Changes in brain functional connectivity and muscle strength independent of elbow flexor atrophy following upper limb immobilization in young females.

Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.

Levodopa alters resting-state functional connectivity more selectively in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is a debilitating motor symptom of Parkinson's disease (PD). Although PD dopaminergic medication (L-DOPA) seems to generally reduce FOG severity, its effect on neural mechanisms of FOG remains to be determined. The purpose of this study was to quantify the effect of L-DOPA on brain resting-state functional connectivity in individuals with FOG. Functional magnetic resonance imaging was acquired at rest in 30 individuals living with PD (15 freezers) in the ON- and OFF- medication state. A seed-to-voxel analysis was performed with seeds in the bilateral basal ganglia nuclei, the thalamus and the mesencephalic locomotor region. In freezers, medication-state contrasts revealed numerous changes in resting-state functional connectivity, not modulated by L-DOPA in non-freezers. In freezers, L-DOPA increased the functional connectivity between the seeds and regions including the posterior parietal, the posterior cingulate, the motor and the medial prefrontal cortices. Comparisons with non-freezers revealed that L-DOPA generally normalizes brain functional connectivity to non-freezers levels but can also increase functional connectivity, possibly compensating for dysfunctional networks in freezers. Our findings suggest that L-DOPA could contribute to a better sensorimotor, attentional, response inhibition and limbic processing to prevent FOG when triggers are encountered but could also contribute to FOG by interfering with the processing capacity of the striatum. This study shows that levodopa taken to control PD symptoms induces changes in functional connectivity at rest, in freezers only. Increases (green) in functional connectivity of GPe, GPi, putamen and thalamus with cognitive, sensorimotor and limbic cortical regions of the Interference model (blue) was observed. Our results suggest that levodopa can normalize connections similar to non-freezers or increases connectivity to compensate for dysfunctional networks.

Adjusting gait step-by-step: Brain activation during split-belt treadmill walking.

When walking on a split-belt treadmill, where each leg is driven at a different speed, a temporary change is made to the typical steady-state walking pattern. The exact ways in which the brain controls these temporary changes to walking are still unknown. Ten young adults (23±3y) walked on a split-belt treadmill for 30 min on 2 separate occasions: tied-belt control with both belts at comfortable walking speed, and continuous adjustment where speed ratio between belts changed every 15 seconds. 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) imaging measured whole brain glucose metabolism distribution, or activation, during each treadmill walking condition. The continuous adjustment condition, compared to the tied-belt control, was associated with increased activity of supplementary motor areas (SMA), posterior parietal cortex (PPC), anterior cingulate cortex and anterior lateral cerebellum, and decreased activity of posterior cingulate and medial prefrontal cortex. In addition, peak activation of the PPC, SMA and PFC were correlated with cadence and temporal gait variability. We propose that a "fine-tuning" network for human locomotion exists which includes brain areas for sensorimotor integration, motor planning and goal directed attention. These findings suggest that distinct regions govern the inherent flexibility of the human locomotor plan to maintain a successful and adjustable walking pattern.

Intersegmental coordination patterns are differently affected in Parkinson's disease and cerebellar ataxia.

The law of intersegmental coordination (Borghese et al. 1996) may be altered in pathological conditions. Here we investigated the contribution of the basal ganglia (BG) and the cerebellum to lower limb intersegmental coordination by inspecting the plane's orientation and other parameters pertinent to this law in patients with idiopathic Parkinson's disease (PD) or cerebellar ataxia (CA). We also applied a mathematical model that successfully accounts for the intersegmental law of coordination observed in control subjects (Barliya et al. 2009). In the present study, we compared the planarity index (PI), covariation plane (CVP) orientation, and CVP orientation predicted by the model in 11 PD patients, 8 CA patients, and two groups of healthy subjects matched for age, height, weight, and gender to each patient group (Ctrl_PD and Ctrl_CA). Controls were instructed to alter their gait speed to match those of their respective patient group. PD patients were examined after overnight withdrawal of anti-parkinsonian medications (PD-off-med) and then on medication (PD-on-med). PI was above 96% in all gait conditions in all groups suggesting that the law of intersegmental coordination is preserved in both BG and cerebellar pathology. However, the measured and predicted CVP orientations rotated in PD-on-med and PD-off-med compared with Ctrl_PD and in CA vs. Ctrl_CA. These rotations caused by PD and CA were in opposite directions suggesting differences in the roles of the BG and cerebellum in intersegmental coordination during human locomotion. NEW & NOTEWORTHY Kinematic and muscular synergies may have a role in overcoming motor redundancies, which may be reflected in intersegmental covariation. Basal ganglia and cerebellar networks were suggested to be involved in crafting and modulating synergies. We thus compared intersegmental coordination in Parkinson's disease and cerebellar disease patients and found opposite effects in some aspects. Further research integrating muscle activities as well as biomechanical and neural control modeling are needed to account for these findings.

Turning Stability in Individuals With Parkinson Disease.

BACKGROUND AND PURPOSE: Although instability during turning is a disabling feature of Parkinson disease (PD), little is known about the associated postural characteristics. Our goals were to compare turning stability between individuals with PD and healthy individuals and to investigate whether dopaminergic medication improves turning stability. METHODS: Nineteen older adults with mild to moderate PD and 19 healthy individuals walked straight or walked and turned 180° to the right or left. The turning direction was visually cued before (preplanned) or during (unplanned) straight walking. Participants with PD were assessed off and on medication. As a proxy for mediolateral stability, we calculated the difference between pelvis lateral displacement and the lateral edge of the support base. RESULTS: While healthy individuals regulated mediolateral stability in a steady-state manner during turning, mediolateral stability in PD was reduced for crossover steps (narrow steps by the foot contralateral to the turning direction) and increased for side steps (widening steps by the foot ipsilateral to the turning direction) (P ≤ 0.008). Individuals with PD turned with narrower step width (P ≤ 0.024) and smaller pelvis displacement than healthy individuals (P ≤ 0.002). Dopaminergic medication only improved mediolateral stability while using side steps to initiate unplanned turns (P < 0.001). DISCUSSION AND CONCLUSIONS: Turning stability was compromised in PD, but only for crossover steps with a narrow support base. As dopaminergic medication showed limited effect on turning stability, rehabilitation plays an important role to promote safe turning strategies with a specific emphasis on sustainment of a wide support base.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A236).

More Falls in Cerebellar Ataxia When Standing on a Slow Up-Moving Tilt of the Support Surface.

We investigated how subjects with cerebellar ataxia (CA) adapt their postural stability and alignment to a slow and small tilt of the support surface allowing for online postural corrections. Eight subjects with CA and eight age- and gender-matched healthy control subjects participated in the study. Subjects stood eyes closed for 1 min after which the support surface was tilted 5° toes-up at a ramp velocity of 1°/s. The toes-up position was held for 2.5 min after which the surface rotated back down to level with identical tilt characteristics. As reflected by the large number of falls, subjects with CA had marked difficulty adapting their posture to the up-moving incline in contrast to control subjects. Subjects with CA who lost their balance had faster trunk velocity and excessive backward trunk reorientation beginning within the first second after onset of the tilting surface. In contrast, the down-moving tilt to level did not result in instability in CA subjects. These results suggest that instability and falls associated with CA derive from an inability to maintain trunk orientation to vertical while standing on a slow-moving or unstable surface. This study underscores the importance of the cerebellum in the online sensory control of the upper body orientation during small amplitude and slow velocity movements of the support surface.

Surface-based partial-volume correction for high-resolution PET.

Tissue radioactivity concentrations, measured with positron emission tomography (PET) are subject to partial volume effects (PVE) due to the limited spatial resolution of the scanner. Last generation high-resolution PET cameras with a full width at half maximum (FWHM) of 2-4mm are less prone to PVEs than previous generations. Corrections for PVEs are still necessary, especially when studying small brain stem nuclei or small variations in cortical neuroreceptor concentrations which may be related to cytoarchitectonic differences. Although several partial-volume correction (PVC) algorithms exist, these are frequently based on a priori assumptions about tracer distribution or only yield corrected values of regional activity concentrations without providing PVE corrected images. We developed a new iterative deconvolution algorithm (idSURF) for PVC of PET images that aims to overcome these limitations by using two innovative techniques: 1) the incorporation of anatomic information from a cortical gray matter surface representation, extracted from magnetic resonance imaging (MRI) and 2) the use of anatomically constrained filtering to attenuate noise. PVE corrected images were generated with idSURF implemented into a non-interactive processing pipeline. idSURF was validated using simulated and clinical PET data sets and compared to a frequently used standard PVC method (Geometric Transfer Matrix: GTM). The results on simulated data sets show that idSURF consistently recovers accurate radiotracer concentrations within 1-5% of true values. Both radiotracer concentrations and non-displaceable binding potential (BPnd) values derived from clinical PET data sets with idSURF were highly correlated with those obtained with the standard PVC method (R(2) = 0.99, error = 0%-3.2%). These results suggest that idSURF is a valid and potentially clinically useful PVC method for automatic processing of large numbers of PET data sets.

Improving Cutaneous Wound Healing in Diabetic Mice Using Naturally Derived Tissue-Engineered Biological Dressings Produced under Serum-Free Conditions.

Long-term diabetes often leads to chronic wounds refractory to treatment. Cell-based therapies are actively investigated to enhance cutaneous healing. Various cell types are available to produce biological dressings, such as adipose-derived stem/stromal cells (ASCs), an attractive cell source considering their abundancy, accessibility, and therapeutic secretome. In this study, we produced human ASC-based dressings under a serum-free culture system using the self-assembly approach of tissue engineering. The dressings were applied every 4 days to full-thickness 8-mm splinted skin wounds created on the back of polygenic diabetic NONcNZO10/LtJ mice and streptozotocin-induced diabetic K14-H2B-GFP mice. Global wound closure kinetics evaluated macroscopically showed accelerated wound closure in both murine models, especially for NONcNZO10/LtJ; the treated group reaching 98.7% ± 2.3% global closure compared to 76.4% ± 11.8% for the untreated group on day 20 (p=0.0002). Histological analyses revealed that treated wounds exhibited healed skin of better quality with a well-differentiated epidermis and a more organized, homogeneous, and 1.6-fold thicker granulation tissue. Neovascularization, assessed by CD31 labeling, was 2.5-fold higher for the NONcNZO10/LtJ treated wounds. We thus describe the beneficial impact on wound healing of biologically active ASC-based dressings produced under an entirely serum-free production system facilitating clinical translation.

Resting-state Functional Connectivity of the Motor and Cognitive Areas is Preserved in Masters Athletes.

Aging is characterized by a decline in physical and cognitive functions, often resulting in decreased quality of life. Physical activity has been suggested to potentially slow down various aspects of the aging process, a theory that has been supported by studies of Masters Athletes (MA). For example, MA usually have better cognitive and physical functions than age-matched sedentary and healthy older adults (OA), making them a valuable model to gain insights into mechanisms that promote physical and cognitive function with aging. The purpose of this study was to identify differences in resting-state functional connectivity (rs-FC) of motor and cognitive regions between MA and OA and determine if these differences in the resting brain are associated with differences in cognitive and physical performance between groups. Fifteen MA (9 males) and 12 age-matched OA (six males) were included. rs-FC images were compared to identify significant between-groups differences in brain connectivity. There was higher connectivity between the cognitive and motor networks for the OA group, whereas the MA group had stronger connectivity between different regions within the same network, both for the cognitive and the motor networks. These results are in line with the literature suggesting that aging reduces the segregation between functional networks and causes regions within the same network to be less strongly connected. High-level physical activity practiced by the MA most likely contributes to attenuating aging-related changes in brain functional connectivity, preserving clearer boundaries between different functional networks, which may ultimately favor maintenance of efficient cognitive and sensorimotor processing.

Reorganization of Brain Resting-state Functional Connectivity Following 14 Days of Elbow Immobilization in Young Females.

Limb immobilization is known to cause significant decreases in muscle strength and muscle mass as early as two days following the onset of immobilization. However, the decline in strength surpasses the decline in muscle mass, suggesting that factors in addition to muscle loss, such as neuroplasticity, contribute to the decrease in force production. However, little is known regarding immobilization-induced neural changes, although sensorimotor regions seem to be the most affected. The present study aimed to determine whether brain functional organization is altered following 14 days of unilateral elbow immobilization. Functional organization was quantified using resting-state functional connectivity, a measure of the synchronicity of the spontaneous discharge of different brain regions at rest. Data was obtained from twelve healthy young females before and after completing the immobilization period. A seed-to-voxel analysis was performed using seeds associated with cortical, subcortical, and cerebellar sensorimotor regions of the brain. The results showed changes predominantly involving cerebellar connectivity. For example, the immobilization period caused a decrease in connectivity between the motor cerebellar region of the immobilized arm and the left temporal lobe, and an increase between the same cerebellar region and the supplementary motor area. Overall, changes in connectivity occurred in regions typically associated with error detection and motor learning, suggesting a potential functional reorganization of the brain within 14 days of elbow immobilization.

The Effect of Different Types of Exercise on Sleep Quality and Architecture in Parkinson Disease: A Single-Blinded Randomized Clinical Trial Protocol.

OBJECTIVES: The purpose of this trial is to (1) determine the best exercise modality to improve sleep quality and sleep architecture in people with Parkinson disease (PD); (2) investigate whether exercise-induced improvements in sleep mediate enhancements in motor and cognitive function as well as other non-motor symptoms of PD; and (3) explore if changes in systemic inflammation after exercise mediate improvements in sleep. METHODS: This is a multi-site, superiority, single-blinded randomized controlled trial. One hundred fifty persons with PD and sleep problems will be recruited and randomly allocated into 4 intervention arms. Participants will be allocated into 12 weeks of either cardiovascular training, resistance training, multimodal training, or a waiting list control intervention. Assessments will be conducted at baseline, immediately after each intervention, and 8 weeks after each intervention by blinded assessors. Objective sleep quality and sleep architecture will be measured with polysomnography and electroencephalography. Motor and cognitive function will be assessed with the Unified PD Rating Scale and the Scale for Outcomes in PD-Cognition, respectively. Subjective sleep quality, fatigue, psychosocial functioning, and quality of life will be assessed with questionnaires. The concentration of inflammatory biomarkers in blood serum will be assessed with enzyme-linked immunosorbent assays. IMPACT: This study will investigate the effect of different types of exercise on sleep quality and architecture in PD, exploring interactions between changes in sleep quality and architecture with motor and cognitive function and other non-motor symptoms of the disease as well as mechanistic interactions between systemic inflammation and sleep. The results will provide important practical information to guide physical therapists and other rehabilitation professionals in the selection of exercise and the design of more personalized exercise-based treatments aimed at optimizing sleep, motor, and cognitive function in people with PD.

Upregulation of the parietal cortex improves freezing of gait in Parkinson's disease.

BACKGROUND The posterior parietal cortex (PPC) is a key brain area for visuospatial processing and locomotion. It has been repetitively shown to be involved in the neural correlates of freezing of gait (FOG), a common symptom of Parkinson's disease (PD). However, current neuroimaging modalities do not allow to precisely determine the role of the PPC during real FOG episodes. OBJECTIVES The purpose of this study was to modulate the PPC cortical excitability using repetitive transcranial magnetic stimulation (rTMS) to determine whether the PPC contributes to FOG or compensates for dysfunctional neural networks to reduce FOG. METHODS Fourteen participants with PD who experience freezing took part in a proof of principle study consisting of three experimental sessions targeting the PPC with inhibitory, excitatory, and sham rTMS. Objective FOG outcomes and cortical excitability measurements were acquired before and after each stimulation protocol. RESULTS Increasing PPC excitability resulted in significantly fewer freezing episodes and percent time frozen during a FOG-provoking task. This reduction in FOG most likely emerged from the trend in PPC inhibiting the lower leg motor cortex excitability. CONCLUSION Our results suggest that the recruitment of the PPC is linked to less FOG, providing support for the beneficial role of the PPC upregulation in preventing FOG. This could potentially be linked to a reduction of the cortical input burden on the basal ganglia prior to FOG. Excitatory rTMS interventions targeting the PPC may have the potential to reduce FOG.

Motor Memory Consolidation Deficits in Parkinson's Disease: A Systematic Review with Meta-Analysis.

BACKGROUND: The ability to encode and consolidate motor memories is essential for persons with Parkinson's disease (PD), who usually experience a progressive loss of motor function. Deficits in memory encoding, usually expressed as poorer rates of skill improvement during motor practice, have been reported in these patients. Whether motor memory consolidation (i.e., motor skill retention) is also impaired is unknown. OBJECTIVE: To determine whether motor memory consolidation is impaired in PD compared to neurologically intact individuals. METHODS: We conducted a pre-registered systematic review (PROSPERO: CRD42020222433) following PRISMA guidelines that included 46 studies. RESULTS: Meta-analyses revealed that persons with PD have deficits in retaining motor skills (SMD = -0.17; 95% CI = -0.32, -0.02; p = 0.0225). However, these deficits are task-specific, affecting sensory motor (SMD = -0.31; 95% CI -0.47, -0.15; p = 0.0002) and visuomotor adaptation (SMD = -1.55; 95% CI = -2.32, -0.79; p = 0.0001) tasks, but not sequential fine motor (SMD = 0.17; 95% CI = -0.05, 0.39; p = 0.1292) and gross motor tasks (SMD = 0.04; 95% CI = -0.25, 0.33; p = 0.7771). Importantly, deficits became non-significant when augmented feedback during practice was provided, and additional motor practice sessions reduced deficits in sensory motor tasks. Meta-regression analyses confirmed that deficits were independent of performance during encoding, as well as disease duration and severity. CONCLUSION: Our results align with the neurodegenerative models of PD progression and motor learning frameworks and emphasize the importance of developing targeted interventions to enhance motor memory consolidation in PD.

Linear and angular control of circular walking in healthy older adults and subjects with cerebellar ataxia.

Linear and angular control of trunk and leg motion during curvilinear navigation was investigated in subjects with cerebellar ataxia and age-matched control subjects. Subjects walked with eyes open around a 1.2-m circle. The relationship of linear to angular motion was quantified by determining the ratios of trunk linear velocity to trunk angular velocity and foot linear position to foot angular position. Errors in walking radius (the ratio of linear to angular motion) also were quantified continuously during the circular walk. Relative variability of linear and angular measures was compared using coefficients of variation (CoV). Patterns of variability were compared using power spectral analysis for the trunk and auto-covariance analysis for the feet. Errors in radius were significantly increased in patients with cerebellar damage as compared to controls. Cerebellar subjects had significantly larger CoV of feet and trunk in angular, but not linear, motion. Control subjects also showed larger CoV in angular compared to linear motion of the feet and trunk. Angular and linear components of stepping differed in that angular, but not linear, foot placement had a negative correlation from one stride to the next. Thus, walking in a circle was associated with more, and a different type of, variability in angular compared to linear motion. Results are consistent with increased difficulty of, and role of the cerebellum in, control of angular trunk and foot motion for curvilinear locomotion.

A case of eruptive xanthomas associated with pregnancy unmasking a G188E heterozygous mutation of the lipoprotein lipase gene: A case report.

A case of eruptive xanthomas with exceptionally high levels of blood triglycerides without any complication during pregnancy is reported. Eruptive xanthomas may develop in the setting of severe hypertriglyceridemia. Clinically, patients present with small and smooth papules with a characteristic yellow hue. The condition can also be associated with morbid systemic complications. Estrogen replacement therapy is a known cause of secondary hypertriglyceridemia. Estrogen increase in pregnancy is associated with a physiologic elevation of blood triglycerides in order to provide sufficient nutrition for the fetus. However, in the setting of primary dyslipidemia, severe hypertriglyceridemia can occur. The case presented here was explained by a partial primary lipoprotein lipase deficiency with a heterozygous G188E mutation of the LPL gene. The delivery by induced labor and the introduction of fenofibrate led to a rapid decrease of triglycerides and a resolution of cutaneous lesions without any complication for the patient or her baby.

Differential Effects of Speech and Language Therapy and rTMS in Chronic Versus Subacute Post-stroke Aphasia: Results of the NORTHSTAR-CA Trial.

BACKGROUND & OBJECTIVE: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5-45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. METHODS: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. RESULTS: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P <.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR = .77) than chronic patients (Mdn = .15/IQR = 1.68/P = .015). There was no significant rTMS effect in the chronic aphasia group. CONCLUSIONS: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02020421.

Potential Non-invasive Brain Stimulation Targets to Alleviate Freezing of Gait in Parkinson's Disease.

Freezing of gait (FOG) is a common motor symptom in Parkinson's disease (PD). Although FOG reduces quality of life, affects mobility and increases the risk of falls, there are little to no effective treatments to alleviate FOG. Non-invasive brain stimulation (NIBS) has recently yielded attention as a potential treatment to reduce FOG symptoms however, stimulation parameters and protocols remain inconsistent and require further research. Specifically, targets for stimulation require careful review. Thus, with current neuroimaging and neuro-electrophysiological evidence, we consider potential cortical targets thought to be involved in the pathophysiology of FOG according to the Interference model, and within reach of NIBS. We note that the primary motor cortex, the supplementary motor area and the dorsolateral prefrontal cortex have already drawn attention as NIBS targets for FOG, but based on neuroimaging evidence the premotor cortex, the medial prefrontal cortex, the cerebellum, and more particularly, the posterior parietal cortex should be considered as potential regions for stimulation. We also discuss different methodological considerations, such as stimulation type, medication state, and hemisphere to target, and future perspectives for NIBS protocols in FOG.

Analysis of Human Head Motion and Robotic Compensation for PET Imaging Studies.

Functional medical imaging systems can provide insights into brain activity during various tasks, but most current imaging systems are bulky devices that are not compatible with many human movements. Our motivating application is to perform Positron Emission Tomography (PET) imaging of subjects during sitting, upright standing and locomotion studies on a treadmill. The proposed long-term solution is to construct a robotic system that can support an imaging system surrounding the subject's head, and then move the system to accommodate natural motion. This paper presents the first steps toward this approach, which are to analyze human head motion, determine initial design parameters for the robotic system, and verify the concept in simulation.

Identification of Predictors of Abnormal Calcium, Magnesium and Phosphorus Blood Levels in the Emergency Department: A Retrospective Cohort Study.

PURPOSE: With rising healthcare costs limiting access to care, the judicious use of diagnostic tests has become a critical issue for many jurisdictions. Calcium, magnesium and phosphorus serum levels are regularly performed tests in the emergency department, but their clinical relevance have come into question. Authors sought to determine risk factors that could predict abnormal calcium, magnesium and phosphorus serum levels, as well as identify patients who may need corrective interventions. METHODS: A retrospective cohort study was conducted in two academic hospitals in Québec City. Demographic and clinical characteristics of 1008 patients who had serum calcium and/or magnesium and/or phosphorus levels drawn by an emergency physician were collected. Multivariate logistic regression models were fitted to obtain adjusted odds ratios for each risk factor for abnormal calcium or magnesium or phosphorus blood levels, and for a required intervention. RESULTS: Among patients for whom calcium, magnesium and phosphorus were tested in the Emergency Department, the most significant risk factors (OR>2) for electrolytic abnormality were as follows: hypocalcemia - respiratory distress, diuretics (excluding loop and thiazide), anti-neoplastic medication, long QTc, chronic kidney disease (CKD); hypercalcemia - bone pain, vitamin D, hallucinations; hypomagnesemia - diabetes, corticosteroids; hypermagnesemia - poor extremity perfusion, CKD, furosemide; hypophosphatemia - seizure; hyperphosphatemia - phosphate-binders, CKD, peripheral vascular atherosclerotic disease. Of all patients tested, 3.4% received a corrective intervention initiated by the emergency physician. Predictors of intervention on an electrolyte abnormality include poor peripheral perfusion, nausea and chronic obstructive pulmonary disease (COPD). CONCLUSION: Emergency physicians can potentially reduce the unnecessary testing of calcium, magnesium and phosphorus blood levels by targeting patients with high-acuity conditions or chronic comorbidities such as CKD, diabetes and COPD.

Canadian Platform for Trials in Noninvasive Brain Stimulation (CanStim) Consensus Recommendations for Repetitive Transcranial Magnetic Stimulation in Upper Extremity Motor Stroke Rehabilitation Trials.

Objective. To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process. Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results. Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions. The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.