High-Temporal/High-Spatial Resolution Breast Magnetic Resonance Imaging Improves Diagnostic Accuracy Compared With Standard Breast Magnetic Resonance Imaging in Patients With High Background Parenchymal Enhancement.

PURPOSE: To compare breast magnetic resonance imaging (MRI) diagnostic performance using a standard high-spatial resolution protocol versus a simultaneous high-temporal/high-spatial resolution (HTHS) protocol in women with high levels of background parenchymal enhancement (BPE). MATERIALS AND METHODS: We conducted a retrospective study of contrast-enhanced breast MRIs performed at our institution before and after the introduction of the HTHS protocol. We compared diagnostic performance of the HTHS and standard protocol by comparing cancer detection rate (CDR) and positive predictive value of biopsy (PPV3) among women with high BPE (ie, marked or moderate). RESULTS: Among women with high BPE, the HTHS protocol demonstrated increased CDR (23.6 per 1,000 patients v 7.9 per 1,000 patients; P = 0. 013) and increased PPV3 (16.0% v 6.3%; P = .021) compared with the standard protocol. This corresponded to a 9.8% (95% CI, 1.29 to 18.3) decrease in the proportion of unnecessary biopsies among high-BPE patients and an additional cancer yield of 15.7 per 1,000 patients (95% CI, 1.3 to 18.3). CONCLUSION: Among women with high BPE, HTHS MRI improved diagnostic performance, leading to an additional cancer yield of 15.7 cancers per 1,000 women and concomitantly decreasing unnecessary biopsies by 9.8%. A multisite prospective trial is warranted to confirm these findings and to pave the way for more widespread clinical implementation.

Raccoon Roundworm (Baylisascaris procyonis) Undetected in Endangered Key Largo Woodrat (Neotoma floridana smalli) Endemic Range.

Raccoon roundworm (Baylisascaris procyonis) negatively affects woodrat (Neotoma spp.) populations but is not known to occur in the endemic range of endangered Key Largo woodrats (Neotoma floridana smalli). Rectal swabs from 23 raccoons (Procyon lotor) in Key Largo were screened for raccoon roundworm by PCR. All tests were negative, suggesting continued absence.

The effects of multiple early life stressors on adolescent alcohol consumption.

Alcohol use disorder is pervasive and effects the health of millions. Identifying factors such as early life stress that contribute to the development of alcohol use disorder is therefore critical, especially those that contribute to adolescent drinking, a strong predictor of AUD development. The majority of prior studies have examined early life effects on adult drinking, but have not studied intake during adolescence, and no prior studies have examined how the effects of multiple stressors may be additive. Therefore, this study determined if experiencing individual or multiple stressors increases adolescent alcohol intake. Male Long Evans rats underwent either early or late maternal separation (postnatal day 2-9 or 13-20), early adolescent social defeat (PND 30-40), both, or neither. All rats were then given two-hour access to alcohol, and voluntary intake assessed daily in late adolescence (PND 41-51). In adulthood, sensitivity to alcohol's sedative effects was assessed using loss and regain of righting reflex tests. Results indicate that experiencing maternal separation (at either time point) or social defeat increased adolescent alcohol consumption, but experiencing the combined stressors did not, and that no stressor significantly affected body weight during adolescence or loss and regain of righting reflex in adulthood. Overall, this pattern of effects suggests that experiencing any individual early life stressor may increase adolescent alcohol intake, in agreement with prior literature, but that the combined effects of multiple early life stressors may be more complicated.

Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics.

The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial signatures can reveal a station's history, such as marine-associated bacteria in a hurricane-flooded station. Some evidence of pathogens was found (Bacillus anthracis), but a lack of reported cases in NYC suggests that the pathogens represent a normal, urban microbiome. This baseline metagenomic map of NYC could help long-term disease surveillance, bioterrorism threat mitigation, and health management in the built environment of cities.

Association between domestic violence and HIV serostatus among married and formerly married women in Kenya.

The prevalence of both domestic violence (DV) and HIV among Kenyan women is known to be high, but the relationship between them is unknown. Nationally representative cross-sectional data from married and formerly married (MFM) women responding to the Kenya Demographic and Health Survey 2008/2009 were analyzed adjusting for complex survey design. Multivariable logistic regressions were used to assess the covariate-adjusted associations between HIV serostatus and any reported DV as well as four constituent DV measures: physical, emotional, sexual, and aggravated bodily harm, adjusting for covariates entered into each model using a forward stepwise selection process. Covariates of a priori interest included those representing marriage history, risky sexual behavior, substance use, perceived HIV risk, and sociodemographic characteristics. The prevalence of HIV among MFM women was 10.7% (any DV: 13.1%, no DV: 8.6%); overall prevalence of DV was 43.4%. Among all DV measures, only physical DV was associated with HIV (11.9%; adjusted odds ratio: 2.01, p <.05). Efforts by the government and women's groups to monitor and improve policies to reduce DV, such as the Sexual Offences Act of 2006, are urgently needed to curb HIV, as are policies that seek to provide DV counseling and treatment to MFM women.

What Are We Putting in Our Food That Is Making Us Fat? Food Additives, Contaminants, and Other Putative Contributors to Obesity.

The "chemical obesogen" hypothesis conjectures that synthetic, environmental contaminants are contributing to the global epidemic of obesity. In fact, intentional food additives (e.g., artificial sweeteners and colors, emulsifiers) and unintentional compounds (e.g., bisphenol A, pesticides) are largely unstudied in regard to their effects on overall metabolic homeostasis. With that said, many of these contaminants have been found to dysregulate endocrine function, insulin signaling, and/or adipocyte function. Although momentum for the chemical obesogen hypothesis is growing, supportive, evidence-based research is lacking. In order to identify noxious synthetic compounds in the environment out of the thousands of chemicals that are currently in use, tools and models from toxicology should be adopted (e.g., functional high throughput screening methods, zebrafish-based assays). Finally, mechanistic insight into obesogen-induced effects will be helpful in elucidating their role in the obesity epidemic as well as preventing and reversing their effects.

Effects of thiol antioxidant ß-mercaptoethanol on diet-induced obese mice.

AIMS: Obesity and insulin resistance are associated with increased oxidant stress. However, treatments of obese subjects with different types of antioxidants often give mixed outcomes. In this work, we sought to determine if long-term supplementation of a thiol antioxidant, ß-mercaptoethanol, to diet-induced obese mice may improve their health conditions. MAIN METHODS: Middle-age mice with pre-existing diet-induced obesity were provided with low concentration ß-mercaptoethanol (BME) in drinking water for six months. Animals were assessed for body composition, gripping strength, spontaneous physical and metabolic activities, as well as insulin and pyruvate tolerance tests. Markers of inflammation were assessed in plasma, fat tissue, and liver. KEY FINDINGS: BME-treated mice gained less fat mass and more lean mass than the control animals. They also showed increased nocturnal locomotion and respiration, as well as greater gripping strength. BME reduced plasma lipid peroxidation, decreased abdominal fat tissue inflammation, reduced fat infiltration into muscle and liver, and reduced liver and plasma C-reactive protein. However, BME was found to desensitize insulin signaling in vivo, an effect also confirmed by in vitro experiments. SIGNIFICANCE: Long-term supplementation of low dose thiol antioxidant BME improved functional outcomes in animals with pre-existing obesity. Additional studies are needed to address the treatment impact on insulin sensitivity if a therapeutic value is to be explored.

Fibroblasts from type 1 diabetics exhibit enhanced Ca(2+) mobilization after TNF or fat exposure.

The effects of cytokine and fatty acid treatment on signal transduction in dermal fibroblasts from type 1 diabetics and matched controls were compared. Chronic exposure to TNF, accentuated Ca(2+) mobilization in response to bradykinin (BK) in cells from both controls and diabetics; responses were three-fold greater in cells from diabetics than in controls. Similarly, with chronic exposure to IL-1ß, BK-induced Ca(2+) mobilization was accentuated in cells from type 1 diabetics compared to the controls. Pretreatment with the protein synthesis inhibitor cycloheximide or the protein kinase C inhibitor calphostin C prior to the addition of TNF completely abrogated the TNF-induced increment in peak bradykinin response. Ca(2+) transients induced by depleting endoplasmic reticulum (ER) Ca(2+) with thapsigargin were also greater in TNF treated fibroblasts than in untreated cells, with greater increases in cells from diabetics. Exposing fibroblasts for 48 hours to 2 mM oleate also increased both the peak bradykinin response and the TNF-induced increment in peak response, which were significantly greater in diabetics than controls. These data indicate that cells from diabetic patients acquire elevated ER Ca(2+) stores in response to both cytokines and free fatty acids,and thus exhibit greater sensitivity to environmental inflammatory stimuli and elevated lipids.

Type and amount of lipids influence the molecular and textural properties of a soy soft pretzel.

Altering baked goods by the addition of nutrient-rich ingredients, such as soy and ground almonds, affects the water and lipid distribution of the product and, subsequently, its final quality. Here, we studied how three lipid sources, shortening, canola oil, and ground almonds, affected texture and water distribution in a baked soy pretzel and the molecular mobility in the dough. Pretzel crumb from all formulations exhibited 40-43% moisture with a little more than half present as "freezable" water. Firmness and chewiness decreased with increased shortening and canola oil, whereas firmness and chewiness increased with additional almonds. In contrast, neither springiness nor cohesiveness was affected by the lipid quantity or source. Finally, magnetic resonance imaging of the soy pretzel dough revealed two or three populations of dough components that have distinct molecular mobilities. With increased lipid content, the mobility of each population increased in magnitude and heterogeneity. Interestingly, almonds had the smallest effect on the molecular mobility of the dough but had the largest effect on textural properties. These results provide quantitative insight into the mechanisms by which the lipid source can influence molecular properties that have textural implications for bakery products.

Isoflavone retention during processing, bioaccessibility, and transport by Caco-2 cells: effects of source and amount of fat in a soy soft pretzel.

The impact of source and amount of lipid used to prepare a soy soft pretzel on the bioaccessibility and transport of isoflavones was investigated using the coupled in vitro digestion/Caco-2 human cell model. Pretzels were prepared without or with 2.9 or 6.0% exogenous lipid from either shortening, canola oil, ground almond, or ground hazelnut. The isoflavone backbone structure was stable during pretzel production, although there was partial conversion from malonyl and acetyl glucosides to simple glucosides and aglycones. Endogenous ß-glucosidase activity in ground almond facilitated partial conversion of simple glucosides to aglycones during proofing, resulting in a slight decrease in bioaccessibility of isoflavones as compared with other sources of lipid. Amount and source of lipid did not affect bioaccessibility or uptake and metabolism of isoflavones by Caco-2 cells, although transport across the monolayer was greater with the lesser amount of shortening. These results suggest that the isoflavone structure, but not source or amount of lipid in a soy pretzel, may affect bioavailability of isoflavones.

The effects of soy on freezable bread dough: a magnetic resonance study.

Hygroscopic soy ingredients were hypothesised to slow the rate of water migration in unleavened bread dough during frozen storage. Thawed soy (18% dry weight) and wheat dough samples were assessed using non-destructive nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) for up to 8 wks frozen storage time. MRI suggested a spatially homogeneous, net increase in proton mobility with frozen storage and, with solution state proton NMR, distinct "free" and "bound" states were discerned. T(2) relaxation times of the majority proton population suggested increased mobility with frozen storage time, and statistical difference from the fresh sample was seen later for the soy samples than the wheat samples. As seen by (13)C-solid state NMR, the crystallinity of the starch was not affected by either soy addition or frozen storage. In conclusion, addition of soy to bakery products led to slightly enhanced preservation of "fresh" characteristics of the dough during frozen storage.

A comparison of satiety, glycemic index, and insulinemic index of wheat-derived soft pretzels with or without soy.

The consumption of nutrient-poor snack foods in Western diets is thought to be contributing to the increasing prevalence of obesity and diabetes. Soy offers unique potential to provide high quality protein, dietary fiber, and phytochemicals to snack foods to produce a more healthful nutritional profile. In this study, 27.3% of wheat flour was replaced with soy ingredients in a soft pretzel and evaluated for impact on satiety, glycemic index (GI), and insulinemic index (II). We first tested the soy pretzel for consumer acceptability by 51 untrained sensory panelists on a 9-point hedonic scale. Second, in a crossover trial, 20 healthy adults consumed soy and traditional pretzels (1000 kJ or 239 kcal each) after an overnight fast. They reported their levels of satiety on a 10 cm visual analog scale (VAS) for 2 h postprandially. Third, 12 healthy, non-diabetic subjects consumed soy or traditional pretzels (50 ± 2 g available carbohydrates) to determine the GI and II of both products. Blood glucose and insulin responses were monitored for 2 h after consumption and compared to a glucose reference. It was found that a consumer-acceptable soy soft pretzel had a lower mean (±SD) GI than its traditional counterpart: 39.1 (±20.4) for soy and 66.4 (±15.3) for wheat, (p = 0.002). However, soy addition did not statistically affect II (p = 0.15), or satiety (p = 0.91). In conclusion, a nutrient-dense soy pretzel formulation with 27.3% of wheat flour replaced by soy ingredients had attenuated postprandial glycemia without significantly affecting insulinemia or satiety in healthy adults.

The temporal fate of drugs in decomposing porcine tissue.

Drug levels in decomposed individuals are difficult to interpret. Concentrations of 16 drugs were monitored in tissues (blood, brain, liver, kidney, muscle, and soil) from decomposing pigs for 1 week. Pigs were divided into groups (n = 5) with each group receiving four drugs. Drug cocktails were prepared from pharmaceutical formulations. Intracardiac pentobarbital sacrifice was 4 h after dosing, with tissue collection at 4, 24, 48, 96, and 168 h postdosing. Samples were frozen until assay. Detection and quantitation of drugs were through solid phase extraction followed by gas chromatograph/mass spectrometer analysis. Brain and kidneys were not available after 48 h; liver and muscle persisted for 1 week. Concentration of drugs increased during decomposition. During 1 week of decomposition, muscle showed average levels increasing but concentrations in liver were increased many fold, compared to muscle. Attempting to interpret drug levels in decomposed bodies may lead to incorrect conclusions about cause and manner of death.

Ligand-induced changes in the structure and dynamics of Escherichia coli peptide deformylase.

Peptide deformylase (PDF) is an enzyme that is responsible for removing the formyl group from nascently synthesized polypeptides in bacteria, attracting much attention as a potential target for novel antibacterial agents. Efforts to develop potent inhibitors of the enzyme have progressed on the basis of classical medicinal chemistry, combinatorial chemistry, and structural approaches, yet the validity of PDF as an antibacterial target hangs, in part, on the ability of inhibitors to selectively target this enzyme in favor of structurally related metallohydrolases. We have used (15)N NMR spectroscopy and isothermal titration calorimetry to investigate the high-affinity interaction of EcPDF with actinonin, a naturally occurring potent EcPDF inhibitor. Backbone amide chemical shifts, residual dipolar couplings, hydrogen-deuterium exchange, and (15)N relaxation reveal structural and dynamic effects of ligand binding in the immediate vicinity of the ligand-binding site as well as at remote sites. A comparison of the crystal structures of free and actinonin-bound EcPDF with the solution data suggests that most of the consequences of the ligand binding to the protein are lost or obscured during crystallization. The results of these studies improve our understanding of the thermodynamic global minimum and have important implications for structure-based drug design.