Alcohol as a Modifiable Risk Factor for Alzheimer’s Disease—Evidence from Experimental Studies

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can modulate cerebral AD pathology include Toll-like receptors, protein kinase-B (Akt)/mammalian target of rapamycin (mTOR) pathway, cyclic adenosine monophosphate (cAMP) response element-binding protein phosphorylation pathway, glycogen synthase kinase 3-β, cyclin-dependent kinase-5, insulin-like growth factor type-1 receptor, modulation of β-amyloid (Aβ) synthesis and clearance, microglial mediated, and brain endothelial alterations. Besides these brain-centric pathways, alcohol-mediated liver injury may significantly affect brain Aβ levels through alterations in the peripheral-to-central Aβ homeostasis. This article reviews published experimental studies (cell culture and AD rodent models) to summarize the scientific evidence and probable mechanisms (both cerebral and hepatic) by which alcohol promotes or protects against AD progression

Parents unwittingly leak their children's data:a GDPR time bomb?

There are many apps available for parents that are designed to help them monitor their pregnancy or child’s development. These apps require parents to share information about themselves or their children in order to utilise many of the apps’ features. However, parents remain concerned about their children’s privacy, indicating a privacy paradox between concerns and actions. The research presented here conducted an analysis of parenting apps alongside a survey of parents to determine if their concerns regarding sharing information about their children was at odds with their use of parenting apps.A survey of 75 parents found that they had strong concerns around the availability of information about their children but were using apps within which they shared this information. Parents were not giving consideration to the information requested when using apps. This should be of concern to developers given the growing awareness of users’ rights in relation to managing their data.We propose new guidelines for app developers to better protect children’s privacy and to improve trust relationships between developers and users

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

Differences in trauma history and psychopathology between PTSD patients with and without co-occurring dissociative disorders

Wabnitz P, Gast U, Catani C. Differences in trauma history and psychopathology between PTSD patients with and without co-occurring dissociative disorders. European Journal of Psychotraumatology. 2013;2013(4): 21452.Background: The interplay between different types of potentially traumatizing events, posttraumatic symptoms, and the pathogenesis of PTSD or major dissociative disorders (DD) has been extensively studied during the last decade. However, the phenomenology and nosological classification of posttraumatic disorders is currently under debate. The current study was conducted to investigate differences between PTSD patients with and without co-occurring major DD with regard to general psychopathology, trauma history, and trauma-specific symptoms. Methods: Twenty-four inpatients were administered the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and the Mini-Structured Clinical Interview for DSM-IV Dissociative Disorders (MINI-SKID-D) to assess DD and PTSD. Additionally, participants completed questionnaires to assess general psychopathology and health status. Results: Symptom profiles and axis I comorbidity were similar in all patients. Traumatic experiences did not differ between the two groups, with both reporting high levels of childhood trauma. Only trauma-specific avoidance behavior and dissociative symptoms differed between groups. Conclusion: Results support the view that PTSD and DD are affiliated disorders that could be classified within the same diagnostic category. Our results accord with a typological model of dissociation in which profound forms of dissociation are specific to DD and are accompanied with higher levels of trauma-specific avoidance in DD patients

Oxy-fuel combustion of coal and biomass blends

The ignition temperature, burnout and NO emissions of blends of a semi-anthracite and a high-volatile bituminous coal with 10 and 20 wt.% of olive waste were studied under oxy-fuel combustion conditions in an entrained flow reactor (EFR). The results obtained under several oxy-fuel atmospheres (21%O2–79%CO2, 30%O2–70%CO2 and 35%O2–65%CO2) were compared with those attained in air. The results indicated that replacing N2 by CO2 in the combustion atmosphere with 21% of O2 caused an increase in the temperature of ignition and a decrease in the burnout value. When the O2 concentration was increased to 30 and 35%, the temperature of ignition was lower and the burnout value was higher than in air conditions. A significant reduction in ignition temperature and a slight increase in the burnout value was observed after the addition of biomass, this trend becoming more noticeable as the biomass concentration was increased. The emissions of NO during oxy-fuel combustion were lower than under air-firing. However, they remained similar under all the oxy-fuel atmospheres with increasing O2 concentrations. Emissions of NO were significantly reduced by the addition of biomass to the bituminous coal, although this effect was less noticeable in the case of the semi-anthracite.This work was carried out with financial support from the Spanish MICINN (Project PS-120000-2005-2) co-financed by the European Regional Development Fund. M.V.G. and L.A. acknowledge funding from the CSIC JAE-Doc and CSIC JAE-Pre programs, respectively, co-financed by the European Social Fund. J.R. acknowledges funding from the Government of the Principado de Asturias (Severo Ochoa program).Peer reviewe

New perspectives on realism, tractability, and complexity in economics

Fuzzy logic and genetic algorithms are used to rework more realistic (and more complex) models of competitive markets. The resulting equilibria are significantly different from the ones predicted from the usual static analysis; the methodology solves the Walrasian problem of how markets can reach equilibrium, starting with firms trading at disparate prices. The modified equilibria found in these complex market models involve some mutual self-restraint on the part of the agents involved, relative to economically rational behaviour. Research (using similar techniques) into the evolution of collaborative behaviours in economics, and of altruism generally, is summarized; and the joint significance of these two bodies of work for public policy is reviewed. The possible extension of the fuzzy/ genetic methodology to other technical aspects of economics (including international trade theory, and development) is also discussed, as are the limitations to the usefulness of any type of theory in political domains. For the latter purpose, a more differentiated concept of rationality, appropriate to ill-structured choices, is developed. The philosophical case for laissez-faire policies is considered briefly; and the prospects for change in the way we ‘do economics’ are analysed

Modulation of Hepatic Amyloid Precursor Protein and Lipoprotein Receptor-Related Protein 1 by Chronic Alcohol Intake: Potential Link Between Liver Steatosis and Amyloid-β

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting a potential link between liver injury and microglial loss in the brain. Intragastric alcohol feeding significantly affected two hepatic proteins important in amyloid-beta (Aβ) processing by the liver: 1) alcohol feeding downregulated lipoprotein receptor-related protein 1 (LRP1, ∼46%), the major receptor in the liver that removes Aβ from blood and peripheral organs, and 2) alcohol significantly upregulated APP (∼2-fold), a potentially important source of Aβ in the periphery and brain. The decrease in hepatic LRP1 and increase in hepatic APP likely switches the liver from being a remover or low producer of Aβ to an important source of Aβ in the periphery, which can impact the brain. The downregulation of LRP1 and upregulation of APP in the liver was observed in the first week of intragastric alcohol feeding, and also occurred in other alcohol feeding models (NIAAA binge alcohol model and intragastric alcohol feeding to rats). Modulation of hepatic LRP1 and APP does not seem alcohol-specific, as ob/ob mice with significant steatosis also had declines in LRP1 and increases in APP expression in the liver. These findings suggest that liver steatosis rather than alcohol-induced liver injury is likely responsible for regulation of hepatic LRP1 and APP. Both obesity and alcohol intake have been linked to AD and our data suggests that liver steatosis associated with these two conditions modulates hepatic LRP1 and APP to disrupt Aβ processing by the liver to promote AD

Association of iron overload based quantitative T2* MRI technique and carotid intima-media thickness in patients with beta-thalassemia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis is that high iron status is associated with increased risk of atherosclerosis. We investigated the potential role of iron as an additional risk factor promoting atherosclerosis among beta-thalassemic patients.</p> <p>Methods</p> <p>In this cross-sectional study, the liver iron load was assessed by quantitative T2* MRI technique and intima-media thickness (IMT) of the common carotid artery by high-resolution ultrasound among 119 patients (62 male, 57 female) with beta-thalassemia (major and intermediate) whose age ranged from 10 to 50 years with a mean of 25.6 years. The patients were divided into three groups according to the severity of iron loading, obtained by T2*MRI technique: group I (normal), group II (mild) and group III (moderate and severe) iron load.</p> <p>For elimination of the effect of age on carotid IMT values, the patients also were divided into four age groups (10-19 y, 20-29 y, 30-39 y and 40-50 y). Mean carotid IMT based on the severity of iron loading were compared at different age groups, using one way ANOVA analysis for assessing the effect of iron loading on carotid IMT. Pearson's coefficient of correlation were used to assess the degree of correlation between studied variables (liver T2*, IMT, age).</p> <p>Results</p> <p>There were significant differences in mean carotid IMT based on the severity of iron loading at different age groups, with P = 0.003 at 20-29 y, P = 0.006 at 30-39 y and p = 0.037 at 40-50 y. Age (p = 0.001) and liver T2*(p = 0.003) had significant correlation with mean carotid IMT independently.</p> <p>At the age group of 10-19 years, there were not significant differences in mean carotid IMT based on the liver iron loading (p = 0.661).</p> <p>No significant differences also are seen in mean carotid IMT between male and female (p = 0.41).</p> <p>Conclusions</p> <p>This study identified a relationship between body iron status and carotid IMT. This relationship support to the hypothesis of a link between body iron load and atherosclerosis.</p