Playing the flashbulb memory game: A comment on Cubelli and Della Sala

Flashbulb memory (FBM) is a term coined in 1977 by Brown and Kulik referring to vivid, detailed, and long-lasting memories for the reception context of important public events. Across the years, different authors have tried to establish that FBMs either exist or are virtually indistinguishable from ordinary autobiographical memory formations. In the present study we review studies in favour/against the FBM hypothesis focusing on two main issues: First, FBM accuracy appears to be difficult if not impossible to prove; secondly memory distortions and forgetting do not exclude that FBMs are formed and maintained. Personal and social consequentiality are considered to be crucial factors in determining real FBMs, although reconstructive processes also operate on these formations. We finally propose that, striving to play a kind of FBM game, researchers have sometimes failed to focus on real FBMs, misinterpreting the meaning of the camera metaphor and adopting research strategies open to criticisms and invalidation

11 x 11 Domineering is Solved: The first player wins

We have developed a program called MUDoS (Maastricht University Domineering Solver) that solves Domineering positions in a very efficient way. This enables the solution of known positions so far (up to the 10 x 10 board) much quicker (measured in number of investigated nodes). More importantly, it enables the solution of the 11 x 11 Domineering board, a board up till now far out of reach of previous Domineering solvers. The solution needed the investigation of 259,689,994,008 nodes, using almost half a year of computation time on a single simple desktop computer. The results show that under optimal play the first player wins the 11 x 11 Domineering game, irrespective if Vertical or Horizontal starts the game. In addition, several other boards hitherto unsolved were solved. Using the convention that Vertical starts, the 8 x 15, 11 x 9, 12 x 8, 12 x 15, 14 x 8, and 17 x 6 boards are all won by Vertical, whereas the 6 x 17, 8 x 12, 9 x 11, and 11 x 10 boards are all won by Horizontal

The Role of NEDD4 E3 Ubiquitin–Protein Ligases in Parkinson’s Disease

Parkinson’s disease (PD) is a debilitating neurodegenerative disease that causes a great clinical burden. However, its exact molecular pathologies are not fully understood. Whilst there are a number of avenues for research into slowing, halting, or reversing PD, one central idea is to enhance the clearance of the proposed aetiological protein, oligomeric α-synuclein. Oligomeric α-synuclein is the main constituent protein in Lewy bodies and neurites and is considered neurotoxic. Multiple E3 ubiquitin-protein ligases, including the NEDD4 (neural precursor cell expressed developmentally downregulated protein 4) family, parkin, SIAH (mammalian homologues of Drosophila seven in absentia), CHIP (carboxy-terminus of Hsc70 interacting protein), and SCFFXBL5 SCF ubiquitin ligase assembled by the S-phase kinase-associated protein (SKP1), cullin-1 (Cul1), a zinc-binding RING finger protein, and the F-box domain/Leucine-rich repeat protein 5-containing protein FBXL5), have been shown to be able to ubiquitinate α-synuclein, influencing its subsequent degradation via the proteasome or lysosome. Here, we explore the link between NEDD4 ligases and PD, which is not only via α-synuclein but further strengthened by several additional substrates and interaction partners. Some members of the NEDD4 family of ligases are thought to crosstalk even with PD-related genes and proteins found to be mutated in familial forms of PD. Mutations in NEDD4 family genes have not been observed in PD patients, most likely because of their essential survival function during development. Following further in vivo studies, it has been thought that NEDD4 ligases may be viable therapeutic targets in PD. NEDD4 family members could clear toxic proteins, enhancing cell survival and slowing disease progression, or might diminish beneficial proteins, reducing cell survival and accelerating disease progression. Here, we review studies to date on the expression and function of NEDD4 ubiquitin ligases in the brain and their possible impact on PD pathology.</jats:p

Hear-Communicate-Remember: Feasibility of delivering an integrated intervention for family caregivers of people with dementia and hearing impairment via telehealth

PURPOSE: To evaluate the feasibility of Hear-Communicate-Remember, a training programme developed for family caregivers of people with dementia and hearing impairment that integrated hearing, communication and memory strategies, which was intended to be delivered via telehealth. MATERIALS AND METHODS: Participants included six dyads consisting of adults with dementia and hearing impairment and their family caregivers. Data collection involved a combination of semi-structured interviews, self-report questionnaires and field notes. RESULTS: Analysis of the qualitative interviews revealed four themes: appropriateness of intervention resources, considerations for the delivery of intervention via telehealth, knowledge and application of intervention strategies, and impact of the intervention on day-to-day life. Results from the satisfaction survey indicated that caregiver participants were mostly satisfied with all aspects of the intervention except the use of some technological components. The field notes described challenges with implementation via telehealth. CONCLUSIONS: Future research involving a cohort comparison study with a larger cohort of dyads is needed to establish treatment efficacy

A rare Von Hippel–Lindau disease that mimics acute myelitis: case report and review of the literature

Von Hippel–Lindau disease (VHL) comprises a series of complicated clinical manifestations. We hereby report one unique case of VHL with a natural history that mimics acute myelitis. MRI and biopsy in this patient showed multiple solid hemangioblastomas of the central nervous system and kidney. This study further confirmed that VHL is of highly clinical, imaging, and pathological heterogeneity. Diagnosis for VHL should be based on combination of clinical, radiological, pathological, and genetic data

Is nebulized saline a placebo in COPD?

BACKGROUND: Many trials of nebulized therapy have used nebulized saline as a "placebo". However, nebulized isotonic saline is sometimes used to assist sputum expectoration and relieve breathlessness in COPD patients. We designed this study to establish if nebulized saline had a placebo effect or a clinical effect. METHODS: 40 patients were studied following hospital admission for exacerbated COPD (mean FEV1 30% predicted). Patients were randomised to single-blind administration of either 4 mls of nebulized isotonic saline using an efficient nebulizer (active group n = 20) or an inefficient nebulizer (placebo group n = 20). Spirometry and subjective breathlessness scores (Modified Likert Scale) were measured before nebulized treatment and 10 minutes after treatment. RESULTS: There was no significant change in FEV1 after active or placebo nebulized saline treatment. Patients reported a 4% improvement in mean breathlessness score following placebo (Wilcoxon test; p = 0.37) compared with 23% improvement following active nebulized saline (p = 0.0001). 65% of patients given active nebulized saline but only 5% of the placebo group reported that mucus expectoration was easier after the treatment. CONCLUSIONS: This study lends support to the current use of nebulized saline to relieve breathlessness (possibly by facilitating sputum clearance) in COPD patients. Lung function was not affected. Nebulized saline can therefore be used as a placebo in bronchodilator studies involving COPD patients but it cannot be used as a placebo in trials assessing symptom relief

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Enhanced chlorhexidine skin penetration with 1,8-cineole

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 μm slices to a depth of 2000 μm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection