Biomedical subjects

Tom De Smet

Publications and source records attributed to Tom De Smet.

4 recordsLinked to original sources

PubMed2025

TamL is a Key Player of the Outer Membrane Homeostasis in Bacteroidota.

In Proteobacteria, the outer membrane protein TamA and the inner membrane-anchored protein TamB form the Translocation and Assembly Module (TAM) complex, which facilitates the transport of autotransporters, virulence factors, and likely lipids across the two membranes. In Bacteroidota, TamA is replaced by TamL, a TamA-like lipoprotein with a lipid modification at its N-terminus that likely anchors it to the outer membrane. This structural difference suggests that TamL may have a distinct function compared to TamA. However, the role of TAM in bacterial phyla other than Proteobacteria remains unexplored. Our study aimed to elucidate the function of TamL in Flavobacterium johnsoniae, an environmental Bacteroidota. Unlike its homologs in Proteobacteria, we found that TamL and TamB are essential in F. johnsoniae. Through genetic, phenotypic, proteomic, and lipidomic analyses, we show that TamL depletion severely compromises outer membrane integrity, as evidenced by reduced cell viability, altered cell shape, increased susceptibility to membrane-disrupting agents, and elevated levels of outer membrane lipoproteins. Notably, we did not observe an overall decrease in the levels of β-barrel outer membrane proteins, nor substantial alterations in outer membrane lipid composition. By pull-down assays, we found TamL co-purifying with TamB in F. johnsoniae, suggesting an interaction. Furthermore, we found that while TamL and TamB monocistronic genes are conserved among Bacteroidota, only some species encode multiple TamL, TamB and TamA proteins. To our knowledge, this study is the first to provide functional insights into a TAM subunit beyond Proteobacteria.

Bacterial Outer Membrane Proteins↗

PubMed2006

Closed loops in anaesthesia.

Closed-loop systems are able to make their own decisions and to try to reach and maintain a preset target. As a result, they might help the anaesthetist to optimise the titration of drug administration without any overshoot, controlling physiological functions and guiding monitoring variables. Thanks to the development of fast computer technology and more reliable pharmacological effect measures, the study of automation in anaesthesia has regained popularity. This short review focuses on the most recently developed and tested feedback systems in anaesthesia. Various new approaches for controlling the administration of intravenous and inhaled hypnotic-anaesthetic drugs have recently been published. For analgesics, a framework for further research has been presented in the literature. For other drugs, such as muscle relaxants and haemodynamic agents, only short reviews can be found. Until now, most of these systems have had to be under development. The challenge is now fully to establish the safety, efficacy, reliability and utility of closed-loop anaesthesia so that it can be adopted in the clinical setting. Besides, their role in optimising the controlled variables and control models, these systems have to be tested in extreme circumstances in order to test their robustness.

Anesthesia↗

PubMed2004

Performance evaluation of two published closed-loop control systems using bispectral index monitoring: a simulation study.

BACKGROUND: Although automated closed-loop control systems may improve quality of care, their safety must be proved under extreme control conditions. This study describes a simulation methodology to test automated controllers and its application in a comparison of two published controllers for Bispectral Index (BIS)-guided propofol administration. METHODS: A patient simulator was developed to compare controllers. Using input scripts to dictate patient characteristics, target BIS values, and the time course of surgical events, the simulator continuously monitors the infusion pump under control and generates BIS values as a composite of modeled response to drug, perceived stimulation, and random noise. The simulator formats the output stream of BIS data as input to the controller under test to emulate the serial output of the actual BIS monitor. A published model-based controller and a classic proportional integral derivative controller were compared when using the BIS value as a controlled variable. Each controller was tested using a set of 10 virtual patients undergoing a fixed surgical profile that was repeated with BIS targets set at 30, 50, and 70. Controller performance was assessed using median (absolute) prediction error, divergence, wobble, and percentage time within BIS target range metrics. RESULTS: The median prediction error was significantly smaller for the proportional integral derivative controller than for the model-based controller. The median absolute prediction error was smaller for the model-based controller than for the proportional integral derivative controller for each BIS target, reaching statistical significance for targets 30 and 50. CONCLUSIONS: When simulating closed-loop control of BIS using propofol, the use of a patient-individualized, model-based adaptive closed-loop system with effect site control resulted in better control of BIS compared with a standard proportional integral derivative controller with plasma site control. Even under extreme conditions, the modeled-based controller exhibited no behavioral problems.

Algorithms↗

PubMed2002

Closed-loop control of anaesthesia.

PURPOSE OF REVIEW: Closed-loop systems are able to make decisions on their own and try to reach and maintain a preset target. As a result, they might help the anaesthesiologist in optimizing the titration of drug administration without overshooting, controlling physiological functions and guiding monitoring variables. Thanks to the development of fast computer technology and more reliable pharmacological effect measures, the study of automation in anaesthesia has regained popularity. RECENT FINDINGS: This short review focuses on the most recently developed and tested feed-back systems in anaesthesia. Various new approaches for controlling the administration of intravenous and inhaled hypnotic-anaesthetic drugs have been published recently. For analgesics, a framework for further research has been presented in the literature. For other drugs, such as muscle relaxants and haemodynamics, a short review can be found. SUMMARY: Until now, most of these systems are still under development. The challenge is now to establish fully the safety, efficacy, reliability and utility of closed-loop anaesthesia for its adoption into the clinical setting. Besides the optimization of controlled variables and control models, these systems have to be tested in extreme circumstances.

Journal Article↗