The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms

In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will discuss how models of drug addiction and relapse should more systematically evaluate these different types of stimuli to better understand the neurobiology underlying craving and relapse. In this way, behavioral and pharmacotherapeutic interventions may be better tailored to promote drug use cessation outcomes and long-term abstinence

Accumbens Cholinergic Interneurons Mediate Cue-Induced Nicotine Seeking and Associated Glutamatergic Plasticity

Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs), which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes is unknown. ChIs represent less than 1% of the accumbens neuronal population and are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine-seeking behavior. Using chemogenetics in transgenic rats expressing Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bidirectionally manipulated before cue-induced reinstatement. Following nicotine self-administration and extinction, ChIs were activated or inhibited before a cue reinstatement session. Following reinstatement, whole-cell electrophysiology from NAcore MSNs was used to assess changes in plasticity, measured via AMPA/NMDA (A/N) ratios. Chemogenetic inhibition of ChIs inhibited cued nicotine seeking and resulted in decreased A/N, relative to control animals, whereas activation of ChIs was unaltered, demonstrating that ChI inhibition may modulate plasticity underlying cue-induced nicotine seeking. These results demonstrate that ChI neurons play an important role in mediating cue-induced nicotine reinstatement and underlying synaptic plasticity within the NAcore

Qwu?gwes - A Squaxin Island tribal heritage wet site, Puget Sound, USA

The Qwu?gwes wet site is located at the very head of Puget Sound in Washington State, USA (fig 1). Puget Sound has been referred to as an inland sea, but is better termed as a large glacially cut fjord that is approximately 145km long, running north to south, where the ocean salt water from the Pacific mixes with fresh water draining from the surrounding watersheds. Puget Sound was formed into the north–south fjord it is today by glaciers that advanced from the north at least four times, scouring and carving it for millions of years (Waitt & Thorson 1983). The Vashon Stade was the last major advance, reaching its maximum about 18,000 years ago, covering everything between the Olympic and the Cascade mountains and spreading as far south as our specific region of study. As the Vashon Stade retreated, its melting ice created a massive fresh water lake that released through the Black Lake spillway at the head of Eld Inlet, our site location, and down the Chehalis River drainage to the Pacific Ocean. Once the glaciers melted far enough north, the Straits of Juan de Fuca were open and salt water from the Pacific Ocean entered Puget Sound, making it the salt water ‘inland sea’ it is today (fig 1). Our research area encompasses the southern reaches of the traditional territory of the Lushootseed-speaking Coast Salish People and language family, sometimes referred to as Puget [Sound] Salish (Suttles & Lane 1990, 485–502; Thompson & Kinkade 1990, 38; fig 1). Few systematic archaeological investigations have occurred in this region, especially in the southern section of Lushootseed traditional territory, so this paper should be considered a much needed synthesis of a well-preserved waterlogged site. Qwu?gwes forms the main reference point for our synthesized presentations, and this work is based on the original papers presented by the authors at the 11th International Wetland Archaeology Research Project (WARP) conference in Edinburgh (21–24 September 2005). This joint investigation of the Squaxin Island Tribe and South Puget Sound Community College has been ongoing for several years and provides both a scientific and cultural perspective of the many findings. Earlier publications stress the basis of this joint co-operative effort and the need for co-ordinated scientific and Native cultural understandings and explanations (Foster & Croes 2002, 2004)

The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging: Methodology and Baseline Characteristics of 1112 Individuals Recruited for a Longitudinal Study of Alzheimer\u27s Disease

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer\u27s disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline

A web-based intervention (RESTORE) to support self-management of cancer-related fatigue following primary cancer treatment: a multi-centre proof of concept randomised controlled trial

Purpose: Cancer-related fatigue (CRF) is a frequent and distressing symptom experienced after cancer treatment. RESTORE is the first web-based resource designed to enhance self-efficacy to manage CRF following curative-intent treatment. The aim of this study is to test the proof of concept and inform the design of an effectiveness trial. Methods: A multi-centre parallel-group two-armed (1:1) exploratory randomised controlled trial (RCT) with qualitative process evaluation was employed in the study. Participants (≥18 years; ≤5 years post treatment with moderate to severe fatigue) were recruited and randomly assigned to RESTORE or a leaflet. Feasibility and acceptability were measured by recruitment, attrition, intervention adherence, completion of outcome measures and process evaluation. Change in self-efficacy to manage CRF was also explored. Outcome measures were completed at baseline (T0), 6 weeks (T1) and 12 weeks (T2). Data were analysed using mixed-effects linear regression and directed content analysis. Results: One hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [−0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested. Conclusion: Proof of concept was achieved. The RESTORE intervention should be subject to a definitive trial with some adjustments. Provision of an effective supportive resource would empower cancer survivors to manage CRF after treatment completion

Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance

A web-based intervention (RESTORE) to support self-management of cancer-related fatigue following primary cancer treatment: a multi-centre proof of concept randomised controlled trial

. A web-based intervention (RESTORE) to support self-management of cancer-related fatigue following primary cancer treatment: a multi-centre proof of concept randomised controlled trial. Supportive Care in Cancer, Results One hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [−0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested

Introduction to “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates”

Abstract Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS)

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening