Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms

Looking toward future clinical diagnostic instruments, there is little debate as to the features that need improvement over the current state-of-the-art. Increasing the speed and sensitivity of the assays, while reducing costs are clear goals. Recently, it has become possible to microminiaturize fluidic and sensing components using micromachining and precision injection molding. There has been a large amount of interest and effort in the area of miniaturization of such systems, yet not all of the properties of fluidics and sensing methods improve as they are drastically reduced in size. It is clear that implementing miniaturized diagnostic instruments is not a matter of simply shrinking their conventional counterparts, nor of automating existing manual procedures. What is required to harness the full potential of scaling technologies is the use of design methods that take into account scaling effects and the development of completely new processing approaches. Beginning with a general overview of the relevant scaling principles, sample preparation and detection approaches are addressed in this context.     

Learning to control arm stiffness under static conditions

We used a robotic device to test the idea that impedance control involves a process of learning or adaptation that is acquired over time and permits the voluntary control of the pattern of stiffness at the hand. The tests were conducted in statics. Subjects were trained over the course of 3 successive days to resist the effects of one of three different kinds of mechanical loads: single axis loads acting in the lateral direction, single axis loads acting in the forward/backward direction, and isotropic loads that perturbed the limb in eight directions about a circle. We found that subjects in contact with single axis loads voluntarily modified their hand stiffness orientation such that changes to the direction of maximum stiffness mirrored the direction of applied load. In the case of isotropic loads, a uniform increase in endpoint stiffness was observed. Using a physiologically realistic model of two-joint arm movement, the experimentally determined pattern of impedance change could be replicated by assuming that coactivation of elbow and double joint muscles was independent of coactivation of muscles at the shoulder. Moreover, using this pattern of coactivation control we were able to replicate an asymmetric pattern of rotation of the stiffness ellipse that was observed empirically. These findings are consistent with the idea that arm stiffness is controlled through the use of at least two independent co-contraction commands.     

Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)‐β1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF‐β1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01–p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001–p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO‐induced kidney fibrosis and dysfunction.     

Flavonoids from Iris songarica and their antioxidant and estrogenic activity

A new dihydroflavonol, songaricol ( 1) and seven known flavonoids, ayamenin A ( 2), irisflavone A ( 3), 5,7-dihydroxy-2',6-dimethoxyisoflavone ( 4), irilin B ( 5), 5,3'-dihydroxy-7,8,2'-trimethoxyisoflavone ( 6) and irisoid A ( 7) were isolated from rhizome and roots of IRIS SONGARICA. Structure elucidation of 1 was achieved through extensive NMR and circular dichroism techniques. Compounds 1, 5 and 7 showed antioxidant activity in HL-60 cells (IC50 values of 21, 11 and 3.8 microg/mL), whereas 2, 5 and the previously isolated irisone B were able to show estrogenic response (EC50 values of 305.5, 159.7 and 322.0 microg/mL) in yeast cells expressing human estrogen receptor (ER-alpha).     

The nonadrenergic noncholinergic-mediated relaxation of corpus cavernosum was impaired in chronic lithium-treated rats: improvement with l-arginine

One-third of lithium-treated men complain from sexual dysfunction, although the exact mechanisms of which are not yet known. In this study we investigated the effect of chronic lithium (LiCl, 600 mg/l for 30 days) administration on the neurogenic relaxation of isolated rat corpus cavernosum. The corporal strips were precontracted with phenylephrine and electrical field stimulation (EFS) was applied to obtain relaxation. Relaxation to EFS was significantly (P<0.001) impaired in LiCl-treated rats. The nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME; 100 microM) inhibited the relaxation to EFS in both LiCl-treated and control rats. The NO precursor l-arginine, at per se noneffective concentration (0.1 mM), significantly (P<0.001) enhanced the EFS-induced relaxation of LiCl-treated corporal strips. The relaxation responses to the NO donor sodium nitroprusside were similar between two groups. These data demonstrate that chronic lithium treatment could impair the NO-mediated neurogenic relaxation of rat corpus cavernosum which could be prevented by l-arginine.     

The response of circulating omentin-1 concentration to 16-week exercise training in male children with obesity

Objectives: The purpose of the present study was to investigate the effects of the 16-week exercise training program on serum omentin-1 in relation to change in insulin resistance in obese male children.

Methods: Thirty-two obese male children, aged 9–12 years, were randomly assigned into Exercise Group (ExG; n = 16) and Control Group (CG; n = 16). ExG participated in a 16-week exercise training program which combined various forms of aerobic activities and resistance training. Body composition, body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment estimate of insulin resistance (HOMA2-IR), blood lipids and serum omentin-1 were assessed before and after 16 weeks of training.

Results: Exercise training significantly decreased body mass (7.5%), BMI (7.6%), WC (4.3%), body fat % (15%), fasting insulin (18.5%), total cholesterol (TC) (5.4%), low-density lipoprotein cholesterol (LDL-C) (17%) and triglyceride (TG) (7.4%) compared to CG. Between-groups comparison showed a considerable exercise-induced upregulation in omentin-1 (ES = 89; P < 0.05) levels. Furthermore, in ExG serum omentin-1 levels were significantly increased from 24.5 ± 8.4 to 35.9 ± 9.3 ng/ml (45%; P < 0.001) after the training program, which was accompanied with significantly decreased fasting insulin (P < 0.001). The changes in omentin-1 concentrations correlated with the changes in BMI (r = ?0.67, P < 0.001), WC (r = ?0.62, P = 0.002), body fat % (r = ?0.50, P = 0.004), insulin (r = ?0.65, P = 0.001), HOMA2-IR (r = ?0.60, P = 0.004), TC (r = ?0.53, P = 0.004) and LDL-C (r = ?0.51, P = 0.004) in ExG. BMI (β = ?0.50, P = 0.009) and fasting insulin (β = ?0.54, P = 0.006) changes were found to be independent predictors of omentin-1 increment in multiple regression analysis.

Conclusion: Exercise training resulted in a significant increase in serum omentin-1 concentrations in children with obesity. The ?ndings suggest that exercise-induced changes in omentin-1 may be associated with the bene?cial effects of exercise on reduced insulin and weight lost.     

Friction Stir Welding/Processing of Mg-Based Alloys: A Critical Review on Advancements and Challenges

Friction stir welding (FSW) and friction stir processing (FSP) are two of the most widely used solid-state welding techniques for magnesium (Mg) and magnesium alloys. Mg-based alloys are widely used in the railway, aerospace, nuclear, and marine industries, among others. Their primary advantage is their high strength-to-weight ratio and usefulness as a structural material. Due to their properties, it is difficult to weld using traditional gas- or electric-based processes; however, FSW and FSP work very well for Mg and its alloys. Recently, extensive studies have been carried out on FSW and FSP of Mg-based alloys. This paper reviews the context of future areas and existing constraints for FSW/FSP. In addition, in this review article, in connection with the FSW and FSP of Mg alloys, research advancement; the influencing parameters and their influence on weld characteristics; applications; and evolution related to the microstructure, substructure, texture and phase formations as well as mechanical properties were considered. The mechanisms underlying the joining and grain refinement during FSW/FSP of Mg alloys-based alloys are discussed. Moreover, this review paper can provide valuable and vital information regarding the FSW and FSP of these alloys for different sectors of relevant industries.