Morrow, Melissa M

Incorporating sex as a biological variable (SABV) into basic and medical research requires a deliberate plan that weaves concepts of basic genetics, cellular and molecular physiology, and pharmacology into translational medicine. An R4 approach (Right content to the Right learner at the Right time with the Right modality) allows for content to be available in a variety of formats that reinforces the concepts at staged levels of integration. Weaving SABV throughout the varied formats of the R4 approach within the Clinical and Translational Research Training Programs, into the mentoring and training of scholars in NIH Building Interdisciplinary Careers in Women's Health (BIRCWH), and into the Career Enhancement Core of the Specialized Centers of Research Excellence (SCORE) on sex differences through curriculum, case-based approach and journal clubs, and workshops ensures that learners grasp its fundamental relevancy to their own research and beyond. In addition, the collaborative work among the BIRCWH and SCORE programs brings collective expertise from centers around the United States to individual programs through development of best practices and materials. These collective efforts assure that the next generation of basic, clinical, and translational scientists will bring the dimension of SABV into their research and clinical practice.

Abstract Background/Objective Chronic pain is commonly reported in individuals with spinal cord injuries (SCIs), with recent prevalence reported as high as 80%. Uncontrolled pain is known to decrease quality of life, attenuate mood, and impact sleep. Spinal cord stimulation (SCS) for the treatment of refractory pain was first used in the SCI population in 1972. To date there have been no randomized controlled trials examining the effect of SCS on neuropathic pain post‐SCI. A literature review in 2009 identified 27 studies, the majority prior to 2000, that included at least 1 patient with SCI. Given the significant advancements in the field of SCS, this review examines the updated evidence of SCS for the treatment of neuropathic pain in individuals with SCI and provides guidance on future investigations. Methods MEDLINE and EMBASE databases were searched. All published reports, case series, and clinical trials reviewing SCS for neuropathic pain that included at least 1 individual with SCI were included. Results The initial search identified 376 reports, of which 22 met inclusion criteria, for a total of 69 patients. All reports were of very low quality. A majority of the reported patients were male, underwent tonic stimulation, and reportedly experienced improvement in pain and spasticity, with decreased use of pain medication. Conclusions The synthesized findings from primarily case studies support the safety of SCS in SCI with the suggestion of potential pain relief benefit; however, data from low‐quality studies are insufficient for informing clinical practice. A well‐designed, prospective clinical trial is proposed to further investigate this indication.

PurposeThe purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound (MBI/US) system designed to enable, in real‐time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI.MethodsThe MBI/US system was constructed by modifying an existing dual‐head cadmium zinc telluride (CZT)‐based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual‐head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real‐time MBI/US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI.ResultsCombined MBI/US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI.ConclusionThe MBI/US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real‐time, registered US imaging of MBI‐detected lesions may obviate the need to proceed to more expensive procedures such as contrast‐enhanced breast MRI for diagnostic workup or biopsy of MBI findings.

The purpose of this study was to validate a commercially available inertial measurement unit (IMU) system against a standard lab-based motion capture system for the measurement of shoulder elevation, elbow flexion, trunk flexion/extension, and neck flexion/extension kinematics. The validation analyses were applied to 6 surgical faculty members performing a standard, simulated surgical training task that mimics minimally invasive surgery. Three-dimensional joint kinematics were simultaneously recorded by an optical motion capture system and an IMU system with 6 sensors placed on the head, chest, and bilateral upper and lower arms. The sensor-to-segment axes alignment was accomplished manually. The IMU neck and trunk IMU flexion/extension angles were accurate to within 2.9 ± 0.9 degrees and 1.6 ± 1.1°, respectively. The IMU shoulder elevation measure was accurate to within 6.8 ± 2.7° and the elbow flexion measure was accurate to within 8.2 ± 2.8°. In the Bland-Altman analyses, there were no significant systematic errors present; however, there was a significant inversely proportional error across all joints. As the gold standard measurement increased, the IMU underestimated the magnitude of the joint angle. This study reports acceptable accuracy of a commercially available IMU system; however, results should be interpreted as protocol specific.

Shoulder pain and pathology are common in manual wheelchair (MWC) users with paraplegia, and the biomechanical mechanism of injury is largely unknown. Establishing patterns of MRI characteristics in MWC users would help advance understanding of the mechanical etiology of rotator cuff disease, thus improving the logic for prescribed interventions. The purpose of this study was to report detailed shoulder MRI findings in a sample of 10 MWC users with anterolateral shoulder pain. The imaging assessments were performed using our standardized MRI Assessment of the Shoulder (MAS) guide. The tendon most commonly torn was the supraspinatus at the insertion site in the anterior portion in either the intrasubstance or articular region. Additionally, widespread tendinopathy, CA ligament thickening, subacromial bursitis, labral tears, and AC joint degenerative arthrosis and edema were common. Further reporting of detailed shoulder imaging findings is needed to confirm patterns of tears in MWC users regarding probable tendon tear zone, region, and portion. This investigation was a small sample observational study and did not yield data that can define patterns of pathology. However, synthesis of detailed findings from multiple studies could define patterns of pathological MRI findings allowing for associations of imaging findings to risk factors including specific activities.

Repeated durations of dynamic activity with high ground reaction forces (GRFs) and loading rates (LRs) can be beneficial to bone health. To fully characterize dynamic activity in relation to bone health, field-based measurements of gait kinetics are desirable to assess free-living lower-extremity loading. The study aims were to determine correlations of peak vertical GRF and peak vertical LR with ankle peak vertical accelerations, and of peak resultant GRF and peak resultant LR with ankle peak resultant accelerations, and to compare them to correlations with tibia, thigh, and waist accelerations. GRF data were collected as ten healthy subjects (26 [19–34] years) performed 8–10 walking trials at velocities ranging from 0.19 to 3.05 m/s while wearing ankle, tibia, thigh, and waist accelerometers. While peak vertical accelerations of all locations were positively correlated with peak vertical GRF and LR (r2 > .53, P < .001), ankle peak vertical accelerations were the most correlated (r2 > .75, P < .001). All peak resultant accelerations were positively correlated with peak resultant GRF and LR (r2 > .57, P < .001), with waist peak resultant acceleration being the most correlated (r2 > .70, P < .001). The results suggest that ankle or waist accelerometers give the most accurate peak GRF and LR estimates and could be useful tools in relating physical activity to bone health.

This study aimed to define accelerations measured at the waist and lower extremities over a range of gait velocities to provide reference data for choosing the appropriate accelerometer for field-based human activity monitoring studies. Accelerations were measured with a custom activity monitor (± 16g) at the waist, thighs, and ankles in 11 participants over a range of gait velocities from slow walking to running speeds. The cumulative frequencies and peak accelerations were determined. Cumulative acceleration amplitudes for the waist, thighs, and ankles during gait velocities up to 4.8 m/s were within the standard commercial g-range (± 6g) in 99.8%, 99.0%, and 96.5% of the data, respectively. Conversely, peak acceleration amplitudes exceeding the limits of many commercially available activity monitors were observed at the waist, thighs, and ankles, with the highest peaks at the ankles, as expected. At the thighs, and more so at the ankles, nearly 50% of the peak accelerations would not be detected when the gait velocity exceeds a walking velocity. Activity monitor choice is application specific, and investigators should be aware that when measuring high-intensity gait velocity activities with commercial units that impose a ceiling at ± 6g, peak accelerations may not be measured.

A three-dimensional (3D) geometric model for predicting muscle forces in the shoulder complex is proposed. The model was applied throughout the range of arm elevation in the scapular plan. In vitro testing has been performed on 13 cadaveric shoulders. The objectives were to determine homogeneous values of physiological parameters of shoulder muscles and to locate sites of muscular attachment to any bone of the shoulder complex. Muscular fiber lengths, lengths of contractile element (CE), and muscle volumes were measured, corresponding physiological cross-sectional area (PCSA) were calculated, and force/length muscle relations were found. An in vivo biplanar radiography was performed on five volunteers. The photogrammetric reconstruction of bone axes and landmarks were coupled with a geometric modeling of bones and muscle sites of attachment. Muscular paths were drawn and changes in lengths during movement have been estimated. Directions of muscle forces are the same as that of muscular path at the point of attachment to bone. Magnitudes of muscular forces were found from muscle lengths coupled with force/length relations. Passive forces were directly determined contrary to active muscle forces. A resulting active muscle force is calculated from balancing weight and passive forces at each articular center. Active muscle forces were calculated by distributing the resulting force among active muscles based on the muscular PCSA values.