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Background: Stroke is a leading cause of long-term disability. Greater rehabilitation therapy after stroke is known to improve functional outcomes. This study examined therapy doses during the first year of stroke recovery and identified factors that predict rehabilitation therapy dose. Methods: Adults with new radiologically confirmed stroke were enrolled 2 to 10 days after stroke onset at 28 acute care hospitals across the United States. Following an initial assessment during acute hospitalization, the number of physical therapy, occupational therapy, and speech therapy sessions were determined at visits occurring 3, 6, and 12 months following stroke. Negative binomial regression examined whether clinical and demographic factors were associated with therapy counts. False discovery rate was used to correct for multiple comparisons. Results: Of 763 patients enrolled during acute stroke admission, 510 were available for follow-up. Therapy counts were low overall, with most therapy delivered within the first 3 months; 35.0% of patients received no physical therapy; 48.8%, no occupational therapy, and 61.7%, no speech therapy. Discharge destination was significantly related to cumulative therapy; the percentage of patients discharged to an inpatient rehabilitation facility varied across sites, from 0% to 71%. Most demographic factors did not predict therapy dose, although Hispanic patients received a lower cumulative amount of physical therapy and occupational therapy. Acutely, the severity of clinical factors (grip strength and National Institutes of Health Stroke Scale score, as well as National Institutes of Health Stroke Scale subscores for aphasia and neglect) predicted higher subsequent therapy doses. Measures of impairment and function (Fugl-Meyer, modified Rankin Scale, and Stroke Impact Scale Activities of Daily Living) assessed 3 months after stroke also predicted subsequent cumulative therapy doses. Conclusions: Rehabilitative therapy doses during the first year poststroke are low in the United States. This is the first US-wide study to demonstrate that behavioral deficits predict therapy dose, with patients having more severe deficits receiving higher doses. Findings suggest directions for identifying groups at risk of receiving disproportionately low rehabilitation doses.

Federal administrations have been addressing the problem of hunger in Brazil since the days of Lula da Silva. An extensive review of the literature shows that the fight against hunger reached its highest level of priority during the Lula da Silva administrations (2003–2010), where it was organized with an institutional structure and seen as an international model for public policy. Every subsequent government since then has given less attention to it, ending in the complete neglect of the issue under the Bolsonaro administration. Governos federais têm abordado o problema da fome no Brasil desde a época de Lula da Silva. Uma revista exhaustiva da literatura aponta que a luta contra a fome atingiu o seu apogeu quando lhe foi atribuída máxima proridade na agenda política federal durante os governos Lula da Silva (2003–2010) onde era organizada com base numa estrutura institucional que é hoje celebrada como modelo internacional de política pública. Desde então, cada governo sucessivo prestou cada vez menos atenção à fome, acabando no descaso completo do assunto sob o governo Bolsonaro.

The way people communicate — be it verbally, visually, or via text– is indicative of personality traits. In social media the concept of the status update is used for individuals to communicate to their social networks in an always-on fashion. In doing so individuals utilize various kinds of speech acts that, while primarily communicating their content, also leave traces of their personality dimensions behind. We human-coded a set of Facebook status updates from the myPersonality dataset in terms of speech acts label and then experimented with surface level linguistic features including lexical, syntactic, and simple sentiment detection to automatically label status updates as their appropriate speech act. We apply supervised learning to the dataset and using our features are able to classify with high accuracy two dominant kinds of acts that have been found to occur in social media. At the same time we used the coded data to perform a regression analysis to determine which speech acts are significant of certain personality dimensions. The implications of our work allow for automatic large-scale personality identification through social media status updates.

The cardiac action potential (AP) is vital for understanding healthy and diseased cardiac biology and drug safety testing. However, techniques for high throughput cardiac AP measurements have been limited. Here, we introduce a novel technique for reliably increasing the coupling of cardiomyocyte syncytium to planar multiwell microelectrode arrays, resulting in a stable, label-free local extracellular action potential (LEAP). We characterized the reliability and stability of LEAP, its relationship to the field potential, and its efficacy for quantifying AP morphology of human induced pluripotent stem cell derived and primary rodent cardiomyocytes. Rise time, action potential duration, beat period, and triangulation were used to quantify compound responses and AP morphology changes induced by genetic modification. LEAP is the first high throughput, non-invasive, label-free, stable method to capture AP morphology from an intact cardiomyocyte syncytium. LEAP can accelerate our understanding of stem cell models, while improving the automation and accuracy of drug testing.

Background Motor learning has been investigated using various paradigms, including serial reaction time tasks (SRTT) that examine upper extremity reaching and pointing while seated. Few studies have used a stepping SRTT, which could offer additional insights into motor learning involving postural demands. For a task to measure motor learning, naive participants must demonstrate a) improved performance with task practice, and b) a dose-response relationship to learning the task. Research question Is a stepping SRTT feasible and efficacious for measuring motor learning? Methods In this prospective study, 20 participants stood on an instrumented mat and were presented with stimuli on a computer screen. They stepped to the corresponding positions on the mat as quickly as possible. Presented stimuli included random sequences and a blinded imbedded repeating sequence. Three days after completing the randomly assigned practice dose [high dose group (n = 10) performed 4320 steps; low dose group (n = 10) performed 144 steps], a retention test of 72 steps was performed. Feasibility was measured as the proportion of participants who completed the assigned practice dose without adverse events. Efficacy was measured as within-group performance improvement on the random sequences and on the repeating sequence (paired t-tests), as well as a dose-response relationship to learning both types of sequences (independent t-tests). Results All participants (mean age 26.8 years) completed all practice sessions without adverse events, indicating feasibility. High dose practice resulted in performance improvement while low dose did not; a dose-response relationship was found, with high dose practice resulting in greater learning of the task than low dose practice, indicating efficacy. Significance This stepping SRTT is a feasible and efficacious way to measure motor learning, which could provide critical insights into anticipatory stepping, postural control, and fall risk. Future research is needed to determine feasibility, efficacy, and optimal practice dosages for older and impaired populations.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor—1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world’s population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index

Background Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI ( Methods To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. Discussion The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. Trial registration ClinicalTrials.gov, NCT02632422. Registered 16 December 2015

Greater consumption of oily fish, and elevated plasma levels of the long-chain marine-derived omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been strongly and consistently associated with a reduced incidence of heart attacks, strokes, cognitive decline, Alzheimer's disease and cancers. Despite international guidelines recommending eating oily fish at least once per week (> 250mg/day DHA and EPA), many people do not eat fish, and only a small minority of the world's population have optimal omega-3-PUFA plasma and tissue levels. Hence, in this project, we studied the bioavailability and blood pressure lowering effects of recently developed alternatives to oily fish, namely chicken-meat and eggs naturally enriched with algae-sourced omega-3-PUFAs.This was a double-blinded, controlled, randomised trial. Using a 2X2 factorial design, 161 healthy participants were randomized to eat at least 3 portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least 3 omega-3-PUFA enriched (or control) eggs/week, for 6 months.Compared to control foods, eating enriched eggs, enriched chicken-meat and the combination for 6 months, resulted in plasma EPA increments (μg/g) of 3.1[2.8], 8.8[2.9]* & 4.7[2.9], plasma DHA increments (μg/g) of 5.1[3.7], 9.3[3.8]* & 13.1[3.9]*, and omega-3-index (sum of EPA + DHA as a percentage of total fatty acids in erythrocytes, %) increments of 0.9[0.3]*, 0.7[0.4]* & 1.5[0.4]*, respectively. Mean 24-hour ambulatory blood pressure (systolic/diastolic, mmHg) declined with the enriched foods 0.3[1.3]/-0.2[1.0], -0.7[1.4]/-1.4[1.0], & -1.9[1.4]/-2.9[1.0]*, respectively. Data provided as mean difference[SEM], and * denotes p < 0.05.Regular consumption of omega-3-PUFA enriched chicken-meat and eggs resulted in statistically significant and clinically relevant increases in plasma and red cell levels of DHA and EPA. Both plasma and red cell bioavailability were similar to those previously described for oily fish. Furthermore, blood pressure, an important biomarker of cardiovascular health, decreased in those eating the omega-3-PUFA enriched foods. Omega-3-PUFA enriched chicken-meat and eggs offers consumers an attractive additional alternative to eating oily fish. Unlike many lifestyle interventions, long-term large population health benefits are not dependent on willingness of people to make long-lasting dietary changes, but on the widespread availability of a range of inexpensive, commonly eaten, naturally enriched foods.

Glioblastoma (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-18 months. Immune effector T cells are a promising therapy due to their innate cytotoxicity. In addition, engineering chimeric antigen receptors (CAR) to target tumor-associated or neo-antigens can lend high specificity. The ability to assess the efficacy and potency of such T cell therapies in vitro at high throughputs is vital for the preclinical development of these promising therapies. Cellular impedance assays offer a sensitive, non-destructive, and label-free method to continuously monitor cancer cell proliferation and immune cell-mediated cytotoxicity in real-time, revealing not only the potency but also the kinetics of T cell killing. Here, we used co-culture to compare the cytolytic potency and kinetics of naïve activated T Cells and targeted GD2 CAR-T cells against glioma stem cells (GSC), a subpopulation of glioblastoma cells. Patient-derived N08 GSCs were plated at 50k cells per well on a PEI and laminin-coated CytoView-Z 96-well plates, and their impedance was continuously monitored on the Maestro Z impedance platform (Axion BioSystems). After 48 hours, human naïve activated T Cells (ImmunoCult CD3/CD28 activation media) or GD2 CAR-T cells were added at varying effector:target ratios ranging from 0.1:1 to 10:1. Impedance and cytolysis were subsequently monitored for up to 7 days. The addition of activated T Cells or GD2 CAR-T Cells resulted in cell swelling, followed by a decrease in impedance consistent with T cell-mediated lysis of GSCs. GD-2 CAR-T Cells resulted in a significantly higher percent cytolysis of GSCs compared to naïve activated T Cells after 7 days of exposure. In addition, the kill time 50, defined as the time to reach 50% cytolysis of target cells, was shorter for GD-2 CAR-T Cells compared to naïve activated T Cells. Cytotoxic function was validated with subsequent flow cytometry and cytokine analysis. After 7 days in co-culture, GD2 CAR-T cells exhibited markers of chronic activation, including greater CD8 expression than CD4, upregulation of CD69 (33% of cells), and induction of GrB (70%). Initial exhaustion was suggested by expression of PD1 (80% cells) and LAG3 (35%), but not TIM3. Overall, both naïve activated T-Cells and GD2 CAR-T Cells were effective for cytolysis of GSCs, with CAR-T exhibiting more efficient killing. CAR-T Cells engineered to target the GD2 antigen exhibited stronger potency and faster kinetics, suggesting greater clinical potential against glioblastoma. Citation Format: Heather Brant Hayes, Meghan T. Logun, Stacie A. Chvatal, Katie Mueller, Nicole Piscopo, Amritava Das, Krishanu Saha, Daniel C. Millard, Lohitash Karumbaiah. Kinetics and potency of T cell and CAR-T cell mediated cytolysis of glioma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1552.

Emerging Issues in Cochlear ImplantationThe American Cochlear Implant Alliance (ACI Alliance) was incorporated in the late 2011 as a non-profit organization of cochlear implant clinicians from acro...

Objective: Herein, we describe the disease burden and age-related changes of congenital-onset myotonic dystrophy (CDM) in childhood. Methods: Children with CDM and age-matched controls aged 0 to 13 years were enrolled. Participants were divided into cohorts based on the following age groups: 0–2, 3–6, and 7–13 years. Each cohort received age-appropriate evaluations including functional testing, oral facial strength testing, neuropsychological testing, quality-of-life measurements, and ECG. Independent-samples t test or Wilcoxon 2-sample test was used to compare the differences between children with CDM and controls. Probability values less than 0.05 are reported as significant. Results: Forty-one participants with CDM and 29 healthy controls were enrolled. The 6-minute walk was significantly different between CDM (258.3 m [SD 176.0]) and control participants (568.2 m [SD 73.2]). The mean lip force strength was significantly different in CDM (2.1 N [SD 2.8)] compared to control participants (17.8 N [SD 7.6]). In participants with CDM, the mean IQ (65.8; SD 18.4) was 3 SDs below the mean compared to standardized norms. Measurements of grip strength, sleep quality, and quality of life were also significantly different. Strength measures (oral facial strength, grip strength, and 6-minute walk) correlated with each other but not with participant IQ. Conclusions: This work identifies important phenotypes associated with CDM during childhood. Several measures of strength and function were significantly different between participants with CDM and controls and may be useful during future therapeutic trials.

Glioblastoma (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-15 months. Immune system effector T cells are a promising therapy due to their high specificity and innate cytotoxicity. The ability to assess the efficacy and potency of T cell therapies in vitro and with high throughput is vital for the further development of this promising therapy. Cellular impedance-based assays offer a sensitive, label-free, and nondestructive method to continuously monitor cancer cell proliferation and immune cell-mediated cytotoxicity in real-time and at high throughputs, revealing not only the potency but also the kinetics of T cell therapies. Here, we investigated the targeting potency of activated human T cells on human U87MG glioma cell monolayers across multiple cell densities. U87MG cells were plated at 10k, 25k, and 50k cells per well on a PDL-coated CytoView-Z 96-well plate (n=12 wells per density), and their impedance was continuously monitored on the Maestro Z impedance platform. After 24 hours, activated patient-derived T Cells (ImmunoCult CD3/CD28 activation media) were added in a 10:1 effector:target ratio. Impedance and cytolysis were subsequently monitored for another 120 hours. As expected, higher densities proliferated faster and reached a higher impedance level at 24 hours. The addition of activated human T cells resulted in a decrease of the impedance signal consistent with T cell-mediated lysis of the glioma cells. The highest density of T cells (500k) exhibited the fastest rate of U87 cytolysis, with a Kill Time 50 of 35 hours. All densities reached 100% cytolysis by 100 hours. Overall, activated human T cells were highly effective for cytolysis of U87MG glioma cell monolayers of varying densities. The cellular impedance assay revealed high potency, with kinetics that varied across cell densities despite the same effector:target ratios. Citation Format: Stacie A. Chvatal, Meghan T. Logun, Heather B. Hayes, Daniel C. Millard, Lohitash Karumbaiah. Kinetics and potency of T Cell-mediated cytolysis of glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2187.

Background & Aim Glioblastoma is an aggressive brain cancer with no effective treatments and a prognosis of 12-15 months. Immune system effector T cells are a promising therapy due to their high specificity and innate cytotoxicity. Assessing the efficacy and potency of T cell therapies in vitro and with high throughput is vital for development of this promising therapy. Cellular impedance-based assays offer sensitive, label-free, and continuous monitoring of cell proliferation and immune cell-mediated cytotoxicity, revealing both the potency and kinetics of T cell killing. Here, we investigated the targeting potency of activated human T cells on human U87MG glioma and patient-derived glioma cells. Methods, Results & Conclusion U87MG and patient-derived glioma cells were plated at densities ranging from 10k to 50k cells per well on a PDL-coated CytoView-Z 96-well plate (n=12 wells per density). After 24 hours, activated patient-derived T Cells (ImmunoCult CD3/CD28 activation media) were added in a 10:1 effector:target ratio. Impedance and cytolysis were continuously monitored for over 120 hours. As expected, higher densities of glioma cells proliferated faster and reached a higher impedance level at 24 hours. Addition of activated human T cells resulted in a decrease in impedance consistent with T cell-mediated lysis of the glioma cells. The highest density of T cells (500k) exhibited the fastest rate of U87 cytolysis, with a Kill Time 50 of 35 hours. All densities reached 100% cytolysis by 100 hours. Overall, activated human T cells were highly effective for cytolysis of U87MG and patient-derived glioma cells. The cellular impedance assay revealed high potency, with kinetics that varied across cell densities despite the same effector:target ratios.

PURPOSE The purpose of this study was to investigate the physical activity levels in children with congenital myotonic dystrophy (CDM), and to examine whether patient clinical and functional characteristics correlated to physical activity. METHODS Twenty-five children with CDM were assessed on functional measures, clinical measures, and physical activity levels. RESULTS Results support that children with CDM spend the majority of their time inactive. There was a negative correlation between inactivity and cytosine-thymine-guanine repeats, suggesting increased inactivity with increased CDM severity. Age, body mass index, and lean muscle mass may be factors influencing activity levels. CONCLUSIONS Children in this study received one-third the recommended steps per day. The number of steps per day is not correlated with clinical measures.

Incomplete spinal cord injury (iSCI) often leads to partial disruption of spinal pathways that are important for motor control of walking. Persons with iSCI present with deficits in walking ability in part because of inconsistent leg kinematics during stepping. Although kinematic variability is important for normal walking, growing evidence indicates that excessive variability may limit walking ability and increase reliance on assistive devices (AD) after iSCI. The purpose of this study was to assess the effects of iSCI-induced impairments on kinematic variability during overground walking. We hypothesized that iSCI results in greater variability of foot and joint displacement during overground walking compared with controls. We further hypothesized that variability is larger in persons with limited walking speed and greater reliance on ADs. To test these hypotheses, iSCI and control subjects walked overground. Kinematic variability was quantified as step-to-step foot placement variability (end-point), and variability in hip-knee, hip-ankle, and knee-ankle joint space (angular coefficient of correspondence [ACC]). We characterized sensitivity of kinematic variability to cadence, auditory cue, and AD. Supporting our hypothesis, persons with iSCI exhibited greater kinematic variability than controls, which scaled with deficits in overground walking speed (p

Persons with incomplete spinal cord injury (iSCI) face ongoing struggles with walking, including reduced speed and increased reliance on assistive devices (ADs). The forces underlying body weight support and gait, as measured by ground reaction forces (GRFs), are likely altered after iSCI because of weakness and AD dependence but have not been studied. The purpose of this study was to examine GRF production during overground walking after iSCI, because greater insight into GRF constraints is important for refining therapeutic interventions. Because of reduced and discoordinated motor output after iSCI, we hypothesized that persons with iSCI would exert smaller GRFs and altered GRF modifications to increased cadence compared with able-bodied (AB) persons, especially when using an AD. Fifteen persons with chronic iSCI, stratified into no AD (n = 7) and AD (n = 8) groups, walked across an instrumented walkway at self-selected and fast (115% self-selected) cadences. Fifteen age-matched AB controls walked at their own cadences and iSCI-matched conditions (cadence and AD). Results showed fore-aft GRFs are reduced in persons with iSCI compared with AB controls, with reductions greatest in persons dependent on an AD. When controlling for cadence and AD, propulsive forces were still lower in persons with iSCI. Compared with AB controls, persons with iSCI demonstrated altered GRF modifications to increased cadence. Persons with iSCI exhibit different stance-phase forces compared with AB controls, which are impacted further by AD use and slower walking speed. Minimizing AD use and/or providing propulsive biofeedback during walking could enhance GRF production after iSCI.

The intact neuromotor system prepares for object grasp by first opening the hand to an aperture that is scaled according to object size and then closing the hand around the object. After cervical spinal cord injury (SCI), hand function is significantly impaired, but the degree to which object-specific hand aperture scaling is affected remains unknown. Here we hypothesized that persons with incomplete cervical SCI have a reduced maximum hand opening capacity but exhibit novel neuromuscular coordination strategies that permit object-specific hand aperture scaling during reaching. To test this hypothesis, we measured hand kinematics and surface electromyography (EMG) from seven muscles of the hand and wrist during attempts at maximum hand opening as well as reaching for four balls of different diameters. Our results showed that persons with SCI exhibited significantly reduced maximum hand aperture compared to able-bodied (AB) controls. However, persons with SCI preserved the ability to scale peak hand aperture with ball size during reaching. Persons with SCI also used distinct muscle coordination patterns that included increased co-activity of flexors and extensors at the wrist and hand compared to AB controls. These results suggest that motor planning for aperture modulation is preserved even though execution is limited by constraints on hand opening capacity and altered muscle co-activity. Thus, persons with incomplete cervical SCI may benefit from rehabilitation aimed at increasing hand opening capacity and reducing flexor-extensor co-activity at the wrist and hand.

Objective:To test the hypothesis that daily acute intermittent hypoxia (AIH) combined with hand opening practice improves hand dexterity, function, and maximum hand opening in persons with chronic, motor-incomplete, cervical spinal cord injury.Methods:Six participants completed the double-blind, crossover study. Participants received daily (5 consecutive days) AIH (15 episodes per day: 1.5 minutes of fraction of inspired oxygen [FIo2] = 0.09, 1-minute normoxic intervals) followed by 20 repetitions of hand opening practice and normoxia (sham, FIo2 = 0.21) + hand opening practice. Hand dexterity and function were quantified with Box and Block and Jebsen-Taylor hand function tests. We also recorded maximum hand opening using motion analyses and coactivity of extensor digitorum and flexor digitorum superficialis muscles using surface EMG.Results:Daily AIH + hand opening practice improved hand dexterity, function, and maximum hand opening in all participants. AIH + hand opening practice improved Box and Block Test scores vs baseline in 5 participants (p = 0.057) and vs sham + hand opening practice in all 6 participants (p = 0.016). All participants reduced Jebsen-Taylor Hand Function Test (JTHF) time after daily AIH + hand opening practice (−7.2 ± 1.4 seconds) vs baseline; 4 of 6 reduced JTHF time vs sham + hand opening practice (p = 0.078). AIH + hand opening practice improved maximum hand aperture in 5 of 6 participants (8.1 ± 2.7 mm) vs baseline (p = 0.018) and sham + hand opening practice (p = 0.030). In 5 participants, daily AIH–induced changes in hand opening were accompanied by improved EMG coactivity (p = 0.029).Conclusions:This report suggests the need for further study of AIH as a plasticity “primer” for task-specific training in spinal cord injury rehabilitation. Important clinical questions remain concerning optimal AIH dosage, patient screening, safety, and effect persistence.ClinicalTrials.gov identifier:NCT01272336.

Incomplete spinal cord injury (iSCI) disrupts motor control and limits the ability to coordinate muscles for overground walking. Inappropriate muscle activity has been proposed as a source of clinically observed walking deficits after iSCI. We hypothesized that persons with iSCI exhibit lower locomotor complexity compared to able-body (AB) controls as reflected by fewer motor modules, as well as, altered module composition and activation.Eight persons with iSCI and eight age-matched AB controls walked overground at prescribed cadences. Electromyograms of fourteen single leg muscles were recorded. Non-negative matrix factorization was used to identify the composition and activation of motor modules, which represent groups of consistently co-activated muscles that accounted for 90% of variability in muscle activity.Motor module number, composition, and activation were significantly altered in persons with iSCI as compared to AB controls during overground walking at self-selected cadences. However, there was no significant difference in module number between persons with iSCI and AB controls when cadence and assistive device were matched.Muscle coordination during overground walking is impaired after chronic iSCI.Our results are indicative of neuromuscular constraints on muscle coordination after iSCI. Altered muscle coordination contributes to person-specific gait deficits during overground walking.

Abnormal gait caused by stroke or other pathological reasons can greatly impact the life of an individual. Being able to measure and analyze that gait is often critical for rehabilitation. Motion analysis labs and many current methods of gait analysis are expensive and inaccessible to most individuals. The low-cost, wearable, and wireless insole-based gait analysis system in this study provides kinetic measurements of gait by using low-cost force sensitive resistors. This paper describes the design and fabrication of the insole and its evaluation in six control subjects and four hemiplegic stroke subjects. Subject-specific linear regression models were used to determine ground reaction force plus moments corresponding to ankle dorsiflexion/plantarflexion, knee flexion/extension, and knee abduction/adduction. Comparison with data simultaneously collected from a clinical motion analysis laboratory demonstrated that the insole results for ground reaction force and ankle moment were highly correlated (all >0.95) for all subjects, while the two knee moments were less strongly correlated (generally >0.80). This provides a means of cost-effective and efficient healthcare delivery of mobile gait analysis that can be used anywhere from large clinics to an individual's home.

Objectives: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI). Methods: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio 2 ] = 0.09) or daily normoxia (dSHAM, Fio 2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349). Results: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p Conclusions: dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI. Classification of evidence: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI.

Afferent feedback alters muscle activity during locomotion and must be tightly controlled. As primary afferent depolarization-induced presynaptic inhibition (PAD-PSI) regulates afferent signaling, we investigated hindlimb PAD-PSI during locomotion in an in vitro rat spinal cord-hindlimb preparation. We compared the relation of PAD-PSI, measured as dorsal root potentials (DRPs), to observed ipsilateral and contralateral limb endpoint forces. Afferents activated during stance-phase force strongly and proportionately influenced DRP magnitude in the swinging limb. Responses increased with locomotor frequency. Electrical stimulation of contralateral afferents also preferentially evoked DRPs in the opposite limb during swing (flexion). Nerve lesioning, in conjunction with kinematic results, support a prominent contribution from toe Golgi tendon organ afferents. Thus, force-dependent afferent feedback during stance binds interlimb sensorimotor state to a proportional PAD-PSI in the swinging limb, presumably to optimize interlimb coordination. These results complement known actions of ipsilateral afferents on PAD-PSI during locomotion.

This review covers the recent advances in the synthesis of enantiomerically pure hydroxylamine’s employing nitrones as starting materials. Nucleophilic additions of organometallic reagents to nitrones are the most common way for introducing a hydroxyamino group into carbon skeletons with the concomitant formation of a new carbon-carbon bond. Addition of nucleophiles derived from enolates, cyanide or fluorinated derivatives allows the preparation of complex structures. Radical additions and, in particular samarium diiodidemediated reductive coupling of nitrones with carbonyl compounds and α,β-unsaturated esters have also been considered. All these approaches provide efficient methods of preparation of enantiomerically pure hydroxylamine’s that are valuable synthetic intermediates., We thank for their support of our programs: MINECO (Madrid, Spain) and FEDER Program (Project CTQ2013-44367-C2-1-P) and the Government of Aragon (Group E-10). H.H. thanks UE (Erasmus program) for a mobility grant. M.G. thanks MECD for a FPU pre-doctoral grant.

Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord–hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations.

Previous studies showed that treatment with 17-β-estradiol-3-benzoate (EB) reduces isoproterenol (ISOP) stimulated water intake by ovariectomized rats. This effect was observed 48 h after the second of two EB injections, suggesting that the attenuation is attributable to classic EB actions to alter gene expression. However, in addition to classic, slowly-occurring, genomic effects, estrogens have more rapidly-occurring effects that may be nongenomic or ‘nonclassical’ genomic effects. Thus, it is possible that the EB attenuation of water intake stimulated by ISOP is genomic, nongenomic, or both. Accordingly, we measured ISOP-induced water intake by OVX rats at different times after EB injections, using time points likely to indicate classic genomic effects (48 h or 24 h) or nonclassical genomic or nongenomic effects (90 min). We also examined EB effects on body weight, uterine weight, and plasma volume and Na+ concentration in the same animals using the same time points and EB dose. EB treatment decreased water intake stimulated by ISOP in both the 24-h and 48-h groups; however, water intake in the 90-min group was not affected by EB. Uterine weight was unchanged 90 min after EB, but was increased 24 h after the first injection of EB. In contrast, body weight decreased after EB, but not until 48 h after the second EB injection. Finally, EB did not alter plasma Na+ concentration or hematocrit, though plasma protein concentration increased transiently 24 h after EB treatment. Taken together, these findings suggest that the behavioral, morphological, and physiological effects of EB likely are attributable to slowly-occurring, classic genomic actions of estrogens. Moreover, the time course of the observed effects varied, suggesting tissue-specific differences in estrogen receptor density or subtype, or in co-activators or co-repressors that, ultimately, determine the timing and direction of EB effects.

Background and purpose Resistance exercise via negative, eccentrically induced work (RENEW) has been shown to be associated with improvements in strength, mobility, and balance in multiple clinical populations. However, RENEW has not been reported for individuals with multiple sclerosis (MS). Methods Nineteen individuals with MS (8 men, 11 women; age mean = 49 ± 11 years; Expanded Disability Status Scale [EDSS] mean = 5.2 ± 0.9) were randomized into either standard exercise (STAND) or standard exercise and RENEW training (RENEW) for 3×/week for 12 weeks. Outcome measures were lower extremity strength (hip/knee flexion and extension, ankle plantar and dorsiflexion, and the sum of these individual values [sum strength]); Timed Up and Go (TUG), 10-m walk, self-selected pace (TMWSS) and maximal-pace (TMWMP), stair ascent (S-A) and descent (S-D) and 6-Minute Walk Test (6MWT), Berg Balance Scale (BBS), Fatigue Severity Scale (FSS). Results No significant time effects or interactions were observed for strength, TUG, TMWSS, TMWMP, or 6MWT. However, the mean difference in sum strength in the RENEW group was 38.60 (representing a 15% increase) compared to the sum strength observed in the STAND group with a mean difference of 5.58 (a 2% increase). A significant interaction was observed for S-A, S-D, and BBS as the STAND group improved whereas the RENEW group did not improve in these measures. Discussion and conclusions Contrary to results in other populations, the addition of eccentric training to standard exercises did not result in significantly greater lower extremity strength gains in this group of individuals with MS. Further this training was not as effective as standard exercise alone in improving balance or the ability to ascend and descend stairs. Following data collection, reassessment of required sample size indicates we were likely underpowered to detect strength differences between groups.

The neonatal rodent spinal cord maintained in vitro is a powerful model system to understand the central properties of spinal circuits generating mammalian locomotion. We describe three enabling approaches that incorporate afferent input and attached hindlimbs. (i) Sacral dorsal column stimulation recruits and strengthens ongoing locomotor-like activity, and implementation of a closed positive-feedback paradigm is shown to support its stimulation as an untapped therapeutic site for locomotor modulation. (ii) The spinal cord hindlimbs-restrained preparation allows suction electrode electromyographic recordings from many muscles. Inducible complex motor patterns resemble natural locomotion, and insights into circuit organization are demonstrated during spontaneous motor burst 'deletions', or following sensory stimuli such as tail and paw pinch. (iii) The spinal cord hindlimbs-pendant preparation produces unrestrained hindlimb stepping. It incorporates mechanical limb perturbations, kinematic analyses, ground reaction force monitoring, and the use of treadmills to study spinal circuit operation with movement-related patterns of sensory feedback while providing for stable whole-cell recordings from spinal neurons. Such techniques promise to provide important additional insights into locomotor circuit organization.

This study had three goals: (1) to document the literacy skills of deaf adolescents who received cochlear implants (CIs) as preschoolers; (2) to examine reading growth from elementary grades to high school; (3) to assess the contribution of early literacy levels and phonological processing skills, among other factors, to literacy levels in high school.A battery of reading, spelling, expository writing, and phonological processing assessments were administered to 112 high school (CI-HS) students, ages 15.5 to 18.5 yrs, who had participated in a reading assessment battery in early elementary grades (CI-E), ages 8.0 to 9.9 yrs. The CI-HS students' performance was compared with either a control group of hearing peers (N = 46) or hearing norms provided by the assessment developer.Many of the CI-HS students (47 to 66%) performed within or above the average range for hearing peers on reading tests. When compared with their CI-E performance, good early readers were also good readers in high school. Importantly, the majority of CI-HS students maintained their reading levels over time compared with hearing peers, indicating that the gap in performance was, at the very least, not widening for most students. Written expression and phonological processing tasks posed a great deal of difficulty for the CI-HS students. They were poorer spellers, poorer expository writers, and displayed poorer phonological knowledge than hearing age-mates. Phonological processing skills were a critical predictor of high school literacy skills (reading, spelling, and expository writing), accounting for 39% of variance remaining after controlling for child, family, and implant characteristics.Many children who receive CIs as preschoolers achieve age-appropriate literacy levels as adolescents. However, significant delays in spelling and written expression are evident compared with hearing peers. For children with CIs, the development of phonological processing skills is not just important for early reading skills, such as decoding, but is critical for later literacy success as well.

We are grateful to the following oral programs across the United States that identified participants and either submitted test results or facilitated our conducting the necessary testing: Auditory/Oral School of New York (Brooklyn, NY), Beth Israel Medical Center (New York, NY), Bolesta Center (Tampa, FL), Bucks County Intermediate Unit #22, Hearing Support Program (Doylestown, PA), Buffalo Hearing and Speech Center (Buffalo, NY), Concord Area Special Education Collaborative Speech, Hearing, Language Impaired Program (Concord, MA), Children's Choice for Hearing and Talking, CCHAT Center (Sacramento, CA), Charlotte Eye, Ear, Nose and Throat Associates (Charlotte, NC), Child's Voice (Chicago, IL), Central Institute for the Deaf (St. Louis, MO), Clarke School East (Canton, MA), Clarke Jacksonville Auditory/Oral Center (Jacksonville, FL), The Clarke School for the Deaf (Northampton, MA), Clarke Pennsylvania Auditory/Oral Center (Bryn Mawr, PA), DePaul School for Hearing and Speech (Pittsburgh, PA), Desert Voices Oral Learning Center (Phoenix, AZ), Echo Horizon School (Culver City, CA), HEAR in New Hampshire (Hooksett, NH), Hearing Impaired Program (HIP) of Bergen County Special Services (Midland Park, NJ), John Tracy Clinic (Los Angeles, CA), June A. Reynolds, Inc., Auditory-Verbal Inclusion Program for Hearing Impaired Children (Beverly, MA), Jean Weingarten Peninsula Oral School for the Deaf (Redwood City, CA), Listen and Learn (San Jose, CA), Listen and Talk (Seattle, WA), Magnolia Speech School (Jackson, MS), Moog Center for Deaf Education (St. Louis, MO), The Moog School (Columbia, MO), Northern Voices (Roseville, MN), Ohio Valley Voices (Loveland, OH), Omaha Hearing School (Omaha, NE), Oralingua School for the Hearing Impaired (Whittier, CA), Orange County Auditory―Oral Program for the Hearing Impaired (Orlando, FL), St. Joseph's Institute for the Deaf (St. Louis, MO), St. Joseph's Institute for the Deaf at Carle (Urbana, IL), St. Joseph's Institute for the Deaf (Kansas City, KS), Summit Speech School (New Providence, NJ), Sunshine Cottage School for Deaf Children (San Antonio, TX), Tucker Maxon Oral School (Portland, OR), The Hearing Impaired Program of the School District of Waukesha (Waukesha, WI). We also thank the parents who granted permission for their child's results to be included in this database. Statistical analyses were conducted by Dr. Michael J. Strube, Psychology Department, Washington University (St. Louis, MO). These data were presented in April 2007 at the 11th Cochlear Implant Conference (Charlotte, NC). No conflicts of interest were reported. Correspondence should be sent to Ann Geers, 167 Rocky Knob Road, Clyde, NC 28721 (e-mail: ageers@earthlink.net).

Although the spinal cord contains the pattern-generating circuitry for producing locomotion, sensory feedback reinforces and refines the spatiotemporal features of motor output to match environmental demands. In vitro preparations, such as the isolated rodent spinal cord, offer many advantages for investigating locomotor circuitry, but they lack the natural afferent feedback provided by ongoing locomotor movements. We developed a novel preparation consisting of an isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs free to step on a custom-built treadmill. This preparation combines the neural accessibility of in vitro preparations with the modulatory influence of sensory feedback from physiological hindlimb movement. Locomotion induced by N-methyl d-aspartate and serotonin showed kinematics similar to that of normal adult rat locomotion. Changing orientation and ground interaction (dorsal-up locomotion vs ventral-up air-stepping) resulted in significant kinematic and electromyographic changes that were comparable to those reported under similar mechanical conditions in vivo. We then used two mechanosensory perturbations to demonstrate the influence of sensory feedback on in vitro motor output patterns. First, swing assistive forces induced more regular, robust muscle activation patterns. Second, altering treadmill speed induced corresponding changes in stride frequency, confirming that changes in sensory feedback can alter stride timing in vitro. In summary, intact hindlimbs in vitro can generate behaviorally appropriate locomotor kinematics and responses to sensory perturbations. Future studies combining the neural and chemical accessibility of the in vitro spinal cord with the influence of behaviorally appropriate hindlimb movements will provide further insight into the operation of spinal motor pattern-generating circuits.