Muscle and Limb Mechanics.

Understanding of the musculoskeletal system has evolved from the collection of individual phenomena in highly selected experimental preparations under highly controlled and often unphysiological conditions. At the systems level, it is now possible to construct complete and reasonably accurate models of the kinetics and energetics of realistic muscles and to combine them to understand the dynamics of complete musculoskeletal systems performing natural behaviors. At the reductionist level, it is possible to relate most of the individual phenomena to the anatomical structures and biochemical processes that account for them. Two large challenges remain. At a systems level, neuroscience must now account for how the nervous system learns to exploit the many complex features that evolution has incorporated into muscle and limb mechanics. At a reductionist level, medicine must now account for the many forms of pathology and disability that arise from the many diseases and injuries to which this highly evolved system is inevitably prone. © 2017 American Physiological Society. Compr Physiol 7:429-462, 2017.

Validated Predictions of Metabolic Energy Consumption for Submaximal Effort Movement.

Physical performance emerges from complex interactions among many physiological systems that are largely driven by the metabolic energy demanded. Quantifying metabolic demand is an essential step for revealing the many mechanisms of physical performance decrement, but accurate predictive models do not exist. The goal of this study was to investigate if a recently developed model of muscle energetics and force could be extended to reproduce the kinematics, kinetics, and metabolic demand of submaximal effort movement. Upright dynamic knee extension against various levels of ergometer load was simulated. Task energetics were estimated by combining the model of muscle contraction with validated models of lower limb musculotendon paths and segment dynamics. A genetic algorithm was used to compute the muscle excitations that reproduced the movement with the lowest energetic cost, which was determined to be an appropriate criterion for this task. Model predictions of oxygen uptake rate (VO2) were well within experimental variability for the range over which the model parameters were confidently known. The model's accurate estimates of metabolic demand make it useful for assessing the likelihood and severity of physical performance decrement for a given task as well as investigating underlying physiologic mechanisms.

Major remaining gaps in models of sensorimotor systems.

Experimental descriptions of the anatomy and physiology of individual components of sensorimotor systems have revealed substantial complexity, making it difficult to intuit how complete systems might work. This has led to increasing efforts to develop and employ mathematical models to study the emergent properties of such systems. Conversely, the development of such models tends to reveal shortcomings in the experimental database upon which models must be constructed and validated. In both cases models are most useful when they point up discrepancies between what we think we know and possibilities that we may have overlooked. This overview considers those components of complete sensorimotor systems that currently appear to be potentially important but poorly understood. These are generally omitted completely from modeled systems or buried in implicit assumptions that underlie the design of the model.

Useful properties of spinal circuits for learning and performing planar reaches.

OBJECTIVE: We developed a detailed model of the spinal circuitry plus musculoskeletal system (SC + MS) for the primate arm and investigated its role in sensorimotor control, learning and storing of movement repertoires. APPROACH: Recently developed models of spinal circuit connectivity, neurons and muscle force/energetics were integrated and in some cases refined to construct the most comprehensive model of the SC + MS to date. The SC + MS's potential contributions to center-out reaching movement were assessed by employing an extremely simple model of the brain that issued only step commands. MAIN RESULTS: The SC + MS was able to generate physiological muscle dynamics underlying reaching across different directions, distances, speeds, and even in the midst of strong dynamic perturbations (i.e. viscous curl field). For each task, there were many different combinations of brain inputs that generated physiological performance. Natural patterns of recruitment and low metabolic cost emerged for about half of the learning trials when a purely kinematic cost function was used and for all of the trials when an estimate of metabolic energy consumption was added to the cost function. Solutions for different tasks could be interpolated to generate intermediate movement and the range over which interpolation was successful was consistent with experimental reports. SIGNIFICANCE: This is the first demonstration that a realistic model of the SC + MS is capable of generating the required dynamics of center-out reaching. The interpolability observed is important for the feasibility of storing motor programs in memory rather than computing them from internal models of the musculoskeletal plant. Successful interpolation of command programs required them to have similar muscle recruitment patterns, which are thought by many to arise from hard-wired muscle synergies rather than learned as in our model system. These properties of the SC + MS along with its tendency to generate energetically efficient solutions might usefully be employed by motor cortex to generate voluntary behaviors such as reaching to targets.

Mammalian muscle model for predicting force and energetics during physiological behaviors.

Muscles convert metabolic energy into mechanical work. A computational model of muscle would ideally compute both effects efficiently for the entire range of muscle activation and kinematic conditions (force and length). We have extended the original Virtual Muscle algorithm (Cheng , 2000) to predict energy consumption for both slow- and fast-twitch muscle fiber types, partitioned according to the activation process (E(a)), cross-bridge cycling (E(xb)) and ATP/PCr recovery (E(recovery)). Because the terms of these functions correspond to identifiable physiological processes, their coefficients can be estimated directly from the types of experiments that are usually performed and extrapolated to dynamic conditions of natural motor behaviors. We also implemented a new approach to lumped modeling of the gradually recruited and frequency modulated motor units comprising each fiber type, which greatly reduced computational time. The emergent behavior of the model has significant implications for studies of optimal motor control and development of rehabilitation strategies because its trends were quite different from traditional estimates of energy (e.g., activation, force, stress, work, etc.). The model system was scaled to represent three different human experimental paradigms in which muscle heat was measured during voluntary exercise; predicted and observed energy rate agreed well both qualitatively and quantitatively.

Pyosalpinx as a sequela of labial fusion in a post-menopausal woman: a case report.

INTRODUCTION: Complete labia fusion is a rare clinical entity in post-menopausal women. The most common complications of this presentation are infections of the urinary tract and retention of urine in the vagina. We present the case of a post-menopausal woman with adnexal mass and abdominal pain due to fusion of the labia majora. To the best of our knowledge this is the first report in the literature of this complication. CASE PRESENTATION: A 78-year-old Caucasian woman was admitted to our hospital due to abdominal pain and urination difficulty, along with fever and leucocytosis. On examination the labial majora were fused. Computed tomography of the abdomen revealed a cystic formation in the anatomical area of the right adnexa. Our patient had developed a pyosalpinx as a Sequela of labial fusion. At laparoscopy the right pyosalpinx was identified and resected, whereas the labia majora were reconstructed via dissection and separation. CONCLUSIONS: Labial fusion is a rare clinical entity in post-menopausal women and can have serious and unexpected complications. Though this presentation is rare, a clinical examination must be performed in detail in order to gain valuable information for an accurate diagnosis. Post-operational instruction must be given to patients in order to prevent the re-occurrence of the fusion and its complications.

Modeling the potentiality of spinal-like circuitry for stabilization of a planar arm system.

The design of control systems for limb prostheses seems likely to benefit from an understanding of how sensorimotor integration is achieved in the intact system. Traditional BMIs guess what movement parameters are encoded by brain activity and then decode them to drive prostheses directly. Modeling the known structure and emergent properties of the biological decoder itself is likely to be more effective in bridging from normal brain activity to functionally useful limb movement. In this study, we have extended a model of spinal circuitry (termed SLR for spinal-like regulator; see Raphael, G., Tsianos, G. A., & Loeb G. E. 2010, Spinal-like regulator facilitates control of a two-degree-of-freedom wrist. The Journal of Neuroscience, 30(28), 9431-9444.) to a planar elbow-shoulder system to investigate how the spinal cord contributes to the control of a musculoskeletal system with redundant and multiarticular musculature and interaction (Coriolis) torques, which are common control problems for multisegment linkages throughout the body. The SLR consists of a realistic set of interneuronal pathways (monosynaptic Ia-excitatory, reciprocal Ia-inhibitory, Renshaw inhibitory, Ib-inhibitory, and propriospinal) that are driven by unmodulated step commands with learned amplitudes. We simulated the response of a planar arm to a brief, oblique impulse at the hand and investigated the role of cocontraction in learning to resist it. Training the SLR without cocontraction led to generally poor performance that was significantly worse than training with cocontraction. Further, removing cocontraction from the converged solutions and retraining the system achieved better performance than the SLR responses without cocontraction. Cocontraction appears to reshape the solution space, virtually eliminating the probability of entrapment in poor local minima. The local minima that are entered during learning with cocontraction are favorable starting points for learning to perform the task when cocontraction is abruptly removed. Given the control system's ability to learn effectively and rapidly, we hypothesize that it will generalize more readily to the wider range of tasks that subjects must learn to perform, as opposed to BMIs mapped to outputs of the musculoskeletal system.

Understanding haptics by evolving mechatronic systems.

Haptics can be defined as the characterization and identification of objects by voluntary exploration and somatosensory feedback. It requires multimodal sensing, motor dexterity, and high levels of cognitive integration with prior experience and fundamental concepts of self versus external world. Humans have unique haptic capabilities that enable tool use. Experimental animals have much poorer capabilities that are difficult to train and even more difficult to study because they involve rapid, subtle, and variable movements. Robots can now be constructed with biomimetic sensing and dexterity, so they may provide a suitable platform on which to test theories of haptics. Robots will need to embody such theories if they are ever going to realize the long-standing dream of working alongside humans using the same tools and objects.

Spinal-like regulator facilitates control of a two-degree-of-freedom wrist.

The performance of motor tasks requires the coordinated control and continuous adjustment of myriad individual muscles. The basic commands for the successful performance of a sensorimotor task originate in "higher" centers such as the motor cortex, but the actual muscle activation and resulting torques and motion are considerably shaped by the integrative function of the spinal interneurons. The relative contributions of brain and spinal cord are less clear for reaching movements than for automatic tasks such as locomotion. We have modeled a two-axis, four-muscle wrist joint with realistic musculoskeletal mechanics and proprioceptors and a network of regulatory circuitry based on the classical types of spinal interneurons (propriospinal, monosynaptic Ia-excitatory, reciprocal Ia-inhibitory, Renshaw inhibitory, and Ib-inhibitory pathways) and their supraspinal control (via biasing activity, presynaptic inhibition, and fusimotor gain). The modeled system has a very large number of control inputs, not unlike the real spinal cord that the brain must learn to control to produce desired behaviors. It was surprisingly easy to program this model to emulate actual performance in four very different but well described behaviors: (1) stabilizing responses to force perturbations; (2) rapid movement to position target; (3) isometric force to a target level; and (4) adaptation to viscous curl force fields. Our general hypothesis is that, despite its complexity, such regulatory circuitry substantially simplifies the tasks of learning and producing complex movements.

High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding.

BACKGROUND: The best antisecretory treatment after endoscopic hemostasis in patients with ulcer bleeding is still in quest. OBJECTIVES: To compare pantoprazole and somatostatin continuous infusion after endoscopic hemostasis in patients with bleeding peptic ulcers. PATIENTS AND METHODS: A total of 164 consecutive patients with a bleeding peptic ulcer, after successful endoscopic hemostasis, were randomly assigned to receive, double blindly, continuous IV infusion of pantoprazole 8 mg/h for 48 h after a bolus of 40 mg (group P) or somatostatin 250 microg/h for 48 h after a bolus of 250 microg (group-S). Twenty-four-hour pH-metry was performed in the last 30 patients in each group. Endoscopy was performed, in case of bleeding nonrecurrence, every 48 h until disappearance of stigmata. RESULTS: Bleeding recurrence: group S 14 patients (17%) versus group P 4 (5%) (P=0.046). In multivariate analysis, bleeding recurrence was 4.57 (CI 1.31-15.91) times more frequent in group S (P=0.02). There was no difference in the need for surgery and mortality. Acid suppression over pH 6: group S 82.9% of the time versus group P 81.5% (P=0.97). Acid suppression over pH 6 for >85% of the time: group S 14 (47%) patients versus group P 17 (57%) (P=0.44). Disappearance of endoscopic stigmata after 48 h: group S 25/68 patients (37%) versus group P 72/78 (92%) (P<0.0001). No major side effects identified in either study group. CONCLUSIONS: In patients with a bleeding ulcer, after successful endoscopic hemostasis, despite equipotent acid suppression, pantoprazole continuous infusion was superior to somatostatin to prevent bleeding recurrence and quick disappearance of the endoscopic stigmata. Nevertheless, no differences were seen in the need for surgery and mortality.