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Impaired polymorphonuclear leukocyte (PMNL) functions contribute to increased infections and cardiovascular diseases in chronic kidney disease (CKD). Uremic toxins reduce hydrogen sulfide (H2S) levels and the anti-oxidant and anti-inflammatory effects of H2S. Its biosynthesis occurs as a side process of transsulfuration and in the disposal of adenosylhomocysteine, a transmethylation inhibitor and proposed uremic toxin. PMNL chemotaxis was measured by the under-agarose method, phagocytosis, and oxidative burst by flow cytometry in whole blood and apoptosis by determining DNA content by flow cytometry and morphological features by fluorescence microscopy. Sodium hydrogen sulfide (NaHS), diallyl trisulphide (DATS) and diallyl disulphide (DADS), cysteine, and GYY4137 were used as H2S-producing substances. Increased H2S concentrations did not affect chemotaxis and phagocytosis. NaHS primed PMNL oxidative burst activated by phorbol 12-myristate 13-acetate (PMA) or E. coli. Both DATS and cysteine significantly decreased E. coli-activated oxidative burst but had no effect on PMA stimulation. While NaHS, DADS, and cysteine attenuated PMNL apoptosis, GYY4137 decreased their viability. Experiments with signal transduction inhibitors suggest that the intrinsic apoptosis pathway is mainly involved in GYY4137-induced PMNL apoptosis and that GYY4137 and cysteine target signaling downstream of phosphoinositide 3-kinase.

Masting, the spatial synchronization of interannual variation in seed production, can enhance reproductive efficiency through positive density‐dependent processes (DD) that result in economies of scale (EOS), such as decreased pollen limitation and predator satiation in years of high reproduction.While the general occurrence of such EOS effects has been documented for masting species, few studies simultaneously investigated how spatial and temporal variation in reproduction affects pollination and predation. Furthermore, it is unclear whether the same mechanisms apply to co‐occurring species with different levels of conspecific density, pollen limitation, and seed defences.Here, we use a long‐term dataset with high spatial resolution of seed production of European beech (Fagus sylvatica), Norway spruce (Picea abies), and silver fir (Abies alba) in a primeval montane forest to investigate the relationship between reproductive effort, pollination efficiency and predispersal predation by insects.We found that, along the temporal axis, the proportion of sound (fertilized and unpredated) seeds correlated positively with annual seed production over the 14‐year study period in all three species, most strongly in beech and only weakly in silver fir. Moreover, the results show that in beech, spatial seed density interacts with plot‐wide annual seed rain to enhance DD effects on seed predation, suggesting additive effects of synchronous reproduction on fitness benefits.Synthesis: For both pollination and predispersal predation in beech and spruce, the strongest DD effects occur at low levels of reproduction and quickly reach asymptotes at higher levels, suggesting the presence of thresholds in different EOS mechanisms. As variability and synchrony in mast‐seeding are expected to decline with climate change, EOS effects driven by DD may remain stable until the threshold is reached, at which sudden declines would result in devastating effects on the availability of viable seeds for germination and recruitment. [ABSTRACT FROM AUTHOR]

Although anticoagulation therapy has evolved from non-specific drugs (i.e., heparins and vitamin K antagonists) to agents that directly target specific coagulation factors (i.e., direct oral anticoagulants, argatroban, fondaparinux), thrombosis remains a leading cause of death worldwide. Direct oral anticoagulants (i.e., factor IIa- and factor Xa-inhibitors) now dominate clinical practice because of their favorable pharmacological profile and ease of use, particularly in venous thromboembolism (VTE) treatment and stroke prevention in atrial fibrillation. However, despite having a better safety profile than vitamin K antagonists, their bleeding risk is not insignificant. This is true for all currently available anticoagulants, and a high bleeding risk is considered a contraindication to anticoagulation. As a result, ongoing research focuses on developing future anticoagulants with an improved safety profile. Several promising approaches to reduce the bleeding risk involve targeting the intrinsic (or contact activation) pathway of coagulation, with the ultimate goal of preventing thrombosis without impairing hemostasis. Based on epidemiological data on hereditary factor deficiencies and preclinical studies factor XI (FXI) emerged as the most promising candidate target. In this review, we highlight unmet clinical needs of anticoagulation therapy, outlay the rationale and evidence for inhibiting FXI, discuss FXI inhibitors in current clinical trials, conduct an exploratory meta-analysis on their efficacy and safety, and provide an outlook on the potential clinical application of these novel anticoagulants.

The article discusses the potential role of lipid-lowering drugs in preventing venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism. While VTE is a common and serious condition, it often receives less attention compared to other cardiovascular events. The study reviewed data from 45 randomized controlled trials and found that lipid-lowering therapies, particularly high-intensity statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the risk of VTE. However, the absolute risk reduction is small, and the combination of these drugs is not recommended for primary VTE prevention due to the low number needed to treat (NNT) and potential side effects. Further research is needed to evaluate the use of lipid-lowering drugs for secondary VTE prevention. [Extracted from the article]

Abstract Background Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID‐19). However, reported VTE rates differ substantially. Objectives We aimed at evaluating available data and estimating the prevalence of VTE in patients with COVID‐19. Methods We conducted a systematic literature search (MEDLINE, EMBASE, World Health Organization COVID‐19 database) to identify studies reporting VTE rates in patients with COVID‐19. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta‐analysis. Subgroup analyses were performed for different settings (intensive care unit [ICU] vs non‐ICU hospitalization and screening vs no screening) and the association of d‐dimer levels and VTE risk was explored. Results Eighty‐six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60.1% men, 19.4% ICU patients) were included in quantitative analysis. The overall VTE prevalence estimate was 14.1% (95% confidence interval [CI], 11.6‐16.9), 40.3% (95% CI, 27.0‐54.3) with ultrasound screening and 9.5% (95% CI, 7.5‐11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE prevalence of 7.9% (95% CI, 5.1‐11.2) in non‐ICU and 22.7% (95% CI, 18.1‐27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non‐ICU and ICU patients was 3.5% (95% CI, 2.2‐5.1) and 13.7% (95% CI, 10.0‐17.9). Patients developing VTE had higher d‐dimer levels (weighted mean difference, 3.26 µg/mL; 95% CI, 2.76‐3.77) than non‐VTE patients. Conclusion VTE occurs in 22.7% of patients with COVID‐19 in the ICU, but VTE risk is also increased in non‐ICU hospitalized patients. Patients developing VTE had higher d‐dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID‐19 are needed to improve prevention of VTE.

Abstract Background The COVID‐19 pandemic has focused medical attention on treating affected patients and protecting others from infection. However, concerns have been raised regarding the pandemic´s impact and associated containment measures (eg curfew, lockdown) on non–coronavirus disease 2019 (COVID‐19)–related acute medical diseases. Objectives To investigate changes in the incidence of pulmonary embolism (PE) during the COVID‐19 pandemic compared to the period before the pandemic and reference periods in previous years. Methods In this single‐center study, we explored all diagnostic imaging tests performed for suspected PE between weeks 1 and 17 of the years 2018, 2019, and 2020. Incidence of PE (ie, primary outcome) was analyzed. Secondary outcomes included number of imaging tests for suspected PE. Results Compared to weeks 1 to 11, 2020, an abrupt decline in PE diagnosis (mean weekly rate, 5.2; 95% confidence interval [CI], 3.8‐6.6 vs 1.8; 95% CI, 0.0‐3.6) and imaging tests (mean weekly rate, 32.5; 95% CI, 27.5‐37.6 vs. 17.3; 95% CI, 11.6‐23.1) was observed from week 12, with beginning of the containment measures and public lockdown in Austria. Compared to weeks 12 to 17 of 2018 and 2019, PE incidence and imaging tests were similarly decreased from 5.3 (95% CI, 3.6‐7.1) to 1.8 (95% CI, 0.0‐3.6) and 31.5 (95% CI, 27.1‐35.9) to 17.3 (95% CI, 11.6‐23.1), respectively. The median simplified pulmonary embolism severity index (sPESI) score of PE patients during the pandemic was higher than in all other PE patients (3; interquartile range, 1‐3 vs 1; interquartile range, 0‐2; P = .002). Conclusion Our study demonstrates that the COVID‐19 pandemic has an impact on non–COVID‐19–related acute diseases as shown by the decline in incidence of PE and imaging procedures for diagnostic workup. Further studies from other hospitals are needed to confirm our findings.

Abstract In modern wildlife ecology, spatial population genetic methods are becoming increasingly applied. Especially for animal species in fragmented landscapes, preservation of gene flow becomes a high priority target in order to restore genetic diversity and prevent local extinction. Within Central Europe, the Alps represent the core distribution area of the black grouse, Lyrurus tetrix. At its easternmost Alpine range, events of subpopulation extinction have already been documented in the past decades. Molecular data combined with spatial analyses can help to assess landscape effects on genetic variation and therefore can be informative for conservation management. Here, we addressed whether the genetic pattern of the easternmost Alpine black grouse metapopulation system is driven by isolation by distance or isolation by resistance. Correlative ecological niche modeling was used to assess geographic distances and landscape resistances. We then applied regression‐based approaches combined with population genetic analyses based on microsatellite data to disentangle effects of isolation by distance and isolation by resistance among individuals and subpopulations. Although population genetic analyses revealed overall low levels of genetic differentiation, the ecological niche modeling showed subpopulations to be clearly delimited by habitat structures. Spatial genetic variation could be attributed to effects of isolation by distance among individuals and isolation by resistance among subpopulations, yet unknown effects might factor in. The easternmost subpopulation was the most differentiated, and at the same time, immigration was not detected; hence, its long‐term survival might be threatened. Our study provides valuable insights into the spatial genetic variation of this small‐scale metapopulation system of Alpine black grouse.

The risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. We conducted a three-stage nested case–control study within the framework of a prospective registry, including 347 AF patients. First, total small RNA-sequencing was performed in 26 patients (13 cases with MACE) and the differential expression of microRNAs was analyzed. Seven candidate microRNAs with promising results in a subgroup analysis on cardiovascular death were selected and measured via using RT-qPCR in 97 patients (42 cases with cardiovascular death). To further validate our findings and investigate broader clinical applicability, we analyzed the same microRNAs in a subsequent nested case–control study of 102 patients (37 cases with early MACE) by using Cox regression. In the microRNA discovery cohort (n = 26), we detected 184 well-expressed microRNAs in circulation without overt differential expression between the cases and controls. A subgroup analysis on cardiovascular death revealed 26 microRNAs that were differentially expressed at a significance level < 0.05 (three of which with an FDR-adjusted p-value

Different species-specific traits of woody plant species, feeding preferences of herbivores together with resulting effects on plant competition are expected to translate into different plant community structures and expressions of biodiversity. We studied the diversity of woody plant species (trees and shrubs) and structural diversity of forest trees, using a 30-year and an 18-year dataset of ungulate exclosure-control plot pairs in a mixed alpine forest community in Austria. We surveyed the tallest individuals per tree species and plot and analyzed the collective of top-height individuals per plot pair. Incidence data for exclosure and control plots were aggregated. Comparing species diversity and diversity of height classes on the plots throughout time, we calculated diversity profiles based on Hill numbers. Diversity of top height individuals and structural diversity, expressed by height classes, were two diversity aspects that differed between exclosures and control plots. Other diversity estimates of woody plant species showed huge variation without significant differences between plots. Height growth was significantly suppressed by ungulate herbivory. Effects of ungulate herbivores in forest ecosystems are highly complex and context-dependent and thus not reducible to simple top-down forces. Long-term surveys provide data that reflect “ultimate” effects of herbivory interacting with other drivers of community dynamics.

Venous and arterial thromboembolism (VTE/ATE) are common complications in cancer patients. Antithrombin deficiency is a risk factor for thrombosis in the general population, but its connection to risk of cancer-associated thrombosis is unclear. We investigated the association of antithrombin activity levels with risk of cancer-associated VTE/ATE and all-cause mortality in an observational cohort study including patients with cancer, the Vienna Cancer and Thrombosis Study. In total, 1127 patients were included (45% female, median age: 62 years). Amongst these subjects, 110 (9.7%) patients were diagnosed with VTE, 32 (2.8%) with ATE, and 563 (49.9%) died. Antithrombin was not associated with a risk of VTE (subdistribution hazard ratio (SHR): 1.00 per 1% increase in antithrombin level; 95% CI: 0.99–1.01) or ATE (SHR: 1.00; 95% CI: 0.98–1.03). However, antithrombin showed a u-shaped association with the risk of all-cause death, i.e., patients with very low but also very high levels had poorer overall survival. In the subgroup of patients with brain tumors, higher antithrombin levels were associated with ATE risk (SHR: 1.02 per 1% increase; 95% CI: 1.00–1.04) and mortality (HR: 1.01 per 1% increase; 95% CI: 1.00–1.02). Both high and low antithrombin activity was associated with the risk of death. However, no association with cancer-associated VTE and ATE across all cancer types was found, with the exception of in brain tumors.

Objective: The purpose of this study was to compare the originally applied frequency allocation of cochlear implant electrodes assigned by default at the time of activation with a more recent frequency allocation that is anatomy-based by a software called OTOPLAN®. Based on a computed tomography scan of the temporal bone, this software calculates the position of each electrode in the cochlea and its corresponding tonotopic frequency. We also evaluated whether patients with a significant mismatch between these two allocations present poorer speech intelligibility. Materials and Methods: Patients who underwent cochlear implantation from 2016 to 2021 at the University Hospital of Liege were included in this retrospective study. We used OTOPLAN® to calculate the tonotopic frequency allocation of each electrode according to its exact position in the cochlear duct. This anatomical frequency mapping was compared with the default frequency mapping at the time of cochlear implant activation. Finally, we compared the mismatch with the patients' auditory performance, represented by the Auditory Capacity Index (ACI). Results: Thirteen patients were included in the study. All patients had a mismatch between the two frequency maps, to a variable extent (200 Hz–1,100 Hz). Frequency shift was significantly inversely correlated with ACI and with the time needed to improve speech intelligibility. Conclusion: Our primary results show that patients with a larger mismatch between default frequency mapping and anatomically assigned frequency mapping experience poorer hearing performance and slower adaptation to a cochlear implant. [ABSTRACT FROM AUTHOR]

Background The clinical presentation of children sensitised to dog dander varies from asymptomatic to severe allergic airway disease, but the genetic mechanisms underlying these differences are not clear. The objective of the present study was to investigate nasal transcriptomic profiles associated with dog dander sensitisation in school children and to reveal clinical symptoms related with these profiles. Methods RNA was extracted from nasal epithelial cell brushings of children sensitised to dog dander and healthy controls. Blood sample analyses included IgE against dog dander, dog allergen molecules, other airborne and food allergens, basophil activation and white blood cell counts. Clinical history of asthma and rhinitis was recorded, and lung function was assessed (spirometry, methacholine provocation and exhaled nitric oxide fraction). Results The most overexpressed gene in children sensitised to dog dander compared to healthy controls was CST1, coding for Cystatin 1. A cluster of these children with enhanced CST1 expression showed lower forced expiratory volume in 1 s, increased bronchial hyperreactivity, pronounced eosinophilia and higher basophil allergen threshold sensitivity compared with other children sensitised to dog dander. In addition, multi-sensitisation to lipocalins was more common in this group. Conclusions Overexpression of CST1 is associated with more severe allergic airway disease in children sensitised to dog dander. CST1 is thus a possible biomarker of the severity of allergic airway disease and a possible therapeutic target for the future treatment of airborne allergy.

The purpose of this study was to develop and test models of scanning activity in football. Gibson's ecological approach of visual perception and exploratory activity provided the theoretical framework for the models. The video-based data analysis consisted of 17 selected matches and 239 players of the Union of European Football Associations (UEFA) U17 and U19 European Championship 2018 and the UEFA U17 and U21 European Championship 2019. The results showed a positive relation between scanning frequency and successful passes, as well as changes in body orientation. Scanning frequency was also related to a player's appearances in national teams and to opponent pressure. Opponent pressure had a large effect on pass result and the player's body orientation. Previous research on the relation between scanning frequency and performance was extended by several contextual predictors. Future research should focus on gaining a deeper understanding of the relation between scanning frequency and further contextual variables related to scanning. [ABSTRACT FROM AUTHOR]

BackgroundIgA nephropathy (IgAN) advances from multiple pathogenic "hits" resulting in poorly O-galactosylated IgA1 glycoforms (Gd-IgA1), production of antibodies and glomerular deposition of immune complexes. A sequence of immune responses arising from plasma cells, T cells and antigen presenting cells (APCs), causes glomerular injury. This study was designed to phenotype subsets of B cells, monocytes and T cells in the peripheral circulation and their association with inflammatory cytokines and kidney function in patients with IgAN, healthy controls (HC) and disease controls with autosomal dominant polycystic kidney disease (ADPKD).MethodsPatients with IgAN (n = 13), median estimated glomerular filtration rate (eGFR) of 57 ml/min/1.73m2 (IQR 42-84), patients with ADPKD (n = 13) matched for kidney function, gender and age and gender and age-matched HC (n = 13) were recruited. CD3+ and CD3- peripheral blood mononuclear cells were isolated and profiled based on their specific surface markers for different subsets of monocytes, B and T cells and analyzed by flow cytometry. Cytokines were analyzed by ELISA.ResultsWe observed a significant decrease in the proportion of pre-switched B cells and plasmablasts, but an increase in long-lived plasma cells in the peripheral circulation of IgAN patients compared to HC. The proportion of non-classical monocytes was significantly higher in IgAN patients compared to both HC and ADPKD. We also report an association between sCD40L levels and the proportion of pre-switched B cells, as well as sCD40L and MCP-1 levels and albuminuria in IgAN patients.ConclusionsWe applied an easy-access method to analyze subsets of immune cells as well as relevant inflammatory mediators in IgAN patients. Our data demonstrate an altered B cell profile that indicates a pathophysiological role of the B cell lineage and an increased proportion of non-classical monocytes that suggests their role in the disease process.

As we are faced with the imminent spread of the raccoon (Procyon lotor L.), a successful and highly adaptable invader in Europe, it is necessary to identify the drivers of its distribution and focal areas of its future management. Being an omnivorous species, raccoons can exert considerable influence on prey species of various taxa. Species distribution models for this invasive species can be useful tools for its management. Using a presence-only model (MaxEnt) based on environmental variables selected by raccoon experts, the presence of raccoons in Austria was predicted. Core areas of raccoon colonization are mainly located in and around cities and river valleys. Identified ecological drivers of raccoon distribution comprise climate and land-cover variables, with temperature parameters (e.g. the number of hot days, mean January temperature), the proportion of coniferous forests, settlements and elevation mainly influencing the model output. The importance of habitat parameters changes with the stage of invasion. In Austria’s established regions, the probability of raccoon presence was best predicted by variables chosen by an expert of the raccoon’s native range, while the predictors chosen by an expert in its introduced range better reflected the situation in recently invaded regions. The significance of climate and land cover in understanding the probability of raccoon presence was shown.

The article discusses the basophil activation test (BAT) as a diagnostic tool for managing patients with IgE-mediated allergies. The authors emphasize the need for standardization and external quality assurance (EQA) of laboratory protocols and results interpretation. A task force was created to develop a consensus protocol for BAT-EQA, and round robin tests were conducted to train participating laboratories. The article presents a proposed standard operating protocol for BAT and highlights the importance of EQA for routine implementation of the assay. The authors conclude that the consensus protocol provides acceptable inter- and intralaboratory variability and can be implemented across Europe. [Extracted from the article]

Successfully managing heavily visited protected riverscapes requires information about visitor preferences for the social, biophysical and infrastructural attributes of river landscapes. This study analyzed the landscape preferences of 520 on-site visitors to the peri-urban Danube Floodplains National Park using an image-based discrete choice experiment. The study explored the effects of various landscape types (water bodies, terrestrial landscapes), recreational infrastructures (trail types, facilities) and trail use conditions (trail user numbers, activities) on respondents’ preferences. The results indicated that natural features, such as floodplain forests in combination with meadows or xeric alluvial biotopes, were preferred, while dense forests and, particularly, open agrarian structures were less preferred. Water bodies with 50% reed cover, few people on the trail, alleys of trees and gravel trails were favored. The outcomes serve as the basis for design recommendations for planned recreational areas surrounding the national park with the aim of absorbing visitors and reducing use pressure on the protected area.

Species distribution models are important tools for wildlife management planning, particularly in the case of invasive species. We employed a recent framework for niche-based invasive species distribution modeling to predict the probability of presence for the invasive raccoon dog (Nyctereutes procyonoides) in Austria. The raccoon dog is an adaptive, mobile and highly reproductive Asiatic canid that has successfully invaded many parts of Europe. It is known to occur in Austria since 1963 and is now widespread in the northern and eastern parts of the country, but its population density remains low. With the help of a species distribution model we identified focal areas for future monitoring and management actions, and we address some management implications for the raccoon dog in Austria. We also determined the environmental predictors of raccoon dog distribution in this alpine country. Its distribution seems to be mainly limited by climatic factors (snow depth, duration of snow cover, winter precipitation and mean annual temperature) and is thus linked to elevation. Consequently, we assumed the Alps to be a barrier for the spread of the invasive raccoon dog in Europe; however, its ecological permeability is expected to increase with ongoing climate change.