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Background Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Methods and Results We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity–Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (β‐2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein–outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), or high‐sensitivity cardiac troponin. Conclusions Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON‐HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. Registration URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Background: The incidence and prevalence of inflammatory bowel diseases (IBD) are increasing around the world, especially in Western countries. The objective of this study was to evaluate the health habits of healthy controls and individuals with IBDs to identify possible risk factors for IBD development. Methods: A case-control study was conducted among Spanish participants over 18 years of age. A self-administered questionnaire was completed by subjects to collect information on several sociodemographic variables and habits, such as the consumption of tobacco, alcohol, antibiotics, nonsteroidal anti-inflammatory agents and macronutrients; anxiety and depression; and quality of life. Results: The main risk factors identified were age; living in an urban environment; anxiety; and excessive consumption of proteins, carbohydrates and fats. In addition, the consumption of fibre had a preventive effect against IBD development. Conclusions: Age, anxiety and living in urban areas pose a risk of suffering from IBD, as does the excessive consumption of certain macronutrients. However, the consumption of fibre has a protective effect on the development of some IBD types.

Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. Results The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Conclusion Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

Abstract The pathogenesis and clinical heterogeneity of Parkinson’s disease (PD) have been evaluated from molecular, pathophysiological, and clinical perspectives. High-throughput proteomic analysis of cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, this is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers and 154 LRRK2 + mutation carriers), 534 controls, and 4135 proteins analyzed. Combining CSF aptamer-based proteomics with genetics we determined protein quantitative trait loci (pQTLs). Analyses of pQTLs together with summary statistics from the largest PD genome wide association study (GWAS) identified 68 potential causal proteins by Mendelian randomization. The top causal protein, GPNMB, was previously reported to be upregulated in the substantia nigra of PD patients. We also compared the CSF proteomes of patients and controls. Proteome differences between GBA + patients and unaffected GBA + controls suggest degeneration of dopaminergic neurons, altered dopamine metabolism and increased brain inflammation. In the LRRK2 + subcohort we found dysregulated lysosomal degradation, altered alpha-synuclein processing, and neurotransmission. Proteome differences between idiopathic patients and controls suggest increased neuroinflammation, mitochondrial dysfunction/oxidative stress, altered iron metabolism and potential neuroprotection mediated by vasoactive substances. Finally, we used proteomic data to stratify idiopathic patients into “endotypes”. The identified endotypes show differences in cognitive and motor disease progression based on previously reported protein-based risk scores.Our findings not only contribute to the identification of new therapeutic targets but also to shape personalized medicine in CNS neurodegeneration.

Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD). CD is a health problem in Western countries such as the US and European nations and is an idiopathic disease; however, certain cases of CD have been associated with intestinal dysbiosis. A systematic review with a meta-analysis was carried out to determine the efficacy of a diet rich in fiber with or without cointervention to improve remission rates for CD. The literature in the PubMed, Scopus, Web of Science, and ClinicalTrials databases was reviewed. The quality of the studies was evaluated using the Johanna Briggs Institute (JBI) scale. This review was conducted in accordance with the structure outlined in the PRISMA statement. In addition, a meta-analysis was performed with a 95% confidence interval (CI) and a random effects model. Eleven studies were included, totaling 2389 patients with CD. Applying a diet rich in fiber with or without the administration of routine therapies improved CD remission rates. Data regarding CD activity, remission time, and adverse effects derived from fiber consumption were analyzed. Consumption of fiber in the diet could improve remission rates for CD patients who receive or do not receive other treatment to maintain remission.

The goal of this study is to estimate the state of consciousness known as Flow, which is associated with an optimal experience and can indicate a person’s efficiency in both personal and professional settings. To predict Flow, we employ artificial intelligence techniques using a set of variables not directly connected with its construct. We analyse a significant amount of data from psychological tests that measure various personality traits. Data mining techniques support conclusions drawn from the psychological study. We apply linear regression, regression tree, random forest, support vector machine, and artificial neural networks. The results show that the multi-layer perceptron network is the best estimator, with an MSE of 0.007122 and an accuracy of 88.58%. Our approach offers a novel perspective on the relationship between personality and the state of consciousness known as Flow.

This work presents the results of a study whose aim is to detect systematic errors about the concept of force among freshmen students. The researchers analysed the results of the Force Concept Inventory test, which was administered to two different groups of students. The results show that, although there were significant performance variations between the two groups, they, nonetheless, shared common incorrect answers that were consistently triggered by the same misconceptions. The analysis proposed in this paper could also be applied in other universities to reveal the students' "a priori" mindset in Newtonian mechanics and serve as a guideline for developing effective computer simulations or other tools. (Contains 2 tables and 5 figures.)

In this work we present an overview of the undergraduate online Physics course that we have implemented in the Moodle platform. This course has been developed as an enhancement of the face-to-face courses. The aim of this course is to create an online learning community which helps both teachers and students to have a virtual space where we can share knowledge through different kinds of supervised activities, chats and forums. As we will show in this paper, the students' response to this initiative has been very good: the online Physics course helps them to reinforce their abilities and knowledge. (Contains 10 figures and 1 table.)

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.

Purpose: To compare the initial mechanical characteristics of 4 systems used to fix tendons to the femur during anterior cruciate ligament reconstruction.Methods: A total of 32 porcine femurs were used to study the following fixation systems: Bioabsorbable interference screw (Stryker, Kalamazoo, MI), Bio-Transfix Cross-pin (Arthrex, Naples, FL), Biosteon Cross-pin (Stryker), and a fixation technique based on wrapping the graft around the femoral condyle itself, thus allowing it to be fixed in place without the use of any hardware. The mechanical characteristics of each system were obtained by a preconditioned failure tensile test.Results: The yield load values (990.9 +/- 242.6 N for Bio-Transfix, 905.1 +/- 158.8 N for Biosteon Cross-pin, 684.4 +/- 119.7 N for the without-hardware system (WHS), and 369.4 +/- 120.1 N for the interference screw) revealed significant differences between the techniques that used cross-pins and the other 2 techniques (P < .006) on the one hand, and between the without hardware technique and the interference screw (P < .004) on the other. The stiffness of the 2 cross-pin fixation systems (117.6 +/- 22.5 N for Bio-Transfix and 112.6 +/- 22.5 N for Biosteon) was greater (P < .01) than those of the other systems (79.4 +/- 15.2 N for the WHS and 68.5 +/- 13 N for the interference screw).Conclusions: The initial biomechanical properties of the 2 cross-pin fixation systems proved to be superior to those of the other 2 systems studied. The WHS fixation system exhibited better mechanical properties than its interference screw counterpart.Clinical Relevance: The better initial mechanical characteristics encountered using the Bio-Transfix and Biosteon Cross-pin systems indicate that these systems are better equipped to bear the loads generated by aggressive rehabilitation. The WHS fixation system provides an alternative to interference screw fixation. [ABSTRACT FROM AUTHOR]