Multi-domain training enhances attentional control

Multi-domain cognitive training potentially increases the likelihood for an overlap in processing component with transfer tasks and everyday life, and hence is a promising training approach for older adults. To empirically test this, 84 healthy older adults aged 65 to 75 years were randomly assigned to one of three single-domain training conditions (inhibition, visuomotor function, spatial navigation) or to the simultaneous training of all three cognitive functions (multi-domain training condition). All participants trained on an iPad at home for 50 training sessions. Before and after the training, and at a six-month follow-up measurement, cognitive functioning and training transfer were assessed with a neuropsychological test battery including tests targeting the trained functions (near transfer) and transfer to executive functions (far transfer: attentional control, working memory, speed). Participants in all four training groups showed a linear increase in training performance over the 50 training sessions. Using a latent difference score model, the multi-domain training group, compared to the single-domain training groups, showed more improvement on the far transfer, executive attentional control composite. Individuals with initially lower baseline performance showed higher training-related improvements, indicating that training compensated for lower initial cognitive performance. At the six-month follow-up, performance on the cognitive test battery remained stable. This is one of the first studies that systematically investigated multi-domain training including comparable single-domain training conditions. Our findings suggest that multi-domain training enhances executive attentional control involved in handling several different tasks at the same time, an aspect in everyday life that is particularly challenging for older people

Dementia risk and dynamic response to exercise: A non-randomized clinical trial

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer’s. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. Methods Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). Results Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. Conclusions Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer’s disease

The impact of Mendelian sleep and circadian genetic variants in a population setting

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint similar to 7 mins earlier and similar to 5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10(-8); and had a 57-minute earlier midpoint sleep, P = 5x10(-7)). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.Peer reviewe

Multistate Shigellosis Outbreak and Commercially Prepared Food, United States

In 2000, shigellosis traced to a commercially prepared dip developed in 406 persons nationwide. An ill employee may have inadvertently contaminated processing equipment. This outbreak demonstrates the vulnerability of the food supply and how infectious organisms can rapidly disseminate through point-source contamination of a widely distributed food item

Uncovering the genomic basis of an extraordinary plant invasion

Invasive species are a key driver of the global biodiversity crisis, but the drivers of invasiveness, including the role of pathogens, remain debated. We investigated the genomic basis of invasiveness in Ambrosia artemisiifolia (common ragweed), introduced to Europe in the late 19th century, by resequencing 655 ragweed genomes, including 308 herbarium specimens collected up to 190 years ago. In invasive European populations, we found selection signatures in defense genes and lower prevalence of disease-inducing plant pathogens. Together with temporal changes in population structure associated with introgression from closely related Ambrosia species, escape from specific microbial enemies likely favored the plant's remarkable success as an invasive species.Peer reviewe

Prediction of fluoroquinolone susceptibility directly from whole-genome sequence data by using liquid chromatography-tandem mass spectrometry to identify mutant genotypes

ABSTRACT Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility. </jats:p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy