Cytokine detection in eiav-infected equine monocyte-derived macrophages using quantitative real-time polymerase chain reaction

The replication of equine infectious anemia virus (EIAV) in macrophages not only leads to cell death, but also to the induction of a variety of cytokines that may affect immune function. Cytokine production may be responsible for the fever, anorexia, hemorrhages, lethargy or thrombocytopenia seen in the acute and chronic phases of equine infectious anemia (EIA). The study of the equine immune system and inflammatory responses, by measuring cytokine expression, can provide important insight into disease pathogenesis in the horse. We have extended studies of virulent and avirulent EIAV clones by examining the effects of Env proteins on cytokine expression in equine monocyte-derived macrophages (EMDM) using EIAV17, EIAV19, EIAV17SU, and EIAV17TM viruses. In the current studies a set of quantitative real-time polymerase chain reaction (QPCR) assays for the equine cytokines IL-1α, IL-1β, IL-6, IL-8 and TNF-α were validated using QPCR primers and probes which were generated for the aforementioned equine genes

Superintendency: Preparation- a School Finance Issue

Educational Administratio

Exploring and understanding the scope and value of the Parkinson’s nurse in the UK (The USP Project): a realist economic evaluation protocol

Introduction There are multiple configurations of specialist nurses working in the field of Parkinson’s. Parkinson’s Nurse Specialists (PNSs) are recognised as playing a pivotal role; however, there is little published evidence to demonstrate their effectiveness. Further evidence is needed to establish which aspects of the PNSs provide the greatest benefit to people with Parkinson’s and their families, and the cost-effectiveness of different models of care. Methods and analysis Realist approaches explain how and why programmes work (or not) through striving to answer the question: what works, for whom and under what circumstances. This research uses a realist evaluation and aims to integrate an economic analysis within the realist framework. We refer to this as ‘realist economic evaluation’. It comprises four phases: (1) developing resource-sensitive initial programme theories (IPTs) using surveys to gain a better understanding of the role and impact (costs and benefits) of the PNSs; (2) testing the IPTs through qualitative interviews and quantitative data analysis; (3) evaluating the cost and resource use implications alongside the benefits associated with the role of the PNSs and (4) iteratively refining the IPTs throughout the project. The IPTs will draw on both quantitative and qualitative data. The result of the study will be a series of refined programme theories, which will explain how specialist nurses work in the field of Parkinson’s in the UK, what impact they have on people with Parkinson’s and their families and carers, and at what cost. Ethics and dissemination Northumbria University, the Health Research Authority and Health and Care Research Wales have approved this study. Key findings will be disseminated throughout the duration of the project online and through social media, and via annual and regional Parkinson’s meetings and the Parkinson’s UK Excellence Network. Academic dissemination will occur through publication and conference presentations

Visual responses in the lateral geniculate evoked by Cx36-independent rod pathways

AbstractEmerging evidence indicates rods can communicate with retinal ganglion cells (RGCs) via pathways that do not involve gap-junctions. Here we investigated the significance of such pathways for central visual responses, using mice lacking a key gap junction protein (Cx36−/−) and carrying a mutation that disrupts cone phototransduction (Gnat2cpfl3). Electrophysiological recordings spanning the lateral geniculate revealed rod-mediated ON and OFF visual responses in virtually every cell from all major anatomical sub-compartments of this nucleus. Hence, we demonstrate that one or more classes of RGC receive input from Cx36-independent rod pathways and drive extensive ON and OFF responses across the visual thalamus

ETHYL GLUCURONIDE: A BIOMARKER TO IDENTIFY ALCOHOL USE BY HEALTH PROFESSIONALS RECOVERING FROM SUBSTANCE USE DISORDERS

Aims: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half-life of alcohol and no other highly specific marker. Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessment of drinking status (up to 5 days). Our aim was to assess the potential value of EtG testing in abstinence-based monitoring programs. Patients and methods: Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained ‘for cause', ‘to verify positive urine alcohol, when drinking was denied' and ‘in high risk individuals'. All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS in addition to standard testing. The main outcome measure were urine specimens positive for EtG versus those positive based on standard testing for alcohol and other drugs. Results: Among the initial 100 random samples collected, no sample was positive for alcohol using standard testing; however, seven were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, eight of eight tests performed ‘for cause' were positive for EtG but negative for all other drugs including urine alcohol. All eight were confirmed positive by self reported drinking by the patient when confronted regarding the positive test result. Of six tests performed to ‘confirm a positive urine alcohol' two were positive for EtG and confirmed positive by self reported drinking. For the other four samples, especially as two are from a diabetic, in vitro fermentation of ethanol is discussed. Conclusions: These data suggest that physicians in monitoring programs have a higher rate of unrecognized alcohol use than previously reported. Incorporation of EtG testing into alcohol abstinence monitoring can strengthen these program

Burning the candle at both ends: Intraretinal signaling of intrinsically photosensitive retinal ganglion cells

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors located in the ganglion cell layer. They project to brain regions involved in predominately non-image-forming functions including entrainment of circadian rhythms, control of the pupil light reflex, and modulation of mood and behavior. In addition to possessing intrinsic photosensitivity via the photopigment melanopsin, these cells receive inputs originating in rods and cones. While most research in the last two decades has focused on the downstream influence of ipRGC signaling, recent studies have shown that ipRGCs also act retrogradely within the retina itself as intraretinal signaling neurons. In this article, we review studies examining intraretinal and, in addition, intraocular signaling pathways of ipRGCs. Through these pathways, ipRGCs regulate inner and outer retinal circuitry through both chemical and electrical synapses, modulate the outputs of ganglion cells (both ipRGCs and non-ipRGCs), and influence arrangement of the correct retinal circuitry and vasculature during development. These data suggest that ipRGC function plays a significant role in the processing of image-forming vision at its earliest stage, positioning these photoreceptors to exert a vital role in perceptual vision. This research will have important implications for lighting design to optimize the best chromatic lighting environments for humans, both in adults and potentially even during fetal and postnatal development. Further studies into these unique ipRGC signaling pathways could also lead to a better understanding of the development of ocular dysfunctions such as myopia

Restoration of Vision with Ectopic Expression of Human Rod Opsin

SummaryMany retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (≈50–100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration

Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype

Abstract The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands

Depressive episodes, symptoms, and trajectories in women recently diagnosed with breast cancer.

Depression carries serious psychosocial, physical, and economic consequences for cancer survivors. Study goals were to characterize patterns and predictors of depressive symptoms and major depressive episodes in recently diagnosed breast cancer patients. Consecutively recruited women (N = 460) completed a validated interview (CIDI) and questionnaire measure (CES-D) of depression within 4 months after invasive breast cancer diagnosis and at six additional assessments across 12 months. Outcomes were major depressive episodes, continuous symptom scores, and latent symptom trajectory classes. Across 12 months, 16.6 % of women met criteria for a major depressive episode. Unemployment predicted depressive episodes after other correlates were controlled. Distinct trajectory classes were apparent: an estimated 38 % of women had chronically elevated symptoms (High trajectory), 20 % recovered from elevated symptoms (Recovery), and 43 % had lower symptoms (Low and Very Low trajectories). Although 96 % of episodes occurred in the High or Recovery classes, 66 % of women in the High trajectory did not have an episode. Women in the Low (vs High) trajectory were more likely to be older, retired, more affluent, and have fewer comorbid diseases and briefer oncologic treatment. Women in the Recovery trajectory (vs High) were more likely to be married and more affluent and have fewer comorbid diseases. Assuming available therapeutic resources, assessment of both depressive symptoms and episodes over several months after diagnosis is important. Identification of patients at risk for persistently high depressive symptoms (e.g., younger, longer treatment course) opens targeted opportunities to prevent and promote rapid recovery from depression