The Concurrent Validity of the Shipley-2 and the WAIS-IV

The recently developed Shipley-2 was compared to the Wechsler Adult Intelligence Scale, 4th edition (WAIS-IV) in order to determine the former\u27s level of concurrent validity as a test of intellectual ability. A convenience sample of 25 clinical subjects were administered both measures at two participating outpatient clinics, and the sum results of this testing were tabulated and then correlated through the use of a statistical software package. Results showed very strong levels of correlation between the five Shipley-2 scores (Vocabulary, Abstraction, Block Patterns, Composite A, and Composite B) and the Full Scale IQ (FSIQ) of the WAIS-IV (r = .549 to .807, p = .01), as well as moderate to strong correlations between the Shipley-2 scale scores and the Index scores from the WAIS-IV. More varied levels of correlation were detected between the WAIS-IV subtests and the various scores from the Shipley-2. These results suggest that the Shipley-2 can be effectively used as a screening tool or quick measure of intellectual ability among an outpatient clinical population or within similar mental health settings. However, a larger and more comprehensive analysis is needed in order to determine the full range of the new Shipley\u27s applicability as a measure of intellectual functioning

A metabolomic investigation of the effects of vitamin E supplementation in humans.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Vitamin E is a nutrient with both antioxidant and non-antioxidant activities and has been shown to modulate the function of a number of cell types in vitro and in human studies. However studies have also shown vitamin E to have detrimental interactions and therefore it is important to establish the extent to which this nutrient influences metabolism. Metabolomics can potentially identify nutrient-metabolism interactions and therefore the aim of this study was to use a non-targeted metabolomic approach to identify changes to the plasma metabolome following vitamin E supplementation in humans. METHODS: A relatively homogenous healthy adult male population (n = 10) provided a fasting blood sample immediately before and after a 4-week vitamin E supplementation regime (400 mg/d of RRR-α-tocopheryl acetate)) on top of their habitual diet. Plasma samples were analysed for vitamin E and clinical markers. Plasma underwent non-targeted metabolite profiling using liquid chromatography/mass spectroscopy and data was processed using multivariate statistical analysis. RESULTS: Plasma vitamin E concentrations were significantly increased following supplementation (p < 0.001). A partial least squares-discriminant analysis (PLS-DA) model was able to discriminate between samples taken pre and post vitamin E supplementation (goodness of fit R2Y = 0.82, predictive ability Q2 = 0.50). Variable influence on projection and PLS-DA loadings highlighted a number of discriminating ions that were confirmed as discriminatory through pairwise analysis. From database searches and comparison with standards these metabolites included a number of lysophosphatidylcholine species (16:0, 18:0, 18:1, 18:2, 20:3 and 22:6) that were increased in intensity post supplementation by varying degrees from 4% to 29% with the greatest changes found for lysoPC 22:6 and 20:3. CONCLUSIONS: Although a small scale study, these results potentially indicate that vitamin E supplementation influences phospholipid metabolism and induces lysoPC generation; a general pro-inflammatory response. Moreover the study identifies novel areas of vitamin E interactions and highlights the potential of metabolomics for elucidating interactions between nutrients and metabolic pathways in nutritional research

Symposium 2: Modern approaches to nutritional research challenges: Targeted and non-targeted approaches for metabolite profiling in nutritional research

The present report discusses targeted and non-targeted approaches to monitor single nutrients and global metabolite profiles in nutritional research. Non-targeted approaches such as metabolomics allow for the global description of metabolites in a biological sample and combine an analytical platform with multivariate data analysis to visualise patterns between sample groups. In nutritional research metabolomics has generated much interest as it has the potential to identify changes to metabolic pathways induced by diet or single nutrients, to explore relationships between diet and disease and to discover biomarkers of diet and disease. Although still in its infancy, a number of studies applying this technology have been performed; for example, the first study in 2003 investigated isoflavone metabolism in females, while the most recent study has demonstrated changes to various metabolic pathways during a glucose tolerance test. As a relatively new technology metabolomics is faced with a number of limitations and challenges including the standardisation of study design and methodology and the need for careful consideration of data analysis, interpretation and identification. Targeted approaches are used to monitor single or multiple nutrient and/or metabolite status to obtain information on concentration, absorption, distribution, metabolism and elimination. Such applications are currently widespread in nutritional research and one example, using stable isotopes to monitor nutrient status, is discussed in more detail. These applications represent innovative approaches in nutritional research to investigate the role of both single nutrients and diet in health and disease

Protection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing Cryptococcus Alkaline Extracts

A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4(+) T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine. IMPORTANCE: The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of β-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. The technology used for antigen extraction and subsequent loading into the glucan particle delivery system is relatively simple and can be applied to vaccine development against other pathogens

Inter-individual responses to a blueberry intervention across multiple endpoints

Inter-individual variation exists in response to diet and in the endpoints related to vascular diseases and cognitive impairment. Therefore, the evaluation and characterisation of responses to a dietary intervention targeting these endpoints is important. A dietary intervention with 37 participants has been performed comparing two forms of blueberry, either whole fresh blueberry (160 g), freeze-dried blueberry powder (20 g) or a placebo control (microcrystalline cellulose), in a 1-week single-blinded cross-over randomised controlled trial (RCT) in a healthy population. The response to the intervention was calculated for each endpoint using the percentage change (±%) compared to the baseline. Extensive inter-individual variation was found in vascular health parameters (−141 to +525%) and cognitive domains (−114 to +96%) post-intervention, but there was no consistent response following the two interventions between and within participants for each endpoint measured. No significant putative discriminating urinary metabolites between interventions were found using supervised multivariate analysis. Although several discriminatory metabolites were found between the responder and non-responder groups, it was not possible to identify predictors of the response using receiver operating curve analysis. To conclude, this is the first blueberry intervention applying quartile divisions to characterise individual responses in vascular and cognitive endpoints following a specific dietary intervention; however, we did not find any consistency in the individual responses to the interventions, and we could not identify a predictive urinary metabolite as a potential biomarker for differentiation between responders and non-responders. However, the overall approach of defining a metabolic signature of response could be used in the future for tailored personalised nutritional advice

Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures

Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs

Effects of chronic consumption of specific fruit (berries, cherries and citrus) on cognitive health: a systematic review and meta-analysis of randomised controlled trials

Objectives: The cognitive-protective effects related to the consumption of a variety of fruits are supported by several intervention studies. This systematic review and meta-analysis compared the magnitude of effects following chronic (≥1 week) consumption of frozen, freeze-dried powder including extracts and juices of fruits, covering berries, cherries and citrus, on cognition and mood in adults. Methods: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until February, 2021. Inclusion criteria were randomised controlled trials assessing memory, executive function, psychomotor speed, mood and mini mental state examination in adult participants ≥18 years of age. Cognition was tested by global or domain specific tasks. Results: Out of 13,861 articles identified, 16 papers were included; 11 studies provided suitable data for meta-analysis. Fourteen studies reported improvement or trend for improvement in cognition, five studies assessed mood and one study supplementing grape juice found trend for mood improvement. From the meta-analysis, cherry juice supplementation was suggested to improve psychomotor speed by -0.37 of standardised mean difference (95% CI [-0.74, 0.01]) in reaction time (P = 0.05). Conclusions: The meta-analysis did not sufficiently support a role for fruits or fruit forms to improve cognition and mood

Institutional Transplant as Political Opportunity: The Practice and Politics of Indian Electricity Regulation

India has a decade-long experience with independent regulatory agencies in public services as an institutional transplant from the industrialized world. Introduced at the behest of international donor agencies, regulators in India are intended, somewhat naively, to provide an apolitical space for decision making to assuage investor concerns over arbitrary administrative actions, and thereby stimulate private investment. In practice, regulators have had to negotiate a terrain over which the state has continued to exercise considerable control. Regulators have also been been shaped in their functioning by national and sub-national political traditions and by administrative and political practices. The result is a hybrid institutional form that combines politics as usual with intriguing new, and unanticipated, opportunities for political intervention. This paper will explore the origins of electricity regulation as a form of institutional isomorphism. It will then compare the regulatory experience in India\u27s electricity sector across two Indian states to understand the implications of transplanting regulatory agencies in the global south. An examination of the process through which regulatory decisions are reached illustrates how existing bureaucratic and technocratic networks, transplanted procedures, and administrative cultures combine to conservatively manage long-standing political tensions around electricity. In seeking to manage those tensions, regulators often take decisions - on tariff setting, for example - based on a political reading that belies the technocratic narrative on which institutional credibility rests. At the same time, civil society groups ranging from residential associations to professional associations to individuals are using newly created regulatory spaces to structure a more deliberative decision process

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry