Comparison of automated infarct core volume measures between non-contrast computed tomography and perfusion imaging in acute stroke code patients evaluated for potential endovascular treatment

Introduction: Patients with small core infarction and salvageable penumbra are likely to benefit from endovascular treatment (EVT). As computed tomography perfusion imaging (CTP) is not always available 24/7 for patient selection, many patients are transferred to stroke centers for CTP. We compared automatically measured infarct core volume (NCCTcore) from the non-contrast computed tomography (NCCT) with ischemic core volume (CTPcore) from CTP and the outcome of EVT to clarify if NCCTcore measurement alone is sufficient to identify patients that benefit from transfer to stroke centers for EVT. Patients and methods: We included all consecutive stroke-code patients imaged with both NCCT and CTP at Helsinki University Hospital during 9/2016-01/2018. NCCTcore and CTPcore volumes were automatically calculated from the acute NCCT images. Follow-up infarct volume (FIV) was measured from 24 h follow-up NCCT to evaluate efficacy of EVT. To study whether NCCTcore could be used to identify patients eligible to EVT, we subgrouped patients based on NCCTcore volumes (>50 mL and > 70 mL). Results: Out of 1743 patients, baseline NCCTcore, CTPcore and follow-up NCCT was available for 288 patients. Median time from symptom onset to baseline imaging was 74 min (IQR 52-118), and time to follow-up imaging 24.15 h (22.25-26.33). Baseline NCCTcore was 20 mL (10-42), CTPcore 4 mL (0-16), and FIV 5 mL (1-49). Out of 288 patients, 23 had NCCTcore > 70 mL and 26 had CTPcore > 70 mL. NCCTcore and CTPcore performed similarly well in predicting large FIV (>70 ml). Conclusion: NCCTcore is a promising tool to identify patients that are not eligible to EVT due to large ischemic cores at baseline imaging.Peer reviewe

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

Is infarct core growth linear? Infarct volume estimation by computed tomography perfusion imaging

Objectives Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/- 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. Materials and Methods All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). Results Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p > .05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. Conclusions Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.Peer reviewe

Grain boundary corrosion in TiO2 bone scaffolds doped with group II cations

A pH drop during the inflammatory phase during bone regeneration can cause corrosion in TiO2 bone scaffolds and the loss of compressive strength. Corrosion as ion leaching and dissolution is confined to grain boundaries. Cationic doping of TiO2 showed to increase the compressive strength but increased the amount of impurities in grain boundaries as well. Therefore, this study showed the different grain boundary formation for Ca, Sr and Mg doped scaffolds and their corrosion behavior. After corrosion, the amorphous phase in grain boundaries was dissolved in all doped scaffolds. Differences occurred due to the formation of an additional crystalline phase in Sr doped scaffolds. The presence of an amorphous and crystalline phase led to an inhomogeneous dissolution in grain boundaries and a significant decrease in compressive strength already after 4 h in contact with an acidic environment. Released ions did not show any cytotoxic effect on hASCs. Mg doped TiO2 scaffolds led to sig- nificant increased osteogenic differentiation.(undefined)info:eu-repo/semantics/publishedVersio

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

Social interactions do not drive territory aggregation in a grassland songbird

Understanding the drivers of animal distributions is a fundamental goal of ecology and informs habitat management. The costs and benefits of colonial aggregations in animals are well established, but the factors leading to aggregation in territorial animals remain unclear. Territorial animals might aggregate to facilitate social behavior such as (1) group defense from predators and/or parasites, (2) cooperative care of offspring, (3) extra-pair mating, and/or (4) mitigating costs of extra-pair mating through kin selection. Using experimental and observational methods, we tested predictions of all four hypotheses in a tallgrass prairie in northeast Kansas, United States. Grasshopper Sparrow (Ammodramus savannarum) males formed clumps of territories in some parts of the site while leaving other apparently suitable areas unoccupied. Despite substantial sampling effort (653 territories and 223 nests), we found no support for any hypothesized social driver of aggregation, nor evidence that aggregation increases nest success. Our results run counter to previous evidence that conspecific interactions shape territory distributions. These results suggest one of the following alternatives: (1) the benefits of aggregation accrue to different life-history stages, or (2) the benefits of territory aggregation may be too small to detect in short-term studies and/or the consequences of aggregation are sufficiently temporally and spatially variable that they do not always appear to be locally adaptive, perhaps exacerbated by changing landscape contexts and declining population sizes

Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADα, and MO25α, in Peutz–Jeghers syndrome

Mutations in LKB1 lead to Peutz–Jeghers syndrome (PJS). However, only a subset of PJS patients harbours LKB1 mutations. We performed a mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADα, and MO25α, in 28 LKB1-negative PJS patients. No disease-causing mutations were detected in the studied genes in PJS patients from different European populations