Heterotopic Ossifications in a Mouse Model of Albright Hereditary Osteodystrophy

Albright hereditary osteodystrophy (AHO) is characterized by short stature, brachydactyly, and often heterotopic ossifications that are typically subcutaneous. Subcutaneous ossifications (SCO) cause considerable morbidity in AHO with no effective treatment. AHO is caused by heterozygous inactivating mutations in those GNAS exons encoding the α-subunit of the stimulatory G protein (Gαs). When inherited maternally, these mutations are associated with obesity, cognitive impairment, and resistance to certain hormones that mediate their actions through G protein-coupled receptors, a condition termed pseudohypoparathyroidism type 1a (PHP1a). When inherited paternally, GNAS mutations cause only AHO but not hormonal resistance, termed pseudopseudohypoparathyroidism (PPHP). Mice with targeted disruption of exon 1 of Gnas (GnasE1−/+) replicate human PHP1a or PPHP phenotypically and hormonally. However, SCO have not yet been reported in GnasE1+/− mice, at least not those that had been analyzed by us up to 3 months of age. Here we now show that GnasE1−/+ animals develop SCO over time. The ossified lesions increase in number and size and are uniformly detected in adult mice by one year of age. They are located in both the dermis, often in perifollicular areas, and the subcutis. These lesions are particularly prominent in skin prone to injury or pressure. The SCO comprise mature bone with evidence of mineral deposition and bone marrow elements. Superficial localization was confirmed by radiographic and computerized tomographic imaging. In situ hybridization of SCO lesions were positive for both osteonectin and osteopontin. Notably, the ossifications were much more extensive in males than females. Because GnasE1−/+ mice develop SCO features that are similar to those observed in AHO patients, these animals provide a model system suitable for investigating pathogenic mechanisms involved in SCO formation and for developing novel therapeutics for heterotopic bone formation. Moreover, these mice provide a model with which to investigate the regulatory mechanisms of bone formation

Elbow medial collateral ligament injuries

Elbow medial collateral ligament sprain occurs when the elbow is subjected to a valgus force exceeding the tensile properties of the medial collateral ligament (MCL). This is an injury seen more often in throwing athletes. Understanding the differential diagnosis of medial elbow pain is paramount to diagnose MCL injury as well as addressing other medial elbow pathology. A natural evolution regarding MCL injury has occurred over the past 20 years, with modifications of the original surgical procedure, specificity and sensitivity analysis of imaging modalities, and physical exam maneuvers to diagnose MCL pathology. In order for the MCL literature to advance further, more biomechanical and long-term clinical outcome data for the respective surgical modifications are needed. This review describes MCL injury pathophysiology, patient evaluation, reconstruction indications/contraindications, and current and evolving surgical techniques

Variable exponent Besov-Morrey spaces

In this paper we introduce Besov-Morrey spaces with all indices variable and study some fundamental properties. This includes a description in terms of Peetre maximal functions and atomic and molecular decompositions. This new scale of non-standard function spaces requires the introduction of variable exponent mixed Morrey-sequence spaces, which in turn are defined within the framework of semimodular spaces. In particular, we obtain a convolution inequality involving special radial kernels, which proves to be a key tool in this work.publishe

Basic Science Considerations in Primary Total Hip Replacement Arthroplasty

Total Hip Replacement is one of the most common operations performed in the developed world today. An increasingly ageing population means that the numbers of people undergoing this operation is set to rise. There are a numerous number of prosthesis on the market and it is often difficult to choose between them. It is therefore necessary to have a good understanding of the basic scientific principles in Total Hip Replacement and the evidence base underpinning them. This paper reviews the relevant anatomical and biomechanical principles in THA. It goes on to elaborate on the structural properties of materials used in modern implants and looks at the evidence base for different types of fixation including cemented and uncemented components. Modern bearing surfaces are discussed in addition to the scientific basis of various surface engineering modifications in THA prostheses. The basic science considerations in component alignment and abductor tension are also discussed. A brief discussion on modular and custom designs of THR is also included. This article reviews basic science concepts and the rationale underpinning the use of the femoral and acetabular component in total hip replacement

Optimal antibiotics duration following surgical management of septic olecranon bursitis: a 12-year retrospective analysis.

Introduction: The absence of a standardized postoperative antibiotic treatment approach for patients with surgically treated septic bursitis results in disparate practices. Methods: We retrospectively reviewed charts of adult patients with surgically treated septic olecranon bursitis at Mayo Clinic sites between 1 January 2000 and 20 August 2022, focusing on their clinical presentation, diagnostics, management, postoperative antibiotic use, and outcomes. Results: A total of 91 surgically treated patients were identified during the study period. Staphylococcus aureus was the most common pathogen (64 %). Following surgery, 92 % (84 of 91 patients) received systemic antibiotics. Excluding initial presentations of bacteremia or osteomyelitis (), the median duration of postoperative antibiotics was 21 d (interquartile range, IQR: 14-29). Postoperative complications were observed in 23 % (21 of 91) of patients, while cure was achieved in 87 % (79 of 91). Active smokers had 4.53 times greater odds of clinical failure compared with nonsmokers (95 % confidence interval, 95 % CI: 1.04-20.50; ). The highest odds of clinical failure were noted in cases without postoperative antibiotic administration (odds ratio, OR: 7.4). Conversely, each additional day of antibiotic treatment, up to 21 d, was associated with a progressive decrease in the odds of clinical failure (OR: 1 at 21 d). Conclusion: The optimal duration of antibiotics postoperatively in this study was 21 d, which was associated with a 7.4-fold reduction in the odds clinical failure compared with cases without postoperative antibiotics. Further validation through a randomized controlled trial is needed