DSCAM promotes axon fasciculation and growth in the developing optic pathway

Acknowledgments We thank Drs. Robert Burgess, Carol Mason, and Eloisa Herrera for helpful discussions; Dr. Thomas Theil for his invaluable advice on the slice culture methods; Francesca Lamb and Emma Smith for technical assistance; and the Institute of Medical Sciences Microscopy and Imaging Facility for assistance with confocal microscopy. This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) doctoral training award studentship and a BBSRC project grant (BB/J00815X/1). Freely available online through the PNAS open access option.Peer reviewedPublisher PD

Dietary Patterns Associated with Alzheimer\u27s Disease and Related Chronic Disease Risk: A Review

The world’s population is growing older due to improved healthcare and nutrition. As a result, Alzheimer’s disease (AD) prevalence is rapidly increasing. The focus of the current research climate is shifting from understanding AD pathology and diagnosis to primary prevention and intervention strategies. Diet represents one potential intervention strategy accessible to all. Accumulating evidence suggests diet plays a major role in risk and development of AD and AD-related chronic diseases of the periphery like cardiovascular disease (CVD) and diabetes. This paper reviews studies that have explored the relationship between “a priori” dietary patterns, AD and AD-related chronic disease risk. The dietary patterns we will review are the healthy eating index, healthy diet indicator, recommended food score, and the Mediterranean diet (MeDi). Our review of the literature suggests a generally positive association between healthy diet patterns, AD and AD-related chronic disease risk; however the magnitude of the protective effect is modest in many studies. Consequently, we can only confidently conclude that the MeDi is associated with reduced AD risk, and further studies on the remaining indices need to be carried out. It is our opinion that a combination of dietary scores could predict overall dietary quality and chronic disease risk to a greater extent than one score individually. Analysis in multi-ethnic cohorts, investigating combinations of scores must be completed before firm conclusions can be reached on the ideal combination of scores. Obtaining further insight into the association between dietary patterns, AD and AD-related chronic disease risk may help in prioritizing public health efforts and provide a stronger basis for recommendations to improve dietary patterns

Redefining disease emergence to improve prioritization and macro-ecological analyses

AbstractMicrobial infections are as old as the hosts they sicken, but interest in the emergence of pathogens and the diseases they cause has been accelerating rapidly. The term ‘emerging infectious disease’ was coined in the mid-1900s to describe changes in disease dynamics in the modern era. Both the term and the phenomena it is meant to characterize have evolved and diversified over time, leading to inconsistencies and confusion. Here, we review the evolution of the term ‘emerging infectious disease’ (EID) in the literature as applied to human hosts. We examine the pathways (e.g., speciation or strain differentiation in the causative agent vs. rapid geographic expansion of an existing pathogen) by which diseases emerge. We propose a new framework for disease and pathogen emergence to improve prioritization. And we illustrate how the operational definition of an EID affects conclusions concerning the pathways by which diseases emerge and the ecological and socioeconomic drivers that elicit emergence. As EIDs appear to be increasing globally, and resources for science level off or decline, the research community is pushed to prioritize its focus on the most threatening diseases, riskiest potential pathogens, and the places they occur. The working definition of emerging infectious diseases and pathogens plays a crucial role in prioritization, but we argue that the current definitions may be impeding these efforts. We propose a new framework for classifying pathogens and diseases as “emerging” that distinguishes EIDs from emerging pathogens and novel potential pathogens. We suggest prioritization of: 1) EIDs for adaptation and mitigation, 2) emerging pathogens for preventive measures, and 3) novel potential pathogens for intensive surveillance

Real life does not always get in the way: verbal memory and the Sustained Attention to Response Task

The Sustained Attention to Response Task (SART) is a go/no-go task where participants must respond frequently to target stimuli and withhold responses from infrequent neutral stimuli. Researchers have shown that the fast and frequent responding characteristic of SART is typically associated with difficulty withholding responses to no-go stimuli. Imposing additional cognitive demands has been shown to further impair task performance. In the present research, participants completed a modified SART task, a narrative memory task, and a dual-task condition where both were done simultaneously. No significant performance impairments were found in the dual- compared to single-task conditions. The tasks’ non-overlapping resource demands, alongside a potential arousing benefit of the memory task, may explain the lack of notable dual-task interference. Future research is needed to better understand the effects of arousal and other factors that may help to uncouple errors of commission from response time, particularly in tasks with high ecological validity

The Resolved Stellar Halo of NGC 253

We have obtained Magellan/IMACS and HST/ACS imaging data that resolve red giant branch stars in the stellar halo of the starburst galaxy NGC 253. The HST data cover a small area, and allow us to accurately interpret the ground-based data, which cover 30% of the halo to a distance of 30 kpc, allowing us to make detailed quantitative measurements of the global properties and structure of a stellar halo outside of the Local Group. The geometry of the halo is significantly flattened in the same sense as the disk, with a projected axis ratio of b/a ~ 0.35 +/- 0.1. The total stellar mass of the halo is estimated to be M_halo ~ 2.5 +/- 1.5 x 10^9 M_sun, or 6% of the total stellar mass of the galaxy, and has a projected radial dependence that follows a power law of index -2.8 +/- 0.6, corresponding to a three-dimensional power law index of ~ -4. The total luminosity and profile shape that we measure for NGC 253 are somewhat larger and steeper than the equivalent values for the Milky Way and M31, but are well within the scatter of model predictions for the properties of stellar halos built up in a cosmological context. Structure within the halo is seen at a variety of scales: there is small kpc-scale density variation and a large shelf-like feature near the middle of the field. The techniques that have been developed will be essential for quantitatively comparing our upcoming larger sample of observed stellar halos to models of halo formation.Comment: ApJ, in press. Version with full resolution figures available at http://www.astro.lsa.umich.edu/~jbailin/papers/bailin_n253halo.pd

Critical roles for the phosphatidylinositide 3-kinase isoforms p110β and p110γ in thrombopoietin-mediated priming of platelet function

Abstract Thrombopoietin (TPO) enhances platelet activation through activation of the tyrosine kinase; JAK2 and the lipid kinase phosphatidylinositide 3-kinase (PI3K). The aim of our study was to identify the PI3K isoforms involved in mediating the effect of TPO on platelet function and elucidate the underlying mechanism. We found that p110β plays an essential role in TPO-mediated (i) priming of protease-activated receptor (PAR)-mediated integrin αIIbβ3 activation and α-granule secretion, (ii) synergistic enhancement of PAR-mediated activation of the small GTPase RAP1, a regulator of integrin activation and (iii) phosphorylation of the PI3K effector Akt. More importantly, the synergistic effect of TPO on phosphorylation of extracellular-regulated kinase (ERK1/2) and thromboxane (TxA2) synthesis was dependent on both p110β and p110γ. p110β inhibition/deletion, or inhibition of p110γ, resulted in a partial reduction, whereas inhibiting both p110β and p110γ completely prevented the synergistic effect of TPO on ERK1/2 phosphorylation and TxA2 synthesis. The latter was ablated by inhibition of MEK, but not p38, confirming a role for ERK1/2 in regulating TPO-mediated increases in TxA2 synthesis. In conclusion, the synergistic effect of TPO on RAP1 and integrin activation is largely mediated by p110β, whereas p110β and p110γ contribute to the effect of TPO on ERK1/2 phosphorylation and TxA2 formation

How Do Patients with Mental Health Diagnoses Use Online Patient Portals? An Observational Analysis from the Veterans Health Administration

Online patient portals may be effective for engaging patients with mental health conditions in their own health care. This retrospective database analysis reports patient portal use among Veterans with mental health diagnoses. Unadjusted and adjusted odds of portal feature use was calculated using logistic regressions. Having experienced military sexual trauma or having an anxiety disorder, post-traumatic stress disorder, or depression were associated with increased odds of portal use; bipolar, substance use, psychotic and adjustment disorders were associated with decreased odds. Future research should examine factors that influence portal use to understand diagnosis-level differences and improve engagement with such tools

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population

Higher coffee consumption is associated with slower cognitive decline and less cerebral Aβ-amyloid accumulation over 126 months: Data from the Australian imaging, biomarkers, and lifestyle study

Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations. Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months. Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to “moderate,” “high,” or “very high” Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume. Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset