Alcohol-related dementia: An update of the evidence

The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome, or WKS) are reviewed. Neuropathological and imaging studies suggest that excessive and prolonged use of alcohol may lead to structural and functional damage that is permanent in nature; however, there is debate about the relative contributions of the direct toxic effect of alcohol (neurotoxicity hypothesis), and the impact of thiamine deficiency, to lasting damage. Investigation of alcohol-related cognitive impairment has been further complicated by differing definitions of patterns of alcohol use and associated lifestyle factors related to the abuse of alcohol. Present diagnostic systems identify two main syndromes of alcohol-related cognitive impairment: ARD and WKS. However, 'alcohol-related brain damage' is increasingly used as an umbrella term to encompass the heterogeneity of these disorders. It is unclear what level of drinking may pose a risk for the development of brain damage or, in fact, whether lower levels of alcohol may protect against other forms of dementia. Epidemiological studies suggest that individuals with ARD typically have a younger age of onset than those with other forms of dementia, are more likely to be male, and often are socially isolated. The cognitive profile of ARD appears to involve both cortical and subcortical pathology, and deficits are most frequently observed on tasks of visuospatial function as well as memory and higher-order (executive) tasks. The WKS appears more heterogeneous in nature than originally documented, and deficits on executive tasks commonly are reported in conjunction with characteristic memory deficits. Individuals with alcohol-related disorders have the potential to at least partially recover - both structurally and functionally - if abstinence is maintained. In this review, considerations in a clinical setting and recommendations for diagnosis and management are discussed. It is well established that excessive and prolonged alcohol use can lead to permanent damage to the structure and function of the brain [1]. Despite this, there is little consensus on the characteristics of a dementia syndrome related to sustained alcohol abuse or its relationship to Wernicke-Korsakoff syndrome (WKS). After a long period of neglect, research interest has increased in recent years and has been spurred on by clinical demand, increased reported rates of alcohol abuse in older people, and increasing alcohol consumption by women [2, 3]. In this paper, we aim to review the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and WKS. To retrieve papers for the purpose of this review, the search terms (alcohol OR alcoholism) AND (dementia OR brain damage OR brain injury OR cognitive impairment) were used as keywords in the Medline and PsycINFO databases. Additional terms included Wernicke's encephalopathy, Korsakoff, and Alcohol Amnestic Disorder. Reference lists were also scanned for relevant papers

Single- and double-scattering production of four muons in ultraperipheral PbPb collisions at the Large Hadron Collider

We discuss production of two $\mu^+\mu^-$ pairs in ultraperipheral ultrarelativistic heavy ion collisions at the LHC. We take into account electromagnetic (two-photon) double-scattering production and for a first time direct $\gamma\gamma$ production of four muons in one scattering. We study the unexplored process $\gamma \gamma \to \mu^+\mu^-\mu^+\mu^-$. We present predictions for total and differential cross sections. Measurable nuclear cross sections are obtained and corresponding differential distributions and counting rates are presented.Comment: 13 pages, 11 figures, 1 tabl

Data curation issues in transitioning a field science collection of long-term research data and artefacts from a local repository to an institutional repository

The SGS-LTER research site was established in 1980 by researchers at Colorado State University as part of a network of long-term research sites within the US LTER Network, supported by the National Science Foundation. Scientists within the Natural Resource Ecology Lab, Department of Forest and Rangeland Stewardship, Department of Soil and Crop Sciences, and Biology Department at CSU, California State Fullerton, USDA Agricultural Research Service, University of Northern Colorado, and the University of Wyoming, among others, have contributed to our understanding of the structure and functions of the shortgrass steppe and other diverse ecosystems across the network while maintaining a common mission and sharing expertise, data and infrastructure.Transition a local 32 year project, the Shortgrass Steppe Long-Term Ecological Research (SGS-LTER), with over 100 data packages and related digital artefacts, to an Institutional Repository (IR) at Colorado State University (CSU) Libraries to ensure persistent, reliable, and interoperable access to our collection of scientific data. Our collaborative team envisions being part of a larger information environment, which enables sharing of knowledge and data - a web of repositories. Poster presented at the 9th International Digital Curation Conference held in San Francisco, California on February 25, 2014. Refereed.This work is supported by NSF Grant Number DEB-0823405, Colorado State University, and the UIUC Data Curation Education at Research Centers (DCERC IMLS Award #RE-02-10-0004-10)

Managing scientific research data: data packaging and organizing materials for curation

The SGS-LTER research site was established in 1980 by researchers at Colorado State University as part of a network of long-term research sites within the US LTER Network, supported by the National Science Foundation. Scientists within the Natural Resource Ecology Lab, Department of Forest and Rangeland Stewardship, Department of Soil and Crop Sciences, and Biology Department at CSU, California State Fullerton, USDA Agricultural Research Service, University of Northern Colorado, and the University of Wyoming, among others, have contributed to our understanding of the structure and functions of the shortgrass steppe and other diverse ecosystems across the network while maintaining a common mission and sharing expertise, data and infrastructure.Presentation held at the Front Range Data Librarian Meeting on June 16, 2014 at CSU Libraries and Natural Resource Ecology Laboratory in Fort Collins, Colorado.NSF Grant DEB-1027319

People with mild cognitive impairment are at increased risk of serious injury

Introduction Data-linkage studies using administrative hospital data have shown that people with dementia have double the rate of injury-related hospitalisations and poorer health outcomes than those without. No previous research has explored whether people with mild cognitive impairment are also at increased risk of serious injury requiring hospitalisation. Objectives and Approach A major barrier to the use of administrative hospital data for undertaking research focusing on people with MCI is that MCI cannot be reliably identified from ICD-10 coded administrative data. To overcome this limitation, hospitalisation and death data was linked to data from participants (community-dwelling 70-90 year olds) enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). MAS participants underwent comprehensive neuropsychological assessments at baseline, then 2, 4 and 6 years’ follow-up to accurately determine cognitive status at each time-period. Linkage to hospital records allowed identification of injury-related hospitalisations and outcomes for the 2-year period following each assessment. Results There were 335 injury-related hospitalisations for the 867 participants; 222 (25.6%) participants had at least one injury-related hospitalisation. After adjusting for age-and-sex, participants in a state of MCI had 1.7 (95%CI 1.2-2.4) times higher odds of an injury-related hospitalisation than participants in a state of normal cognition, whilst participants with dementia had 2.3 (95%CI 1.2-4.4) times higher odds. There was no difference in odds between participants with MCI and dementia. Of the 116 hospitalisations for people with MCI, the majority (79.3%) were due to falls. Non-fracture head injuries (25.9%), upper limb and trunk fractures (13.8% respectively) were the most common injury type. There were no differences in injury type, mean length of stay, or 30-day mortality between people with normal cognition, MCI and dementia. Conclusion/Implications Older people with objectively defined MCI are at higher risk of injury, predominantly as a result of falls, than their cognitively intact peers. Falls-risk screening and fall prevention initiatives may be indicated for people with MCI. Further research is required to determine which cognitive domains contribute to this increased risk

Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome:Results From a European Two-Center Study

BACKGROUND: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits. OBJECTIVES: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010). DESIGN: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time. RESULTS: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or β ≠ 0). CONCLUSION: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits. CLINICAL TRAIL REGISTRATION: www.ClinicalTrials.gov, Identifier: NCT03169088

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform

Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at = 37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (= 27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.Peer reviewe

Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HT™ Protects against Blood-Stage Challenge in Rhesus Macaques

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC50 values correlated with estimated in vivo growth rates

An Anomalous Type IV Secretion System in Rickettsia Is Evolutionarily Conserved

Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.Superimposition of T4SS structural/functional information over previously identified Rickettsia components implicate a functional Rickettsia T4SS. virB4, virB8 and virB9 are duplicated, yet only one copy of each has the conserved features of similar genes in other T4SSs. An extraordinarily duplicated VirB6 gene encodes five hydrophobic proteins conserved only in a short region known to be involved in DNA transfer in A. tumefaciens. virB1, virB2 and virB7 are newly identified, revealing a Rickettsia T4SS lacking only virB5 relative to the vir archetype. Phylogeny estimation suggests vertical inheritance of all components, despite gene rearrangements into an archipelago of five islets. Similarities of Rickettsia VirB7/VirB9 to ComB7/ComB9 proteins of epsilon-proteobacteria, as well as phylogenetic affinities to the Legionella lvh T4SS, imply the Rickettsiales ancestor acquired a vir-like locus from distantly related bacteria, perhaps while residing in a protozoan host. Modern modifications of these systems likely reflect diversification with various eukaryotic host cells.We present the rvh (Rickettsiales vir homolog) T4SS, an evolutionary conserved transporter with an unknown role in rickettsial biology. This work lays the foundation for future laboratory characterization of this system, and also identifies the Legionella lvh T4SS as a suitable genetic model