Decreased copper in alzheimer's disease brain is predominantly in the soluble extractable fraction

Alzheimer's disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble (P<0.05) and total homogenate (P<0.05) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD. © 2013 Alan Rembach et al

Posterior-based proposals for speeding up Markov chain Monte Carlo

Markov chain Monte Carlo (MCMC) is widely used for Bayesian inference in models of complex systems. Performance, however, is often unsatisfactory in models with many latent variables due to so-called poor mixing, necessitating development of application specific implementations. This paper introduces "posterior-based proposals" (PBPs), a new type of MCMC update applicable to a huge class of statistical models (whose conditional dependence structures are represented by directed acyclic graphs). PBPs generates large joint updates in parameter and latent variable space, whilst retaining good acceptance rates (typically 33%). Evaluation against other approaches (from standard Gibbs / random walk updates to state-of-the-art Hamiltonian and particle MCMC methods) was carried out for widely varying model types: an individual-based model for disease diagnostic test data, a financial stochastic volatility model, a mixed model used in statistical genetics and a population model used in ecology. Whilst different methods worked better or worse in different scenarios, PBPs were found to be either near to the fastest or significantly faster than the next best approach (by up to a factor of 10). PBPs therefore represent an additional general purpose technique that can be usefully applied in a wide variety of contexts.Comment: 54 pages, 11 figures, 2 table

Mindfulness-based stress reduction in Parkinson’s disease: a systematic review

Background: Mindfulness based stress reduction (MBSR) is increasingly being used to improve outcomes such as stress and depression in a range of long-term conditions (LTCs). While systematic reviews on MBSR have taken place for a number of conditions there remains limited information on its impact on individuals with Parkinson’s disease (PD). Methods: Medline, Central, Embase, Amed, CINAHAL were searched in March 2016. These databases were searched using a combination of MeSH subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed based on questions from the Cochrane Collaboration risk of bias tool. Results: Two interventions and three papers with a total of 66 participants were included. The interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study reported significantly increased grey matter density (GMD) in the brains of the MBSR group compared to the usual care group. Significant improvements were reported in one study for a number of outcomes including PD outcomes, depression, mindfulness, and quality of life indicators. Only one intervention was of reasonable quality and both interventions failed to control for potential confounders in the analysis. Adverse events and reasons for drop-outs were not reported. There was also no reporting on the costs/benefits of the intervention or how they affected health service utilisation. Conclusion: This systematic review found limited and inconclusive evidence of the effectiveness of MBSR for PD patients. Both of the included interventions claimed positive effects for PD patients but significant outcomes were often contradicted by other results. Further trials with larger sample sizes, control groups and longer follow-ups are needed before the evidence for MBSR in PD can be conclusively judged

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

&lt;b&gt;Background&lt;/b&gt; Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

Rural to Urban Migration and Changes in Cardiovascular risk Factors in Tanzania: A Prospective Cohort Study.

High levels of rural to urban migration are a feature of most African countries. Our aim was to investigate changes, and their determinants, in cardiovascular risk factors on rural to urban migration in Tanzania. Men and women (15 to 59 years) intending to migrate from Morogoro rural region to Dar es Salaam for at least 6 months were identified. Measurements were made at least one week but no more than one month prior to migration, and 1 to 3 monthly after migration. Outcome measures included body mass index, blood pressure, fasting lipids, and self reported physical activity and diet. One hundred and three men, 106 women, mean age 29 years, were recruited and 132 (63.2%) followed to 12 months. All the figures presented here refer to the difference between baseline and 12 months in these 132 individuals. Vigorous physical activity declined (79.4% to 26.5% in men, 37.8% to 15.6% in women, p < 0.001), and weight increased (2.30 kg men, 2.35 kg women, p < 0.001). Intake of red meat increased, but so did the intake of fresh fruit and vegetables. HDL cholesterol increased in men and women (0.24, 0.25 mmoll-1 respectively, p < 0.001); and in men, not women, total cholesterol increased (0.42 mmoll-1, p = 0.01), and triglycerides fell (0.31 mmoll-1, p = 0.034). Blood pressure appeared to fall in both men and women. For example, in men systolic blood pressure fell by 5.4 mmHg, p = 0.007, and in women by 8.6 mmHg, p = 0.001. The lower level of physical activity and increasing weight will increase the risk of diabetes and cardiovascular disease. However, changes in diet were mixed, and may have contributed to mixed changes in lipid profiles and a lack of rise in blood pressure. A better understanding of the changes occurring on rural to urban migration is needed to guide preventive measures

Expanding dispersal studies at hydrothermal vents through species identification of cryptic larval forms

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biology 157 (2010): 1049-1062, doi:10.1007/s00227-009-1386-8.The rapid identification of hydrothermal vent-endemic larvae to the species level is a key limitation to understanding the dynamic processes that control the abundance and distribution of fauna in such a patchy and ephemeral environment. Many larval forms collected near vents, even those in groups such as gastropods that often form a morphologically distinct larval shell, have not been identified to species. We present a staged approach that combines morphological and molecular identification to optimize the capability, efficiency, and economy of identifying vent gastropod larvae from the northern East Pacific Rise (NEPR). With this approach, 15 new larval forms can be identified to species. A total of 33 of the 41 gastropod species inhabiting the NEPR, and 26 of the 27 gastropod species known to occur specifically in the 9° 50’ N region, can be identified to species. Morphological identification efforts are improved by new protoconch descriptions for Gorgoleptis spiralis, Lepetodrilus pustulosus, Nodopelta subnoda, and Echinopelta fistulosa. Even with these new morphological descriptions, the majority of lepetodrilids and peltospirids require molecular identification. Restriction fragment length polymorphism digests are presented as an economical method for identification of five species of Lepetodrilus and six species of peltospirids. The remaining unidentifiable specimens can be assigned to species by comparison to an expanded database of 18S ribosomal DNA. The broad utility of the staged approach was exemplified by the revelation of species-level variation in daily planktonic samples and the identification and characterization of egg capsules belonging to a conid gastropod Gymnobela sp. A. The improved molecular and morphological capabilities nearly double the number of species amenable to field studies of dispersal and population connectivity.Funding was provided by as Woods Hole Oceanographic Institution Deep Ocean Exploration Institute grant to L.M and S. Beaulieu, National Science Foundation grants OCE-0424953, OCE-9712233, and OCE-9619605 to L.M, OCE-0327261 to T.S., and OCE-0002458 to K. Von Damm, and a National Defense Science and Engineering Graduate fellowship to D.A

Neurolymphomatosis mimicking neurosarcoidosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Both neurosarcoidosis and central nervous system lymphoma can be very difficult to diagnose. We describe the case of a patient in whom neurosarcoidosis was strongly suspected, but who was eventually found to have lymphoma. We believe the case to be of interest and practical value to neurologists, oncologists and internists with an interest in inflammatory diseases.</p> <p>Case presentation</p> <p>A diagnosis of neurosarcoidosis was considered in a 49-year-old Caucasian man on the basis of the following symptoms and indications: a cough, bilateral hilar lymphadenopathy confirmed by thoracic computed tomography, the development of an S1 radiculopathy, cerebrospinal fluid abnormalities (raised protein level), bilateral lung hilar and lachrymal gland uptake on a gallium scan, and erythema nodosum confirmed with skin biopsy. These were followed by the development of multiple cranial neuropathies, including seventh nerve palsy. Exhaustive further investigations yielded no evidence for an alternative diagnosis. Treatments with steroids, cyclophosphamide, intravenous immunoglobulin and finally infliximab were of no benefit. He eventually developed cutaneous nodules, a biopsy of which revealed lymphoma that proved resistant to therapy.</p> <p>Conclusion</p> <p>Constant diagnostic vigilance is required in disorders such as neurosarcoidosis.</p

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.&lt;p&gt;&lt;/p&gt; Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.&lt;p&gt;&lt;/p&gt; Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.&lt;p&gt;&lt;/p&gt; Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = &#60;0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = &#60;0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = &#60;0.001 and 5.5%, p = &#60;0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed