Adolescents' intention and self-efficacy to follow Pap testing recommendations after receiving the HPV vaccine.

Human papillomavirus (HPV) vaccines are recommended in the US for girls and women 11-26 y of age. Because these vaccines do not prevent all cervical cancers, Papanicolaou (Pap) screening is still recommended after vaccination. Young women who have been vaccinated may perceive themselves at lower risk for HPV infection and cervical cancer, which could lead to lower intention and self-efficacy to follow cervical cancer screening guidelines, and subsequent nonadherence to Pap testing. The aim of this study was to examine whether perceived risk of human papillomavirus (HPV) after vaccination and other factors are associated with adolescents' intention and self-efficacy to get Pap testing after HPV vaccination. Women 13-21 y of age (N = 339) receiving their first HPV vaccine dose completed a survey. Multivariable logistic regression examined associations between perceived risk of HPV and intention/self-efficacy to get a Pap test while adjusting for other factors. Approximately half of participants reported high intention and half reported high self-efficacy to get a Pap test. Factors significantly associated with high intention were Pap testing history and knowledge about HPV/HPV vaccines; factors significantly associated with high self-efficacy included insurance plan, Pap testing history, communication with clinician about needing a Pap test after vaccination, lifetime number of male sexual partners, and recent smoking. In conclusion, educating adolescents about HPV/HPV vaccines and the need for Pap testing may increase self-efficacy/intention to get a Pap test after vaccination.

Adolescent changes in homeostatic regulation of EEG activity in the delta and theta frequency bands during NREM sleep.

STUDY OBJECTIVES: Slow wave EEG activity in NREM sleep decreases by more than 60% between ages 10 and 20 years. Slow wave EEG activity also declines across NREM periods (NREMPs) within a night, and this decline is thought to represent the dynamics of sleep homeostasis. We used longitudinal data to determine whether these homeostatic dynamics change across adolescence. DESIGN: All-night sleep EEG was recorded semiannually for 6 years. SETTING: EEG was recorded with ambulatory recorders in the subjects' homes. PARTICIPANTS: Sixty-seven subjects in 2 cohorts, one starting at age 9 and one starting at age 12 years. MEASUREMENTS AND RESULTS: For NREM delta (1-4 Hz) and theta (4-8 Hz) EEG, we tested whether the proportion of spectral energy contained in the first NREMP changes with age. We also tested for age changes in the parameters of the process S exponential decline. For both delta and theta, the proportion of energy in the first NREMP declined significantly across ages 9 to 18 years. Process S parameters SWA(0) and TWA(0), respectively, represent slow wave (delta) activity and theta wave activity at the beginning of the night. SWA(0) and TWA(0) declined significantly (P < 0.0001) across ages 9 to 18. CONCLUSIONS: These declines indicate that the intensity of the homeostatic or restorative processes at the beginning of sleep diminished across adolescence. We propose that this change in sleep regulation is caused by the synaptic pruning that occurs during adolescent brain maturation.

The increase in longitudinally measured sleepiness across adolescence is related to the maturational decline in low-frequency EEG power.

OBJECTIVES: A changing sleep schedule that reduces sleep duration is thought to produce the increasing daytime sleepiness of adolescents. We tested the hypothesis that adolescent daytime sleepiness also results from adolescent brain maturational processes indexed by declining delta electroencephalographic (EEG) activity. DESIGN: Data are from the first 3 years of a semilongitudinal study of EEG changes in adolescence. All-night EEG was recorded semiannually. SETTING: EEG was recorded with ambulatory recorders in the subjects' homes. PARTICIPANTS: Thirty-one subjects were 9 years old (cohort C9), and 38 subjects were 12 years old (cohort C12) at the start of the study. MEASUREMENTS: EEG power density (power/minute) was calculated for the first 5 hours of non-rapid eye movement sleep. Subjects rated sleepiness on a modified Epworth Sleepiness Scale. Habitual sleep schedules were assessed with self-reports and actigraphy. RESULTS: In C9 subjects, sleepiness increased slightly and was related only to age. In C12 subjects, the increase in subjective sleepiness was related to changes in age, bedtime, time in bed, and a wide frequency range of EEG power density. Sleepiness was not related to rise time, non-rapid eye movement sleep duration, rapid eye movement sleep duration, or total sleep time. With sleep schedule measures statistically controlled, the increase in sleepiness in the C12 group was strongly related to declining delta power density and, unexpectedly, even more strongly related to declining theta power density. CONCLUSIONS: The data support our hypothesis that, independent of sleep schedule changes, increasing adolescent daytime sleepiness is related to brain maturational changes indexed by declining EEG power. Our working hypothesis is that the declines in delta and theta power are correlates of an adolescent synaptic pruning that reduces waking arousal levels.

The adolescent decline of NREM delta, an indicator of brain maturation, is linked to age and sex but not to pubertal stage.

Two dramatic phenomena of human adolescence are sexual maturation and a steep decline in the delta EEG of non-rapid eye movement (NREM) sleep. It has long been speculated that these developmental changes are causally related. Here, we present the first longitudinal data on this issue. Cohorts of 9- and 12-year-old children (n = 31, 38) were studied with in-home sleep EEG recordings at 6-mo intervals over 2 years. Pubertal (Tanner) stage, height, and weight were obtained at each time point. NREM delta power density (DPD) did not change significantly over ages 9-11 years, and its level did not differ in boys and girls. DPD declined by 25% between ages 12 and 14 years. This decline was parallel in the two sexes, but levels were lower in girls, suggesting that their DPD decline began earlier. Mixed effect analyses demonstrated that DPD was strongly related to age with Tanner stage, height, weight and body mass index controlled but that none of these measures of physical and sexual development was related to DPD with age controlled. NREM delta is the sleep EEG component homeostatically related to prior waking duration and the intensity of waking brain activity. We hypothesize that the DPD decline is caused by age-programmed synaptic pruning that decreases waking brain metabolic rate. This reduced rate would decrease the "substrate" for delta homeostasis. Whether or not this interpretation proves correct, these longitudinal data demonstrate that the delta decline in adolescence reflects brain processes that are not predicted by physical growth or sexual maturation.

Sleep EEG evidence of sex differences in adolescent brain maturation.

STUDY OBJECTIVES: The steep decline in slow-wave (delta) electroencephalogram (EEG) intensity across adolescence is a prominent feature of late brain maturation. As a first step in determining whether the adolescent delta decline is similar in both sexes, we compared cross-sectional sleep EEG data from 9- and 12-year-old boys and girls. DESIGN: All-night EEG recordings, 6 months apart, were conducted on each subject. SETTING: EEG was recorded in the subjects' homes. PARTICIPANTS: Thirty-two 9-year-olds and 38 12-year-olds are enrolled in a 4-year longitudinal study of adolescent sleep. There are equal numbers of each sex in both age cohorts. INTERVENTIONS: N/A. MEASUREMENTS: Using ambulatory recorders, EEG was recorded in the subjects' homes on their normal sleep schedule. For each of the 2 semi-annual recording periods, data from the 10 subjects from each age-sex group with the cleanest (fewest artifacts) signals were selected for crosssectional comparisons of visual scoring and EEG variables. All artifact-free 20-second non-rapid eye movement epochs were analyzed with power spectral and period-amplitude analysis. RESULTS: In the 12-year-old cohort, delta power per minute was 37% higher in boys than girls. The 9-year-old cohort showed no sex difference. A second recording 6 months later produced similar results. CONCLUSION: These cross-sectional data indicate that girls begin the steep adolescent decline in slow-wave EEG earlier than boys. We hypothesize that this reflects an earlier onset of adolescent synaptic pruning in females.

In vivo phage display to identify M cell-targeting ligands.

PURPOSE: The purpose of this study was to use in vivo phage display screening technology to identify novel lead peptides that target delivery to M cells and to follicle-associated epithelium (FAE) of the intestine. METHODS: Phage display libraries were screened in vivo within the gastrointestinal tract of a rat model by successive screenings across four cycles of selection. RESULTS: Following four cycles of in vivo screening, we identified 30 unique peptide sequences that bound to Peyer's patch tissue, human Caco-2, and rat IEC-6 epithelial cells. Two of the lead targeting peptides, peptides P8 (LETTCASLCYPS) and P25 (VPPHPMTYSCQY), were shown to bind to receptors on the surface of human intestinal tissue. The L-form, D-form, retro-inverted D-form, and selective Cys-to-Ala site-directed mutants of peptides P8 and P25 were also shown to retain binding to Caco-2 cell membranes when immobilized on the surface of a model particulate. Finally, the D-peptide analog of peptide P8 (yqcsytmphppv) enhanced the delivery of polystyrene particles to M cells in vivo in a mouse model, and these particles were delivered into Peyer's patch tissue, as determined by confocal microscopy. CONCLUSIONS: In summary, we have identified novel ligands that target M cells and Peyer's patch tissue, and thus may have utility in the targeted oral delivery of vaccines and vaccine carrier systems to the mucosal immune system within the gastrointestinal tract.

Impaired rejection and mucosal injury of small intestinal allografts lacking the interferon-gamma receptor.

Small intestinal mucosal T cell activation results in villous atrophy and crypt hyperplasia. There is conflicting evidence as to whether a Th1 IFN-gamma response may be involved. Using a murine intestinal transplant model of T cell-mediated enteropathy we aimed to study the role of IFN-gamma on the development of villous atrophy and crypt hyperplasia. Isografts or allografts of foetal small intestine from 129SV-/- IFN-gamma receptor knockout mice or wild type mice were implanted under the kidney capsule of Balb/c recipient mice. Grafts were examined histologically at intervals from 2 to 9 days post implantation for signs of rejection. Quantitative rtPCR for IFN-gamma, TNFalpha and IL-4 was conducted on grafts at 5 and 9 days post implantation. In allografts, rejection accompanied by the development of villous atrophy and crypt hyperplasia, occurred in a time-dependent manner. However this process was markedly slower in the IFN-gamma receptor knockout grafts compared to the wild type grafts at 5 days (chi2 = 10.08, P = 0.007) and 9 days post implantation (chi2 = 13.25, P = 0.004). There were also significantly fewer TNFalpha transcripts in allografts of IFN-gamma-/- intestine than in wild type allografts (P = 0.02). IFN-gamma has a partial, but not obligatory, role in the development of villous atrophy and crypt hyperplasia during T cell mediated rejection of intestinal allografts.