The symptoms evolution of long COVID­19 (SE-LC19): a new patient-reported content valid instrument.

BACKGROUND: The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID­19 (SE-LC19), and establish its content validity. METHODS: The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID. A 2-part mixed-method approach was employed. Part 1: Qualitative interviews with a purposive sample of 41 patients with confirmed long COVID were conducted for the content validation of SE-LC19. During cognitive debriefing interviews, patients were asked to describe their understanding of the instrument's instructions, specific symptoms, response options, and recall period to ensure its relevance and comprehensiveness. Five clinicians of different medical specialties who regularly treated patients with long COVID were also interviewed to obtain their clinical expert opinions on SE-LC19. Part 2: Exploratory Rasch Measurement Theory (RMT) analysis was conducted to evaluate the psychometric properties of the SE-LC19 data collected during the interviews. RESULTS: Overall, patients reported that the instructions, questions, recall period, and response options for SE-LC19 were comprehensive and relevant. Minor conceptual gaps reported by patients captured nuances in the experience of some symptoms that could be considered in future studies. Some patients suggested a revision of the recall period from 24 h to 7 days to be able to capture more symptoms given the waxing and waning nature of some symptoms. Clinicians found the instrument comprehensive with minimal suggestions regarding its content. Exploratory RMT analyses provided evidence that the SE-LC19 questionnaire performed as intended. CONCLUSION: The present mixed-methods study in patients with confirmed long COVID supports the content validity and applicability of the SE-LC19 instrument to evaluate the symptoms of patients with long COVID. Further research is warranted to explore the psychometric properties of the instrument and refine a meaningful and robust patient-relevant endpoint for use in different settings such as clinical trials and clinical practice to track the onset, severity, and recovery of long COVID.

Sleep benefits perceptual but not movement-based learning of locomotor sequences.

Practicing complex locomotor skills, such as those involving a step sequence engages distinct perceptual and motor mechanisms that support the recall of learning under new conditions (i.e., skill transfer). While sleep has been shown to enhance learning of sequences of fine movements (i.e., sleep-dependent consolidation), here we examined whether this benefit extends to learning of a locomotor pattern. Specifically, we tested the perceptual and motor learning of a locomotor sequence following sleep compared to wake. We hypothesized that post-practice sleep would increase locomotor sequence learning in the perceptual, but not in the motor domain. In this study, healthy young adult participants (n = 48; 18-33 years) practiced a step length sequence on a treadmill cued by visual stimuli displayed on a screen during training. Participants were then tested in a perceptual condition (backward walking with the same visual stimuli), or a motor condition (forward walking but with an inverted screen). Skill was assessed immediately, and again after a 12-h delay following overnight sleep or daytime wake (n = 12 for each interval/condition). Off-line learning improved following sleep compared to wake, but only for the perceptual condition. Our results suggest that perceptual and motor sequence learning are processed separately after locomotor training, and further points to a benefit of sleep that is rooted in the perceptual as opposed to the motor aspects of motor learning.

Visuospatial cognition predicts performance on an obstructed vision obstacle walking task in older adults.

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.

Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.

OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life. SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews. PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed. PRIMARY AND SECONDARY OUTCOMES: Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model. RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months. CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.

Reduced corticospinal drive and inflexible temporal adaptation during visually guided walking in older adults.

Corticospinal drive during walking is reduced in older adults compared with young adults, but it is not clear how this decrease might compromise one's ability to adjust stepping, particularly during visuomotor adaptation. We hypothesize that age-related changes in corticospinal drive could predict differences in older adults' step length and step time adjustments in response to visual perturbations compared with younger adults. Healthy young (n = 21; age 18-33 yr) and older adults (n = 20; age 68-80 yr) were tested with a treadmill task, incorporating visual feedback of the foot position and stepping targets in real-time. During adaptation, the visuomotor gain was reduced on one side, causing the foot cursor and step targets to move slower on that side of the screen (i.e., split-visuomotor adaptation). Corticospinal drive was quantified by coherence between electromyographic signals in the beta-gamma frequency band (15-45 Hz). The results showed that 1) older adults adapted to visuomotor perturbations during walking, with a similar reduction in error asymmetry compared with younger adults; 2) however, older adults showed reduced adaptation in step time symmetry, despite demonstrating similar adaptation in step length asymmetry compared with younger adults; and 3) smaller overall changes in step time asymmetry was associated with reduced corticospinal drive to the tibialis anterior in the slow leg during split-visuomotor adaptation. These findings suggest that changes in corticospinal drive may affect older adults' control of step timing in response to visual challenges. This could be important for safe navigation when walking in different environments or dealing with unexpected circumstances.NEW & NOTEWORTHY Corticospinal input is essential for visually guided walking, especially when the walking pattern must be modified to accurately step on safe locations. Age-related changes in corticospinal drive are associated with inflexible step time, which necessitates different locomotor adaptation strategies in older adults.

Hummingbird ingestion of low-concentration ethanol within artificial nectar.

Both frugivores and nectarivores are potentially exposed to dietary ethanol produced by fermentative yeasts which metabolize sugars. Some nectarivorous mammals exhibit a preference for low-concentration ethanol solutions compared to controls of comparable caloric content, but behavioural responses to ethanol by nectar-feeding birds are unknown. We investigated dietary preference by Anna's Hummingbirds (Calypte anna) for ethanol-enhanced sucrose solutions. Via repeated binary-choice experiments, three adult male hummingbirds were exposed to sucrose solutions containing 0%, 1% or 2% ethanol; rates of volitional nectar consumption were measured over a 3 h interval. Hummingbirds did not discriminate between 0% and 1% ethanol solutions, but exhibited significantly reduced rates of consumption of a 2% ethanol solution. Opportunistic measurements of ethanol concentrations within hummingbird feeders registered values peaking at about 0.05%. Ethanol at low concentrations (i.e. up to 1%) is not aversive to Anna's Hummingbirds and may be characteristic of both natural and anthropogenic nectars upon which they feed. Given high daily amounts of nectar consumption by hummingbirds, chronic physiological exposure to ethanol can thus be substantial, although naturally occurring concentrations within floral nectar are unknown.

Cortico-Subthalamic Field Potentials Support Classification of the Natural Gait Cycle in Parkinson's Disease and Reveal Individualized Spectral Signatures.

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson's disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4-12 Hz) spectral power during the period before contralateral leg swing. Furthermore, STN shows increased theta frequency (4-8 Hz) coherence with the primary motor through the initiation and early phase of contralateral leg swing. Additional analysis revealed that each patient had specific frequency bands that could detect a significant difference between left and right initial leg swing. Our findings indicate that there are alternating spectral changes between the two hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both the STN and cortical areas at discrete frequency bands that may be used to drive adaptive DBS to improve gait dysfunction in patients with Parkinson's disease.

Corticospinal drive is associated with temporal walking adaptation in both healthy young and older adults.

Healthy aging is associated with reduced corticospinal drive to leg muscles during walking. Older adults also exhibit slower or reduced gait adaptation compared to young adults. The objective of this study was to determine age-related changes in the contribution of corticospinal drive to ankle muscles during walking adaptation. Electromyography (EMG) from the tibialis anterior (TA), soleus (SOL), medial, and lateral gastrocnemius (MGAS, LGAS) were recorded from 20 healthy young adults and 19 healthy older adults while they adapted walking on a split-belt treadmill. We quantified EMG-EMG coherence in the beta-gamma (15-45 Hz) and alpha-band (8-15 Hz) frequencies. Young adults demonstrated higher coherence in both the beta-gamma band coherence and alpha band coherence, although effect sizes were greater in the beta-gamma frequency. The results showed that slow leg TA-TA coherence in the beta-gamma band was the strongest predictor of early adaptation in double support time. In contrast, early adaptation in step length symmetry was predicted by age group alone. These findings suggest an important role of corticospinal drive in adapting interlimb timing during walking in both young and older adults.

Neural Control of Human Locomotor Adaptation: Lessons about Changes with Aging.

Walking patterns are adaptable in response to different environmental demands, which requires neural input from spinal and supraspinal structures. With an increase in age, there are changes in walking adaptation and in the neural control of locomotion, but the age-related changes in the neural control of locomotor adaptation is unclear. The purpose of this narrative review is to establish a framework where the age-related changes of neural control of human locomotor adaptation can be understood in terms of reactive feedback and predictive feedforward control driven by sensory feedback during locomotion. We parse out the effects of aging on (a) reactive adaptation to split-belt walking, (b) predictive adaptation to split-belt walking, (c) reactive visuomotor adaptation, and (d) predictive visuomotor adaptation, and hypothesize that specific neural circuits are influenced differentially with age, which influence locomotor adaptation. The differences observed in the age-related changes in walking adaptation across different locomotor adaptation paradigms will be discussed in light of the age-related changes in the neural mechanisms underlying locomotion.

Visuomotor errors drive step length and step time adaptation during 'virtual' split-belt walking: the effects of reinforcement feedback.

Precise foot placement is dependent on changes in spatial and temporal coordination between two legs in response to a perturbation during walking. Here, we used a 'virtual' split-belt adaptation task to examine the effects of reinforcement (reward and punishment) feedback about foot placement on the changes in error, step length and step time asymmetry. Twenty-seven healthy adults (20 ± 2.5 years) walked on a treadmill with continuous feedback of the foot position and stepping targets projected on a screen, defined by a visuomotor gain for each leg. The paradigm consisted of a baseline period (same gain on both legs), visuomotor adaptation period (split: one high = 'fast', one low = 'slow' gain) and post-adaptation period (same gain). Participants were divided into 3 groups: control group received no score, reward group received increasing score for each target hit, and punishment group received decreasing score for each target missed. Re-adaptation was assessed 24 ± 2 h later. During early adaptation, the slow foot undershot and fast foot overshot the stepping target. Foot placement errors were gradually reduced by late adaptation, accompanied by increasing step length asymmetry (fast < slow step length) and step time asymmetry (fast > slow step time). Only the punishment group showed greater error reduction and step length re-adaptation on the next day. The results show that (1) explicit feedback of foot placement alone drives adaptation of both step length and step time asymmetry during virtual split-belt walking, and (2) specifically, step length re-adaptation driven by visuomotor errors may be enhanced by punishment feedback.

Age differences in adaptation of medial-lateral gait parameters during split-belt treadmill walking.

The split-belt treadmill has been used to examine the adaptation of spatial and temporal gait parameters. Historically, similar studies have focused on anterior-posterior (AP) spatiotemporal gait parameters because this paradigm is primarily a perturbation in the AP direction, but it is important to understand whether and how medial-lateral (ML) control adapts in this scenario. The ML control of balance must be actively controlled and adapted in different walking environments. Furthermore, it is well established that older adults have balance difficulties. Therefore, we seek to determine whether ML balance adaptation differs in older age. We analyzed split belt induced changes in gait parameters including variables which inform us about ML balance control in younger and older adults. Our primary finding is that younger adults showed sustained asymmetric changes in these ML balance parameters during the split condition. Specifically, younger adults sustained a greater displacement between their fast stance foot and their upper body, relative to the slow stance foot, in the ML direction. This finding suggests that younger adults may be exploiting passive dynamics in the ML direction, which may be more metabolically efficient. Older adults did not display the same degree of asymmetry, suggesting older adults may be more concerned about maintaining a stable gait.

Disentangling the energetic costs of step time asymmetry and step length asymmetry in human walking.

The metabolic cost of walking in healthy individuals increases with spatiotemporal gait asymmetries. Pathological gait, such as post-stroke, often has asymmetry in step length and step time which may contribute to an increased energy cost. But paradoxically, enforcing step length symmetry does not reduce metabolic cost of post-stroke walking. The isolated and interacting costs of asymmetry in step time and step length remain unclear, because previous studies did not simultaneously enforce spatial and temporal gait asymmetries. Here, we delineate the isolated costs of asymmetry in step time and step length in healthy human walking. We first show that the cost of step length asymmetry is predicted by the cost of taking two non-preferred step lengths (one short and one long), but that step time asymmetry adds an extra cost beyond the cost of non-preferred step times. The metabolic power of step time asymmetry is about 2.5 times greater than the cost of step length asymmetry. Furthermore, the costs are not additive when walking with asymmetric step time and asymmetric step length: the metabolic power of concurrent asymmetry in step length and step time is driven by the cost of step time asymmetry alone. The metabolic power of asymmetry is explained by positive mechanical power produced during single support phases to compensate for a net loss of center of mass power incurred during double support phases. These data may explain why metabolic cost remains invariant to step length asymmetry in post-stroke walking and suggest how effects of asymmetry on energy cost can be attenuated.

Contributions of spatial and temporal control of step length symmetry in the transfer of locomotor adaptation from a motorized to a non-motorized split-belt treadmill.

Walking requires control of where and when to step for stable interlimb coordination. Motorized split-belt treadmills which constrain each leg to move at different speeds lead to adaptive changes to limb coordination that result in after-effects (e.g. gait asymmetry) on return to normal treadmill walking. These after-effects indicate an underlying neural adaptation. Here, we assessed the transfer of motorized split-belt treadmill adaptations with a custom non-motorized split-belt treadmill where each belt can be self-propelled at different speeds. Transfer was indicated by the presence of after-effects in step length, foot placement and step timing differences. Ten healthy participants adapted on a motorized split-belt treadmill (2 : 1 speed ratio) and were then assessed for after-effects during subsequent non-motorized treadmill and motorized tied-belt treadmill walking. We found that after-effects in step length difference during transfer to non-motorized split-belt walking were primarily associated with step time differences. Conversely, residual after-effects during motorized tied-belt walking following transfer were associated with foot placement differences. Our data demonstrate decoupling of adapted spatial and temporal locomotor control during transfer to a novel context, suggesting that foot placement and step timing control can be independently modulated during walking.

Brain Network Oscillations During Gait in Parkinson's Disease.

Human bipedal walking is a complex motor task that requires supraspinal control for balance and flexible coordination of timing and scaling of many muscles in different environment. Gait impairments are a hallmark of Parkinson's disease (PD), reflecting dysfunction of cortico-basal ganglia-brainstem circuits. Recent studies using implanted electrodes and surface electroencephalography have demonstrated gait-related brain oscillations in the basal ganglia and cerebral cortex. Here, we review the physiological and pathophysiological roles of (1) basal ganglia oscillations, (2) cortical oscillations, and (3) basal ganglia-cortical interactions during walking. These studies extend a novel framework for movement of disorders where specific patterns of abnormal oscillatory synchronization in the basal ganglia thalamocortical network are associated with specific signs and symptoms. Therefore, we propose that many gait dysfunctions in PD arise from derangements in brain network, and discuss potential therapies aimed at restoring gait impairments through modulation of brain network in PD.

Teaching during a pandemic: Using high-impact writing assignments to balance rigor, engagement, flexibility, and workload.

The COVID-19 pandemic has created new challenges for instructors who seek high-impact educational practices that can be facilitated online without creating excessive burdens with technology, grading, or enforcement of honor codes. These practices must also account for the possibility that some students may need to join courses asynchronously and have limited or unreliable connectivity. Of the American Association of Colleges and University's list of 11 high-impact educational practices, writing-intensive courses may be the easiest for science faculty to adopt during these difficult times. Not only can writing assignments promote conceptual learning, they can also deepen student engagement with the subject matter and with each other. Furthermore, writing assignments can be incredibly flexible in terms of how they are implemented online and can be designed to reduce the possibility of cheating and plagiarism. To accelerate the adoption of writing pedagogies, we summarize evidence-based characteristics of effective writing assignments and offer a sample writing assignment from an introductory ecology course. We then suggest five strategies to help instructors manage their workload. Although the details of the sample assignment may be particular to our course, this framework is general enough to be adapted to most science courses, including those taught in-person, those taught online, and those that must be able to switch quickly between the two.

Step time asymmetry but not step length asymmetry is adapted to optimize energy cost of split-belt treadmill walking.

KEY POINTS: The relationship between spatiotemporal gait asymmetry and walking energetics is currently under debate. The split-belt treadmill paradigm has been used to study adaptation of spatiotemporal gait parameters in relation to energetics, but it remains unclear why people reduce asymmetry in step lengths, but prefer asymmetry in step times. In this study we characterized the effects of step time asymmetry and step length asymmetry on energy cost during steady-state walking on a split-belt treadmill at increasing speed-differences. Both the optimal and preferred step time asymmetry increased with greater speed differences, while preferred step lengths remained constant and nearly symmetric. Preferred asymmetric step times were energetically optimal across all speed-difference conditions, while preferred step length asymmetry was not optimal. The findings show that humans will adopt an asymmetric gait that is associated with an energy reduction and suggest that step time asymmetry plays a dominant role in shaping the energetic cost of gait asymmetry. ABSTRACT: Healthy human walking is symmetric and economical; hemiparetic and amputee gait is often asymmetric and requires more energy. Consequently, asymmetry has been attributed to account for the added energy cost of pathological gait. But it is also possible that asymmetric gait may be adopted if it is energetically optimal under certain biomechanical and neurological constraints of the locomotor system. Here, we assessed how preferred asymmetry in step times and step lengths of healthy human gait is adapted during split-belt treadmill walking and tested the hypothesis that asymmetry is adapted to optimize metabolic energy cost. Ten healthy, young participants walked on a split-belt treadmill in three conditions in which the average belt speed was always 1.25 m s-1 and the speed difference between the belts was 0.5 m s-1 , 1.0 m s-1 and 1.5 m s-1 while a range of values of step time asymmetry and step length asymmetry were enforced. We found that preferred step time asymmetry increased with greater speed differences while preferred step length asymmetry remained constant and nearly symmetric. With increasing speed differences participants increased their preferred value of step time asymmetry to coincide with the lowest energy cost. However, our results show that preferred step length asymmetry was not optimal even with extensive experience of split-belt treadmill walking. Overall, our results indicate that humans will adopt an asymmetric gait that is associated with an energy reduction and suggest that step time asymmetry plays a dominant role in shaping the energetic cost of gait asymmetry.

Prevention of lipid loss from hair by surface and internal modification.

Surfactants during routine washing have a tremendous effect on lipid loss from hair. This study aims to understand the loss of lipids from hair upon contact with surfactants and develop a way to prevent the lipid loss. The change in lipid levels depends on the relative hydrophobicity of the lipid. We herein propose that the change in lipid levels can be protected by two modifications. In the case of fatty acids and cholesterol (group A), the concentration difference between virgin hair versus surface modified hair with highly charged polymer was 22 to 32% higher after washing with surfactants while the loss of squalene and wax esters (group B) in response to surfactants still occurred even after the surface modification. In the hair treated by internal modification with the carbodiimide reaction, 52.0 to 81.3% more lipids in group B were prevented than in the untreated hair. Finally, different types of lipids were successfully protected by surface and internal modifications from the surfactant treatment. This study will be the basis for understanding the mechanisms by which surfactants damage the lipid barrier of tissues including hair and for establishing strategies to defend the barrier.

Increased intramuscular coherence is associated with temporal gait symmetry during split-belt locomotor adaptation.

When walking on a split-belt treadmill where one belt moves faster than the other, the nervous system consistently attempts to maintain symmetry between legs, quantified as deviation from double support time or step length symmetry. It is known that the cerebellum plays a critical role in locomotor adaptation. Less is known about the role of corticospinal drive in maintaining this type of proprioceptive-driven locomotor adaptation. The objective of this study was to examine the functional role of oscillatory drive in relation to changes in spatiotemporal gait parameters during split-belt walking adaptation. Eighteen healthy participants adapted and deadapted on a split-belt treadmill; 13 out of 18 participants repeated the paradigm two more times to examine the effects of reexposure. Coherence analysis was used to quantify the coupling between electromyography (EMG) from the proximal (TAprox) and distal tibialis anterior (TAdist) muscle during the swing phase of walking. EMG-EMG coherence was examined within the alpha (8-15 Hz), beta (15-30 Hz), and gamma (30-45 Hz) frequencies. Our results showed that 1) beta- and gamma-band coherence (markers of corticospinal drive) increased during early split-belt walking compared with baseline walking in the slow leg, 2) beta-band coherence decreased from early to late split-belt adaptation in the fast leg, 3) alpha-, beta-, and gamma-band coherence decreased from first to third split-belt exposure in the fast leg, and 4) there was a relationship between higher beta coherence in the slow leg TA and smaller double support asymmetry. Our results suggest that corticospinal drive may play a functional role in the temporal control of split-belt walking adaptation.NEW & NOTEWORTHY This is the first study to examine the functional role of intramuscular coherence in relation to changes in spatiotemporal gait parameters during split-belt walking adaptation. We found that the corticospinal drive measured by intramuscular coherence in tibialis anterior changes with adaptation and that the corticospinal drive is related to temporal but not spatial parameters. This study may give insight as to the specific role of the motor cortex during gait.

Corticospinal control of normal and visually guided gait in healthy older and younger adults.

We investigated age-related differences in corticospinal control of muscle activity during normal and visually guided (VG) walking. Young (n = 15, 22.1 ± 1.7 years) and older (n = 15, 68.3 ± 2.7 years) participants performed normal walking and VG walking requiring precise foot placement based on visual cues. Coherence analysis was used to quantify coupling between electroencephalography and electromyography from the anterior tibial muscle (corticomuscular) and between the 2 ends of the anterior tibial muscle (intramuscular) at 15-50 Hz during the swing phase of walking as markers of corticospinal activity. Our results indicated that corticomuscular and intramuscular coherence was lower in older compared to young participants during both tasks. In addition, coherence was generally greater during VG than during normal walking across age groups, although during late swing, older participants drove several of the observed task-related coherence increases. Performance on the VG task was lower in older compared to young participants and was correlated with task-related corticomuscular coherence modulations within the older group. These results suggest age-related differences in the corticospinal control of walking, with possible implications for precision control of foot placement based on visual information.

Dramatic response to cyclin D-dependent kinase 4/6 inhibitor in refractory poorly differentiated neuroendocrine carcinoma of the breast.

Neuroendocrine tumors are a rare subset of breast carcinomas. Commonly, platinum-based doublet is used as a systemic treatment option for high-grade neuroendocrine carcinomas from lung, gastrointestinal, and genitourinary origins. In comparison to other breast cancers, neuroendocrine carcinomas have unique genomic features and different treatment strategies. We present a patient with high-grade neuroendocrine carcinoma of the breast who had a successful and durable response to the cyclin D-dependent kinase (CDK) 4/6 inhibitor palbociclib in conjunction with endocrine therapy. This patient was refractory to commonly used platinum-based chemotherapy as well as hormone-based treatment. To date, this is the first published case of use of CDK 4/6 inhibitor in primary neuroendocrine carcinoma of the breast.