A Practical Catalytic Reductive Amination of Carboxylic Acids

We report reductive alkylation reactions of amines using carboxylic acids as nominal electrophiles. The two-step reaction exploits the dual reactivity of phenylsilane and involves a silane-mediated amidation followed by a Zn(OAc)2-catalyzed amide reduction. The reaction is applicable to a wide range of amines and carboxylic acids and has been demonstrated on a large scale (305 mmol of amine). The rate differential between the reduction of tertiary and secondary amide intermediates is exemplified in a convergent synthesis of the antiretroviral medicine maraviroc. Mechanistic studies demonstrate that a residual 0.5 equivalents of carboxylic acid from the amidation step is responsible for the generation of silane reductants with augmented reactivity, which allow secondary amides, previously unreactive in zinc/phenylsilane systems, to be reduced

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

This little piggy went to market, this little piggy stayed at home

Materials include: steel, GRP composites, glass, pig, formaldehyde solution, electric motor, 2 tanksfull vie

Physical Impossibility of Death in the Mind of Someone Living

Materials include: tiger shark, glass, steel, 5% formaldehyde solutionfull vie

Reconstruction of the ocular surface using biomaterial templates

This chapter discusses the effect on vision of a large group of pathological conditions, known as ocular surface disorders (OSDs), and presents the therapeutic strategies to reconstruct the abnormal ocular surface. If left untreated, most of the OSDs will lead to partial or total loss of eyesight, especially when limbal stem cell deficiency is involved. An overview of various treatment strategies is presented, with the emphasis on the development of the ex vivo expansion of corneal limbal epithelial cells (presumed to be progenitor or stem cells) and the creation of transplantable epithelial constructs. The use of naturally derived biomaterials (collagen, fibrin, amnion, etc.) or synthetic polymers (polylactides, thermoresponsive polymers, etc.) as substrata in these constructs is critically analyzed. Emphasis is placed on the templates from silk proteins, which are being developed by the authors

Bombyx mori silk fibroin membranes as potential substrata for epithelial constructs used in the management of ocular surface disorders

Membranes were prepared from fibroin, a protein isolated from the domesticated silkworm (Bombyx mori) silk, and evaluated as a potential substratum for corneal limbal epithelial cells. These membranes (i.e., B. mori silk fibroin [BMSF] membranes) were cast from dialyzed solutions of fibroin protein (4% w/v) dispensed into 35-mm-diameter culture dishes and dried at room temperature (23–24°C). The resulting material was transparent, easy to handle, and supported levels of human limbal epithelial (HLE) cell growth comparable to that observed on tissue culture plastic. Remarkably, these results were obtained utilizing a commercial serum-free medium (CnT-20) designed for the ex vivo expansion of corneal epithelial progenitor cells. The potential benefits of serum proteins on this culture system were examined through addition of fetal bovine serum (FBS) either to fibroin stocks prior to membrane casting or by supplementation of the CnT-20 medium. Membranes cast in the presence of FBS displayed increasing opacity and induced little change in HLE growth. Supplementation of CnT-20 medium with FBS deterred cell growth on all substrata, including tissue culture plastic control substrata. The remarkable properties of BMSF membranes demonstrated under serum-free conditions warrant investigation of this material as a substratum in the creation of tissue-engineered constructs for the restoration of diseased or damaged ocular surface