Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.

Repeatability and variability of myocardial perfusion imaging techniques in mice: Comparison of arterial spin labeling and first-pass contrast-enhanced MRI.

PURPOSE: Preclinical imaging of myocardial blood flow (MBF) can elucidate molecular mechanisms underlying cardiovascular disease. We compared the repeatability and variability of two methods, first-pass MRI and arterial spin labeling (ASL), for imaging MBF in mice. METHODS: Quantitative perfusion MRI in mice was performed using both methods at rest, with a vasodilator, and one day after myocardial infarction. Image quality (score of 1-5; 5 best), between-session coefficient of variability (CVbs ), intra-user coefficient of variability (CVintra-user ), and inter-user coefficient of variability (CVinter-user ) were assessed. Acquisition time was 1-2 min for first-pass MRI and approximately 40 min for ASL. RESULTS: Image quality was higher for ASL (3.94 ± 0.09 versus 2.88 ± 0.10; P < 0.05). Infarct zone CVbs was lower with first-pass (17 ± 3% versus 46 ± 9%; P < 0.05). The stress perfusion CVintra-user was lower for ASL (3 ± 1% versus 14 ± 3%; P < 0.05). The stress perfusion CVinter-user was lower for ASL (4 ± 1% versus 17 ± 4%; P < 0.05). CONCLUSION: For low MBF conditions such as infarct, first-pass MRI is preferred due to better repeatability and variability. At high MBF such as at vasodilation, ASL may be more suitable due to superior image quality and lower user variability. First-pass MRI has a substantial speed advantage. Magn Reson Med 75:2394-2405, 2016. © 2015 Wiley Periodicals, Inc.

Interannual trophic behaviour of a pelagic fish predator in the western Mediterranean Sea.

The exploitation of forage fish species can modify the functioning of marine ecosystems potentially impacting the population status of predators. This may be the case for the western Mediterranean Sea, where a reduction in the biomass of two key pelagic forage fish (European anchovy Engraulis encrasicolus and European sardine Sardina pilchardus) could produce a change in the diet composition of their main predators, which would consume alternative preys or change the size of the prey consumed. Here, we aimed to investigate the potential effect of biomass reduction of sardine and anchovy in the western Mediterranean Sea on the trophic preferences of the little tunny (Euthynnus alletteratus), a medium-sized predator that present a high consumption of these forage fish. We compared its interannual trophic ecology by combining the analysis of stomach contents and stable isotopes. Specifically, we examined if the diet of little tunny changed in its main trophic habits (diet composition, prey size, and trophic niche) during a 6-year period. We found that small pelagic fish, especially clupeiformes, were the most important prey group for the little tunny during the study period. However, we found changes in the body size of anchovy and the relative importance of sardine in recent years, probably reflecting the reported reduction in the biomass and body size of these two forage fish in the study area. In addition to these changes, we found an increase in some demersal and benthopelagic species in the diet of little tunny, which could act as an alternative diet resource.

Nonvalvular atrial fibrillation patients anticoagulated with rivaroxaban compared with warfarin exhibit reduced circulating extracellular vesicles with attenuated pro-inflammatory protein signatures.

BACKGROUND: Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; however, these remain poorly characterized. Extracellular vesicles (EVs) are important circulating messengers regulating a myriad of biological and pathological processes and may be highly relevant to the pathophysiology of atrial fibrillation as they reflect alterations in platelet and endothelial biology. However, the effects of rivaroxaban on circulating pro-inflammatory EVs remain unknown. OBJECTIVES: We hypothesized that rivaroxaban's anti-inflammatory properties are reflected upon differential molecular profiles of circulating EVs. METHODS: Differences in circulating EV profiles were assessed using a combination of single vesicle analysis by Nanoparticle Tracking Analysis and flow cytometry, and proteomics. RESULTS: We demonstrate, for the first time, that rivaroxaban-treated non-valvular atrial fibrillation (NVAF) patients (n=8) exhibit attenuated inflammation compared with matched warfarin controls (n=15). Circulating EV profiles were fundamentally altered. Moreover, quantitative proteomic analysis of enriched plasma EVs from six pooled biological donors per treatment group revealed a profound decrease in highly pro-inflammatory protein expression and complement factors, together with increased expression of negative regulators of inflammatory pathways. Crucially, a reduction in circulating levels of soluble P-selectin was observed in rivaroxaban-treated patients (compared with warfarin controls), which negatively correlated with the patient's time on treatment. CONCLUSION: Collectively, these data demonstrate that NVAF patients anticoagulated with rivaroxaban (compared with warfarin) exhibit both a reduced pro-inflammatory state and evidence of reduced endothelial activation. These findings are of translational relevance toward characterizing the anti-inflammatory and cardiovascular-protective mechanisms associated with rivaroxaban therapy.