Polyelectrolyte stabilized nanodiamond dispersions

Colloidal stability of negatively charged nanodiamonds (ND) has been realized with the help of double hydrophilic block copolymers poly(ethylene oxide)-block-poly(dimethylaminoethyl methacrylate)-dodecyl (PEO-bPDMAEMA-C12). The polymers were synthesized through RAFT polymerization of DMAEMA with a PEO macromonomer carrying trithiocarbonate and dodecyl end-groups. The NDs and the polymers were complexed by mixing them in different ratios. In addition to the amount of polymers, the effect of the detailed structure of the polymer was of interest and thus, also polymers with different lengths of the PEO-block were synthesized, as well as a block copolymer without the dodecyl end-group. The composition of the polymer, as well as the complexation conditions were varied to find the route to stable nanoparticles. The optimized complexation method gave colloidally stable ND particles with positively charged PDMAEMA coronas. The colloids were stable at room temperature and also in saline solutions up to 0.154 M NaCl.Peer reviewe

Load-Bearing Biomedical Applications of Diamond-Like Carbon Coatings - Current Status

The current status of diamond-like carbon (DLC) coatings for biomedical applications is reviewed with emphasis on load-bearing coatings. Although diamond-like carbon coating materials have been studied for decades, no indisputably successful commercial biomedical applications for high load situations exist today. High internal stress, leading to insufficient adhesion of thick coatings, is the evident reason behind this delay of the break-through of DLC coatings for applications. Excellent adhesion of thick DLC coatings is of utmost importance for load-bearing applications. According to this review superior candidate material for articulating implants is thick and adherent DLC on both sliding surfaces. With the filtered pulsed arc discharge method, all the necessary requirements for the deposition of thick and adherent DLC are fulfilled, provided that the substrate material is selected properly

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms

The Impact of Intensive Grass Cultivation on Biodiversity - Review

Luken kirjat, raportit, oppaat ja esitteet201

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892

Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1-2 as good and 3-5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094-0.91) ng/ml in controls, 0.79 (0.37-1.6) ng/ml in patients at ICU admission (PPeer reviewe

Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest

Aim: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-ofhospital cardiac arrest (OHCA) of various aetiologies. Methods: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. Results: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) mg/L vs. 8.5 (5.8- 13.2) mg/L at 24 h and 20.4 (8.1-56.6) mg/L vs. 8.2 (5.9-12.1) mg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. Conclusion: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.Peer reviewe

Effects of a Two-Year Home-Based Exercise Training Program on Oxidized LDL and HDL Lipids in Coronary Artery Disease Patients with and without Type-2 Diabetes

We investigated the effect of two-year home-based exercise training program on oxidized low-density lipoprotein LDL (ox-LDL) and high-density lipoprotein HDL (ox-HDL) lipids in patients with coronary artery disease (CAD), both with and without type-2 diabetes (T2D). Analysis of lipoprotein-oxidized lipids was based on the determination of baseline conjugated dienes in lipoprotein lipids. In order to study the effect of an exercise load on ox-LDL and ox-HDL lipids patients in both CAD and CAD + T2D intervention, groups were divided in three based on exercise load (high, medium, and low). During the two-year home-based exercise training program, the study showed that only higher training volume resulted in a decreased concentration of ox-LDL, while the two groups with lower training volumes showed no change. This result indicates that the training load needs to be sufficiently high in order to decrease the concentration of atherogenic ox-LDL lipids in patients with CAD and CAD + T2D. Interestingly, the concentration of ox-HDL did not change in any of the subgroups. This could indicate that the lipid peroxide-transporting capacity of HDL, suggested by results from exercise training studies in healthy adults, may not function similarly in CAD patients with or without T2D. Moreover, the lipid-lowering medication used may have had an influence on these results