The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development. Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot.Aims
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Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
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Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient’s lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations.Aims
Methods
The changes in serum adjusted ionised calcium and parathyroid hormone (PTH) were prospectively studied in 32 patients with isolated tibial fractures, treated conservatively. We measured serum
The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model. We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics.Aims
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To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood. Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR.Aims
Methods
1. The syndrome of osteoporosis is reviewed and its various causes are mentioned. Osteoporosis in youngish patients without any demonstrable cause is referred to as "idiopathic." The scant literature on this condition is reviewed. Its clinical, radiological, biochemical and histological features are considered. 2. A series of thirty-eight cases is analysed, and illustrative case histories are described. The peculiarities of the disease as it is seen in women are discussed, particularly the relationship to pregnancy and lactation, which appear to act as precipitating factors, rather than being primarily causative. 3. The differential diagnosis is discussed. Osteogenesis imperfecta may not always be easy to distinguish; since it is really a "congenital osteoporosis" this is hardly surprising. 4. The following possible etiological factors are propounded (apart from pregnancy): nutritional, occupational, lack of sex hormone, liver dysfunction, loss of protein, diabetes, premature ageing, hypophosphatasia, "alarm reaction," and inheritance. None of them can be incriminated except in the odd case. The relationship between osteoporosis and idiopathic hypercalcuria is mentioned. The only conclusion regarding etiology is that some people are simply more prone to bone loss than are others, and in these a variety of accentuating factors may render the disorder clinically apparent. 5. The treatment of the condition is unsatisfactory, although occasionally a positive calcium balance may be obtained with sex hormones or intravenous infusion of plasma
The primary aim was to determine the influence of COVID-19 on 30-day mortality following hip fracture. Secondary aims were to determine predictors of COVID-19 status on presentation and later in the admission; the rate of hospital acquired COVID-19; and the predictive value of negative swabs on admission. A nationwide multicentre retrospective cohort study was conducted of all patients presenting with a hip fracture to 17 Scottish centres in March and April 2020. Demographics, presentation blood tests, COVID-19 status, Nottingham Hip Fracture Score, management, length of stay, and 30-day mortality were recorded.Aims
Methods
Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.Aims
Methods
This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.Aims
Methods
Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.Aims
Methods
Patients who sustain neck of femur fractures are at high risk of malnutrition. Our intention was to assess to what extent malnutrition was associated with worse patient outcomes. A total of 1,199 patients with femoral neck fractures presented to a large UK teaching hospital over a three-year period. All patients had nutritional assessments performed using the Malnutrition Universal Screening Tool (MUST). Malnutrition risk was compared to mortality, length of hospital stay, and discharge destination using logistic regression. Adjustments were made for covariates to identify whether malnutrition risk independently affected these outcomes.Aims
Methods
Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken.Aims
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To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors.Aims
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To compare rates of serious adverse events in patients undergoing revision knee arthroplasty with consideration of the indication for revision (urgent versus elective indications), and compare these with primary arthroplasty and re-revision arthroplasty. Patients undergoing primary knee arthroplasty were identified in the national Hospital Episode Statistics (HES) between 1 April 1997 to 31 March 2017. Subsequent revision and re-revision arthroplasty procedures in the same patients and same knee were identified. The primary outcome was 90-day mortality and a logistic regression model was used to investigate factors associated with 90-day mortality and secondary adverse outcomes, including infection (undergoing surgery), pulmonary embolism, myocardial infarction, and stroke. Urgent indications for revision arthroplasty were defined as infection or fracture, and all other indications (e.g. loosening, instability, wear) were included in the elective indications cohort.Aims
Methods
The purpose of this study was to develop a personalized outcome prediction tool, to be used with knee arthroplasty patients, that predicts outcomes (lengths of stay (LOS), 90 day readmission, and one-year patient-reported outcome measures (PROMs) on an individual basis and allows for dynamic modifiable risk factors. Data were prospectively collected on all patients who underwent total or unicompartmental knee arthroplasty at a between July 2015 and June 2018. Cohort 1 (n = 5,958) was utilized to develop models for LOS and 90 day readmission. Cohort 2 (n = 2,391, surgery date 2015 to 2017) was utilized to develop models for one-year improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score, KOOS function score, and KOOS quality of life (QOL) score. Model accuracies within the imputed data set were assessed through cross-validation with root mean square errors (RMSEs) and mean absolute errors (MAEs) for the LOS and PROMs models, and the index of prediction accuracy (IPA), and area under the curve (AUC) for the readmission models. Model accuracies in new patient data sets were assessed with AUC.Aims
Methods
MicroRNA-183 ( Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (Aims
Methods
Periprosthetic hip and knee infection remains one of the most severe complications following arthroplasty, with an incidence between 0.5% to 1%. This study compares the outcomes of revision surgery for periprosthetic joint infection (PJI) following hip and knee arthroplasty prior to and after implementation of a specialist PJI multidisciplinary team (MDT). Data was retrospectively analyzed from a single centre. In all, 29 consecutive joints prior to the implementation of an infection MDT in November 2016 were compared with 29 consecutive joints subsequent to the MDT conception. All individuals who underwent a debridement antibiotics and implant retention (DAIR) procedure, a one-stage revision, or a two-stage revision for an acute or chronic PJI in this time period were included. The definition of successfully treated PJI was based on the Delphi international multidisciplinary consensus.Aims
Methods
Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Aims
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