Multi stress system: Microplastics in freshwater and their effects on host microbiota

Microplastics are persistent and complex contaminants that have recently been found in freshwater systems, raising concerns about their presence in aquatic organisms. Plastics tend to be seen as an inert material; however, it is not well known if exposure to plastics for a prolonged time, in combination with organic chemicals, causes organism mortality. Ingestion of microplastics in combination with another pollutant may affect a host organism's fitness by altering the host microbiome. In this study, we investigated how microplastics interact with other pollutants in this multi-stress system, and whether they have a synergistic impact on the mortality of an aquatic organism and its microbiome. We used wild water boatmen Hemiptera (Corixidae) found at lake Erken located in east-central Sweden in a fully factorial two-way microcosm experiment designed with polystyrene microspheres and a commonly used detergent. The microplastic-detergent interaction is manifested as a significant increase in mortality compared to the other treatments at 48 h of exposure. The diversity of the microbial communities in the water was significantly affected by the combined treatment of microplastics and the detergent while the microbial communities in the host were affected by the treatments with microplastics and the detergent alone. Changes in relative abundance in Gammaproteobacteria (family Enterobacteriaceae), were observed in the perturbed treatments mostly associated with the presence of the detergent. This confirms that microplastics can interact with detergents having toxic effects on wild water boatmen. Furthermore, microplastics may impact wild organisms via changes in their microbial communities

When is Alzheimer’s not dementia—Cochrane commentary on The National Institute on Ageing and Alzheimer’s Association Research Framework for Alzheimer’s Disease

Early 2018 saw the release of new diagnostic guidance on Alzheimer’s disease from the National Institute on Ageing and the Alzheimer’s Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer’s disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term ‘Alzheimer’s disease’; and the potential for a research framework to influence clinical practice

The Stressful Effects of Microplastics Associated With Chromium (VI) on the Microbiota of Daphnia Magna

Contamination by microplastics (particles < 1 mm) is a growing and alarming environmental problem in freshwater systems. Evidence suggests that industrial effluents could be one of the critical point sources of microplastics and other pollutants, and their interaction can cause organismal stress and affect host and environmental microbial communities. We tested the individual and combined effects of microplastics and other pollutants on host survival and host associated (commensal) bacterial diversity. We exposed Daphnia magna to 1 mu m microplastic beads with a concentration of approximately 1820 particles/ml and chromium (VI) simultaneously with treatments of 2 and 5 ppm for 72 h. DNA extraction was done to amplify and sequence the ribosomal Bacterial 16S from both the water and the Daphnia. Daphnia experienced low mortality in treatments microplastics (13.3%) and 2 ppm chromium VI (30%) individually. However, the combination of microplastics and 2 ppm chromium (VI) increased the mortality to 74.4%. In the treatments with 5 ppm of chromium (VI) mortality rose to 100% after 30 h of exposure. Microbial diversity changed in response to microplastics, chromium (VI), and both combined exposure. Microplastics and toxic metals can cause dysbiosis of freshwater environmental microbiota, whole host microbiota, and host survival. This work stresses the importance to assess how pollutants' individual and joint effects could affect organisms including their microbiome

Should Doctors Offer Biomarker Testing to Those Afraid to Develop Alzheimer’s Dementia?:Applying the Method of Reflective Equilibrium for a Clinical Dilemma

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium (RE) can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts (e.g. on the clinical validity of the test), ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective.</p

The Framing of "alzheimer's Disease":Differences between Scientific and Lay Literature and Their Ethical Implications

Background and Objectives: The meaning of Alzheimer's disease (AD) is changing in research. It now refers to a pathophysiological process, regardless of whether clinical symptoms are present. In the lay literature, on the other hand, AD is understood as a form of dementia. This raises the question of whether researchers and the lay audience are still talking about the same thing. If not, how will these different understandings of AD shape perspectives on (societal) needs for people with AD? Research Design and Methods: We use framing analysis to retrieve the understandings of the term AD that are upheld in the research literature and in national Dutch newspaper articles. We make explicit how the framings of AD steer our normative attitudes toward the disease. Results: In the analyzed research articles, AD is framed as a pathological cascade, reflected by biomarkers, starting in cognitively healthy people and ending, inevitably, in dementia. In the lay literature, AD is used as a synonym for dementia, and an AD diagnosis is understood as an incentive to enjoy "the time that is left."Discussion and Implications: The two different uses of the term AD in research and in the lay literature may result in misunderstandings, especially those research framings that falsely imply that people with AD biomarkers will inevitably develop dementia. Adoption of the research understanding of AD in clinical practice will have normative implications for our view on priority setting in health care. For example, it legitimizes biomarker testing in people without dementia as improving "diagnostic"certainty. </p

Neuropsychiatric symptoms of cholinergic deficiency occur with degradation of the projections from the nucleus basalis of Meynert

This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosi

Legal Judgement Prediction for UK Courts

Legal Judgement Prediction (LJP) is the task of automatically predicting the outcome of a court case given only the case document. During the last five years researchers have successfully attempted this task for the supreme courts of three jurisdictions: the European Union, France, and China. Motivation includes the many real world applications including: a prediction system that can be used at the judgement drafting stage, and the identification of the most important words and phrases within a judgement. The aim of our research was to build, for the first time, an LJP model for UK court cases. This required the creation of a labelled data set of UK court judgements and the subsequent application of machine learning models. We evaluated different feature representations and different algorithms. Our best performing model achieved: 69.05% accuracy and 69.02 F1 score. We demonstrate that LJP is a promising area of further research for UK courts by achieving high model performance and the ability to easily extract useful features

Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: a systematic review

Suzanne A Ligthart1, Eric P Moll van Charante1, Willem A Van Gool2, Edo Richard21Department of General Practice, 2Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsBackground: Over the last decade, evidence has accumulated that vascular risk factors increase the risk of Alzheimer disease (AD). So far, few randomized controlled trials have focused on lowering the vascular risk profile to prevent or postpone cognitive decline or dementia.Objective: To systematically perform a review of randomized controlled trials (RCTs) evaluating drug treatment effects for cardiovascular risk factors on the incidence of dementia or cognitive decline.Selection criteria: RCTs studying the effect of treating hypertension, dyslipidemia, &amp;shy;hyperhomocysteinemia, obesity, or diabetes mellitus (DM) on cognitive decline or dementia, with a minimum follow-up of 1 year in elderly populations.Outcome measure: Cognitive decline or incident dementia.Main results: In the identified studies, dementia was never the primary outcome. Statins (2 studies) and intensified control of type II DM (1 study) appear to have no effect on prevention of cognitive decline. Studies on treatment of obesity are lacking, and the results of lowering homocysteine (6 studies) are inconclusive. There is some evidence of a preventive effect of antihypertensive medication (6 studies), but results are inconsistent.Conclusion: The evidence of a preventive treatment effect aimed at vascular risk factors on cognitive decline and dementia in later life is scarce and mostly based on secondary outcome parameters. Several important sources of bias such as differential dropout may importantly affect interpretation of trial results.Keywords: cardiovascular risk factors, cognitive decline, dementia, preventio

Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment

Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA. The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive therapy appears to be an appropriate treatment for CAA encephalopathy