Marijuana and Alcohol Use and Attempted Smoking Cessation in Adolescent Boys and Girls

ABSTRACT. Background: This study sought to determine the relationship between the frequency of current marijuana and alcohol use and cigarette quit attempts in male and female adolescent smokers. Methods: Data from a cross-sectional survey of health behaviors in high-school-aged adolescents were analyzed. Current cigarette smokers (n = 804) who reported use of at least 1 cigarette in the past month were divided into those with and without a history of at least 1 quit attempt (a self-reported episode of trying to “stop smoking”). Logistic regression models were fit to describe the association between the frequency of marijuana/alcohol use and a history of cigarette quit attempts. Results: Among the total sample, higher-frequency marijuana use (more than 6 times in the past 30 days) and frequent binge drinking (more than 5 days of binge drinking in the past 30 days) decreased the odds of having a past cigarette quit attempt (higher-frequency marijuana: adjusted odds ratio [AOR] = 0.56, 95% confidence interval [CI] = 0.36–0.86; frequent binge drinking: AOR = 0.49, 95% CI = 0.29–0.83). A significant gender interaction was observed for the relationship between higher-frequency marijuana use and a history of cigarette quit attempts (P = .03), with decreased odds in boys (AOR = 0.41, 95% CI = 0.22–0.77) but not in girls (AOR = 0.71, 95% CI = 0.37–1.33). Conclusions: Adolescent smokers who report higher-frequency marijuana use or frequent binge drinking have a decreased likelihood of a history of a cigarette quit attempt. The gender-related association between higher-frequency marijuana use and a history of quit attempts suggests that boys with greater substance use may need particularly intensive support to initiate quit attempts.     

Synthesis,supramolecular organization and thermotropic phase behaviour of N-acyltris(hydroxymethyl)aminomethane

Herein, we reported the supramolecular organization of N-acyltris(hydroxymethyl)aminomethane (NATM) in the solid state as well as in aqueous solution. Single crystal X-ray diffraction revealed that NATM adopts a fully interdigitized structure. The thermodynamic parameters associated with thermotropic phase behaviour of NATM was determined by differential scanning calorimetry. The molecular packing and phase state of the NATM analyzed by laurdan and prodan fluorescence supports the formation of an interdigitized phase in aqueous solution. The potential application of the self-assembled NATM vesicles was demonstrated through entrapping model drug, Rhodamine B.

Self assembly of N-acyltris(hydroxymethyl)aminomethane into interdigitized vesicles.     

Aryl hydrocarbon receptor signaling,toxicity, and gene expression responses to mono‐methylchrysenes

Polycyclic aromatic hydrocarbons (PAHs) comprise a large family of toxic compounds that come from natural and anthropogenic sources. Chrysene is a PAH with multiple effects, but the toxic potentials of mono‐methylchrysenes are less characterized. A comparison of chrysene and six mono‐methylchrysenes was performed using assays for cytotoxicity, human aryl hydrocarbon receptor (AhR) reporter gene signaling, and AhR‐regulated target gene and protein expression. Sulforhodamine B and trypan blue dye binding assays revealed these chrysenes to be similar in their cytotoxic effects on HepG2 cells. A yeast‐based reporter assay detecting human AhR‐mediated gene expression identified 4‐methylchrysene as being six times more potent and 5‐methylchrysene about one‐third as potent as chrysene. Other methylchrysenes were more similar to chrysene in the ability to act as AhR ligands. The mono‐methylchrysenes all strongly induced CYP1A1 mRNA and protein and moderately induced CYP1B1 expression in HepG2 cells. Levels of CYP1A2 mRNA were induced at higher concentrations of the chrysenes, but protein expression was not significantly altered. The PCR‐based gene expression and immunoblotting analyses indicated induced expression differences across the chrysene members were similar to each other. Overall, the effects of methylated chrysenes were comparable to unsubstituted chrysene, suggesting members of this group may be considered approximately equivalent in their effects. © 2019 Wiley Periodicals, Inc.     

A double‐blind,placebo‐controlled phase II study of the efficacy and safety of 2,2‐dimethylbutyrate (HQK‐1001), an oral fetal globin inducer,in sickle cell disease

This placebo‐controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2‐dimethylbutyrate (HQK‐1001), a fetal globin gene‐inducing short‐chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12–55 years) and 37 subjects (49%) were treated previously with hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/β⁰ thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK‐1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9% (95% confidence interval (CI): 0.1–1.6%) with HQK‐1001 and 0.2% (95% CI: ?0.7–1.1%) with placebo. Absolute increases in Hb F greater than 3% were noted in 9 of 38 subjects (24%) administered HQK‐1001 and 1 of 38 subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK‐1001 and 1.7 with placebo. The most common adverse events in the HQK‐1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK‐1001 at this dose and schedule are not recommended in SCD. Intermittent HQK‐1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation. Am. J. Hematol. 89:709–713, 2014. © 2014 Wiley Periodicals, Inc.     

Large granular lymphocytic leukaemia after solid organ and haematopoietic stem cell transplantation

T-cell large granular lymphocytic leukaemia (T-LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T-LGLL seen at our institution over the last 10 years, we encountered 15 cases following solid organ or haematopoietic stem cell transplantation. Here, we studied the clinical characterization of these cases and compared them to de novo T-LGLL. This experience represented a clear picture of the intricate nature of the disease manifestation and the complexities of several immune mechanisms triggering the clonal expansion.