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We report a biologic approach to improve medial collateral ligament healing using growth factors normally expressed in healing tissue. Our previous in vitro work demonstrated that platelet-derived growth factor-BB and transforming growth factor-beta 1 promoted fibroblast proliferation and matrix synthesis, respectively. There-fore, these growth factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of growth factors could improve healing more than individual growth factors. Thirty-seven rabbits had various doses of growth factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of platelet-derived growth factor-BB, 2) two groups receiving two doses of this growth factor plus transforming growth factor-beta 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of platelet-derived growth factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming growth factor-beta 1 did not lead to any further increase in the structural properties of the complex compared with treatment with platelet-derived growth factor-BB. These encouraging results suggest that use of platelet-derived growth factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments. [ABSTRACT FROM AUTHOR]

Ubiquitin-conjugating enzymes (E2) play a crucial role in the attachment of ubiquitin to proteins. Together with ubiquitin ligases (E3), they catalyze the transfer of ubiquitin (Ub) onto lysines with high chemoselectivity. A subfamily of E2s, including yeast Ubc6 and human Ube2J2, also mediates noncanonical modification of serines, but the structural determinants for this chemical versatility remain unknown. Using a combination of X-ray crystallography, molecular dynamics (MD) simulations, and reconstitution approaches, we have uncovered a two-layered mechanism that underlies this unique reactivity. A rearrangement of the Ubc6/Ube2J2 active site enhances the reactivity of the E2-Ub thioester, facilitating attack by weaker nucleophiles. Moreover, a conserved histidine in Ubc6/Ube2J2 activates a substrate serine by general base catalysis. Binding of RING-type E3 ligases further increases the serine selectivity inherent to Ubc6/Ube2J2, via an allosteric mechanism that requires specific positioning of the ubiquitin tail at the E2 active site. Our results elucidate how subtle structural modifications to the highly conserved E2 fold yield distinct enzymatic activity., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

N -methyl-d-aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting that subunit composition influences neuronal transmission. Here, we used electrophysiological recordings at Schaffer collateral-CA1 synapses partnered with Ca 2+ imaging and glutamate uncaging at boutons of CA3 pyramidal neurones to reveal two populations of pre-NMDARs that contain either the GluN2A or GluN2B subunit. Activation of the GluN2B population decreases action potential-evoked Ca 2+ influx via modulation of small-conductance Ca 2+ -activated K+ channels, while activation of the GluN2A population does the opposite. Critically, the level of functional expression of the subunits is subject to homeostatic regulation, bidirectionally affecting short-term facilitation, thus providing a capacity for a fine adjustment of information transfer. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Amyloids are known as irreversible aggregates associated with neurodegenerative diseases. However, recent evidence shows that a subset of amyloids can form reversibly and fulfill essential cellular functions. Yet, the molecular mechanisms regulating functional amyloids and distinguishing them from pathological aggregates remain unclear. Here, we investigate the conserved principles of amyloid reversibility by studying the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that yeast PK (Cdc19) and human PK (PKM2) form reversible amyloids through a pH-sensitive amyloid core. Stress-induced cytosolic acidification promotes aggregation via protonation of specific glutamate (yeast) or histidine (human) residues within the amyloid core. Mutations mimicking protonation cause constitutive PK aggregation, while non-protonatable PK mutants remain soluble even upon stress. Physiological PK aggregation is coupled to metabolic rewiring and glycolysis arrest, causing severe growth defects when misregulated. Our work thus identifies an evolutionarily conserved, potentially widespread mechanism regulating functional amyloids during stress., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: The supraspinatus (SS) is formed by a larger anterior bipennate muscle with a cord-like tendon and a posterior unipennate muscle with a strap-like tendon. There is a tendinous connection between the 2 SS subunits. Yet, the relative mechanical contribution of the SS cord and SS strap musculotendinous units to load transmission and subsequent shoulder abduction force is unknown. We hypothesized that a simulated SS cord vs. an SS strap tear would generate less shoulder abduction force and, further, an intact SS cord would offset the expected abduction loss from an SS strap tear, but the inverse would not be true., Materials and Methods: Twenty fresh-frozen cadaveric specimens were tested in a shoulder simulator with physiological load vectors applied to the upper and lower subscapularis, SS cord, SS strap, infraspinatus, and teres minor. The roles of the SS cord and SS strap muscles were delineated by varying their loads, while keeping constant loads on other muscles. The randomized testing trials included a native condition and 4 test cases that simulated tears by dropping the load and force transfer via the SS cord-to-SS strap connection by adding the load. Testing was completed at both 0° and 30° of abduction. During each test, shoulder abduction force, rotator cuff strains, and humeral translation were measured., Results: Simulated isolated SS cord and SS strap tears led to a significantly lower shoulder abduction force (P < .001). A simulated cord tear at 0° and 30° reduced the abduction force by 53% and 38%, respectively. A simulated strap tear at 0° and 30° dropped the abduction force by 27% and 23%, respectively. The decline in the abduction force was larger for the SS cord tear vs. SS strap tear (P ≤ .001). An SS cord tear with full-load transfer to the strap was able to recover to native values at both 0° and 30° (P ≥ .288). Likewise, an SS strap tear with full-load transfer to the SS cord showed a similar recovery to native values at both 0° and 30° (P ≥ .155). During full-load transfer, the tendon strain followed the loading pattern. An SS cord tear or SS strap tear did not cause a change in humeral translation (P ≥ .303)., Discussion: The mechanical findings support the efficacy of nonoperative treatment of small (<10 mm) SS tears, 11 because an intact SS strap tendon can effectively offset the abduction loss of a torn SS cord tear and vice versa., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits., Methods: We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients., Results: Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, η p 2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, η p 2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients., Discussion: These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits., (© 2023 American Academy of Neurology.)

Background: Partial distal biceps tears can occur in the short and/or long heads, leading to forearm pain and weakness. Yet, the pathoanatomy of atraumatic and traumatic partial tears are not understood. The goals of this study are to determine the distal biceps partial tear frequency and tear pattern in a cohort of cadaveric specimens., Methods: Fifty three fresh frozen cadavers (average age 70.4 ± 13.8 years, range 32-94) underwent elbow endoscopy to screen for partial tears. The partial tendon tear pattern was classified into either attritional (atraumatic), detachment on the tendon's lateral side, or avulsion (traumatic) rupture of the tendon fibers from bone on both the lateral and medial sides. The specimens were dissected and laser scanned to make 3D models. The tear location, shape, and area were calculated using gross dissection and the 3D models., Results: Atraumatic partial distal biceps tears were identified in 40% of the specimens, 72% involved both the long and short heads, 14% long head, and 14% short head. In all tears, the tendon fibers were only detached from the lateral side. The greatest tear width occurred near the short and long head junction., Conclusion: Atraumatic partial distal biceps tears are common. The tear originates on the lateral side of the tendon at the short and long head junction. All the tear patterns are attritional and no specimen had surgical treatment. This finding supports the current treatment recommendation of an initial period of nonoperative care for symptomatic atraumatic partial distal biceps tears., (© 2023 The Author(s).)

The TGF-β family member activin A modulates neural underpinnings of cognitive and affective functions in an activity-dependent fashion. We have previously shown that exploration of a novel and enriched environment (EE) strongly enhanced activin signaling. Whereas the many beneficial effects of EE are amply documented, the underlying mechanisms remain largely elusive. Here, we examined the hypothesis that EE recruits activin to regulate synaptic plasticity in a coordinated, cognition-promoting manner. Elevated activin levels after EE enhanced CA1 pyramidal cell excitability, facilitated synaptic transmission, and promoted long-term potentiation. These EE-induced changes were largely absent in mice expressing a dominant-negative mutant of activin receptor IB. We then interrogated the impact of activin on network oscillations and functional connectivity, using high-speed Ca 2+ imaging to study spike routing within networks formed by dissociated primary hippocampal cultures. Activin facilitated Ca2+ signaling, enhanced the network strength, and shortened the weighted characteristic path length. In the slice preparation, activin promoted theta oscillations during cholinergic stimulation. Thus, we advance activin as an activity-dependent and very early molecular effector that translates behavioral stimuli experienced during EE exposure into a set of synchronized changes in neuronal excitability, synaptic plasticity, and network activity that are all tuned to improve cognitive functions., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous studies on left hemisphere (LH) stroke patients reported effector-specific (hand, fingers, bucco-facial) differences in imitation performance. Furthermore, imitation performance differed between meaningless (ML) and meaningful (MF) gestures. Recent work suggests that a gesture's meaning impacts the body-part specificity of gesture imitation., Methods: We tested the hypothesis that the gesture's meaning (ML vs MF) affects the lesion correlates of effector-specific imitation deficits (here: bucco-facial vs arm/hand gestures) using behavioural data and support vector regression-based lesion-symptom mapping (SVR-LSM) in a large sample of 194 sub-acute LH stroke patients., Results: Behavioural data revealed a significant interaction between the effector used for imitation and the meaning of the imitated gesture. SVR-LSM analyses revealed shared lesion correlates for impaired imitation independent of effector or gesture meaning in the left supramarginal (SMG) and superior temporal gyri (STG). Besides, within the territory of the left middle cerebral artery, impaired imitation of bucco-facial gestures was associated with more anterior lesions, while arm/hand imitation deficits were associated with more posterior lesions. MF gestures were specifically associated with lesions in the left inferior frontal gyrus and the left insular region. Notably, an interaction of effector-specificity and gesture meaning was also present at the lesion level: A more pronounced difference in imitation performance between the effectors for ML (versus MF) gestures was associated with left-hemispheric lesions in the STG, SMG, putamen, precentral gyrus and white matter tracts., Conclusion: The current behavioural data show that ML gestures are particularly sensitive in assessing effector-specific imitation deficits in LH stroke patients. Moreover, a gesture's meaning modulated the effector-specific lesion correlates of bucco-facial and arm/hand gesture imitation. Hence, it is crucial to consider gesture meaning in apraxia assessments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Recent evidence in healthy participants suggests that a motor subcomponent of working memory (mWM) may exist. We investigated whether this mWM is impaired in patients with a motor-dominant left hemisphere (LH) stroke and apraxia. Furthermore, we hypothesized that a deficient mWM contributes to deficits in motor cognition, that is, apraxia, in LH stroke. The study included 52 patients with LH stroke and 25 age-matched controls. Patients were classified into LH stroke patients with and without apraxia based on deficits in gesture imitation and object use. All participants were examined using the block span test (visuospatial WM), the digit span test (verbal WM), and a novel mWM task. In the latter, participants were presented with static pictures depicting three different actions: actions with objects, meaningless actions, and meaningful actions. In the mWM task, LH stroke patients with apraxia performed worse than age-matched controls. Notably, LH stroke patients with apraxia showed more pronounced mWM deficits than those without apraxia. These results remained significant even after controlling for visuospatial and verbal WM deficits. Regression analyses revealed that LH stroke patients' mWM deficits predicted deficits in imitation. Data provide neuropsychological evidence for a motor subsystem of WM and suggest that deficits in mWM contribute to the severity of apraxia in LH stroke patients., (© 2022 Massachusetts Institute of Technology.)

Background: It is accepted by the orthopaedic community that the rotator cable (RCa) acts as a suspension bridge that stress shields the crescent area (CA). The goal of this study was to determine if the RCa does stress shield the CA during shoulder abduction., Methods: The principal strain magnitude and direction in the RCa and CA and shoulder abduction force were measured in 20 cadaveric specimens. Ten specimens underwent a release of the anterior cable insertion followed by a posterior release. In the other 10, a release of the posterior cable insertion was followed by an anterior release. Testing was performed for the native, single-release, and full-release conditions. The thicknesses of the RCa and CA were measured., Results: Neither the principal strain magnitude nor the strain direction in either the RCa or the CA changed with single or full RCa release (p ≥ 0.493). There were no changes in abduction force after single or full RCa release (p ≥ 0.180). The RCa and CA thicknesses did not differ from one another at any location (p ≥ 0.195)., Conclusions: The RCa does not act as a suspension bridge and does not stress shield the CA. The CA primarily transfers shoulder abduction force to the greater tuberosity., Clinical Relevance: The CA is important in force transmission during shoulder abduction, and efforts should be made to restore its continuity with a repair or reconstruction., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H39)., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Mossy cells (MCs) in the hilus of the dentate gyrus (DG) receive increasing attention as a major player controlling information processing in the DG network. Furthermore, disturbed MC activity has been implicated in widespread neuropsychiatric disorders such as epilepsy and major depression. Using whole-cell patch-clamp recordings from MCs in acute hippocampal slices from wild type and transgenic mice, we demonstrate that activin, a member of the transforming growth factor-β (TGF-β) family, has a strong neuromodulatory effect on MC activity. Disruption of activin receptor signaling reduced MC firing, dampened their excitatory input and augmented their inhibitory input. By contrast, acute application of recombinant activin A strongly increased MC activity and promoted excitatory synaptic drive. Notably, similar changes of MC activity have been observed in a rodent model of depression and after antidepressant drug therapy, respectively. Given that a rise in activin signaling particularly in the DG has been proposed as a mechanism of antidepressant action, our data suggest that the effect of activin on MC excitability might make a considerable contribution in this regard., (© 2022 The Authors. Hippocampus published by Wiley Periodicals LLC.)

Purpose of Review: Distal biceps tendon ruptures (DBTR) are uncommon injuries in 40- to 50-year-old men but occur at a younger age in the athlete population. The distal biceps tendon is an important supinator of the forearm and flexor of the elbow. A complete injury results in limiting function in the upper extremity. The current review evaluates the different options in management and the current literature on return to play in athletes., Recent Findings: The distal biceps tendon inserts on the posterior aspect of the radial tuberosity as two independent heads. The long head footprint is more proximal and posterior giving it a better lever arm for supination. The short head footprint is more distal and anterior giving it a better lever arm for flexion. Surgical anatomic repair is highly recommended among the athlete population, to restore proper function of the upper extremity. There is scarce literature on return to play among athletes. The most recent studies on high-performance athletes are on National Football League (NFL) players. These studies showed that 84-94% of NFL players returned to play at least one game after distal biceps repair. Compared to matched control groups, there was no difference in the player's performance after surgery. Anatomic repair of DBTR results in excellent outcomes, high return to work, and high rate of return to play among athletes. When compared to matched control groups, NFL players have the performance score and play the same number of games after surgery., (© 2022. The Author(s).)

Multimode optical fibers (MMF) have shown considerable potential for minimally invasive diffraction-limited fluorescence imaging of deep brain regions owing to their small size. They also look to be suitable for imaging across long time periods, with repeated measurements performed within the same brain region, which is useful to assess the role of synapses in normal brain function and neurological disease. However, the approach is not without challenge. Prior to imaging, light propagation through a MMF must be characterized in a calibration procedure. Manual repositioning, as required for repeated imaging, renders this calibration invalid. In this study, we provide a two-step solution to the problem consisting of (1) a custom headplate enabling precise reinsertion of the MMF implant achieving low-quality focusing and (2) sensorless adaptive optics to correct translational shifts in the MMF position enabling generation of high-quality imaging foci. We show that this approach achieves fluorescence imaging after repeated removal and reinsertion of a MMF., Competing Interests: The authors declare no conflicts of interest., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Apraxia is characterised by multiple deficits of higher motor functions, primarily caused by left hemisphere (LH) lesions to parietal-frontal praxis networks. While previous neuropsychological and lesion studies tried to relate the various apraxic deficits to specific lesion sites, a comprehensive analysis of the different apraxia profiles and the related (impaired) motor-cognitive processes as well as their differential neural substrates in LH stroke is lacking. To reveal the cognitive mechanisms that underlie the different patterns of praxis and (related) language deficits, we applied principal component analysis (PCA) to the scores of sub-acute LH stroke patients (n = 91) in several tests of apraxia and aphasia. Voxel-based lesion-symptom mapping (VLSM) analyses were then used to investigate the neural substrates of the identified components. The PCA yielded a first component related to language functions and three components related to praxis functions, with each component associated with specific lesion patterns. Regarding praxis functions, performance in imitating arm/hand gestures was accounted for by a second component related to the left precentral gyrus and the inferior parietal lobule. Imitating finger configurations, pantomiming the use of objects related to the face, and actually using objects loaded on component 3, related to the left anterior intraparietal sulcus and angular gyrus. The last component represented the imitation of bucco-facial gestures and was linked to the basal ganglia and LH white matter tracts. The results further revealed that pantomime of (limb-related) object use depended on both the component 2 and 3, which were shared with gesture imitation and actual object use. Data support and extend the notion that apraxia represents a multi-componential syndrome comprising different (impaired) motor-cognitive processes, which dissociate - at least partially - from language processes. The distinct components might be disturbed to a varying degree following LH stroke since they are associated with specific lesion patterns within the LH., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The rotator cable (RCa) is an important articular-sided structure of the cuff capsular complex that helps prevent suture pull out during rotator cuff repairs (RCRs) and plays a role in force transmission. Yet, the RCa cannot be located during bursal-sided RCRs. The purpose of this study is to develop a method to locate the RCa in the subacromial space and compare its bursal- and articular-sided dimensions., Methods: In 20 fresh-frozen cadaveric specimens, the RCa was found from the articular side, outlined with stitches, and then evaluated from the bursal side using an easily identifiable reference point, the intersection of a line bisecting the supraspinatus (SS) tendon and posterior SS myotendinous junction (MTJ). Four bursal-sided lengths were measured on the SS-bisecting line as well as the RCa's outside anteroposterior base. For the articular-sided measurements, the rotator cuff capsular complex was detached from bone and optically scanned creating 3D solid models. Using the 3D models, 4 articular-sided lengths were made, including the RCa's inside and outside anteroposterior base., Results: The RCa's medial arch was located 9.9 ± 5.6 mm from the reference point in 10 intact specimens and 4.1 ± 2.4 mm in 10 torn specimens (P = .007). The RCa's width was 10.9 ± 2.1 mm, and the distance from the lateral edge of the RCa to the lateral SS insertion was 13.9 ± 4.8 mm. The bursal- and articular-sided outside anteroposterior base measured 48.1 ± 6.4 mm and 49.6 ± 6.5 mm, respectively (P = .268). The average inside anteroposterior base measurement was 37.3 ± 5.9 mm., Discussion: The medial arch of the RCa can be reliably located during subacromial arthroscopy using the reference point, analogous to the posterior SS MTJ. The RCa is located 10 mm in intact and 4 mm in torn tendons (P = .007) from the posterior SS MTJ. If the above 6-mm shift in location of the RCa is not taken into consideration during rotator cuff suture placement, it could negatively affect time zero repair strength. The inside anteroposterior base of the RCa measures on average 37 mm; therefore, rotator cuff tears measuring >37 mm are at risk of rupturing part or all of the RCa's 2 humeral attachments, which if not recognized and addressed could impact postoperative function., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Partial avulsions of the short and/or long head of the distal biceps tendon cause pain and loss of strength. The goal of the present study was to quantify the loss of supination and flexion strength following a series of surgical releases designed to simulate partial and complete short and long head traumatic avulsions., Methods: Mechanical testing was performed to measure supination moment arms and flexion force efficiency on 18 adult fresh-frozen specimens in pronation, neutral, and supination. The distal biceps footprint length was divided into 4 equal segments. In 9 specimens (the distal-first group), the tendon was partially cut starting distally by releasing 25%, 50%, and 75% of the insertion site. In the other 9 specimens (the proximal-first group), the releases started proximally. Mechanical testing was performed before and after each release., Results: Significant decreases in the supination moment arm occurred after a 75% release in the distal-first release group; the decrease was 24% in pronation (p = 0.003) and 10% in neutral (p = 0.043). No significant differences in the supination moment arm (p ≥ 0.079) or in flexion force efficiency (p ≥ 0.058) occurred in the proximal-first group., Conclusions: A simulated complete short head avulsion significantly decreased the supination moment arm and therefore supination strength., Clinical Relevance: A mechanical case can be made for repair of partial distal biceps tendon avulsions when the rupture involves ≥75% of the distal insertion site., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJS/G324)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Multimode optical fibers (MMFs), combined with wavefront control methods, have achieved minimally invasive in vivo imaging of neurons in deep-brain regions with diffraction-limited spatial resolution. Here, we report a method for volumetric two-photon fluorescence imaging with a MMF-based system requiring a single transmission matrix measurement. Central to this method is the use of a laser source able to generate both continuous wave light and femtosecond pulses. The chromatic dispersion of pulses generated an axially elongated excitation focus, which we used to demonstrate volumetric imaging of neurons and their dendrites in live rat brain slices through a 60 µm core MMF.

Background: There is no consensus on the treatment of irreparable massive rotator cuff tears. The goal of this systematic review and meta-analysis was to (1) compare patient-reported outcome scores, (2) define failure and reoperation rates, and (3) quantify the magnitude of patient response across treatment strategies., Methods: The MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and Scopus databases were searched for studies including physical therapy and operative treatment of massive rotator cuff tears. The criteria of the Methodological Index for Non-randomized Studies were used to assess study quality. Primary outcome measures were patient-reported outcome scores as well as failure, complication, and reoperation rates. To quantify patient response to treatment, we compared changes in the Constant-Murley score and American Shoulder and Elbow Surgeons (ASES) score with previously reported minimal clinically important difference (MCID) thresholds., Results: No level I or II studies that met the inclusion and exclusion criteria were found. Physical therapy was associated with a 30% failure rate among the included patients, and another 30% went on to undergo surgery. Partial repair was associated with a 45% retear rate and 10% reoperation rate. Only graft interposition was associated with a weighted average change that exceeded the MCID for both the Constant-Murley score and ASES score. Latissimus tendon transfer techniques using humeral bone tunnel fixation were associated with a 77% failure rate. Superior capsular reconstruction with fascia lata autograft was associated with a weighted average change that exceeded the MCID for the ASES score. Reverse arthroplasty was associated with a 10% prosthesis failure rate and 8% reoperation rate., Conclusion: There is a lack of high-quality comparative studies to guide treatment recommendations. Compared with surgery, physical therapy is associated with less improvement in perceived functional outcomes and a higher clinical failure rate., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

While the role of cortical regions in cognitive control processes is well accepted, the contribution of subcortical structures (e.g., the striatum), especially to the control of response interference, remains controversial. Therefore, the present study aimed to investigate the cortical and particularly subcortical neural mechanisms of response interference control (including selective inhibition). Thirteen healthy young participants underwent event-related functional magnetic resonance imaging while performing a unimanual version of the Simon task. In this task, successful performance required the resolution of stimulus-response conflicts in incongruent trials by selectively inhibiting interfering response tendencies. The behavioral results show an asymmetrical Simon effect that was more pronounced in the contralateral hemifield. Contrasting incongruent trials with congruent trials (i.e., the overall Simon effect) significantly activated clusters in the right anterior cingulate cortex, the right posterior insula, and the caudate nucleus bilaterally. Furthermore, a region of interest analysis based on previous patient studies revealed that activation in the bilateral caudate nucleus significantly co-varied with a parameter of selective inhibition derived from distributional analyses of response times. Our results corroborate the notion that the cognitive control of response interference is supported by a fronto-striatal circuitry, with a functional contribution of the caudate nucleus to the selective inhibition of interfering response tendencies.

Visual guidance at the cellular level during neurosurgical procedures is essential for complete tumour resection. We present a compact reflectance confocal microscope with a 20 mm working distance that provided <1.2 µm spatial resolution over a 600 µm × 600 µm field of view in the near-infrared region. A physical footprint of 200 mm × 550 mm was achieved using only standard off-the-shelf components. Theoretical performance of the optical design was first evaluated via commercial Zemax software. Then three specimens from rodents: fixed brain, frozen calvaria and live hippocampal slices, were used to experimentally assess system capability and robustness. Results show great potential for the proposed system to be translated into use as a next generation label-free and contactless neurosurgical microscope., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Focusing light through a step-index multimode optical fiber (MMF) using wavefront control enables minimally-invasive endoscopy of biological tissue. The point spread function (PSF) of such an imaging system is spatially variant, and this variation limits compensation for blurring using most deconvolution algorithms as they require a uniform PSF. However, modeling the spatially variant PSF into a series of spatially invariant PSFs re-opens the possibility of deconvolution. To achieve this we developed svmPSF: an open-source Java-based framework compatible with ImageJ. The approach takes a series of point response measurements across the field-of-view (FOV) and applies principal component analysis to the measurements' co-variance matrix to generate a PSF model. By combining the svmPSF output with a modified Richardson-Lucy deconvolution algorithm, we were able to deblur and regularize fluorescence images of beads and live neurons acquired with a MMF, and thus effectively increasing the FOV., Competing Interests: The authors declare no conflicts of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

In this issue of Molecular Cell, Hu et al. (2020) show that the cytosolic E3 ligase RNF126 reubiquitinates membrane proteins after their extraction from the membrane of the endoplasmic reticulum to target them for proteasomal degradation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In endoplasmic reticulum-associated protein degradation (ERAD), membrane proteins are ubiquitinated, extracted from the membrane, and degraded by the proteasome. The cytosolic ATPase Cdc48 drives extraction by pulling on polyubiquitinated substrates. How hydrophobic transmembrane (TM) segments are moved from the phospholipid bilayer into cytosol, often together with hydrophilic and folded ER luminal protein parts, is not known. Using a reconstituted system with purified proteins from Saccharomyces cerevisiae , we show that the ubiquitin ligase Doa10 (Teb-4/MARCH6 in animals) is a retrotranslocase that facilitates membrane protein extraction. A substrate's TM segment interacts with the membrane-embedded domain of Doa10 and then passively moves into the aqueous phase. Luminal substrate segments cross the membrane in an unfolded state. Their unfolding occurs on the luminal side of the membrane by cytoplasmic Cdc48 action. Our results reveal how a membrane-bound retrotranslocase cooperates with the Cdc48 ATPase in membrane protein extraction., Competing Interests: CS, VV, AS No competing interests declared, (© 2020, Schmidt et al.)

During endoplasmic-reticulum-associated protein degradation (ERAD), misfolded proteins are polyubiquitinated, extracted from the ER membrane and degraded by the proteasome 1-4 . In a process called retrotranslocation, misfolded luminal proteins first need to traverse the ER membrane before ubiquitination can occur in the cytosol. It was suggested that the membrane-embedded ubiquitin ligase Hrd1 forms a retrotranslocation pore regulated by cycles of auto- and deubiquitination 5-8 . However, the mechanism by which auto-ubiquitination affects Hrd1 and allows polypeptides to cross the membrane and whether Hrd1 forms a membrane-spanning pore remained unknown. Here, using purified Hrd1 incorporated into different model membranes, we show that Hrd1 auto-ubiquitination leads to the opening of a pore. Substrate binding increases the pore size and its activity, whereas deubiquitination closes the pore and renders it unresponsive to substrate. We identify two binding sites for misfolded proteins in Hrd1, a low-affinity luminal site and a high-affinity cytoplasmic site formed following auto-ubiquitination of specific lysine residues in Hrd1's RING domain. We propose that the affinity difference between the luminal and cytoplasmic binding sites provides the initial driving force for substrate movement through Hrd1.

Background: The distal biceps tendon externally rotates from proximal to distal before inserting onto the radius. Our hypothesis is that an externally rotated (anatomic) repair would re-create native supination moment arm and flexion force, whereas an internally rotated (nonanatomic) repair would result in reduced force transmission., Methods: The mechanical tests performed in this study measured isometric moment arms and elbow flexion force using a validated elbow simulator as previously published. Mechanical testing was performed on 8 native cadaveric elbows (61 ± 15 years). The distal biceps tendons in all specimens were then incised from their footprint and repaired with anatomic and nonanatomic tendon rotations. After each repair, the specimens were retested. The repair sequence was randomly assigned., Results: Gross observation showed repair site bunching with the nonanatomic repairs. There was no statistical difference in the moment arms between the native, anatomic, and nonanatomic rotations for the 3 forearm angles ( P ≥ .352). Analysis showed no statistical difference in flexion force ratio for the elbow at 90° ( P ≥ .283)., Discussion: The study showed that biceps tendon rotation does not play a role in supination moment arm or flexion force. Twisting the distal biceps tendon around the tendon axis does not change the direction of its applied force on the tuberosity. Tendon bunching in nonanatomic reattachments increases repair site width, which may lead to tendon-ulnar impingement during forearm rotation., (© 2019 Published by Elsevier Inc. on behalf of American Shoulder and Elbow Surgeons.)

Controlling light propagation through a step-index multimode optical fiber (MMF) has several important applications, including biological imaging. However, little consideration has been given to the coupling of fiber and tissue optics. In this Letter, we characterized the effects of tissue-induced light distortions, in particular those arising from a mismatch in the refractive index of the pre-imaging calibration and biological media. By performing the calibration in a medium matching the refractive index of the brain, optimal focusing ability was achieved, as well as a gain in focus uniformity within the field-of-view. These changes in illumination resulted in a 30% improvement in spatial resolution and intensity in fluorescence images of beads and live brain tissue. Beyond refractive index matching, our results demonstrate that sample-induced aberrations can severely deteriorate images from MMF-based systems.

Background: Despite significant benefits, many orthopedic surgeons are hesitant to incorporate diagnostic ultrasound into their practice. This may be because of a lack of comfort, knowledge, and/or training. The purpose of this study was to analyze practice patterns regarding the use of shoulder ultrasound by orthopedic surgeons to diagnose rotator cuff tears., Materials and Methods: We conducted a survey of the members of the American Shoulder and Elbow Surgeons (ASES) regarding their use of ultrasound. A systematic review of the literature on the use of ultrasound in the shoulder by orthopedic surgeons was also performed., Results: Of the members of ASES responding to the survey, 55% are using ultrasound for diagnostic purposes in the shoulder. The leading reason for not using ultrasound as the sole imaging modality prior to performing rotator cuff repair was lack of confidence in the ability to determine the reparability of the tear (83%). Our systematic review showed that for an orthopedic surgeon diagnosing a full-thickness rotator cuff tear, the mean sensitivity was 92% and mean specificity was 89%., Conclusions: Many ASES surgeons are not using ultrasound in the shoulder despite its many potential benefits over magnetic resonance imaging. This is because of a lack of confidence in the ability to quantify fatty infiltration, muscle atrophy, and the level of retraction medial to the acromion. Our systematic review showed that orthopedic surgeons can be accurate in the diagnosis of full-thickness rotator cuff tears. Future research should focus on defining parameters of shoulder ultrasound associated with rotator cuff tendon reparability. Educating surgeons on ultrasound technique, cost, and evidence may be a promising strategy to enhance the value in musculoskeletal care delivery.

Background: Clinical and functional impairment after nonoperative treatment of distal biceps ruptures is not well understood. The goal of this study was to measure patients' perceived disability, kinematic adjustment, and forearm supination power after nonoperative treatment of distal biceps ruptures., Methods: Fourteen individuals after nonoperative treatment of distal biceps ruptures were matched to a control group of 18 uninjured volunteers. Both groups prospectively completed the Disabilities of the Arm, Shoulder and Hand (DASH), Single Assessment Numerical Evaluation (SANE), and Biceps Disability Questionnaire. Both performed a new timed isotonic supination test that was designed to simulate activities of daily life. The isotonic torque dynamometer measures the supination arc, center of supination arc, torque, angular velocity, and power. Motion analysis quantifies forearm and shoulder contributions to the arc of supination., Results: The nonoperative treated group's DASH (23.2 ± 10.3) and SANE (59.6 ± 16.2) scores demonstrated a clinical meaningful impairment. The control group showed no significant differences in kinematic values between dominant and nondominant arms (P = .854). The nonoperative biceps ruptured arms, compared with their uninjured arms, changed supination motion by decreasing the supination arc (P ≤ .036), shifting the center of supination arc to a more pronated position (P ≤ .030), and increasing the shoulder contribution to rotation (P ≤ .001); despite this adaptation, their average corrected power of supination decreased by 47% (P = .001)., Conclusion: Patients should understand that nonoperative treatment for distal biceps ruptures will result in varying degrees of functional loss as measured by the DASH, SANE, and Biceps Disability Questionnaire, change their supination kinematics during repetitive tasks, and that they will lose 47% of their supination power., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses.

Background and Objective: Apraxia is a deficit of motor cognition leading to difficulties in actual tool use, imitation of gestures, and pantomiming object use. To date, little data exist regarding the recovery from apraxic deficits after stroke, and no statistical lesion mapping study investigated the neural correlate of recovery from apraxia. Accordingly, we here examined recovery from apraxic deficits, differential associations of apraxia task (imitation vs. pantomime) and effector (bucco-facial vs. limb apraxia) with recovery, and the underlying neural correlates., Methods: We assessed apraxia in 39 patients with left hemisphere (LH) stroke both at admission and approximately 11 days later. Furthermore, we collected clinical imaging data to identify brain regions associated with recovery from apraxic deficits using voxel-based lesion-symptom mapping (VLSM)., Results: Between the two assessments, a significant recovery from apraxic deficits was observed with a tendency of enhanced recovery of limb compared to bucco-facial apraxia. VLSM analyses revealed that within the lesion pattern initially associated with apraxia, lesions of the left insula were associated with remission of apraxic deficits, whereas lesions to the (inferior) parietal lobe (IPL; supramarginal and angular gyrus) and the superior longitudinal fasciculus (SLF) were associated with persistent apraxic deficits., Conclusions: Data suggest that lesions affecting the core regions (and white matter) of the fronto-parietal praxis network cause more persistent apraxic deficits than lesions affecting other regions (here: the left insula) that also contribute to motor cognition and apraxic deficits.

Distal biceps injuries, which usually occur in active middle-aged men, can result in chronic pain and loss of supination and flexion strength 3 , 4 . Surgical repair of a ruptured distal biceps tendon can reliably decrease pain and improve strength compared with nonoperative management 3 , 4 . However, even following successful healing and rehabilitation of a surgically repaired biceps tendon, full supination strength is rarely restored 5 - 7 . The expected outcome following distal biceps repair using a traditional anterior approach is a measurable loss of rotational strength, especially from neutral to supinated positions 5 , 7 . This deficit can lead to difficulty with occupational and recreational activities 5 , 8 . The center of an uninjured biceps tendon inserts into the radial tuberosity 6.7 mm anterior to its apex 9 , 10 . This posterior location forces the biceps tendon to wrap around the radial protuberance during pronation, thus utilizing the protuberance as a mechanical cam during forceful forearm supination 10 , 11 . The distal biceps tendon comprises a medial short head and lateral long head; the 2 heads are continuations of the proximal muscles 2 , 20 , 21 . The short head inserts distal to the long head on their radial attachment site 2 , 20 , 21 . Performing a distal biceps repair via an anterior approach typically places the center of the reattachment site 12.9 mm anterior to its apex or approximately 6 mm anterior to an uninjured control tendon 9 . This shifts the repair site from its anatomic location (posterior to the radial protuberance) to a new nonanatomic location (on top of the protuberance). This anterior reattachment location decreases the cam effect of the radial protuberance, resulting in an average supination loss of 10% in neutral rotation and 33% in 60° of supination 7 , 10 . A posterior approach to the radial tuberosity using 2 separate intramedullary buttons for the short and long heads reliably positions the distal biceps insertion at its anatomic footprint, which is posterior to the radial protuberance 9 , 10 , 11 . This technique has been named the distal biceps tendon anatomic repair . Not only does it restore the normal supination cam effect of the radial protuberance, but it also provides superior initial fixation strength, with load to failure strength similar to the native tendon 1 . The distal biceps anatomic repair can be divided into the following 9 key steps: Step 1: Preoperative planning; Step 2: Positioning; Step 3: Identifying and retrieving the tendon; Step 4: Preparing the 2 heads of the tendon; Step 5: Posterior exposure of tendon footprint; Step 6: Drilling the short and long-head drill holes; Step 7: Passage of the tendon; Step 8: Unicortical button fixation; Step 9: Alternative fixation: cortical trough; and Step 10: Postoperative management.

Crystal structures of transporters with a LeuT-type structural fold assign core transmembrane domain 6 (TM6') a central role in substrate binding and translocation. Here, the function of TM6' in the sodium/proline symporter PutP, a member of the solute/sodium symporter family, was investigated. A complete scan of TM6' identified eight amino acids as particularly important for PutP function. Of these residues, Tyr-248, His-253, and Arg-257 impact sodium binding, whereas Arg-257 and Ala-260 may participate in interactions leading to closure of the inner gate. Furthermore, the previous suggestion of an involvement of Trp-244, Tyr-248, and Pro-252 in proline binding is further supported. In addition, substitution of Gly-245, Gly-247, and Gly-250 affects the amount of PutP in the membrane. A Cys accessibility analysis suggests an involvement of the inner half of TM6' in the formation of a hydrophilic pathway that is open to the inside in the absence of ligands and closed in the presence of sodium and proline. In conclusion, the results demonstrate that TM6' plays a central role in substrate binding and release on the inner side of the membrane also in PutP and extend the knowledge on functionally relevant amino acids in transporters with a LeuT-type structural fold., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Understanding of the distal biceps anatomy, mechanics, and biology during the last 75 years has greatly improved the physician's ability to advise and to treat patients with ruptured distal tendons. The goal of this paper is to review the past and current advances on complete distal biceps ruptures as well as controversies and future directions that were discussed and debated during the closed American Shoulder and Elbow Surgeons meeting in 2015., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Supination weakness commonly occurs after a distal biceps repair. The goal of this study was to identify factors that could influence postoperative supination strength through a full arc of forearm rotation., Methods: Fifteen patients were prospectively studied and underwent a biceps repair using a posterior approach; this cohort was compared with a randomized selection of 17 anterior repair subjects. All patients underwent postoperative magnetic resonance imaging (MRI). Quantitative MRI analysis determined the insertion site angle of the tendon and supinator fat content. Supination strength was measured in 3 forearm positions. A multiple linear regression analysis was performed to determine the effect of all factors on supination strength., Results: The anterior group had a significantly higher nonanatomic insertion site angle of the tendon than the control group and the posterior group (p < 0.001). The posterior group had significantly greater supinator fat content (p ≤ 0.019) than both the control group and the anterior group. After repair, the posterior group had significantly greater supination strength than the anterior group (p = 0.027). Multiple regression analysis (r = 0.765) found that an anatomic reinsertion of the ruptured tendon (β = 1.159; p < 0.001), posterior approach (β = 0.484; p = 0.043), and limited supinator muscle fat content (β = 0.360; p = 0.013) were significant predictors of the restoration of supination strength in 60° of supination., Conclusions: Future directions for distal biceps tendon repair techniques should focus on restoring an anatomic reattachment site while limiting supinator damage., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The radial tuberosity contributes to the biceps supination moment arm and the elbow flexion moment. The purpose of our study was to compare the impact of a cortical bone trough versus an anatomic repair on measurements of the forearm supination moment arm and elbow flexion force efficiency. Our hypothesis was that a trough repair would decrease the tuberosity height, the native biceps supination moment arm, and elbow flexion force efficiency compared with an anatomic repair., Methods: The isometric supination moment arm and elbow flexion force efficiency were measured in ten matched pairs of cadaveric upper limbs. After testing, the geometry of the proximal aspect of the radius was reconstructed with use of stereophotogrammetry. All of the repair sites were three-dimensionally reconstructed to quantify the disturbance of the trough on native anatomy. The tuberosity distance was defined as the distance between the central axis of the radius and the centroid of the respective repair site., Results: Specimens with a trough repair had a 27% lower supination moment arm at 60° of supination (p = 0.036). There were no differences found for pronation or neutral forearm positioning (p > 0.235). Flexion force efficiency was not significantly different between the trough and anatomic repair groups. The average tuberosity distance was 11.0 ± 2.1 mm for the anatomic repairs and 8.3 ± 1.4 mm for the trough repairs (p = 0.003). The percentage of distance lost due to the trough was 25%. Furthermore, the supination moment arm in the supinated position was significantly correlated with the tuberosity distance., Conclusions: The trough technique resulted in a significant decrease (p = 0.036) in the moment arm of a 60° supinated forearm and a significant reduction (p = 0.003) in radial tuberosity height. The loss of the supination moment arm was correlated with the decrease in tuberosity height, providing evidence that the radial protuberance acts as a mechanical cam., Clinical Relevance: The anterior protuberance of the radial tuberosity functions as a supination cam; therefore, consideration should be given to preserve its topographical anatomy during a distal biceps repair., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The appropriate use criteria (AUC) were developed for full-thickness rotator cuff tears to determine when it is reasonable to recommend nonoperative care, partial repair/débridement, repair, reconstruction, or arthroplasty. The goal of this report was to interpret and summarize the results of the AUC process into clinically relevant terms., Methods: Using the results of the AUC methodology, we systematically interpreted the clinical importance attributed to the various patient and pathologic variables. We then assessed the combination of considerations that would justify the various treatment options using "preference tables.", Results: A nonoperative program was appropriate if the patient had a positive response to conservative care. However, a repair could be maybe appropriate was also accepted. Rotator cuff repair was appropriate when conservative treatment failed in symptomatic patients. Reconstructive measures were recognized primarily in those with chronic massive tears. Most found arthroplasty maybe appropriate only in healthy patients, pseudoparalysis, and chronic massive tears. Surprisingly, neither factors that decreased healing nor adversely affected outcome had a strong influence on the panel's treatment recommendations., Conclusions: The AUC process accounts for clinical experience and considers individual patient and pathologic characteristics of the condition. Overall, the outcome of this exercise does support the current practice for the management of rotator cuff tears (ie, repair of symptomatic tears). However, the minimal importance given to patient and pathologic considerations, well documented to influence outcome, prompts an ongoing effort to refine this important and clinically relevant process., (Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Every year approximately 18 million Americans report shoulder pain, a large percentage of which are a result of rotator cuff disease. Rotator cuff tear progression can be difficult to predict. Factors associated with tear enlargement include increasing symptoms, advanced age, involvement of 2 or more tendons, and rotator cable lesion. Nonsurgical treatment can be effective for patients with full-thickness tears. When conservative treatment fails, surgical repair provides a reliable treatment alternative. Recurrent tears after surgery can compromise outcomes, particularly for younger patients with physically demanding occupations. Revision surgery provides satisfactory results for those with symptomatic re-tears. If the tear is deemed irreparable, addressing concomitant biceps pathology or performing partial repairs can reliably improve pain and potentially reverse pseudoparalysis. The reverse shoulder arthroplasty has limited indications in the setting of rotator cuff tears and should be reserved for patients with painful pseudoparalysis and associated arthropathy., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Hypothesis: This study quantified pain (visual analog pain scale [VAPS]), disability (Disabilities of the Arm, Shoulder and Hand [DASH]) and isometric supination torque at 3 forearm positions in a prospective cohort of biceps-deficient arms to assess the potential for functional return with nonoperative treatment., Materials and Methods: Twenty-three men (50 ± 11 years) with complete unilateral distal biceps avulsion underwent isometric supination strength testing of both limbs at 60° of supination, 0° (neutral), and 60° of pronation. After exclusion of 1 outlier patient, the mean time from injury to evaluation was 44 days (range, 4-455 days). Pain level (VAPS) and functional outcome (DASH) were assessed; supination strength was normalized to the uninjured arm., Results: The uninjured arm was stronger (P < .001), and peak torque varied with forearm position (P < .043). Peak torque was greater in pronation compared with supination, regardless of injury (P < .002). No differences were detected in supination strength as a result of forearm position or arm dominance. Supination strength did not correlate with time from injury to evaluation. One patient regained supination strength (115%) at 60° of pronation and 72% in neutral with a lengthy time from injury. VAPS (5 of 10) and DASH (39 of 100) scores decreased with time and did not relate to supination strength., Conclusion: Biceps tendon rupture led to a 60% decrease in supination strength in the neutrally oriented forearm. Peak torque observations can be explained using forearm moment arms. VAPS and DASH scores decreased with time but did not affect strength. We speculate that supination strength from pronation to neutral can improve as one strengthens the brachioradialis but strength deficits from neutral to supination are more difficult to overcome., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: Lesser tuberosity osteotomy has been shown to decrease postoperative subscapularis dysfunction. The purpose of this study was to determine the effect of osteotomy thickness and suture configuration on repair integrity., Materials and Methods: One side of 12 matched-pair cadaveric shoulders was randomly assigned to either a thick osteotomy (100% of lesser tuberosity height) or a thin osteotomy (50% of height). Both sides of the matched pairs were given the same repair, either (1) compression sutures or (2) compression sutures plus 1 tension suture. This created 4 groups of 6 paired specimens. Computed tomography imaging was used to measure tuberosity dimensions before and after osteotomy to validate fragment height and area. The repairs were loaded cyclically and then loaded to failure. A video system measured fragment displacement. The percent area of osteotomy contact was calculated from the computed tomography and displacement data., Results: The average initial displacement was less in the thin osteotomy groups (P = .011). Adding a tension suture negated this difference. A significant number of thin repair sites compared with thick repair sites remained intact during load-to-failure testing (P = .001). No difference occurred because of maximum load between the repair groups (P = .401), and construct stiffness was greater when a tension suture was used (P = .032). The percent area of osteotomy contact showed no differences between the osteotomy (P = .431) and repair (P = .251) groups., Conclusion: The study showed that thin osteotomies displaced less than thick osteotomies. Adding a tension band improved construct stability and eliminated some failure modes. Our ideal repair was a thin wafer with both tension and compression sutures. This construct had smaller total displacement, a high osteotomy percent contact area, and a high maximum load., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

The reverse shoulder arthroplasty is considered to be one of the most significant technological advancements in shoulder reconstructive surgery over the past 30 years. It is able to successfully decrease pain and improve function for patients with rotator cuff-deficient shoulders. The glenoid is transformed into a sphere that articulates with a humeral socket. The current reverse prosthesis shifts the center of rotation more medial and distal, improving the deltoid's mechanical advantage. This design has resulted in successful improvement in both active shoulder elevation and in quality of life., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Distal biceps tendon ruptures continue to be an important injury seen and treated by upper extremity surgeons. Since the mid-1980s, the emphasis has been placed on techniques that limit complications or improve initial tendon-to-bone fixation strength. Recently, basic science research has expanded the knowledge base regarding the biceps tendon structure, footprint anatomy, and biomechanics. Clinical data have further delineated the results of conservative and surgical management of both partial and complete tears in acute or chronic states. The current literature on the distal biceps tendon is described in detail., (Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Impaired consciousness in epilepsy has a significant negative impact on patients' quality of life yet is difficult to study objectively. Here, we develop an improved prospective Responsiveness in Epilepsy Scale-II (RES-II) and report initial results compared with the earlier version of the scale (RES). The RES-II is simpler to administer and includes both verbal and non-verbal test items. We evaluated 75 seizures (24 patients) with RES and 34 seizures (11 patients) with RES-II based on video-EEG review. The error rate per seizure by test administrators improved markedly from a mean of 2.01 ± 0.04 with RES to 0.24 ± 0.11 with RES-II. Performance during focal seizures showed a bimodal distribution, corresponding to the traditional complex partial vs. simple partial seizure classification. We conclude that RES-II has improved accuracy and testing efficiency compared with the original RES. Prospective objective testing will ultimately lead to a better understanding of the mechanisms of impaired consciousness in epilepsy., (Copyright © 2012. Published by Elsevier Inc.)

Background: This study examined the magnetic resonance imaging (MRI) appearance of an anterior incision distal biceps tendon repair and evaluated the association between appearance and outcome., Materials and Methods: Nineteen patients were randomly recruited to undergo an elbow MRI from a single-surgeon series of distal biceps repairs using an anterior approach. Tendon healing was evaluated by the integrity of the repair, the amount of heterogeneity within the tendon substance, and the presence of heterotopic bone. The angle of tendon insertion on the tuberosity was used to quantify the tendon location from the MRI in the patients and in 10 healthy volunteers. All patients completed the Disabilities of Arm, Shoulder and Hand (DASH) and a visual analog pain scale (VAPS), and 17 patients underwent isometric supination strength testing. MRI findings were statistically compared with the outcome scores., Results: All of the repairs healed to cortical bone. High intrasubstance heterogeneity or heterotopic bone was present in 11 patients (58%). The insertion site angle of the repaired tendons was 73° more anterior than the uninjured controls (P < .001). Average DASH was 7.7 (range, 0-49.2) and VAPS was 0.7 (range, 0-5). At 60° of forearm supination, supination strength was 67% of the uninjured side (P < .01). No significant differences in DASH or VAPS scores were found between groups based on tendon appearance., Conclusions: The distal biceps tendon predictably heals to cortical bone but demonstrates a wide variability in overall morphology that does not influence DASH or VAPS scores. A significant decrease in strength at 60° of supination appears to be an effect of an anterior tendon reattachment location., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Hypothesis: The short head bundle of the distal biceps tendon is more efficient at elbow flexion, and the long head is more efficient at forearm supination., Methods: The short and long head bundles of the distal biceps tendon were separated to the bicipital tuberosity in 6 cadavers. The area and centroid of each bundle insertion were computed from surface points measured within each footprint. Each bundle was individually loaded. The supination torque and flexion load generated were recorded at 90° of elbow flexion. The slope of the torque generated versus biceps load was used to define the supination moment arm. The ratio of the flexion load generated to biceps load applied was used to define the relative flexion efficiency., Results: The short head insertion was positioned distal and anterior relative to the long head and typically included the apex of the tuberosity. The areas of the long and short heads were 59 ± 15 and 94 ± 44 mm(2) (P = .07), respectively. The long head moment arm was significantly higher in supination. The short head had a significantly higher moment arm in neutral and pronation. The ratio of the flexion load to biceps load was 15% higher for the short head., Conclusion: The short and long heads of the biceps have distinct insertions. The short head's insertion allows it to be relatively more efficient at elbow flexion at 90°. In the neutral and pronated forearm, the short head is the relatively more efficient supinator. In the supinated forearm, the long head becomes relatively more efficient at supination., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

The goal of this article is to summarize the current concepts on rotator cuff disease with an emphasis on arthroscopic treatment. Most rotator cuff tears are the result of an ongoing attritional process. Once present, a tear is likely to gradually increase in size. Partial-thickness and subscapularis tears can both be successfully treated arthroscopically if conservative management fails. Partial tears involving greater than 50% of tendon thickness should be repaired. Articular-sided partial tears involving less than 50% of the rotator cuff can reliably be treated with debridement. A more aggressive approach should be considered for low-grade tears (<50%) if they occur on the bursal side. Biomechanical and anatomic studies have shown clear superiority with dual-row fixation compared with single-row techniques. However, current studies have yet to show clear clinical advantage with dual-row over single-row repairs. Biceps tenotomy or tenodesis can reliably provide symptomatic improvement in patients with irreparable massive tears. True pseudoparalysis of the shoulder is a contraindication to this procedure alone and other alternatives should be considered., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)