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DNA damage is a common feature of human spermatozoa associated with an impaired capacity to fertilize the oocyte and an increased mutational load in the offspring. However, the etiology of this damage remains poorly defined. In this study we demonstrate that a major pathway for the induction of DNA damage in mammalian spermatozoa is triggered by exposure to exogenous cell free DNA (cfDNA). Exposure of human and mouse spermatozoa to cfDNA (calf thymus, mouse liver and salmon testes) in vitro induced a dose-dependent increase in sperm DNA damage that could be effectively suppressed by the concomitant presence of DNase. The induction of such damage was not accompanied by any concomitant change in sperm motility or vitality and was not directly associated with the induction of oxidative stress. In vivo the injection of exogenous DNA again precipitated an increase in sperm DNA fragmentation that could be reversed by the prior administration of DNase. Similarly, the induction of a transient unilateral testicular ischemia induced an increase in DNA fragmentation that was evident within 24 h and sustained for at least 14 days via mechanisms that could be completely suppressed by the prior administration of DNase. We conclude that exogenous cfDNA activates a defensive response in human spermatozoa associated with the nuclease-mediated induction of DNA fragmentation, possibly involving the participation of TLR9 and CD4. These novel insights have significant implications for our understanding of DNA fragmentation in the male germ line and open up new pathways for the remediation of this condition. More and more U.S. states are legalizing marijuana use for both recreational and medical purposes. This study estimated the prevalence of current marijuana use and identified its individual-level predictors among adult cancer survivors (CS) living in 15 U.S. states and territories. U.S. nationally representative, cross-sectional data from the 2018 Behavioral Risk Factor Surveillance System Survey (BRFSS) Marijuana Use module were used. A total of 9325 CS was included. Analyses were weighted to account for BRFSS's complex survey design with results generalizable to 4.02 million CS. The outcome was current (past 30-day) marijuana use. Weighted prevalence estimates were computed. Multivariable logistic regression examined individual-level demographic, socio-economic, clinical, and behavioral predictors associated with marijuana use. Weighted analysis indicated that 9.2% reported current marijuana use, 50.5% of which used it for medical reasons with smoking being the main method of administration, 71.3%. Among racial/ethnic groups, non-Hispanic blacks had the highest prevalence of marijuana use (18.6%). The prevalence of current marijuana use decreased with age (P<.001). CS were more likely to use marijuana if they were male, non-Hispanic black (versus non-Hispanic whites), not married, uninsured, current and former tobacco smoker, binge drinker, ever having depressive disorder, and those who had fair/poor health. Marijuana use is prevalent among CS and certain subgroups are at higher risk for marijuana use. With the proliferation of marijuana legalization, identifying high-risk CS for marijuana use and informing them about its risks and safety is critical. Marijuana use is prevalent among CS and certain subgroups are at higher risk for marijuana use. With the proliferation of marijuana legalization, identifying high-risk CS for marijuana use and informing them about its risks and safety is critical.As electronic cigarette (e-cigarette) use continues to rise, it is important to identify individual characteristics that may influence e-cigarette use behavior and potential group-level moderators of effects, such as sex. Initial evidence has suggested that worry, defined as excessive, unrealistic thoughts focused on the possibility of future negative events, may contribute to e-cigarette use behavior. Yet, how these established relations differ across groups, such as male and female e-cigarette users, has not been explored. The present study evaluated the effect of worry on perceived barriers for quitting e-cigarettes, perceptions of benefits for e-cigarette use, and perceived negative consequences of e-cigarette use across sex. The sample included 584 current e-cigarette users (52.2% female, Mage = 35.15 years, SD = 10.27). Analyses indicated a significant interaction between sex and worry on each criterion variable (perceived benefits b = 0.02, SE = 0.01, t = -2.73, p = .01; perceived barriers for quitting e-cigarettes b = -0.45, SE = 0.08, t = -5.70, p ≤ 0.001; negative consequences to use b = -0.033, SE = 0.01, t = -4.50, p less then .001), such that worry was more strongly related to each outcome among males than females. These findings suggest that sex plays a role in e-cigarette use behaviors and that males may constitute a group that is especially vulnerable to the effects of worry on both positive and negative e-cigarette use perceptions and perceived barriers for quitting e-cigarettes. To test the preliminary impact and participant experience/satisfaction of Invite Only VR A Vaping Prevention Game (Invite Only VR), an electronic cigarette (e-cigarette) prevention game prototype using virtual reality (VR) hardware. Forty-seven adolescents (38 boys; mean age=14.23years, SD=0.914) were enrolled to test the preliminary impact of Invite Only VR on knowledge, perceived likelihood of using e-cigarettes, perceptions of harm, attitudes, social norms, and self-efficacy to refuse e-cigarettes using a pre/post design. Experience/satisfaction was measured following gameplay. Paired-samples t-tests and associated effect sizes were used to assess changes in the dependent variables. Descriptive statistics were used to report on gameplay experience/satisfaction. From pre- to post-gameplay, players significantly increased in knowledge (t(34)=-5.594, p<.001, Cohen's d=0.946) and perceptions of e-cigarette harm (t(34)=-3.370, p=.002, Cohen's d=0.530) and decreased their perceived likelihood of using e-cigarettes in the future (t(35)=2.140, p=.039, Cohen's d=1.274). No significant change was found for attitudes towards e-cigarettes, social norm perceptions, nor refusal self-efficacy. Participants reported that they enjoyed playing the game (M=3.00, SD=0.99) and that they would tell their friends to play (M=3.08, SD=0.91). Invite Only VR may help players develop knowledge and correct harm perceptions regarding e-cigarettes while reducing their perceived likelihood of using them in the future. Participant enjoyment also provides an initial indication that the intervention may be acceptable for use with adolescents. Invite Only VR may help players develop knowledge and correct harm perceptions regarding e-cigarettes while reducing their perceived likelihood of using them in the future. https://www.selleckchem.com/products/ag-120-Ivosidenib.html Participant enjoyment also provides an initial indication that the intervention may be acceptable for use with adolescents.
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