Physiological traits of newborn piglets associated with colostrum intake, neonatal survival and preweaning growth

Colostrum intake, which is critical for piglet survival after birth and growth up to weaning, greatly depends on piglet weight and vitality at birth. Our aim was to identify a set of biological variables explaining individual variations in colostrum intake, preweaning growth and risk of dying. Farrowing traits, morphological traits and colostrum intake were determined for 504 piglets born alive from 37 Landrace × Large White sows. A subset of 203 of these piglets was used to measure plasma neonatal concentrations of metabolites and hormones in blood collected from the umbilical cord at birth. From univariate analyses, we established that colostrum intake was positively associated with plasma neonatal concentrations of IGF-I, albumin, thyroid hormones (P < 0.001), and non-esterified fatty acids (P < 0.05), and was negatively associated with concentrations of lactate (P < 0.001). In a multivariable analysis, the variables explaining the variation in colostrum intake were piglet birth weight and rectal temperature 1 h after birth (positive effect, P < 0.001), time of birth after the onset of parturition, and fructose plasma concentrations at birth (negative effects, P < 0.001 and P < 0.05, respectively). Piglets that died within 3 days after birth had lower neonatal concentrations of albumin (P < 0.001), IGF-I and thyroxine (P < 0.01) than surviving piglets. Preweaning growth was positively associated with neonatal concentrations of IGF-I, thyroxine (P < 0.001), albumin and insulin (P < 0.05). Cortisol and glucose concentrations at birth were not related to colostrum intake, neonatal survival or preweaning growth. Multivariable analyses confirmed that colostrum intake was the predominant factor influencing piglet survival within 3 days after birth and preweaning growth. These results provide physiological indicators of piglet colostrum intake, besides birth weight. They also confirm the impact of time of birth during farrowing on colostrum intake and the crucial importance of physiological maturity at birth for postnatal adaptation

Proteomic analysis of adipose tissue during the last weeks of gestation in pure and crossbred Large White or Meishan fetuses gestated by sows of either breed

Abstract Background The degree of adipose tissue development at birth may influence neonatal survival and subsequent health outcomes. Despite their lower birth weights, piglets from Meishan sows (a fat breed with excellent maternal ability) have a higher survival rate than piglets from Large White sows (a lean breed). To identify the main pathways involved in subcutaneous adipose tissue maturation during the last month of gestation, we compared the proteome and the expression levels of some genes at d 90 and d 110 of gestation in purebred and crossbred Large White or Meishan fetuses gestated by sows of either breed. Results A total of 52 proteins in fetal subcutaneous adipose tissue were identified as differentially expressed over the course of gestation. Many proteins involved in energy metabolism were more abundant, whereas some proteins participating in cytoskeleton organization were reduced in abundance on d 110 compared with d 90. Irrespective of age, 24 proteins differed in abundance between fetal genotypes, and an interaction effect between fetal age and genotype was observed for 13 proteins. The abundance levels of proteins known to be responsive to nutrient levels such as aldolase and fatty acid binding proteins, as well as the expression levels of FASN, a key lipogenic enzyme, and MLXIPL, a pivotal transcriptional mediator of glucose-related stimulation of lipogenic genes, were elevated in the adipose tissue of pure and crossbred fetuses from Meishan sows. These data suggested that the adipose tissue of these fetuses had superior metabolic functionality, whatever their paternal genes. Conversely, proteins participating in redox homeostasis and apoptotic cell clearance had a lower abundance in Meishan than in Large White fetuses. Time-course differences in adipose tissue protein abundance were revealed between fetal genotypes for a few secreted proteins participating in responses to organic substances, such as alpha-2-HS-glycoprotein, transferrin and albumin. Conclusions These results underline the importance of not only fetal age but also maternal intrauterine environment in the regulation of several proteins in subcutaneous adipose tissue. These proteins may be used to estimate the maturity grade of piglet neonates

Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD

BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy

A Super-Jupiter orbiting a late-type star: A refined analysis of microlensing event OGLE-2012-BLG-0406

We present a detailed analysis of survey and follow-up observations of microlensing event OGLE-2012-BLG-0406 based on data obtained from 10 different observatories. Intensive coverage of the lightcurve, especially the perturbation part, allowed us to accurately measure the parallax effect and lens orbital motion. Combining our measurement of the lens parallax with the angular Einstein radius determined from finite-source effects, we estimate the physical parameters of the lens system. We find that the event was caused by a $2.73\pm 0.43\ M_{\rm J}$ planet orbiting a $0.44\pm 0.07\ M_{\odot}$ early M-type star. The distance to the lens is $4.97\pm 0.29$\ kpc and the projected separation between the host star and its planet at the time of the event is $3.45\pm 0.26$ AU. We find that the additional coverage provided by follow-up observations, especially during the planetary perturbation, leads to a more accurate determination of the physical parameters of the lens

Evolutionary dynamics of paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder characterized by hemolysis and a high risk of thrombosis, that is due to a deficiency in several cell surface proteins that prevent complement activation. Its origin has been traced to a somatic mutation in the PIG-A gene within hematopoietic stem cells (HSC). However, to date the question of how this mutant clone expands in size to contribute significantly to hematopoiesis remains under debate. One hypothesis posits the existence of a selective advantage of PIG-A mutated cells due to an immune mediated attack on normal HSC, but the evidence supporting this hypothesis is inconclusive. An alternative (and simpler) explanation attributes clonal expansion to neutral drift, in which case selection neither favours nor inhibits expansion of PIG-A mutated HSC. Here we examine the implications of the neutral drift model by numerically evolving a Markov chain for the probabilities of all possible outcomes, and investigate the possible occurrence and evolution, within this framework, of multiple independently arising clones within the HSC pool. Predictions of the model agree well with the known incidence of the disease and average age at diagnosis. Notwithstanding the slight difference in clonal expansion rates between our results and those reported in the literature, our model results lead to a relative stability of clone size when averaging multiple cases, in accord with what has been observed in human trials. The probability of a patient harbouring a second clone in the HSC pool was found to be extremely low ([Formula: see text]). Thus our results suggest that in clinical cases of PNH where two independent clones of mutant cells are observed, only one of those is likely to have originated in the HSC pool.JMP gratefully acknowledges Financial Support by Fundação para a Ciência e Tecnologia (FCT) through grants PTDC/EEI-SII/5081/2014, PTDC/MAT/STA/3358/2014 and UID/BIA/04050/2013. NMP and TL gratefully acknowledge the Financial Support by the F.N.R.S.-F.R.S. through the Televie grant 28479704. The funding organizations had no role in the design of the work, collection and analysis of data, interpretation of data or writing of the manuscript