Prospective comparison of cytomegalovirus quantification in whole blood and plasma samples among hematopoietic stem cell transplant and kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) induces multi-organ pathogenesis in hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) recipients. Effective management involves systematic monitoring for CMV reactivation by quantitative real-time PCR, allowing timely preemptive intervention. However, the optimal blood compartment for CMV surveillance remains undetermined. OBJECTIVE: The aim of the study was to compare the quantification of CMV DNA in paired plasma and whole blood samples. STUDY DESIGN: From June and October 2022, we conducted a prospective study with 390 sets of paired plasma and whole blood specimens collected from 60 HSCT and 24 KT recipients. CMV DNA levels were compared between the cobas® CMV assay on the automated cobas® 6800 system for plasma and the reference assay, Abbott RealTime CMV assay on the m2000 RealTime platform for whole blood. RESULTS: The sensitivity and specificity of CMV quantification in plasma using the cobas® CMV assay were 90.0 % (95 %CI: 81.5 to 95.9) and 94.8 % (95 %CI: 91.8 to 96.8), respectively, compared to whole blood quantification with the Abbott assay. The overall agreement between these two strategies was 0.89 (95 %CI: 0.86-0.91). In samples with quantifiable results, a correlation was observed between the two methods (R2 = 0.62, 95 %CI: 0.65-0.87, p < 0.0001). CMV loads were significantly higher in whole blood, with a mean bias of 0.42 log10 IU/mL (95 %CI: -0.32-1.15). CONCLUSION: The cobas® CMV assay in plasma showed significant concordance with the Abbott RealTime CMV assay in whole blood, confirming the relevance of plasma samples for CMV monitoring in HSCT and KT recipients.

Impact of nutritional factors on in vitro PK/PD modelling of polymyxin B against various strains of Acinetobacter baumannii.

The main objective of this study was to assess the effect of rich artificial cation-adjusted Mueller-Hinton broth (CAMHB) on the growth of three strains of Acinetobacter baumannii (ATCC 19606 and two clinical strains), either susceptible or resistant to polymyxin B (PMB), and on PMB bactericidal activity. A pharmacokinetic (PK)/pharmacodynamic (PD) modelling approach was used to characterize the effect of PMB in various conditions. Time-kill experiments were performed using undiluted CAMHB or CAMHB diluted to 50%, 25% and 10%, with or without Ca2+ and Mg2+ compensation (known to affect PMB activity), and with PMB concentrations ranging from 0.25 to 256 mg/L based on the strain's MIC. For each strain, time-kill replicates were modelled using NONMEM. Unexpectedly, dilution of CAMHB by up to 10-fold did not affect the growth rate of any of the three strains in the absence of PMB. However, the bactericidal activity of PMB increased with medium dilution, resulting in a reduction in the apparent bacterial regrowth of the various strains observed after a few hours. Data for each strain were well characterized by a PK/PD model, with two bacterial subpopulations with different susceptibility to PMB (more susceptible and less susceptible). The impact of medium dilution and cation compensation showed relatively high, unexplained between-strain variability. Further studies are needed to characterize the mechanism underlying the medium dilution effect.

Crisscross multilayering of cell sheets.

Hydrostatic skeletons such as the Hydra's consist of two stacked layers of muscle cells perpendicularly oriented. In vivo, these bilayers first assemble, and then the muscle fibers of both layers develop and organize with this crisscross orientation. In the present work, we identify an alternative mechanism of crisscross bilayering of myoblasts in vitro, which results from the prior local organization of these active cells in the initial monolayer. The myoblast sheet can be described as a contractile active nematic in which, as expected, most of the +1/2 topological defects associated with this nematic order self-propel. However, as a result of the production of extracellular matrix (ECM) by the cells, a subpopulation of these comet-like defects does not show any self-propulsion. Perpendicular bilayering occurs at these stationary defects. Cells located at the head of these defects converge toward their core where they accumulate until they start migrating on top of the tail of the first layer, while the tail cells migrate in the opposite direction under the head. Since the cells keep their initial orientations, the two stacked layers end up perpendicularly oriented. This concerted process leading to a crisscross bilayering is mediated by the secretion of ECM.

Prognostic factors of Pasteurella infections: a single-center retrospective cohort study over a 14-year period (2005-2018).

BACKGROUND: Pasteurella spp. can lead to fatal infections in humans. OBJECTIVE: To assess prognostic factors of invasive pasteurellosis. METHODS: We conducted a single retrospective cohort study of local versus invasive Pasteurella infections from January 1, 2005, to December 31, 2018, in the Amiens-Picardie University Hospital, France. RESULTS: Forty-five (20.9%) invasive pasteurellosis and 22 (10.2%) complicated local infections were reported among a total of 215 Pasteurella infections. The mortality rate among invasive infections was 22.2% (10/ 45) whereas no death was recorded in local infections group. Non-drug-induced prothrombin time test <70% of standard and platelet counts <100,000/mm3 were more frequent in non-survivors than in survivors (p=0.005 and p=0.019) in univariate analyses. A history of neoplasia (adjusted OR=13.62, p=0.020), an evidence of bacteremia (adjusted OR=20.68, p=0.025), and hemoglobin level <10 g/dL (adjusted OR=17.80, p=0.028) were identified as poor prognostic factors in multivariate analyses. CONCLUSION: Invasive pasteurellosis appears as a serious disease in vulnerable patients, particularly if bacteremia and/or coagulopathies occur.

A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin B In Vitro.

The inoculum effect (i.e., reduction in antimicrobial activity at large starting inoculum) is a phenomenon described for various pathogens. Given that limited data exist regarding inoculum effect of Acinetobacter baumannii, we evaluated killing of A. baumannii by polymyxin B, a last-resort antibiotic, at several starting inocula and developed a pharmacokinetic-pharmacodynamic (PKPD) model to capture this phenomenon. In vitro static time-kill experiments were performed using polymyxin B at concentrations ranging from 0.125 to 128 mg/L against a clinical A. baumannii isolate at four starting inocula from 105 to 108 CFU/mL. Samples were collected up to 30 h to quantify the viable bacterial burden and were simultaneously modeled in the NONMEM software program. The expression of polymyxin B resistance genes (lpxACD, pmrCAB, and wzc), and genetic modifications were studied by RT-qPCR and DNA sequencing experiments, respectively. The PKPD model included a single homogeneous bacterial population with adaptive resistance. Polymyxin B effect was modeled as a sigmoidal Emax model and the inoculum effect as an increase of polymyxin B EC50 with increasing starting inoculum using a power function. Polymyxin B displayed a reduced activity as the starting inoculum increased: a 20-fold increase of polymyxin B EC50 was observed between the lowest and the highest inoculum. No effects of polymyxin B and inoculum size were observed on the studied genes. The proposed PKPD model successfully described and predicted the pronounced in vitro inoculum effect of A. baumannii on polymyxin B activity. These results should be further validated using other bacteria/antibiotic combinations and in vivo models.

The 2020 motile active matter roadmap.

Activity and autonomous motion are fundamental in living and engineering systems. This has stimulated the new field of 'active matter' in recent years, which focuses on the physical aspects of propulsion mechanisms, and on motility-induced emergent collective behavior of a larger number of identical agents. The scale of agents ranges from nanomotors and microswimmers, to cells, fish, birds, and people. Inspired by biological microswimmers, various designs of autonomous synthetic nano- and micromachines have been proposed. Such machines provide the basis for multifunctional, highly responsive, intelligent (artificial) active materials, which exhibit emergent behavior and the ability to perform tasks in response to external stimuli. A major challenge for understanding and designing active matter is their inherent nonequilibrium nature due to persistent energy consumption, which invalidates equilibrium concepts such as free energy, detailed balance, and time-reversal symmetry. Unraveling, predicting, and controlling the behavior of active matter is a truly interdisciplinary endeavor at the interface of biology, chemistry, ecology, engineering, mathematics, and physics. The vast complexity of phenomena and mechanisms involved in the self-organization and dynamics of motile active matter comprises a major challenge. Hence, to advance, and eventually reach a comprehensive understanding, this important research area requires a concerted, synergetic approach of the various disciplines. The 2020 motile active matter roadmap of Journal of Physics: Condensed Matter addresses the current state of the art of the field and provides guidance for both students as well as established scientists in their efforts to advance this fascinating area.

IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity.

Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine-2,3-dioxygenase (IDO) in steady-state lymph nodes (LNs). IDO expression by LN pDCs was closely dependent on MHCII-mediated, antigen-dependent, interactions with Treg. We further established that IDO production by pDCs was necessary to confer suppressive function to Tregs. During EAE development, IDO expression by pDCs was required for the generation of Tregs capable of dampening the priming of encephalitogenic T cell and disease severity. Thus, we describe a novel crosstalk between pDCs and Tregs: Tregs shape tolerogenic functions of pDCs prior to inflammation, such that pDCs in turn, promote Treg suppressive functions during autoimmunity.