Rationale
Cocaine use disorder (CUD) is associated with cognitive deficits that have been linked to poor treatment outcomes. An improved understanding of cocaine’s deleterious effects on cognition ...may help optimize pharmacotherapies. Emerging evidence implicates abnormalities in glutamate neurotransmission in CUD and drugs that normalize glutamatergic homeostasis (e.g.,
N
-acetylcysteine NAC) may attenuate CUD-related relapse behavior.
Objectives
The present studies examined the impact of chronic cocaine exposure on touchscreen-based models of learning (repeated acquisition) and cognitive flexibility (discrimination reversal) and, also, the ability of NAC to modulate cocaine self-administration and its capacity to reinstate drug-seeking behavior.
Methods
First, stable repeated acquisition and discrimination reversal performance was established. Next, high levels of cocaine-taking behavior (2.13–3.03 mg/kg/session) were maintained for 150 sessions during which repeated acquisition and discrimination reversal performance was probed periodically. Finally, the effects of NAC treatment were examined on cocaine self-administration and, subsequently, extinction and reinstatement.
Results
Cocaine self-administration significantly impaired performance under both cognitive tasks; however, discrimination reversal was disrupted considerably more than acquisition. Performance eventually approximated baseline levels during chronic exposure. NAC treatment did not perturb ongoing self-administration behavior but was associated with significantly quicker extinction of drug-lever responding. Cocaine-primed reinstatement did not significantly differ between groups.
Conclusions
The disruptive effects of cocaine on learning and cognitive flexibility are profound but performance recovered during chronic exposure. Although the effects of NAC on models of drug-taking and drug-seeking behavior in monkeys are less robust than reported in rodents, they nevertheless suggest a role for glutamatergic modulators in CUD treatment programs.
Saccharomyces paradoxus
is commonly isolated from environmental samples in Northern Europe and North America, but is rarely found associated with fermentation. However, as novelty has become a ...selling point in beer markets, interest toward non-conventional and local yeasts is increasing. Here, we report the first comprehensive investigation of the brewing potential of the species. Eight wild strains of
S. paradoxus
were isolated from oak trees growing naturally in Finland, screened in a series of fermentation trials and the most promising strain was selected for lager beer brewing at pilot scale (40 l). Yeasts were evaluated according to their ability to utilize wort sugars, their production of flavour-active aroma volatiles, diacetyl and organic acids, and sensorial quality of beers produced. All strains could assimilate maltose but this occurred after a considerable lag phase. Once adapted, most wild strains reached attenuation rates close to 70%. Adaptation to maltose could be maintained by re-pitching and with appropriate handling of the adapted yeast. Fermentation at 15 °C with the best performing strain was completed in 17 days. Maltose was consumed as efficiently as with a reference lager yeast, but no maltotriose use was observed. Bottled beers were evaluated by a trained sensory panel, and were generally rated as good as, or better than, reference beers.
S. paradoxus
beers were considered full-bodied and had a relatively clean flavour profile despite the presence of the clove-like 4-vinyl guaiacol. In conclusion,
S. paradoxus
exhibits a number of traits relevant to brewing, and with appropriate handling could be applied industrially.
The Nordic countries have been able to raise living standards and curb inequalities without compromising economic growth. But with social inequalities on the rise how do they fare when compared to ...countries with alternative welfare models, such as the United Kingdom, the Netherlands and Germany?
Taking a comparative perspective, this book casts new light on the changing inequalities in Europe. It will be invaluable for students and policy makers interested in European social policy and living conditions.
The first aim of this systematic review was to evaluate the evidence for family psychoeducation (FPE) interventions for major depressive disorder (MDD). A second aim was to compare the efficacy of ...different modes of delivering face‐to‐face FPE interventions. Ten studies (based on nine distinct samples) were identified comprising four single‐family studies, four multifamily studies, one single versus multifamily comparative study, and one peer‐led, mixed‐diagnosis study. Seven studies measured patient functioning and six reported positive outcomes. Six studies measured carer's well‐being and four reported positive outcomes. Results provide preliminary evidence that FPE leads to improved outcomes for patient functioning and family–carer's well‐being for persons with depression. The implications for future development and delivery of FPE interventions for MDD are discussed.
ObjectivesMusculoskeletal pain often occurs at multiple sites concurrently. The aim of this study was to examine the associations between multi-site pain and self-rated work ability and retirement ...plans among actively working people.MethodsThe Health 2000 Survey was carried among a representative sample of Finnish adults. Musculoskeletal pain during the preceding month in the lower back, neck or shoulders, upper extremities, hips and lower extremities, and work ability and intentions to retire early were assessed. Subjects were also clinically examined. Analyses were restricted to 30–64-year-old subjects actively working during the preceding 12 months who provided information on work ability outcomes (population-weighted number of subjects=4087). Log-binomial regression was used to estimate prevalence ratios of reduced work ability.ResultsSingle-site pain was reported by 33% of subjects, 20%, 9% and 4% reported pain in two, three and four sites, respectively, and 8%–15% reported poor work ability. Every fifth person had thought about retiring early. Age- and gender-adjusted risks of poor physical work ability and own prognosis of poor future work ability increased from 2 for single-site pain to 8 for pain at four sites. Risks remained considerably elevated after adjustment for various covariates, including clinical musculoskeletal disorders and functional capacity. Poor current work ability was most affected by multi-site pain at older age (50–64 years) and intentions to retire early at age 40–49 years.ConclusionsCo-occurring pain is a considerable threat to work ability. Workers with multi-site pain may benefit from targeted preventive measures to sustain their work ability. Future studies should also consider multi-site pain as an important risk factor for reduced work ability.
Anhedonia, the loss of pleasure from previously rewarding activities, is implicated in several neuropsychiatric conditions, including major depressive disorder (MDD). In order to accelerate drug ...development for mood disorders, quantitative approaches are needed to objectively measure responsiveness to reward as a means to identify deficits. One such approach, the probabilistic reward task (PRT), uses visual discrimination methodology to quantify reward learning. In this computerized task, humans make visual discriminations, and probabilistic contingencies are arranged such that correct responses to one alternative are rewarded more often (rich) than correct responses to the other (lean). Healthy participants consistently develop a response bias in favor of the rich alternative. However, participants with MDD typically exhibit lower response biases, and this blunting correlates with current and future anhedonia. The present studies validated a touchscreen-based PRT in rodents with formal and functional similarity to the human task. First, rats were trained to discriminate between two lines that differed in length. Next, parametric manipulations of probabilistic contingencies, line-length stimuli, and drug treatment (amphetamine, 0.32-3.2 mg/kg; scopolamine, 0.1-1.0 mg/kg; oxycodone, 0.1-1.0 mg/kg) on response bias were evaluated. Results demonstrated orderly shifts in bias and discriminability that varied as a function of, respectively, the asymmetry of rich/lean probabilities and disparity in line lengths. Drugs that enhance reward responsiveness (amphetamine and scopolamine, but not oxycodone) increased bias, verifying pharmacological task sensitivity. Finally, performance outcomes under optimized conditions were replicated in female rats. Collectively, the touchscreen-based rodent PRT appears to have high preclinical value as a quantitative assay of reward learning.
Abstract Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain ...incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol LDL-C), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene ( R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms.
A number of practice guidelines are available to set the benchmark for best practice when working with individuals with intellectual disabilities and co‐morbid mental health concerns. However, ...dissemination and implementation of such guidelines in the context of psychologists' work settings has received little attention. The aim of this qualitative study was to investigate adherence to current practice guidelines by Australian psychologists working with this specialist population and explore organizational factors that may facilitate or hinder evidence‐based practice implementation. Thirty‐eight Australian psychologists from government disability and non‐government disability organizations working primarily with individuals with intellectual disability participated in eight semistructured focus groups. Psychologists were presented with a summary of a current Australian practice guideline in dual disabilities and asked about their views of best practice adherence and implementation of the guideline including facilitative and hindering factors influencing implementation. Psychologists reported views consistent with current Australian best practice standards but noted a number of barriers impacting on adherence. Facilitators and hindrances to best practice implementation were discussed in relation to views on applicability of current guideline, organizational level considerations, organizational resources and training, organizational operations, and systemic considerations. Findings highlight the importance of a collaborative and systemic approach in order for practice guidelines to be effectively implemented for psychologists working with disabilities. Implications for policy development and training are discussed.
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