PK/PD modelling and simulation of longitudinal meropenem in vivo effects against Escherichia coli and Klebsiella pneumoniae strains with high MICs.

Background: Carbapenem-resistant bacteria pose a threat to public health. Characterising the pharmacokinetics-pharmacodynamics (PKPD) of meropenem longitudinally in vivo against resistant bacteria could provide valuable information for development and translation of carbapenem-based therapies.

Objectives: To assess the time course of meropenem effects in vivo against strains with high MIC to predict PK/PD indices and expected efficacy in patients using a modelling approach.

No Future Growth Enhancement Expected at the Northern Edge for European Beech due to Continued Water Limitation.

With ongoing global warming, increasing water deficits promote physiological stress on forest ecosystems with negative impacts on tree growth, vitality, and survival. How individual tree species will react to increased drought stress is therefore a key research question to address for carbon accounting and the development of climate change mitigation strategies. Recent tree-ring studies have shown that trees at higher latitudes will benefit from warmer temperatures, yet this is likely highly species-dependent and less well-known for more temperate tree species.

Apramycin efficacy against carbapenem- and aminoglycoside-resistant Escherichia coli and Klebsiella pneumoniae in murine bloodstream infection models.

Background: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed.

Methods: The resistance gene annotations of 40 888 blood-culture isolates were analysed.

Genomic evaluation for breeding and genetic management in Cordia africana, a multipurpose tropical tree species.

Background: Planting tested forest reproductive material is crucial to ensure the increased resilience of intensively managed productive stands for timber and wood product markets under climate change scenarios. Single-step Genomic Best Linear Unbiased Prediction (ssGBLUP) analysis is a cost-effective option for using genomic tools to enhance the accuracy of predicted breeding values and genetic parameter estimation in forest tree species. Here, we tested the efficiency of ssGBLUP in a tropical multipurpose tree species, Cordia africana, by partial population genotyping.

Plant agronomy, leaf ecophysiology, yield and quality data of interspecific grafted across an elevation gradient.

In-field data were collected in Costa Rica between 2018-2021 on newly planted grafted and non-grafted coffee plants grown under artificial shade nets and across an elevation gradient (1050, 1250 and 1450 m.a.s.

Effect of yeast species and processing on intestinal microbiota of Atlantic salmon (Salmo salar) fed soybean meal-based diets in seawater.

Background: Yeasts are gaining attention as alternative ingredients in aquafeeds. However, the impact of yeast inclusion on modulation of intestinal microbiota of fish fed plant-based ingredients is limited. Thus, the present study investigates the effects of yeast and processing on composition, diversity and predicted metabolic capacity of gut microbiota of Atlantic salmon smolt fed soybean meal (SBM)-based diet.

Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents.

Antimicrobial resistance has become one of the greatest threats to human health, and new antibacterial treatments are urgently needed. As a tool to develop novel therapies, animal models are essential to bridge the gap between preclinical and clinical research. However, despite common usage of models that mimic clinical infection, translational challenges remain high.

Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections.

The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosing regimens and progressing drug candidates into the clinic. The Innovative Medicines Initiative-funded "Collaboration for prevention and treatment of MDR bacterial infections" (COMBINE) consortium is establishing a validated and globally harmonized preclinical model to increase reproducibility and more reliably translate results from animals to humans.

Translational in vitro and in vivo PKPD modelling for apramycin against Gram-negative lung pathogens to facilitate prediction of human efficacious dose in pneumonia.

Objectives: New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy.

Effects of Yeast Species and Processing on Intestinal Health and Transcriptomic Profiles of Atlantic Salmon () Fed Soybean Meal-Based Diets in Seawater.

The objective of the current study was to examine the effects of yeasts on intestinal health and transcriptomic profiles from the distal intestine and spleen tissue of Atlantic salmon fed SBM-based diets in seawater. (CJ) and (WA) yeasts were heat-inactivated with spray-drying (ICJ and IWA) or autolyzed at 50 °C for 16 h (ACJ and AWA), followed by spray-drying. Six diets were formulated, one based on fishmeal (FM), a challenging diet with 30% soybean meal (SBM) and four other diets containing 30% SBM and 10% of each of the four yeast fractions (i.

Modulation of Atlantic salmon (Salmo salar) gut microbiota composition and predicted metabolic capacity by feeding diets with processed black soldier fly (Hermetia illucens) larvae meals and fractions.

Background: Black soldier fly (Hermetia illucens) is a promising insect species to use as a novel ingredient in fish feeds. Black soldier fly larvae consists of three major fractions, namely protein, lipid, and exoskeleton. These fractions contain bioactive compounds that can modulate the gut microbiota in fish such as antimicrobial peptides, lauric acid, and chitin.

Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis.

Background: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided.

The Spleen as a Target to Characterize Immunomodulatory Effects of Down-Stream Processed Yeasts in Atlantic Salmon Exposed to a Dietary Soybean Meal Challenge.

Aquaculture feeds have changed dramatically from being largely based on fishmeal (FM) towards increased use of plant protein sources, which could impact the fish's immune response. In order to characterize immunomodulatory properties of novel functional ingredients, this study used four diets, one based on FM, a challenging diet with 40% soybean meal (SBM), and two diets containing 40% SBM with 5% of yeast exposed to different down-stream processing conditions: heat-inactivated (ICJ) or autolysation (ACJ). The immunomodulatory effects of the diets were analyzed in the spleen of Atlantic salmon after 37 days of feeding, using a transcriptomic evaluation by RNA sequencing (RNA-seq) and the detection of specific immunological markers at the protein level through indirect Enzyme-linked Immunosorbent Assay (indirect ELISA).

Fecal Excretion and Whole-Body Retention of Macro and Micro Minerals in Atlantic Salmon Fed Torula Yeast Grown on Sugar Kelp Hydrolysate.

Yeast is a microbial feed ingredient that can be produced from non-food biomasses. Brown seaweed contains high levels of complex carbohydrates that are not digested to any extent by monogastric animals but can be used as carbon sources for yeast production. The objective of this study was to investigate how minerals originating from brown macroalgae ( are incorporated in yeast and to assess the bioavailability of these different minerals as well as their accumulation into different organs of Atlantic salmon.

Evaluation of candidate template beam models for a matched TrueBeam treatment delivery system.

Purpose: To explore candidate RayStation beam models to serve as a class-specific template for a TrueBeam treatment delivery system.

Methods: Established validation techniques were used to evaluate three photon beam models: a clinically optimized model from the authors' institution, the built-in RayStation template, and a hybrid consisting of the RayStation template except substituting average MLC parameter values from a recent IROC survey. Comparisons were made for output factors, dose profiles from open fields, as well as representative VMAT test plans.

Dietary Inclusion of Black Soldier Fly () Larvae Meal and Paste Improved Gut Health but Had Minor Effects on Skin Mucus Proteome and Immune Response in Atlantic Salmon ().

The present study investigated effects of dietary inclusion of black soldier fly larvae (BSFL) () meal and paste on gut health, plasma biochemical parameters, immune response and skin mucus proteome in pre-smolt Atlantic salmon (). The seven-week experiment consisted of seven experimental diets: a control diet based on fishmeal and plant protein (Control-1); three BSFL meal diets, substituting 6.25% (6.

Impact of down-stream processing on functional properties of yeasts and the implications on gut health of Atlantic salmon (Salmo salar).

Yeasts are becoming popular as novel ingredients in fish feeds because of their potential to support better growth and concomitantly ensure good fish health. Here, three species of yeasts (Cyberlindnera jadinii, Blastobotrys adeninivorans and Wickerhamomyces anomalus), grown on wood sugars and hydrolysates of chicken were subjected to two down-stream processes, either direct heat-inactivation or autolysis, and the feed potential of the resulting yeast preparations was assessed through a feeding trial with Atlantic salmon fry. Histological examination of distal intestine based on widening of lamina propria, showed that autolyzed W.

Comparison of catheter reconstruction techniques for the lunar ovoid channels of the Venezia applicator.

Purpose: The aim of this study was to compare catheter reconstruction methods for lunar ovoid channels of the Venezia advanced gynecological applicator (Elekta, Sweden).

Material And Methods: Three available lunar ovoid sizes (22, 26, and 30 mm effective diameter) were evaluated. Computed tomography (CT) scans were performed with a dummy wire inserted and with the Flexitron source position simulator (SPS) at step sizes of 5 mm from the most distal dwell position.

Evaluation of ionization chamber stability checks using various sources.

Purpose: It is important to check stability of ionization chambers in between regular calibration cycles. Stability checks can include individual Co irradiations, use of a beta-emitting check source, or redundant measurements in megavoltage photon beams. While Co irradiators are considered stable, they are rarely found in the clinical setting.

Model-Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin.

Apramycin represents a subclass of aminoglycoside antibiotics that has been shown to evade almost all mechanisms of clinically relevant aminoglycoside resistance. Model-informed drug development may facilitate its transition from preclinical to clinical phase. This study explored the potential of pharmacokinetic/pharmacodynamic (PK/PD) modeling to maximize the use of in vitro time-kill and in vivo preclinical data for prediction of a human efficacious dose (HED) for apramycin.

A convex windowless extrapolation chamber to measure surface dose rate from Ru/ Rh episcleral plaques.

Purpose: A convex windowless extrapolation chamber was developed as a primary measurement device to determine surface dose rate from curved Ru/ Rh episcleral plaques.

Methods: A convex extrapolation chamber without an entrance window was constructed for this work, and surface dose rate measurements were performed with two curved CCB-type Ru/ Rh plaques (S/N 2545 and 2596) manufactured by Eckert & Ziegler BEBIG. FARO Gage measurements were performed to verify the radius of curvature for the convex electrode and the concave plaque surface.