Temperature control in sepsis

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) and therapeutic hypothermia may be aimed at slowing metabolic activities and protecting organs from inflammation. Although high fever (>39.5°C) control is usually performed in critically ill patients, available cohorts and randomized controlled trials do not support its use to improve sepsis prognosis. Finally, both spontaneous and therapeutic hypothermia are associated with poor outcomes in sepsis

Air and Steam Gasification of Almond Biomass

Experiments were performed on a laboratory scale fluidized bed gasifier to characterize the gasification products of almond shell and hull removed in nut processing operations and to determine the effect of gasifying media on bed agglomeration. The higher heating value of syngas during air gasification of almond biomass ranged from 4 to 6 MJ m(-3) while gas concentrations ranged from 14 to 18% H-2, 3-4% CH4, 43-50% N-2, 16-19% CO, and 16-17% CO2. For steam gasification, higher heating value was 10-12 MJ m(-3) and gas concentrations were 35-40% H-2, 5-7% CH4, 17-21% N-2, 18-21% CO, and 16-18% CO2. The high level of potassium in the almond shells led to strong corrosion and bed agglomeration due to flue gas transport of potassium compounds. These resulting pervasive kalsilite reactions were significantly worse under air gasification than under steam gasification. As a result of prolonged duration and elevated temperature approaching 1,000 degrees C, the corrosinal reaction changes to formation of an adhesive potassium distillate melt locally forming strong bonds. This latter is interpreted as a result of aerosol transported of melt particles.California Energy Commission [PIR-07-002, PIR-11-008]; Almond Board of California; USDA-NIFA/UC Agricultural Experiment Station; California Almond Hullers and Processors AssociationThis work was supported by the California Energy Commission [PIR-07-002 and PIR-11-008]. We also acknowledge the generous support of the Almond Board of California, the California Almond Hullers and Processors Association, and USDA-NIFA/UC Agricultural Experiment Station

Influence of the Human Lipidome on Epicardial Fat Volume in Mexican American Individuals

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume. Aim: The focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American individuals. Methods: We performed lipidomic profiling on 200 Mexican American individuals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma samples. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype. Results: After correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume. Conclusion: Our results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our individuals could precede CVD with increased EAT volume

Stability of Surface-Immobilized Lubricant Interfaces under Flow

The stability and longevity of surface-stabilized lubricant layers is a critical question in their application as low- and nonfouling slippery surface treatments in both industry and medicine. Here, we investigate lubricant loss from surfaces under flow in water using both quantitative analysis and visualization, testing the effects of underlying surface type (nanostructured versus flat), as well as flow rate in the physiologically relevant range, lubricant type, and time. We find lubricant losses on the order of only ng/cm2 in a closed system, indicating that these interfaces are relatively stable under the flow conditions tested. No notable differences emerged between surface type, flow rate, lubricant type, or time. However, exposure of the lubricant layers to an air/water interface did significantly increase the amount of lubricant removed from the surface, leading to disruption of the layer. These results may help in the development and design of materials using surface-immobilized lubricant interfaces for repellency under flow conditions.Chemistry and Chemical BiologyEngineering and Applied Science

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼ 456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P \u3c 1 × 10−3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. Results Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. Conclusions For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making

Pharmacocinétique du méropénème et de la pipéracilline sous épuration extra-rénale chez l'enfant en réanimation

The pharmacokinetics of beta-lactams, in particular that of meropenem and piperacillin-tazobactam, plays a crucial role in the treatment of infections in children in intensive care. The problem in children in intensive care is the large number of intra-individual and inter-individual variability factors, including allometry. The variability is even greater in the event of renal failure which may lead to the need for continuous renal replacement therapy (CRRT), potentially increasing the variability of pharmacokinetics. We first carried out a survey of pediatric intensive care units which revealed a great variability in the prescription and adaptation of antibiotics in children in intensive care under extra-renal purification. These results highlight the importance of an individualized approach and clinical consensus to optimize therapeutic efficacy and minimize the risks associated with this vulnerable population. We then developed 2 population pharmacokinetic models for respectively meropenem and piperacillin, two antibiotics among the most used in pediatric intensive care. Optimal exposure to meropenem in pediatric intensive care children under CRRT requires individualization of dosing regimens based on effluent flow, body weight, and CRRT with reduced intermittent doses under low CRRT effluent flow. and continuous infusion under high effluent flow. Optimal exposure to piperacillin in pediatric intensive care children on CRRT has been achieved using continuous infusions with increasing doses for bacteria with high MICs, except for anuric patients who require intermittent and less frequent doses. Finally, we developed an ex vivo model in order to study more precisely the impact explained by physiology. Altogether, we have highlighted the current gaps in knowledge and have carried out studies aimed at improving the use of beta-lactams in this specific population. The results of these studies shed light on the optimization and adaptation of the doses of meropenem and piperacillin in children in intensive care under CRRT.La pharmacocinétique des béta-lactamines, en particulier celle du méropénème et de la pipéracilline-tazobactam, joue un rôle crucial dans le traitement des infections chez les enfants en réanimation. La problématique chez les enfants en réanimation est le nombre important de facteurs de variabilité intra-individuelle et inter-individuelle, incluant l'allométrie. La variabilité est encore plus importante en cas de défaillance rénale pouvant conduire à la nécessité d'une épuration extra-rénale continue (EERC), augmentant potentiellement la variabilité de la pharmacocinétique. Nous avons d'abord réalisé une enquête auprès des réanimateurs pédiatriques qui a révélé une grande variabilité dans la prescription et l'adaptation des antibiotiques chez les enfants en réanimation sous épuration extra-rénale. Ces résultats soulignent l'importance d'une approche individualisée et d'un consensus clinique pour optimiser l'efficacité thérapeutique et minimiser les risques associés à cette population vulnérable. Nous avons ensuite développé 2 modèles de pharmacocinétique de population pour respectivement le méropénème et la pipéracilline, deux antibiotiques parmi les plus utilisés en réanimation pédiatrique. L'exposition optimale au méropénème chez les enfants en réanimation pédiatrique sous EERC nécessite une individualisation des schémas posologiques en fonction du débit d'effluent, du poids corporel et de l'EERC avec des doses intermittentes réduites sous un faible débit d'effluent EERC et une perfusion continue sous un débit d'effluent élevé. L'exposition optimale à la pipéracilline chez les enfants en réanimation pédiatrique sous EERC a été obtenue en utilisant des perfusions continues avec des doses croissantes pour les bactéries à CMI élevée, sauf pour les patients anuriques qui nécessitent des doses intermittentes et moins fréquentes. Enfin, nous avons développé un modèle ex vivo afin d'étudier plus précisément l'impact expliqué par la physiologie. Au total, nous avons mis en évidence les lacunes actuelles dans les connaissances et avons mené à bien des études visant à améliorer l'utilisation des béta-lactamines dans cette population spécifique. Les résultats de ces études apportent des éclaircissements sur l'optimisation et l'adaptation des doses de méropénème et de pipéracilline chez les enfants en réanimation sous EERC

Pharmacokinetics of meropenem and piperacillin under renal replacement therapy in pediatric intensive care unit

La pharmacocinétique des béta-lactamines, en particulier celle du méropénème et de la pipéracilline-tazobactam, joue un rôle crucial dans le traitement des infections chez les enfants en réanimation. La problématique chez les enfants en réanimation est le nombre important de facteurs de variabilité intra-individuelle et inter-individuelle, incluant l'allométrie. La variabilité est encore plus importante en cas de défaillance rénale pouvant conduire à la nécessité d'une épuration extra-rénale continue (EERC), augmentant potentiellement la variabilité de la pharmacocinétique. Nous avons d'abord réalisé une enquête auprès des réanimateurs pédiatriques qui a révélé une grande variabilité dans la prescription et l'adaptation des antibiotiques chez les enfants en réanimation sous épuration extra-rénale. Ces résultats soulignent l'importance d'une approche individualisée et d'un consensus clinique pour optimiser l'efficacité thérapeutique et minimiser les risques associés à cette population vulnérable. Nous avons ensuite développé 2 modèles de pharmacocinétique de population pour respectivement le méropénème et la pipéracilline, deux antibiotiques parmi les plus utilisés en réanimation pédiatrique. L'exposition optimale au méropénème chez les enfants en réanimation pédiatrique sous EERC nécessite une individualisation des schémas posologiques en fonction du débit d'effluent, du poids corporel et de l'EERC avec des doses intermittentes réduites sous un faible débit d'effluent EERC et une perfusion continue sous un débit d'effluent élevé. L'exposition optimale à la pipéracilline chez les enfants en réanimation pédiatrique sous EERC a été obtenue en utilisant des perfusions continues avec des doses croissantes pour les bactéries à CMI élevée, sauf pour les patients anuriques qui nécessitent des doses intermittentes et moins fréquentes. Enfin, nous avons développé un modèle ex vivo afin d'étudier plus précisément l'impact expliqué par la physiologie. Au total, nous avons mis en évidence les lacunes actuelles dans les connaissances et avons mené à bien des études visant à améliorer l'utilisation des béta-lactamines dans cette population spécifique. Les résultats de ces études apportent des éclaircissements sur l'optimisation et l'adaptation des doses de méropénème et de pipéracilline chez les enfants en réanimation sous EERC.The pharmacokinetics of beta-lactams, in particular that of meropenem and piperacillin-tazobactam, plays a crucial role in the treatment of infections in children in intensive care. The problem in children in intensive care is the large number of intra-individual and inter-individual variability factors, including allometry. The variability is even greater in the event of renal failure which may lead to the need for continuous renal replacement therapy (CRRT), potentially increasing the variability of pharmacokinetics. We first carried out a survey of pediatric intensive care units which revealed a great variability in the prescription and adaptation of antibiotics in children in intensive care under extra-renal purification. These results highlight the importance of an individualized approach and clinical consensus to optimize therapeutic efficacy and minimize the risks associated with this vulnerable population. We then developed 2 population pharmacokinetic models for respectively meropenem and piperacillin, two antibiotics among the most used in pediatric intensive care. Optimal exposure to meropenem in pediatric intensive care children under CRRT requires individualization of dosing regimens based on effluent flow, body weight, and CRRT with reduced intermittent doses under low CRRT effluent flow. and continuous infusion under high effluent flow. Optimal exposure to piperacillin in pediatric intensive care children on CRRT has been achieved using continuous infusions with increasing doses for bacteria with high MICs, except for anuric patients who require intermittent and less frequent doses. Finally, we developed an ex vivo model in order to study more precisely the impact explained by physiology. Altogether, we have highlighted the current gaps in knowledge and have carried out studies aimed at improving the use of beta-lactams in this specific population. The results of these studies shed light on the optimization and adaptation of the doses of meropenem and piperacillin in children in intensive care under CRRT