Продукты ограниченного протеолиза: подходы к обнаружению и диагностические возможности в оценке тяжести патологии при эндогенной интоксикации

ПРОДУКТЫ ОГРАНИЧЕННОГО ПРОТЕОЛИЗАПРОТЕИНАЗО-ИНГИБИТОРНАЯ СИСТЕМАОТРАВЛЕНИЕ /ДИАГН /ОСЛЭНДОГЕННАЯ ИНТОКСИКАЦИЯ /ДИАГН /ОСЛСРЕДНЕМОЛЕКУЛЯРНАЯ ПЕПТИДНАЯ ФРАКЦИЯПАТОЛОГИЧЕСКИЕ ПРОЦЕССЫЛАБОРАТОРНЫЕ МЕТОДЫ И ПРОЦЕДУРЫБЕЛКОВО-ПЕПТИДНЫЕ КОМПОНЕНТ

Plastic Population Effects and Conservative Leaf Traits in a Reciprocal Transplant Experiment Simulating Climate Warming in the Himalayas

Climate warming poses considerable challenges for alpine plant species, especially for competitively inferior ones with resource-conservative adaptations to cold climates. The Himalayas are warming at rates considerably faster than the global average, so it is particularly important to assess how and through which mechanisms alpine plant species are affected there. We employed a demographic approach in a climate change experiment, where vegetation turfs were transplanted reciprocally between the central parts of the study species’ (Viola biflora L. var. rockiana) range and the warmer range margin, with a temperature difference of ca. 1°C. In addition, turfs were also transplanted outside the range to warmer habitats, simulating two different scenarios of climate warming, +1 and +4°C. Transplanting to warmer sites negatively impacted population growth rates (λ), survival and clonality, but did not affect growth and fecundity, while the productivity of the plant community increased. The reciprocal transplants to the colder habitat showed the opposite effects, for both V. biflora and the plant community, indicating plastic responses of the study species, driven by changes in plant–plant competition. However, the leaf traits underlying the modeled population growth rates were origin-site specific and not affected by the climate-change treatments over the study period, suggesting local adaptation of growth form to competition in the warmer range margin, and to climate adversity in the colder range center. The transplants outside the present species’ range showed consistently stronger reductions in population growth rate and survival, with mortality of 90–100% in the +4°C treatment. This illustrates that climatic changes beyond species’ present climatic ranges pose a serious risk for range contraction and extinction for Himalayan alpine species in the near future. As V. biflora seems mostly limited by competition under warming, its persistence in a future climate may become increasingly dependent on keeping competitive effects from the surrounding community low, for instance by management interventions like grazing and mowing

Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines.The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations.A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low- to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders.This guideline emphasizes the paucity of evidence of benefit - and potential for harm - of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI

Structural Changes are More Important than Compositional Changes in Driving Biomass Loss in Ugandan Forest Fragments

Aboveground biomass (AGB) contained in privately-owned forests is less frequently measured than in forest reserves despite their greater likelihood of degradation. We demonstrate how density changes in contrast to species compositional changes have driven AGB changes in privately-owned fragments in Uganda over two decades. Data on tree assemblages in fragments were obtained by re-sampling a 1990 dataset in 2010 and AGB estimated using generalised allometric equation that incorporates diameter at breast height (DBH) and species-specific wood density. AGB were highly variable between fragments and over time. Structural changes contributed a higher proportion of change in AGB than species compositional changes in all forests. Non-pioneer species constituted over 50% of AGB in reserve forest, in contrast to private forests where pioneer species dominated. Our study demonstrates the potential of private forests to hold comparable AGB to plantation. Reduction in exploitation pressure is required if fragments are to mitigate carbon emissions

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis

Background: For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. Methods: A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Five studies including 1116 patients reported major complications in 25 (4.9 per cent) of 510 patients in the antibiotic and 41 (8.4 per cent) of 489 in the appendicectomy group: risk difference -2.6 (95 per cent c.i. -6.3 to 1.1) per cent (low-quality evidence). Minor complications occurred in 11 (2.2 per cent) of 510 and 61 (12.5 per cent) of 489 patients respectively: risk difference -7.2 (-18.1 to 3.8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8.2 (95 per cent c.i. 5.2 to 11.8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22.6 (15.6 to 30.4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. Conclusion: The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value-and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.Peer reviewe

Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus : systematic review and meta-analysis of randomised and non-randomised studies

Objective To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Eligibility criteria Randomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs. Data collection and analysis Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. A modified Cochrane tool for randomised controlled trials and a modified version of the Newcastle-Ottawa scale for observational studies were used to assess bias. We pooled data from randomised controlled trials using Peto odds ratios, and conducted four prespecified subgroup analyses and a post hoc subgroup analysis. Because of variation in outcome measures and forms of data, we describe the results of observational studies without a pooled analysis. Results 60 studies (n=353 639), consisting of 55 randomised controlled trials (n=33 350) and five observational studies (three retrospective cohort studies, and two case-control studies; n=320 289) were included. Pooled estimates of 55 randomised controlled trials (at low or moderate risk of bias involving 37 pancreatitis events, raw event rate 0.11%) did not suggest an increased risk of pancreatitis with incretins versus control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1 agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses according to the type of control, mode, duration of treatment, and individual incretin agents suggested no differential effect by subgroups, and sensitivity analyses by alternative statistical modelling and effect measures did not show important differences in effect estimates. Three retrospective cohort studies (moderate to high risk of bias, involving 1466 pancreatitis events, raw event rate 0.47%) also did not suggest an increased risk of pancreatitis associated with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and 0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to 1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls) also suggested no significant association (adjusted odds ratio 0.98, 0.69 to 1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of bias, however, suggested that the use of either exenatide or sitagliptin was associated with significantly increased odds of acute pancreatitis (use within two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13). Conclusions The available evidence suggests that the incidence of pancreatitis among patients using incretins is low and that the drugs do not increase the risk of pancreatitis. Current evidence, however, is not definitive, and more carefully designed and conducted observational studies are warranted to definitively establish the extent, if any, of increased risk

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes : systematic review and meta-analysis of randomised and observational studies

Objectives To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Eligibility criteria Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Data collection and analysis Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Results Eligible studies included 43 trials (n=68 775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1 777 358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15 701 v 33/12 591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18 554 v 552/18 474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. Conclusions The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use

Doubtful outcome of the validation of the Rome II questionnaire: validation of a symptom based diagnostic tool

<p>Abstract</p> <p>Background</p> <p>Questionnaires are used in research and clinical practice. For gastrointestinal complaints the Rome II questionnaire is internationally known but not validated. The aim of this study was to validate a printed and a computerized version of Rome II, translated into Swedish. Results from various analyses are reported.</p> <p>Methods</p> <p>Volunteers from a population based colonoscopy study were included (n = 1011), together with patients seeking general practice (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67). The questionnaire consists of 38 questions concerning gastrointestinal symptoms and complaints. Diagnoses are made after a special code. Our validation included analyses of the translation, feasibility, predictability, reproducibility and reliability. Kappa values and overall agreement were measured. The factor structures were confirmed using a principal component analysis and Cronbach's alpha was used to test the internal consistency.</p> <p>Results and Discussion</p> <p>Translation and back translation showed good agreement. The questionnaire was easy to understand and use. The reproducibility test showed kappa values of 0.60 for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for the predictability when the diagnoses by the questionnaire were compared to the diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and 0.49 and 86% for IBS. Corresponding figures for the agreement between the printed and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76 and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS 0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly validated before even if diagnoses made by the Rome criteria have been compared to diagnoses made in clinical practice.</p> <p>Conclusion</p> <p>The accuracy of the Swedish version of the Rome II is of doubtful value for clinical practice and research. The results for reproducibility and reliability were acceptable but the outcome of the predictability test was poor with IBS as an exception. The agreement between the digital and the paper questionnaire was good.</p

Buffering effects of soil seed banks on plant community composition in response to land use and climate

Aim Climate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life‐history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this. Location Europe. Time period 1978–2014. Major taxa studied Flowering plants. Methods Using a space‐for‐time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2,796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient. Results Soil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land‐use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer. Main conclusions High seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life‐history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time‐lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected

Multiscale mapping of plant functional groups and plant traits in the High Arctic using field spectroscopy, UAV imagery and Sentinel-2A data

The Arctic is warming twice as fast as the rest of the planet, leading to rapid changes in species composition and plant functional trait variation. Landscape-level maps of vegetation composition and trait distributions are required to expand spatially-limited plot studies, overcome sampling biases associated with the most accessible research areas, and create baselines from which to monitor environmental change. Unmanned aerial vehicles (UAVs) have emerged as a low-cost method to generate high-resolution imagery and bridge the gap between fine-scale field studies and lower resolution satellite analyses. Here we used field spectroscopy data (400-2500 nm) and UAV multispectral imagery to test spectral methods of species identification and plant water and chemistry retrieval near Longyearbyen, Svalbard. Using the field spectroscopy data and Random Forest analysis, we were able to distinguish eight common High Arctic plant tundra species with 74% accuracy. Using partial least squares regression (PLSR), we were able to predict corresponding water, nitrogen, phosphorus and C:N values (r (2) = 0.61-0.88, RMSEmean = 12%-64%). We developed analogous models using UAV imagery (five bands: Blue, Green, Red, Red Edge and Near-Infrared) and scaled up the results across a 450 m long nutrient gradient located underneath a seabird colony. At the UAV level, we were able to map three plant functional groups (mosses, graminoids and dwarf shrubs) at 72% accuracy and generate maps of plant chemistry. Our maps show a clear marine-derived fertility gradient, mediated by geomorphology. We used the UAV results to explore two methods of upscaling plant water content to the wider landscape using Sentinel-2A imagery. Our results are pertinent for high resolution, low-cost mapping of the Arctic.Peer reviewe