Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life

Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life

Broad Repertoire of T Cell Autoreactivity Directly from Islets of Donors with Type 1 Diabetes (T1D)

Type 1 diabetes (T1D) is an autoimmune disease characterized by the infiltration of lymphocytes into the insulin-producing β-cells in the pancreas. We have isolated live T cells sorted or grown directly from the isolated, handpicked islets of human donors with T1D. We received ~500 islet equivalent EQ of variable purity (10-90%) from 12 donors with T1D (disease duration 0.42-20 years) and from seven control donors and two donors with type 2 diabetes (T2D). A total of 321 T cell lines and clones were derived from the islets of donors with T1D (3 lines from the 9 control donors). These are 131 CD4+ lines and clones, 47 CD8+ lines and 143 lines that contain both CD4+ and CD8+ T cells. From 50 lines and clones examined to date, we have determined the autoreactivity of 19 and have seen a broad repertoire of T cell autoreactivity in the islets, including characterized targets and post-translationally modified targets. Autoreactivity of CD4+ T cell lines was to three different peptides from glutamic acid decarboxylase 65 (GAD; GAD115-127, GAD274-286, GAD555-567), proinsulin76-90, and to chromogranin A or proinsulin expressed by DR4+DQ8+ B cells transduced with lentivirus containing constructs with the open reading frames corresponding to whole autoantigens. Reactivity to modified peptides included the glucose-regulated protein 78 and islet amyloid polypeptide with arginine to citrulline modifications (GRP78292-305(Arg-Cit297) and IAPP65-84(Arg-Cit 73, 81)), deaminations (IA-2545-562(Gln-Glu 548, 551, 556), and to several insulin hybrid peptides. These autoreactive CD4+ T cell lines and clones secreted only pro-inflammatory cytokines (IFN-γ, TNFα) upon peptide stimulation. For CD8+ T cells from islets, from one donor with T1D, we saw binding of a pool of HLA-A2 pentamers loaded with insulin B10-18, IA-2797-805 and insulin specific glucose-6-phosphatase catalytic subunit related protein, IGRP265-273. These results have implications for the development of successful prevention and reversal therapeutic strategies in T1D

Luxury brands consumption: The segment of “Chandlers”

The purpose of this paper is to introduce the segment of “chandlers” to the Russian academic society and to describe the specifics of their contemporary consumer behavior. The term “chandler” for this study was borrowed from American classical literature and applied to marketing. The study was conducted in April 2016 and comprised of two stages. The first stage was a series of in-depth interviews with seven representatives of the target audience from Moscow. It allowed to formulate the hypotheses which were proved/disproved by these hypotheses during the online survey. 117 relevant respondents were chosen for the study (72 — from Moscow, 45 — from regional city Ufa). The results allowed to formulate a preliminary conclusion there are no сhandlers in Ufa now. The most popular luxury brands for the Moscow сhandlers and specifics of their consumption were determined. This research is the first descriptive step to understanding the specifics of contemporary сhandlers — how they manage to consume luxury in the form of material artefacts and services, while being kept on a shoestring budget. The research entails a few limitations. The investigation comprised only a limited numbers of the respondents from Russian cities as Moscow and Ufa. In future, more consumers will be involved in the sample to cover more cities in Russia and respondents from other countries will be included. Upon the research completion a range of the recommendations has been provided to the luxury producers whose brands are already presented in Moscow and also for those who are planning to open their stores there. The results may serve as a guide for marketing tools development in the luxury industry. The originality of the paper lies in the term “chandlers’ segment” which is introduced in marketing theory for the first time

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Perceiving depth order during pursuit eye movement

Pursuit eye movements alter retinal motion cues to depth. For instance, the sinusoidal retinal velocity profile produced by a translating, corrugated surface resembles a sinusoidal shear during pursuit. One way to recover the correct spatial phase of the corrugationÕs profile (i.e. which part is near and which part is far) is to combine estimates of shear with extra-retinal estimates of translation. In support of this hypothesis, we found the corrugationÕs spatial phase appeared ambiguous when retinal shear was viewed without translation, but unambiguous when translated and viewed with or without a pursuit eye movement. The eyes lagged the sinusoidal translation by a small but persistent amount, raising the possibility that retinal slip could serve as the disambiguating cue in the eye-moving condition. A yoked control was therefore performed in which measured horizontal slip was fed back into a fixated shearing stimulus on a trial-by-trial basis. The results showed that the corrugationÕs phase was only seen unambiguously during the real eye movement. This supports the idea that extra-retinal estimates of eye velocity can help disambiguate ordinal depth structure within moving retinal images

Head-centred motion perception in the ageing visual system

Stationary objects appear to move in the opposite direction to a pursuit eye movement (Filehne illusion) and moving objects appear slower when pursued (Aubert-Fleischl phenomenon). Both illusions imply that extra-retinal, eye-velocity signals lead to lower estimates of speed than corresponding retinal motion signals. Intriguingly, the velocity (i.e. speed and direction) of the Filehne illusion depends on the age of the observer, especially for brief display durations (Wertheim and Bekkering, 1992). This suggests relative signal size changes as the visual system matures. To test the signal-size hypothesis, we compared the Filehne illusion and Aubert-Fleischl phenomenon in young and old observers using short and long display durations. The trends in the Filehne data were similar to those reported by Wertheim and Bekkering. However, we found no evidence for an effect of age or duration in the Aubert-Fleischl phenomenon. The differences between the two illusions could not be reconciled on the basis of actual eye movements made. The findings suggest a more complicated explanation of the combined influence of age and duration on head-centred motion perception than that described by the signal-size hypothesis

Pharmaceutical, cellular and genetic therapies for Huntington's disease

HD (Huntington's disease) is a devastating neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the huntingtin protein. Presently, there is no known cure for HD and existing symptomatic treatments are limited. However, recent advances have identified multiple pathological mechanisms involved in HD, some of which have now become the focus of therapeutic intervention. In this review, we consider progress made towards developing safe and effective pharmaceutical-, cell- and genetic-based therapies, and discuss the extent to which some of these therapies have been successfully translated into clinical trials. These new prospects offer hope for delaying and possibly halting this debilitating disease

Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease

BACKGROUND Alzheimer's disease (AD) is the most common form of dementia. The incidence of AD rises exponentially with age and its prevalence will increase significantly worldwide in the next few decades. Inflammatory processes have been suspected in the pathogenesis of the disease. OBJECTIVES To review the efficacy and side effects of aspirin, steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of AD, compared to placebo. SEARCH METHODS We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 12 April 2011 using the terms: aspirin OR "cyclooxygenase 2 inhibitor" OR aceclofenac OR acemetacin OR betamethasone OR celecoxib OR cortisone OR deflazacort OR dexamethasone OR dexibruprofen OR dexketoprofen OR diclofenac sodium OR diflunisal OR diflusinal OR etodolac OR etoricoxib OR fenbufen OR fenoprofen OR flurbiprofen OR hydrocortisone OR ibuprofen OR indometacin OR indomethacin OR ketoprofen OR lumiracoxib OR mefenamic OR meloxicam OR methylprednisolone OR nabumetone OR naproxen OR nimesulide OR "anti-inflammatory" OR prednisone OR piroxicam OR sulindac OR tenoxicam OR tiaprofenic acid OR triamcinolone OR NSAIDS OR NSAID. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmacuetical registries) and grey literature sources. SELECTION CRITERIA All randomised controlled trials assessing the efficacy of aspirin, steroidal and non-steroidal anti-inflammatory drugs in AD. DATA COLLECTION AND ANALYSIS One author assessed risk of bias of each study and extracted data. A second author verified data selection. MAIN RESULTS Our search identified 604 potentially relevant studies. Of these, 14 studies (15 interventions) were RCTs and met our inclusion criteria. The numbers of participants were 352, 138 and 1745 for aspirin, steroid and NSAIDs groups, respectively. One selected study comprised two separate interventions. Interventions assessed in these studies were grouped into four categories: aspirin (three interventions), steroids (one intervention), traditional NSAIDs (six interventions), and selective cyclooxygenase-2 (COX-2) inhibitors (five interventions). All studies were evaluated for internal validity using a risk of bias assessment tool. The risk of bias was low for five studies, high for seven studies, and unclear for two studies.There was no significant improvement in cognitive decline for aspirin, steroid, traditional NSAIDs and selective COX-2 inhibitors. Compared to controls, patients receiving aspirin experienced more bleeding while patients receiving steroid experienced more hyperglycaemia, abnormal lab results and face edema. Patients receiving NSAIDs experienced nausea, vomiting, elevated creatinine, elevated LFT and hypertension. A trend towards higher death rates was observed among patients treated with NSAIDS compared with placebo and this was somewhat higher for selective COX-2 inhibitors than for traditional NSAIDs. AUTHORS' CONCLUSIONS Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD