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61), but reduced risk was found in upper limb melanomas (hazard ratio (HR) = 0.70, 95% confidence interval (CI) 0.51-0.96; high versus low PA). Non-significant reduced risks were found for seasonal outdoor walking &gt;2 h/day versus 30-60 min/day (summer HR = 0.81, 95% CI 0.66-1.00; autumn HR = 0.74, 95%CI 0.55-1.01). Seasonal PAs were not associated with melanoma risk. In conclusion, we found positive associations between overall PA and sunbathing vacations and indoor tanning, and, unlike literature, inverse association between overall PA and sunburns. Our results do not support a positive association between PA and melanoma risk in Norwegian women.In June 2016, California implemented a Tobacco 21 (T21) policy that increased the minimum sale age of tobacco products from 18 to 21. [https://www.selleckchem.com/products/hs-173.html Selleck HS-173] This study examined the association between California's T21 policy and smoking behavior (ever, current, daily, and nondaily) in 18-20 year-olds using data from the 2012-2019 Behavioral Risk Factor Surveillance System (n = 15,863). The annual change in odds of smoking among 18-20 year-olds post-policy (July 2016-December 2019) was compared with the pre-policy period (January 2012 - June 2016) 1) within California and 2) compared with states without a T21 policy. As a sensitivity analysis, 21-23 year-olds in California were used as the referent. Difference-in-difference estimates (D-I-D) were calculated using adjusted logistic regression and compared the post to pre-policy change in trends in California to the referent groups. Before California's T21 policy, there was an 11% annual decrease in the odds of ever smoking among 18-20 year-olds in California and a 6% decrease in the referent states. After the policy, these trends did not change significantly. Results for current smoking were similar. For daily smoking, there was an 8% annual decrease before the policy and a 26% annual decrease after the policy among 18-20 year-olds in California; D-I-D estimates were 0.80 (95% CI 0.57, 1.14) using referent states as the comparison and 0.62 (95% CI 0.41, 0.95) using 21-23 year-olds in California as the comparison. There was an association between California's T21 policy and a decrease in daily smoking among 18-20 year-olds, compared with 21-23 year-olds, more than three years post-implementation.Cognition and behavior are tightly linked to synaptic function. A growing body of evidence suggests that aberrant neurotransmission, caused by changes in synaptic protein expression levels, may be a major cause underlying different brain disorders. These changes in expression result in abnormal synaptic organization or function, leading to impaired neurotransmission and unbalanced circuit operations. Here, we review the data supporting the involvement of mutations in genes coding for kainate receptor (KAR) subunits in the pathogenesis of psychiatric disorders and Down syndrome (DS). We show that most of these mutations do not affect the biophysical properties or the receptors, but rather alter subunit expression levels. On the basis of reports studying KAR genes mutations in mouse models of autism spectrum disorders and DS, we illustrate how deviations from the physiological regulatory role that these receptors play in neurotransmitter release and plasticity give rise to synaptic alterations that lead to behavioral and cognitive deficits underlying these disorders.Early life adversity can set the trajectory for later psychiatric disorders, including substance use disorders. There are a host of neurobiological factors that may play a role in the negative trajectory. The current review examines preclinical evidence suggesting that early life adversity specifically involving social factors (maternal separation, adolescent social isolation and adolescent social defeat) may influence drug abuse vulnerability by strengthening corticotropin-releasing factor (CRF) systems and weakening oxytocin (OT) systems. In adulthood, pharmacological and genetic evidence indicates that both CRF and OT systems are directly involved in drug reward processes. With early life adversity, numerous studies show an increase in drug abuse vulnerability measured in adulthood, along a concomitant strengthening of CRF systems and a weakening of OT systems. Mechanistic studies, while relatively few in number, are generally consistent with the theme that strengthened CRF systems and weakened OT systems mediate, at least in part, the link between early life adversity and drug abuse vulnerability. Establishing a direct role of CRF and OT in mediating the relation between early life social stressors and drug abuse vulnerability will inform clinical researchers and practitioners toward the development of intervention strategies to reduce risk among those suffering from early life adversities. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.Highly palatable foods and substance of abuse have intersecting neurobiological, metabolic and behavioral effects relevant for understanding vulnerability to conditions related to food (e.g., obesity, binge eating disorder) and drug (e.g., substance use disorder) misuse. Here, we review data from animal models, clinical populations and epidemiological evidence in behavioral, genetic, pathophysiologic and therapeutic domains. Results suggest that consumption of highly palatable food and drugs of abuse both impact and conversely are regulated by metabolic hormones and metabolic status. Palatable foods high in fat and/or sugar can elicit adaptation in brain reward and withdrawal circuitry akin to substances of abuse. Intake of or withdrawal from palatable food can impact behavioral sensitivity to drugs of abuse and vice versa. A robust literature suggests common substrates and roles for negative reinforcement, negative affect, negative urgency, and impulse control deficits, with both highly palatable foods and substances of abuse. Candidate genetic risk loci shared by obesity and alcohol use disorders have been identified in molecules classically associated with both metabolic and motivational functions. Finally, certain drugs may have overlapping therapeutic potential to treat obesity, diabetes, binge-related eating disorders and substance use disorders. Taken together, data are consistent with the hypotheses that compulsive food and substance use share overlapping, interacting substrates at neurobiological and metabolic levels and that motivated behavior associated with feeding or substance use might constitute vulnerability factors for one another.Heightened novelty and sensation seeking are associated with an increased risk of substance use disorder in clinical populations. In rats, sensation seeking is often examined by measuring locomotor reactivity to a novel environment. So-called high responders (HR) acquire self-administration of psychostimulants more quickly and consume higher amounts of drug compared to low responder (LR) rats, indicating that the HR trait might confer a stronger addiction propensity. However, studies of addiction-like behaviors in HR vs LR rats have typically utilized self-administration paradigms that do not dissociate individual differences in the hedonic/reinforcing and motivational properties of a drug. Moreover, little attention has been given to whether HR rats are more susceptible to drug-access conditions that promote a state-dependent addiction phenotype. We report that on a behavioral economics task, HR rats have higher preferred brain-cocaine levels compared to LR rats but do not differ with respect to their demand elasticity for cocaine. In contrast, when tested on an intermittent access schedule of cocaine self-administration, which has been shown to promote several addiction-related endophenotypes, HR rats exhibited greater escalation of intake and more drastic reductions in cocaine demand elasticity. Together, these data indicate that the HR trait does not confer higher extant addiction behavior, but rather that this phenotype is associated with a propensity for addiction that remains dormant until it is actuated by intermittent drug intake. These findings reveal a 'trait' (HR) by 'state' (intermittent drug intake) interaction that produces a strong addiction phenotype.Phospholipases A2 (PLA2s) and PLA2-like proteins are significant components of snake venoms. Some of these proteins act as potent toxins causing muscle necrosis, which may lead to amputation in severe envenomings. Fundamental aspects of the mechanism of action of these toxins are still not completely known. Myotoxin-I is a catalytically active Asp49 PLA2 from the venom of Bothrops asper, a medically relevant pit viper from Central America. Myotoxin-II is a catalytically inactive Lys49 PLA2-homolog also present in the venom of this snake. For the first time, the in vivo cellular localization of these myotoxins was studied in mouse skeletal muscle using immunofluorescence. Results showed that after 5 min of injection in the gastrocnemius muscle, both toxins initially interacted with the sarcolemma, and some colocalization with nuclei was already evident, especially for Mt-II. After 3 h of injection, a significant colocalization with the nuclei was observed for both toxins. These in vivo results confirm the importance of the initial interaction of these toxins with the sarcolemma and furthermore highlight the internalization and interaction of the toxins with nuclei during their pathophysiological activities, as observed in recent studies using cell culture.<br /><br /> To evaluate perspectives of youth regarding diverted stimulant use among a contemporary sample of adolescents and young adults.<br /><br /> This study used MyVoice, a longitudinal national text message survey of American youth. In February 2019, 1228 MyVoice youth were asked 4 open-ended questions to elicit their perspectives on diverted stimulant use. Responses were assessed using thematic analysis, and quantitative results were summarized using descriptive statistics.<br /><br /> Of 1228 youth, 906 responded to at least one survey question (relative risk, 74%). Respondents' ages ranged from 14 to 24years with a mean age of 18.8±2.9years, 57% were female, and 66% identified as White. Peer pressure and coping were commonly perceived reasons for diversion, and respondents believed that many youth misuse stimulants. Many were aware of health risks of misuse, but few mentioned potential legal consequences. Youth thought stimulants could be obtained from peers, people with a prescription, dealers, and family, and some mentioned access through unnecessary prescriptions.<br /><br /> The perspectives of a national sample of youth suggest that stimulant diversion continues to be a significant problem among American youth, with many noting that diverted stimulants are easy to obtain and are used to self-treat mental health issues. Standardized interventions at schools and in healthcare settings, as well as universal screening for diversion and mental health conditions, may combat this public health concern.<br /><br />The perspectives of a national sample of youth suggest that stimulant diversion continues to be a significant problem among American youth, with many noting that diverted stimulants are easy to obtain and are used to self-treat mental health issues. Standardized interventions at schools and in healthcare settings, as well as universal screening for diversion and mental health conditions, may combat this public health concern.