Person:

Knight, John

Background: TH2-dependent diseases vary in severity according to genotype, but relevant gene polymorphisms remain largely unknown. The integrin CD11a is a critical determinant of allergic responses, and allelic variants of this gene might influence allergic phenotypes.

Objective: We sought to determine major CD11a allelic variants in mice and human subjects and their importance to allergic disease expression.

Methods: We sequenced mouse CD11a alleles from C57BL/6 and BALB/c strains to identify major polymorphisms; human CD11a single nucleotide polymorphisms were compared with allergic disease phenotypes as part of the international HapMap project. Mice on a BALB/c or C57BL/6 background and congenic for the other strain's CD11a allele were created to determine the importance of mouse CD11a polymorphisms in vivo and in vitro.

Results: Compared with the C57BL/6 allele, the BALB/c CD11a allele contained a nonsynonymous change from asparagine to aspartic acid within the metal ion binding domain. In general, the BALB/c CD11a allele enhanced and the C57BL/6 CD11a allele suppressed TH2 cell–dependent disease caused by the parasite Leishmania major and allergic lung disease caused by the fungus Aspergillus niger. Relative to the C57BL/6 CD11a allele, the BALB/c CD11a allele conferred both greater T-cell adhesion to CD54 in vitro and enhanced TH2 cell homing to lungs in vivo. We further identified a human CD11a polymorphism that significantly associated with atopic disease and relevant allergic indices.

Conclusions: Polymorphisms in CD11a critically influence TH2 cell homing and diverse TH2-dependent immunopathologic states in mice and potentially influence the expression of human allergic disease.

Alcohol is strongly linked to the leading causes of adolescent and adult mortality and health problems, making medical settings such as primary care and emergency departments important venues for addressing alcohol use. Extensive research evidence supports the effectiveness of alcohol screening and brief interventions (SBIs) in medical settings, but this valuable strategy remains underused, with medical staff citing lack of time and training as major implementation barriers. Technology-based tools may offer a way to improve efficiency and quality of SBI delivery in such settings. This review describes the latest research examining the feasibility and efficacy of computer- or other technology-based alcohol SBI tools in medical settings, as they relate to the following three patient populations: adults (18 years or older); pregnant women; and adolescents (17 years or younger). The small but growing evidence base generally shows strong feasibility and acceptability of technology-based SBI in medical settings. However, evidence for effectiveness in changing alcohol use is limited in this young field.

Background: Heavy alcohol use among U.S. college students is a major contributor to young adult morbidity and mortality. The aim of this study was to examine whether college alcohol policy enforcement levels predict changes in student drinking and related behaviors in a state system of public colleges and universities, following a system-wide change to a stricter policy. Methods: Students and administrators at 11 Massachusetts public colleges/universities completed surveys in 1999 (N of students = 1252), one year after the policy change, and again in 2001 (N = 1074). We calculated policy enforcement scores for each school based on the reports of deans of students, campus security chiefs, and students, and examined the correlations between perceived enforcement levels and the change in student drinking rates over the subsequent two year period, after weighting the 2001 data to adjust for demographic changes in the student body. Results: Overall rates of any past-30-days drinking, heavy episodic drinking, and usual heavy drinking among past-30-days drinkers were all lower in 2001 compared to 1999. School-level analyses (N = 11) found deans' baseline reports of stricter enforcement were strongly correlated with subsequent declines in heavy episodic drinking (Pearson's r = -0.73, p = 0.011). Moreover, consistently high enforcement levels across time, as reported by deans, were associated with greater declines in heavy episodic drinking. Such relationships were not found for students' and security chiefs' reports of enforcement. Marijuana use did not rise during this period of decline in heavy drinking. Conclusions: Study findings suggest that stronger enforcement of a stricter alcohol policy may be associated with reductions in student heavy drinking rates over time. An aggressive enforcement stance by deans may be an important element of an effective college alcohol policy.