Duchenne muscular dystrophy (DMD) is a prevalent childhood neuromuscular disease characterized by progressive skeletal and cardiac muscle degeneration due to dystrophin protein deficiency. Despite ongoing drug development efforts, no cure exists, with limited success in preclinical studies. To expedite DMD drug development, we introduce an innovative organ-on-a-chip (OOC) platform. This microfluidic device sustains up to six 3D patient-derived skeletal muscle tissues, enabling real-time evaluation of anti-DMD treatments. Our in vitro model recreates myotube integrity loss, a hallmark of DMD, by encapsulating myogenic precursors in a fibrin-composite matrix using a PDMS casting mold. Continuous contractile regimes mimic sarcolemmal instability, monitored through tissue contractibility and Creatine Kinase (CK) levels—an established marker of muscle damage. We further enhance our platform with a nanoplasmonic CK biosensor, enabling rapid, label-free, and real-time sarcolemmal damage assessment. Combining these elements, our work demonstrates the potential of OOCs in accelerating drug development for DMD and similar neuromuscular disorders

The risk of falls in patients undergoing orthopedic procedures is particularly significant in terms of health and socioeconomic effects. The literature analyzed closely this risk following procedures performed on the lower limb, but the implications following procedures on the upper limb remain to be investigated. Interestingly, it is not clear whether the increased risk of falling in patients undergoing shoulder surgery is due to preexisting risk factors at surgery or postoperative risk factors, such as anesthesiologic effects, opioid medications used for pain control, or brace use. Only one prospective study examined gait and fall risk in patients using a shoulder abduction brace (SAB) after shoulder surgery, revealing that the brace adversely affected gait kinematics with an increase in the risk of falls. The main purpose of the study was to investigate the influence of SAB on gait parameters in patients undergoing shoulder surgery. Patients undergoing elective shoulder surgery (arthroscopic rotator cuff repair, reverse total shoulder arthroplasty, and Latarjet procedure), who used a 15° SAB in the postoperative period, were included. Conversely, patients age > 65 years old, with impaired lower extremity function (e.g., fracture sequelae, dysmorphism, severe osteo-articular pathology), central and peripheral nervous system pathologies, and cardiac/respiratory/vascular insufficiency were excluded. Participants underwent kinematic analysis at four different assessment times: preoperative (T0), 24 hours after surgery (T1), 1 week after surgery (T2), and 1 week after SAB removal (T3). The tests used for kinematic assessment were the Timed Up and Go (TUG) and the 10-meter test (10MWT), both of which examine functional mobility. Agility and balance were assessed by a TUG test (transitions from sitting to standing and vice versa, walking phase, turn-around), while gait (test time, cadence, speed, and pelvic symmetry) was evaluated by the 10MWT. Gait and functional mobility parameters during 10MWT and TUG tests were assessed using the BTS G-Walk sensor (G-Sensor 2). One-way ANOVA for repeated measures was conducted to detect the effects of SAB on gait parameters and functional mobility over time. Statistical analysis was performed with IBM®SPSS statistics software version 23.0 (SPSS Inc., Chicago, IL, USA), with the significant level set at p<0.05. 83% of the participants had surgery on the right upper limb. A main effect of time for the time of execution (duration) (p=0.01, η2=0.148), speed (p<0.01, η2=0.136), cadence (p<0.01, η2=0.129) and propulsion-right (R) (p<0.05, η2=0.105) and left (L) (p<0.01, η2=0.155) in the 10MWT was found. In the 10MWT, the running time at T1 (9.6±1.6s) was found to be significantly longer than at T2 (9.1±1.3s, p<0.05) and at T3 (9.0±1.3s, p=0.02). Cadence at T1 (109.7±10.9steps/min) was significantly lower than at T2 (114.3 ±9.3steps/min, p<0.01) and T3 (114.3±9.3steps/min, p=0.02). Velocity at T1 (1.1±0.31m/s) was significantly lower than at T2 (1.2± 0.21m/s, p<0.05). No difference was found in the pelvis symmetry index. No significant differences were found during the TUG test except for the final rotation phase with T2 value significantly greater than T3 (1.6±0.4s vs 1.4±0.3s, p<0.05). No statistically significant differences were found between T0 and T2 and between T0 and T3 in any of the parameters analyzed. Propulsion-R was significantly higher at T3 than T1 (p<0.01), whereas propulsion-L was significantly lower at T1 than T0 (p<0.05) and significantly higher at T2 and T3 than T1 (p<0.01). Specifically, the final turning phase was significantly higher at T2 than T3 (p<0.01); no significant differences were found for the duration, sit to stand, mid-turning and stand to sit phases. The results demonstrated that the use of the abduction brace affects functional mobility 24 hours after shoulder surgery but no effects were reported at longer term observations

Calcium is an important element for a wide range of physiological functions including muscle contraction, neuronal activity, exocytosis, blood coagulation and cell communication. In the musculoskeletal system calcium is crucial for the structural integrity of bones, teeth, intervertebral disc and articular cartilage. At the cellular level calcium acts as a second messenger. Calcium signalling uses intracellular calcium ions to drive intracellular communication and signal transduction processes. When calcium enters the cell it exerts allosteric regulatory effects on many enzymes and proteins. Examining the role of calcium in chondrocyte biology is important for understanding the role for this divalent ion in the metabolic modulation of chondrocyte function in health and disease. This includes the study of calcium transport systems such as channels, transporters and pumps involved in calcium homeostasis in chondrocytes and how existing pharmacological drugs act on these transport systems. L-type calcium channel blockers are drugs used as cardiac antiarrhythmics or antihypertensives, depending on whether the drugs have higher affinity for the heart (the phenylalkylamines, like verapamil), or for the blood vessels (the dihydropyridines, like nifedipine). L-type calcium channels are present in many musculoskeletal tissues including skeletal muscle, smooth muscle, bone and cartilage. L-type calcium channel inhibitors like nifedipine used for the treatment of some forms of hypertension modulate calcium-mediated events in chondrocytes under dynamic loading, thus affecting metabolism, osmotic responses and extracellular matrix turnover in cartilage. The aim of our work is to understand the impact of L-type calcium channel inhibitors used for the treatment of hypertension on chondrocytes and on the chondrogenic differentiation of bone marrow derived mesenchymal stem cells (MSCs). This knowledge will enhance our understanding of the development of osteoarthritis (OA) and may lead to new opportunities for chondroprotection and regenerative medicine for OA. We have used electrophysiology to demonstrate L-type calcium currents in chondrocytes immediately after pharmacological activation with the calcium channel opener Bay-K8644. We have also used immunohistochemistry to demonstrate expression of the a1C subunit Ca. v. 1.2 (CACNA1C) in human chondrocytes and MSCs. Inhibitors of L-type calcium channels such as nifedipine downregulate mitochondrial respiration and ATP production in MSCs but not in chondrocytes. Nifedipine inhibits proliferation of chondrocytes and enhances glycolytic capacity in chondrocytes, promoting glycolytic reserve in both MSCs and chondrocytes. Nifedipine can also stimulate chondrogenic differentiation in MSCs (with or without growth factors). Metabolic responses to nifedipine differs in mesenchymal stem cells and chondrocytes highlighting important metabolic differences between these cells. In summary, antihypertensive drugs such as nifedipine can affect the biological function of chondrocytes and MSCs and may modulate the course of OA progression and impact on cartilage repair

Background. We herein report a case of isolated hip pain in a four year old boy. The unique aspect of this case study is the unusual history, presentation, ultrasonography, MRI and blood culture results, which lead to the diagnosis and treatment of adductor pyomyositis with a rare organism (Streptococcus Mitis) in a temperate country. The objectives of this case study is to discuss the key learning outcomes with respect to assessment and management of this case. Methods. The patient presented with a one day history of malaise, fever, left groin pain and inability to weight bear on the left leg. There was no history of any trauma, predisposing infections or recent travel. A working diagnosis of transient synovitis / septic arthritis of the hip was made on clinical examination. Results. Plain radiograph and ultrasound of the hip was normal with no effusion. Two consecutive blood cultures suggested Streptococcus Mitis bacteriaemia and MRI scan confirmed pyomyositis of the left hip adductors that was too small to drain. Streptococcus Mitis is a normal commensal organism of the oral cavity however it can lead to opportunistic infections particularly endocarditis. Echocardiogram revealed no cardiac complications, in particular no endocarditic vegetation. Patient was treated with intravenous benzylpenicillin for a week followed by oral phenoxymethylpenicillin for a week. Conclusion. Adductor pyomyositis must be considered as a differential diagnosis in a child with unusual presentation of hip pain. When an ultrasound is normal, MRI scan is warranted to confirm diagnosis. Septic screen should include blood cultures. The commonest causative organisms are the Staphylococcus family. However if Streptococcus Mitis is isolated, cardiac sources of infection resulting in septic emboli must be investigated. Repeated MRI scans are required particularly if the patient does not respond to medical management. Level of Evidence. IV

Introduction. The interstitial fluid of bone fluid flow is supplied by flowing blood. Blood flow is determined by three kinds of muscles: cardiac, smooth, and skeletal. Cardiac muscle establishes baseline blood pressure. Smooth muscle controls vessel diameter and skeletal muscle creates intermittent intravascular pressure pulses. For the tibia the relevant skeletal muscle is the gastrocnemius which functions as a muscle pump. This study tested the hypotheses: 1) skeletal muscle-caused pressure pulses increase cortical blood flow, 2) extravasation of vascular fluid and, consequently, interstitial bone fluid flow are enhanced by resultant increased microvascular pressure and 3) bone healing is enhanced by increased bone fluid flow. Methods. Eighteen skeletally mature female New Zealand white rabbits were implanted with bone chamber windows (BCIs) as described previously. The windows were exposed at three weeks and observed weekly until Week 10 using intravital microscopy. During observation, the subject was suspended in prone position in a mesh fabric torso sling jacket so as to eliminate gravity-based reaction forces. Electrodes of a transcutaneous electrical nerve stimulator (TENS) were gel-glued at each rabbits gastroc-soleus position; but activated only in the 11 experimentals. A 4Hz 2.8 ± 1.3V impulse was delivered for 60 minutes. Still and video images were obtained at 0, 2, and 60 minutes following injection of 1μm fluorescent microspheres. Each such injection was followed by injection of 70 kD FITC- or RITC-dextran to define vascularity and capillary filtration. Additional still images were obtained at 5, 30, and 55 minutes. Muscle contraction forces during TENS were obtained acutely following the Week 10 observation with a Futek force transducer cell through an attached nylon suture. Bone mineral density was obtained at Week 3 and Week 10 with a Stratec pQCT and associated software. Data were analyzed statistically using a Wilcoxon signed rank test. Results. All three hypotheses were supported statistically by the data. The average force produced by TENS stimulated gastrocnemius contraction was 18.98 ± 9.42 N/kg muscle. This produced a microstrain of 192μe in bone around the BCI. Bloodflow results are shown in the figure. On average, flow decreased in controls by 12.6% and increased in experimentals by about 2%. Capillary filtration in experimentals was about 34.6% higher than controls after 60 minutes of TENS. Bone formation rate was 62.5% higher with TENS. Conclusion. In order to understand the role of fluid flows in bone physiology, we need to know the how and where of movement. These results suggest the part played by skeletal muscle in bone fluid movement cannot be ignored. As with many evolutionary adaptations, the muscle pump's hydrodynamic contribution to bone may be redundant and merely serve as a backup to percolation from poroelastic deformation. On the other hand, it may be crucial in disuse osteoporosis instigating conditions such as microgravity. The measured increases in capillary filtration and blood flow suggest that intravascular pressure which drives the former and resultant percolation has been increased by the muscle pump. It follows that fluid shear on cortical bone cells also increased. The challenge now is to obtain local flow measurements that would tell us how much

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice. Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1. +. ) and stem cell factor receptor, CD117 (c-kit. +. ) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1. +. mononuclear cell (MNC. sca-1+. ) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC. sca-1+,c-kit+. counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours. Sca-1. +. mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium. Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures

The ‘cement reaction’ is a recognised cardio-respiratory response to methylmethacrylate bone cement, characterised by hypotension, reduced cardiac output, and on occasion fatal circulatory collapse. It is seen in 0.5-1% of cemented hip arthroplasties during the insertion and pressurisation of cement into the femur, and is believed to be secondary to marrow thromboembolism, the vasodilatory effect of methylmethacrylate, or a combination of the two. A number of steps, within the operating surgeon's control, can be undertaken to reduce the risk of the ‘cement reaction’ occurring. An e-mail based questionnaire was sent to all trainees and consultants in the West of Scotland containing eight questions relating to cementing technique when performing hemiarthroplasty of the hip. The questions related to measures to reduce the potential for ‘cement reaction’, e.g.: whether or not they routinely use a cement restrictor. Seventy-two complete replies were received. For five of the eight measures, the surgeons routinely employed the suggested practices. For the remaining three, the consensus opinion was contrary to the suggested practice for reduction of the risk of ‘cement reaction’. These were with respect to the surgical approach employed, whether or not to attempt to remove all cancellous bone from the proximal femur, and the use, or not, of a venting tube during cement insertion. In all three cases, the difference was statistically significant on chi-squared testing. The cohort of surgeons questioned routinely employ more than half of the methods suggested to reduce the potential for ‘cement reaction’ in hemiarthroplasty of the hip. Further surveys of why they do, or do not, undertake certain practices during cementing would help improve awareness of ‘cement reaction’, and perhaps reduce the incidence of this potentially fatal phenomenon

Hyponatraemia is one of the most common electrolyte disorders in the elderly and has considerable associated morbidity and mortality. In this study we report the prevalence and independent risk factors for the development of post-operative hyponatraemia after surgery for hip fracture. We conducted a retrospective cohort study of 144 consecutive patients who underwent surgery after sustaining a hip fracture. Patient medical case-notes, operative notes and online biochemistry results were used to obtain relevant data which was entered into a database. Pre-operative (30/144, 21%) and post-operative hyponatraemia (49/144, 34%) was common. However, most cases were mild (plasma sodium >130 mmol/l) and only 1% of pre-operative and 6% of post-operative patients had moderate/severe hyponatraemia (plasma sodium <130mmol/l). One of 3 post-operative deaths involved a patient with moderate hyponatraemia as a consequence of severe congestive cardiac failure. In order to determine the independent relationship between several reported risk factors and hyponatraemia we constructed a multivariable logistic regression model. Female gender, pre-operative hyponatraemia and hypotonic fluid administration were all significantly associated with the development of post-operative hyponatraemia. Age and thiazide diuretics both had positive risk associations however were not statistically significant. Hyponatraemia is a common problem in hip fracture patients. While the majority of cases in this series were mild, 6% of patients suffered from moderate/severe hyponatraemia post-operatively. Female gender, pre-operative hyponatraemia and hypotonic fluid administration are all important and independent risk factors for the development of hyponatraemia. Hypotonic intravenous fluids should be avoided unless clinically indicated in this patient group

Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

Objectives

We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change.

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’).

Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared.

Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model.

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically.

Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets.

Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel.

We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains.

Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion.