Pre-implantation mouse embryos cultured In vitro under different oxygen concentrations show altered ultrastructures

Abstract Assisted Reproductive Technologies routinely utilize different culture media and oxygen (O2) concentrations to culture human embryos. Overall, embryos cultured under physiological O2 tension (5%) have improved development compared to embryos cultured under atmospheric O2 conditions (20%). The mechanisms responsible for this remain unclear. This study aimed to evaluate the effect of physiologic (5%) or atmospheric O2 (20%) tension on the microscopic ultrastructure of pre-implantation mouse embryos using Transmission Electron Microscopy (TEM). Embryos flushed out of the uterus after natural mating were used as the control. For use as the control, 2-cells, 4-cells, morulae, and blastocysts were flushed out of the uterus after natural fertilization. In vitro fertilization (IVF) was performed using potassium simplex optimized medium (KSOM) under different O2 tensions (5% and 20%) until the blastocyst stage. After collection, embryos were subjected to the standard preparative for light microscopy (LM) and TEM. We found that culture in vitro under 5% and 20% O2 results in an increase of vacuolated shaped mitochondria, cytoplasmic vacuolization and presence of multi-vesicular bodies at every embryonic stage. In addition, blastocysts generated by IVF under 5% and 20% O2 showed a lower content of heterochromatin, an interruption of the trophectodermal and inner cell mass cell membranes, an increased density of residual bodies, and high levels of glycogen granules in the cytoplasm. In conclusion, this study suggests that in vitro culture, particularly under atmospheric O2 tension, causes stage-specific changes in preimplantation embryo ultrastructure. In addition, atmospheric (20%) O2 is associated with increased alterations in embryonic ultrastructure; these changes may explain the reduced embryonic development of embryos cultured with 20% O2

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS). CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation

The saturation assumption yields optimal convergence of two-level adaptive BEM

We consider the convergence of adaptive BEM for weakly-singular and hypersingular integral equations associated with the Laplacian and the Helmholtz operator in 2D and 3D. The local mesh-refinement is driven by some two-level error estimator. We show that the adaptive algorithm drives the underlying error estimates to zero. Moreover, we prove that the saturation assumption already implies linear convergence of the error with optimal algebraic rates

First principles theory of fluctuations in vortex liquids and solids

Consistent perturbation theory for thermodynamical quantities in type II superconductors in magnetic field at low temperatures is developed. It is complementary to the existing expansion valid at high temperatures. Magnetization and specific heat are calculated to two loop order and compare well to existing Monte Carlo simulations and experiments.Comment: 3 .ps fig. In press Phys. Rev.

Divergence-type 2+1 dissipative hydrodynamics applied to heavy-ion collisions

We apply divergence-type theory (DTT) dissipative hydrodynamics to study the 2+1 space-time evolution of the fireball created in Au+Au relativistic heavy-ion collisions at $\sqrt{s_{NN}}=$200 GeV. DTTs are exact hydrodynamic theories that do no rely on velocity gradient expansions and therefore go beyond second-order theories. We numerically solve the equations of motion of the DTT for Glauber initial conditions and compare the results with those of second-order theory based on conformal invariants (BRSS) and with data. We find that the charged-hadron minumum-bias elliptic flow reaches its maximum value at lower $p_T$ in the DTT, and that the DTT allows for a value of $\eta/s$ slightly larger than that of the BRSS. Our results show that the differences between viscous hydrodynamic formalisms are a significant source of uncertainty in the precise extraction of $\eta/s$ from experiments.Comment: v4: 29 pages, 12 figures, minor changes. Final version as published in Phys. Rev.

Linking the hydrodynamic and kinetic description of a dissipative relativistic conformal theory

We use the entropy production variational method to associate a one particle distribution function to the assumed known energy-momentum and entropy currents describing a relativistic conformal fluid. Assuming a simple form for the collision operator we find this one particle distribution function explicitly, and show that this method of linking the hydro and kinetic description is a non trivial generalization of Grad's ansatz. The resulting constitutive relations are the same as in the conformal dissipative type theories discussed in J. Peralta-Ramos and E. Calzetta, Phys. Rev. D {\bfseries 80}, 126002 (2009). Our results may prove useful in the description of freeze-out in ultrarelativistic heavy-ion collisions.Comment: v2: 23 pages, no figures, accepted in Phys. Rev.

The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto's thyroiditis: an immunohisto-chemical characterization

Hepatocyte growth factor (HGF) exerts proliferative activities in thyrocytes upon binding to its tyrosine kinase receptor c-met and is also expressed in benign thyroid nodules as well as in Hashimoto's thyroiditis (HT)

Abiraterone acetate in metastatic castration-resistant prostate cancer after chemotherapy. A retrospective “Real Life” analysis of activity and safety

Abiraterone acetate (AA) is a potent, selective androge (CYP17) biosynthesis inhibitor, which showed to improve overall survival (HR = 0.646) in mCRPC patients progressing after docetaxel. In this retrospective analysis we assessed the safety and efficacy of AA in patients affected with mCRPC progressing after chemotherapy, treated in the normal clinical practice, in several Italian Oncologic Units, after the approval of the drug from the Italian Drug Agency (AIFA)