Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
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BACKGROUNDLung protective ventilation is considered standard of care in the intensive care unit. However, modifying the ventilator settings can be challenging and is time consuming. Closed loop modes of ventilation are increasingly attractive for use in critically ill patients. With closed loop ventilation, settings that are typically managed by the ICU professionals are under control of the ventilator's algorithms.OBJECTIVESTo describe the effectiveness, safety, efficacy and workload with currently available closed loop ventilation modes.DESIGNSystematic review of randomised clinical trials.DATA SOURCESA comprehensive systematic search in PubMed, Embase and the Cochrane Central register of Controlled Trials search was performed in January 2023.ELIGIBILITY CRITERIARandomised clinical trials that compared closed loop ventilation with conventional ventilation modes and reported on effectiveness, safety, efficacy or workload.RESULTSThe search identified 51 studies that met the inclusion criteria. Closed loop ventilation, when compared with conventional ventilation, demonstrates enhanced management of crucial ventilator variables and parameters essential for lung protection across diverse patient cohorts. Adverse events were seldom reported. Several studies indicate potential improvements in patient outcomes with closed loop ventilation; however, it is worth noting that these studies might have been underpowered to conclusively demonstrate such benefits. Closed loop ventilation resulted in a reduction of various aspects associated with the workload of ICU professionals but there have been no studies that studied workload in sufficient detail.CONCLUSIONSClosed loop ventilation modes are at least as effective in choosing correct ventilator settings as ventilation performed by ICU professionals and have the potential to reduce the workload related to ventilation. Nevertheless, there is a lack of sufficient research to comprehensively assess the overall impact of these modes on patient outcomes, and on the workload of ICU staff.
MULTIFILE
Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers. Aim: To analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol. Methods: After determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction. Results: Kinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax. Conclusion: High (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.
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