Uncontrolled haemorrhage in pelvic fracturesdCan the inevitable be avoided?

Pelvic fractures carry a considerable risk for morbidity and mortality. Half or more of the early deaths in these patients have been attributed directly to haemorrhage. The transfusional requirements are four times higher for open pelvic fractures compared with a similar group of closed pelvic fractures. The loss of the tamponade effect by disruption of the pelvic soft tissues and the energy imparted play a central role in this potentially life threatening situation. We reported a case of open pelvic fracture in which persistent haemorrhage was stopped by giving recombinant activated coagulation factor VIIa as our last resort.     

Olfactory jump reflex habituation in Drosophila and effects of classical conditioning mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity.     

A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation,Differential Signaling,and Relevance to Oncogenic Transformations

We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/continuum stochastic dynamics protocols to study the dimer-mediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. These authors contributed equally     

DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

Clinical spotlight review for the management of choledocholithiasis

Choledocholithiasis is a common presentation of symptomatic cholelithiasis that can result in biliary obstruction, cholangitis, and pancreatitis. A systematic English literature search was conducted in PubMed to determine the appropriate management strategies for choledocholithiasis. The following clinical spotlight review is meant to critically review the available evidence and provide recommendations for the work-up, investigations as well as the endoscopic, surgical and percutaneous techniques in the management of choledocholithiasis.