Effectiveness of a home training program on improving pinch force perception in older adults.

BACKGROUND: Hand function is reduced with aging which can lead to impairments in the performance of daily activities and eventually loss of independence. The ability to perceive the forces being applied to an object is an important component of hand control that also declines with age. However, the extent to which force perception can be improved through training remains largely unknown. PURPOSE: This study evaluated the effectiveness of a home-training program focused on improving force perception in older adults. STUDY DESIGN: Quasi-experimental - Uncontrolled trial. METHODS: Eleven independent, healthy adults (mean age: 77.2 ± 6.8 years) participated in a home-based sensorimotor hand training program 6 days/week for 6 weeks. Force perception, the primary outcome variable, was measured as the ability to reproduce a pinch force equal to 25% maximum voluntary contraction in the absence of visual feedback using either the ipsilateral remembered or contralateral concurrent (CC) hand. We also measured hand strength, dexterity, tactile acuity, and cognition before and after training. RESULTS: After the program was completed, participants showed a 35% reduction in absolute (p < 0.01, confidence interval (CI): [7.3, 33.2], effect sizes (ES): 0.87) and constant (p = 0.05, CI: [0.0, 34.9], ES: 0.79) force matching errors in the CC condition. Improvements in dominant hand dexterity (Purdue pegboard test) (p < 0.05, CI: [0.2, 2.4], ES: 0.60) and tactile sensitivity (JVP thresholds) (p < 0.05, CI: [-1.7, -0.1], ES: 0.94), as well as cognition (Trail Making Test B) (p < 0.05, CI: [-24,1. -1.6], ES: 0.30) were also observed post-training. CONCLUSIONS: The results suggest that home-hand training can be an effective way to improve force perception among older adults.

An intergenerational service-learning approach to improve hand function in older adults.

Homebound older adults are at greater risk for functional impairments, social isolation, and loss of independence. Adequate hand function is needed to perform many daily activities, yet is understudied, particularly in the homebound population. The purpose of this study was to pilot test an intergenerational program in which pre-health college students were trained to deliver hand exercises to homebound older adults receiving Meals on Wheels (MOW) services. Eight MOW clients (mean age: 80.1 ± 12.9y) and 17 students completed the program. Students visited clients 2×/week for 6 weeks and engaged in hand exercises and meaningful conversations. Measures of hand strength, dexterity, self-reported function, self-efficacy, depression, and social isolation were taken before and after the program. Clients and students also completed a post-program experience survey. Significant improvements in pinch strength were observed, and 75% of clients reported better upper limb mobility after training. Survey feedback was positive with clients saying they enjoyed interacting with college students, while students praised the hands-on nature of the program and engagement with older adults. Results from this pilot study demonstrate an intergenerational approach to deliver hand training is feasible and underscores the value of using such models to increase access to care for homebound older adults.

Is maximum grip strength a reliable predictor of hand limitations among older adults?

BACKGROUND: Grip strength is commonly used to assess hand function among older adults. While shown to be associated with disability, the degree to which grip strength specifically predicts hand limitations is unknown. AIMS: The primary aim of this study was to evaluate grip strength as a predictor of hand limitations. METHODS: Using the 2011-14 National Health and Nutrition Examination Survey (NHANES), we classified older adults reporting one or more hand limitations versus those with no limitations. Odds ratios were used to assess the association between grip strength (separated into quartiles) and the likelihood of a hand limitation while controlling for sex, race/ethnicity, education level, income, and pain. Receiver operator characteristic (ROC) curves were used to evaluate the degree to which grip strength discriminates between older adults with and without a hand limitation. RESULTS: We identified 2064 older adults (age ≥ 65), 31% of whom reported a hand-related limitation. Older adults with very low grip strength (weakest quartile) were more likely to report at least one limitation (OR: 6.1, 95% CI: 3.2, 11.8) than those with high grip strength (strongest quartile). However, grip strength had poor to moderate discrimination of hand limitations (ROC area under curves: 0.65-0.81). DISCUSSION: While self-reported hand limitations were associated with lower grip strength; overall, it is a relatively poor predictor of hand impairments among older adults. CONCLUSION: Better assessments are needed to adequately evaluate upper extremity impairments to help older adults maintain functional independence.

Home-based movement therapy in neonatal brachial plexus palsy: A case study.

STUDY DESIGN: Case report. INTRODUCTION: The value of movement-based therapy in peripheral nerve injury conditions such as neonatal brachial plexus palsy (NBPP) is unclear. PURPOSE OF THE STUDY: To determine the effectiveness of a home-based movement therapy program in a 17 year old female patient with a right NBPP pan-plexopathy. METHODS: Home training consisted of arm reaching and object manipulation tasks using devices which recorded performance. Training occurred for 1 h/day, 5 days/week for 6 weeks with periodic webcam supervision. Pre- and post clinical, functional and kinematic assessments were performed in a laboratory setting. RESULTS: Following training, shoulder flexion and elbow extension active range of motion increased by 13° and 9°, respectively, and functional ability also improved. Reach movement duration decreased significantly with a concomitant improvement in movement coordination. CONCLUSIONS: These results demonstrate that movement therapy has the potential to improve motor function in NBPP years after the initial insult. LEVEL OF EVIDENCE: 4.

Racial/Ethnic Differences in Self-Reported Upper Limb Limitations Among U.S. Older Adults.

BACKGROUND: The development of disability related to activities of daily living (ADL) is of great concern in the aging population, particularly for Hispanic and Non-Hispanic (NH) Black older adults, where disability prevalence is greater compared to NH Whites. ADL-disability is typically measured across many functional tasks without differentiating upper- versus lower-limb limitations, hindering our understanding of disability burden. Despite the importance of the upper limbs for completing ADL and known age-related declines in function, racial/ethnic differences in upper limb function remain largely unknown. METHODS: We identified 4 292 NH White, NH Black, and Mexican American older adults (≥65) from the 2011-2018 waves of the National Health and Nutrition Examination Survey (NHANES). We classified participants as having a limitation based on their ability to complete 5 upper-limb tasks (preparing meals, eating, dressing, reaching overhead, and grasping small objects) and compared limitation rates across racial/ethnic groups. RESULTS: Compared to NH Whites, NH Black older adults had significantly greater odds of reporting difficulties preparing meals (odds ratio [OR]: 1.36, 95% confidence interval [95% CI]: 1.01, 1.86) and dressing (OR: 1.55, 95% CI: 1.19, 2.02), while Mexican Americans had greater difficulty preparing meals (OR: 1.70, 95% CI: 1.12, 2.58), dressing (OR: 1.63, 95% CI: 1.12, 2.36), and grasping small objects (OR: 1.48, 95% CI: 1.06, 2.07). CONCLUSIONS: Our results demonstrate differences in self-reported upper limb ADL-disability across racial/ethnic groups, particularly for Mexican American older adults. Such findings underscore the need for routine monitoring of upper limb function throughout adulthood to identify limitations and target therapeutic interventions before independence is compromised.

Recovery of Shoulder, Elbow, and Forearm Movement After Nerve Reconstruction for Neonatal Brachial Plexus Palsy.

BACKGROUND AND OBJECTIVES: There is a relative dearth of published data with respect to recovery of upper extremity movement after nerve reconstruction for neonatal brachial plexus palsy (NBPP). This study aimed to demonstrate long-term recovery of active range of motion (AROM) at the shoulder, elbow, and forearm after nerve reconstruction for NBPP and to compare that with patients managed nonoperatively. METHODS: We interrogated a prospectively collected database of all patients evaluated for NBPP at a single institution from 2005 to 2020. AROM measurements for shoulder, elbow, and forearm movements were collected at every visit up to 5 years of follow-up and normalized between 0 and 1. We used generalized estimated equations to predict AROM for each movement within local age windows over 5 years and compared the operative and nonoperative cohorts at each age interval. RESULTS: In total, >13 000 collected datapoints representing 425 conservatively and 99 operatively managed children were included for analysis. At 5 years, absolute recovery of AROM after nerve reconstruction was ∼50% for shoulder abduction and forward flexion, ∼65% for shoulder external rotation, and ∼75% for elbow flexion and forearm supination, with ∼20% loss of elbow extension AROM. Despite more limited AROM on presentation for the operative cohort, at 5 years, there was no significant difference between the groups in AROM for shoulder external rotation, elbow extension, or forearm supination, and, in Narakas grade 1-2 injury, shoulder abduction and forward flexion. CONCLUSION: We demonstrate recovery of upper extremity AROM after nerve surgery for NBPP. Despite more severe presenting injury, operative patients had similar recovery of AROM when compared with nonoperative patients for shoulder external rotation, elbow extension, forearm supination, and, for Narakas grade 1-2 injury, shoulder abduction and forward flexion.

Quantifying Patient-Initiated Upper Extremity Movement After Surgical Reconstruction for Adult Pan-Brachial Plexus Injury.

BACKGROUND AND OBJECTIVES: Determining functional recovery in adult patients with traumatic pan-brachial plexus injury (pBPI) is hampered by the fact that most outcome measures are collected in the clinical setting and may not reflect arm use in the real world. This study's objectives were to demonstrate the feasibility of using wearable motion sensor technology to quantify spontaneous arm movement in adult patients with pBPI after surgical reconstruction and report the time and intensity with which the affected arm was used. METHODS: Twenty-nine patients with pBPI who underwent surgical reconstruction at least 2 years prior were included in this study. Study participants wore an accelerometer on bilateral arms for 7 days. The vector time (VT) and magnitude with which each arm moved were collected and divided by the same values collected from the uninjured arm to generate a ratio (VT and vector magnitude [VM], respectively) to quantify differences between the arms. Correlations between VT, VM, and patient demographic and physician-elicited clinical measures were calculated. Patients were enrolled at Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan, and data analysis was performed at the University of Michigan. RESULTS: Twelve patients had pan-avulsion injuries, and 17 patients had C5 rupture with C6-T1 avulsion injuries. All underwent nerve reconstruction with contralateral C7 or ipsilateral C5 nerve roots as donors. At mean 7.3 years after surgery, the mean VT ratio was 0.54 ± 0.13 and the mean VM ratio was 0.30 ± 0.13. Both VT and VM ratios were significantly correlated with patient employment and movements at the elbow and forearm. CONCLUSION: Wearable motion detection technology can capture spontaneous, real-world movements of the arm in patients who have undergone surgical reconstruction for pBPI. Despite severe injuries, these patients are able to use their affected arm 50% of the time and with 30% of the intensity of their unaffected arm, which is positively correlated with return to work after injury. These data support the use of surgical reconstruction for pBPI.

Quantifying real-world upper limb activity via patient-initiated spontaneous movement in neonatal brachial plexus palsy.

BACKGROUND: Neonatal brachial plexus palsy (NBPP) results in muscle weakness and impaired somatosensory function of the arm. Current functional assessment is primarily based on clinician-elicited measurements including muscle strength and range of motion. To what extent these measures are representative of real-world arm movement is unclear. OBJECTIVE: To determine the feasibility of using body-worn accelerometers to remotely assess arm movements in children with NBPP. DESIGN: Prospective criterion validity study of accelerometry versus clinician assessment. SETTING: Academic medical center. PARTICIPANTS: Nine adolescents with NBPP and nine age- and gender-matched control adolescents participated in the study. All were enrolled in school and participated in community activities. INTERVENTIONS: Not applicable. METHODS: Standard clinician-elicited measurements were collected. For assessing spontaneous arm movements, participants wore activity monitors during all waking hours for 7 days. Results were expressed as ratios of affected to unaffected arm motion for duration and magnitude and correlated with traditional clinic-based assessments. Spearman correlations were used to determine relationships between accelerometry results and traditional assessments. A p value <.05 was considered statistically significant. MAIN OUTCOME MEASUREMENTS: Accelerometry measurements of arm motion and traditional clinical assessments. RESULTS: Compared to control ratios, duration of arm movement and magnitude ratios were reduced in the NBPP group, particularly for arm magnitude due to reduced affected arm movement and an increase in unaffected arm movement. Ratios were highly correlated with shoulder function and, to a lesser extent, with elbow function. CONCLUSION: Real-world arm use is an appropriate outcome measure that reflects functional recovery. This study demonstrates the feasibility of wearable technology to quantify duration and intensity of spontaneous arm movement in children with NBPP. Accelerometry also allows for the association between traditional clinician-elicited assessment measures and spontaneous arm movements, demonstrating the importance of the shoulder as a focus of treatment in NBPP.

Enhanced Street Crossing Features are Associated with Higher Post-Stroke Physical Quality of Life.

BACKGROUND: Features of the physical environment may affect post-stroke recovery, but empirical evidence is limited. This study examines associations between features of the physical environment and post-stroke physical quality of life (PH-QOL). METHODS: The study sample included stroke survivors enrolled in the Caring for Adults Recovering from the Effects of Stroke project, a prospective cohort. Features of the physical environment surrounding participants' home addresses were audited using Google Earth. Audits captured information about crossings (e.g. curb-cuts; range 0-4), street segments (e.g. sidewalks; range 0-17.5), and a route (e.g. parks; range 0-27) near participants' home. Summary scores were categorized into tertials representing "few," "some," and "many" pedestrian-friendly features. Post-stroke PH-QOL was measured by the SF-12 (range 0-100) around 6 to 12-, 18-, 27-, and 36-months post-stroke. Linear mixed models were used to estimate PH-QOL over time. Chained multiple imputation was used to account for missing data. RESULTS: Two hundred and seventy-five participants were eligible, among whom 210 had complete data. Most participants lived in areas with "few" features to promote outdoor mobility. Participants living in environments with "some" crossing features had a 4.90 (95% CI: 2.32, 7.48) higher PH-QOL score across the observation period in comparison to participants living in environments with "few" crossing features. Features of the physical environment along street segments and routes were not associated with post-stroke PH-QOL. CONCLUSION: Crossing features are associated with post-stroke PH-QOL. Modifying features of the physical environment at nearby crossings, such as curb-cuts, may be a promising strategy for increasing PH-QOL.

Use of a Novel Theory-Based Pragmatic Tool to Evaluate the Quality of Instructor-Led Exercise Videos to Promote Youth Physical Activity at Home: Preliminary Findings.

BACKGROUND: Exercise videos that work to minimize cognitive load (the amount of information that working memory can hold at one time) are hypothesized to be more engaging, leading to increased PA participation. PURPOSE: To use a theory-based pragmatic tool to evaluate the cognitive load of instructor-led exercise videos associated with the Interrupting Prolonged Sitting with ACTivity (InPACT) program. METHODS: Exercise videos were created by physical education teachers and fitness professionals. An evaluation rubric was created to identify elements each video must contain to reduce cognitive load, which included three domains with four components each [technical (visual quality, audio quality, matching modality, signaling), content (instructional objective, met objective, call-to-action, bias), and instructional (learner engagement, content organization, segmenting, weeding)]. Each category was scored on a 3-point scale from 0 (absent) to 2 (proficient). A video scoring 20-24 points induced low cognitive load, 13-19 points induced moderate cognitive load, and less than 13 points induced high cognitive load. Three reviewers independently evaluated the videos and then agreed on scores and feedback. RESULTS: All 132 videos were evaluated. Mean video total score was 20.1 ± 0.7 points out of 24. Eighty-five percent of videos were rated low cognitive load, 15% were rated moderate cognitive load, and 0% were rated high cognitive load. The following components scored the highest: audio quality and matching modality. The following components scored the lowest: signaling and call-to-action. CONCLUSIONS: Understanding the use of a pragmatic tool is a first step in the evaluation of InPACT at Home exercise videos. Our preliminary findings suggest that the InPACT at Home videos had low cognitive load. If future research confirms our findings, using a more rigorous study design, then developing a collection of instructor-led exercise videos that induce low cognitive load may help to enhance youth physical activity participation in the home environment.

Compromised encoding of proprioceptively determined joint angles in older adults: the role of working memory and attentional load.

Perceiving the positions and movements of one's body segments (i.e., proprioception) is critical for movement control. However, this ability declines with older age as has been demonstrated by joint angle matching paradigms in the absence of vision. The aim of the present study was to explore the extent to which reduced working memory and attentional load influence older adult proprioceptive matching performance. Older adults with relatively HIGH versus LOW working memory ability as determined by backward digit span and healthy younger adults, performed memory-based elbow position matching with and without attentional load (i.e., counting by 3 s) during target position encoding. Even without attentional load, older adults with LOW digit spans (i.e., 4 digits or less) had larger matching errors than younger adults. Further, LOW older adults made significantly greater errors when attentional loads were present during proprioceptive target encoding as compared to both younger and older adults with HIGH digit span scores (i.e., 5 digits or greater). These results extend previous position matching results that suggested greater errors in older adults were due to degraded input signals from peripheral mechanoreceptors. Specifically, the present work highlights the role cognitive factors play in the assessment of older adult proprioceptive acuity using memory-based matching paradigms. Older adults with LOW working memory appear prone to compromised proprioceptive encoding, especially when secondary cognitive tasks must be concurrently executed. This may ultimately result in poorer performance on various activities of daily living.

Measuring Hand Sensory Function and Force Control in Older Adults: Are Current Hand Assessment Tools Enough?

BACKGROUND: The ability to grasp and manipulate objects is essential for performing activities of daily living. However, there is limited information regarding age-related behavioral differences in hand sensorimotor function due, in part, to the lack of assessment tools capable of measuring subtle but important differences in hand function. The purpose of this study was to demonstrate performance differences in submaximal force control and tactile pattern recognition in healthy older adults using 2 custom-designed sensorimotor assessment tools. METHODS: Sensorimotor function was assessed in 13 healthy older adults (mean age 72.2 ± 5.5 years, range: 65-84 years) and 13 young adults (mean age 20 ± 1.4 years, range: 19-23 years). Clinical assessments included the Montreal Cognitive Assessment (MoCA), monofilament testing, maximum voluntary contraction (MVC), and Grooved Pegboard Test. Sensorimotor assessments included submaximal (5, 20% MVC) grip force step-tracking and tactile pattern recognition tasks. RESULTS: Clinical assessments revealed no or minimal group differences in MVC, monofilament thresholds, and MoCA. However, sensorimotor assessments showed that older adults took longer to discriminate tactile patterns and had poorer accuracy than young adults. Older adults also produced submaximal forces less smoothly than young adults at the 20% force level while greater variability in force maintenance was seen at 5% but not 20% MVC. CONCLUSIONS: These results demonstrate the ability to integrate higher-order tactile information and control low grip forces is impaired in older adults despite no differences in grip strength or cognition. These findings underscore the need for more sensitive evaluation methods that focus on sensorimotor ability reflective of daily activities.

"Well in in this neighborhood I have walked, not at all": Stroke survivors lived experience in the outdoor environment.

Stroke survivors face unique challenges in the outdoor environment when returning to their home community following a stroke. Challenges include navigating uneven terrain, social stigma, and adapting to changes in functioning. Outdoor environments may serve as potential points of intervention to promote independence and participation post stroke. This study aimed to understand lived post-stroke experience in the outdoor environment as it pertains to independent mobility. METHODS: Qualitative semi-structured interviews were conducted with 20 stroke survivors (8 males, 12 females; mean age 64.2 years: range 45 years-90 years). Participants were eligible if they were over the age of 45, could communicate in English, lived outside a nursing home, able to walk safely outdoors, were a minimum of six-months post stroke, and had no severe cognitive impairment. Interviews with participants were tape recorded, audio files were transcribed verbatim, codes were created and applied to transcripts, and themes were generated using interpretative phenomenological analysis. RESULTS: Post-stroke experiences in the outdoor environment were multidimensional. Three themes emerged from the stroke survivors' description of personal experiences in the outdoor environment. These themes included feelings of vigilance, employing adaptation strategies, and management of dynamic relations between the self and context. DISCUSSION: The findings highlight the post-stroke experience traversing the outdoor environment. Investing in the public outdoor environment to remove barriers and install facilitators could reduce feelings of apprehension and hypervigilance while walking in the outdoor environment. Future research is needed to evaluate the role of environmental interventions on hypervigilance in the outdoor environment post stroke.

The Relationship Between Environmental Exposures and Post-Stroke Physical Activity.

INTRODUCTION: Post-stroke physical activity has widespread health benefits. Environmental exposures may shape post-stroke physical activity behavior. This study investigates the relationships between environmental exposures and post-stroke physical activity. METHODS: Stroke survivors (n=374) from a cohort of Black and White adults with post-stroke accelerometer data (2009-2013) were eligible for this study. Participants' home addresses were linked with secondary data to capture environmental characteristics, including annual density of neighborhood resources (e.g., parks, physical activity facilities, and intellectual stimulation destinations), 2010 neighborhood SES, 2010 neighborhood crime, and daily information on extremely cold days. Post-stroke light physical activity and moderate-to-vigorous physical activity were captured using accelerometers over a 7-day period. Linear regression and 2-part/hurdle models were used to estimate the relationship between the density of neighborhood resources with light physical activity and with moderate-to-vigorous physical activity, respectively. Analyses were conducted in 2021. RESULTS: A 10% increase in the number of extremely cold days was associated with 6.37 fewer minutes of daily light physical activity (95% CI= -11.37, -1.37). A 1-SD increase in neighborhood SES was associated with greater odds (OR=1.10, 95% CI=1.02, 1.19) of doing any moderate-to-vigorous physical activity. Among participants obtaining any moderate-to-vigorous physical activity, a 1-unit (count/km2) increase in destinations for intellectual stimulation was associated with 0.99 (95% CI=0.02, 1.97) more minutes of daily moderate-to-vigorous physical activity. All other environmental exposures were not associated with post-stroke light physical activity or moderate-to-vigorous physical activity. CONCLUSIONS: Environmental exposures may facilitate physical activity participation among stroke survivors. This study found that weather, neighborhood SES, and proximity to destinations for intellectual stimulation were associated with physical activity over and above individual factors.

Quantifying long-term upper-limb activity using wearable motion sensors after nerve reconstruction for neonatal brachial plexus palsy.

OBJECTIVE: Standard, physician-elicited clinical assessment tools for the evaluation of function after nerve reconstruction for neonatal brachial plexus palsy (NBPP) do not accurately reflect real-world arm function. Wearable activity monitors allow for the evaluation of patient-initiated, spontaneous arm movement during activities of daily living. In this pilot study, the authors demonstrate the feasibility of using body-worn sensor technology to quantify spontaneous arm movement in children with NBPP 10 years after nerve reconstruction and report the timing and magnitude of recovered arm movement. METHODS: Eight children with NBPP who underwent brachial plexus reconstruction approximately 10 years prior were recruited to take part in this single-institution prospective pilot study. Per the treatment protocol of the authors' institution, operated patients had severe, nonrecovering nerve function at the time of surgery. The patients were fitted with an activity monitoring device on each of the affected and unaffected arms, which were worn for 7 consecutive days. The duration (VT) and power (VM) with which each arm moved during the patient's normal daily activities were extracted from the accelerometry data and ratios comparing the affected and unaffected arms were calculated. Demographic data and standard physician-elicited clinical measures of upper-extremity function were also collected. RESULTS: Three children underwent nerve grafting and transfer and 5 children underwent graft repair only. The mean (± SD) active range of motion was 98° ± 53° for shoulder abduction, 130° ± 24° for elbow flexion, and 39° ± 34° for shoulder external rotation. The median Medical Research Council grade was at least 2.5 for all muscle groups. The median Mallet grade was at least 2 for all categories, and 13.5 total. The VT ratio was 0.82 ± 0.08 and the VM ratio was 0.53 ± 0.12. CONCLUSIONS: Wearable activity monitors such as accelerometers can be used to quantify spontaneous arm movement in children who underwent nerve reconstruction for NBPP at long-term follow-up. These data more accurately reflect complex, goal-oriented movement needed to perform activities of daily living. Notably, despite severe, nonrecovering nerve function early in life, postsurgical NBPP patients use their affected arms more than 80% of the time that they use their unaffected arms, paralleling results in patients with NBPP who recovered spontaneously. These data represent the first long-term, real-world evidence to support brachial plexus reconstruction for patients with NBPP.

Discovery of a novel series of nonacidic benzofuran EP1 receptor antagonists.

We describe the discovery and optimization of a novel series of benzofuran EP(1) antagonists, leading to the identification of 26d, a novel nonacidic EP(1) antagonist which demonstrated efficacy in preclinical models of chronic inflammatory pain.

Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults.

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.

Influence of task on interlimb coordination in adults with cerebral palsy.

OBJECTIVE: To examine movement time and kinematic properties of unilateral and bilateral reaching movements in adults with cerebral palsy (CP), focusing on how different types of bilateral movements, simultaneous or sequential, may influence interlimb coordination. DESIGN: Quantitative study using between-group repeated-measures analyses. SETTING: Motor control laboratory at a research university. PARTICIPANTS: Adults with hemiplegic CP (n=11; mean age ± SD, 33±10y; 4 men) and age-matched controls (mean age ± SD, 32±9y; 4 men). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Movement time (MT), maximum deviation from a straight trajectory to the target, and peak speed. RESULTS: Although adults with hemiplegic CP showed strong unilateral deficits, bilateral simultaneous reaching movements were temporally and spatially coupled. Movement of the less affected arm slowed to match the movement of the more affected arm. In contrast, bilateral sequential movements improved MTs of the less affected and more affected arms. CONCLUSIONS: Bilateral sequential movements were conducive to faster MT compared with unilateral or bilateral simultaneous movements. Training that includes bilateral sequential movements may be beneficial to adults with hemiplegic CP. Upper-limb movements are coordinated in a variety of ways to perform routine bilateral tasks. Some bilateral tasks, such as stacking boxes, require more symmetric movements of the upper limbs. Other bilateral tasks, such as opening the refrigerator with 1 hand while placing an item on the shelf with the other hand, emphasize coordinated sequential action between upper limbs. Despite the prevalence of integrative upper-limb use, the control of different forms of bilateral movement is not well understood. A more comprehensive knowledge of upper-limb bilateral movements may hold important implications for developing more effective upper-limb movement therapies.

Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain.

Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP(1) receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 414.9g/mol and poor in vivo metabolic stability in the rat and resulted in the identification of compound 7i (GSK345931A) which demonstrated good metabolic stability in the rat and lower molecular weight (381.9g/mol). In addition, 7i (GSK345931A) showed measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain.

Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.

We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.