Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies

Plasma antioxidants from chocolate

There is some speculation that dietary flavonoids from chocolate, in particular (-)epicatechin, may promote cardiovascular health as a result of direct antioxidant effects or through antithrombotic mechanisms. Here we show that consumption of plain, dark chocolate results in an increase in both the total antioxidant capacity and the (-)epicatechin content of blood plasma, but that these effects are markedly reduced when the chocolate is consumed with milk or if milk is incorporated as milk chocolate. Our findings indicate that milk may interfere with the absorption of antioxidants from chocolate in vivo and may therefore negate the potential health benefits that can be derived from eating moderate amounts of dark chocolate

On Lagrangian mechanics and the implicit material point method for large deformation elasto-plasticity

The material point method is ideally suited to modelling problems involving large deformations where conventional mesh-based methods would struggle. However, total and updated Lagrangian approaches are unsuitable and non-ideal, respectively, in terms formulating equilibrium for the method. This is due to the basis functions, and particularly the derivatives of the basis functions, of material point methods normally being dened based on an unformed, and sometimes regular, background mesh. It is possible to map the basis function spatial derivatives using the deformation at a material point but this introduces additional algorithm complexity and computational expense. This paper presents a new Lagrangian statement of equilibrium which is ideal for material point methods as it satises equilibrium on the undeformed background mesh at the start of a load step. The formulation is implemented using a quasi-static implicit algorithm which includes the derivation of the consistent tangent to achieve optimum convergence of the global equilibrium iterations. The method is applied to a number of large deformation elasto-plastic problems, with a specic focus of the convergence of the method towards analytical solutions with the standard, generalised interpolation and CPDI2 material point methods. For the generalised interpolation method, dierent domain updating methods are investigated and it is shown that all of the current methods are degenerative under certain simple deformation elds. A new domain updating approach is proposed that overcomes these issues. The proposed material point method framework can be applied to all existing material point methods and adopted for implicit and explicit analysis, however its advantages are mainly associated with the former

Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002). Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs)

A risk-based framework for assessing the effectiveness of stratospheric aerosol geoengineering

Open Access journalCopyright: © 2014 Ferraro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Geoengineering by stratospheric aerosol injection has been proposed as a policy response to warming from human emissions of greenhouse gases, but it may produce unequal regional impacts. We present a simple, intuitive risk-based framework for classifying these impacts according to whether geoengineering increases or decreases the risk of substantial climate change, with further classification by the level of existing risk from climate change from increasing carbon dioxide concentrations. This framework is applied to two climate model simulations of geoengineering counterbalancing the surface warming produced by a quadrupling of carbon dioxide concentrations, with one using a layer of sulphate aerosol in the lower stratosphere, and the other a reduction in total solar irradiance. The solar dimming model simulation shows less regional inequality of impacts compared with the aerosol geoengineering simulation. In the solar dimming simulation, 10% of the Earth's surface area, containing 10% of its population and 11% of its gross domestic product, experiences greater risk of substantial precipitation changes under geoengineering than under enhanced carbon dioxide concentrations. In the aerosol geoengineering simulation the increased risk of substantial precipitation change is experienced by 42% of Earth's surface area, containing 36% of its population and 60% of its gross domestic product.Natural Environment Research Council (NERC

Effectiveness of interventions to promote healthy diet in primary care: systematic review and meta-analysis of randomised controlled trials

Background A diet rich in fruit, vegetables and dietary fibre and low in fat is associated with reduced risk of chronic disease. This review aimed to estimate the effectiveness of interventions to promote healthy diet for primary prevention among participants attending primary care.&lt;p&gt;&lt;/p&gt; Methods A systematic review of trials using individual or cluster randomisation of interventions delivered in primary care to promote dietary change over 12 months in healthy participants free from chronic disease or defined high risk states. Outcomes were change in fruit and vegetable intake, consumption of total fat and fibre and changes in serum cholesterol concentration.&lt;p&gt;&lt;/p&gt; Results Ten studies were included with 12,414 participants. The design and delivery of interventions were diverse with respect to grounding in behavioural theory and intervention intensity. A meta-analysis of three studies showed an increase in fruit consumption of 0.25 (0.01 to 0.49) servings per day, with an increase in vegetable consumption of 0.25 (0.06 to 0.44) serving per day. A further three studies that reported on fruit and vegetable consumption together showed a pooled increment of 0.50 (0.13 to 0.87) servings per day. The pooled effect on consumption of dietary fibre, from four studies, was estimated to be 1.97 (0.43 to 3.52) gm fibre per day. Data from five studies showed a mean decrease in total fat intake of 5.2% of total energy (1.5 to 8.8%). Data from three studies showed a mean decrease in serum cholesterol of 0.10 (-0.19 to 0.00) mmol/L.&lt;p&gt;&lt;/p&gt; Conclusion Presently-reported interventions to promote healthy diet for primary prevention in primary care, which illustrate a diverse range of intervention methods, may yield small beneficial changes in consumption of fruit, vegetables, fibre and fat over 12 months. The present results do not exclude the possibility that more effective intervention strategies might be developed.&lt;p&gt;&lt;/p&gt

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

&lt;p&gt;Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.&lt;/p&gt; &lt;p&gt;Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.&lt;/p&gt; &lt;p&gt;Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.&lt;/p&gt; &lt;p&gt;Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.&lt;/p&gt

Heterozygous <em>COL17A1 </em>variants are a frequent cause of amelogenesis imperfecta

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Background: Collagen XVII is most typically associated with human disease when biallelic COL17A1 variants (&gt;230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. Methods: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for COL17A1 variants. Patient phenotypes were assessed by clinical examination and analyses of affected teeth. Results: Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. Conclusion: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care