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Additional file 1: Supplementary Figure 1. Study Workflow Diagram.

AbstractBackgroundOver the last decade, there have been a number of changes in the Canadian landscape - the deconstruction of alcohol policy in some provinces, the legalization of cannabis, increased availability of gambling options, and the increase in opioid use and its associated problems. Have there been concomitant changes in societal images of addictions?MethodsA general population survey on societal images of addictions was conducted in multiple countries in 2008 - Finland, Sweden, Canada (Canadian sample size:N = 864; 40% response rate), and part of Russia (St Petersburg). We repeated the same survey in 2018 in Canada (N = 813; response rate = 23%). The survey assessed perceptions of the seriousness of different issues to society - including items about alcohol, tobacco, marijuana, gambling, misuse of medical drugs, and drugs like amphetamine, cocaine, or heroin - among other items (e.g., pollution, violent crime, prostitution).ResultsThere were increases in perceptions of the seriousness of misuse of medical drugs (p = .001), of illicit drugs (p = .005), ratings of the seriousness of cannabis use (p = .02), and a decrease in ratings of gambling as a social problem (p = .04). Ratings of the seriousness of alcohol and tobacco as social problems did not display significant changes over time (p > .05).ConclusionsThere has been some variation in societal perceptions of the seriousness of different addictions. Increases in perceptions of the seriousness of misusing medical drugs and the use of illicit drugs may reflect increases in societal concerns about opioid use and its associated problems. Despite substantial changes in alcohol control policies, the legalization of cannabis, and the increased availability of options for gambling, there appears to be very little associated change in societal perceptions regarding these addictive behaviours.

The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress.

Congenital amusia in its most common form is a disorder characterized by a musical pitch processing deficit. Although pitch is involved in conveying emotion in music, the implications for pitch deficits on musical emotion judgements is still under debate. Relatedly, both limited and spared musical emotion recognition was reported in amusia in conditions where emotion cues were not determined by musical mode or dissonance. Additionally, assumed links between musical abilities and visuo-spatial attention processes need further investigation in congenital amusics. Hence, we here test to what extent musical emotions can influence attentional performance. Fifteen congenital amusic adults and fifteen healthy controls matched for age and education were assessed in three attentional conditions: executive control (distractor inhibition), alerting, and orienting (spatial shift) while music expressing either joy, tenderness, sadness, or tension was presented. Visual target detection was in the normal range for both accuracy and response times in the amusic relative to the control participants. Moreover, in both groups, music exposure produced facilitating effects on selective attention that appeared to be driven by the arousal dimension of musical emotional content, with faster correct target detection during joyful compared to sad music. These findings corroborate the idea that pitch processing deficits related to congenital amusia do not impede other cognitive domains, particularly visual attention. Furthermore, our study uncovers an intact influence of music and its emotional content on the attentional abilities of amusic individuals. The results highlight the domain-selectivity of the pitch disorder in congenital amusia, which largely spares the development of visual attention and affective systems.

Purpose of Review This review will present the latest evidence on the impacts of sugar taxes on obesity with a focus on sugar-sweetened beverages (SSB). Recent Findings Evidence of direct impacts of SSB taxation policies on obesity prevalence continues to be limited. Natural experiments involving SSB taxation policies implemented in Mexico and Berkley, CA, indicate that this type of intervention alters beverage consumption patterns. Naturalistic evidence in combination with modeling studies suggests that SSB taxation is a viable anti-obesity policy. However, researchers and public health practitioners need to be vigilant of industry tactics to curtail SSB lowering efforts. Summary To maximize the impacts of SSB taxation, it should be combined with interventions that increase access to non-sweetened beverages, educate consumers about alternative healthy beverages, and explore taxation of other non-nutritive foods and beverages. Furthermore, both intended and unintended consequences of interventions should be closely monitored.

Many scholars have proposed that parent-child attachment security should favor child sleep. Research has yet, however, to provide convincing support for this hypothesis. The current study used objective measures of sleep and attachment to assess the longitudinal links between mother-child attachment security and subsequent sleep, controlling for child dependency. Sixty-two middle-class families (30 girls) were met twice, when children were 15 months (Wave 1; W1) and 2 years of age (Wave 2; W2). At W1, mother-child attachment was assessed with the observer version of the Attachment Q-Sort. At W2, children wore an actigraph monitor for 72 hr. Results indicated that children more securely attached to their mothers subsequently slept more at night and had higher sleep efficiency, and these predictions were not confounded by child dependency. These findings suggest a unique role for secure attachment relationships in the development of young children's sleep regulation, while addressing methodological issues that have long precluded consensus in this literature.

Abstract Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference −0.64, 95% confidence interval −0.68 to −0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530 .

Prostate cancer is the second leading cause of cancer-related death among Norwegian men. Metastatic prostate adenocarcinomas are primarily treated with androgen deprivation therapy (ADT). Although this treatment is initially effective in most patients, castration-resistant prostate cancer (CRPC) nearly always develops. Resistance to ADT appears to be driven by molecular mechanisms driving reactivation of or enhanced androgen signaling. The treatment landscape of CRPC is rapidly changing and is associated with appearance of more clinically aggressive disease variants that often are indifferent to androgen signaling, such as neuroendocrine prostate cancer (NEPC). NEPC is likely preceded by neuroendocrine transdifferentiation (NEtD), a process induced by both ADT and β2-adrenergic receptor (ADRB2) signaling. The aims of this thesis were to investigate the role of ADRB2 in development of therapy-resistant prostate cancer. Protein and mRNA levels of ADRB2 were associated with clinical endpoints across multiple cohorts. Preclinical model systems with varying ADRB2 expression levels were challenged with androgen-targeted therapies to unravel the functional involvement of ADRB2 in development of therapy resistance. We showed that tumors with low pre-treatment ADRB2 levels resisted androgen-targeted therapy through better retaining androgen levels. Low-ADRB2 tumors were unable to undergo ADT-induced NEtD and represent a model for androgen-driven CRPC adenocarcinoma. ADRB2 was shown to be essential for ADT-induced NEtD, which suggests that high-ADRB2 tumors are more likely to develop aggressive, androgen-indifferent prostate cancers like NEPC. In keeping with the pivotal role of sympathetic nerves in prostate cancer, and epidemiological studies showing a benefit of β-adrenergic receptor blockade, the presented findings suggest that targeting ADRB2 signaling is a promising therapeutic strategy in the management of advanced prostate cancer.

Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and transactivation of its receptor has been implicated in the pathogenesis of later-stage disease. As EGF signaling is altered by the acetylation status of histone proteins, we measured the effects of the histone deacetylase (HDAC) inhibitor, vorinostat, in mediating renal enlargement in diabetes focusing on the EGF-EGF receptor (EGFR) axis. In cultured proximal tubule (normal rat kidney) cells, vorinostat treatment reduced EGFR protein and mRNA, and attenuated cellular proliferation. Within 72 h of diabetes induction with streptozotocin, urinary EGF excretion was increased approximately threefold and was unaffected by vorinostat, even though the kidneys of vorinostat-treated diabetic rats had reduced tubular epithelial cell proliferation. Daily treatment of diabetic rats with vorinostat for 4 weeks blunted renal growth and glomerular hypertrophy. Thus, early renal changes in diabetes are amenable to epigenetic intervention. Attenuating effects of HDAC inhibition, although multifactorial, are likely to be mediated in part through downregulation of the EGFR.

Additional file 1. PRISMA-P 2015 Checklist.