Patients with advanced kidney disease are at risk for cognitive impairment, which may persist after kidney transplantation. We sought to understand changes in neurocognitive function domains ...utilizing comprehensive cognitive assessments.
Prospective cohort study.
Single-center study of patients undergoing kidney transplantation.
Kidney transplantation.
Changes in neurocognitive function as measured by the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Parts A and B (TRAIL A and B) before transplantation (baseline) and compared to 3 months and 12 months posttransplant.
Wilcoxon signed-rank and linear mixed effect models were utilized to assess changes in neurocognitive scores at 3 months and 12 months compared to baseline.
Thirty-two patients were included with a mean age of 45 years, 47% female, 85% White, and 62% with at least some college education. Hypertension and diabetes were etiologies of kidney disease in 31% and 25% of patients, respectively. Baseline RBANS and TRAIL A and B scores averaged 84.7±14, 40.4±9.9, and 41±11.5, respectively. Although there were posttransplant improvements in immediate and delayed memory at 3 months, these were not sustained at 12 months. There were no significant differences from baseline at 3 months and 12 months in RBANS index scores for language, visuospatial/constructional abilities, and attention. Compared to baseline, TRAIL A scores were not significantly different at 3 months but were significantly improved at 12 months, whereas TRAIL B scores improved significantly at both 3 months and 12 months.
Single-center design and small sample size.
Utilizing comprehensive cognitive assessments, we found improvements in attention and executive function in the first posttransplant year as measured by TRAIL A and B. However, there was no significant change in global cognition as measured by RBANS. These findings identify cognitive domains for potential intervention in the posttransplant population.
Previous authors have reported power-pedaling rate relationships for maximal cycling. However, the joint-specific power-pedaling rate relationships that contribute to pedal power have not been ...reported. We determined absolute and relative contributions of joint-specific powers to pedal power across a range of pedaling rates during maximal cycling. Ten cyclists performed maximal 3 s cycling trials at 60, 90, 120, 150, and 180 rpm. Joint-specific powers were averaged over complete pedal cycles, and extension and flexion actions. Effects of pedaling rate on relative joint-specific power, velocity, and excursion were assessed with regression analyses and repeated-measures ANOVA. Relative ankle plantar flexion power (25 to 8%; P = .01; R(2) = .90) decreased with increasing pedaling rate, whereas relative hip extension power (41 to 59%; P < .01; R(2) = .92) and knee flexion power (34 to 49%; P < .01; R(2) = .94) increased with increasing pedaling rate. Knee extension powers did not differ across pedaling rates. Ankle joint angular excursion decreased with increasing pedaling rate (48 to 20 deg) whereas hip joint excursion increased (42 to 48 deg). These results demonstrate that the often-reported quadratic power-pedaling rate relationship arises from combined effects of dissimilar joint-specific power-pedaling rate relationships. These dissimilar relationships are likely influenced by musculoskeletal constraints (ie, muscle architecture, morphology) and/or motor control strategies.
Background Prior studies have demonstrated lengthening of normal small intestinal segments using mechanical expanders. The present study assesses the feasibility of intestinal lengthening in rats ...that have undergone extensive small intestinal resection. Methods Female rats underwent small intestinal resection. After 6 weeks, the animals underwent the placement of a mechanical expander device with or without gradual mechanical lengthening. After 3 weeks, the intestinal segments were retrieved for analyses. Results Isolated intestinal segments without mechanical lengthening did not change in length, whereas isolated intestinal segments that were mechanically lengthened more than doubled their initial length. The total alkaline phosphatase activity was 2.4 μmol/min in the isolated intestinal segments and 4.9 μmol/min in the mechanically lengthened segments. The total lactase activity was 0.005 μmol/min in the isolated intestinal segments and 0.007 μmol/min in the mechanically lengthened segments. Smooth muscle thickness was 370 μm in the isolated intestinal segments and 530 μm in the mechanically lengthened segments. Conclusion Mechanical small bowel lengthening was achieved in intestinal segments after extensive small intestinal resection. There was an increase in the total alkaline phosphatase activity and preservation of the total lactase activity. Mechanical lengthening may be a useful technique to increase intestinal length in patients with short bowel syndrome.
Movement in echinoderms is facilitated by the coordinated activity of thousands of individually addressable and reversibly adhesive tube feet. To investigate the potential applicability of these ...unique biological actuators as a locomotory structure for robotics applications, we describe here the design, fabrication, and evaluation of an elastomeric structural analogue. The synthetic tube feet were modeled as bistable deformable domes, containing an embedded magnet to facilitate the reversible attachment to ferromagnetic materials. Two unique robots were developed using the bistability of these domes - CircleBot, which is capable of rolling on ferrous surfaces using a pull and roll technique, and PlanarBot, which uses a programmed deflection direction in the domes to move in a plane.
In five healthy subjects and 18 patients, cine magnetic resonance (MR) imaging of the heart was performed with a true fast imaging with steady-state precession (FISP) sequence. Results were compared ...both quantitatively and qualitatively with those at cine fast low-angle shot (FLASH) MR imaging. The blood-myocardial contrast-to-noise ratio (CNR) was 2.0 times higher and the normalized (for measurement time and pixel size) blood-myocardial CNR was 4.0 times higher for true FISP compared with FLASH MR imaging. Qualitative scores for image quality were significantly higher with true FISP MR imaging. Segmented cine true FISP MR imaging generated high-contrast MR images of the heart in healthy subjects and in patients with heart disease and produced image quality superior to that with cine FLASH MR imaging.
The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone ...Antagonist) trial.
Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics.
TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years).
The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region.
In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist TOPCAT; NCT00094302)
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Because the activities of HER family members are elevated and/or aberrant in a variety of human neoplasms, these cell surface receptors are receiving increasing attention as potential therapeutic ...targets. In the present study, we examined the effect of combining the HER family tyrosine kinase inhibitor CI1033 (PD 183805) with the topoisomerase (topo) I poison 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, in a number of different cell lines. Colony-forming assays revealed that the antiproliferative effects of simultaneous treatment with CI1033 and SN-38 were synergistic in T98G glioblastoma cells and HCT8 colorectal carcinoma cells, whereas sequential treatments were additive at best. In additional studies examining the mechanistic basis for these findings in T98G cells, immunoblotting revealed that the inhibitory effects of CI1033 on epidermal growth factor receptor autophosphorylation were unaffected by SN-38. Likewise, CI1033 had no effect on topo I polypeptide levels, localization, or activity. Nonetheless, CI1033 markedly enhanced the number of covalent topo I-DNA complexes stabilized by SN-38 or the related agent topotecan (TPT). Analysis of intracellular SN-38 levels by high-performance liquid chromatography and intracellular TPT levels by flow microfluorometry revealed that CI1033 increased the steady-state accumulation of SN-38 and TPT by 9.4 +/- 1.9- and 1.8 +/- 0.2-fold, respectively. Further evaluation revealed that the initial rate of TPT uptake was unaffected by CI1033, whereas the rate of efflux was markedly diminished. Additional studies demonstrated that T98G and HCT8 cells express the breast cancer resistance protein (BCRP), a recently cloned ATP binding cassette transporter. Moreover, CI1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not empty vector. Conversely, CI1033 accumulation was diminished in cells expressing BCRP, suggesting that CI1033 is a substrate for this efflux pump. These results indicate that CI1033 can modulate the accumulation and subsequent cytotoxicity of two widely used topo I poisons in cells that have no history of previous exposure to these agents.
•Silver nanowires (AgNW) were supersonically sprayed onto a copper substrate.•Silver nanowires were well connected because of self-sintering or fusion resulting from supersonic impacts.•The optimal ...thickness was identified that maximizes critical heat flux and the effective heat transfer coefficient.•The surface temperature of the heat source decreased substantially during efficient heat.
Rapid production of nanoscale-textured surfaces for microscale devices is important for commercial applications. In this study, we introduce a commercially viable method to fabricate nanotextured surfaces used in pool-boiling heat-transfer applications. Silver nanowires were supersonically sprayed onto copper substrates with good adhesive strength. The coating method required little time and could be adapted for roll-to-roll processing. The fabricated nanotextured surfaces showed a significantly increased critical heat flux (CHF) and effective heat transfer coefficient (heff), as evidenced by the release of numerous bubbles from nanotextured nucleation sites during pool-boiling. The silver nanowires were well connected either by self-sintering or due to the fusion induced by supersonic impacts with the copper substrate. The thickness of the coated layer could be controlled by the number of spray sweeps/passes and the optimal thickness for maximizing CHF and heff was identified. The nanotextured surfaces were characterized by scanning electron microscopy and by bubble formation and release as visualized with a charge-coupled device camera.
Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In ...primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16(INK4a) tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors.
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