The role of deubiquitinating enzymes in cancer drug resistance

Cancer Chemotherapy and Pharmacology - Drug resistance is a well-known phenomenon leading to a reduction in the effectiveness of pharmaceutical treatments. Resistance to chemotherapeutic agents can...     

Recent advances in three‐dimensional bioprinting of stem cells

In spite of being a new field, three‐dimensional (3D) bioprinting has undergone rapid growth in the recent years. Bioprinting methods offer a unique opportunity for stem cell distribution, positioning, and differentiation at the microscale to make the differentiated architecture of any tissue while maintaining precision and control over the cellular microenvironment. Bioprinting introduces a wide array of approaches to modify stem cell fate. This review discusses these methodologies of 3D bioprinting stem cells. Fabricating a fully operational tissue or organ construct with a long life will be the most significant challenge of 3D bioprinting. Once this is achieved, a whole human organ can be fabricated for the defect place at the site of surgery.     

Unusual objects in the root canal of deciduous teeth: a report of two cases

Accidental foreign body ingestion or aspiration is a common problem in children. Children often have a habit of inserting objects into their mouth. Some of these objects can be accidentally ingested or even aspirated which can be frightening and a stressful experience. But the presence of foreign objects in the teeth are rare. The foreign objects in the teeth may act as a potential source of infection and pain. In most of the cases, children avoid informing their parents due to fear of punishment. This paper presents two cases of foreign objects embedded in the deciduous teeth. In both the cases, parents were not aware of foreign body ingestion by their children.     

Evaluation of antimicrobial efficacy of various root canal filling materials used in primary teeth: a microbiological study

The primary goal of endodontic treatment in primary teeth is to eliminate infection, and to retain the tooth in a functional state until their nornal exfoliation time without endangering the permanent dentition or the general health of the child. The complexity of the pulp canal system in primary teeth presents a discerning problem for chemo-mechanical preparation. One of the factors determining the success of endodontic treatment in infected primary teeth is the sealing material that should encompass among other factors a potent bactericidal effect and the capacity to resorb along with the roots of primary teeth. This study evaluated the antimicrobial effectiveness of 5 root canal filing materials and a negative control agent against 23 strains of bacteria isolated from infected root canals of primary molar teeth and 3 non standard bacterial strains using agar diffusion assay. The materials were Zinc oxide and Eugenol (ZOE), Zinc oxide-Eugenol and Formocresol (ZOE+FC), Calcium hydroxide and sterile water (CAOH+H2O), Zinc oxide and Camphorated phenol (ZO+CP), Calcium hydroxide and Iodoform (Metapex) and Vaseline (Control). All the materials except Vaseline showed varied antimicrobial activity against the test bacteria. The zones of inhibition were ranked into 4 inhibition categories based on the proportional distribution of the data. All the 26 bacterial isolates were classified under 4 groups based on Aerobic/Anaerobic and Gram positive/Gram negative. Statistical analysis was carried out to compare the antimicrobial effectiveness between materials tested with each of the bacterial groupings. ZOE+FC produced strong inhibtion against most bacteria when compared to ZOE, ZO+CP and CAOH+H2O. Metapex and Vaseline were found to be non inhibitory     

In Vivo Evaluation of a Closed Loop Monitoring Strategy for Induced Paralysis

Objective. Reliable closed loop infusion systems for regulating paralysis level can be a great convenience to the anesthesiologists in automating their task. This paper describes the in vivo performance evaluation of a self-tuning controller that is designed to accommodate large varations in patient drug sensitivity, drug action delays and environmental interfering noise. Methods. The infusion system was evaluated in six adult mongrel dogs. Following the manual induction of paralysis by an anesthesiologist, the controller regulated the infusion of vecuronium to maintain a desired level of paralysis. The integrated EMG response of the hypothenar muscle to a train-of-four stimulation of the ulnar nerve quantified the depth of paralysis. The controller's robustness was tested by contaminating the sensed twitch signal with electrocautery noise and electrode disconnection. Results. The controller reached the initial level of paralysis of 100% in about 4.0 minutes and arrived at the desired level of 90% with an overshoot of 6.38% (±6.82). It maintained the desired level of paralysis with a 2.04% (±1.20) mean offset at 90% and 0.4% (±0.5) mean offset at 80% steady state level, respectively. The mean infusion rate to sustain 90% and 80% paralysis were 2.70 (±2.05) and 2.15 (±2.57) ((mg/kg)/min), respectively. Conclusions. The system adapted to a large variation in the sample subject drug sensitivity. It remained stable despite large amplitude disturbances and maintained the paralysis at the desired level following the removal of the disturbances.     

A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

The year in Cardiothoracic and Vascular Anesthesia: selected highlights from 2011

There have been rapid advances in oral anticoagulation. The oral factor Xa inhibitors rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran recently have been rigorously evaluated. These novel anticoagulants will usher in a new paradigm for perioperative anticoagulation. Perioperative blood conservation in cardiac surgery recently has been highlighted in the updated guidelines by the Society of Cardiovascular Anesthesiologists and the Society of Thoracic Surgeons. These recommendations reflect a comprehensive evaluation of the recent evidence to optimize transfusion practice. Transcatheter mitral valve repair continues to mature. Transcatheter aortic valve implantation for aortic stenosis has entered the clinical mainstream, with randomized trials showing its superiority over medical management and its equivalency to surgical valve replacement in high-risk patients. This transformational technology represents a major leadership opportunity for the cardiac anesthesiologist. Minimally invasive valve surgery has shown effectiveness in high-risk patients. Radial access is equivalent to femoral access for percutaneous coronary intervention in acute coronary syndromes but significantly reduces the risk of local vascular complications. Recent trials have further clarified the roles of medical therapy, percutaneous coronary intervention, and coronary artery bypass surgery in patients with significant coronary artery disease and left ventricular dysfunction. The past year has witnessed major advances in cardiovascular practice with new drugs, new devices, and new guidelines. The coming year most likely will advance these achievements to enhance the care of patients.     

Cost-Effective Isolation of a Process Impurity of Pregabalin

Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin.     

Quantification of a Pharmacodynamic ERK End Point in Melanoma Cell Lysates: Toward Personalized Precision Medicine

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