Comparison of Complications, Metalwork Removal and Cost Between Locking and Tubular Plates for Lateral Malleolus Fractures Fixation.

Introduction Ankle fractures are common injuries in orthopaedic practice. Open reduction with internal fixation is the main line of management of displaced ankle fractures in fit patients. The study aims to analyse the complications, re-operation rate and cost difference between one-third tubular and locking plates which are the most frequently used constructs in lateral malleolus fractures. Materials and methods The total number of presented ankle fractures from April to August during the years 2015, 2017 and 2019 to our Tertiary Hospital in the United Kingdom were screened. Data including operative fixation, plate used, complication rates, the need for revision surgery and metalwork removal were collected from the hospital's electronic Virtual Trauma Board. Patients who had less than one-year follow-up were excluded. Results A total of 174 patients were included which represents more than half of presented ankle fractures (56%) with a decline in the mean age of operated patients from 56.4 in 2015 to 46.2 in 2019. The majority of fixation used tubular plates (n=122) versus (n=52) for locking plates. Locking plate fixation doubled from 10 in 2015 to 23 in 2019. However, they only contributed to 27% of the total operated ankle fractures. Despite the initial higher complications and removal rates of locking plates in 2015 (P<0.042 and P<0.038 respectively), there was no significant difference in overall complications, revision rates, and metalwork removal between locking plates and tubular plates (p=0.084, FEp= 0.158 and p=0.096 respectively). There was an estimated extra cost of £15938.60 for the use of locking plates during the study timeline. Conclusion There was no significant difference in overall complications, revision surgery and metalwork removal between tubular and locking plates in treating lateral malleolus fractures despite the significantly higher cost of locking constructs. Further studies are needed to illustrate the trend and cost-effective analysis of the tubular and locking plates in treating ankle fractures.

Auditing RadExam: Employing Psychometrics to Improve Exam Quality.

INTRODUCTION: RadExam is a question item and exam database jointly developed by the Association of Program Directors in Radiology and the American College of Radiology to provide formative resident assessment, offering performance metrics benchmarked against institutional and national resident performance. Beyond resident performance, data is available on question and exam performance. Despite considerable investment in the education and training of its question writers and editors and meticulous attention to current psychometrically validated methods, it was anticipated a minority of exam questions would still perform poorly. Audits were performed to identify these questions, identify reasons for poor performance, and modify or replace so-affected questions. Exam performance was also assessed. METHODS: Two audits were performed, the first after the February-May 2018 RadExam pilot phase, and the second nearly 1 year after the full implementation of RadExam. In each audit, RadExam subspecialty editors evaluated all exam questions and exams using statistical data: question and test number of administrations, question p value, question Discrimination Index (DI), question Bloom's taxonomy learning level, exam P-value, and the number of image-based questions in each exam. Identified questions were modified or removed and replaced. RESULTS: Audit 1 was performed after the administration of 3114 exams comprised of 2520 questions administered across 100 residency programs. Audit 1 identified 617 questions with DI <0.1 and 565 questions with unacceptable P-values, all of which were modified or replaced. Audit 2 was performed after the administration of 16,416 exams, comprised of 2,507 questions. Audit 2 identified 229 questions with DI <0.1 and 290 questions with unacceptable P-values, representing a 49.1% decrease in total flagged questions compared to Audit 1. Statistically significant decreases were seen in questions with both DI and P-values outside of the desired range across nearly all subspecialties. CONCLUSION: The positive impact of our audit system on question and exam performance was reflected in a significant decrease in the number of questions flagged and improved overall exam performance in Audit 2. This illustrates the positive impact of Audit 1.

Spontaneous regression of squamous cell carcinoma in the setting of dental infection and needle biopsy.

To our knowledge, this is the first reported case of spontaneous regression of squamous cell carcinoma within a lymph node. We speculate that prior dental infection, fever, and biopsy incited an antitumor immune reaction.

Capturing the interactome of newly transcribed RNA.

We combine the labeling of newly transcribed RNAs with 5-ethynyluridine with the characterization of bound proteins. This approach, named capture of the newly transcribed RNA interactome using click chemistry (RICK), systematically captures proteins bound to a wide range of RNAs, including nascent RNAs and traditionally neglected nonpolyadenylated RNAs. RICK has identified mitotic regulators amongst other novel RNA-binding proteins with preferential affinity for nonpolyadenylated RNAs, revealed a link between metabolic enzymes/factors and nascent RNAs, and expanded the known RNA-bound proteome of mouse embryonic stem cells. RICK will facilitate an in-depth interrogation of the total RNA-bound proteome in different cells and systems.

Diacylglycerol triggers Rim101 pathway-dependent necrosis in yeast: a model for lipotoxicity.

The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21-dependent sensing complex and the activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity, i.e., high-fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved.

IP3-mediated STIM1 oligomerization requires intact mitochondrial Ca2+ uptake.

Mitochondria contribute to cell signaling by controlling store-operated Ca(2+) entry (SOCE). SOCE is activated by Ca(2+) release from the endoplasmic reticulum (ER), whereupon stromal interacting molecule 1 (STIM1) forms oligomers, redistributes to ER-plasma-membrane junctions and opens plasma membrane Ca(2+) channels. The mechanisms by which mitochondria interfere with the complex process of SOCE are insufficiently clarified. In this study, we used an shRNA approach to investigate the direct involvement of mitochondrial Ca(2+) buffering in SOCE. We demonstrate that knockdown of either of two proteins that are essential for mitochondrial Ca(2+) uptake, the mitochondrial calcium uniporter (MCU) or uncoupling protein 2 (UCP2), results in decelerated STIM1 oligomerization and impaired SOCE following cell stimulation with an inositol-1,4,5-trisphosphate (IP3)-generating agonist. Upon artificially augmented cytosolic Ca(2+) buffering or ER Ca(2+) depletion by sarcoplasmic or endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitors, STIM1 oligomerization did not rely on intact mitochondrial Ca(2+) uptake. However, MCU-dependent mitochondrial sequestration of Ca(2+) entering through the SOCE pathway was essential to prevent slow deactivation of SOCE. Our findings show a stimulus-specific contribution of mitochondrial Ca(2+) uptake to the SOCE machinery, likely through a role in shaping cytosolic Ca(2+) micro-domains.

Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation.

Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPARγ gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle.