Increased understanding of the molecular mechanisms of tumor heterogeneity combined with rapid advances in the field of pharmacogenetics and pharmacogenomics have fuelled studies on individualizing anticancer therapy. Doxorubicin (Adriamycin), is an anthracycline glycoside antibiotic originally produced by Streptomyces peucetius var. caesius, and is widely used either as a single agent or in combination with other chemotherapeutic regimens for curative, adjuvant, and palliative treatment in cancer patients. The pharmacogenetics of doxorubicin has not been well characterized. The polygenic influence of functional candidate gene variants across doxorubicin biochemical pathway is hypothesized to contribute to its heterogeneity in disposition, influencing the efficacy of treatment and occurrence of adverse effects like cardiomyopathy in patients undergoing doxorubicin based adjuvant and neo-adjuvant chemotherapy. The pharmacogenetics of Asian population differs from that of other ethnic groups, particularly from Caucasian and African populations, and indicates an important role of ethnicity in determining predictive end points during chemotherapy and in individualizing treatment. This review comprehensively examines the pharmacogenetics of the regulatory nuclear receptor Pregnane-X Receptor (PXR), influx (SLC22A16) and efflux drug transporters (ABCB1, ABCG2, ABCC5, ABCB5 and RLIP76) and drug metabolizing enzymes (CBR1, CBR3) across the biochemical pathway of doxorubicin in Asian breast cancer patients receiving doxorubicin based adjuvant chemotherapy. The influence of functional genetic variants on the inter-individual variability in pharmacokinetics of doxorubicin and its major metabolite are also discussed. The incorporation of non-genetic factors and subsequent validation of these findings in different patient and population groups will be valuable in tailoring doxorubicin dosage regimens to an individual to maximize therapeutic efficacy and minimize adverse reactions, leading to improved clinical outcomes.

No abstract

Smile is one of the most natural and important expressions of human emotion. Man uses his lips mainly to register his emotions. Thus, the slightest asymmetry or weakness around the lips and mouth may transform this pleasant expression into embarrassment and distortion. The circumoral musculature, the major part of which is supplied by the marginal mandibular branch of the facial nerve, is the main factor in this expression. Therefore, an injury to this nerve during a surgical procedure can distort the expression of the smile as well as other facial expressions. This nerve often gets injured by surgeons in operative procedures in the submandibular region, like excision of the submandibular gland due to lack of accurate knowledge of variations in the course, branches and relations. In the present study, 50 facial halves were dissected to study the origin, entire course, termination, branches, muscles supplied by it, its anastomoses with other branches of facial nerve on the same as well as on the opposite side and its relations with the surrounding structures. The marginal mandibular branch of the facial nerve was found superficial to the facial artery and (anterior) facial vein in all the cases (100%). Thus the facial artery can be used as an important landmark in locating the marginal mandibular nerve during surgical procedures. Such a study can help in planning precise and accurate incisions and in preventing the unrecognized severance of this nerve during surgical procedures.

Electroactive polymers undergo physical deformation in response to external voltage stimuli. These electrically activated polymers possess extraordinary features making them capable of use as lightweight sensors and actuators in manifold applications. The characteristics of applied voltage and environmental conditions, especially the moisture content surrounding the polymer, have a combined influence on the dynamical behavior of these polymers. In order to characterize these polymers under varying environmental conditions, this paper discusses the experimental procedure and modeling techniques used to derive a representative model. Validation of the model derived is provided by comparison tests of the simulated model results and those for experimental specimens. Ionic polymer-metal composites are used for this humidity and electrodynamical study. Insight into the numerous applications of electroactive polymers as actuators is given. The extended model allows for controller design for typical tracking problems. The control architecture presented includes a model reference adaptive scheme along with pole-placement control strategies for achieving the goal of tracking. A genetic algorithm approach is employed to carry out the optimization for the control action. The resulting tracking control of ionic polymer-metal composites, acting as actuators, is simulated. Simulations show that tracking results can be achieved with a correlation of 99% and a root mean square error of less than 30%.

Cereal Chem. 79(6):834-837Amaranth meal is a rich source of proteins, carbohydrates, and minerals with a low amount of anti-nutritional factors. It exhibits good functional properties. The effect of NaCl and NaHCO 3 salts and pH level on the functional properties of amaranth meal was studied. The water absorption capacity and protein solubility were improved in the presence of the salts. Protein solubility was high at extreme pH values and minimum at pH 4. Foaming capacity was poor in the presence of the two salts, while foam stability was better at lower concentrations of NaCl (0.2-0.6M). Changes in pH had a pronounced effect on the foaming properties of amaranth meal. Salts did not change the emulsification properties but significantly increased the relative viscosity of amaranth seed meal at higher concentrations of NaCl and NaHCO 3 (0.6-1.0M). Relative viscosity was highest at pH 10 and lowest at pH 4. Functionality has been defined as any property of a food ingredient, except its nutritional value, that has a great impact on its utilization. The functional properties directly or indirectly affect the processing applications, food quality, and ultimately their acceptance and utilization in food and food formulations. The use of soybean as a source of nutritious food and substitute for meat is due to the knowledge of the functional properties of its flour and other products (Volkert and Klein 1979).Amaranth is the world's most nutritious pseudo-cereal grain with multiple uses (Teutonico and Knorr 1985). It is one of those rare plants whose leaves are eaten as a vegetable while the seeds are used as cereals. Amaranth grows vigorously; resists drought, heat, and pests; and adapts readily to new environments, including some that are inhospitable to conventional cereal crops.Amaranth produces a higher yield of seeds than most common cereals. With a protein content of 16%, amaranth seed compares well with the conventional cultivars of wheat (12-14%), rice (7-10%), maize (9-10%), and other widely consumed cereals (Chang and Sosulski 1985). Amaranth proteins have nearly twice the lysine content of wheat protein, three times that of maize, and as much as milk, the standard of nutritional excellence. With so much to its credit, amaranth crops are still playing a secondary role to crops like rice and wheat on our dinner plates. Therefore, the challenge is to incorporate it into existing food formulations to modify the functional and nutritional qualities, and to create new products from it.A good amount of work has been done on the proximate composition, nutritional value, and genetic potential of this crop (Raina and Datta 1992; Bejosano and Corke 1998), but very little is known about its functional attributes. This investigation deals with the functional properties of amaranth meal in the presence of salts and at various pH levels, to evaluate its utilization in various products. The effect of salts is important because salts are integral constituents of food product formulations; concentrations of 0.2-0.3M are commo...

No abstract

Ureteral peristalsis can be considered as a series of waves on the ureteral wall, which transfers the urine along the ureter toward the bladder. The stones that form in the kidney and migrate to the ureter can create a substantial health problem due to the pain caused by interaction of the ureteral walls and stones during the peristaltic motion. Three-dimensional (3D) computational fluid dynamics (CFD) simulations were carried out using the commercial code ansys fluent to solve for the peristaltic movement of the ureter, with and without stones. The effect of stone size was considered through the investigation of varying obstructions of 5%, 15%, and 35% for fixed spherical stone shape. Also, an understanding of the effect of stone shape was obtained through separate CFD calculations of the peristaltic ureter with three different types of stones, a sphere, a cube, and a star, all at a fixed obstruction percentage of 15%. Velocity vectors, mass flow rates, pressure gradients, and wall shear stresses were analyzed along one bolus of urine during peristalsis of the ureteral wall to study the various effects. It was found that the increase in obstruction increased the backflow, pressure gradients, and wall shear stresses proximal to the stone. On the other hand, with regard to the stone shape study, while the cube-shaped stones resulted in the largest backflow, the star-shaped stone showed highest pressure gradient magnitudes. Interestingly, the change in stone shape did not have a significant effect on the wall shear stress at the obstruction level studied here.

No abstract