Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

Diabetes is a risk factor for Alzheimer’s disease and it is associated with significant memory loss. In the present study, we hypothesized that the soluble epoxide hydrolase (sEH) inhibitor N-[1-(1-oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy)phenyl)-urea (also known as TPPU) could alleviate diabetes-aggravated Alzheimer’s disease-like symptoms by improving memory and cognition, and reducing the oxidative stress and inflammation associated with this condition. Also, we evaluated the effect of edaravone, an antioxidant on diabetes-induced Alzheimer’s-like complications and the additive effect of docosahexaenoic acid (DHA) on the efficacy of TPPU. Diabetes was induced in male Sprague-Dawley rats by intraperitoneally administering streptozotocin (STZ). Six weeks after induction of diabetes, animals were either treated with vehicle, edaravone (3 or 10 mg/kg), TPPU (1 mg/kg) or TPPU (1 mg/kg) + DHA (100 mg/kg) for 2 weeks. The results demonstrate that the treatments increased the memory response of diabetic rats, in comparison to untreated diabetic rats. Indeed, DHA + TPPU were more effective than TPPU alone in reducing the symptoms monitored. All drug treatments reduced oxidative stress and minimized inflammation in the brain of diabetic rats. Expression of the amyloid precursor protein (APP) was increased in the brain of diabetic rats. Treatment with edaravone (10 mg/kg), TPPU or TPPU + DHA minimized the level of APP. The activity of acetylcholinesterase (AChE) which metabolizes acetylcholine was increased in the brain of diabetic rats. All the treatments except edaravone (3 mg/kg) were effective in decreasing the activity of AChE and TPPU + DHA was more efficacious than TPPU alone. Intriguingly, the histological changes in hippocampus after treatment with TPPU + DHA showed significant protection of neurons against STZ-induced neuronal damage. Overall, we found that DHA improved the efficacy of TPPU in increasing neuronal survival and memory, decreasing oxidative stress and inflammation possibly by stabilizing anti-inflammatory and neuroprotective epoxides of DHA. In the future, further evaluating the detailed mechanisms of action of sEH inhibitor and DHA could help to develop a strategy for the management of Alzheimer’s-like complications in diabetes

Landscape-level human disturbance results in loss and contraction of mammalian populations in tropical forests

Tropical forests hold most of Earth's biodiversity and a higher concentration of threatened mammals than other biomes. As a result, some mammal species persist almost exclusively in protected areas, often within extensively transformed and heavily populated landscapes. Other species depend on remaining remote forested areas with sparse human populations. However, it remains unclear how mammalian communities in tropical forests respond to anthropogenic pressures in the broader landscape in which they are embedded. As governments commit to increasing the extent of global protected areas to prevent further biodiversity loss, identifying the landscape-level conditions supporting wildlife has become essential. Here, we assessed the relationship between mammal communities and anthropogenic threats in the broader landscape. We simultaneously modeled species richness and community occupancy as complementary metrics of community structure, using a state-of-the-art community model parameterized with a standardized pan-tropical data set of 239 mammal species from 37 forests across 3 continents. Forest loss and fragmentation within a 50-km buffer were associated with reduced occupancy in monitored communities, while species richness was unaffected by them. In contrast, landscape-scale human density was associated with reduced mammal richness but not occupancy, suggesting that sensitive species have been extirpated, while remaining taxa are relatively unaffected. Taken together, these results provide evidence of extinction filtering within tropical forests triggered by anthropogenic pressure occurring in the broader landscape. Therefore, existing and new reserves may not achieve the desired biodiversity outcomes without concurrent investment in addressing landscape-scale threats

Reference ranges for Doppler indices of umbilical and fetal middle cerebral arteries and cerebroplacental ratio: systematic review.

OBJECTIVE: To assess studies reporting reference ranges for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR), using a set of predefined methodological quality criteria for study design, statistical analysis and reporting methods. METHODS: This was a systematic review of observational studies in which the primary aim was to create reference ranges for UA and MCA Doppler indices and CPR in fetuses of singleton gestations. A search for relevant articles was performed in MEDLINE, EMBASE, CINAHL, Web of Science (from inception to 31 December 2016) and references of the retrieved articles. Two authors independently selected studies, assessed the risk of bias and extracted the data. Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was assigned to each study. Linear multiple regression analysis assessing the association between quality scores and study characteristics was performed. RESULTS: Thirty-eight studies met the inclusion criteria. The highest potential for bias was noted in the following fields: 'ultrasound quality control measures', in which only two studies demonstrated a comprehensive quality-control strategy; 'number of measurements taken for each Doppler variable', which was apparent in only three studies; 'sonographer experience', in which no study on CPR reported clearly the experience or training of the sonographers, while only three studies on UA Doppler and four on MCA Doppler did; and 'blinding of measurements', in which only one study, on UA Doppler, reported that sonographers were blinded to the measurement recorded during the examination. Sample size estimations were present in only seven studies. No predictors of quality were found on multiple regression analysis. Reference ranges varied significantly with important clinical implications for what is considered normal or abnormal, even when restricting the analysis to the highest scoring studies. CONCLUSIONS: There is considerable methodological heterogeneity in studies reporting reference ranges for UA and MCA Doppler indices and CPR, and the resulting references have important implications for clinical practice. There is a need for the standardization of methodologies for Doppler velocimetry and for the development of reference standards, which can be correctly interpreted and applied in clinical practice. We propose a set of recommendations for this purpose. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Global Roadkill Data: a dataset on terrestrial vertebrate mortality caused by collision with vehicles

Roadkill is widely recognized as one of the primary negative effects of roads on many wildlife species and also has socioeconomic impacts when they result in accidents. A comprehensive dataset of roadkill locations is essential to evaluate the factors contributing to roadkill risk and to enhance our comprehension of its impact on wildlife populations and socioeconomic dimensions. We undertook a compilation of roadkill records, encompassing both published and unpublished data gathered from road surveys or opportunistic sources. GLOBAL ROADKILL DATA includes 208,570 roadkill records of terrestrial vertebrates from 54 countries across six continents, encompassing data collected between 1971 and 2024. This dataset serves to minimise the collection of redundant data and acts as a valuable resource for local and macro scale analysis regarding rates of roadkill, road- and landscape-related features associated with risk of roadkill, vulnerability of species to road traffic, and populations at risk of local extinction. The objective of this dataset is to promote scientific progress in infrastructure ecology and terrestrial vertebrate conservation while limiting the socio-economic costs

Masses of heavy–light mesons with two-loop static potential in a variational approach

In this work, we investigate the masses of a few heavy–light mesons with variational method, taking into account the two-loop effects in the static Cornell potential. Specifically, we consider two wave functions, Gaussian and Coulomb. Our analysis suggests that phenomenologically such approach is more successful in the heavy flavored meson sector than the stationary state perturbation theory and other approximation methods. </jats:p