Citations

Purpose. To gather consumer input about approaches to providing energy composition information for foods on fast-food restaurant menus. Design. We asked a subset of individuals (n = 150) in an experimental study about the influence of nutrition labeling on fast-food meal choices to evaluate calorie information on mock fast-food menus in various formats. Setting. Three community sites in the Minneapolis-St. Paul, Minnesota, metropolitan area. Subjects. Adolescents and adults who ate fast food at least once per week were recruited. Measures. Via a series of open- and close-ended questions, participants gave feedback about several formats for providing energy composition information for foods on fast-food restaurant menus. Analysis. Means and frequencies were calculated, and χ 2 tests were conducted. Results. When asked to compare a menu that provided calorie information for each menu item with a menu that provided the number of minutes of running that would be required to burn the calories contained in each menu item, 71.0% of participants preferred the calorie information over the physical activity information. Participants also compared two approaches to providing caloric reference information on the menu (average daily calorie needs per day vs. per meal), and 61.3% preferred the calorie needs—per-meal format. Conclusion. Our results may be useful in designing approaches to providing energy composition information for foods on fast-food restaurant menus.

Abstract Human blood eosinophils exposed ex vivo to hematopoietic cytokines (e.g., IL-5 or GM-CSF) subsequently display enhanced responsiveness to numerous chemoattractants, such as chemokines, platelet-activating factor, or FMLP, through a process known as priming. Airway eosinophils, obtained by bronchoalveolar lavage after segmental Ag challenge, also exhibit enhanced responsiveness to selected chemoattractants, suggesting that they are primed during cell trafficking from the blood to the airway. Earlier work has shown that chemoattractants stimulate greater activation of ERK1 and ERK2 following IL-5 priming in vitro, thus revealing that ERK1/ERK2 activity can be a molecular readout of priming under these circumstances. Because few studies have examined the intracellular mechanisms regulating priming as it relates to human airway eosinophils, we evaluated the responsiveness of blood and airway eosinophils to chemoattractants (FMLP, platelet-activating factor, CCL11, CCL5, CXCL8) with respect to degranulation, adherence to fibronectin, or Ras–ERK signaling cascade activation. When compared with blood eosinophils, airway eosinophils exhibited greater FMLP-stimulated eosinophil-derived neurotoxin release as well as augmented FMLP- and CCL11-stimulated adherence to fibronectin. In airway eosinophils, FMLP, CCL11, and CCL5 stimulated greater activation of Ras or ERK1/ERK2 when compared with baseline. Ras activation by FMLP in blood eosinophils was also enhanced following IL-5 priming. These studies are consistent with a model of in vivo priming of eosinophils by IL-5 or related cytokines following allergen challenge, and further demonstrate the key role of priming in the chemoattractant-stimulated responses of eosinophils. These data also demonstrate the importance of the Ras–ERK signaling pathway in the regulation of eosinophil responses to chemoattractants in the airway. Human airway eosinophils respond to several chemoattractants with increased activation of the Ras–ERK cascade, eosinophil-derived neurotoxin release, and adherence to fibronectin relative to blood eosinophils.

ABSTRACT Nonprimate animal models of HIV-1 infection are prevented by missing cellular cofactors and by antiviral actions of species-specific host defense factors. These blocks are profound in rodents but may be less abundant in certain Carnivora. Here, we enabled productive, spreading replication and passage of HIV-1 in feline cells. Feline fibroblasts, T-cell lines, and primary peripheral blood mononuclear cells supported early and late HIV-1 life cycle phases in a manner equivalent to that of human cells, except that produced virions had low infectivity. Stable expression of feline immunodeficiency virus (FIV) Vif-green fluorescent protein (GFP) in HIV-1 entry receptor-complemented feline (CrFK) cells enabled robust spreading HIV-1 replication. FIV Vif colocalized with feline APOBEC3 (fA3) proteins, targeted them for degradation, and prevented G→A hypermutation of the HIV-1 cDNA by fA3CH and fA3H. HIV-1 Vif was inactive against fA3s as expected and even paradoxically augmented restriction in some assays. In an interesting contrast, simian immunodeficiency virus SIVmac Vif had substantial anti-fA3 activities, which were complete against fA3CH and partial against fA3H. Moreover, both primate lentiviral Vifs colocalized with fA3s and could be pulled down from cell lysates by fA3CH. HIV-1 molecular clones that encode FIV Vif or SIVmac Vif (HIV-1 VF and HIV-1 VS ) were then constructed. These viruses replicated productively in HIV-1 receptor-expressing CrFK cells and could be passaged serially to uninfected cells. Thus, with the exception of entry receptors, the cat genome can supply the dependency factors needed by HIV-1, and a main restriction can be countered by vif chimerism. The results raise the possibility that the domestic cat could yield an animal model of HIV-1 infection.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

AbstractGenome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Background— Microbubble safety concerns led to changes in product recommendations for patients with pulmonary hypertension. Noninvasive estimation of right ventricular systolic pressure (RVSP) is equivalent to pulmonary artery systolic pressure in the absence of pulmonary outflow obstruction. We analyzed the short- and long-term outcomes of patients who received microbubble contrast and those who did not during stress echocardiography (SE) according to resting RVSP. Methods and Results— From November 2003 to December 2007, 26 774 patients underwent SE. RVSP (mean, 32.6�9.6 mm Hg) was measured in 16 434 patients. Of these, 6164 (37.5%) received contrast for left ventricular opacification and 10 270 (62.5%) did not. Short-term (≤72 hours and ≤30 days) and long-term (4.3 years) end points were death and myocardial infarction. Analysis was done for rest RVSP cut-points ≥35, ≥50, and ≥60 mm Hg and tricuspid regurgitant velocities ≥2.7 ms −1 and ≥3.5 ms −1 . Adjusted Cox regression models were used. The contrast cohort comprised older patients (age, 67�12 versus 64�14 years; P <0.001), who were more likely to have positive SE results (35% versus 30%, P <0.001) compared with the noncontrast cohort. Using RVSP ≥50 mm Hg, there was no significant difference in short-term events between the contrast and noncontrast cohorts. For long-term events, there was no significant difference between both cohorts (adjusted hazard ratios [95% confidence intervals] for death, 1.10 [0.80 to 1.50], P =0.56; and myocardial infarction, 0.34 [0.11 to 1.03], P =0.06). Similar results were obtained at different RVSP and tricuspid regurgitant cut-points. Contrast agent–related adverse effects occurred in <1% of patients. Conclusion— RVSP had no impact on predisposition to adverse outcomes in patients undergoing contrast SE in the population studied.

We report the use of an allograft prosthetic composite for reconstruction of the skeletal defect in complex revision total hip replacement for severe proximal femoral bone loss. Between 1986 and 1999, 72 patients (20 men, 52 women) with a mean age of 59.9 years (38 to 78) underwent reconstruction using this technique. At a mean follow-up of 12 years (8 to 20) 57 patients were alive, 14 had died and one was lost to follow-up. Further revision was performed in 19 hips at a mean of 44.5 months (11 to 153) post-operatively. Causes of failure were aseptic loosening in four, allograft resorption in three, allograft nonunion in two, allograft fracture in four, fracture of the stem in one, and deep infection in five. The survivorship of the allograft-prosthesis composite at ten years was 69.0% (95% confidence interval 67.7 to 70.3) with 26 patients remaining at risk. Survivorship was statistically significantly affected by the severity of the pre-operative bone loss (Paprosky type IV; p = 0.019), the number of previous hip revisions exceeding two (p = 0.047), and the length of the allograft used (p = 0.005).