Predictive value of PSA velocity over early clinical and pathological parameters in patients with localized prostate cancer who undergo radical retropubic prostatectomy

OBJECTIVES: To analyze the behavior of the prostate specific antigen velocity (PSAV) in localized prostate adenocarcinoma. MATERIALS AND METHODS: We conducted a retrospective study of 500 men who had localized prostate adenocarcinoma, who underwent radical retropubic prostatectomy between January 1986 and December 1999. The PSAV was calculated for each patient and subsequently, the values were correlated with 5 groups: age, initial PSA value, clinical stage, tumor volume and Gleason score. RESULTS: The behavior of PSAV presented statistic significance with an increment between 1.3 ng/mL and 9.6 ng/mL, ranging from 38.6% and 59.8% when compared with the initial PSA value (p < 0.0001), clinical stage (p = 0.0002), tumor volume (p < 0.0001) and Gleason score (p = 0.0009). CONCLUSION: PSAV up to 2.5 ng/mL/year is associated with factors of good prognosis, such as initial PSA below 10 mg/mL, clinical stage T1, tumor volume below 20% and Gleason score lower than 7.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Division of UrologyUNIFESP, EPM, Division of UrologySciEL

Preparation and evaluation of PEG-coated zein nanoparticles for oral drug delivery purposes

The aim was to produce PEG-coated nanoparticles (NP-PEG), with mucus-permeating properties, for oral drug delivery purposes by using simple procedures and regulatory-approved compounds in order to facilitate a po- tential clinical development. For this purpose, zein nanoparticles were prepared by desolvation and, then, coated by incubation with PEG 35,000. The resulting nanocarriers displayed a mean size of about 200 nm and a negative zeta potential. The presence of PEG on the surface of nanoparticles was evidenced by electron microscopy and confirmed by FTIR analysis. Likely, the hydrophobic surface of zein nanoparticles (NP) was significantly reduce by their coating with PEG. This increase of the hydrophilicity of PEG-coated nanoparticles was associated with an important increase of their mobility in pig intestinal mucus. In laboratory animals, NP-PEG (fluorescently labelled with Lumogen® Red 305) displayed a different behavior when compared with bare nanoparticles. After oral administration, NP appeared to be trapped in the mucus mesh, whereas NP-PEG were capable of crossing the protective mucus layer and reach the epithelium. Finally, PEG-coated zein nanoparticles, prepared by a simple and reproducible method without employing reactive reagents, may be adequate carriers for promoting the oral bioavailability of biomacromolecules and other biologically active compounds with low permeability propertie

Zein-based nanospheres and nanocapsules for the encapsulation and oral delivery of quercetin

In this study, the ability of zein nanospheres (NS) and zein nanocapsules containing wheat germ oil (NC) to enhance the bioavailability and efficacy of quercetin was evaluated. Both types of nanocarriers had similar physico-chemical properties, including size (between 230 and 250 nm), spherical shape, negative zeta potential, and surface hydrophobicity. However, NS displayed a higher ability than NC to interact with the intestinal epithelium, as evidenced by an oral biodistribution study in rats. Moreover, both types of nanocarriers offered similar loading efficiencies and release profiles in simulated fluids. In C. elegans, the encapsulation of quercetin in nanospheres (Q-NS) was found to be two twice more effective than the free form of quercetin in reducing lipid accumulation. For nanocapsules, the presence of wheat germ oil significantly increased the storage of lipids in C. elegans; although the incorporation of quercetin (Q-NC) significantly counteracted the presence of the oil. Finally, nanoparticles improved the oral absorption of quercetin in Wistar rats, offering a relative oral bioavailability of 26% and 57% for Q-NS and Q-NC, respectively, compared to a 5% for the control formulation. Overall, the study suggests that zein nanocarriers, particularly nanospheres, could be useful in improving the bioavailability and efficacy of quercetin

Association between diet-quality scores, adiposity, total cholesterol and markers of nutritional status in European adults: findings from the Food4Me study

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index, HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean Diet Score, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry, objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids, and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants (n = 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men (p < 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index (p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour (p trend < 0.05). We observed no association between DQS and TC. To conclude, higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Objectively measured physical activity in european adults: cross-sectional findings from the Food4Me study

Introduction Physical inactivity has been estimated to be responsible for more than 5.3 million deaths worldwide [1]. Moreover, among European men and women, approximately 7.3% of all deaths in 2008 might be attributable to inactivity compared with 3.7% to obesity [2] and there is strong evidence to suggest that even small increases in physical activity (PA) would lower the risk for many non-communicable diseases [1–3]. Yet, levels of PA across populations remain low [4]. To tackle this public health issue, the US Centers for Disease Control and Prevention and the American College of Sports Medicine produced standardized PA guidelines 20 years ago [5]. Since then, the World Health Organization (WHO), the European Union, and most countries around the world, have included PA guidelines in their health policies. Guidelines for Americans and Europeans have been updated to include recommendations for adolescents and for older adults [6–9]. For adults aged 18–64 years old, the WHO recommends a minimum of 150 min of moderate intensity PA per week, 75 min of vigorous intensity PA or an equivalent amount of moderate and vigorous PA (MVPA) [9]. In 2008, 34.8% of adults 15 years or older were insufficiently active in Europe [4]. Regular surveillance is needed to update these prevalence estimates and to evaluate the effectiveness of PA policies and promotion programs in European countries. In this context, the objective assessment of PA is a key issue. Prevalence of physical inactivity has been mainly derived from self-reported measures such as the Baecke questionnaire [10] or the International Physical Activity Questionnaire (IPAQ) [11]. These questionnaires have been, and still are, widely used due to their simple administration and low cost [12]. However, PA is frequently misreported, which leads to considerable measurement error [13–15]. Accelerometers offer a potential solution because they measure PA objectively. Given that they are small and easy to wear, store data up to several weeks and are acceptable in terms of reliability, these devices are now used increasingly in large studies to assess PA in children, adolescents and adults [16]. Although some European countries have reported adherence to PA guidelines using accelerometers in large cohorts [17–19], comparisons between European countries measured according to the same standardized protocols and concurrently are lacking. Between 2012 and 2014, PA was assessed objectively by accelerometry in the participants of the Food4Me Proof-of-Principle (PoP) study. The Food4Me Study was a web-based randomized controlled trial on personalized nutrition, across seven European countries: Germany, Greece, Ireland, The Netherlands, Poland, Spain and the United Kingdom. The aim of the current paper is to describe and compare PA in adults from these countries, and evaluate adherence to PA guidelines, using baseline data from the Food4Me PoP study

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

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

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