Prevalence of and associated factors for adult attention deficit hyperactivity disorder in young Swiss men.

OBJECTIVE: The present study aimed to measure the prevalence of adult attention deficit hyperactivity disorder (ADHD) in a large, representative sample of young Swiss men and to assess factors associated with this disorder. METHODS: Our sample consisted of 5656 Swiss men (mean age 20 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed with the World Health Organization (WHO) adult ADHD Self Report Screener (ASRS). Logistic regression analyses were conducted to assess the association between ADHD and several socio-demographic, clinical and familial factors. RESULTS: The prevalence of ADHD was 4.0%, being higher in older and French-speaking conscripts. A higher prevalence also was identified among men whose mothers had completed primary or high school/university and those with a family history of alcohol or psychiatric problems. Additionally, adults with ADHD demonstrated impairment in their professional life, as well as considerable mental health impairment. CONCLUSION: Our results demonstrate that ADHD is common among young Swiss men. The impairments in function and mental health we observed highlight the need for further support and interventions to reduce burden in affected individuals. Interventions that incorporate the whole family also seem crucial.

Health literacy and substance use in young Swiss men.

OBJECTIVES: The purpose of the present study was to describe health literacy and its association with substance use among young men. METHODS: The present study was part of the Cohort Study on Substance Use Risk Factors that included 11,930 Swiss males participating in initial screening from August 2010 to July 2011. Self-completed questionnaires covered use of three substances and three components of health literacy. RESULTS: Roughly 22 % reported having searched the Internet for health information and 16 % for information on substances over the past 12 months. At-risk and not at-risk users of alcohol (adjusted odds ratio (AOR) = 2.50 and 1.46), tobacco (AOR = 2.51 and 1.79) and cannabis (AOR = 4.86 and 3.53) searched for information about substances significantly more often via the Internet than abstainers. Furthermore, at-risk users reported better knowledge of risks associated with substance use and a marginally better ability to understand health information than abstainers. CONCLUSIONS: Substance users appear to be more informed and knowledgeable about the risks of substance use than non-users. Consequently, interventions that focus only on information provision may be of limited benefit for preventing substance use.

Health-risk behaviors and quality of life among young men.

PURPOSE: To examine the associations between substance use and other health-risk behaviors and quality of life (QOL) among young men. METHODS: The analytical sample consisted of 5,306 young Swiss men who participated in the Cohort Study on Substance Use Risk Factors. Associations between seven distinct self-reported health-risk behaviors (risky single-occasion drinking; volume drinking; cigarette smoking; cannabis use; use of any other illicit drugs; sexual intercourse without a condom; low physical activity) were assessed via chi-square analysis. Logistic regression analyses were conducted to study the associations between each particular health-risk behavior and either physical or mental QOL (assessed with the SF-12v2) while adjusting for socio-demographic variables and the presence of all other health-risk behaviors. RESULTS: Most health-risk behaviors co-occurred. However, low physical activity was not or negatively related to other health-risk behaviors. Almost all health-risk behaviors were associated with a greater likelihood of compromised QOL. However, sexual intercourse without a condom (not associated with both physical and mental QOL) and frequent risky single-occasion drinking (not related to mental QOL after adjusting for the presence of other health-risk behaviors; positively associated with physical QOL) differed from this pattern. CONCLUSIONS: Health-risk behaviors are mostly associated with compromised QOL. However, sexual intercourse without a condom and frequent risky single-occasion drinking differ from this pattern and are therefore possibly particularly difficult to change relative to other health-risk behaviors.

Beverage preferences and associated drinking patterns, consequences and other substance use behaviours.

BACKGROUND: Studies about beverage preferences in a country in which wine drinking is relatively widespread (like Switzerland) are scarce. Therefore, the main aims of the present study were to examine the associations between beverage preferences and drinking patterns, alcohol-related consequences and the use of other substances among Swiss young men. METHODS: The analytical sample consisted of 5399 Swiss men who participated in the Cohort Study on Substance Use Risk Factors (C-SURF) and had been drinking alcohol over the preceding 12 months. Logistic regression analyses were conducted to study the associations between preference for a particular beverage and (i) drinking patterns, (ii) negative alcohol-related consequences and (iii) the (at-risk) use of cigarettes, cannabis and other illicit drugs. RESULTS: Preference for beer was associated with risky drinking patterns and, comparable with a preference for strong alcohol, with the use of illicit substances (cannabis and other illicit drugs). In contrast, a preference for wine was associated with low-risk alcohol consumption and a reduced likelihood of experiencing at least four negative alcohol-related consequences or of daily cigarette smoking. Furthermore, the likelihood of negative outcomes (alcohol-related consequences; use of other substances) increased among people with risky drinking behaviours, independent of beverage preference. CONCLUSIONS: In our survey, beer preference was associated with risky drinking patterns and illicit drug use. Alcohol polices to prevent large quantities of alcohol consumption, especially of cheaper spirits like beer, should be considered to reduce total alcohol consumption and the negative consequences associated with these beverage types.

Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.

Peroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes. However, PPARdelta's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARdelta decreases intestinal adenoma growth in Apc(Min/+) mice and inhibits tumor-promoting effects of a PPARdelta agonist GW501516. More importantly, we found that activation of PPARdelta up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARdelta agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer.

Body mass index and health-related quality of life among young Swiss men.

BACKGROUND: Studies about the association between body mass index (BMI) and health-related quality of life (HRQOL) are often limited, because they 1) did not include a broad range of health-risk behaviors as covariates; 2) relied on clinical samples, which might lead to biased results; and 3) did not incorporate underweight individuals. Hence, this study aims to examine associations between BMI (from being underweight through obesity) and HRQOL in a population-based sample, while considering multiple health-risk behaviors (low physical activity, risky alcohol consumption, daily cigarette smoking, frequent cannabis use) as well as socio-demographic characteristics. METHODS: A total of 5 387 young Swiss men (mean age = 19.99; standard deviation = 1.24) of a cross-sectional population-based study were included. BMI was calculated (kg/m²) based on self-reported height and weight and divided into 'underweight' (<18.5), 'normal weight' (18.5-24.9), 'overweight' (25.0-29.9) and 'obese' (≥30.0). Mental and physical HRQOL was assessed via the SF-12v2. Self-reported information on physical activity, substance use (alcohol, cigarettes, and cannabis) and socio-demographic characteristics also was collected. Logistic regression analyses were conducted to study the associations between BMI categories and below average mental or physical HRQOL. Substance use variables and socio-demographic variables were used as covariates. RESULTS: Altogether, 76.3% were normal weight, whereas 3.3% were underweight, 16.5% overweight and 3.9% obese. Being overweight or obese was associated with reduced physical HRQOL (adjusted OR [95% CI] = 1.58 [1.18-2.13] and 2.45 [1.57-3.83], respectively), whereas being underweight predicted reduced mental HRQOL (adjusted OR [95% CI] = 1.49 [1.08-2.05]). Surprisingly, obesity decreased the likelihood of experiencing below average mental HRQOL (adjusted OR [95% CI] = 0.66 [0.46-0.94]). Besides BMI, expressed as a categorical variable, all health-risk behaviors and socio-demographic variables were associated with reduced physical and/or mental HRQOL. CONCLUSIONS: Deviations from normal weight are, even after controlling for important health-risk behaviors and socio-demographic characteristics, associated with compromised physical or mental HRQOL among young men. Hence, preventive programs should aim to preserve or re-establish normal weight. The self-appraised positive mental well-being of obese men noted here, which possibly reflects a response shift, might complicate such efforts.

Different internalization properties of the alpha1a- and alpha1b-adrenergic receptor subtypes: the potential role of receptor interaction with beta-arrestins and AP50.

The internalization properties of the alpha1a- and alpha1b-adrenergic receptors (ARs) subtypes transiently expressed in human embryonic kidney (HEK) 293 cells were compared using biotinylation experiments and confocal microscopy. Whereas the alpha1b-AR displayed robust agonist-induced endocytosis, the alpha1a-AR did not. Constitutive internalization of the alpha1a-AR was negligible, whereas the alpha1b-AR displayed significant constitutive internalization and recycling. We investigated the interaction of the alpha1-AR subtypes with beta-arrestins 1 and 2 as well as with the AP50 subunit of the clathrin adaptor complex AP2. The results from both coimmunoprecipitation experiments and beta-arrestin translocation assays indicated that the agonistinduced interaction of the alpha1a-AR with beta-arrestins was much weaker than that of the alpha1b-AR. In addition, the alpha1a-AR did not bind AP50. The alpha1b-AR mutant M8, lacking the main phosphorylation sites in the receptor C tail, was unable to undergo endocytosis and was profoundly impaired in binding beta-arrestins despite its binding to AP50. In contrast, the alpha1b-AR mutant DeltaR8, lacking AP50 binding, bound beta-arrestins efficiently, and displayed delayed endocytosis. RNA interference showed that beta-arrestin 2 plays a prominent role in alpha1b-AR endocytosis. The findings of this study demonstrate differences in internalization between the alpha1a- and alpha1b-AR and provide evidence that the lack of significant endocytosis of the alpha1a-AR is linked to its poor interaction with beta-arrestins as well as with AP50. We also provide evidence that the integrity of the phosphorylation sites in the C tail of the alpha1b-AR is important for receptor/beta-arrestin interaction and that this interaction is the main event triggering receptor internalization.

Loss of Memo, a novel FGFR regulator, results in reduced lifespan.

Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)2D production and normal calcium homeostasis.

DSM-IV and DSM-5 alcohol use disorder among young Swiss men.

BACKGROUND AND AIMS: Previous studies suggest that the new DSM-5 criteria for alcohol use disorder (AUD) will increase the apparent prevalence of AUD. This study estimates the 12-month prevalence of AUD using both DSM-IV and DSM-5 criteria and compares the characteristics of men in a high risk sample who meet both, only one and neither sets of diagnostic criteria. DESIGN, SETTING AND PARTICIPANTS: 5943 Swiss men aged 18-25 years who participated in the Cohort Study on Substance Use Risk Factors (C-SURF), a population-based cohort study recruited from three of the six military recruitment centres in Switzerland (response rate = 79.2%). MEASUREMENTS: DSM-IV and DSM-5 criteria, alcohol use patterns, and other substance use were assessed. FINDINGS: Approximately 31.7% (30.5-32.8) of individuals met DSM-5 AUD criteria [21.2% mild (20.1-22.2); 10.5% moderate/severe (9.7-11.3)], which was less than the total rate when DSM-IV criteria for alcohol abuse (AA) and alcohol dependence (AD) were combined [36.8% overall (35.5-37.9); 26.6% AA (25.4-27.7); 10.2% AD (9.4-10.9)]. Of 2479 respondents meeting criteria for either diagnoses, 1585 (63.9%) met criteria for both. For those meeting DSM-IV criteria only (n = 598, 24.1%), hazardous use was most prevalent, whereas the criteria larger/longer use than intended and tolerance to alcohol were most prevalent for respondents meeting DSM-5 criteria only (n = 296, 11.9%). Two in five DSM-IV alcohol abuse cases and one-third of DSM-5 mild AUD individuals fulfilled the diagnostic criteria due to the hazardous use criterion. The addition of the craving and excluding of legal criterion, respectively, did not affect estimated AUD prevalence. CONCLUSIONS: In a high-risk sample of young Swiss males, prevalence of alcohol use disorder as diagnosed by DSM-5 was slightly lower than prevalence of DSM-IV diagnosis of dependence plus abuse; 63.9% of those who met either criterion met criteria for both.

Asymmetric cancer cell division regulated by AKT.

Human tumors often contain slowly proliferating cancer cells that resist treatment, but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating "G0-like" progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small-molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur.

Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.

Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.

Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor delta signaling is critical to pregnancy success.

Successful pregnancy depends on well coordinated developmental events involving both maternal and embryonic components. Although a host of signaling pathways participate in implantation, decidualization, and placentation, whether there is a common molecular link that coordinates these processes remains unknown. By exploiting genetic, molecular, pharmacological, and physiological approaches, we show here that the nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) delta plays a central role at various stages of pregnancy, whereas maternal PPARdelta is critical to implantation and decidualization, and embryonic PPARdelta is vital for placentation. Using trophoblast stem cells, we further elucidate that a reciprocal relationship between PPARdelta-AKT and leukemia inhibitory factor-STAT3 signaling pathways serves as a cell lineage sensor to direct trophoblast cell fates during placentation. This novel finding of stage-specific integration of maternal and embryonic PPARdelta signaling provides evidence that PPARdelta is a molecular link that coordinates implantation, decidualization, and placentation crucial to pregnancy success. This study is clinically relevant because deferral of on time implantation leads to spontaneous pregnancy loss, and defective trophoblast invasion is one cause of preeclampsia in humans.

The Swiss cohort study on substance use risk factors : findings of two waves

Aim: To summarize published findings in peer-reviewed journals of the first two waves of the Swiss Cohort Study on Substance Use Risk Factors (C-SURF), a longitudinal study assessing risk and protective factors of 5,987 young men during the phase of emerging adulthood (20 years at baseline, followed-up 15 months later). Methods: Included were 33 studies published until November 2014 focusing on substance use. Results: Substance use in early adulthood is a prevalent and stable behavior. The 12-month prevalence of nonmedical use of prescription drugs (10.6%) lies between that of cannabis (36.4%) and other illicit drugs such as ecstasy (3.7%) and cocaine (3.2%). Although peer pressure in the form of misconduct is associated with increased substance use, other aspects such as peer involvement in social activities may have beneficial effects. Regular sport activities are associated with reduced substance use, with the exception of alcohol use. Young men are susceptible to structural conditions such as the price of alcohol beverages or the density of on-premise alcohol outlets. Particularly alcohol use in public settings such as bars, discos or in parks (compared with private settings such as the home) is associated with alcohol-related harm, including injuries or violence. Being a single parent versus nuclear family has no effect on alcohol use, but active parenting does. Besides parenting, religiousness is an important protective factor for both legal and illegal substance use. Merely informing young men about the risks of substance use may not be an effective preventive measure. At-risk users of licit and illicit substances are more health literate, e. g., for example, they seek out more information on the internet than non-at-risk-users or abstainers. Discussion: There are a number of risk and protective substance use factors, but their associations with substance use do not necessarily agree with those found outside Europe. In the United States, for example, heavy alcohol use in this age group commonly takes place in private settings, whereas in Switzerland it more often takes place in public settings. Other behaviors, such as the nonmedical use of prescription drugs, appear to be similar to those found overseas, which may show the need for targeted preventive actions. C-SURF findings point to the necessity of establishing European studies to identify factors for designing specific preventive actions.