Housing Conditions Differentially Affect Physiological and Behavioural Stress Responses of Zebrafish, as well as the Response to Anxiolytics

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of group and individually housed fish, and found that individually housed individuals have lower basal cortisol levels. In our second experiment we found ethanol appeared to have an anxiolytic effect with individually housed fish but not those that were group housed. In our final experiment, we examined the effects of changing the fishes' water prior to tank diving as an additional acclimation procedure. We found that this had no effect on individually housed fish, but appeared to affect the typical tank diving responses of the group housed individuals. In conclusion, we demonstrate that housing represents an important factor in obtaining reliable data from this methodology, and should be considered by researchers interested in comparative models of anxiety in zebrafish in order to refine their approach and to increase the power in their experiments

Response to reduced nicotine content cigarettes among smokers differing in tobacco dependence severity

This study examines whether tobacco dependence severity moderates the acute effects of reducing nicotine content in cigarettes on the addiction potential of smoking, craving/withdrawal, or smoking topography. Participants (N = 169) were daily smokers with mild, moderate, or high tobacco-dependence severity using the Heaviness of Smoking Index. Following brief abstinence, participants smoked research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg nicotine/g tobacco) in a within-subject design. Results were analyzed using repeated measures analysis of co-variance. No main effects of dependence severity or interactions with nicotine dose were noted in relative reinforcing effects in concurrent choice testing or subjective effects on the modified Cigarette Evaluation Questionnaire. Demand for smoking in the Cigarette Purchase Task was greater among more dependent smokers, but reducing nicotine content decreased demand independent of dependence severity. Dependence severity did not significantly alter response to reduced nicotine content cigarettes on the Minnesota Tobacco Withdrawal Scale nor Questionnaire of Smoking Urges-brief (QSU) Factor-2 scale; dependence severity and dose interacted significantly on the QSU-brief Factor-1 scale, with reductions dependent on dose among highly but not mildly or moderately dependent smokers. Dependence severity and dose interacted significantly on only one of six measures of smoking topography (i.e., maximum flow rate), which increased as dose increased among mildly and moderately but not highly dependent smokers. These results suggest that dependence severity has no moderating influence on the ability of reduced nicotine content cigarettes to lower the addiction potential of smoking, and minimal effects on relief from craving/withdrawal or smoking topography

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

Promoting smoking abstinence among patients with chronic obstructive pulmonary disease: Initial feasibility

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S., with the majority of COPD deaths attributable to cigarette smoking. Despite this, individuals with COPD have a higher prevalence of smoking, poorer quit rates, and higher relapse rates compared to smokers without a COPD diagnosis. We examined the feasibility of an incentives-based intervention for producing an initial period of biochemically-verified smoking abstinence among daily smokers with COPD. Participants were randomly assigned to a Contingent (n = 13) or Noncontingent (n = 16) incentives condition and visited the clinic for 14 consecutive days. Contingent participants earned vouchers with monetary value contingent on breath carbon monoxide (CO) levels during Study Days 1–5 and urinary cotinine during Days 6–14. Voucher earnings began at $9.00 and increased by$1.50 with each subsequent negative sample for maximum possible of $362.50. Noncontingent participants received vouchers of comparable value independent of smoking status. Differences between conditions varied across study days for daily smoking abstinence (X2 = 45.27, p < 0.0001), CO (F(13, 280) = 1.95, p = 0.025), and cotinine (F(13, 279) = 2.20, p = 0.010), with generally higher rates of abstinence and lower CO and cotinine levels observed in the Contingent vs. Noncontingent conditions. Results from this randomized pilot study support the potential efficacy of an incentives-based intervention for reducing cigarette smoking among individuals with COPD. Further research efforts should seek to promote and evaluate longer-term abstinence and associated changes in respiratory function. Keywords: Chronic obstructive pulmonary disease, Smoking, Behavioral intervention, Financial incentives, Vouchers, Contingency management, Carbon monoxide, Cotinin