Capillary electrophoretic separation of nanoparticles

In the present work, CdSe nanocrystals (NCs) synthesized with a trioctylphosphine surface passivation layer were modified using amphiphilic molecules to form a surface bilayer capable of providing stable NCs aqueous solutions. Such modified nanocrystals were used as a test solute in order to analyze new electrophoretic phenomena, by applying a micellar plug as a separation tool for discriminating nanocrystals between micellar and micelle-free zones during electrophoresis. The distribution of NCs between both zones depended on the affinity of nanocrystals towards the micellar zone, and this relies on the kind of surface ligands attached to the NCs, as well as electrophoretic conditions applied. In this case, the NCs that migrated within a micellar zone can be focused using a preconcentration mechanism. By modifying electrophoretic conditions, NCs were forced to migrate outside the micellar zone in the form of a typical CZE peak. In this situation, a two-order difference in separation efficiencies, in terms of theoretical plates, was observed between focused NCs (N ~ 107) and a typical CZE peak for NCs (N ~ 105). By applying the amino-functionalized NCs the preconcentration of NCs, using a micellar plug, was examined, with the conclusion that preconcentration efficiency, in terms of the enhancement factor for peak height (SEFheight) can be, at least 20. The distribution effect was applied to separate CdSe/ZnS NCs encapsulated in silica, as well as surface-modified with DNA, which allows the estimation of the yield of conjugation of biologically active molecules to a particle surface

A Non-Coding RNA Within the Rasgrf1 Locus in Mouse Is Imprinted and Regulated by Its Homologous Chromosome in Trans

BACKGROUND: Rasgrf1 is imprinted in mouse, displaying paternal allele specific expression in neonatal brain. Paternal expression is accompanied by paternal-specific DNA methylation at a differentially methylated domain (DMD) within the locus. The cis-acting elements necessary for Rasgrf1 imprinting are known. A series of tandem DNA repeats control methylation of the adjacent DMD, which is a methylation sensitive enhancer-blocking element. These two sequences constitute a binary switch that controls imprinting and represents the Imprinting Control Region (ICR). One paternally transmitted mutation, which helped define the ICR, induced paramutation, in trans, on the maternal allele. Like many imprinted genes, Rasgrf1 lies within an imprinted cluster. One of four noncoding transcripts in the cluster, AK015891, is known to be imprinted. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that an additional noncoding RNA, AK029869, is imprinted and paternally expressed in brain throughout development. Intriguingly, any of several maternally inherited ICR mutations affected expression of the paternal AK029869 transcript in trans. Furthermore, we found that the ICR mutations exert different trans effects on AK029869 at different developmental times. CONCLUSIONS/SIGNIFICANCE: Few trans effects have been defined in mammals and, those that exist, do not show the great variation seen at the Rasgrf1 imprinted domain, either in terms of the large number of mutations that produce the effects or the range of phenotypes that emerge when they are seen. These results suggest that trans regulation of gene expression may be more common than originally appreciated and that where trans regulation occurs it can change dynamically during development

Green qualities in the neighbourhood and mental health - results from a longitudinal cohort study in Southern Sweden

Background: Poor mental health is a major issue worldwide and causality is complex. For diseases with multifactorial background synergistic effects of person-and place-factors can potentially be preventive. Nature is suggested as one such positive place-factor. In this cohort study we tested the effect of defined green qualities (Serene, Space, Wild, Culture, Lush) in the environment at baseline on mental health at follow-up. We also studied interaction effects on mental health of those place factors and varied person factors (financial stress, living conditions, and physical activity). Methods: Data on person factors were extracted from a longitudinal (years 1999/2000 and 2005) population health survey (n = 24945). The participants were geocoded and linked to data on green qualities from landscape assessments, and stored in the Geographical Information System (GIS). Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated, and multivariate logistic analyses were performed. Results: Mental health was not affected by access to the chosen green qualities, neither in terms of amount nor in terms of any specific quality. However, we found a reduced risk for poor mental health at follow-up among women, through a significant interaction effect between physical activity and access to the qualities Serene or Space. For men the tendencies were similar, though not significant. Regarding the other three green qualities, as well as amount of qualities, no statistically certain synergistic effects were found. Likewise, no significant synergies were detected between green qualities and the other person-factors. Only advanced exercise significantly reduced the risk for poor mental health among women, but not for men, compared to physical inactivity. Conclusions: The results do not directly support the hypothesis of a preventive mental health effect by access to the green qualities. However, the additive effect of serene nature to physical activity contributed to better mental health at follow-up. This tendency was equal for both sexes, but statistically significant only for women. Objective landscape assessments may be important in detangling geographic determinants of health. This study stresses the importance of considering interaction effects when dealing with disorders of multifactorial background

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Influence of aerobic fitness on gastrointestinal barrier integrity and microbial translocation following a fixed-intensity military exertional heat stress test

Purpose: Exertional-heat stress adversely disrupts gastrointestinal (GI) barrier integrity, whereby subsequent microbial translocation (MT) can result in potentially serious health consequences. To date, the influence of aerobic fitness on GI barrier integrity and MT following exertional-heat stress is poorly characterised. Method: Ten untrained (UT; VO2max = 45 ± 3 ml·kg−1·min−1) and ten highly trained (HT; VO2max = 64 ± 4 ml·kg−1·min−1) males completed an ecologically valid (military) 80-min fixed-intensity exertional-heat stress test (EHST). Venous blood was drawn immediately pre- and post-EHST. GI barrier integrity was assessed using the serum dual-sugar absorption test (DSAT) and plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using plasma Bacteroides/total 16S DNA. Results: UT experienced greater thermoregulatory, cardiovascular and perceptual strain (p < 0.05) than HT during the EHST. Serum DSAT responses were similar between the two groups (p = 0.59), although Δ I-FABP was greater (p = 0.04) in the UT (1.14 ± 1.36 ng·ml−1) versus HT (0.20 ± 0.29 ng·ml−1) group. Bacteroides/Total 16S DNA ratio was unchanged (Δ; -0.04 ± 0.18) following the EHST in the HT group, but increased (Δ; 0.19 ± 0.25) in the UT group (p = 0.05). Weekly aerobic training hours had a weak, negative correlation with Δ I-FABP and Bacteroides/total 16S DNA responses. Conclusion: When exercising at the same absolute workload, UT individuals are more susceptible to small intestinal epithelial injury and MT than HT individuals. These responses appear partially attributable to greater thermoregulatory, cardiovascular, and perceptual strain

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 .)

Standards and Protocols for Data Acquisition and Reporting for Studies of the Electrochemical Reduction of Carbon Dioxide

Objective evaluation of the performance of electrocatalysts for CO2 reduction has been complicated by a lack of standardized methods for measuring and reporting activity data. In this perspective, we advocate that standardizing these practices can aid in advancing research efforts toward the development of efficient and selective CO2 reduction electrocatalysts. Using information taken from experimental studies, we identify variables that influence the measured activity of CO2 reduction electrocatalysts and propose procedures to account for these variables in order to improve the accuracy and reproducibility of reported data. We recommend that catalysts be measured under conditions which do not introduce artifacts from impurities, from either the electrolyte or counter electrode, and advocate the acquisition of data measured in the absence of mass transport effects. Furthermore, measured rates of electrochemical reactions should be normalized to both the geometric electrode area as well as the electrochemically active surface area to facilitate the comparison of reported catalysts with those previously known. We demonstrate that, when these factors are accounted for, the CO2 reduction activities of Ag and Cu measured in different laboratories exhibit little difference. Adoption of the recommendations presented in this perspective would greatly facilitate the identification of superior catalysts for CO2 reduction arising solely from changes in their composition and pretreatment