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Purpose: To analyze the demographics and trends of orthopaedic surgeons entering the U.S. orthopaedic sports medicine workforce over the past decade., Methods: This was a cross-sectional study of allopathic medical students, orthopaedic surgery residents, and orthopaedic sports medicine fellows in the United States (2013-2022) that leveraged data from the Accreditation Council for Graduate Medical Education and American Medical Association. Disparities in demographic representation between orthopaedic sports medicine fellows and the 2020 U.S. population census were quantified with participation-to-prevalence ratios (PPRs). A PPR between 0.8 and 1.2 was classified as equivalent representation and a PPR<0.8 was classified as under-representation, relative to the U.S., Results: The representation of female, Hispanic, Black, and Asian trainees decreased at each stage of the training pipeline to orthopaedic sports medicine fellowship training. In contrast, the representation of White trainees increased at each stage of the training pipeline. Over the study period, there were modest increases in female (9.9% to 12.6%) and Hispanic (1.2% to 1.7%) trainee representation in orthopaedic sports medicine. In contrast, Asian (16.6% to 5.6%) and Black (5.1% to 1.9%) trainee representation decreased. Relative to the US population, female (PPR = 0.22), Black (PPR = 0.30), Hispanic (PPR = 0.19), Native Hawaiian/Pacific Islander (PPR = 0.01), and Native American/Alaskan Native (PPR = 0.00) trainees were under-represented. In contrast, male (PPR = 1.79), Asian (PPR = 1.96), and White (PPR = 1.36) trainees were over-represented in orthopaedic sports medicine., Conclusions: There is limited diversity in the emerging orthopaedic sports medicine workforce relative to the U.S., Population: Improvements in the representation of female, Black, and Hispanic trainees in orthopaedic sports medicine has been marginal relative to trends observed at U.S. allopathic medical schools., Clinical Relevance: Promoting diversity and inclusion in the orthopaedic sports medicine workforce can create more surgical provider options for diverse patient populations in the United States., Competing Interests: Disclosures All authors (J.S., H.S.S., W.N.N., O.O.K., J.D.K.) 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 © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To compare MRI with 3D reconstructions and 3D-CT with respect to assessment of glenoid wear in osteoarthritic shoulders., Methods: 3D reconstructions were generated for CT and MR (utilizing the Dixon technique) imaging performed on 29 osteoarthritic shoulders. Two reviewers independently performed glenoid morphometric measurements and evaluated glenoid erosion. Mean differences between the two modalities were calculated. Inter-observer agreement was calculated using kappa coefficient., Results: The combined mean absolute difference (bias) in glenoid version between 3D-CT and 3D-MRI was 2.7° ± 1.6° (range 0.15-7.85, P value = 0.7). The combined mean absolute difference in glenoid inclination between 3D-CT and 3D-MRI was 6.8° ± 4.1° (range 0.8°-15.75°, P value = 0.17). No significant inter-reader variation in glenoid version and inclination measurements on 3D-CT and 3D-MRI was found (P > 0.05). The inter-reader reliability for both CT and MRI was high for Walch grading of glenoid bone loss (κ = 1, κ = 0.81, respectively)., Conclusions: 3D-MRI is comparable to 3D-CT with respect to axial glenoid bone loss, as measured by glenoid version. However, for coronal bone loss estimation, measured by glenoid inclination, 3D-CT remains the gold standard. Thus, 3D-MR can be used as an alternative for preoperative assessment of glenoid version in arthritic shoulders., (© 2022. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: The aims of this study were to examine variances in inpatient opioid consumption after total shoulder arthroplasty (TSA) and to determine factors influencing inpatient opioid utilization., Methods: The sample included patients undergoing elective TSA at a tertiary-level institution between January 2016 and April 2018. Opioid consumption during the inpatient stay was converted into morphine milligram equivalents (MMEs), accounting for dosage and route of administration. The MMEs were calculated per patient encounter and used to calculate mean opioid consumption. Bivariate linear regression analysis was performed to assess the impact of patient-related factors and surgery-related factors on inpatient opioid consumption., Results: Altogether 20 surgeons performed 622 TSAs. The average opioid dose per encounter was 47.4 ± 65.7 MME/d. MMEs prescribed varied significantly among surgeon providers (P < .01). Pre-existing psychiatric disorders (P = .00012), preoperative opioid use (P = .0013), highest quartile of median household income (P = .048), current-smoker status (P < .001), age < 60 years (P < .01), and general anesthesia (vs. regional anesthesia, P = .005) were associated with significant inpatient opioid consumption after TSA. Sex, race, American Society of Anesthesiologists status, replacement type (anatomic TSA vs. reverse TSA), and prior shoulder surgery did not show any significant differences., Conclusion: There is considerable variation in inpatient opioid consumption after TSA at the same institution. Knowledge of modifiable and nonmodifiable risk factors that increase inpatient opioid consumption will help to optimize multimodal analgesia protocols for TSA., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are being increasingly employed as a part of multimodal non-opioid strategies to treat postoperative pain. In the present study, we sought to review the effects of short-term NSAID use on musculoskeletal soft-tissue healing., Methods: We performed a scoping review of all studies that included the use of NSAIDs and their effect on healing of soft tissues, which for the purpose of this review refers to non-osseous musculoskeletal tissue such as ligament, tendon, labrum, and meniscus. The inclusion criteria encompassed all studies (human, animal, and in vitro) that evaluated the effect of NSAIDs on soft-tissue healing. Subgroup analyses, wherever applicable, were conducted on the basis of the type of NSAID (cyclooxygenase [COX]-specific or nonspecific) and the type of study (human, animal, or in vitro). Relevant metadata from each study were abstracted, and descriptive statistics were used to summarize the results., Results: A total of 44 studies met the inclusion criteria, including 3 human studies, 33 animal studies, and 8 in vitro studies. These studies included 4 different NSAIDs in the human subgroup, 16 different NSAIDs in the animal subgroup, and 7 different NSAIDs in the in vitro subgroup. The majority of reported studies (including 1 of 2 human studies, 10 of 14 animal studies, and 3 of 3 in vitro studies) demonstrated that COX-2-selective inhibitors had negative impact on soft-tissue healing. In contrast, the majority of human and animal studies (2 of 2 and 19 of 30, respectively) demonstrated that nonselective COX inhibitors had no negative effect on the healing of labrum, tendons, and ligaments. The majority of in vitro studies demonstrated that NSAIDs have a harmful effect on biological processes involved in tendon-healing and regeneration (tenocyte proliferation, collagen and glycosaminoglycan synthesis)., Conclusions: Current limited evidence demonstrates that selective COX-2 inhibitors can negatively affect healing of musculoskeletal soft tissue after surgical repair. In contrast, the majority of studies demonstrate that nonselective COX inhibitors have no negative effect on musculoskeletal soft-tissue healing. Additional high-quality human clinical trials are necessary to provide more definitive conclusions.

Adjuvant-containing drug products can be exposed to high levels of interfacial shear during manufacture. This may affect the integrity of the adjuvant, alter its interaction with the drug substance or change the physical characteristics of the drug product. In this study, a solid-liquid interfacial shear device was used to investigate the shear response of aluminum phosphate adjuvant alone and two adjuvant containing vaccine drug products (DP1 and DP2). The relationship between the shear sensitivity of each and its resuspension properties was determined. Changes in the particle dimensions of the bulk adjuvant were minimal at shear strain rates of 10,900 s(-1) . However, at 25,500 s(-1) , the median particle diameter was reduced from 6.2 to 3.5 μm and was marked by the presence of sub-micron fines. A formulation without drug substance and DP2 produced similar shear responses but with less impact on particle diameter. The behavior of DP1 was less predictable. Sheared DP1 was characterized by prolonged sedimentation because of the presence of fine particulates and required in excess of 300 rotations to resuspend after extended storage. The study confirms that the solid-liquid interfacial shear device may be applied to understand product shear sensitivity associated with vaccine manufacturing., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Background: Body size is associated with increased brachial systolic blood pressure (SBP) and aortic stiffness. The aims of this study were to determine the relationships between central SBP and body size (determined by body mass index (BMI), waist circumference and waist/hip ratio) in health and disease. We also sought to determine if aortic stiffness was correlated with body size, independent of BP., Methods: BMI, brachial BP and estimated central SBP (by SphygmoCor and radial P2) were recorded in controls (n=228), patients with diabetes (n=211), coronary artery disease (n=184) and end-stage kidney disease (n=68). Additional measures of waist circumference and arterial stiffness (aortic and brachial pulse wave velocity (PWV)) were recorded in a subgroup of 75 controls (aged 51 ± 12 years) who were carefully screened for factors affecting vascular function., Results: BMI was associated with brachial (r=0.30; P<0.001) and central SBP (r=0.29; P<0.001) in the 228 controls, but not the patient populations (r<0.13; P>0.15 for all comparisons). In the control subgroup, waist circumference was also significantly correlated with brachial SBP (r=0.29; P=0.01), but not central SBP (r=0.22; P=0.07). Independent predictors of aortic PWV in the control subgroup were brachial SBP (β=0.43; P<0.001), age (β=0.37; P<0.001), waist circumference (β=0.39; P=0.02) and female sex (β=-0.24; P=0.03), but not BMI., Conclusion: In health, there are parallel increases in central and brachial SBP as BMI increases, but these relationships are not observed in the presence of chronic disease. Moreover, BP is a stronger correlate of arterial stiffness than body size.

Plant leucine rich repeat (LRR) proteins have diverse functions and cellular locations. An important unresolved question involves the role of the cysteine-rich capping domains which flank the LRR domain. Such studies have been hampered by difficulties in producing recombinant LRR proteins in yields sufficient for biochemical analysis. We have used Escherichia coli to overproduce Leucine Rich Protein (LRP), a small model LRR protein from tomato containing approximately five LRRs. The LRP capping domain sequences resemble those from plant disease resistance proteins and receptor-like protein kinases. LRP was purified as a soluble, crystallizable, monomeric protein by renaturation of a GST-fusion protein. The four cysteine residues in LRP were found to form two disulfide bonds, one each in the N- and C-terminal LRR-capping domains, the presence of which is necessary to protect the LRR domain from proteolysis in vitro. Fluorescence and CD spectroscopies together with molecular modelling revealed that structural features of the N-capping domain may be destabilised on reduction. These include a tryptophan stacking interaction and a long alpha-helix of residues 30-44. LRP deletion mutants lacking the capping domains showed a propensity to aggregate and increased proteolytic sensitivity. These results have important implications for future structure-function studies of plant LRR proteins.

The Hrp pilus plays an essential role in the long-distance type III translocation of effector proteins from bacteria into plant cells. HrpA is the structural subunit of the Hrp pilus in Pseudomonas syringae pv. tomato (Pst) DC3000. Little is known about the molecular features in the HrpA protein for pilus assembly or for transporting effector proteins. From previous collections of nonfunctional HrpA derivatives that carry random pentapeptide insertions or single amino acid mutations, we identified several dominant-negative mutants that blocked the ability of wild-type Pst DC3000 to elicit host responses. The dominant-negative phenotype was correlated with the disappearance of the Hrp pilus in culture and inhibition of wild-type HrpA protein self-assembly in vitro. Dominant-negative HrpA mutants can be grouped into two functional classes: one class exerted a strong dominant-negative effect on the secretion of effector proteins AvrPto and HopPtoM in culture, and the other did not. The two classes of mutant HrpA proteins carry pentapeptide insertions in discrete regions, which are interrupted by insertions without a dominant-negative effect. These results enable prediction of possible subunit-subunit interaction sites in the assembly of the Hrp pilus and suggest the usefulness of dominant-negative mutants in dissection of the role of the wild-type HrpA protein in various stages of type III translocation: protein exit across the bacterial cell wall, the assembly and/or stabilization of the Hrp pilus in the extracellular space, and Hrp pilus-mediated long-distance transport beyond the bacterial cell wall.

Tomatinase, an extracellular enzyme belonging to family 3 of the glycosyl hydrolases, is produced by the fungal tomato-leaf pathogen Septoria lycopersici and detoxifies the saponin alpha-tomatine. An efficient strategy for purification of the enzyme from fungal culture medium has been developed. Single crystals have been grown by vapour diffusion at 289 K from 17.5%(w/v) PEG 4K, 5%(v/v) 2-propanol and 0.1 M sodium acetate pH 4.5 as precipitant. When cryoprotected at 100 K, these crystals diffract to at least 3.0 A and belong to space group P2(1)2(1)2. Based on an estimated molecular weight of 110 kDa for the glycosylated protein and assuming two molecules in the asymmetric unit, the crystals contain approximately 46% solvent.

The X-ray crystal structure of the apo-form of the Fur protein from Rhizobium leguminosarum has been solved at 2.7 A resolution. Small-angle X-ray scattering was used to give information on the solution conformation of the protein. The Fur homodimer folds into two domains. The N-terminal domain is formed from the packing of two helix-turn-helix motifs while the C-terminal domain appears primarily to stabilize the dimeric state of the protein.

Nuclease E colicins that exert their cytotoxic activity through either non-specific DNase or specific rRNase action are inhibited by immunity proteins in a high affinity interaction that gives complete protection to the producing host cell from the deleterious effects of the toxin. Previous X-ray crystallographic analysis of these systems has revealed that in both cases, the immunity protein inhibitor forms its highly stable complex with the enzyme by binding as an exosite inhibitor-adjacent to, but not obscuring, the enzyme active site. The structures of the free E9 DNase domain and its complex with an ssDNA substrate now show that inhibition is achieved without deformation of the enzyme and by occlusion of a limited number of residues of the enzyme critical in recognition and binding of the substrate that are 3' to the cleaved scissile phosphodiester. No sequence or structural similarity is evident between the two classes of cytotoxic domain, and the heterodimer interfaces are also dissimilar. Thus, whilst these structures suggest the basis for specificity in each case, they give few indications as to the basis for the remarkably strong binding that is observed. Structural analyses of complexes bearing single site mutations in the immunity protein at the heterodimer interface reveal further differences. For the DNases, a largely plastic interface is suggested, where optimal binding may be achieved in part by rigid body adjustment in the relative positions of inhibitor and enzyme. For the rRNases, a large solvent-filled cavity is found at the immunity-enzyme interface, suggesting that other considerations, such as that arising from the entropy contribution from bound water molecules, may have greater significance in the determination of rRNase complex affinity than for the DNases.