Assessment of a new undergraduate module in musculoskeletal medicine.

BACKGROUND: Despite the high prevalence of musculoskeletal disorders seen by primary care physicians, numerous studies have demonstrated deficiencies in the adequacy of musculoskeletal education at multiple stages of medical education. The aim of this study was to assess a newly developed module in musculoskeletal medicine for use at European undergraduate level (i.e., the medical-school level). METHODS: A two-week module in musculoskeletal medicine was designed to cover common musculoskeletal disorders that are typically seen in primary care. The module incorporated an integrated approach, including core lectures, bedside clinical examination, and demonstration of basic practical procedures. A previously validated examination in musculoskeletal medicine was used to assess the cognitive knowledge of ninety-two students on completion of the module. A historical control group (seventy-two students) from a prior course was used for comparison. RESULTS: The new module group (2009) performed significantly better than the historical (2006) control group in terms of score (62.3% versus 54.3%, respectively; p \u3c 0.001) and pass rate (38.4% versus 12.5%, respectively; p = 0.0002). In a subgroup analysis of the new module group, students who enrolled in the graduate entry program (an accelerated four-year curriculum consisting of students who have already completed an undergraduate university degree) were more likely to perform better in terms of average score (72.2% versus 57%, respectively; p \u3c 0.001) and pass rates (70.9% versus 21.4%, respectively; p \u3c 0.001) compared with students who had enrolled via the traditional undergraduate route. In terms of satisfaction rates, the new module group reported a significantly higher satisfaction rate than that reported by the historical control group (63% versus 15%, respectively; p \u3c 0.001). CONCLUSIONS: In conclusion, the musculoskeletal module described in this paper represents an educational advance at undergraduate (i.e., medical-school) level as demonstrated by the improvement in scores in a validated examination. As pressure on medical curricula grows to accommodate advancing medical knowledge, it is important to continue to improve, assess, and consolidate the position of musculoskeletal medicine in contemporary medical education

The benefits and limitations of animal models for translational research in cartilage repair.

Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair

Outcome of periacetabular osteotomy for the management of acetabular dysplasia: experience in an academic centre.

Periacetabular osteotomy (PAO) is a very effective reconstructive procedure for treatment of acetabular dysplasia. An orthopaedic paediatric surgeon and a reconstructive hip arthroplasty surgeon performed this procedure together in the early phase of their learning curve and then performed it individually. The early clinical and radiographic results of 85 consecutive PAOs performed in this academic orthopaedic unit were reviewed. The mean Merle-d\u27Aubigné score increased from 12.4 preoperatively to 16 at follow-up. Pre-operatively 73 hips were anteverted and 12 were neutral or retroverted. The mean angle of Wiberg improved from 5 degrees to 21 degrees (p \u3c 0.0001) in anteverted hips, and from 9 degrees to 30 degrees in neutral or retroverted hips. The mean angle of Lequesne and de Sèze improved from 6 degrees to 35 degrees (p \u3c 0.0001) in anteverted hips, and in neutral or retroverted hips from 9 degrees to 30 degrees (p \u3c 0.0001). The acetabular index improved from 26 degrees to 8 degrees (p \u3c 0.0001) in anteverted hips, and from 21 degrees to 7 degrees (p \u3c 0.0001) in neutral or retroverted hips. Over the 7 year period the blood loss and operative time improved from 2000 ml to 900 ml and 4 hours to 2 hours respectively. Four hips (four patients) required conversion to total hip replacement. The radiographic correction and improved clinical scores are similar to those in previous studies. This study shows a survival rate of 94% at 58 months following periacetabular osteotomy. The learning curve and the early results of this procedure performed in our academic unit are encouraging

Metabolic Changes in Skin Caused by Scd1 Deficiency: A Focus on Retinol Metabolism

We previously reported that mice with skin-specific deletion of stearoyl-CoA desaturase-1 (Scd1) recapitulated the skin phenotype and hypermetabolism observed in mice with a whole-body deletion of Scd1. In this study, we first performed a diet-induced obesity experiment at thermoneutral temperature (33°C) and found that skin-specific Scd1 knockout (SKO) mice still remain resistant to obesity. To elucidate the metabolic changes in the skin that contribute to the obesity resistance and skin phenotype, we performed microarray analysis of skin gene expression in male SKO and control mice fed a standard rodent diet. We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebaceous gland hypoplasia, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXRα. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly, we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. Furthermore, SEB-1 sebocytes treated with retinol and SCD inhibitor also display an elevation in retinoic acid-induced genes. These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin phenotype

Total Hip Arthroplasty in the Setting of Post-traumatic Arthritis Following Acetabular Fracture: A Systematic Review

Background: Acetabular fractures are frequently associated with post-traumatic arthritis (PTA), for which total hip arthroplasty (THA) has emerged as the established procedure. The purpose of this systematic review is to report the patient outcomes, complications, and implant survival of delayed THA for patients with PTA following acetabular fracture. Methods: A systematic review was performed in December 2021 as per Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines to identify all studies reporting outcomes of delayed THA performed for PTA with a history of acetabular fracture. From an initial screen of 893 studies, 29 studies which met defined inclusion criteria including minimum 12 months of follow-up and minimum 10 THA were included in the final review. Results: A total of 1220 THA were reported across 29 studies, with 1174 THA completing a minimum of 1-year follow-up at a mean of 86 months. All 29 studies reported upon complications, with a control included in 6 for comparison. Higher complication rates were observed both in patients who had prior open reduction internal fixation and conservative treatment, most notably infection which was observed following 3.6% THA. The total joint revision rate was 9.7%. An improvement was noted in all 25 studies which recorded patient-reported outcomes, with a mean rise in the Harris hip score from 45 to 86 across 18 studies. Conclusions: THA may reduce reported pain levels and improve functional outcomes in selected patients experiencing PTA following acetabular fractures. There is an increased risk of complications, necessitating careful consideration when planning the operation and open discussion with prospective patients and caregivers

Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes

CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chemical probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934 (CAMKK2 IC50 = 3 nM), a total of 32 compounds, composed of single ring, 5,6-, and 6,6-fused heteroaromatic cores were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. These compounds were evaluated in vitro in biochemical and cellular assays for CAMKK2 inhibition. Compared to GSK650394 and STO-609, thirteen of our compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had greatly improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs aimed at the identification of CAMKK2 chemical probes and clinical candidates</div