Shoulder position and handedness differentially affect excitability and intracortical inhibition of hand muscles.

Individuals with stroke show distinct differences in hand function impairment when the shoulder is in adduction, within the workspace compared to when the shoulder is abducted, away from the body. To better understand how shoulder position affects hand control, we tested the corticomotor excitability and intracortical control of intrinsic and extrinsic hand muscles important for grasp in twelve healthy individuals. Motor evoked potentials (MEP) using single and paired-pulse transcranial magnetic stimulation were elicited in extensor digitorum communis (EDC), flexor digitorum superficialis (FDS), first dorsal interosseous (FDI), and abductor pollicis brevis (APB). The shoulder was fully supported in horizontal adduction (ADD) or abduction (ABD). Separate mixed-effect models were fit to the MEP parameters using shoulder position (or upper-extremity [UE] side) as fixed and participants as random effects. In the non-dominant UE, EDC showed significantly greater MEPs in shoulder ABD than ADD. In contrast, the dominant side EDC showed significantly greater MEPs in ADD compared to ABD; %facilitation of EDC on dominant side showed significant stimulus intensity x position interaction, EDC excitability was significantly greater in ADD at 150% of the resting threshold. Intrinsic hand muscles of the dominant UE received significantly more intracortical inhibition (SICI) when the shoulder was in ADD compared to ABD; there was no position-dependent modulation of SICI on the non-dominant side. Our findings suggest that these resting-state changes in hand muscle excitabilities reflect the natural statistics of UE movements, which in turn may arise from as well as shape the nature of shoulder-hand coupling underlying UE behaviors.

Reducing overprescribing of antibiotics for suspected urinary tract infections in a health sciences campus student health service.

AIMS: Recommendations for the management of women with suspected uncomplicated lower urinary tract infections (UTIs) include presumptive antibiotics with or without obtaining a urine culture (UCx). However, with increasing antibiotic resistance, efforts to decrease antibiotic usage are vital. Therefore, the objective of this study was to determine if the presumptive treatment of women with suspected uncomplicated UTIs is contributing to unnecessary antibiotic usage. METHODS: We retrospectively reviewed all nonpregnant female patients presenting to our student health services clinic with UTI symptoms from December 2016 to May 2017 who had UCx sent. Clinical information, symptoms, office urine dip, and UCx results were reviewed. Patients with positive and negative UCx were compared. RESULTS: A total of 67 patients were included for analysis. Presenting symptoms included dysuria (59/60, 98%), frequency (41/45, 91%), and urgency (27/27, 100%). Office urine dip was performed on 33 of 67 (49%) patients. Dips were positive for leukocytes (88%), blood (79%), and nitrites (18%). All patients in the study were prescribed antibiotics, most commonly nitrofurantoin (82%). Culture results were negative in 29 of 67 (43%). There were no significant differences in duration of symptoms, presenting symptoms, or urine dip results between patients with a negative UCx and those with a positive UCx. CONCLUSIONS: In our study, we found a significant negative UCx rate in women with symptoms of uncomplicated UTI, representing a cohort of patients who were exposed to antibiotics unnecessarily. In addition, we found no difference in presenting symptoms or urine dip results to help distinguish patients with a positive UCx.

Neural coupling between homologous muscles during bimanual tasks: effects of visual and somatosensory feedback.

While the effects of sensory feedback on bimanual tasks have been studied extensively at two ends of the motor control hierarchy, the cortical and behavioral levels, much less is known about how it affects the intermediate levels, including neural control of homologous muscle groups. We investigated the effects of somatosensory input on the neural coupling between homologous arm muscles during bimanual tasks. Twelve subjects performed symmetric elbow flexion/extension tasks under different types of sensory feedback. The first two types involve visual feedback, with one imposing stricter force symmetry than the other. The third incorporated somatosensory feedback via a balancing apparatus that forced the two limbs to produce equal force levels. Although the force error did not differ between feedback conditions, the somatosensory feedback significantly increased temporal coupling of bilateral force production, indicated by a high correlation between left/right force profiles (P < 0.001). More importantly, intermuscular coherence between biceps brachii muscles was significantly higher with somatosensory feedback than others (P = 0.001). Coherence values also significantly differed between tasks (flexion/extension). Notably, whereas feedback type mainly modulated coherence in the α- and γ-bands, task type only affected ß-band coherence. Similar feedback effects were observed for triceps brachii muscles, but there was also a strong phase effect on the coherence values (P < 0.001) that could have diluted feedback effects. These results suggest that somatosensory feedback can significantly increase neural coupling between homologous muscles. Additionally, the between-task difference in ß-band coherence may reflect different neural control strategies for the elbow flexor and extensor muscles. NEW & NOTEWORTHY: This study investigated the effects of somatosensory feedback during bimanual tasks on the neural coupling between arm muscles, which remains largely unexplored. Somatosensory feedback using a balancing apparatus, compared with visual feedback, significantly increased neural coupling between homologous muscles (indicated by intermuscular coherence values) and improved temporal correlation of bilateral force production. Notably, feedback type modulated coherence in the α- and γ-bands (more subcortical pathways), whereas task type mainly affected ß-band coherence (corticospinal pathway).

Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter volumes in these clusters related to verbal working memory capacity, but not other cognitive functions. Further, grey matter volumes in these areas were greater in stroke survivors than healthy control subjects. To confirm this result, 10 chronic left hemisphere stroke survivors with no history of aphasia were identified. Grey matter volumes in right temporoparietal clusters were greater in stroke survivors with aphasia compared to those without history of aphasia. These findings suggest that the grey matter structure of right hemisphere posterior dorsal stream language homologues independently contributes to language production abilities in chronic left hemisphere stroke, and that these areas may undergo hypertrophy after a stroke causing aphasia.

Activation and intermuscular coherence of distal arm muscles during proximal muscle contraction.

In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles controlling the hand could be an important aspect of motor control due to the necessary coordination of distal and proximal segments during functional activities. This study aimed to elucidate the effects of concurrent activation of elbow muscles on the coordination between hand muscles performing a grip task. Eleven healthy subjects performed precision grip tasks while a constant extension or flexion moment was applied to their elbow joints, inducing a sustained submaximal contraction of elbow muscles to counter the applied torque. Activation of four hand muscles was measured during each task condition using surface electromyography (EMG). When concurrent activation of elbow muscles was induced, significant changes in the activation levels of the hand muscles were observed, with greater effects on the extrinsic finger extensor (23.2 % increase under 30 % elbow extensor activation; p = 0.003) than extrinsic finger flexor (14.2 % increase under 30 % elbow flexor activation; p = 0.130). Elbow muscle activation also induced involuntary changes in the intrinsic thumb flexor activation (44.6 % increase under 30 % elbow extensor activation; p = 0.005). EMG-EMG coherence analyses revealed that elbow muscle activation significantly reduced intermuscular coherence between distal muscle pairs, with its greatest effects on coherence in the ß-band (13-25 Hz) (average of 17 % decrease under 30 % elbow flexor activation). The results of this study provide evidence for involuntary, muscle-specific interactions between distal and proximal UE muscles, which may contribute to UE motor performance in health and disease.

Cortical effects of repetitive finger flexion- vs. extension-resisted tracking movements: a TMS study.

While the cortical effects of repetitive motor activity are generally believed to be task specific, the task parameters that modulate these effects are incompletely understood. Since there are differences in the neural control of flexor vs. extensor muscles, the type of muscles involved in the motor task of interest may be one important parameter. In addition, the role each muscle plays in the task, such as whether or not it is the prime mover, is another potentially important task parameter. In the present study, use-dependent cortical plasticity was examined in healthy volunteers performing a robotic waveform tracking task with either the extensor digitorum communis (EDC) or flexor digitorum superficialis (FDS) acting as the prime mover. Transcranial magnetic stimulation was used to measure corticospinal excitability (CE) and short-interval intracortical inhibition of lower and higher threshold corticospinal neurons (SICI(L) and SICI(H), respectively) before and after a flexion- or extension-resisted finger tracking task. After repetitive performance of the tracking task, there was a significant decrease in SICI(L) targeting the EDC, while no change in CE targeting EDC was observed. In contrast, the reverse pattern was observed in the FDS: a significant increase in CE with no change in SICI(L). There was also a tendency toward increased SICI(H) targeting whichever muscle was acting as the prime mover, although this effect did not reach statistical significance. We conclude that there is a difference in patterns of use-dependent plasticity between extrinsic finger flexor and extensor muscles performing the same task.

Upper extremity kinematics: development of a quantitative measure of impairment severity and dissimilarity after stroke.

Background: Strokes are a leading cause of disability worldwide, with many survivors experiencing difficulty in recovering upper extremity movement, particularly hand function and grasping ability. There is currently no objective measure of movement quality, and without it, rehabilitative interventions remain at best informed estimations of the underlying neural structures' response to produce movement. In this article, we utilize a novel modification to Procrustean distance to quantify curve dissimilarity and propose the Reach Severity and Dissimilarity Index (RSDI) as an objective measure of motor deficits. Methods: All experiments took place at the Medstar National Rehabilitation Hospital; persons with stroke were recruited from the hospital patient population. Using Fugl-Meyer (FM) scores and reach capacities, stroke survivors were placed in either mild or severe impairment groups. Individuals completed sets of reach-to-target tasks to extrapolate kinematic metrics describing motor performance. The Procrustes method of statistical shape analysis was modified to identify reaching sub-movements that were congruous to able-bodied sub-movements. Findings: Movement initiation proceeds comparably to the reference curve in both two- and three-dimensional representations of mild impairment movement. There were significant effects of the location of congruent segments between subject and reference curves, mean velocities, peak roll angle, and target error. These metrics were used to calculate a preliminary RSDI score with severity and dissimilarity sub-scores, and subjects were reclassified in terms of rehabilitation goals as Speed Emphasis, Strength Emphasis, and Combined Emphasis. Interpretation: The modified Procrustes method shows promise in identifying disruptions in movement and monitoring recovery without adding to patient or clinician burden. The proposed RSDI score can be adapted and expanded to other functional movements and used as an objective clinical tool. By reducing the impact of stroke on disability, there is a significant potential to improve quality of life through individualized rehabilitation.

A Novel Procrustes Analysis Method to Quantify Multi-Joint Coordination of the Upper Extremity after Stroke.

Upper extremity motor impairment affects about 80% of persons after strokes. For stroke rehabilitation, upper limb kinematic assessments have increasingly been used as primary or secondary outcome measures. There is currently no universal standardized scale for categorizing multi-joint upper extremity movement. We propose a modified Procrustes statistical shape method as a quantitative analysis that can recognize segments of movement where multiple limb segments are coordinating movement. Rather than rely solely on discrete kinematic values to contrast movement, this method allows evaluation of how movement progresses. The Procrustes analysis of able-bodied movement showed that the hand and forearm segments moved in a more coordinated manner during initiation. The shoulder and elbow become more coordinated during movement completion. In impaired movement, this coordination between the hand and forearm is disrupted as the arm decelerates. The utilization of Procrustes analysis may be a step towards developing a comprehensive and universal quantitative tool that does not require changes to existing treatments or increase patient burden.Clinical relevance- This modified Procrustes Shape Analysis method can be applied by clinicians to motion capture data from patients suffering upper extremity movement deficits to objectively identify multi-joint coordination and recovery.

Transcranial magnetic stimulation for the prediction and enhancement of rehabilitation treatment effects.

In this update on rehabilitation technology, transcranial magnetic stimulation (TMS), a technique that allows noninvasive stimulation of the brain, is examined. The background and basic principles of TMS are reviewed, and its usefulness as a tool to inform and possibly augment the rehabilitation process is discussed. The three main paradigms by which TMS is applied-physiological measurement, disruption/virtual lesion studies, and modulation of cortical excitability-are discussed relative to the types of scientific information each paradigm can provide and their potential clinical usefulness in the future. One of the more exciting prospects is that, when combined with rehabilitation training, TMS modulation of cortical excitability could potentially enhance the effects of rehabilitation and lead to greater levels of recovery than are currently attainable with rehabilitation alone. It is concluded that current studies must focus on the mechanisms of recovery based on the specific structures and processes affected by the disorder and the neural effects of specific rehabilitation interventions in order for the potential of TMS-augmented rehabilitation to be realized.

Respiratory Viral and Bacterial Exacerbations of COPD-The Role of the Airway Epithelium.

COPD is a leading cause of death worldwide, with acute exacerbations being a major contributor to disease morbidity and mortality. Indeed, exacerbations are associated with loss of lung function, and exacerbation frequency predicts poor prognosis. Respiratory infections are important triggers of acute exacerbations of COPD. This review examines the role of bacterial and viral infections, along with co-infections, in the pathogenesis of COPD exacerbations. Because the airway epithelium is the initial site of exposure both to cigarette smoke (or other pollutants) and to inhaled pathogens, we will focus on the role of airway epithelial cell responses in regulating the pathophysiology of exacerbations of COPD. This will include an examination of the interactions of cigarette smoke alone, and in combination with viral and bacterial exposures in modulating epithelial function and inflammatory and host defense pathways in the airways during COPD. Finally, we will briefly examine current and potential medication approaches to treat acute exacerbations of COPD triggered by respiratory infections.

Rhinovirus-Induced Modulation of Epithelial Phenotype: Role in Asthma.

Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how HRV-induced modulation of several aspects of epithelial cell phenotype could contribute to the development of asthma or to the induction of exacerbations. Modification of epithelial proinflammatory and antiviral responses are considered, as are alterations in an epithelial barrier function and cell phenotype. The contributions of the epithelium to airway remodeling and to the potential modulation of immune responses are also considered. The potential interactions of each type of HRV-induced epithelial phenotypic changes with allergic sensitization and allergic phenotype are also considered in the context of asthma development and of acute exacerbations.

Roles of Lesioned and Nonlesioned Hemispheres in Reaching Performance Poststroke.

Background. Severe poststroke arm impairment is associated with greater activation of the nonlesioned hemisphere during movement of the affected arm. The circumstances under which this activation may be adaptive or maladaptive remain unclear. Objective. To identify the functional relevance of key lesioned and nonlesioned hemisphere motor areas to reaching performance in patients with mild versus severe arm impairment. Methods. A total of 20 participants with chronic stroke performed a reaching response time task with their affected arm. During the reaction time period, a transient magnetic stimulus was applied over the primary (M1) or dorsal premotor cortex (PMd) of either hemisphere, and the effect of the perturbation on movement time (MT) was calculated. Results. For perturbation of the nonlesioned hemisphere, there was a significant interaction effect of Site of perturbation (PMd vs M1) by Group (mild vs severe; P < .001). Perturbation of PMd had a greater effect on MT in the severe versus the mild group. This effect was not observed with perturbation of M1. For perturbation of the lesioned hemisphere, there was a main effect of site of perturbation (P < .05), with perturbation of M1 having a greater effect on MT than PMd. Conclusions. These results demonstrate that, in the context of reaching movements, the role of the nonlesioned hemisphere depends on both impairment severity and the specific site that is targeted. A deeper understanding of these individual-, task-, and site-specific factors is essential for advancing the potential usefulness of neuromodulation to enhance poststroke motor recovery.

The effect of time since stroke, gender, age, and lesion size on thalamus volume in chronic stroke: a pilot study.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = - 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = - 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.

Proprioceptive Sonomyographic Control: A novel method for intuitive and proportional control of multiple degrees-of-freedom for individuals with upper extremity limb loss.

Technological advances in multi-articulated prosthetic hands have outpaced the development of methods to intuitively control these devices. In fact, prosthetic users often cite "difficulty of use" as a key contributing factor for abandoning their prostheses. To overcome the limitations of the currently pervasive myoelectric control strategies, namely unintuitive proportional control of multiple degrees-of-freedom, we propose a novel approach: proprioceptive sonomyographic control. Unlike myoelectric control strategies which measure electrical activation of muscles and use the extracted signals to determine the velocity of an end-effector; our sonomyography-based strategy measures mechanical muscle deformation directly with ultrasound and uses the extracted signals to proportionally control the position of an end-effector. Therefore, our sonomyography-based control is congruent with a prosthetic user's innate proprioception of muscle deformation in the residual limb. In this work, we evaluated proprioceptive sonomyographic control with 5 prosthetic users and 5 able-bodied participants in a virtual target achievement and holding task for 5 different hand motions. We observed that with limited training, the performance of prosthetic users was comparable to that of able-bodied participants and thus conclude that proprioceptive sonomyographic control is a robust and intuitive prosthetic control strategy.

Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke.

OBJECTIVE: To test the hypothesis that somatosensory stimulation would enhance the effects of training functional hand tasks immediately after practice and 1 day later in chronic subcortical stroke patients. DESIGN: Single-blinded and randomized, crossover study. SETTING: Human research laboratory. PARTICIPANTS: Nine chronic subcortical stroke patients. INTERVENTIONS: Three separate sessions of motor training preceded by (1) synchronous peripheral nerve stimulation (PNS), (2) no stimulation, or (3) asynchronous PNS. MAIN OUTCOME MEASURES: Time to complete the Jebsen-Taylor Hand Function Test (JTHFT time) and corticomotor excitability tested with transcranial magnetic stimulation. RESULTS: After familiarization practice, during which all patients reached a performance plateau, training under the effects of PNS reduced JTHFT time by 10% beyond the post-familiarization plateau. This behavioral gain was accompanied by a specific reduction in GABAergically mediated intracortical inhibition in the motor cortex. These findings were not observed after similar practice under the influence of no stimulation or asynchronous PNS sessions. CONCLUSIONS: Somatosensory stimulation may enhance the training of functional hand tasks in patients with chronic stroke, possibly through modulation of intracortical GABAergic pathways.

Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site.

Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity) framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.

Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients With Hand Paralysis.

In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.

Role of contralesional hemisphere in paretic arm reaching in patients with severe arm paresis due to stroke: A preliminary report.

Stroke is highly prevalent and a leading cause of serious, long-term disability among American adults. Impaired movement (i.e. paresis) of the stroke-affected arm is a major contributor to post-stroke disability, yet the mechanisms of upper extremity motor recovery are poorly understood, particularly in severely impaired patients who lack hand function. To address this problem, we examined the functional relevance of the contralesional hemisphere in paretic arm motor performance in individuals with severe arm paresis. Twelve individuals with severe stroke-induced arm paresis (Upper Extremity Fugl-Meyer Assessment=17.1 ± 8.5; maximum score=66) participated in the study. Participants performed a reaching response time task with their paretic arm. At varying time intervals following a 'Go' cue, a pair of transcranial magnetic stimulation (TMS) pulses were delivered to contralesional hemisphere primary motor (M1) or dorsal pre-motor cortex (PMd) to momentarily disrupt the pattern of neural firing. Response time components and hand-path characteristics were compared across the 2 sites for trials with and without TMS disruption. There was no significant effect of TMS disruption on overall Response time or Reaction time, but Movement time was significantly longer (i.e. slower) with disruption of the contralesional hemisphere (p=0.015), regardless of which area was stimulated. Peak hand-path velocity and hand-path smoothness were also significantly lower (p=0.005 and p<0.0001, respectively) with TMS disruption of the contralesional hemisphere. The data from this study provide evidence supporting a functionally relevant role of contralesional hemisphere motor areas in paretic arm reaching movements in individuals with severe post-stroke arm impairment.

High-Intensity, Unilateral Resistance Training of a Non-Paretic Muscle Group Increases Active Range of Motion in a Severely Paretic Upper Extremity Muscle Group after Stroke.

Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this "cross education" phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains.

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange.

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knock-ins, as well as single-nucleotide insertions, deletions and substitutions, in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selections are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic-resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ∼2 weeks.