The Effects of Color on Cognitive Performance

Typically, assessments are administered on white pieces of paper. This research experiment was designed to test the effects of colored paper on an individual’s cognitive performance. Researchers have administered an IQ test to approximately 60 male and female undergraduate participants. Participants were recruited through the NERD System and were given partial credit in their individual classes. The IQ tests were printed on four different colors of paper and given out to participants at random. It was hypothesized that utilizing colored paper on an administered test will increase the individual’s cognitive performance. Results will be discussed in terms of increasing cognitive performance in educational and work environments

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC

Identifying opportunities for upstream evaluations relevant to child and maternal health:a UK policy-mapping review

Objective: Interventions to tackle the social determinants of health can improve outcomes during pregnancy and early childhood, leading to better health across the life course. Variation in content, timing and implementation of policies across the 4 UK nations allows for evaluation. We conducted a policy-mapping review (1981–2021) to identify relevant UK early years policies across the social determinants of health framework, and determine suitable candidates for evaluation using administrative data. Methods: We used open keyword and category searches of UK and devolved Government websites, and hand searched policy reviews. Policies were rated and included using five criteria: (1) Potential for policy to affect maternal and child health outcomes; (2) Implementation variation across the UK; (3) Population reach and expected effect size; (4) Ability to identify exposed/eligible group in administrative data; (5) Potential to affect health inequalities. An expert consensus workshop determined a final shortlist. Results: 336 policies and 306 strategy documents were identified. Policies were mainly excluded due to criteria 2–4, leaving 88. The consensus workshop identified three policy areas as suitable candidates for natural experiment evaluation using administrative data: pregnancy grants, early years education and childcare, and Universal Credit. Conclusion: Our comprehensive policy review identifies valuable opportunities to evaluate sociostructural impacts on mother and child outcomes. However, many potentially impactful policies were excluded. This may lead to the inverse evidence law, where there is least evidence for policies believed to be most effective. This could be ameliorated by better access to administrative data, staged implementation of future policies or alternative evaluation methods

Identifying opportunities for upstream evaluations relevant to child and maternal health: a UK policy-mapping review

OBJECTIVE: Interventions to tackle the social determinants of health can improve outcomes during pregnancy and early childhood, leading to better health across the life course. Variation in content, timing and implementation of policies across the 4 UK nations allows for evaluation. We conducted a policy-mapping review (1981-2021) to identify relevant UK early years policies across the social determinants of health framework, and determine suitable candidates for evaluation using administrative data. METHODS: We used open keyword and category searches of UK and devolved Government websites, and hand searched policy reviews. Policies were rated and included using five criteria: (1) Potential for policy to affect maternal and child health outcomes; (2) Implementation variation across the UK; (3) Population reach and expected effect size; (4) Ability to identify exposed/eligible group in administrative data; (5) Potential to affect health inequalities. An expert consensus workshop determined a final shortlist. RESULTS: 336 policies and 306 strategy documents were identified. Policies were mainly excluded due to criteria 2-4, leaving 88. The consensus workshop identified three policy areas as suitable candidates for natural experiment evaluation using administrative data: pregnancy grants, early years education and childcare, and Universal Credit. CONCLUSION: Our comprehensive policy review identifies valuable opportunities to evaluate sociostructural impacts on mother and child outcomes. However, many potentially impactful policies were excluded. This may lead to the inverse evidence law, where there is least evidence for policies believed to be most effective. This could be ameliorated by better access to administrative data, staged implementation of future policies or alternative evaluation methods

Molecular Origins of the Compatibility Between Glycosaminoglycans and Aβ40 Amyloid Fibrils

The Aβ peptide forms extracellular plaques associated with Alzheimer's disease. In addition to protein fibrils, amyloid plaques also contain non-proteinaceous components, including glycosaminoglycans (GAGs). We have shown previously that the GAG low molecular weight heparin (LMWH) binds to Aβ40 fibrils with a three-fold-symmetric (3Q) morphology with higher affinity than Aβ40 fibrils in alternative structures, Aβ42 fibrils, or amyloid fibrils formed from other sequences. Solid-state NMR (SSNMR) analysis of the GAG-3Q fibril complex revealed an interaction site at the corners of the 3Q fibril structure, but the origin of the binding specificity remained obscure. Here, employing a library of short heparin polysaccharides modified at specific sites, we show that the NS or 6-OS glucosamine sulfates, but not the 2-OS iduronate sulfate, of heparin is required for 3Q binding, indicating selectivity in the interactions of the GAG with the fibril that extends beyond general electrostatic complementarity. By creating 3Q fibrils containing point substitutions in the amino acid sequence, we also show that charged residues at the fibril three-fold apices provide the majority of the binding free energy, while charged residues elsewhere are less critical for binding. The results indicate, therefore, that LMWH binding to 3Q fibrils requires a precise molecular complementarity of the sulfate moieties on the GAG and charged residues displayed on the fibril surface. Differences in GAG binding to fibrils with distinct sequence and/or structure may thus contribute to the diverse etiology and progression of amyloid diseases

Supporting shared decision-making and people’s understanding of medicines : An exploration of the acceptability and comprehensibility of patient information

ACKNOWLEDGEMENTS The research team would like to thank the community pharmacy management and staff for all their assistance in facilitating recruitment. Thanks also to our colleague Alyson Brown, Robert Gordon University, for her help with recruitment and to Linda Collins, Healthcare Improvement Scotland, for assisting with project materials. We are incredibly grateful to all participants who gave up their time to participate in the research and who provided such valuable feedback.Peer reviewedPublisher PD

Atomic Details of the Interactions of Glycosaminoglycans with Amyloid-β Fibrils

The amyloid plaques associated with Alzheimer's disease (AD) comprise fibrillar amyloid-β (Aβ) peptides as well as non-protein factors including glycosaminoglycan (GAG) polysaccharides. GAGs affect the kinetics and pathway of Aβ self-assembly and can impede fibril clearance; thus, they may be accessory molecules in AD. Here we report the first high-resolution details of GAG-Aβ fibril interactions from the perspective of the saccharide. Binding analysis indicated that the GAG proxy heparin has a remarkably high affinity for Aβ fibrils with 3-fold cross-sectional symmetry (3Q). Chemical synthesis of a uniformly 13C-labeled octasaccharide heparin analogue enabled magic-angle spinning solid-state NMR of the GAG bound to 3Q fibrils, and measurements of dynamics revealed a tight complex in which all saccharide residues are restrained without undergoing substantial conformational changes. Intramolecular 13C-15N dipolar dephasing is consistent with close (<5 Å) contact between GAG anomeric position(s) and one or more histidine residues in the fibrils. These data provide a detailed model for the interaction between 3Q-seeded Aβ40 fibrils and a major non-protein component of AD plaques, and they reveal that GAG-amyloid interactions display a range of affinities that critically depend on the precise details of the fibril architecture

Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction†

We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells was reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1