Understanding Rates of Marijuana Use and Consequences Among Adolescents in a Changing Legal Landscape.

Purpose of Review:There is not one answer to address whether marijuana use has increased, decreased, or stayed the same given changes in state legalization of medical and non-medical marijuana in the USA. Recent Findings:Evidence suggests some health benefits for medical marijuana; however, initiation of marijuana use is a risk factor for developing problem cannabis use. Though use rates have remained stable over recent years, about one in three 10th graders report marijuana use, most adolescents do not view the drug as harmful, and over 650,000 youth aged 12 to 17 struggle with cannabis use disorder. Summary:Although the health benefits of medical marijuana are becoming better understood, more research is needed. Intervention and prevention programs must better address effects of marijuana, acknowledging that while there may be some benefits medically, marijuana use can affect functioning during adolescence when the brain is still developing

A text message intervention for quitting cigarette smoking among young adults experiencing homelessness: study protocol for a pilot randomized controlled trial.

BackgroundCigarette smoking is much more prevalent among young people experiencing homelessness than in the general population of adolescents and young adults. Although many young homeless smokers are motivated to quit, there are no empirically-evaluated smoking cessation programs for this population. It is important that any such program address the factors known to be associated with quitting-related outcomes among homeless young people, to provide ongoing support in a way that accommodates the mobility of this population, and does not rely on scarce service provider resources for its delivery. The objective of this project is to develop and pilot test a text messaging-based intervention (TMI), as an adjunct to brief cessation counseling and provision of nicotine patches, to help homeless young people who want to quit smoking.Methods/designThis pilot study will utilize a cluster cross-over randomized controlled design with up to 80 current smokers who desire to quit and are recruited from three drop-in centers serving young people experiencing homelessness in the Los Angeles area. All participants will be provided with a minimum standard of care: a 30-min group-based smoking cessation counseling session and free nicotine replacement. Half of these smokers will then also receive the TMI, as an adjunct to this standard care, which will provide 6 weeks of ongoing support for quitting. This support includes continued and more intensive education regarding nicotine dependence, quitting smoking, and relapse; does not require additional agency resources; can be available "on demand" to users; and includes features to personalize the quitting experience. This study will investigate whether receiving the TMI adjunct to standard smoking cessation care results in greater reductions in cigarette smoking compared to standard care alone over a 3-month period.DiscussionThis study has the potential to address an important gap in the clinical research literature on cigarette smoking cessation and provide empirical support for using a TMI to provide ongoing assistance and support for quitting among young smokers experiencing homelessness. Trial registration ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585

A computer-assisted motivational social network intervention to reduce alcohol, drug and HIV risk behaviors among Housing First residents.

BackgroundIndividuals transitioning from homelessness to housing face challenges to reducing alcohol, drug and HIV risk behaviors. To aid in this transition, this study developed and will test a computer-assisted intervention that delivers personalized social network feedback by an intervention facilitator trained in motivational interviewing (MI). The intervention goal is to enhance motivation to reduce high risk alcohol and other drug (AOD) use and reduce HIV risk behaviors.Methods/designIn this Stage 1b pilot trial, 60 individuals that are transitioning from homelessness to housing will be randomly assigned to the intervention or control condition. The intervention condition consists of four biweekly social network sessions conducted using MI. AOD use and HIV risk behaviors will be monitored prior to and immediately following the intervention and compared to control participants' behaviors to explore whether the intervention was associated with any systematic changes in AOD use or HIV risk behaviors.DiscussionSocial network health interventions are an innovative approach for reducing future AOD use and HIV risk problems, but little is known about their feasibility, acceptability, and efficacy. The current study develops and pilot-tests a computer-assisted intervention that incorporates social network visualizations and MI techniques to reduce high risk AOD use and HIV behaviors among the formerly homeless. CLINICALTRIALS.Gov identifierNCT02140359

Risk evaluations and condom use decisions of homeless youth: a multi-level qualitative investigation.

BackgroundHomeless youth are at higher risk for sexually transmitted infections and unwanted pregnancy than non-homeless youth. However, little is known about how they evaluate risk within the context of their sexual relationships. It is important to understand homeless youths' condom use decisions in light of their sexual relationships because condom use decisions are influenced by relationship dynamics in addition to individual attitudes and event circumstances. It is also important to understand how relationship level factors, sexual event circumstances, and individual characteristics compare and intersect.MethodsTo explore these issues, we conducted semi-structured interviews with 37 homeless youth in Los Angeles County in 2011 concerning their recent sexual relationships and analyzed the data using systematic methods of team-based qualitative data analysis.ResultsWe identified themes of risk-related evaluations and decisions at the relationship/partner, event, and individual level. We also identified three different risk profiles that emerged from analyzing how different levels of risk intersected across individual respondents. The three profiles included 1) Risk Takers, who consistently engage in risk and have low concern about consequences of risk behavior, 2) Risk Avoiders, who consistently show high concern about protection and consistently avoid risk, and 3) Risk Reactors, those who are inconsistent in their concerns about risk and protection and mainly take risks in reaction to relationship and event circumstances.ConclusionsInterventions targeting homeless youth should reflect multiple levels of risk behavior and evaluation in order to address the diversity of risk profiles. Relationship/partner-, event-, and individual-level factors are all important but have different levels of importance for different homeless youth. Interventions should be tailored to address the most important factor contributing to homeless youth reproductive needs

Gateway to Curiosity: Medical Marijuana Ads and Intention and Use during Middle School

Abstract Over the past several years, medical marijuana has received increased attention in the media, and marijuana use has increased across the United States. Studies suggest that as marijuana has become more accessible and adults have become more tolerant regarding marijuana use, adolescents perceive marijuana as more beneficial and are more likely to use if they are living in an environment that is more tolerant of marijuana use. One factor that may influence adolescents' perceptions about marijuana and marijuana use is their exposure to advertising of this product. We surveyed 6 th -8 th grade youth in 2010 and 2011 in 16 middle schools in southern California (n= 8214; 50% male; 52% Hispanic; mean age = 13) and assessed exposure to advertising for medical marijuana, marijuana intentions and marijuana use. Cross-lagged regressions showed a reciprocal association of advertising exposure with marijuana use and intentions during middle school. Greater initial medical marijuana advertising exposure was significantly associated with a higher probability of marijuana use and stronger intentions to use one year later, and initial marijuana use and stronger intentions to use were associated with greater medical marijuana advertising exposure one year later. Prevention programs need to better explain medical marijuana to youth, providing information on the context for proper medical use of this drug and the potential harms from use during this developmental period. Furthermore, as this is a new frontier, it is important to consider regulating medical marijuana advertisements, as is currently done for alcohol and tobacco products. Keywords adolescents; medical marijuana; advertising; marijuana use Teen marijuana use is rising across the United States HHS Public Access Author Manuscript Author Manuscript Author Manuscript Author Manuscript risk youth found that most of these youth perceived marijuana use as "normal," with 90% voicing positive attitudes toward marijuana use In this study, we focus on advertising for medical marijuana. People who have a medical marijuana card typically have a doctor's recommendation to use marijuana, and are afforded some protection from arrest and criminal sanctions. Some studies have begun to assess how legalization of medical marijuana has affected attitudes toward marijuana. In a large study in Montana across several counties, Friese and Grube (2013) assessed 17,482 adolescents age 13-19 and examined the association between adolescent marijuana use and voter approval of medical marijuana and number of medical marijuana cards issued. They found that youth were more likely to report greater lifetime and past 30 day use of marijuana when they lived in counties with a higher percentage of voters approving legalization of medical marijuana; the number of medical marijuana cards was not related to marijuana use Exposure to medical marijuana advertising may be an important influence on adolescents' perceptions about marijuana and marijuana use. Many studies have shown, for example, that there is a strong association between alcohol advertising and subsequent drinking among youth Given the potential problems that marijuana use during adolescence can cause in later life, we need to better understand the factors that may affect intentions to use and initiation during this developmental period. We know of no prior research in this area; therefore, the current longitudinal study takes an important first look at the cross-lagged associations of advertising for medical marijuana on younger adolescents' intentions to use marijuana in the next six months and their actual marijuana use. We examined cross-lagged associations longitudinally because the reinforcing spirals model of media exposure and risk behavior has shown that exposure and behavior can mutually reinforce each other and potentially increase risk-taking behavior over time Method The sample comprised 6 th -8 th grade students initially recruited in 2008 in 16 middle schools across three school districts in southern California to evaluate the CHOICE substance use prevention program for middle school students (D 'Amico, et al., 2012). Schools were selected and matched to their nearest neighbor school based on the squared Euclidean distance measure, estimated using publicly available information on ethnic diversity, approximate size, and standardized test scores (D 'Amico, et al., 2012). Across all schools, 92% of parents returned a consent form at the baseline, and approximately 71% of parents gave permission for their child to participate in the original Author Manuscript Author Manuscript Author Manuscript Author Manuscript study. Ninety-four percent of consented students completed the baseline survey, which is higher or comparable to other school-based survey completion rates with this population We began to collect data on exposure to medical marijuana advertising at wave 4 because a proposition to legalize marijuana was being discussed in the California Senate in January 2010 and was added to the California ballot in November 2010 (California Proposition 19, also known as the Regulate, Control & Tax Cannabis Act). The mean age of the sample at this time was 13. Youth were ethnically and racially diverse (e.g., 52% Hispanic; 17% Asian) and rates of substance use across waves were comparable to national samples Surveys Responses were protected by a Certificate of Confidentiality from the National Institutes of Health; procedures were approved by the individual schools and the institution's internal review board. Covariates included age, gender, race/ethnicity, academic performance, and intervention status. Of note, there were no intervention effects on marijuana use, and initial intervention effects on alcohol use were no longer significant after wave 3 of the study (when we began collecting data on exposure to medical marijuana advertising); nonetheless, we controlled for CHOICE participation in the present analyses. Exposure to medical marijuana advertising: "In the past three months, how often have you seen advertisements for medical marijuana on billboards, in magazines, or somewhere else?" (response options ranged from 1=not at all to 7=every day). Advertising exposure was highly skewed and dichotomized as no exposure versus any exposure. Youth who were exposed reported seeing ads on average about once a month. Intention to smoke marijuana: "Do you think you will use any marijuana in the next six months?" (response options ranged from 1=definitely no to 4=definitely yes). Marijuana use: "During the past month, how many times did you use marijuana (pot, weed, grass, hash)?" (response options ranged from 1=0 days to 7=20 to 30 days). We dichotomized marijuana use into "any use" versus "no use" given that past month use rates were low, as expected for this age group, and models would not converge using the continuous measure. Results The analytic sample comprised 8,214 individuals who responded at waves 4 or 5. Maximum likelihood (ML) estimation was employed using Mplus 6.11 (Muthén & Muthén, 2011) with standard errors corrected for clustering at the school level. ML was used rather than the default WLSMV for several reasons. First, the assumptions that must be made when estimating models with missing data are more restrictive with WLSMV than with ML Twenty-two percent of adolescents at wave 4 and 30% at wave 5 reported seeing at least one advertisement for medical marijuana on billboards, in magazines, or somewhere else in the past three months. With regard to demographic and academic covariates, higher academic performance was associated with greater exposure to advertising (p < .01), being male (p = . 014), and Asian (relative to white; p < .01) were associated with being exposed to fewer advertisements. For marijuana use at wave 4, higher academic performance was associated with greater likelihood of use (p < .01) and being of Asian descent or other race was associated with lower likelihood of use (p < .01 and p = .03, respectively). For intentions to use, higher academic performance was associated with higher intentions (p < .01), and being of Asian descent (p < .01) was associated with lower intentions. For the cross-lagged regression models, at both waves, as expected, these younger adolescents reported fairly low levels of past month marijuana use (wave 4: 3.3%; wave 5: 4.8%) and low intentions to use in the next six months (wave 4: mean = 1.41, sd = 0.95; wave 5: mean = 1.48, sd = 0.98). Exposure to medical marijuana ads at wave 4 predicted stronger intentions to use (b = 0.73, SE=0.06, OR = 2.07, p < .001), and actual use (b = 0.79, SE = 0.25, OR = 2.20, p = .002) at wave 5. Thus, youth who reported seeing any ads for medical marijuana were twice as likely as youth who reported never seeing an ad to use marijuana and to report higher intentions to use marijuana one year later. Marijuana use at wave 4 (b = 1.07, SE = 0.10, OR = 2.92, p <.001) and intentions to use (b = 0.09, SE=0.03, OR = 1.09, p = 0.008) also predicted exposure to medical marijuana ads at wave 5. For example, youth who reported marijuana use were almost three times as likely to report seeing ads one year later

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Utilizing Targeted Gene Therapy with Nanoparticles Binding Alpha v Beta 3 for Imaging and Treating Choroidal Neovascularization

Purpose: The integrin αvβ3 is differentially expressed on neovascular endothelial cells. We investigated whether a novel intravenously injectable αvβ3 integrin-ligand coupled nanoparticle (NP) can target choroidal neovascular membranes (CNV) for imaging and targeted gene therapy. Methods: CNV lesions were induced in rats using laser photocoagulation. The utility of NP for in vivo imaging and gene delivery was evaluated by coupling the NP with a green fluorescing protein plasmid (NP-GFPg). Rhodamine labeling (Rd-NP) was used to localize NP in choroidal flatmounts. Rd-NP-GFPg particles were injected intravenously on weeks 1, 2, or 3. In the treatment arm, rats received NP containing a dominant negative Raf mutant gene (NP-ATPμ-Raf) on days 1, 3, and 5. The change in CNV size and leakage, and TUNEL positive cells were quantified. Results: GFP plasmid expression was seen in vivo up to 3 days after injection of Rd-NP-GFPg. Choroidal flatmounts confirmed the localization of the NP and the expression of GFP plasmid in the CNV. Treating the CNV with NP-ATPμ-Raf decreased the CNV size by 42% (P<0.001). OCT analysis revealed that the reduction of CNV size started on day 5 and reached statistical significance by day 7. Fluorescein angiography grading showed significantly less leakage in the treated CNV (P<0.001). There were significantly more apoptotic (TUNEL-positive) nuclei in the treated CNV. Conclusion: Systemic administration of αvβ3 targeted NP can be used to label the abnormal blood vessels of CNV for imaging. Targeted gene delivery with NP-ATPμ-Raf leads to a reduction in size and leakage of the CNV by induction of apoptosis in the CNV

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN