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Mutations in calreticulin (mutCALR) are the second most common drivers of myeloproliferative neoplasms (MPNs) and yet, the current therapeutic landscape lacks a selective agent for mutCALR-expressing MPNs. Here we show that the monoclonal antibody INCA033989 selectively targets mutCALR-positive cells. INCA033989 antagonized mutCALR-driven signaling and proliferation in engineered cell lines and primary CD34+ cells from patients with MPN. No antibody binding or functional activity was observed in cells lacking mutCALR. In a mouse model of mutCALR-driven MPN, treatment with a INCA033989 mouse surrogate antibody effectively prevented the development of thrombocytosis and accumulation of megakaryocytes in the bone marrow. INCA033989 reduced the pathogenic self-renewal of mutCALR-positive disease-initiating cells in both primary and secondary transplantations, illustrating its disease-modifying potential. In summary, we describe a novel mutCALR-targeted therapy for MPNs, a monoclonal antibody that selectively inhibits the oncogenic function of MPN cells without interfering with normal hematopoiesis., (Copyright © 2024 American Society of Hematology.)

Orthopneumoviruses characteristically form membrane-less cytoplasmic inclusion bodies (IBs) wherein RNA replication and transcription occur. Here, we report a strategy whereby the orthopneumoviruses sequester various components of the translational pre i nitiation complex machinery into viral inclusion bodies to facilitate translation of their own mRNAs- PIC -pocketing. Electron microscopy of respiratory syncytial virus (RSV)-infected cells revealed bi-phasic organization of IBs, specifically, spherical "droplets" nested within the larger inclusion. Using correlative light and electron microscopy, combined with fluorescence in situ hybridization, we showed that the observed bi-phasic morphology represents functional compartmentalization of the inclusion body and that these domains are synonymous with the previously reported inclusion body-associated granules (IBAGs). Detailed analysis demonstrated that IBAGs concentrate nascent viral mRNA, the viral M2-1 protein as well as components of eukaryotic translation initiation factors (eIF), eIF4F and eIF3, and 40S complexes involved in translation initiation. Interestingly, although ribopuromycylation-based imaging indicates that the majority of viral mRNA translation occurs in the cytoplasm, there was some evidence for intra-IBAG translation, consistent with the likely presence of ribosomes in a subset of IBAGs imaged by electron microscopy. Mass spectrometry analysis of sub-cellular fractions from RSV-infected cells identified significant modification of the cellular translation machinery; however, interestingly, ribopuromycylation assays showed no changes to global levels of translation. The mechanistic basis for this pathway was subsequently determined to involve the viral M2-1 protein interacting with eIF4G, likely to facilitate its transport between the cytoplasm and the separate phases of the viral inclusion body. In summary, our data show that these viral organelles function to spatially regulate early steps in viral translation within a highly selective bi-phasic biomolecular condensate., Importance: Respiratory syncytial viruses (RSVs) of cows and humans are a significant cause of morbidity and mortality in their respective populations. These RNA viruses replicate in the infected cells by compartmentalizing the cell's cytoplasm into distinct viral microdomains called inclusion bodies (IBs). In this paper, we show that these IBs are further compartmentalized into smaller structures that have significantly different density, as observed by electron microscopy. Within smaller intra-IB structures, we observed ribosomal components and evidence for active translation. These findings highlight that RSV may additionally compartmentalize translation to favor its own replication in the cell. These data contribute to our understanding of how RNA viruses hijack the cell to favor replication of their own genomes and may provide new targets for antiviral therapeutics in vivo ., Competing Interests: The authors declare no conflict of interest.

Viruses routinely employ strategies to prevent the activation of innate immune signaling in infected cells. Respiratory syncytial virus (RSV) is no exception, as it encodes two accessory proteins (NS1 and NS2) which are well established to block interferon signaling. However, RSV-encoded mechanisms for inhibiting NF-κB signaling are less well characterized. In this study, we identified RSV-mediated antagonism of this pathway, independent of the NS1 and NS2 proteins and indeed distinct from other known viral mechanisms of NF-κB inhibition. In both human and bovine RSV-infected cells, we demonstrated that the p65 subunit of NF-κB is rerouted to perinuclear puncta in the cytoplasm, which are synonymous with viral inclusion bodies (IBs), the site for viral RNA replication. Captured p65 was unable to translocate to the nucleus or transactivate a NF-κB reporter following tumor necrosis factor alpha (TNF-α) stimulation, confirming the immune-antagonistic nature of this sequestration. Subsequently, we used correlative light electron microscopy (CLEM) to colocalize the RSV N protein and p65 within bovine RSV (bRSV) IBs, which are granular, membraneless regions of cytoplasm with liquid organelle-like properties. Additional characterization of bRSV IBs indicated that although they are likely formed by liquid-liquid phase separation (LLPS), they have a differential sensitivity to hypotonic shock proportional to their size. Together, these data identify a novel mechanism for viral antagonism of innate immune signaling which relies on sequestration of the NF-κB subunit p65 to a biomolecular condensate-a mechanism conserved across the Orthopneumovirus genus and not host-cell specific. More generally, they provide additional evidence that RNA virus IBs are important immunomodulatory complexes within infected cells. IMPORTANCE Many viruses replicate almost entirely in the cytoplasm of infected cells; however, how these pathogens are able to compartmentalize their life cycle to provide favorable conditions for replication and to avoid the litany of antiviral detection mechanisms in the cytoplasm remains relatively uncharacterized. In this manuscript, we show that bovine respiratory syncytial virus (bRSV), which infects cattle, does this by generating inclusion bodies in the cytoplasm of infected cells. We confirm that both bRSV and human RSV viral RNA replication takes place in these inclusion bodies, likely meaning these organelles are a functionally conserved feature of this group of viruses (the orthopneumoviruses). Importantly, we also showed that these organelles are able to capture important innate immune transcription factors (in this case NF-KB), blocking the normal signaling processes that tell the nucleus the cell is infected, which may help us to understand how these viruses cause disease., (Copyright © 2020 Jobe et al.)

The measles virus (MeV), a member of the genus Morbillivirus , is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus-cell and cell-cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell-cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell-cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell-cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype.

Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective against Trypanosoma brucei in the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner. Antibodies were conjugated to a pyrrolobenzodiazepine (PBD) toxin and killed T. brucei in vitro at picomolar concentrations. A single therapeutic dose (0.25 mg/kg) of a HpHbR antibody-PBD conjugate completely cured a T. brucei mouse infection within 2 days with no re-emergence of infection over a subsequent time course of 77 days. These experiments provide a demonstration of how ADCs can be exploited to treat protozoal diseases that desperately require new therapeutics., Competing Interests: A.L.G.M., S.R., A.M.S., T.J.V. and R.M. are employees of Medimmune. F.D., C.S.B. and P.H. are employees of Spirogen. Toxins SG3199/SG3249 and SG3552/SG3376 are subject to international patents, WO 2011/130598 A1 and WO 2014/140862 A2, respectively.

Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease in young cattle and is closely related to human RSV (HRSV), which causes severe respiratory disease in infants and the elderly. The RSV genome encodes a small hydrophobic (SH) protein with viroporin activity. Previous studies have shown that recombinant BRSV lacking the SH gene (rBRSVΔSH) is attenuated in the lungs, but not in the upper respiratory tract, of calves and mucosal vaccination with rBRSVΔSH induced long-lasting protective immunity. Attenuation of rBRSVΔSH may be due to the ability of this virus to induce an early innate response as rBRSVΔSH induces higher levels of pro-inflammatory cytokines than wild-type (wt) rBRSV. In this study, we investigated the effects of the BRSV SH protein on NF-κB p65 phosphorylation, a master step in the regulation of pro-inflammatory cytokines. Expression of SH resulted in the inhibition of NF-κB p65 phosphorylation in response to BRSV infection and extracellular lipopolysaccharide, and a reduction in the production of pro-inflammatory cytokines. In contrast, rBRSVΔSH does not inhibit NF-κB p65 phosphorylation in bovine antigen-presenting cells, including monocytes, macrophages and dendritic cells, resulting in increased expression of pro-inflammatory cytokines and increased activation of T cells compared to cells infected with wt BRSV. These findings highlight an important role for the BRSV SH protein in immune modulation.

Background: There are no validated upper extremity instruments designed specifically to evaluate the performance and function of overhead athletes. Current shoulder and elbow scoring systems may not be sensitive to subtle changes in performance in this high-demand population., Hypothesis: The scoring system developed in this study will be valid, reliable, and responsive in the evaluation of overhead athletes., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Based on the results of a pilot questionnaire administered to 21 overhead athletes, a final 10-item questionnaire was developed. Two hundred eighty-two healthy, competitive overhead athletes completed the new questionnaire, as well as 2 established upper extremity questionnaires, and were self-assigned into injury categories: (1) playing without pain, (2) playing with pain, and (3) not playing due to pain. Correlations between the scores and differences between injury categories were measured. Responsiveness testing was performed in an additional group of 55 injured athletes, comparing their scores before and after an intervention., Results: The new score showed high correlation with the Disabilities of the Arm, Shoulder and Hand (DASH) score and the DASH sports/performing arts module. The new score correctly stratified overhead athletes by injury category (P < .0001). The new score also demonstrated excellent responsiveness, varying appropriately with improvements in injury category after treatment of injuries (P < .05)., Conclusion: The new patient-reported instrument is valid and responsive in the evaluation of overhead athletes. Reliability was also demonstrated for the 13-item pilot questionnaire. The results support its use for the functional assessment of overhead athletes in future studies.

Eighty-three athletes with medial elbow instability underwent reconstruction of the anterior band of the ulnar collateral ligament with a muscle-splitting approach without transposition of the ulnar nerve. The purposes of this study were to describe postoperative neurologic outcomes in all 83 athletes and to describe the 2-year follow-up in 33 athletes. Postoperatively, 5% of this group had transient ulnar nerve symptoms, all of which resolved with nonoperative management. There were no reoperations for nerve dysfunction and no permanent nerve problems. At 2- to 4-year follow-ups, 93% of the highly competitive athletes who had not had a prior surgical procedure had an excellent result. All athletes, regardless of whether they had a prior procedure, were able to return to their sport. These surgical modifications to the ulnar collateral ligament reconstruction yielded a decreased postoperative complication rate and improved outcomes compared with the results of prior procedures.

The elbow is subjected to enormous valgus stresses during the throwing motion, which places the overhead-throwing athlete at considerable risk for injury. Injuries involving the structures of the medial elbow occur in distinct patterns. Although acute injuries of the medial elbow can occur, the majority are overuse injuries as a result of the repetitive forces imparted to the elbow by throwing. Injury to the ulnar collateral ligament complex results in valgus instability. Valgus extension overload leads to diffuse osseous changes within the elbow joint and secondary posteromedial impingement. Overuse of the flexor-pronator musculature may result in medial epicondylitis and occasional muscle tears and ruptures. Ulnar neuropathy is a common finding that may be due to a variety of factors, including traction, friction, and compression of the ulnar nerve. Advances in nonoperative and operative treatment regimens specific to each injury pattern have resulted in the restoration of elbow function and the successful return of most injured overhead athletes to competitive activities. With further insight into the relevant anatomy, biomechanics, and pathophysiology involved in overhead activities and their associated injuries, significant contributions can continue to be made toward prevention and treatment of these injuries.

The purpose of this study was to compare subjects with subacromial impingement and subjects with normal shoulders with respect to muscle activity. Fifteen subjects in each group were studied by means of fine-wire electromyography. The middle deltoid and rotator cuff muscles were evaluated during isotonic scaption from 30 to 120 degrees. Overall, the impingement group demonstrated decreased mean muscle activity in comparison with the group of normal subjects. The magnitude of diminished activity was statistically significantly different (P < .05) during the 30- to 60-degrees arc for the infraspinatus, subscapularis, and middle deltoid muscles; in addition, the infraspinatus muscle demonstrated significantly depressed activity during the 60- to 90-degrees arc. In the impingement group, the supraspinatus and teres minor revealed a diminution of muscle function in comparison with shoulders in the normal group; the difference was not significant. This study demonstrates that muscle activity in subjects with impingement is most notably decreased in the first arc of motion. Also of clinical relevance is the fact that the inferior force vector (from the infraspinatus and subscapularis) is less functional in subjects with impingement than is the superior compressive vector (from the supraspinatus). Thus, humeral head depression during the critical first portion of elevation may be insufficient in people with subacromial impingement.

Purpose: The purpose of this study was to review a large group of patients who had arthroscopy of the elbow to determine the efficacy and relative risks of this procedure., Type of Study: We retrospectively reviewed a convenient sample of 172 patients who underwent 187 arthroscopies of the elbow over a 7-year period., Materials and Methods: All patients had their charts and radiographs reviewed, and 104 of these patients were also contacted for a telephone interview at an average follow-up of 42.3 months (range, 7 to 115 months)., Results: The procedures were performed primarily by 7 different surgeons, using all 3 standard operating positions and a variety of arthroscopic portals. The most common diagnosis was posterior impingement in 96 patients (51%), followed by loose bodies in 72 patients (31%), and degenerative joint disease in 32 patients (22%). The average preoperative modified Figgie score was 27.7 points (range, 17-43) for all patients. The average postoperative score was 45.4 points (range, 29-50), with the largest increase occurring in the pain score. There were 51 patients (56%) with an excellent surgical result, 37 patients (36%) with a good result, 12 patients (11%) with a fair result, and 4 patients (4%) with a poor result. The average modified Figgie score increased from 31.2 points (range, 22-43) to 46.9 (range, 29-50) postoperatively in professional athletes; from 26.3 to 42.6 in patients who had Workers' Compensation claims but were not professional athletes; from 29.4 to 45.6 in patients with a diagnosis of loose bodies; and from 30.1 to 43.7 in patients with degenerative joint disease. There were 3 known surgical complications (1.6%) overall, 1 of which was a patient who had a transection of the ulnar nerve requiring microsurgical repair. Of the 104 patients who were contacted, 6 patients felt that their symptoms had not improved after surgery. Eight of the 55 baseball players contacted were not able to return to their same level of competition., Conclusions: Arthroscopy of the elbow appears to be a safe and efficacious procedure with a relatively low complication rate.

Thirteen overhand-throwing athletes who failed at least 3 months of physical therapy while restricted from throwing and who demonstrated a positive modified relocation test at 90 degrees, 110 degrees, and/or 120 degrees were clinically and arthroscopically examined. On arthroscopic examination, all patients demonstrated articular surface pathology. Eleven patients had fraying of the undersurface of the rotator cuff, and 10 patients had fraying of the posterosuperior labrum. With 90 degrees shoulder abduction, 8 patients had rotator cuff contact with the posterosuperior labrum. When the shoulder was abducted to 110 degrees, all patients demonstrated such contact. At 120 degrees of abduction, 12 patients revealed contact. The presence or absence of pain during the modified relocation test correlated with the presence or absence of cuff contact with the posterosuperior labrum 79% of the time. Six patients had a positive modified relocation test at all levels of abduction. These patients included 2 with SLAP lesions, 1 with a Bankart lesion, and 1 with a complete tear of the rotator cuff.

The purpose of this study was to compare the effect of increasing loads and doubling speed on the deltoid and rotator cuff muscles during isotonic scapular plane abduction (scaption) with neutral humeral rotation. These muscles were studied in 16 volunteers with asymptomatic shoulders with the use of fine wire electromyography. The addition of load to the arm during scaption caused an increase in electromyographic activity during the first 90 degrees of motion. Furthermore electromyographic activity decreased during the final 30 degrees of motion with each increase in load. Doubling the speed caused an increase in electromyographic activity during the first 60 degrees of motion while causing a decrease in activity in the final 60 degrees. This study demonstrates the response of the rotator cuff and deltoid muscles to varying loads and speeds during the most basic shoulder motion. With the data obtained in this study, rehabilitation exercises and experimental shoulder models can be refined to reflect this more physiologic situation.

The purpose of this study was to describe the extra- and intra-articular anatomic relationships present during the Neer and Hawkins tests. Nine fresh-frozen cadaveric shoulders were positioned in the impingement position described by Neer (n = 5) or that described by Hawkins (n = 4), embedded in polyurethane, and studied with the use of a cross-sectional technique. All shoulders placed in the Neer position demonstrated soft tissue contact with the medial acromion and contact between the articular surface of the rotator cuff tendons and the anterosuperior glenoid rim. Shoulders placed in the Hawkins position demonstrated consistent contact between soft tissues and the coracoacromial ligament. In all Hawkins positioned shoulders, contact between the articular surface of the rotator cuff tendons and the anterosuperior glenoid was observed. The subscapularis tendon was deformed by the coracoid in 1 of the Hawkins positioned specimens. Although factors inherent to human subjects such as edema and muscle tone may influence the anatomy, these provocative tests for subacromial impingement appear to elicit contact consistent with impingement.

Summary: The purpose of this article is to describe the outcome of an arthroscopic examination and the pathology in symptomatic shoulders of 41 professional overhand throwing athletes. With the arm in the position of the relocation test, 100% of the subjects had either contact between the rotator cuff undersurface and the posterosuperior glenoid rim or osteochondral lesions. Other key findings included undersurface cuff fraying in 93%, posterosuperior labral fraying in 88%, and anterior labral fraying in 36% of the subjects. This study supports the concept of impingement of the posterior cuff undersurface with the posterosuperior glenoid rim in the overhand throwing athlete with shoulder pain.

Athletes who participate in overhand sports may sustain a host of injuries to the medial elbow. The chronic repetitive stress caused by the high velocity nature of the overhand throwing mechanism predisposes these athletes to overuse injuries. Medial collateral ligament instability and ulnar neuritis are common disorders seen in this patient population. A thorough understanding of the anatomy of the medial elbow as well as the pathophysiology of these disorders and their nonsurgical and surgical treatments are essential to providing these athletes with optimal care and hastening their return to sports.

The purpose of this study was to describe the electromyographic (EMG) pattern and relative intensities of 8 shoulder muscles during the volleyball serve and spike in 15 professional or collegiate-level athletes. The EMG analysis was synchronized with high-speed cinematography to discern phases of the spike and serve. During the spike, the anterior deltoid and supraspinatus functioned together to elevate and place the humerus throughout all phases. During cocking the infraspinatus and teres minor acted together to rotate the humerus externally. In acceleration, however, these muscles behaved independently; activity of the teres minor remained high, whereas the activity of the infraspinatus declined. The anterior wall muscles functioned to decelerate the humerus during cocking and acted as internal rotators during acceleration. Muscle activities recorded for the serve followed similar patterns as those seen for the spike, but with lower amplitudes. These data illustrate the complex sequence of shoulder muscle activity necessary to play competitive volleyball.

The inability to perform the "liftoff" test has been attributed to a subscapularis muscle or tendon injury. The goals of this study were to evaluate the activity of the glenohumeral muscles during performance of the "liftoff" maneuver and to identify the most effective initial upper extremity placement that isolates the subscapularis musculotendinous unit. In the first phase of this study 15 subjects accomplished four proposed versions to the "liftoff" test while their intramuscular electromyographic activity in select glenohumeral muscles was recorded. The second phase of this study assessed the ability of five subjects with a nonfunctional subscapularis musculotendinous unit to perform the same proposed versions. On the basis of electromyographic data none of the proposed versions to the "liftoff" maneuver isolated the upper and lower subscapularis muscle from either the teres major, latissimus dorsi, posterior deltoid, or rhomboid muscles (p > 0.05). In the presence of a nonfunctional subscapularis musculotendinous unit, the subjects were able to perform all of the proposed versions of the "liftoff" maneuver except one: elevation of the dorsum of the hand from the posterior-inferior border of the scapula (maximum internal rotation test). Although significant electromyographic activity was generated in the potentially confounding shoulder girdle muscles during the maximum internal rotation "liftoff" test, a successful test appears to be dependent on the isolated glenohumeral internal rotation function of the subscapularis muscle.

The purpose of this study was to describe the activity of eight shoulder muscles during the windmill fast-pitch softball throw. Ten collegiate female pitchers were analyzed with intramuscular electromyography, high-speed cinematography, and motion analysis. The supraspinatus muscle fired maximally during arm elevation from the 6 to 3 o'clock position phase, centralizing the humeral head within the glenoid. The posterior deltoid and teres minor muscles acted maximally from the 3 to 12 o'clock position phase to continue arm elevation and externally rotate the humerus. The pectoralis major muscle accelerated the arm from the 12 o'clock position to ball release phase. The serratus anterior muscle characteristically acted to position the scapula for optimal glenohumeral congruency, and the subscapularis muscle functioned as an internal rotator and to protect the anterior capsule. Although the windmill softball pitch is overtly different from the baseball pitch, several surprising similarities were revealed. The serratus anterior and pectoralis major muscles work in synchrony and seem to have similar functions in both pitches. Although the infraspinatus and teres minor muscles are both posterior cuff muscles, they are characteristically uncoupled during the 6 to 3 o'clock position phase, with the infraspinatus muscle acting more independently below 90 degrees. Subscapularis muscle activity seems important in dynamic anterior glenohumeral stabilization and as an internal rotator in both the baseball and softball throws.

The medical collateral ligament is a common site of injury in baseball pitchers, causing substantial morbidity and loss of pitching time. Twenty-six skilled baseball pitchers with medial collateral ligament insufficiency were studied before surgery with high-speed cinematography and fine-wire electromyography of eight muscles around the elbow. Data from the pitchers with injured elbows were compared with data obtained from uninjured pitchers. The flexor carpi radialis muscle in the pitchers with medial collateral ligament deficiencies revealed significantly decreased firing during the acceleration and deceleration phase of the fastball when compared with that of the pitchers with normal elbows, and the flexor carpi radialis muscle was significantly depressed during the early cocking and deceleration phases. The extensor muscles revealed slightly increased activity in the injured elbows; however, this was not statistically significant. Although the muscles of the flexor pronator group (especially the flexor carpi ulnaris muscle and the flexor digitorum superficialis muscles) are anatomically positioned to provide dynamic stability of the elbow, they did not demonstrate increased electrical activity in pitchers with medial collateral ligament deficiencies. This finding suggests that the muscles on the medial side of the elbow do not supplant the role of the medial collateral ligament during the fastball pitch.

This study compared the electromyographic activity of rotator cuff and scapular muscles between subjects with anterior instability and subjects with normal shoulders. Thirty-eight patients were studied; 23 had anterior instability that was subsequently surgically confirmed, and 15 had normal shoulders. Fine wire electrodes were inserted into the subscapularis (upper and lower portions), supraspinatus, infraspinatus, rhomboid, serratus anterior, and trapezius (upper and lower portions) muscles. Abduction, scapular plane abduction (scaption), and forward flexion were performed over the range of motion and later divided into 30 degrees intervals. In both abduction and scaption, the supraspinatus demonstrated significantly less electromyographic activity from 30 degrees to 60 degrees in shoulders with anterior instability compared with normal shoulders (p < 0.05). During all three motions, shoulders with anterior instability demonstrated significantly less electromyographic activity in the serratus anterior when compared with normal shoulders (p < 0.05). This occurred at 30 degrees to 120 degrees of abduction and at 0 degree to 120 degrees of scaption and forward flexion. None of the other muscles demonstrated significant differences. These differences during planar motions were similar to those demonstrated during challenging overhead sport motions. Early rehabilitation efforts should focus both on the rotator cuff and scapular muscles to establish smooth, coordinated shoulder motion.

In summary, a sport-specific exercise program for golfers includes warming up, stretching, strengthening, and cardiovascular conditioning. The goals of such a program incorporated with playing the game of golf are to optimize performance and prevent injuries. The integration of each of these components represents a well-balanced fitness approach to sport and enhances the enjoyment of the game.

This discussion and the three case examples illustrate different etiologies of shoulder problems in the golfer. Age and the mechanics of an individual swing are factors to consider when defining the core problem. In summarizing shoulder pain in the golfer, perhaps the key point is that a thorough patient evaluation is essential to diagnose the problem accurately. It is only with a specific and accurate diagnosis that an optimal treatment program can be designed, and successful outcomes will be the result.

In the young throwing athlete with shoulder pain, it is essential to recognize that glenohumeral joint instability (occult subluxation, rather than impingement) is the primary underlying pathology. Fortunately, conservative management is effective in most chronic overuse injuries. For those athletes with continued symptoms, surgical intervention may become necessary. The anterior capsulolabral reconstruction addresses the problem of glenohumeral joint instability by correcting the capsular redundancy, labrum damage, or both. The authors believe this most recent surgical technique and postoperative rehabilitation program has resulted in a significant improvement in our ability to more predictably and successfully return these athletes to prior competitive levels.

As golf increases in popularity, more golfers seek the proper mechanics necessary for the perfect golf swing. Surprisingly little scientific work has been published on the contribution of the hip and knee muscles during the golf swing even though most professionals have recognized their vital contribution. Recent studies have described the electromyographic (EMG) muscle activity of the shoulder, back, and trunk during the golf swing. The purpose of this study was to describe the electrical muscle activity in seven hip and knee muscles of both the left (lead) and right (trail) leg in competitive golfers while performing the golf swing. Sixteen golfers were studied with indwelling electrodes and high-speed cinematography. The EMG was synchronized with the film to discern five phases of the golf swing. Means, SDs, and t-tests were done. The results revealed that the trail hip extensors and abductors in conjunction with the lead adductor magus initiated pelvic rotation during forward swing. The lead hamstrings maintained a flexed knee and provided a stable base on which pelvic rotation took place. The peak EMG muscle activity recorded in the hips and knees occurred in an earlier phase than that measured previously in the trunk and shoulder. This confirmed the sequential firing pattern of the hip and knee muscles that takes place during the competitive golf swing. Information gained from this study can be used by players and coaches to optimize performance and to minimize injury.

To describe the relationship of the pronator teres, flexor carpi radialis, flexor digitorum superficialis, and flexor carpi ulnaris muscles to the medial collateral ligament at 30 degrees, 90 degrees, and 120 degrees of elbow flexion, we dissected 11 cadaveric specimens. The flexor carpi ulnaris muscle is the predominant musculotendinous unit overlying the medial collateral ligament in the majority of cases and is the only one at 120 degrees of elbow flexion. The flexor digitorum superficialis muscle is the only other significant contributor. The medial collateral ligament is the primary stabilizer of the medial elbow with elbow flexion greater than 30 degrees, as in throwing. The flexor carpi ulnaris muscle, because of its position directly over the medial collateral ligament, and the flexor digitorum superficialis muscle, with its near proximity and relatively large bulk, are the specific muscles best suited to provide medial elbow support. This is especially relevant to overhand throwing athletes who encounter extreme valgus force across the elbow during the cocking and acceleration phases of the throwing motion. Exercise and conditioning of the medial elbow musculature, specifically the flexor digitorum superficialis muscle and the flexor carpi ulnaris muscle, may prevent injury or assist in rehabilitation of medial elbow instability, especially in overhand throwing athletes.

The need to investigate shoulder injury in swimmers other than the young and elite is evident, as all ages and levels are represented in the 100 million Americans who classify themselves as swimmers. To investigate the differences between young, highly competitive collegiate swimmers and older, less elite swimmers, a survey questionnaire was distributed to 100 collegiate and 100 master's swim teams. Questions regarding swimming routines, performance standards, and several possible predisposing factors associated with "swimmer's shoulder," as implicated in the literature, were investigated. As expected, the results revealed that the collegiate group swam the higher yardage, with considerably faster times in both the 50- and the 1,000-yd freestyle, and more than double the number of workouts per week. However, the collegiate and master's group reported similar percentages, 47 and 48%, respectively, experiencing shoulder pain lasting 3 weeks or more, despite the lesser distances and intensities associated with the latter group. Chi-square analysis revealed no association between shoulder pain and perceived level of flexibility, hand paddle usage, or breathing side for either group. However, over 50% of the swimmers with shoulder pain in both groups perceived that increased intensities and/or distance provoked shoulder pain, indicating that fatigue may be the issue to avoid and on which to focus. Strengthening the muscles of the shoulder, specifically those shown to have a propensity to fatigue, provides a strong defense against injury, as fatigue of the shoulder muscles may be the initial antecedent to swimmer's shoulder. These results give the swimmer, coach, and medical practitioner feedback to consider for a swimmer of any age or level.

To describe the role of the scapular muscles in the golf swing, we studied 15 competitive male golfers. Four muscles were studied bilaterally using dynamic electromyography and cinematography. In the trailing arm, the levator scapulae elevates while the rhomboid muscles retract the scapula during takeaway; both then stabilize the scapula through the remainder of the swing. In the leading arm, these muscles retract the scapula during forward swing and acceleration. The trapezius muscle in the trailing arm also demonstrates high activity during takeaway to aid in scapular retraction. In the leading arm, trapezius activity is high in forward swing and through the remainder of the swing to promote scapular retraction. The serratus anterior muscle activity is high in the trailing arm during forward swing and through the remainder of the swing to maximize scapular protraction. In the leading arm, the serratus anterior muscle has constant activity through all phases of the swing, which may explain the clinical scenario of muscle fatigue in high demand golfers. The golf swing and uncoiling action requires that the scapular muscles work in synchrony to maximize swing arc and clubhead speed. This study demonstrates the importance of the scapular muscles in the golf swing and the need for specific strengthening exercises.

The purpose of this study was to describe and compare electrical activity patterns in 12 shoulder muscles during the breaststroke in 25 competitive swimmers who had normal shoulders and in 14 who had painful shoulders while they performed this stroke in a pool. The electromyographic analysis was synchronized with high-speed cinematography to discern phases of the breaststroke. Means, standard deviations, and t-tests were done for each phase. The differences in muscle activity between the two groups of swimmers demonstrated an increase in the internal rotators in the group with painful shoulders. They also demonstrated a decrease in the teres minor, supraspinatus, and the upper trapezius muscles. These factors increase the risk of impingement. Both the serratus anterior and teres minor muscles in the swimmers with normal shoulders consistently fired at or above 15% manual muscle test throughout the breaststroke cycle and were thus subject to fatigue. Based on these results, exercises for the breaststroke swimmer should be directed toward endurance training of the serratus anterior and teres minor muscles while balancing the internal and external rotators of the shoulder as well as the deltoid and supraspinatus muscles.

During a 7-month period, 32 consecutive athletes underwent anterior capsulolabral reconstruction with modifications, consisting of a horizontal capsulotomy (rather than a T-capsulotomy) and suture anchors (rather than drill holes); 31 patients were available for follow-up examinations. At preoperative examinations all patients demonstrated positive relocation tests; 22 were diagnosed with recurrent anterior subluxation and 9 with recurrent anterior dislocation. After surgery, all patients underwent a rehabilitation program. Followup included physical examination, subjective questions, and radiographs. At a minimum of 24 months' followup, results measured by modified Rowe score were 24 patients (77%) excellent, 6 (19%) good, and 1 (3%) failure. Eighty-one percent of the patients returned to the same sport at the same level of competition, 13% returned to the same sport at a lower level of competition, and 6% did not return to the preinjury sport. Radiographic analyses at 2 years' followup revealed all Mitek anchors were well seated in the bone of the glenoid neck. No complications of the suture anchors occurred. This modification of anterior capsulolabral reconstruction simplified the procedure and allowed a more aggressive early rehabilitation program with 97% good or excellent results.

Throughout the ages, instability has been noted to be the underlying problem in shoulder dysfunction of the young, overhand-throwing athlete. Impingement and rotator cuff tears are progressive symptoms of this instability. The classic theory of impingement describes a mechanism for "outside impingement," which is most often seen in the older, nonathletic population. The mechanism for "inside impingement" in the younger, athletic population is a pinching of the cuff undersurface on the posterosuperior glenoid labrum. In this younger group, the first treatment of choice is rehabilitation. If that fails, the surgical procedure with successful outcome is the ACLR coupled with a progressive rehabilitation program.

Standard posterior shoulder surgical approaches include infraspinatus tendon detachment and infraspinatus-teres minor interval development. Cadaveric and clinical investigation of a new infraspinatus-splitting approach to the posterior glenohumeral joint was undertaken to assess efficacy in providing exposure, preserving tendon attachment, and avoiding neurologic compromise. Infraspinatus musculotendinous and neural anatomy was examined in 20 cadavers. Four patients with posterior shoulder instability underwent posterior capsulorrhaphy through this infraspinatus-splitting approach, followed by electrodiagnostic testing. Infraspinatus muscle was bipennate in all specimens, the tendinous interval an average 14 mm inferior to the scapular spine at the glenoid rim. The infraspinatus-splitting interval bisected the posterior glenoid rim at its midpoint, whereas the infraspinatusteres minor interval crossed the glenoid rim's lower quarter. The suprascapular nerve provided sole innervation to the infraspinatus muscle in all specimens, entering the infraspinous fossa at the notch as a single trunk 22 mm medial to the glenoid rim. Minimum branching variability was observed. Electrodiagnostic testing showed no evidence of axonal damage or muscle denervation in either infraspinatus pennate bundle. Limiting infraspinatus-splitting dissection medially to 1.5 cm from the posterior glenoid rim prevents damage to any interval-crossing suprascapular nerve branches. Posterior shoulder surgery through a horizontal, longitudinal infraspinatus tendon-splitting approach provides excellent exposure of posterior capsule, labrum, and glenoid, without requiring tendon detachment or causing neurologic compromise.

There are two distinct pathological categories of shoulder injury. In the older population, shoulder injury is generally a result of the degenerative aging process. In the younger population, it is commonly a result of the repetitiousness of an overhead sport. In the latter group, instability is typically the core problem, leading to the continuum of subluxation, impingement, and rotator cuff tear. A classification scheme, proposing four definitive types of shoulder injury, assists in directing an effective management program. Once diagnosed (the first step of treatment) a conservative rehabilitation program that emphasizes strengthening of the glenohumeral protectors, scapulohumeral pivotors, humeral positioners, and power drivers is advised. The surgery of choice, for the small minority who fail to respond to the rehabilitation program, is the anterior capsulolabral reconstruction. A sports medicine team working together with the athlete is instrumental in his/her return to sport.

The muscle firing pattern in 12 muscles throughout the lower extremity, trunk, and upper extremity during the batting swing is described in this study. The two hamstring muscles studied and the gluteal muscle had a similar pattern of high muscle activity during pre-swing and early swing, and then rapidly diminished. The vastus medialis demonstrated peak activity between 95 and 110% maximum muscle test (MMT) throughout the swing phases and follow-through. The erector spinae demonstrated activity from 85 to 185% MMT during the swing phases. The abdominal obliques showed greater than 100% MMT during the swing phases and follow-through. The supraspinatus and serratus anterior showed relatively low muscle activity (less than 40% MMT). These results show that batting is a sequence of coordinated muscle activity, beginning with the hip, followed by the trunk, and terminating with the arms. Power in the swing is initiated in the hip, and therefore exercises that emphasize such strength development are indicated. The maintained, high muscle activity in the trunk muscles indicates a need for back and abdominal stabilization and rotation exercises. The relatively low level of activity in the four scapulohumeral muscles tested indicated that emphasis should be placed on the trunk and hip muscles for a batter's strengthening program.

In the overhand or throwing athlete, the shoulder is extremely vulnerable to injury due to the repetitive, high-energy forces. When these stresses are applied at a rate that exceeds that of tissue repair, progressive damage to the shoulder's stabilizing structures can occur. With continued throwing, the static restraints become progressively attenuated, allowing anterior glenohumeral subluxation. Initially, the dynamic stabilizers can compensate for this mild instability with increased muscle activity. Prolonged activity, however, may lead to fatigue. Over time, these compensatory mechanisms can become overloaded. The humeral head then may subluxate anteriorly, where it contacts with the coracoacromial arch, ultimately leading to subacromial impingement. Posterosuperior glenoid impingement may also occur as anterior humeral translation allows the undersurface of the tendinous portions of the supraspinatus and infraspinatus to impinge along the posterosuperior border of the glenoid rim. Fortunately, conservative management is effective in most chronic overuse injuries and includes an initial period of relative rest (avoidance of throwing), oral nonsteroidal antiinflammatory medication, a physical therapy program structured to provide local modalities to reduce inflammation, and a strengthening program for the rotator cuff and scapular rotators. For those athletes with continued symptoms, surgical intervention may become necessary. The appropriate surgical treatment depends on the diagnosis. In the young throwing athlete with shoulder pain, it is essential to recognize that instability or occult subluxation, rather than impingement, is the primary underlying pathology. The anterior capsulolabral reconstruction addresses the problem of instability by correcting the capsular redundancy or labral damage or both. When performed in the manner described, muscle attachments and proprioceptive muscle fibers are not disturbed and full shoulder range of motion can quickly be achieved. This most recent surgical technique and postoperative rehabilitation program has resulted in a significant improvement in the ability to correct instability in those athletes who have failed a prolonged course of conservative care. Prevention of these injuries may be attained, it is hoped, through continued research into the basic biomechanics and the pathoanatomy associated with overhand sports.(ABSTRACT TRUNCATED AT 400 WORDS)

It is generally believed that tennis players using a double-handed backhand rarely develop lateral epicondylitis since the helping arm appears to absorb more energy and changes the mechanics of the swing. The purpose of this paper was to compare muscle activity about the elbow in single- and double-handed backhand strokes in competitive tennis players. Muscle activity in 3 elbow extensors, a wrist flexor, and a forearm pronator of the dominant arm was compared during the single-handed (N = 14) and double-handed (N = 13) backhand ground strokes using indwelling electromyography and high-speed cinematography. Significantly higher activity was seen in the double-handed technique in the flexor carpi radialis muscle in the preparation phase and in the pronator teres muscle in the acceleration phase. Higher flexor carpi radialis muscle activity in preparation of the double-handed stroke appeared to be a function of the double-handed grip used on the racquet, and the increased pronator teres muscle activity in acceleration indicated maintenance of greater pronation provided by the grip of the non-dominant hand. The decreased occurrence of lateral epicondylitis in players using a double-handed backhand may not be caused by decreased extensor activity, but rather by factors associated with flawed stroke mechanics more often seen in the single-handed technique.

Golf is a popular sport for both men and women. The trunk is the most common area of injury during the golf swing. The purpose of this study was to describe and compare the muscle firing patterns in the trunk during the golf swing. Twenty-three golfers with handicaps of five or below volunteered for this study. Surface electromyographic electrodes were placed on the abdominal oblique and erector spinae muscles bilaterally. High-speed cinematography was used in conjunction with the electromyographic electrodes. The results demonstrated relatively low activity in all muscles during takeaway (below 30% of maximal muscle test), and relatively high and constant activity throughout the rest of the swing (above 30% maximal muscle test, with the exception of the contralateral erector spinae during late follow-through, which was 28% maximal muscle test). This high and constant activity demonstrated the importance of the trunk muscles during a golf swing. These results indicate the need for an effective preventive and rehabilitative exercise program for the golfer.