes-A, and G-BLUP, respectively. The B-LASSO predictions also showed the least bias (0.02, 0.03 and 0.10 SD units less than Bayes-A, R-Boost and G-BLUP, respectively) as measured by mean difference between genomic predictions and progeny test results. The R-Boosting algorithm provided genomic predictions with regression coefficients closer to unity, which is an alternative measure of bias, for 4 out of 5 traits and also resulted in mean squared errors estimates that were 2%, 10%, and 12% smaller than B-LASSO, Bayes-A, and G-BLUP, respectively. The observed prediction accuracy obtained with these methods was within the range of values expected for a population of similar size, suggesting that the prediction method and reference population described herein are appropriate for implementation of routine genome-assisted evaluations in Spanish dairy cattle. R-Boost is a competitive marker regression methodology in terms of predictive ability that can accommodate large data sets.

Genotyping strategies for genomic selection in small dairy cattle populations.

This study evaluated different female-selective genotyping strategies to increase the predictive accuracy of genomic breeding values (GBVs) in populations that have a limited number of sires with a large number of progeny. A simulated dairy population was utilized to address the aims of the study. The following selection strategies were used: random selection, two-tailed selection by yield deviations, two-tailed selection by breeding value, top yield deviation selection and top breeding value selection. For comparison, two other strategies, genotyping of sires and pedigree indexes from traditional genetic evaluation, were included in the analysis. Two scenarios were simulated, low heritability (h 2 = 0.10) and medium heritability (h 2 = 0.30). GBVs were estimated using the Bayesian Lasso. The accuracy of predicted GBVs using the two-tailed strategies was better than the accuracy obtained using other strategies (0.50 and 0.63 for the two-tailed selection by yield deviations strategy and 0.48 and 0.63 for the two-tailed selection by breeding values strategy in low- and medium-heritability scenarios, respectively, using 1000 genotyped cows). When 996 genotyped bulls were used as the training population, the sire' strategy led to accuracies of 0.48 and 0.55 for low- and medium-heritability traits, respectively. The Random strategies required larger training populations to outperform the accuracies of the pedigree index; however, selecting females from the top of the yield deviations or breeding values of the population did not improve accuracy relative to that of the pedigree index. Bias was found for all genotyping strategies considered, although the Top strategies produced the most biased predictions. Strategies that involve genotyping cows can be implemented in breeding programs that have a limited number of sires with a reliable progeny test. The results of this study showed that females that exhibited upper and lower extreme values within the distribution of yield deviations may be included as training population to increase reliability in small reference populations. The strategies that selected only the females that had high estimated breeding values or yield deviations produced suboptimal results.

Coordinated and sequential activation of neutral and acidic DNases during interdigital cell death in the embryonic limb.

Interdigital tissue regression during embryonic development is one of the most representative model systems of morphogenetic cell death, but the degenerative cascade accounting for this process awaits clarification. Although the canonical apoptotic caspase pathway appears to be activated in the interdigital mesenchyme committed to die, neither genetic nor chemical blockage of caspases or their downstream effectors, is sufficient to prevent cell death. Hence, alternative and/or complementary dying pathways must also be responsible for this degenerative process. In this work we have chosen to study the endonucleases during the regression of the interdigital tissue of avian embryos to gain insights into the molecular mechanisms accounting for programmed cell death in this system. We show that caspase activated DNase, which is a neutral DNase associated with the caspase apoptotic pathway, appears to be the main endonuclease only at an initial phase of interdigit regression. However at peak stages of the degenerative process, the acidic DNases L-DNase II and lysosomal DNase IIB become predominant in the system and markers for cell autophagy become moderately up-regulated. Consistent with the activation of acidic endonucleases we observed that microenvironmental pH value in the interdigits decreased to levels only appropriate for acidic enzymes. Furthermore, we found that overexpression of lysosomal DNase IIB in embryonic limb mesoderm promoted cell death, which was also accompanied by up-regulation and activation of L-DNase II. Up-regulation of acidic DNases was maintained in interdigits explanted to culture dishes, where the participation of exogenous professional phagocytes of hematopoietic origin is avoided. Finally, and consistent with all our findings, up-regulation of acidic DNases was much reduced in the webbed interdigits of duck embryos, characterized by a rudimentary interdigital degenerative process. We conclude that the regression of the interdigital tissue involves a coordinated and sequential activation of the caspase and lysosomal degenerative molecular cascades.

[Surgical removal of peripapillary choroidal neovascularization in young patients]. / Extracción quirúrgica de la neovascularización coroidea peripapilar en pacientes jóvenes.

PURPOSE: To analyze anatomical and visual outcomes after subretinal surgery for peripapillary choroidal neovascularization (CNV) not associated with age-related macular degeneration (AMD). METHODS: Five eyes from five patients with peripapillary CNV who had been treated by subretinal surgery were retrospectively analyzed. RESULTS: The patients averaged 32 years of age (range, 11 to 49, SD 14.5 years) and mean follow-up was 31.4 months (range, 8 to 48, SD 20.8 months). Best corrected visual acuity was 0.05 (range, 0.001 to 0.16, SD 0.07) before surgery and 0.64 (range, 0.2 to 0.9, SD 0.26) after surgery (p=0.005; Student's t test for paired data). Neither intraoperative nor postoperative incidences occurred. CONCLUSIONS: Surgical removal may be considered one of the therapeutic options to treat peripapillary CNV not related to AMD.

Intravitreous bevacizumab to treat subfoveal choroidal neovascularization in highly myopic eyes: short-term results.

AIM: To describe the anatomical and visual outcome of subfoveal and juxtafoveal choroidal neovascularization (CNV) in highly myopic eyes treated by intravitreal bevacizumab. METHODS: Prospective, nonrandomized, multicentric, interventional pilot study. Twenty-six highly myopic eyes from 25 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections with 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and optical coherence tomography at baseline and then monthly. Fluorescein angiography was performed at baseline and at month 3. RESULTS: Patients averaged 49.5 years of age (SD 16.0, range 29-82). Five patients were male and 20 were female. BCVA at baseline averaged 20/62 (range 20/200-20/32) and 20/38 (range 20/160-20/20) at month 6. Average central foveal thickness was 282.4 microm (SD 68.3, range 168-447) at baseline and 224.0 microm (SD 46, range 132-294) at month 6. Fifteen eyes were naïve for treatment and 11 eyes had been previously treated by photodynamic therapy (PDT) (average 2.5 PDT sessions). Leakage from CNV had ceased in all eyes at month 3 and CNV was still closed at month 6. Neither ocular nor systemic safety issues appeared during the follow-up. CONCLUSIONS: Intravitreal bevacizumab seems to be an effective and safe therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.