Use of a randomised single case experimental design to evaluate therapy for unilateral neglect

Unilateral spatial neglect is a disabling disorder, or set of disorders, that commonly occurs after stroke. Previous research suggests that tactile stimulation may reduce neglect, albeit temporarily. This study evaluated the effectiveness of a therapy package combining stimulation of the affected hand and the behavioural technique of self‐instructional training. A randomised single case design, consisting of 12 phases (six treatment and six no treatment) administered in a random order, was used. Two research participants were assessed three times per phase using measures of impairment and activity. Analyses were by visual inspection, fitting linear regression lines to each phase and t test comparisons of these slopes in the treatment and no treatment phases. Visual inspection showed (1) marked variability within a phase, and (2) positive slopes were not more likely for treatment than no treatment for either participant. There was no significant difference on t test between the mean treatment and no treatment slopes on impairment or activity level measures. This study did not demonstrate evidence of effectiveness of the new therapy for neglect. Compliance by participants was poor indicating low acceptability of the therapy regime. Despite the results from these two participants, the study raises important methodological issues for practising clinicians and researchers. Clinical randomised single case designs have difficulties as well as advantages when used with a condition as variable as neglect. Despite this, these designs and the analysis of differential recovery rates warrant further investigation, and could be used to determine the effectiveness of therapy for other post‐stroke cognitive impairments.     

MicroRNA‐21 (miR‐21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA‐21 (miR‐21) expression in the kidney following acute kidney injury. This study investigated the potential of miR‐21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR‐21 was found to be readily detectable in HMP by RT‐qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117–1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post‐perfusion. MiR‐21 quantification at 60 min post‐perfusion correlated with eGFR at 6 and 12 months post‐transplantation. These data suggest that miR‐21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR‐21 may be such a marker.     

Metabolic clues regarding the enhanced performance of elite endurance athletes from orchiectomy-induced hormonal changes

This article examines the metabolic performance of an elite cyclist, Lance Armstrong, before and after his diagnosis with testicular cancer. Although a champion cyclist in 1-day events prior to his diagnosis of testicular cancer at age 25, he was not a contender in multi-day endurance cycle races such as the 3-week Tour de France. His genetic makeup and physiology (high VO2max, long femur, strong heavy build) coupled with his ambition and motivation enabled him at an early age to become one of the best 1-day cyclists in the world. Following his cancer diagnosis, he underwent a unilateral orchiectomy, brain surgery and four cycles of chemotherapy. After recovering, he returned to cycling and surprisingly excelled in the Tour de France, winning this hardest of endurance events 7 years running. This dramatic transformation from a 1-day to a 3-week endurance champion has led many to query how this is possible, and under the current climate, has led to suggestions of doping as to the answer to this metamorphosis. Physiological tests following his recovery indicated that physiological parameters such as VO2max were not affected by the unilateral orchiectomy and chemotherapy. We propose that his dramatic improvement in recovery between stages, the most important factor in winning multi-day stage races, is due to his unilateral orchiectomy, a procedure that results in permanent changes in serum hormones. These hormonal changes, specifically an increase in gonadotropins (and prolactin) required to maintain serum testosterone levels, alter fuel metabolism; increasing hormone sensitive lipase expression and activity, promoting increased free fatty acid (FFA) mobilization to, and utilization by, muscles, thereby decreasing the requirement to expend limiting glycogen stores before, during and after exercise. Such hormonal changes also have been associated with ketone body production, improvements in muscle repair and haematocrit levels and may facilitate the loss of body weight, thereby increasing power to weight ratio. Taken together, these hormonal changes act to limit glycogen utilization, delay fatigue and enhance recovery thereby allowing for optimal performances on a day-to-day basis. These insights provide the foundation for future studies on the endocrinology of exercise metabolism, and suggest that Lance Armstrong's athletic advantage was not due to drug use.     

Two new secoiridoid glucosides and a new lignan from the roots of <Emphasis Type="Italic">Ilex pubescens</Emphasis>

Two new secoiridoid glucosides, ilexpublignoside (1), pubzenoside (2), and a new lignan, ilexlignan B (3), along with seven known compounds (4–10) were isolated from the roots of Ilex pubescens for the first time. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including IR, UV, HR-ESI–MS, CD, NMR experiments, as well as comparison with the reported data.     

Analysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP

Multipoint linkage analysis is an important approach for localizing disease‐associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use marker allele frequencies determined by admixture proportions averaged over the entire sample. However, admixture proportions vary among pedigrees and throughout the genome in a family‐specific manner. Here, we evaluate several approaches to model admixture in linkage analysis, providing different levels of detail about ancestral origin. To perform our evaluations, for specification of marker allele frequencies, we used data on 67 Caribbean Hispanic admixed families from the Alzheimer's Disease Sequencing Project. Our results show that choice of admixture model has an effect on the linkage analysis results. Variant‐specific admixture proportions, computed for individual families, provide the most detailed regional admixture estimates, and, as such, are the most appropriate allele frequencies for linkage analysis. This likely decreases the number of false‐positive results, and is straightforward to implement.