Immune Response to an Acute Moderate Dose of Alcohol in Healthy Young Adults.

Prior research on alcohol and the immune system has tended to focus on binge doses or chronic heavy drinking. The aim of this single-session preliminary study was to characterize immune response to moderate alcohol (0.60 g alcohol per kilogram body weight) in healthy, nonchronic drinkers. The sample (N = 11) averaged 26.6 years of age and was balanced in gender. Plasma samples were collected at baseline and 1, 2 and 3 hours postconsumption. Markers of microbial translocation [lipopolysaccharide (LPS)] and innate immune response [LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and selected cytokines] were measured using immunoassays. Participants completed self-report questionnaires on subjective alcohol response and craving. Linear mixed models were used to assess changes in biomarkers and self-report measures. Breath alcohol concentration peaked at 0.069 ± 0.008% 1 hour postconsumption. LPS showed a significant linear decrease. LBP and sCD14 showed significant, nonlinear (U-shaped) trajectories wherein levels decreased at 1 hour then rebounded by 3 hours. Of nine cytokines tested, only MCP-1 and IL-8 were detectable in ≥50% of samples. IL-8 did not change significantly. MCP-1 showed a significant linear decrease and also accounted for significant variance in alcohol craving, with higher levels associated with stronger craving. Results offer novel evidence on acute immune response to moderate alcohol. Changes in LBP and sCD14, relative to LPS, may reflect their role in LPS clearance. Results also support further investigation into the role of MCP-1 in alcohol craving. Limitations include small sample size and lack of a placebo condition.

Adolescent Access to Patient-Centered Medical Homes.

OBJECTIVES: To analyze the distribution of patient-centered medical homes (PCMHs) among US adolescents, and to examine whether disparities exist among subgroups. STUDY DESIGN: Data on adolescents ages 12-17 years (n = 34 601) from the 2011-2012 National Survey of Children's Health were used in this cross-sectional study to determine what proportion had access to a PCMH. Multivariable logistic regression was used to calculate the odds of having a PCMH, adjusting for sociodemographic characteristics and special health care needs. Comparisons were made to distribution of PCMH in 2007. RESULTS: Although most US adolescents had a usual source of care (91%), only about one-half (51%) had access to a PCMH. Disparities in the prevalence of PCMHs were seen by race/ethnicity, poverty, and having special health care needs. There were lower adjusted odds in having a PCMH for Hispanic (aOR, 0.56; 95% CI, 0.45-0.68) and black adolescents (aOR, 0.55; 95% CI, 0.46-0.66) compared with white adolescents. Those living below 4 times the poverty level had lower adjusted odds of PCMH access. Adolescents with 3-5 special health care needs had lower adjusted odds (aOR, 0.43; 95% CI, 0.35-0.52) of having a PCMH compared with adolescents without any special health care needs. Other than receiving family centered care, every component of PCMH was slightly lower in 2011-2012 compared with 2007. CONCLUSIONS: PCMH access was lower among minorities, those living in poverty, and those with multiple special health care needs. These disparities in PCMH access among these typically underserved groups call for further study and interventions that would make PCMHs more accessible to all adolescents.

Cerebral Metabolites on the Descending Limb of Acute Alcohol: A Preliminary 1H MRS Study.

AIMS: Chronic alcohol use is associated with cerebral metabolite abnormalities, yet alcohol's acute effects on neurometabolism are not well understood. This preliminary study investigated cerebral metabolite changes in vivo on the descending limb of blood alcohol in healthy moderate drinkers. METHODS: In a pre/post design, participants (N = 13) completed magnetic resonance imaging (MRI) scans prior to and approximately 5 hours after consuming a moderate dose of alcohol (0.60 grams alcohol per kilogram of body weight). Magnetic resonance spectroscopy (1H MRS) was used to quantify cerebral metabolites related to glutamatergic transmission (Glx) and neuroimmune activity (Cho, GSH, myo-inositol) in the thalamus and frontal white matter. RESULTS: Breath alcohol concentration (BrAC) peaked at 0.070±0.008% (mean ± standard deviation) and averaged 0.025±0.011% directly prior to the descending limb scan. In the thalamus, Glx/Cr and Cho/Cr were significantly elevated on the descending limb scan relative to baseline. BrAC area under the curve, an index of alcohol exposure during the session, was significantly, positively associated with levels of Glx/Cr, Cho/Cr and GSH/Cr in the thalamus. GSH/Cr on the descending limb was inversely correlated with subjective alcohol sedation. CONCLUSIONS: This study offers preliminary evidence of alcohol-related increases in Glx/Cr, Cho/Cr and GSH/Cr on the descending limb of blood alcohol concentration. Findings add novel information to previous research on neurometabolic changes at peak blood alcohol in healthy individuals and during withdrawal in individuals with alcohol use disorder.

Identification and characterization of mutant clones with enhanced propagation rates from phage-displayed peptide libraries.

A target-unrelated peptide (TUP) can arise in phage display selection experiments as a result of a propagation advantage exhibited by the phage clone displaying the peptide. We previously characterized HAIYPRH, from the M13-based Ph.D.-7 phage display library, as a propagation-related TUP resulting from a G→A mutation in the Shine-Dalgarno sequence of gene II. This mutant was shown to propagate in Escherichia coli at a dramatically faster rate than phage bearing the wild-type Shine-Dalgarno sequence. We now report 27 additional fast-propagating clones displaying 24 different peptides and carrying 14 unique mutations. Most of these mutations are found either in or upstream of the gene II Shine-Dalgarno sequence, but still within the mRNA transcript of gene II. All 27 clones propagate at significantly higher rates than normal library phage, most within experimental error of wild-type M13 propagation, suggesting that mutations arise to compensate for the reduced virulence caused by the insertion of a lacZα cassette proximal to the replication origin of the phage used to construct the library. We also describe an efficient and convenient assay to diagnose propagation-related TUPS among peptide sequences selected by phage display.