74 research outputs found

    Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

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    <p>Abstract</p> <p>Background</p> <p>Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of α<sub>ν</sub>β<sub>3 </sub>integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets.</p> <p>Methods</p> <p>New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with α<sub>ν</sub>β<sub>3 </sub>integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition <it>in vivo </it>of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and <sup>19</sup>F MRS was performed at 11.7T. Integrated <sup>19</sup>F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with α<sub>ν</sub>β<sub>3 </sub>integrin targeted PFC nanoparticles, <sup>19</sup>F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry.</p> <p>Results</p> <p>Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control animals. Nanoparticles were successfully detected in all samples scanned at 3.0T. PECAM endothelial staining and α<sub>ν</sub>β<sub>3 </sub>integrin staining revealed the presence of neovasculature within the valve leaflets.</p> <p>Conclusion</p> <p>Integrin-targeted PFC nanoparticles specifically detect early angiogenesis in sclerotic aortic valves of cholesterol fed rabbits. These techniques may be useful for assessing atherosclerotic components of preclinical aortic valve disease in patients and could assist in defining efficacy of medical therapies.</p

    Childhood sexual trauma and subsequent parenting beliefs and behaviors

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    Using propensity-matched controls, the present study examines the long-term adjustment of women reporting Childhood Sexual Trauma (CST) at or before the age of 14 in terms of parenting efficacy and parenting behavior. Data for these analyses were obtained from mother reports and from observational protocols from a longitudinal study of low-income, rural families. The novel use of propensity-matched controls to create a control group matched on family of origin variables provides evidence that, when women with CST are compared with the matched comparison women, females who experienced CST show poorer functioning across multiple domains of parenting (sensitivity, harsh intrusiveness, boundary dissolution), but not in parenting efficacy. Follow up moderation analyses suggest that the potential effects of trauma on parenting behaviors are not attenuated by protective factors such as higher income, higher education, or stable adult relationships. Implications for interventions with childhood sexual trauma histories and directions for future study are proposed

    Tobacco Smoke Mediated Induction of Sinonasal Microbial Biofilms

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    Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than non-smokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Measurement of the bbb\overline{b} dijet cross section in pp collisions at s=7\sqrt{s} = 7 TeV with the ATLAS detector

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    Search for dark matter in association with a Higgs boson decaying to bb-quarks in pppp collisions at s=13\sqrt s=13 TeV with the ATLAS detector

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