Severe injury activates many stress-related and inflammatory pathways that can lead to a systemic hypermetabolic state. Prior studies using perfused hypermetabolic rat livers have identified intrinsic metabolic flux changes that were not dependent upon the continual presence of elevated stress hormones and substrate loads. We investigated the hypothesis that such changes may be due to persistent alterations in gene expression. A systemic hypermetabolic response was induced in rats by applying a moderate burn injury followed 2 days later by cecum ligation and puncture (CLP) to produce sepsis. Control animals received a sham-burn followed by CLP, or a sham-burn followed by sham-CLP. Two days after CLP, livers were analyzed for gene expression changes using DNA microarrays and for metabolism alterations by ex vivo perfusion coupled with Metabolic Flux Analysis. Burn injury prior to CLP increased fluxes while decreases in gene expression levels were observed. Conversely, CLP alone significantly increased metabolic gene expression, but decreased many of the corresponding metabolic fluxes. Burn injury combined with CLP led to the most dramatic changes, where concurrent changes in fluxes and gene expression levels occurred in about 1/3 of the reactions. The data are consistent with the notion that in this model, burn injury prior to CLP increased fluxes through post-translational mechanisms with little contribution of gene expression, while CLP treatment up-regulated the metabolic machinery by transcriptional mechanisms. Overall, these data show that mRNA changes measured at a single time point by DNA microarray analysis do not reliably predict metabolic flux changes in perfused livers.

IntroductionPatient progress, the movement of patients through a hospital system from admission to discharge, is a foundational component of operational effectiveness in healthcare institutions. Optimal patient progress is a key to delivering safe, high-quality and high-value clinical care. The Baystate Patient Progress Initiative (BPPI), a cross-disciplinary, multifaceted quality and process improvement project, was launched on March 1, 2014, with the primary goal of optimizing patient progress for adult patients.MethodsThe BPPI was implemented at our system’s tertiary care, academic medical center, a high-volume, high-acuity hospital that serves as a regional referral center for western Massachusetts. The BPPI was structured as a 24-month initiative with an oversight group that ensured collaborative goal alignment and communication of operational teams. It was organized to address critical aspects of a patient’s progress through his hospital stay and to create additional inpatient capacity. The specific goal of the BPPI was to decrease length of stay (LOS) on the inpatient adult Hospital Medicine service by optimizing an interdisciplinary plan of care and promoting earlier departure of discharged patients. Concurrently, we measured the effects on emergency department (ED) boarding hours per patient and walkout rates.ResultsThe BPPI engaged over 300 employed clinicians and non-clinicians in the work. We created increased inpatient capacity by implementing daily interdisciplinary bedside rounds to proactively address patient progress; during the 24 months, this resulted in a sustained rate of discharge orders written before noon of more than 50% and a decrease in inpatient LOS of 0.30 days (coefficient: −0.014, 95% CI [−0.023, −0.005] P< 0.005). Despite the increase in ED patient volumes and severity of illness over the same time period, ED boarding hours per patient decreased by approximately 2.1 hours (coefficient: −0.09; 95% CI [−0.15, −0.02] P = 0.007). Concurrently, ED walkout rates decreased by nearly 32% to a monthly mean of 0.4 patients (coefficient: 0.4; 95% CI [−0.7, −0.1] P= 0.01).ConclusionThe BPPI realized significant gains in patient progress for adult patients by promoting earlier discharges before noon and decreasing overall inpatient LOS. Concurrently, ED boarding hours per patient and walkout rates decreased.

Locomotion, scratching, and stabilization of the body orientation in space are basic motor functions which are critically important for animal survival. Their execution requires coordinated activity of muscles located in the left and right halves of the body. Commissural interneurons (CINs) are critical elements of the neuronal networks underlying the left-right motor coordination. V0 interneurons (characterized by the early expression of the transcription factor Dbx1) contain a major class of CINs in the spinal cord (excitatory, V0 V ; inhibitory, V0 D ), and a small subpopulation of excitatory ipsilaterally projecting interneurons. The role of V0 CINs in left-right coordination during forward locomotion was demonstrated earlier. Here, to reveal the role of glutamatergic V0 and other V0 subpopulations in control of backward locomotion, scratching, righting behavior, and postural corrections, kinematics of these movements performed by wild-type mice and knock-out mice with glutamatergic V0 or all V0 interneurons ablated were compared. Our results suggest that the functional effect of excitatory V0 neurons during backward locomotion and scratching is inhibitory, and that the execution of scratching involves active inhibition of the contralateral scratching central pattern generator mediated by excitatory V0 neurons. By contrast, other V0 subpopulations are elements of spinal networks generating postural corrections. Finally, all V0 subpopulations contribute to the generation of righting behavior. We found that different V0 subpopulations determine left-right coordination in the anterior and posterior parts of the body during a particular behavior. Our study shows a differential contribution of V0 subpopulations to diverse motor acts that provides new insight to organization of motor circuits.

Mice are frequently used in analyses of the locomotor system. Although forward locomotion (FWL) in intact mice has been studied previously, backward locomotion (BWL) in mice has never been analyzed. The aim of the present study was to compare kinematics of FWL and BWL performed in different environmental conditions (i.e., in a tunnel, on a treadmill, and on an air-ball). In all setups, the average speed and step amplitude during BWL were significantly reduced compared with FWL. The cycle duration varied greatly during both FWL and BWL. The average swing duration during BWL was twice shorter than during FWL on each setup. Mice exhibited different interlimb coordinations (trot and walk with lateral or diagonal sequence) during BWL but only one gait (walk with lateral sequence) during FWL. Location of the rostro-caudal paw trajectory in relation to the hip projection to the surface (HP) depended on hip height. With low hip height, the trajectory was displaced either rostrally (anterior steps) or caudally (posterior steps) to HP. With high hip height, HP was near the middle of the trajectory (middle steps). During FWL, all three forms of steps were observed in the tunnel and predominantly anterior and posterior steps on the treadmill and air-ball, respectively. During BWL, only anterior steps were observed. Intralimb coordination depended on the form of stepping. Limb joints were coordinated to keep the hip at approximately constant height during stance and to have the smallest functional limb length during swing when the limb passed under the hip. NEW & NOTEWORTHY Mice are extensively used for the analysis of the locomotor system. This study is the first examination of the kinematics of forward and backward locomotor movements in different environmental conditions in mice. Obtained results represent a benchmark for studies based on manipulations of activity of specific populations of neurons to reveal their roles in control of specific aspects of locomotion.

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The inflammatory response initiated upon burn injury is also associated with extensive metabolic adjustments. While there is a significant body of literature on the characterization of these changes at the metabolite level, little is known on the mechanisms of induction, especially with respect to the role of gene expression. We have comprehensively analyzed changes in gene expression in rat livers during the first 7 d after 20% total body surface area burn injury using Affymetrix microarrays. A total of 740 genes were significantly altered in expression at 1, 2, 4, and 7 d after burn injury compared to sham-burn controls. Functional classification based on gene ontology terms indicated that metabolism, transport, signaling, and defense/inflammation response accounted for more than 70% of the significantly altered genes. Fisher least-significant difference post-hoc testing of the 740 differentially expressed genes indicated that over 60% of the genes demonstrated significant changes in expression either on d 1 or on d 7 postburn. The gene expression trends were corroborated by biochemical measurements of triglycerides and fatty acids 24 h postburn but not at later time points. This suggests that fatty acids are used, at least in part, in the liver as energy substrates for the first 4 d after injury. Our data also suggest that long-term regulation of energy substrate utilization in the liver following burn injury is primarily at the posttranscriptional level. Last, relevance networks of significantly expressed genes indicate the involvement of key small molecules in the hepatic response to 20% total body surface area burn injury.

Single steps in different directions are often used for postural corrections. However, our knowledge about the neural mechanisms underlying their generation is scarce. This study was aimed to characterize the corrective steps generated in response to disturbances of the basic body configuration caused by forward, backward or outward displacement of the hindlimb, as well as to reveal location in the CNS of the corrective step generating mechanisms. Video recording of the motor response to translation of the supporting surface under the hindlimb along with contact forces and activity of back and limb muscles was performed in freely standing intact and in fixed postmammillary rabbits. In intact rabbits, displacement of the hindlimb in any direction caused a lateral trunk movement towards the contralateral hindlimb, and then a corrective step in the direction opposite to the initial displacement. The time difference between onsets of these two events varied considerably. The EMG pattern in the supporting hindlimb was similar for all directions of corrective steps. It caused the increase in the limb stiffness. EMG pattern in the stepping limb differed in steps with different directions. In postmammillary rabbits the corrective stepping movements, as well as EMG patterns in both stepping and standing hindlimbs were similar to those observed in intact rabbits. This study demonstrates that the corrective trunk and limb movements are generated by separate mechanisms activated by sensory signals from the deviated limb. The neuronal networks generating postural corrective steps reside in the brainstem, cerebellum, and spinal cord.

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