Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Bond Strength of Adhesive Systems to Calcium Silicate-Based Materials: A Systematic Review and Meta-Analysis of In Vitro Studies

Since the adhesion of resin composites to calcium silicate-based cement is considered challenging. Therefore, the best adhesion strategy should be indicated. This review aimed to assess the effect of different adhesive systems on the bond strength of resin composite to calcium silicate-based cement through a systematic review and meta-analysis. The subsequent PICOS framework used was: population, calcium silicate-based cement; intervention, use of self-etch adhesive systems; control, use of total-etch adhesive systems; outcome, bond strength; study design, in vitro studies. The literature search was conducted independently by two reviewers up to 18 February 2021. Electronic databases (PubMed, ISI Web of Science, SciELO, Scopus, and Embase) were searched for applicable articles. In vitro manuscripts studying the effect of adhesive systems on the bond strength of calcium silicate-based cement were considered. The meta-analyses were performed using Review Manager Software version 5.3.5 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Bond strength comparisons were made considering the type of calcium silicate-based cement (Mineral Trioxide Aggregate (MTA), Biodentine&trade;, or TheraCal LC&reg;). A p-value &lt; 0.05 was considered statistically significant. A total of 7321 studies were retrieved in databases searched. After full-text evaluation, 37 eligible papers were assessed for qualitative analysis, leaving a total of 22 papers for the quantitative analysis. According to the meta-analysis, the bond strength values of resin composite materials to MTA and TheraCal LC&reg; cement were favored when a total-etch adhesive system was used (p &le; 0.02). On the other hand, the meta-analysis of the bond strength of resin-based materials to Biodentine&trade; calcium silicate-based cement was similar between both approaches (p = 0.12). The in vitro evidence suggests that the bond strength of resin-based materials to both MTA and TheraCal LC&reg; cement was preferred by using the total-etch adhesive strategy. However, when bonding to Biodentine&trade;, the use of self-etch or total-etch strategies displayed promising results. Given the lack of evidence related to the chemical interaction of self-etch adhesive materials with the bioceramics, if self-etch adhesives are used for bonding resin-based restorations to calcium silicate-based cement, a pretreatment with phosphoric acid could be recommended

Morphological and population genomic evidence that human faces have evolved to signal individual identity

Facial recognition plays a key role in human interactions, and there has been great interest in understanding the evolution of human abilities for individual recognition and tracking social relationships. Individual recognition requires sufficient cognitive abilities and phenotypic diversity within a population for discrimination to be possible. Despite the importance of facial recognition in humans, the evolution of facial identity has received little attention. Here we demonstrate that faces evolved to signal individual identity under negative frequency-dependent selection. Faces show elevated phenotypic variation and lower between-trait correlations compared to other traits. Regions surrounding face-associated SNPs show elevated diversity consistent with frequency-dependent selection. Genetic variation maintained by identity signaling tends to be shared across populations and, for some loci, predates the origin of Homo sapiens. Studies of human social evolution tend to emphasize cognitive adaptations but we show that social evolution has shaped patterns of human phenotypic and genetic diversity as well