Feasibility and Acceptability of Computerised Cognitive Training of Everyday Cognition in Parkinson's Disease.

Objectives: We piloted a computerised cognitive training battery in a group of participants with Parkinson's disease without dementia to investigate the relevance of the training to daily life and the feasibility and the acceptability of the tasks. Previous studies of CT have had limited success in the benefits of training, extending to improvements in everyday function. By taking a pragmatic approach and targeting training to the cognitive skills affected by Parkinson's disease (planning, attention, and recollection), whilst using tasks that emulated real-life scenarios, we sought to understand whether participants perceived the training to be effective and to identify the elements of the training that elicited beneficial effects. Methods: Four participants completed a cognitive training session comprising three distinct tasks 5 days a week over two weeks. Participants completed baseline questionnaires examining health-related quality of life, everyday cognition, and apathy before the training period, after the last session, and two weeks after the last session. An interview was held after participants had completed the training. Results: The findings indicated that participants felt the training was acceptable, enhanced their awareness, and encouraged them to monitor their thinking abilities. The group interview indicated that the training was feasible; participants felt the tasks had potential to improve everyday performance, but more supporting information should be provided to facilitate this transfer. Responses to the questionnaires reflected these findings, indicating improvement for some participants' cognition and quality of life. Objective measures supported the subjective reports; there were improvements in some but not all domains. Performance on the planning and recollection tasks improved over the training period, and the evidence for improvement on the attention task was mixed. Conclusion: This study has found that pragmatic computer-based training with real-life outcomes is both feasible and acceptable and should be evaluated more extensively using controlled methods

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

Discovery of a black smoker vent field and vent fauna at the Arctic Mid-Ocean Ridge

The Arctic Mid-Ocean Ridge (AMOR) represents one of the most slow-spreading ridge systems on Earth. Previous attempts to locate hydrothermal vent fields and unravel the nature of venting, as well as the provenance of vent fauna at this northern and insular termination of the global ridge system, have been unsuccessful. Here, we report the first discovery of a black smoker vent field at the AMOR. The field is located on the crest of an axial volcanic ridge (AVR) and is associated with an unusually large hydrothermal deposit, which documents that extensive venting and long-lived hydrothermal systems exist at ultraslow-spreading ridges, despite their strongly reduced volcanic activity. The vent field hosts a distinct vent fauna that differs from the fauna to the south along the Mid-Atlantic Ridge. The novel vent fauna seems to have developed by local specialization and by migration of fauna from cold seeps and the Pacific

Genomic screen for loci associated with tobacco usage in Mission Indians

BACKGROUND: The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California. METHODS: A structured diagnostic interview was used to define two tobacco use phenotypes: 1) any regular tobacco usage (smoked daily for one month or more) and 2) persistent tobacco usage (smoked at least 10 cigarettes a day for more than one year). Heritability was determined and a linkage analysis was performed, using genotypes for a panel 791 microsatellite polymorphisms, for the two phenotypes using variance component methods implemented in SOLAR. RESULTS: Analyses of multipoint variance component LOD scores for the two tobacco use phenotypes revealed two scores that exceeded 2.0 for the regular use phenotype: one on chromosomes 6 and one on 8. Four other loci on chromosomes 1,7,13, and 22 were found with LOD scores between 1.0 and 1.5. Two loci of interest were found on chromosomes 1 and 4 for the persistent use phenotype with LOD scores between 1.3–1.5. Bivariate linkage analysis was conducted at the site on chromosome 4 for persistent tobacco use and an alcohol drinking severity phenotype previously identified at this site. The maximum LOD score for the bivariate analysis for the region was 3.4, however, there was insufficient power to exclude coincident linkage. CONCLUSION: While not providing evidence for linkage to specific chromosomal regions these results identify regions of interest in the genome in this Mission Indian population, for tobacco usage, some of which were identified in previous genome scans of non-native populations. Additionally, these data lend support for the hypothesis that cigarette smoking, alcohol dependence and other consumptive behaviors may share some common risk and/or protective factors in this Mission Indian population

Central metabolism in Mycobacterium smegmatis during the transition from O2-rich to O2-poor conditions as studied by isotopomer-assisted metabolite analysis

Isotopomer-assisted metabolite analysis was used to investigate the central metabolism of Mycobacterium smegmatis and its transition from normal growth to a non-replicating state under a hypoxic environment. Tween 80 significantly promoted aerobic growth by improving O2 transfer, while only small amount was degraded and metabolized via the TCA cycle for biomass synthesis. As the bacillus encountered hypoxic stress, isotopomer analysis suggested: (1) isocitrate lyase activity increased, which further induced glyoxylate pathway and glycine dehydrogenase for replenishing NAD+; (2) the relative amount of acetyl-CoA entering the TCA cycle was doubled, whereas little entered the glycolytic and pentose phosphate pathways

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact

Human Solid Tumor Xenografts in Immunodeficient Mice Are Vulnerable to Lymphomagenesis Associated with Epstein-Barr Virus

Xenografting primary human solid tumor tissue into immunodeficient mice is a widely used tool in studies of human cancer biology; however, care must be taken to prove that the tumors obtained recapitulate parent tissue. We xenografted primary human hepatocellular carcinoma (HCC) tumor fragments or bulk tumor cell suspensions into immunodeficient mice. We unexpectedly observed that 11 of 21 xenografts generated from 16 independent patient samples resembled lymphoid neoplasms rather than HCC. Immunohistochemistry and flow cytometry analyses revealed that the lymphoid neoplasms were comprised of cells expressing human CD45 and CD19/20, consistent with human B lymphocytes. In situ hybridization was strongly positive for Epstein-Barr virus (EBV) encoded RNA. Genomic analysis revealed unique monoclonal or oligoclonal immunoglobulin heavy chain gene rearrangements in each B-cell neoplasm. These data demonstrate that the lymphoid neoplasms were EBV-associated human B-cell lymphomas. Analogous to EBV-associated lymphoproliferative disorders in immunocompromised humans, the human lymphomas in these HCC xenografts likely developed from reactivation of latent EBV in intratumoral passenger B lymphocytes following their xenotransplantation into immunodeficient recipient mice. Given the high prevalence of latent EBV infection in humans and the universal presence of B lymphocytes in solid tumors, this potentially confounding process represents an important pitfall of human solid tumor xenografting. This phenomenon can be recognized and avoided by routine phenotyping of primary tumors and xenografts with human leukocyte markers, and provides a compelling biological rationale for exclusion of these cells from human solid tumor xenotransplantation assays

Psychological and physical correlates of musculoskeletal symptoms in male professional divers and offshore workers

Background: Underwater divers are more likely to complain of musculoskeletal symptoms than a control population. Accordingly, we conducted a study to determine whether musculoskeletal symptoms reflected observable physical disorder, to ascertain the relationship between symptoms and measures of mood, memory and executive function and to assess any need for future screening. Methods: A 10% random sample of responders to a prior postal health questionnaire was examined (151 divers, 120 non-diving offshore workers). Participants underwent physical examination and a neuropsychological test battery for memory and executive function. Participants also completed the Hospital Anxiety and Depression Scale for anxiety (HADSa) and depression (HADSd), and questionnaires for physical health-related quality of life (SF36 PCS), mental health-related quality of life (SF36 MCS), memory (Cognitive Failures Questionnaire (CFQ), Prospective and Retrospective Memory Questionnaire (PRMQ)), executive function (dysexecutive syndrome questionnaire (DEX)), musculoskeletal symptoms (MSS) and general unrelated symptom reporting. Results: Of participants with moderate/severe musculoskeletal symptoms, 52% had physical signs, and of participants with no symptoms, 73% had no physical signs. There was no difference in the prevalence of signs or symptoms between groups. Musculoskeletal symptoms were associated with lower SF36 PCS for both groups. In divers, musculoskeletal symptoms were associated with higher general unrelated symptom reporting and poorer scoring for HADSa, PRMQ, CFQ and DEX with scores remaining within the normative range. A positive physical examination was associated with general unrelated symptom reporting in divers. There were no differences in neuropsychological test scores attributable to either group or musculoskeletal symptoms. Conclusions: Musculoskeletal symptoms were associated with physical signs, but this was not a strong effect. Reporting of musculoskeletal symptoms by the divers studied was also associated with a tendency to report symptoms generally or somatisation, and caution should be exercised regarding their interpretation as an indication of physical disease or their use for health screening

Analysis of Transcriptional Regulatory Pathways of Photoreceptor Genes by Expression Profiling of the Otx2-Deficient Retina

In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease