Changes in Dynamic Mean Ankle Moment Arm in Unimpaired Walking Across Speeds, Ramps, and Stairs.

Understanding the natural biomechanics of walking at different speeds and activities is crucial to develop effective assistive devices for persons with lower-limb impairments. While continuous measures such as joint angle and moment are well-suited for biomimetic control of robotic systems, whole-stride summary metrics are useful for describing changes across behaviors and for designing and controlling passive and semi-active devices. Dynamic mean ankle moment arm (DMAMA) is a whole-stride measure representing the moment arm of the ground reaction impulse about the ankle joint-effectively, how "forefoot-dominated" or "hindfoot-dominated" a movement is. DMAMA was developed as a target and performance metric for semi-active devices that adjust once per stride. However, for implementation in this application, DMAMA must be characterized across various activities in unimpaired individuals. In our study, unimpaired participants walked at "slow," "normal," and "fast" self-selected speeds on level ground and at a normal self-selected speed while ascending and descending stairs and a 5-degree incline ramp. DMAMA measured from these activities displayed a borderline-significant negative sensitivity to walking speed, a significant positive sensitivity to ground incline, and a significant decrease when ascending stairs compared to descending. The data suggested a nonlinear relationship between DMAMA and walking speed; half of the participants had the highest average DMAMA at their "normal" speed. Our findings suggest that DMAMA varies substantially across activities, and thus, matching DMAMA could be a valuable metric to consider when designing biomimetic assistive lower-limb devices.

Wearable sensing for understanding and influencing human movement in ecological contexts.

Wearable sensors offer a unique opportunity to study movement in ecological contexts - that is, outside the laboratory where movement happens in ordinary life. This article discusses the purpose, means, and impact of using wearable sensors to assess movement context, kinematics, and kinetics during locomotion, and how this information can be used to better understand and influence movement. We outline the types of information wearable sensors can gather and highlight recent developments in sensor technology, data analysis, and applications. We close with a vision for important future research and key questions the field will need to address to bring the potential benefits of wearable sensing to fruition.

Prenatal diagnosis of SMPD4 loss - A neurodevelopmental disorder with microcephaly, arthrogryposis and structural brain anomalies.

SMPD4 loss is a rare neurodevelopmental disorder that leads to severe mental and physical disability and early death in infancy. Most cases of this genetic condition have been diagnosed postnatally. This article focuses on the prenatal findings of affected fetuses. The phenotypes can include growth restriction, arthrogryposis (clenched hands, foot deformity), as well as cerebral abnormalities (simplified gyral pattern/lissencephaly, cerebellar hypoplasia, corpus callosum deformity). SMPD4 loss is detectable via exome sequencing. Here, two fetuses displayed a homozygotic pathogen variant in the SMPD4 gene, encoding for the enzyme Sphingomyelinase-4. Both parents were heterozygous carriers of the pathogenic variant. On detection of the above mentioned signs exome sequencing is indicated, with focus on the SMPD4 gene.

Age-related changes in gait biomechanics and their impact on the metabolic cost of walking: Report from a National Institute on Aging workshop.

Changes in old age that contribute to the complex issue of an increased metabolic cost of walking (mass-specific energy cost per unit distance traveled) in older adults appear to center at least in part on changes in gait biomechanics. However, age-related changes in energy metabolism, neuromuscular function and connective tissue properties also likely contribute to this problem, of which the consequences are poor mobility and increased risk of inactivity-related disease and disability. The U.S. National Institute on Aging convened a workshop in September 2021 with an interdisciplinary group of scientists to address the gaps in research related to the mechanisms and consequences of changes in mobility in old age. The goal of the workshop was to identify promising ways to move the field forward toward improving gait performance, decreasing energy cost, and enhancing mobility for older adults. This report summarizes the workshop and brings multidisciplinary insight into the known and potential causes and consequences of age-related changes in gait biomechanics. We highlight how gait mechanics and energy cost change with aging, the potential neuromuscular mechanisms and role of connective tissue in these changes, and cutting-edge interventions and technologies that may be used to measure and improve gait and mobility in older adults. Key gaps in the literature that warrant targeted research in the future are identified and discussed.

SARS-CoV-2 seropositivity and seroconversion in patients undergoing active cancer-directed therapy

Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. To gauge the effectiveness of these measures at the University of Pennsylvania, we conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between 5/21/2020 and 10/8/2020. Participants completed questionnaires and had up to five serial blood collections. Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95%CI 0.0-4.1%) over 14.8 person-years of follow up, with a median of 13 healthcare visits per patient. These results suggest that cancer patients receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.

Mechanisms of gait phase entrainment in healthy subjects during rhythmic electrical stimulation of the medial gastrocnemius.

Studies have shown that human gait entrains to rhythmic bursts of ankle torque for perturbation intervals both slightly shorter and slightly longer than the natural stride period while walking on a treadmill and during overground walking, with phase alignment such that the torque adds to ankle push-off. This study investigated whether human gait also entrains to align the phase of rhythmic electrical stimulation of the gastrocnemius muscle with the timing of ankle push-off. In addition, this study investigated the muscle response to electrical stimulation at different phases of the gait cycle. We found that for both treadmill and overground walking entrainment was observed with phasing that aligned the stimuli with ankle push-off or just before foot contact. Achilles tendon wave speed measurements showed a significant difference (increase) in tendon load when electrical stimulation was applied just after foot contact and during swing phase, with a greater increase for higher amplitudes of electrical stimulation. However, stimulation did not increase tendon load when the timing coincided with push-off. Stride period measurements also suggest the effect of electrical stimulation is sensitive to the gait phase it is applied. These results confirmed that timing aligned with push-off is an attractor for electrical stimulation-induced perturbations of the medial gastrocnemius, and that the muscle response to stimulation is sensitive to timing and amplitude. Future research should investigate other muscles and timings and separate sensory vs. motor contributions to these phenomena.

Rates of COVID-19-related Outcomes in Cancer compared to non-Cancer Patients

Cancer patients are a vulnerable population postulated to be at higher risk for severe COVID-19 infection. Increased COVID-19 morbidity and mortality in cancer patients may be attributable to age, comorbidities, smoking, healthcare exposure, and cancer treatments, and partially to the cancer itself. Most studies to date have focused on hospitalized patients with severe COVID-19, thereby limiting the generalizability and interpretability of the association between cancer and COVID-19 severity. We compared outcomes of SARS-CoV-2 infection in 323 patients enrolled prior to the pandemic in a large academic biobank (n=67 cancer patients and n=256 non-cancer patients). After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer was independently associated with higher odds of hospitalization (OR 2.16, 95% CI 1.12-4.18) and 30-day mortality (OR 5.67, CI 1.49-21.59). These associations were primarily driven by patients with active cancer. These results emphasize the critical importance of preventing SARS-CoV-2 exposure and mitigating infection in cancer patients.

Ankle Control in Walking and Running: Speed- and Gait-Related Changes in Dynamic Mean Ankle Moment Arm.

The human foot-ankle complex uses heel-to-toe ground contact progression in walking, but primarily forefoot contact in high-speed running. This qualitative change in ankle control is clear to the runner, but current measures of ankle behavior cannot isolate the effect, and it is unknown how it changes across moderate speeds. We investigated this dynamic ankle control across a range of walking and running speeds using a new measure, the dynamic mean ankle moment arm (DMAMA): the ratio of sagittal ankle moment impulse to ground reaction force impulse on a single limb. We hypothesized that DMAMA would increase with speed in both walking and running, indicating more forefoot-dominated gait with ground reaction forces more anterior to the ankle. Human subjects walked (1.0-2.0 m/s) and ran (2.25-5.25 m/s) on an instrumented treadmill with motion capture and pressure insoles to estimate DMAMA. DMAMA decreased with increasing walking speed, then increased upon the transition to running, and increased further with increasing running speed. These results provide quantitative evidence that walking becomes more hindfoot-dominated as speed increases-similar to behavior during acceleration-and that running is more forefoot-dominated than walking. The instantaneous center of pressure (COP) at initial ground contact did not follow the same trends. The discrepancy highlights the value of DMAMA in summarizing ankle control across the whole stance phase. DMAMA may provide a useful outcome metric for evaluating biomimetic prostheses and for quantifying foot contact styles in running.

Analyzing Gait in the Real World Using Wearable Movement Sensors and Frequently Repeated Movement Paths.

Assessing interventions for mobility disorders using real-life movement remains an unsolved problem. We propose a new method combining the strengths of traditional laboratory studies where environment is strictly controlled, and field-based studies where subjects behave naturally. We use a foot-mounted inertial sensor, a GPS receiver and a barometric altitude sensor to reconstruct a subject's path and detailed foot movement, both indoors and outdoors, during days-long measurement using strapdown navigation and sensor fusion algorithms. We cluster repeated movement paths based on location, and propose that on these paths, most environmental and behavioral factors (e.g., terrain and motivation) are as repeatable as in a laboratory. During each bout of movement along a frequently repeated path, any synchronized measurement can be isolated for study, enabling focused statistical comparison of different interventions. We conducted a 10-day test on one subject wearing athletic shoes and sandals each for five days. The algorithm detected four frequently-repeated straight walking paths with at least 300 total steps and repetitions on at least three days for each condition. Results on these frequently-repeated paths indicated significantly lower foot clearance and shorter stride length and a trend toward decreased stride width when wearing athletic shoes vs. sandals. Comparisons based on all straight walking were similar, showing greater statistical power, but higher variability in the data. The proposed method offers a new way to evaluate how mobility interventions affect everyday movement behavior.

Monitoring Motor Symptoms During Activities of Daily Living in Individuals With Parkinson's Disease.

This literature review addressed wearable sensor systems to monitor motor symptoms in individuals with Parkinson's disease (PD) during activities of daily living (ADLs). Specifically, progress in monitoring tremor, freezing of gait, dyskinesia, bradykinesia, and hypokinesia was reviewed. Twenty-seven studies were found that met the criteria of measuring symptoms in a home or home-like setting, with some studies examining multiple motor disorders. Accelerometers, gyroscopes, and electromyography sensors were included, with some studies using more than one type of sensor. Five studies measured tremor, five studies examined bradykinesia or hypokinesia, thirteen studies included devices to measure dyskinesia or motor fluctuations, and ten studies measured akinesia or freezing of gait. Current sensor technology can detect the presence and severity of each of these symptoms; however, most systems require sensors on multiple body parts, which is challenging for remote or ecologically valid observation. Different symptoms are detected by different sensor placement, suggesting that the goal of detecting all symptoms with a reduced set of sensors may not be achievable. For the goal of monitoring motor symptoms during ADLs in a home setting, the measurement system should be simple to use, unobtrusive to the wearer and easy for an individual with PD to put on and take off. Machine learning algorithms such as neural networks appear to be the most promising way to detect symptoms using a small number of sensors. More work should be done validating the systems during unscripted and unconstrained ADLs rather than in scripted motions.

Sensitivity of biomechanical outcomes to independent variations of hindfoot and forefoot stiffness in foot prostheses.

Many studies have reported the effects of different foot prostheses on gait, but most results cannot be generalized because the prostheses' properties are seldom reported. We varied hindfoot and forefoot stiffness in an experimental foot prosthesis, in increments of 15N/mm, and tested the parametric effects of these variations on treadmill walking in unilateral transtibial amputees, at speeds from 0.7 to 1.5m/s. We computed outcomes such as prosthesis energy return, center of mass (COM) mechanics, ground reaction forces, and joint mechanics, and computed their sensitivity to component stiffness. A stiffer hindfoot led to reduced prosthesis energy return, increased ground reaction force (GRF) loading rate, and greater stance-phase knee flexion and knee extensor moment. A stiffer forefoot resulted in reduced prosthetic-side ankle push-off and COM push-off work, and increased knee extension and knee flexor moment in late stance. The sensitivity parameters obtained from these tests may be useful in clinical prescription and further research into compensatory mechanisms of joint function.

Light-sheet microscopy for everyone? Experience of building an OpenSPIM to study flatworm development.

BACKGROUND: Selective plane illumination microscopy (SPIM a type of light-sheet microscopy) involves focusing a thin sheet of laser light through a specimen at right angles to the objective lens. As only the thin section of the specimen at the focal plane of the lens is illuminated, out of focus light is naturally absent and toxicity due to light (phototoxicity) is greatly reduced enabling longer term live imaging. OpenSPIM is an open access platform (Pitrone et al. 2013 and OpenSPIM.org) created to give new users step-by-step instructions on building a basic configuration of a SPIM microscope, which can in principle be adapted and upgraded to each laboratory's own requirements and budget. Here we describe our own experience with the process of designing, building, configuring and using an OpenSPIM for our research into the early development of the polyclad flatworm Maritigrella crozieri - a non-model animal. RESULTS: Our OpenSPIM builds on the standard design with the addition of two colour laser illumination for simultaneous detection of two probes/molecules and dual sided illumination, which provides more even signal intensity across a specimen. Our OpenSPIM provides high resolution 3d images and time lapse recordings, and we demonstrate the use of two colour lasers and the benefits of two color dual-sided imaging. We used our microscope to study the development of the embryo of the polyclad flatworm M. crozieri. The capabilities of our microscope are demonstrated by our ability to record the stereotypical spiral cleavage pattern of M. crozieri with high-speed multi-view time lapse imaging. 3D and 4D (3D + time) reconstruction of early development from these data is possible using image registration and deconvolution tools provided as part of the open source Fiji platform. We discuss our findings on the pros and cons of a self built microscope. CONCLUSIONS: We conclude that home-built microscopes, such as an OpenSPIM, together with the available open source software, such as MicroManager and Fiji, make SPIM accessible to anyone interested in having continuous access to their own light-sheet microscope. However, building an OpenSPIM is not without challenges and an open access microscope is a worthwhile, if significant, investment of time and money. Multi-view 4D microscopy is more challenging than we had expected. We hope that our experience gained during this project will help future OpenSPIM users with similar ambitions.

Mechanisms of Gait Asymmetry Due to Push-Off Deficiency in Unilateral Amputees.

Unilateral lower-limb amputees exhibit asymmetry in many gait features, such as ground force, step time, step length, and joint mechanics. Although these asymmetries result from weak prosthetic-side push-off, there is no proven mechanistic explanation of how that impairment propagates to the rest of the body. We used a simple dynamic walking model to explore possible consequences of a unilateral impairment similar to that of a transtibial amputee. The model compensates for reduced push-off work from one leg by performing more work elsewhere, for example during the middle of stance by either or both legs. The model predicts several gait abnormalities, including slower forward velocity of the body center-of-mass during intact-side stance, greater energy dissipation in the intact side, and more positive work overall. We tested these predictions with data from unilateral transtibial amputees (N = 11) and nonamputee control subjects (N = 10) walking on an instrumented treadmill. We observed several predicted asymmetries, including forward velocity during stance phases and energy dissipation from the two limbs, as well as greater work overall. Secondary adaptations, such as to reduce discomfort, may exacerbate asymmetry, but these simple principles suggest that some asymmetry may be unavoidable in cases of unilateral limb loss.

Case report: Anti-N-methyl-D-aspartate receptor encephalitis and its anesthetic implications.

We describe the anesthetic management and implications of 2 patients with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. Anti-NMDA receptor encephalitis is a neurological disorder caused by production of antibodies to the NMDA receptor. The NMDA receptor is the target of many drugs used in anesthesia. It is important to understand the pharmacologic interactions these anesthetics have with a disabled NMDA receptor while preparing an anesthetic plan for patients with anti-NMDA receptor encephalitis. Symptoms of the disease such as psychosis, paroxysmal sympathetic hyperactivity, and central hypoventilation pose risks to the induction and maintenance of anesthesia in these patients.