Combined expectancies of alcohol and e-cigarette use relate to higher alcohol use

Electronic cigarettes (e-cigs) were created to approximate the look, feel, and experience of using a cigarette. Since cigarette and alcohol use co-occur, we hypothesized that e-cig and alcohol use also co-occur, likely due to shared positive drug expectations. Using self-report data from two independent samples of community-dwelling alcohol using adults, the present study: (1) modified the Nicotine and Other Substance Interaction Expectancy Questionnaire (NOSIE) to assess expectancies of combined e-cig and alcohol use (i.e. the individuals perceived likelihood of using e-cigs and alcohol together; NOSIE-ER); and (2) examined the relationships among e-cig use, expectancies, and alcohol use across e-cig use status. In the first sample (N=692, mean age=32.6, SD=9.74, 50.7% female, 82.2% Caucasian), exploratory factor analysis suggested the presence of two factors: (1) alcohol use leads to e-cig use (Scale 1; α=0.85); and (2) e-cig use leads to alcohol use (Scale 2; α=0.91). In the second sample (N=714, mean age=34.1, SD=10.89, 47.8% female, 75.6% Caucasian), confirmatory factor analysis supported this factor structure (χ(2)=47.00, p<0.01, df=19; RMSEA=0.08, 90% CI=0.05-0.11; TLI=0.99; CFI=0.99). Compared to non e-cig users, e-cig users had significantly higher problematic alcohol use in both samples (b's=0.09 to 0.14, p's<.05). Expectancies of combined e-cig and alcohol use were significantly related to problematic alcohol use (b's=-0.92 to 0.26, p's<.05). In sum, e-cig use is related to alcohol use and expectancies of combined e-cig and alcohol use; consequently, reshaping of beliefs about needs or desires to co-use could be a prime point of intervention

UPPS-P Model Impulsivity and Marijuana Use Behaviors in Adolescents: A Meta-Analysis

Background Impulsivity is often included as a risk factor in models of adolescent marijuana use behaviors; however, the magnitude of the association between impulsivity and marijuana use behaviors is variable across studies. The present study reviewed existent literature to 1) quantify the relationship between separable impulsivity-related traits and both marijuana use and negative marijuana consequences and 2) quantify the size of the effect of gender on these relationships. Method Thirty-eight studies (41 independent samples) were meta-analyzed using a random effects model to examine the relationship between impulsivity traits and marijuana use behaviors. Results Marijuana use was significantly related to all impulsivity-related traits except lack of perseverance (r’s ranging from 0.13–0.23, p’s < 0.01). Negative marijuana consequences were only significantly related to sensation seeking, lack of planning, and positive urgency (r’s ranging from 0.37–0.39, p’s < 0.01). Effects were small for marijuana use, but medium for negative marijuana consequences. Gender was not a significant moderator of any relationships. Conclusions Impulsivity-related traits had more robust relationships with negative marijuana consequences than marijuana use, suggesting impulsivity-related traits are important in differentiating adolescents most likely to experience negative consequences from marijuana use. Few relationships examined gender and many of the impulsivity-related traits, other than sensation seeking. Data and trends suggest a more multi-dimensional approach to marijuana use and consequences is warranted

Interview; kunst of kliederen; “De ene graffiti is de andere niet”

De aanpak van graffiti staat bij veel gemeenten hoog op de agenda. Het tegengaan van overlast en verloedering is hierbij meestal de belangrijkste reden. Maar om een aanpak echt te laten slagen, moet er volgens onderzoekster Gabry Vanderveen eerst goed worden nagegaan welke vormen van graffiti voor overlast zorgen en op welke plekken de schilderingen bijdragen aan de verloedering.Overig prod. v. wetensch. act.Faculteit der Rechtsgeleerdhei

Crystalline cataract caused by a heterozygous missense mutation in γD-crystallin (CRYGD)

Purpose: To describe phenotypic characteristics of two pedigrees manifesting early onset crystalline cataract with mutations in the γD-crystallin gene (CRYGD). Methods: A detailed medical history was obtained from two Caucasian pedigrees manifesting autosomal dominant congenital cataracts. Genomic DNA was extracted from saliva (DNA Genotek). Single Nucleotide Polymorphism (SNP) based genome analysis of the larger pedigree revealed linkage to an 8.2 MB region on chromosome 2q33-q35 which encompassed the crystallin-gamma gene cluster (CRYG). Exons and flanking introns of CRYGA, CRYGB, CRYGC and CRYGD were amplified and sequenced to identify disease-causing mutations. Results: A morphologically unique cataract with extensive refractile “crystals ” scattered throughout the nucleus and perinuclear cortex was found in the probands from both pedigrees. A heterozygous C→A mutation was identified at position 109 of the coding sequence (R36S of the processed protein) in exon 2 of CRYGD and this missense mutation was found to cosegregate with the disease in the larger family; this mutation was then identified in affected individuals of pedigree 2 as well. Conclusions: The heterozygous 109C→A CRYGD missense mutation is associated with a distinct crystalline cataract in two US Caucasian pedigrees. This confirms crystalline cataract formation with this mutation, as previously reported in sporadic childhood case from the Czech Republic and in members of a Chinese family

Beliefs About the Direct Comparison of E-Cigarettes and Cigarettes

Background: Recent data suggests that positive beliefs about electronic cigarettes (e-cigs) use can lead to later e-cig use. Considering that many advertisements claim that e-cigs are superior to cigarettes, individuals' likelihood to view e-cigs more favorably than cigarettes can also influence subsequent e-cig use; however, no studies have directly assessed such a comparison. Objectives: The present study created and validated the Comparing E-Cigarettes and Cigarettes questionnaire (CEAC), which asks individuals to directly compare e-cigs and cigarettes on a number of dimensions, in two independent samples. Methods: In sample 1 (451 undergraduates; mean age = 20.35, SD = 5.44, 72.4% female, 73.4% Caucasian) we explored the factor structure of the CEAC and in sample 2 (699 community adults collected via Amazon's Mechanical Turk; mean age = 34.04, SD = 10.9, 47.7% female, 83.3% Caucasian) we replicated the factor structure. Results: Exploratory factor analysis suggested a three-factor structure: General Benefits (α = 0.80), General Effects (α = 0.86), and Health Benefits (α = 0.88), which was replicated via confirmatory factor analysis, χ2 = 4.36; RMSEA = 0.07, 90% CI = 0.06–0.08; TLI = 0.99; CFI = 0.99, and was relatively invariant across product use and gender. Individuals reported viewing e-cigs as safer and more beneficial than cigarettes and these beliefs were higher in e-cig users. Conclusions: Future work should establish how these comparative beliefs are influenced by e-cig use and/or influence subsequent transition to and increases in e-cig use. Although e-cigs are likely less harmful than cigarettes, and thus these comparative beliefs represent that state of nature, e-cigs are not completely without risk

Transitioning from cigarettes to electronic cigarettes increases alcohol consumption

Objective Electronic cigarettes (e-cigs) are a nicotine delivery device that have recently been linked to alcohol use. Many individuals that smoke cigarettes transition to e-cigs as an alternative to cigarette use, despite potential negative health effects of e-cigs. No research to date has examined how former smokers that have transitioned to e-cigs differ from former smokers that do not use e-cigs, particularly in relation to alcohol use. Further, no research has examined how former smokers that use e-cigs regularly or socially may differ in alcohol consumption. Method Using an online community dwelling sample (Former smokers N=198, mean age=34.70, SD=11.45, 56.1% female, 78.3% Caucasian, 37.9% e-cig users), the present study assessed smoking status and alcohol use, with the latter assessed using a Timeline Followback calendar and the Alcohol Use Disorder Identification Test (AUDIT). Results In all former smokers, total drinks (b=4.01, p=0.02) and average drinks per drinking day (b=0.61, p=.01) were both related to e-cig use status, with e-cig users reporting higher alcohol consumption. Among e-cig using former smokers, social users, but not regular users, showed positive relationships with AUDIT scores, b=1.90, p=.02, total drinks, b=9.12, p<.001, average drinks, b=0.98, p=.006, and hazardous drinking status, OR=3.21, p=.01. Conclusions Findings suggest that: (1) former smokers who use e-cigs may have a potential for higher alcohol use; and (2) those who use e-cigs socially may be at heightened risk for hazardous patterns of alcohol consumption. This should be taken into consideration by healthcare providers

Early Nutrition and Weight Gain in Preterm Newborns and the Risk of Retinopathy of Prematurity

Objective: To identify nutritional and weight gain limitations associated with retinopathy of prematurity (ROP) severity among very preterm newborns. Patients and Methods 1180 infants <28 weeks GA at birth with ROP examination results were grouped and analyzed by quartile of weekly total calorie, carbohydrate, protein, and lipid intake, as well as growth velocity between postnatal days 7 and 28 (adjusted for GA and birth weight Z-score). ROP was categorized by development of no, mild (<prethreshold), type 2, or type 1 ROP, as well as markers of ROP severity including stage 3 ROP, zone 1 disease, and plus disease. Associations between nutritional intake and ROP severity were compared. Results: Greater risk for Type 1 ROP (risk/95% confidence intervals) was found for infants with lowest quartile receipt of lipids (2.1/1.1, 3.8), total calories (2.2/1.4, 3.6), and carbohydrates (1.7/1.1, 2.9). Development of zone 1 ROP was associated with lipid or total calorie intake in the lowest quartile, and development of stage 3 ROP was associated with lowest quartile of total calorie intake. Growth velocity in the lowest quartile was associated with increased risk of any ROP, including type 1 ROP. Conclusion: The risk of developing severe ROP in extremely premature infants might be reduced by improving nutritional support, specifically targeting lipids and total calories, and perhaps by improving weight gain

Effectiveness and Preclinical Safety Profile of Doxycycline to Be Used “Off-Label” to Induce Therapeutic Transgene Expression in a Phase I Clinical Trial for Glioma

Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer in adults; it carries a dismal prognosis despite improvements in standard of care. We developed a combined gene therapy strategy using (1) herpes simplex type 1-thymidine kinase in conjunction with the cytotoxic prodrug ganciclovir to kill actively proliferating tumor cells and (2) doxycycline (DOX)-inducible Fms-like tyrosine kinase 3 ligand (Flt3L), an immune stimulatory molecule that induces anti-GBM immunity. As a prelude to a phase I clinical trial, we examined the efficacy and safety of this approach (Muhammad et al., 2010, 2012). In the present article, we investigated the efficacy and safety of the ?off-label? use of the antibiotic DOX to turn on the high-capacity adenoviral vector (HC-Ad) encoding therapeutic Flt3L expression. DOX-inducible Flt3L expression in male Lewis rats was assessed using DOX doses of 30.8?mg/kg/day (low-DOX) or 46.2?mg/kg/day (high-DOX), which are allometrically equivalent (Voisin et al., 1990) to the human doses that are recommended for the treatment of infections: 200 or 300?mg/day. Naïve rats were intracranially injected with 1?109 viral particles of HC-Ad-TetOn-Flt3L, and expression of the therapeutic transgene, that is, Flt3L, was assessed using immunohistochemistry in brain sections after 2 weeks of DOX administration via oral gavage. The results show robust expression of Flt3L in the rat brain parenchyma in areas near the injection site in both the low-DOX and the high-DOX groups, suggesting that Flt3L will be expressed in human glioma patients at a DOX dose of 200 or 300?mg/day. These doses have been approved by the U.S. Food and Drug Administration to treat infections in humans and would thus be considered safe for an off-label use to treat GBM patients undergoing HC-Ad-mediated gene therapy in a phase I clinical trial.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140104/1/humc.2013.139.pd

Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn “On” Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model

Glioblastoma multiforme (GBM) is the most commonly occurring primary brain cancer in adults, in whom its highly infiltrative cells prevent total surgical resection, often leading to tumor recurrence and patient death. Our group has discovered a gene therapy approach for GBM that utilizes high-capacity ?gutless? adenoviral vectors encoding regulatable therapeutic transgenes. The herpes simplex type 1-thymidine kinase (TK) actively kills dividing tumor cells in the brain when in the presence of the prodrug, ganciclovir (GCV), whereas the FMS-like tyrosine kinase 3 ligand (Flt3L) is an immune-stimulatory molecule under tight regulation by a tetracycline-inducible ?Tet-On? activation system that induces anti-GBM immunity. As a prelude to a phase I clinical trial, we evaluated the safety and efficacy of Food and Drug Administration (FDA)?approved doses of the tetracycline doxycycline (DOX) allometrically scaled for rats. DOX initiates the expression of Flt3L, which has been shown to recruit dendritic cells to the brain tumor microenvironment?an integral first step in the development of antitumor immunity. The data revealed a highly safe profile surrounding these human-equivalent doses of DOX under an identical therapeutic window as proposed in the clinical trial. This was confirmed through a neuropathological analysis, liver and kidney histopathology, detection of neutralizing antibodies, and systemic toxicities in the blood. Interestingly, we observed a significant survival advantage in rats with GBM receiving the 300?mg/day equivalent dosage of DOX versus the 200?mg/day equivalent. Additionally, rats rejected ?recurrent? brain tumor threats implanted 90 days after their primary brain tumors. We also show that DOX detection within the plasma can be an indicator of optimal dosing of DOX to attain therapeutic levels. This work has significant clinical relevance for an ongoing phase I clinical trial in humans with primary GBM and for other therapeutic approaches using Tet-On transactivation system in humans.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140103/1/hgtb.2015.168.pd