In vivo hemoglobin and water concentrations, oxygen saturation, and scattering estimates from near-infrared breast tomography using spectral reconstruction.

RATIONALE AND OBJECTIVES: Near-infrared (NIR) imaging has its niche in quantifying and characterizing functional changes in tissue relating to vascularity and metabolic status. Here, NIR tomography was applied to study mammographically normal breast tissue in vivo by evaluating relationships between functional parameters so obtained to clinical representers in an effort to understand factors influencing tissue compositional changes. MATERIALS AND METHODS: A new spectral reconstruction method that is considered to provide the most accurate estimates of hemoglobin level, oxygen saturation, water fraction, scattering power, and amplitude was used to assess healthy breast tissue imaged in vivo by means of NIR tomography. The approach directly recovers functional parameters with inherent inclusion of spectral behavior enforced through the incorporation of a priori model assumptions. Sixty subjects were imaged by using a frequency-domain instrument followed by spectral image reconstruction and statistical analysis for significant correlations. RESULTS: The new analysis shows statistically significant inverse correlations between body mass index and breast total hemoglobin and water fractions. Water fraction also correlated inversely with age and separated certain categories of breast density. Average scatter power was indicative of breast radiographic density composition, whereas scatter amplitude varied inversely with breast diameter. Total hemoglobin correlated with water fraction, whereas water correlated with scatter power. CONCLUSION: The changes observed here are attributable to volume fraction alterations and provide some of the most comprehensive data on breast composition variations with demographic factors.

Potential for the 2G single nucleotide polymorphism in the promoter of matrix metalloproteinase to enhance gene expression in normal stromal cells.

The 1G/2G polymorphism of matrix metalloproteinase 1 (MMP-1) affects activity of the promoter in transient transfections, and has been associated with the incidence or invasiveness of five types of cancer. In light of these findings, and because stromal cells may contribute to tumor cell invasion, we used quantitative real-time reverse transcription-PCR to measure endogenous MMP-1 mRNA expression in 34 human foreskin fibroblasts homozygous or heterozygous for the 1G and 2G alleles. We measured basal, cytokine, and growth factor induced MMP-1 mRNA expression. The genotype of the MMP-1 promoter polymorphism was not predictive of mean MMP-1 mRNA expression. However, within the population of cell lines with at least one 2G polymorphism, there were more individuals with higher levels of MMP-1 mRNA after treatment with a cytokine or growth factors. Our data suggest that the presence of the 2G polymorphism does not significantly affect mean expression levels of a population but may increase the potential for an individual to have higher MMP-1 expression in response to growth factors and cytokines.

Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction.

BACKGROUND: The role of the angiotensin II type 2 receptor (AT2-R) in left ventricular (LV) remodeling may depend on the underlying stimulus. We hypothesized that cardiac AT2-R overexpression in transgenic (TG) mice would attenuate remodeling after myocardial infarction (MI). METHODS AND RESULTS: Ten wild-type (WT) C57BL/6 mice and 12 TG mice that overexpress the AT2-R in the heart were studied by cardiac MRI at baseline and days 1, 7, and 28 post-MI induced by 1 hour of occlusion of the LAD followed by reperfusion. Short-axis imaging from apex to base was used to determine LV mass index, end-diastolic and end-systolic volume indices (EDVI, ESVI), regional wall thickness and thickening, and ejection fraction (EF). Gadolinium-DTPA was infused 20 minutes before day 1 imaging to assess infarct size. At baseline, heart rate, blood pressure, LV mass index, and EDVI were similar between groups. Baseline ESVI was lower (0.20+/-0.07 versus 0.45+/-0.15 microL/g, P<0.001) and EF higher (82.3+/-4.9% versus 67.7+/-5.3%, P<0.001) in TG than WT. Infarct size was similar (36.6+/-7.2% in WT, 34.0+/-7.8% in TG, P=NS). When controlled for baseline differences, ESVI was significantly less and EF significantly higher at all time points in TG versus WT. At day 28, ESVI was 1.05+/-0.32 microL/g in TG and 1.63+/-0.41 microL/g in WT, P<0.03, and EF was 47.3+/-5.8% versus 34.1+/-9.2%, P<0.003, respectively. Regional wall thickness and thickening were greater in TG both at baseline and at day 28. At day 28, blood pressure and LV dP/dt were higher in TG. CONCLUSIONS: Cardiac AT2-R overexpression improves LV systolic function at baseline and preserves function during post-MI remodeling.

Effect of viewing smoking in movies on adolescent smoking initiation: a cohort study.

BACKGROUND: Exposure to smoking in movies has been linked with adolescent smoking initiation in cross-sectional studies. We undertook a prospective study to ascertain whether exposure to smoking in movies predicts smoking initiation. METHOD: We assessed exposure to smoking shown in movies in 3547 adolescents, aged 10-14 years, who reported in a baseline survey that they had never tried smoking. Exposure to smoking in movies was estimated for individual respondents on the basis of the number of smoking occurrences viewed in unique samples of 50 movies, which were randomly selected from a larger sample pool of popular contemporary movies. We successfully re-contacted 2603 (73%) students 13-26 months later for a follow-up interview to determine whether they had initiated smoking. FINDINGS: Overall, 10% (n=259) of students initiated smoking during the follow-up period. In the highest quartile of exposure to movie smoking, 17% (107) of students had initiated smoking, compared with only 3% (22) in the lowest quartile. After controlling for baseline characteristics, adolescents in the highest quartile of exposure to movie smoking were 2.71 (95% CI 1.73-4.25) times more likely to initiate smoking compared with those in the lowest quartile. The effect of exposure to movie smoking was stronger in adolescents with non-smoking parents than in those whose parent smoked. In this cohort, 52.2% (30.0-67.3) of smoking initiation can be attributed to exposure to smoking in movies. INTERPRETATION: Our results provide strong evidence that viewing smoking in movies promotes smoking initiation among adolescents.

Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants.

The purpose of this study was to determine the effects of inhibitors of Rho kinase (ROK) and matrix metalloproteinases (MMPs) on angiogenesis and tumor growth and to evaluate ROK activity in human prostate cancer PC3 cells and endothelial cells (HUVECs). Vacuolation by endothelial cells and lumen formation, the earliest detectable stages of angiogenesis, were inhibited by the ROK inhibitor Wf-536. Combining Wf-536 with the MMP inhibitor Marimastat greatly enhanced in vitro inhibition of endothelial vacuolation, lumen and cord formation, and VEGF- and HGF-stimulated endothelial sprout formation from aorta. Inhibition of sprout formation by the two inhibitors was synergistic. Both agents inhibited migration of HUVECs. The regulatory subunit (MYPT1) of the myosin phosphatase was phosphorylated in PC3 cells and HUVECs, and phosphorylation of MYPT1 and the myosin regulatory light chain was reduced by Wf-536, providing direct evidence of ROK activity. Early treatment of immuno-incompetent mice bearing xenotransplants of PC3 cells with a combination of Wf-536 plus Marimastat with or without Paclitaxel, significantly inhibited tumor growth, prevented tumor growth escape after discontinuation of Paclitaxel, and increased survival.

Use of cigarettes and alcohol by preschoolers while role-playing as adults: "Honey, have some smokes".

OBJECTIVE: To examine preschoolers' attitudes, expectations, and perceptions of tobacco and alcohol use. DESIGN: Structured observational study. Children used props and dolls to act out a social evening for adults. As part of the role play, each child selected items from a miniature grocery store stocked with 73 different products, including beer, wine, and cigarettes, for an evening with friends. SETTING: A behavioral laboratory at the Department of Psychological and Brain Sciences, Dartmouth College. PATIENTS: One hundred twenty children, 2 to 6 years old, participated individually in the role-playing. MAIN OUTCOME MEASURE: Whether or not a child purchased cigarettes or alcohol at the store. RESULTS: Children purchased a mean of 17 of the 73 products in the store. Thirty-four children (28.3%) bought cigarettes and 74 (61.7%) bought alcohol. Children were more likely to buy cigarettes if their parents smoked (adjusted odds ratio [OR], 3.90; 95% confidence interval [CI], 1.20-12.63). Children were more likely to buy beer or wine if their parents drank alcohol at least monthly (adjusted OR, 3.04; 95% CI, 1.02-9.10) or if they viewed PG-13- or R-rated movies (adjusted OR, 5.10; 95% CI, 1.14-22.90). Children's play behavior suggests that they are highly attentive to the use and enjoyment of alcohol and tobacco and have well-established expectations about how cigarettes and alcohol fit into social settings. CONCLUSIONS: The data suggest that observation of adult behavior, especially parental behavior, may influence preschool children to view smoking and drinking as appropriate or normative in social situations. These perceptions may relate to behaviors adopted later in life.

Adolescent weight status and receptivity to food TV advertisements.

OBJECTIVE: This study examined the relationship between adolescent weight status and food advertisement receptivity. DESIGN: Survey-based evaluation with data collected at baseline (initial and at 2 months), and at follow-up (11 months). SETTING: New Hampshire and Vermont. PARTICIPANTS: Students (n = 2,281) aged 10-13 in 2002-2005. MAIN OUTCOME MEASURE: Overweight. ANALYSIS: Generalized estimating equations to model the relationship between identifying a food advertisement as their favorite and being overweight. RESULTS: Overall, 35.9% of the adolescents were overweight. Less than one fifth named a food advertisement as their favorite (16.1%). Most of the food advertisements were for less-healthful food (89.6%). After controlling for school, age, sex, sociodemographics, physical activity, number of TV sessions watched, and having a TV in the bedroom, overweight adolescents were significantly less likely to be receptive to food advertisements (relative risk = 0.83, 95% confidence interval 0.70, 0.98) compared to non-overweight adolescents. CONCLUSIONS AND IMPLICATIONS: This study provides preliminary evidence that normal-weight adolescents are receptive to unhealthful food advertisements. Longitudinal studies are needed to evaluate whether consistent exposure to advertisements for unhealthful food, particularly if they are promoted with healthful behaviors such as being physically active, influence adolescents' food choices, and ultimately their body mass index, over the long term.

Parental attitudes about cigarette smoking and alcohol use in the Motion Picture Association of America rating system.

OBJECTIVE: To evaluate whether parents want smoking and alcohol use to be considered in movie ratings. DESIGN: Data were collected as part of a longitudinal study of adolescent health behavior involving 2564 parent/child dyads from northern New England. Parents (n = 2401) were surveyed at wave 2 about movie ratings. Qualitative interviews were conducted with a subset of parents (n = 62) 15 months later. SETTING: Participants were surveyed by telephone. PARTICIPANTS: Most parents (94.9%; n = 2279) were mothers, 52.5% were younger than 40 years, and 90.6% were white, and children were aged 9 to 15 years. MAIN OUTCOME MEASURES: Whether cigarette and alcohol use should be included as movie ratings criteria and if movies with cigarette or alcohol use should be rated R. RESULTS: About 52% (n = 1242) and 66% (n = 1579) of parents believed cigarette or alcohol use, respectively, should be used as movie ratings criteria; 28.9% (n = 693) supported an R rating for movies with smoking and 41.9% (n = 1003) supported R ratings for alcohol. In adjusted models, parents were more likely to support adding cigarette and alcohol use as ratings criteria if they believed the current ratings were not useful, they restricted their children from watching R-rated movies, and they were nondrinkers. Nonsmoking parents were more likely to support an R rating for smoking. Interviews revealed that parents may underestimate the impact of movie smoking and drinking. CONCLUSIONS: Although a majority of parents supported including smoking or drinking in ratings criteria, fewer favored R ratings. Parental support could be a key factor in determining the impact of modifications to the Motion Picture Association of America rating system.

Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma.

BACKGROUND: It is unknown whether neoadjuvant chemoradiotherapy, compared with adjuvant chemoradiotherapy, decreases the rate of local recurrence after resection of pancreatic adenocarcinoma. STUDY DESIGN: This is a retrospective case review of 102 patients with pancreatic adenocarcinoma who underwent pancreatic resection between 1993 and 2005. RESULTS: Of 102 patients with pancreatic adenocarcinoma who underwent surgical resection, 19 (19%) had no additional treatment, 41 (40%) underwent adjuvant chemoradiotherapy, and 42 (41%) were treated preoperatively with neoadjuvant chemoradiotherapy. Patients selected to receive neoadjuvant therapy were more likely to have locally advanced tumors. Based on initial CT scan, the percentage of patients with unresectable or borderline resectable tumors in the neoadjuvant group was 67%, compared with 22% in the adjuvant group. Nevertheless, patients receiving neoadjuvant chemoradiotherapy were less likely to have a local recurrence develop than patients receiving adjuvant chemoradiotherapy (5% versus 34%, p = 0.02). For those patients with tumors determined to be resectable on initial CT scan, local recurrences were observed in 31% (10 of 32) of patients in the adjuvant therapy group, compared with only 7% (1 of 14) of the neoadjuvant group. Intraoperative radiation therapy, administered to 51% of patients, was not associated with a lower rate of local recurrence. CONCLUSIONS: Neoadjuvant chemoradiotherapy is associated with improved local tumor control in patients undergoing resection for pancreatic carcinoma.

SunSafe in the Middle School Years: a community-wide intervention to change early-adolescent sun protection.

OBJECTIVE: Rising rates of skin cancer associated with early-life sun exposure make it important to improve adolescent sun-protection practices. Our study objective was to determine if a multicomponent community-wide intervention could alter the decline in sun protection that begins in early adolescence. METHODS: A randomized, controlled trial was conducted in 10 communities to assess the impact of the SunSafe in the Middle School Years program. The intervention sought to (1) educate and activate adults and peers to role model and actively promote sun-protection practices and (2) create a pro-sun protection community environment. It targeted school personnel, athletic coaches, lifeguards, and clinicians and enlisted teens as peer advocates. Annual observations of cross-sectional samples of teens at community beach/pool sites were used to assess the impact of 1 and 2 years of intervention exposure compared to grade-matched controls. The outcome was percent of body surface protected by sunscreen, clothing, or shade. RESULTS: Observers determined the sun protection level of 1927 adolescents entering 6th to 8th grades. After 2 years of intervention exposure, adolescents at the beach/pool in intervention communities were significantly better protected than those in control communities. Over 2 years, the percent of body surface area protected declined by 23% in the control arm but only 8% in intervention arm. After intervention, the average percent of body surface protected at intervention sites (66.1%) was significantly greater than control sites (56.8%). Teens in intervention communities reported sun-protection advice from more adult sources, were more likely to use sunscreen, and applied it more thoroughly than control-site teens. CONCLUSIONS: Our multicomponent model addressing adolescent sun protection shows the power of engaging teens and adults from across the community as role models and educators. This new ecological approach shows promise in changing adolescent sun protection behaviors and reducing skin cancer risks.

Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms.

PURPOSE: To prospectively assess quantitatively the inherent contrast of electromagnetic (EM) properties that can be imaged by using available technology in women with abnormal findings at conventional breast imaging who underwent subsequent biopsy. MATERIALS AND METHODS: The protocol was HIPAA compliant and approved by the institutional review board. All participants provided informed consent. Fifty-three women with normal (Breast Imaging Reporting and Data System [BI-RADS] category 1) and ninety-seven women with abnormal (BI-RADS category 4 or 5) screening mammograms were imaged with three EM imaging methods: electrical impedance spectroscopy (EIS), microwave imaging spectroscopy (MIS), and near-infrared spectral tomography (NIR). A region-of-interest (ROI) analysis was used to assess the EM image properties for comparison of findings with conventional image findings and correlation with specific pathologic parameters for women with abnormal findings. Statistical analyses were conducted. RESULTS: One hundred fifty participants (age range, 35-81 years) were included. EM image property contrast ratios of 150%-200% were found in breast abnormality ROIs relative to the ipsilateral breast background. Analysis of variance demonstrated significant differences in ROI image summaries of mammographically normal versus abnormal breasts for EIS, across diagnostic groups for NIR, and for MIS (analysis restricted to lesions larger than 1 cm(3)). Receiver operating curve (ROC) analysis of the EM properties for cancers among subjects with BI-RADS category 4 or 5, compared with the EM properties for the subjects with normal breasts (BI-RADS category 1), yielded areas under the ROC curve ranging from 0.67 to 0.81. Pathologic correlations with mean vessel density, mean vessel area, and epithelium-to-stroma ratio suggest a biological origin of the EM image properties associated with disease. CONCLUSION: Results from EM breast examinations provide statistical evidence of a mean increase in image contrast of 150%-200% between abnormal (benign and malignant) and normal breast tissue.

Travel distance and season of diagnosis affect treatment choices for women with early-stage breast cancer in a predominantly rural population (United States).

OBJECTIVE: Current standards of care for early-stage breast cancer include either breast-conserving surgery (BCS) with post-operative radiation or mastectomy. A variety of factors influence the type of treatment chosen. In northern, rural areas, daily travel for radiation can be difficult in winter. We investigated whether proximity to a radiation treatment facility (RTF) and season of diagnosis affected treatment choice for New Hampshire women with early-stage breast cancer. METHODS: Using a population-based cancer registry, we identified all women residents of New Hampshire diagnosed with stage I or II breast cancer during 1998-2000. We assessed factors influencing treatment choices using multivariate logistic regression. RESULTS: New Hampshire women with early-stage breast cancer were less likely to choose BCS if they live further from a RTF (P < 0.001). Of those electing BCS, radiation was less likely to be used by women living >20 miles from a RTF (P = 0.002) and those whose diagnosis was made during winter (P = 0.031). CONCLUSION: Our findings indicate that a substantial fraction of women with early-stage breast cancer in New Hampshire receive suboptimal treatment by forgoing radiation because of the difficulty traveling for radiation in winter. Future treatment planning strategies should consider these barriers to care in cold rural regions.

Expression of "Spot 14" (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker.

Most breast cancers are "lipogenic", defined by high fatty acid synthase (FAS) content and dependence on fatty acid synthesis for growth and survival. S14 (Spot 14; THRSP) is a nuclear protein that activates genes required for fatty acid synthesis. The S14 gene is amplified in approximately 15% of breast cancers, but clinical correlates of its expression were unknown. We analyzed 131 breast cancers by immunohistochemistry for S14 and FAS. Staining was graded 0, 1, or 2+, and scores were correlated with traditional tumor markers, histological features, and outcome. S14 and FAS staining were related to tumor size (p=0.05 for S14, p=0.038 for FAS), but not to stage. S14 but not FAS scores correlated with tumor grade in both DCIS (p=0.003) and invasive cases (p<0.001). Invasive cases (pooled node - and +) with weak S14 staining (n=21) showed no recurrence over 3000 d follow-up, including 10 cases with lymph node involvement, whereas 32% of 67 strongly-staining tumors recurred (log rank p<0.0001). S14 scores did not cosegregate with sex steroid receptors, Her2/neu, or cyclin D1. Low level S14 expression is associated with prolonged disease-free survival in invasive cases, including those with nodal metastasis. High-level expression of S14 identifies a subset of high-risk breast cancers that is not specified by analysis of sex steroid receptors, Her2/neu, or cyclin D1, and provides a molecular correlate to histologic features that predict recurrence.

Parental rules and monitoring of children's movie viewing associated with children's risk for smoking and drinking.

OBJECTIVES: Evidence suggests that media portrayals of tobacco and alcohol use are important predictors of adolescent smoking and drinking. We examined the role of parents in monitoring and limiting children's movie exposure and whether or not this was associated with a lower risk of adolescent smoking and drinking. DESIGN: We surveyed 2606 child-parent dyads between 2002 and 2003. We asked children (9-12 years of age) how often their parents engaged in specific behaviors to monitor their movie viewing and if their parents allowed them to watch R-rated movies. We also surveyed children about parental monitoring of nonmedia-related behaviors. The primary outcomes were risk of smoking and drinking alcohol, defined by attitudinal susceptibility or early experimentation with either substance. RESULTS: Less than half (45.0%) the children were prohibited from watching R-rated movies. Of those who were allowed to watch R-rated movies, one third (34.7%) always viewed them with a parent and two thirds (65.3%) sometimes watched them without a parent. Less than 10% of the children reported that their parents consistently engaged in all 4 movie-monitoring behaviors. Even after controlling for parental monitoring of nonmedia-related behaviors and other covariates, children were at lower risk of smoking and drinking if their parents prohibited them from watching R-rated movies. Parental coviewing of R-rated movies was associated with a lower risk of child smoking but not drinking if parents consistently monitored what their children watched. CONCLUSIONS: Parental rules and monitoring of children's movie viewing may have a protective influence on children's risk for smoking and drinking, over and above parental monitoring of nonmedia related behaviors. This highlights a potential role for parents in preventing early initiation of tobacco and alcohol use among adolescents.

Tumor-related immunity in prostate cancer patients treated with human recombinant granulocyte monocyte-colony stimulating factor (GM-CSF).

BACKGROUND: Granulocyte monocyte-colony stimulating factor (GM-CSF) supports the survival, expansion, and differentiation of lymphoid and myeloid derived dendritic cells (DCs). We hypothesized that systemic therapy with GM-CSF in prostate cancer patients could augment prostate cancer-related immunity and induce clinical response. METHODS: Eligible patients were randomly assigned to receive either 125 or 250 microg/m(2) GM-CSF subcutaneously three times a week until clinical progression. Prostate-specific antigen (PSA) T cell precursor frequencies were determined by a flow cytometric method. RESULTS: We were able to show, for the first time, a statistically significant correlation between pre-treatment PSA level and PSA-specific CD4(+) T cell precursors and a trend between pre-treatment PSA level and PSA-specific CD8(+) T cell precursors (P<0.0001 and P=0.059, respectively). CONCLUSIONS: These results suggest that existent immunity to PSA in prostate cancer patients may be a promising target for future immunotherapeutic approaches to prostate cancer.

Pigmentary characteristics and moles in relation to melanoma risk.

Although benign and atypical moles are considered key melanoma risk factors, previous studies of their influence were small and/or institution-based. We conducted a population-based case-control study in the state of New Hampshire. Individuals of ages 20-69 with an incident diagnosis of first primary cutaneous melanoma were ascertained through the New Hampshire State Cancer Registry. Controls were identified through New Hampshire driver's license lists and frequency-matched by age and gender to cases. We interviewed 423 eligible cases and 678 eligible controls. Host characteristics, including mole counts, were evaluated using logistic regression analyses. Our results showed that pigmentary factors, including eye color (OR = 1.57 for blue eyes compared to brown), hair color (OR = 1.85 for blonde/red hair color compared to brown/black), freckles before age 15 (OR = 2.39 for freckles present compared to absent) and sun sensitivity (OR = 2.25 for peeling sunburn followed by no tan or a light tan and 2.42 for sunburn followed by tan compared to tanning immediately), were related to melanoma risk; these associations held after adjustment for sun-related factors and for moles. In analyses confined to skin examination participants, the covariate-adjusted effects of benign and atypical moles were moderately strong. Compared to 0-4 benign moles, risk increased steadily for 5-14 moles (OR = 1.71), 15-24 moles (OR = 3.55) and >or= 25 moles (OR = 4.33). Risk also increased with the number of atypical moles; compared to none, the ORs for having 1, 2-3, or >or= 4 atypical moles were 2.08, 1.84 and 3.80, respectively. Although risk was highest for those with multiple benign and atypical moles, the interaction was not of statistical significance. Our findings, arising from the first population- and incidence-based study to evaluate atypical moles in relation to melanoma risk, confirm the importance of host susceptibility, represented by pigmentary factors and the tendency to develop benign or atypical moles, in the etiology of this disease.

Exposure to movie smoking: its relation to smoking initiation among US adolescents.

OBJECTIVE: Regional studies have linked exposure to movie smoking with adolescent smoking. We examined this association in a representative US sample. DESIGN/METHODS: We conducted a random-digit-dial survey of 6522 US adolescents aged 10 to 14 years. Using previously validated methods, we estimated exposure to movie smoking, in 532 recent box-office hits, and examined its relation with adolescents having ever tried smoking a cigarette. RESULTS: The distributions of demographics and census region in the unweighted sample were almost identical to 2000 US Census estimates, confirming representativeness. Overall, 10% of the population had tried smoking. Quartile (Q) of movie smoking exposure was significantly associated with the prevalence of smoking initiation: 0.02 of adolescents in Q1 had tried smoking; 0.06 in Q2; 0.11 in Q3; and 0.22 in Q4. This association did not differ significantly by race/ethnicity or census region. After controlling for sociodemographics, friend/sibling/parent smoking, school performance, personality characteristics, and parenting style, the adjusted odds ratio for having tried smoking were 1.7 (95% confidence interval [CI]: 1.1, 2.7) for Q2, 1.8 (95% CI: 1.2, 2.9) for Q3, and 2.6 (95% CI: 1.7, 4.1) for Q4 compared with adolescents in Q1. The covariate-adjusted attributable fraction was 0.38 (95% CI: 0.20, 0.56), suggesting that exposure to movie smoking is the primary independent risk factor for smoking initiation in US adolescents in this age group. CONCLUSIONS: Smoking in movies is a risk factor for smoking initiation among US adolescents. Limiting exposure of young adolescents to movie smoking could have important public health implications.

Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake.

The interplay between pathogen-encoded virulence factors and host cell signaling networks is critical for both the establishment and clearance of microbial infections. Yersinia uptake into host cells serves as an in vitro model for exploring how host cells respond to Yersinia adherence. In this study, we provide insight into the molecular nature and regulation of signaling networks that contribute to the uptake process. Using a reconstitution approach in Fak(-/-) fibroblasts, we have been able to specifically address the interplay between Fak, Cas and Pyk2 in this process. We show that both Fak and Cas play roles in the Yersinia uptake process and that Cas can function in a novel pathway that is independent of Fak. Fak-dependent Yersinia uptake does not appear to involve Cas-Crk signaling. By contrast, Cas-mediated uptake in the absence of Fak requires Crk as well as the protein tyrosine kinases Pyk2 and Src. In spite of these differences, the requirement for Rac1 activity is a common feature of both pathways. Furthermore, blocking the function of either Fak or Cas induces similar morphological defects in Yersinia internalization, which are manifested by incomplete membrane protrusive activity that is consistent with an inhibition of Rac1 activity. Pyk2 also functions in Yersinia uptake by macrophages, which are physiologically important for clearing Yersinia infections. Taken together, these data provide new insight into the host cellular signaling networks that are initiated upon infection with Y. pseudotuberculosis. Importantly, these findings also contribute to a better understanding of other cellular processes that involve actin remodeling, including the host response to other microbial pathogens, cell adhesion and migration.

Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography.

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic density. Total hemoglobin concentration correlated inversely to body mass index, likely because lower body mass indicates proportionately less fat and more glandular tissue, and glandular tissue contains greater vascularity, hence, more total hemoglobin. Optical scattering was correlated to breast diameter, subject age, and radiographic density. In the radiographic density, fatty breasts had low scattering power and extremely dense breasts had higher values. This observation is consistent with low attenuation of conventional x-rays with fat and higher attenuation in glandular tissues. Optically, fatty tissues have large scatterers leading to a low scattering power, whereas glandular or fibrous tissues have more cellular and collagen-based structures that lead to high scattering power. The study presents correlative data supporting the hypothesis that optical measurements of absorption and scattering can provide physiologically relevant information about breast tissue composition. These breast constituents vary significantly between individuals and can be altered because of changes in breast physiology or pathological state.