The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation.

Purpose-The side-to-side (SS) tendon suture technique was designed to function as a repair that permits immediate post-operative activation and mobilization of a transferred muscle. This study was designed to test the strength and stiffness of the SS technique against a variation of the Pulvertaft (PT) repair technique.Methods-Flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were harvested from four fresh cadavers and used as a model system. Seven SS and six PT repairs were performed using the FDS as the donor and the FDP as the recipient tendon. For SS repairs, the FDS was woven through one incision in the FDP, and was joined with four cross-stitch running sutures down both sides, and one double-loop suture at each tendon free end; for PT repairs, FDS was woven through three incisions in FDP, joined with a double-loop suture at both ends of the overlap, and four evenly spaced mattress sutures between the ends. Tendon repairs were placed in a tensile testing machine, pre-conditioned and tested to failure.Results-There were no statistically significant differences in cross-sectional area (p=0.99) or initial length (p=0.93) between SS and PT repairs. Therefore, all comparisons between methods were made using measures of loads and deformations, rather than stresses and strains.. All failures occurred in the repair region, rather than at the clamps. However, failure mechanisms were different between the two techniques-PT repairs failed by the suture knots either slipping or pulling through the tendon material, followed by the FDS tendon pulling through the FDP tendon; SS repairs failed by shearing of fibers within the FDS. Load at first failure (p < 0.01), ultimate load (p < 0.001), and repair stiffness (p < 0.05) were all significantly different between SS and PT techniques; in all cases the mean value for SS was higher than for PT.Discussion-The SS repair, using a cross-stitch suture technique, was significantly stronger and stiffer compared to the PT repair using a mattress suture technique. This suggests that using SS repairs could enable patients to load the repair soon after surgery. Ultimately, this should reduce the risk of developing adhesions and result in improved functional outcome and fewer complications in the acute post-operative period. Future work will address the specific mechanisms (for example, suture-

Background and objectivesPercutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducing needle followed by the delivery of electric current. This modality has been reported to treat chronic pain as well as postoperative pain following knee and foot surgery. However, it remains unknown if this analgesic technique may be used in ambulatory patients following upper extremity surgery. The purpose of this proof-of-concept study was to investigate various lead implantation locations and evaluate the feasibility of using percutaneous brachial plexus PNS to treat surgical pain following ambulatory rotator cuff repair in the immediate postoperative period.MethodsPreoperatively, an electrical lead (SPR Therapeutics, Cleveland, Ohio) was percutaneously implanted to target the suprascapular nerve or brachial plexus roots or trunks using ultrasound guidance. Postoperatively, subjects received 5 min of either stimulation or sham in a randomized, double-masked fashion followed by a 5 min crossover period, and then continuous stimulation until lead removal postoperative days 14–28.ResultsLeads (n=2) implanted at the suprascapular notch did not appear to provide analgesia, and subsequent leads (n=14) were inserted through the middle scalene muscle and placed to target the brachial plexus. Three subjects withdrew prior to data collection. Within the recovery room, stimulation did not decrease pain scores during the first 40 min of the remaining subjects with brachial plexus leads, regardless of which treatment subjects were randomized to initially. Seven of these 11 subjects required a single-injection interscalene nerve block for rescue analgesia prior to discharge. However, subsequent average resting and dynamic pain scores postoperative days 1–14 had a median of 1 or less on the Numeric Rating Scale, and opioid requirements averaged less than 1 tablet daily with active stimulation. Two leads dislodged during use and four fractured on withdrawal, but no infections, nerve injuries, or adverse sequelae were reported.ConclusionsThis proof-of-concept study demonstrates that ultrasound-guided percutaneous PNS of the brachial plexus is feasible for ambulatory shoulder surgery, and although analgesia immediately following surgery does not appear to be as potent as local anesthetic-based peripheral nerve blocks, the study suggests that this modality may provide analgesia and decrease opioid requirements in the days following rotator cuff repair. Therefore, it suggests that a subsequent, large, randomized clinical trial with an adequate control group is warranted to further investigate this therapy in the management of surgical pain in the immediate postoperative period. However, multiple technical issues remain to be resolved, such as the optimal lead location, insertion technique, and stimulating protocol, as well as preventing lead dislodgment and fracture.Trial registration number NCT02898103.

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The relationship between muscle mechanical conditions and gene expression was investigated by varying both stress and contraction mode imposed upon rat dorsiflexors (n = 25), activating them at high or low frequencies (150 Hz or 40 Hz) either eccentrically or isometrically. Muscle physiological, immunohistochemical and gene expression changes were then measured 24 h after the exercise bout. Peak stress was the best predictor of muscle injury, independent of contraction mode (i.e. eccentric or isometric). When peak stresses were matched, no physiological or immunohistochemical differences were detected between isometric and eccentric contractions. The expression of certain myogenic regulatory and muscle ankyrin repeat protein (MARP) genes (myoD, myogenin, MLP and CARP) depended both on peak muscle stress achieved during contraction and contraction mode. In contrast, Arpp/Ankrd2 was dramatically upregulated only by eccentric contractions, but not by isometric contractions, even though the stress level of the eccentric contractions varied over a three-fold range and overlapped with that of the isometric group. The role that Arpp/Ankrd2 upregulation plays in the biological response to eccentric contraction remains to be determined, as does the control mechanism whereby the expression of certain genes (such as myoD, myogenin, MLP and CARP) is sensitive to muscle stress while another (Arpp/Ankrd2) is sensitive only to contraction mode.

Summary We characterized the architecture, fiber type, titin isoform distribution, and collagen content of 27 portions of 22 muscles in the murine forelimb. The mouse thoracic limb was different from the human arm in that it had the extensor digitorum lateralis muscle and no brachioradialis muscle. Architecturally, the mouse forelimb differed from humans with regard to load bearing, having a much larger contribution from extensors than flexors. In mice, the extensor:flexor PCSA ratio is 2.7 while in humans it is only 1.4. When the architectural difference index was calculated, similarities became especially apparent between flexors and extensors of the distal thoracic limb, as well pronators. Discriminant analysis revealed that biochemical measures of collagen, titin, and myosin heavy chain were all strong between-species discriminators. In terms of composition, when compared to similar muscles in humans, mice had, on average, faster muscles with higher collagen content and larger titin isoforms. This report establishes the anatomical and biochemical properties of mouse forelimb muscles. Given the prevalence of this species in biological studies, these data will be invaluable for studying the biological basis of mouse muscle structure and function.

The relative contributions of CD11a/CD18 and CD11b/CD18 to the dynamics and strength of neutrophil adhesion to intercellular adhesion molecule (ICAM)-1–transfected cells were examined over the time course of chemotactic stimulation. Suspensions of neutrophils and transfectants were sheared in a cone-plate viscometer, and formation of heterotypic aggregates was measured by 2-color flow cytometry. The 2-body collision theory was used to compute adhesion efficiency, defined as the proportion of collisions between neutrophils and target cells that resulted in capture. ICAM-1 surface density and shear rate both regulated adhesion efficiency. Target cells expressing approximately 1000 ICAM-1 sites/μm2 (Ilow) were captured with an efficiency of 0.15 at 100 s−1, which decreased to zero at 300 s−1. At 8-fold higher ICAM-1 expression (Ihigh) corresponding to levels measured on interleukin-1–stimulated endothelium, efficiency was 0.3 at 100 s−1 and remained above background to 900 s−1. Shear alone was sufficient for CD11a/CD18-mediated adhesion to ICAM-1, and stimulation with formyl-methionyl-leucyl-phenylalanine boosted capture efficiency through CD11a/CD18 by 4-fold. In comparison, CD11b/CD18 supported one third of this efficiency, but was necessary for aggregate stability over several minutes of shear and at shear stresses exceeding 5 dyne/cm2. Hydrodynamics influenced capture efficiency predominantly through the collisional contact duration, predicted to be approximately 9 milliseconds for successful capture of Ilow and 4 milliseconds for Ihigh. The implication is that an increase in ICAM-1 from resting levels to those on inflamed endothelium effectively increases the permissible shear in which capture through β2-integrins may occur. Neutrophil adhesion to ICAM-1 appears to be a cooperative and sequential process of CD11a-dependent capture followed by CD11b-mediated stabilization.

We examined the architectural properties of the rotator cuff muscles in 10 cadaveric specimens to understand their functional design. Based on our data and previously published joint angle-muscle excursion data, sarcomere length operating ranges were modeled through all permutations in 75 masculine medial and lateral rotation and 75 masculine abduction at the glenohumeral joint. Based on physiologic cross-sectional area, the subscapularis would have the greatest force-producing capacity, followed by the infraspinatus, supraspinatus, and teres minor. Based on fiber length, the supraspinatus would operate over the widest range of sarcomere lengths. The supraspinatus and infraspinatus had relatively long sarcomere lengths in the anatomic position, and were under relatively high passive tensions at rest, indicating they are responsible for glenohumeral resting stability. However, the subscapularis contributed passive tension at maximum abduction and lateral rotation, indicating it plays a critical role in glenohumeral stability in the position of apprehension. These data illustrate the exquisite coupling of muscle architecture and joint mechanics, which allows the rotator cuff to produce near maximal active tensions in the midrange and produce passive tensions in the various end-range positions. During surgery relatively small changes to rotator cuff muscle length may result in relatively large changes in shoulder function.