Mechanisms for Aerobic Degradation of Commercial Naphthenic Acids

Naphthenic acids (NAs) are a class of thousands of carboxylic acids associated with petroleum degradation. They become dissolved in oil sands process waters (OSPW) during the bitumen extraction process, and the resulting process waters can elicit toxicity to aquatic organisms. NAs are weakly biodegradable, but have half-lives of months to years, making it difficult to treat NAs with bioremediation. Two methods for promoting aerobic degradation (cometabolism and mycoremediation) were investigated as proof of concept for effectiveness in degrading commercial NAs. A reciprocating reactor inoculated with a white rot fungus, Pleurotus pulmonaris, was built and compared to an uninoculated reactor to determine the effects of this fungus on NA degradation. Inoculated reactors were more effective than uninoculated reactors in removing NAs, with zero-order half lives of 32 and 39 hours, respectively. This demonstrated the usefulness of both P. pulmonaris and a reciprocating reactor in promoting aerobic NA degradation. Cometabolic NA degradation using different substrates and substrate concentrations was investigated at bench scale. This study confirmed that cometabolic substrate addition increases NA removal rate in comparison to unamended degradation. It also showed that the concentration ratio of substrate to NAs affects the removal rate of NAs. This has important implications to the design of a constructed wetland treatment system for ecological risk mitigation of OSPW, where wetland detritus may serve as a cometabolic substrate to promote NA degradation

Hematological profile of East African short-horn zebu calves from birth to 51 weeks of age

This paper is the first attempt to accurately describe the hematological parameters for any African breed of cattle, by capturing the changes in these parameters over the first 12 months of an animal’s life using a population-based sample of calves reared under field conditions and natural disease challenge. Using a longitudinal study design, a stratified clustered random sample of newborn calves was recruited into the IDEAL study and monitored at 5-weekly intervals until 51 weeks of age. The blood cell analysis performed at each visit included: packed cell volume; red cell count; red cell distribution width; mean corpuscular volume; mean corpuscular hemoglobin concentration; hemoglobin concentration; white cell count; absolute lymphocyte, eosinophil, monocyte, and neutrophil counts; platelet count; mean platelet volume; and total serum protein. The most significant age-related change in the red cell parameters was a rise in red cell count and hemoglobin concentration during the neonatal period. This is in contrast to what is reported for other ruminants, including European cattle breeds where the neonatal period is marked by a fall in the red cell parameters. There is a need to establish breed-specific reference ranges for blood parameters for indigenous cattle breeds. The possible role of the postnatal rise in the red cell parameters in the adaptability to environmental constraints and innate disease resistance warrants further research into the dynamics of blood cell parameters of these breeds.Wellcome Trust (project no.079445).http://link.springer.com/journal/580hb2013ab201

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Detection of micro-RNA/gene interactions involved in angiogenesis using machine learning techniques

Motivation: Angiogenesis is the process responsible for the growth of new blood vessels from existing ones. It is also associated with the development of cancer, as tumors need to be irrigated by blood vessels for growing. New cancer therapies appear that exploit angiogenesis inhibitors, also called angiostatic agents, to asphyxiate and starve the tumors. Better understanding the regulatory mechanisms that control angiogenesis is thus fundamental. Recently, short non-coding RNA molecules, called micro-RNAs, have been discovered that are involved in post- transcriptional regulation of gene expressions. These molecules bind to RNA messengers following the base pairing rules, preventing them from being translated into proteins and/or tagging them for degradation. The main goal of this work is to use computational approaches to identify micro-RNAs involved in angiogenesis. Method: In order to identify genes involved in angiogenesis, bovine endothelial cells were treated by a known angiogenesis inhibitor [1], prolactin 16K, and their gene expression profile was compared to the profile of untreated cells. The genes were then divided into three classes: up-regulated, down-regulated, and unaffected genes. The 3'UTR regions of these genes were then analysed by machine learning techniques. Different approaches were considered. First, we described each gene by a vector of motif counts in their 3'UTR regions and used machine learning techniques to rank the motifs according to their relevance for separating the genes into the different classes. We considered successively motifs corresponding to the seeds of known micro- RNAs and also all possible motifs of a given length. To rank the motifs, we compared ensemble of decision trees and linear support vector machines. Second, we considered an approach called Segment and Combine that was proposed in [2]. Finally, we also carried out an exhaustive search of all motifs of a given length that satisfy some constraints on specificity and coverage with respect to a given gene category. Results: The ability of the different approaches at identifying relevant motifs was first assessed on genes predicted to be the target of some known miRNAs. In this simple setting, most methods were able to identify the micro-RNA seed. The results obtained on the genes regulated by prolactin 16K are also very encouraging. We were able to identify one micro-RNA already known to play a role in angiogenesis and several motifs are predicted by different approaches as very specific of up- or down-regulation by prolactin 16K. Their relationship with known micro-RNAs is certainly worth exploring. Conclusion: Machine learning approaches are promising techniques for the identification of micro-RNA/gene interactions. Future work will concern the application of the same kind of techniques on promoters for the identification of transcription factor binding sites

“True” Antiphospholipid Syndrome in COVID-19: Contribution of the Follow-up of Antiphospholipid Autoantibodies

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