Recent ucsdsom_ors_oapdeposits items

Percutaneous analgesic device enabling both local anesthetic delivery and electrical stimulation (neuromodulation) of peripheral nerves: a pilot feasibility study (case series)

Thu, 6 Nov 2025 00:00:00 +0000

BACKGROUND: A novel device integrating both local anesthetic delivery and peripheral nerve stimulation (PNS) to treat postoperative pain is under development. The device uses a catheter-over-needle design that permits ultrasound-guided percutaneous insertion. An integrated electrode and pulse generator enable PNS for up to 28 days. Such an approach may represent a paradigm shift in postoperative pain management by enabling the delivery of (1) a single-injection peripheral nerve block, (2) a continuous peripheral nerve block, and (3) neuromodulation-all through a single system that can be placed in a timeframe comparable with that of a traditional single-injection nerve block. The current prospective pilot study was executed under a US Food and Drug Investigational Device Exemption to develop insertion and management protocols, as well as assess the feasibility and safety of using the device to treat postoperative pain. METHODS: Preoperatively, adults (n=20) undergoing moderate-to-severely...

Choline in immunity: a key regulator of immune cell activation and function

Thu, 11 Sep 2025 00:00:00 +0000

Nutrient availability is a strong determinant of cell function. Immune cells, which must rapidly activate transcriptional, proteomic, and metabolic programs to fulfill their functional roles, depend on nutrient supply to generate the building blocks needed for the production of immune effectors. While glucose, glutamine, and amino acids are well-recognized as critical energy sources and carbon donors during immune activation, the contribution of choline, a vitamin-like metabolite, has been overlooked. Once taken up by cells, choline plays a vital role in several biological processes. It is a precursor for phosphatidylcholine, the primary phospholipid in cellular membranes, and is also essential for synthesizing the neurotransmitter acetylcholine. Additionally, when directed toward mitochondria and betaine synthesis, choline serves as a methyl donor for histone and protein methylation, key processes that regulate gene expression and cellular activity. In this review, we examine...

Animal Models of Disc Degeneration Using Puncture Injury: A 20 Year Perspective

Sat, 2 Aug 2025 00:00:00 +0000

Background: Intervertebral disc (IVD) degeneration (IVDD) is a major cause of global disability. Three papers on puncture models of IVDD were published 20 years ago, transforming the application of preclinical animal models for pathophysiology and therapeutic screening studies. Methods: Narrative review describing historic and current usage of preclinical puncture models of IVDD, documenting their introduction to induce slow, progressive IVDD and evolution to include many injury types broadly called "puncture models." IVDD puncture models were reviewed for variability in species, needle gauge, puncture depth, IVD compartment, injectates, angle of puncture, motion of needle, and IVDD phenotype mimicked. Results: IVD puncture models gained prominence following seminal 2005 publications describing needle puncture to induce slow, progressive IVDD for screening therapies. Specific details of puncture methods were described for controlling injury severity to induce IVDD phenotypes,...

Factors Associated With 30-Day Readmission in Hand Surgery Patients.

Sat, 12 Apr 2025 00:00:00 +0000

BACKGROUND: Surgical patient hospital readmissions are costly to the health care system. The Affordable Care Act Hospital Readmissions Reduction Program introduced penalties for high hospital readmission rates. We performed a retrospective study evaluating factors associated with readmission in hand surgical inpatients. METHODS: We performed a retrospective chart review on 566 patients admitted to a level 1 trauma center for hand trauma or infection from January 1, 2016, to December 31, 2019. Data included demographics, social history, medical problems, comorbidities, procedure details, and admission and readmission details. A multivariable regression analysis was performed to identify factors associated with hospital readmission within 30 days. RESULTS: Cigarette smoking (P = .048), bite wound (P = .038), laceration wound (P = .028), laceration repair (P < .01), open reduction internal fixation (P = .041), and disposition to a skilled nursing...

Descriptive Epidemiology of Venous Thromboembolism in Pediatric Orthopedic Patients

Fri, 11 Apr 2025 00:00:00 +0000

Background: Consensus regarding which children within orthopedics would benefit from venous thromboembolism (VTE) prophylaxis is lacking. Our objective was to explore the incidence and epidemiology of VTE within pediatric orthopedics through a multicenter review across the United States. Methods: Encompassing 13 pediatric centers nationwide, VTE incidence rates with 95% confidence interval (CIs) were determined for all pediatric nonorthopedic patients (PNOPs) in general (age 0-18 years) and compared with pediatric orthopedic patients (POPs) from both inpatient and outpatient settings between 2014 and 2017. Demographics, risk factors, presence of prophylaxis, treatment, and outcomes for POP VTEs were analyzed using descriptive statistics. Results: Of 10,040,937 total unique patients, the overall 4-year VTE incidence for PNOPs was 2.1 per 10,000 patients (CI 2.01-2.19). Of 141,545 POPs, the VTE incidence was 8.0 per 10,000 patients (CI 6.61-9.63). The weighted median age for POP...

Intraoperative Neuromonitoring During Periacetabular Osteotomy Provides Actionable Alerts

Fri, 4 Apr 2025 00:00:00 +0000

Background: Bernese periacetabular osteotomy (PAO) for symptomatic acetabular dysplasia and femoroacetabular impingement has become increasingly common, with a corresponding increase in the incidence of adverse outcomes. The rate of major neurological injury (excluding lateral femoral cutaneous nerve injury) during PAO has been reported to be around 2%. Previous publications have recommended the use of intraoperative neuromonitoring (IONM) to mitigate risk of major neurological injury during PAO, but its use has not become universal among PAO surgeons as it has among spine surgeons. The purpose of this study was to report the incidence and clinical significance of IONM alerts in a single-surgeon, consecutive cohort of patients treated with Bernese PAO. Methods: After a permanent peripheral nerve injury during a PAO without IONM, IONM has been used at our institution in every PAO. Motor evoked potentials and somatosensory monitoring are performed throughout the procedure. We conducted...

Intrinsic Skeletal Muscle Function and Contraction-Stimulated Glucose Uptake Do Not Vary by Time-of-Day in Mice

Mon, 24 Mar 2025 00:00:00 +0000

A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at 4 times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the 4 time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of...

Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics

Mon, 17 Mar 2025 00:00:00 +0000

Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood–brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and...

Comparison of tibiofibular syndesmosis stability following treatment of proximal, middle, and distal third fibula fractures

Fri, 31 Jan 2025 00:00:00 +0000

PurposeWhile treatment modalities for Maisonneuve fractures involving the proximal third of the fibula are established, no studies to date have reported outcomes associated with syndesmotic-only fixation of middle third fibular shaft fractures. The purpose of this study was to evaluate outcomes associated with syndesmotic-only fixation in the treatment of Maisonneuve fractures involving the middle third of the fibula.MethodsA retrospective review was conducted on 257 cases of syndesmotic ankle instability with associated fibular fractures at a level 1 trauma center between 2013 and 2023. Patients were divided into cohorts based on fibular fracture location in the proximal, middle, or distal third of the fibula. The Chi-square test of independence, two-sample t-test, and analysis of variance were used to compare outcome measures between cohorts.ResultsSixty-six patients were identified including 48% (n = 32) with proximal third fibular fractures, 20% (n = 13) with middle third...

From Voxels to Physiology: A Review of Diffusion Magnetic Resonance Imaging Applications in Skeletal Muscle

Wed, 22 Jan 2025 00:00:00 +0000

Skeletal muscle has a classic structure function relationship; both skeletal muscle microstructure and architecture are directly related to force generating capacity. Biopsy, the gold standard for evaluating muscle microstructure, is highly invasive, destructive to muscle, and provides only a small amount of information about the entire volume of a muscle. Similarly, muscle fiber lengths and pennation angles, key features of muscle architecture predictive of muscle function, are traditionally studied via cadaveric dissection. Noninvasive techniques such as diffusion magnetic resonance imaging (dMRI) offer quantitative approaches to study skeletal muscle microstructure and architecture. Despite its prevalence in applications for musculoskeletal research, clinical adoption is hindered by a lack of understanding regarding its sensitivity to clinically important biomarkers such as muscle fiber cross-sectional area. This review aims to elucidate how dMRI has been utilized to study...

Do Computerized Tomography Scans Change Management in Carpometacarpal Dislocations and Fracture-Dislocations?

Wed, 25 Dec 2024 00:00:00 +0000

BACKGROUND: Concomitant carpal injuries with dislocations and fracture-dislocations of the carpometacarpal joints (CMCD/FD) are often hard to see on plain radiographs, making advanced imaging a useful diagnostic adjunct. We aim to: (1) characterize bony injury patterns with CMCD/FD; and (2) determine the frequency that preoperative computed tomography (CT) scans change surgical management. METHODS: A retrospective review was performed of patients who underwent operative fixation of CMCD/FD from 2006 to 2021. X-ray and CT scan diagnoses were reviewed and correlated to intraoperative findings and procedures performed. Statistical analyses were performed to evaluate the frequency in which CT scans changed management and the frequency of new intraoperative diagnoses. RESULTS: Seventy-five patients were identified. All patients had a preoperative x-ray, and 27 patients (36%) additionally had a CT scan. Patients who sustained high-velocity trauma were significantly more likely to obtain...

Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series

Tue, 24 Dec 2024 00:00:00 +0000

Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi-system disorder associated with germline or mosaic variants within the PI3K-mTOR-GATOR1 signaling pathways. Patients with HME typically develop drug-resistant epilepsy necessitating extensive evaluation, hemispherectomy, and long-term management. We describe the role of a multidisciplinary team (MDT) for the diagnosis and management of recent patients with HME at UCLA who underwent hemispherectomy. Genetic evaluation identified nine patients with the following variants: NPRL3 x2 germline, PIK3CA mosaicism x4, MTOR mosaicism x1, AKT3 mosaicism x1, unknown x1. Each patient's MDT comprised 4-9 specialties. One child with a MTOR variant had persistent epilepsy after hemispherectomy, but addition of everolimus resulted in an 80% decrease in seizure frequency. Another child with hemihypertrophy and PIK3CA mosaic variant was offered targeted PIK3CA inhibitor treatment, alpelisib, for overgrowth. A third child...

Non-invasive evaluation of Achilles tendon and its enthesis using ultrashort echo time adiabatic T1ρ (UTE-Adiab-T1ρ) magnetic resonance imaging (MRI) in psoriatic arthritis

Mon, 23 Dec 2024 00:00:00 +0000

PURPOSE: This cross-sectional study investigates the utility of the quantitative ultrashort echo time (UTE) adiabatic T_1ρ (UTE-Adiab-T_1ρ) magnetic resonance imaging (MRI) in detecting potential differences in Achilles tendons and entheses of patients with psoriatic arthritis disease (PsA) compared with asymptomatic volunteers. MATERIAL AND METHOD: The Achilles tendons of forty-four PsA patients (59 ± 15 years old, 38 % female) and thirty-seven asymptomatic volunteers (32 ± 10 years old, 51 % female) were scanned on a 3 T clinical scanner in the sagittal plane using a 3-inch surface coil. The 3D UTE-Adiab-T_1ρ sequences with fat saturation (FS) were used to measure UTE-Adiab-T_1ρ. Tenderness of the tendons, the SF-12 health survey, and visual analog scale (VAS) were recorded for the patients. The Kruskal Wallis test was used to examine the differences in UTE-Adiab-T1_ρ values between...

Expert-Based Consensus on the Principles of Pavlik Harness Management of Developmental Dysplasia of the Hip

Wed, 11 Dec 2024 00:00:00 +0000

Developmental dysplasia of the hip (DDH) is the most common orthopaedic disorder in newborns. While the Pavlik harness is one of the most frequently used treatments for DDH, there is immense variability in treatment parameters reported in the literature and in clinical practice, leading to difficulties in standardizing teaching and comparing outcomes. In the absence of definitive quantitative evidence for the optimal Pavlik harness management strategy for DDH, we addressed this problem by obtaining international expert-based consensus on the subject. METHODS: An initial list of items relevant to Pavlik harness treatment was derived by a review of the literature. Delphi methodology was used to guide serial rounds of surveying and obtaining feedback from content matter experts from the International Hip Dysplasia Institute (IHDI), which continued in the same manner until consensus based on standard statistical analysis was reached. This was followed by a corroboration of face validity...

A Maternal Western-Style Diet Impairs Skeletal Muscle Lipid Metabolism in Adolescent Japanese Macaques.

Sat, 7 Dec 2024 00:00:00 +0000

Maternal consumption of a Western-style diet (mWD) during pregnancy alters fatty acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact of these fetal adaptations and the pathways underlying disordered lipid metabolism are incompletely understood. Therefore, we tested whether a mWD chronically fed to lean, insulin-sensitive adult Japanese macaques throughout pregnancy and lactation would impact skeletal muscle oxidative capacity and lipid metabolism in adolescent offspring fed a postweaning (pw) Western-style diet (WD) or control diet (CD). Although body weight was not different, retroperitoneal fat mass and subscapular skinfold thickness were significantly higher in pwWD offspring consistent with elevated fasting insulin and glucose. Maximal complex I (CI)-dependent respiration in muscle was lower in mWD offspring in the presence of fatty acids, suggesting that mWD impacts muscle integration of lipid with nonlipid oxidation. Abundance of...

Human Septal Cartilage Tissue Engineering: Current Methodologies and Future Directions

Fri, 6 Dec 2024 00:00:00 +0000

Nasal septal cartilage tissue engineering is a promising and dynamic field with the potential to provide surgical options for patients with complex reconstruction needs and mitigate the risks incurred by other tissue sources. Developments in cell source selection, cell expansion, scaffold creation, and three-dimensional (3D) bioprinting have advanced the field in recent years. The usage of medicinal signaling cells and nasal chondroprogenitor cells can enhance chondrocyte proliferation, stimulate chondrocyte growth, and limit chondrocyte dedifferentiate. New scaffolds combined with recent innovations in 3D bioprinting have allowed for the creation of more durable and customizable constructs. Future developments may increase technical accessibility and manufacturability, and lower costs, to help incorporate these methods into pre-clinical studies and clinical applications of septal cartilage tissue engineering.

Ultrashort echo time MRI detects significantly lower collagen but higher pore water in the tibial cortex of female patients with osteopenia and osteoporosis

Thu, 5 Dec 2024 00:00:00 +0000

Ultrashort echo time (UTE) MRI can quantify the major proton pool densities in cortical bone, including total (TWPD), bound (BWPD), and pore water (PWPD) proton densities, as well as the macromolecular proton density (MMPD), associated with the collagen content, which is calculated using macromolecular fraction (MMF) from UTE magnetization transfer (UTE-MT) modeling. This study aimed to investigate the differences in water and collagen contents in tibial cortical bone, between female osteopenia (OPe) patients, osteoporosis (OPo) patients, and young participants (Young). Being postmenopausal and above 55 yr old were the inclusion criteria for OPe and OPo groups. The tibial shaft of 14 OPe (72.5 ± 6.8 yr old), 31 OPo (72.0 ± 6.4 yr old), and 31 young subjects (28.0 ± 6.1 yr old) were scanned using a knee coil on a clinical 3T scanner. Basic UTE, inversion recovery UTE, and UTE-MT sequences were performed. Investigated biomarkers were compared between groups using...

Pharmacokinetics, Fecal Output, and Grimace Scores in Rabbits Given Long-acting Buprenorphine or Fentanyl for Postsurgical Analgesia.

Wed, 13 Nov 2024 00:00:00 +0000

The New Zealand white rabbit (Oryctolagus cuniculus) is a frequently used surgical model. Pain management after surgery is a critical aspect of animal welfare. Recently, a long-acting buprenorphine formulation (Ethiqa XR; EXR) was approved for use in rats and mice but has not yet been investigated in rabbits. The current study aimed to determine whether a single subcutaneous dose of 0.15mg/kg of EXR could achieve and maintain therapeutic buprenorphine plasma concentrations (0.1ng/mL) for 72h in male and female rabbits. We also evaluated the safety profiles of EXR and the fentanyl patch (FP) by assessing fecal output after surgery, because opioids are known to decrease intestinal motility. Behavior and pain scores were compared for rabbits that received either EXR or the FP after undergoing an annulus puncture procedure to induce osteoarthritis. EXR at 0.15mg/kg SC provided a shorter time to onset and sustained analgesia for 72h in male and female rabbits, whereas the FP provided...

Growth modulation response in vertebral body tethering depends primarily on magnitude of concave vertebral body growth

Wed, 13 Nov 2024 00:00:00 +0000

PurposeThere is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT.MethodsA multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years.ResultsFifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p < 0.001), 3D spine length growth (r = 0.36, p = 0.008), and decreased convex disc height (r = − 0.42,...

Deep Convolutional Neural Network for Dedicated Regions-of-Interest Based Multi-Parameter Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of the Knee Joint

Tue, 12 Nov 2024 00:00:00 +0000

We proposed an end-to-end deep learning convolutional neural network (DCNN) for region-of-interest based multi-parameter quantification (RMQ-Net) to accelerate quantitative ultrashort echo time (UTE) MRI of the knee joint with automatic multi-tissue segmentation and relaxometry mapping. The study involved UTE-based T1 (UTE-T1) and Adiabatic T1ρ (UTE-AdiabT1ρ) mapping of the knee joint of 65 human subjects, including 20 normal controls, 29 with doubtful-minimal osteoarthritis (OA), and 16 with moderate-severe OA. Comparison studies were performed on UTE-T1 and UTE-AdiabT1ρ measurements using 100%, 43%, 26%, and 18% UTE MRI data as the inputs and the effects on the prediction quality of the RMQ-Net. The RMQ-net was modified and retrained accordingly with different combinations of inputs. Both ROI-based and voxel-based Pearson correlation analyses were performed. High Pearson correlation coefficients were achieved between the RMQ-Net predicted UTE-T1 and UTE-AdiabT1ρ results and...

Correction: Defining the volume of consultations for musculoskeletal infection encountered by pediatric orthopaedic services in the United States

Mon, 16 Sep 2024 00:00:00 +0000

[This corrects the article DOI: 10.1371/journal.pone.0234055.].

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

Fri, 30 Aug 2024 00:00:00 +0000

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief,...

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Fri, 30 Aug 2024 00:00:00 +0000

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository...

Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

Fri, 30 Aug 2024 00:00:00 +0000

Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model to examine the impact of a maternal Western-style diet (WSD) alone, or in combination with obesity (Ob/WSD), on fetal skeletal muscle metabolism studied in the early third trimester. We find that fetal muscle responds to Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and metabolic switches (CPT-1, PDK4) that promote lipid utilization over glucose oxidation. Ob/WSD fetuses also had reduced mitochondrial content, diminished oxidative capacity, and lower mitochondrial efficiency in muscle. The decrease in oxidative capacity and glucose metabolism was persistent in primary myotubes from Ob/WSD fetuses despite no additional lipid-induced stress. Switching obese mothers to a healthy diet prior to pregnancy did...

Calorie Restriction-Induced Increase in Skeletal Muscle Insulin Sensitivity Is Not Prevented by Overexpression of the p55α Subunit of Phosphoinositide 3-Kinase

Fri, 30 Aug 2024 00:00:00 +0000

Introduction: The Phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in skeletal muscle insulin-stimulated glucose uptake. While whole-body and tissue specific knockout (KO) of individual or combinations of the regulatory subunits of PI3K (p85α, p55α, and p50α or p85β); increase insulin sensitivity, no study has examined whether increasing the expression of the individual regulatory subunits would inhibit insulin action in vivo. Therefore, the objective of this study was to determine whether skeletal muscle-specific overexpression of the p55α regulatory subunit of PI3K impairs skeletal muscle insulin sensitivity, or prevents its enhancement by caloric restriction. Methods: We developed a novel "floxed" mouse that, through the Cre-LoxP approach, allows for tamoxifen (TMX)-inducible and skeletal muscle-specific overexpression of the p55α subunit of PI3K (referred to as, 'p55α-mOX'). Beginning at 10 weeks of age, p55α-mOX mice and their...

Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis

Fri, 30 Aug 2024 00:00:00 +0000

AIMS: Activation of the NAD⁺ dependent protein deacetylase SIRT1 has been proposed as a therapeutic strategy to treat mitochondrial dysfunction and insulin resistance in skeletal muscle. However, lifelong overexpression of SIRT1 in skeletal muscle does not improve parameters of mitochondrial function and insulin sensitivity. In this study, we investigated whether temporal overexpression of SIRT1 in muscle of adult mice would affect skeletal muscle mitochondrial function and insulin sensitivity. METHODS: To circumvent potential effects of germline SIRT1 overexpression, we utilized an inducible model of SIRT1 overexpression in skeletal muscle of adult mice (i-mOX). Insulin sensitivity was assessed by 2-deoxyglucose uptake, muscle maximal respiratory function by high-resolution respirometry and systemic energy expenditure was assessed by whole body calorimetry. RESULTS: Although SIRT1 was highly, and specifically, overexpressed in skeletal muscle of i-mOX compared to WT...

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

Fri, 30 Aug 2024 00:00:00 +0000

BACKGROUND: Reversible ε-amino acetylation of lysine residues regulates transcription as well as metabolic flux; however, roles for specific lysine acetyltransferases in skeletal muscle physiology and function are unknown. In this study, we investigated the role of the related acetyltransferases p300 and cAMP response element-binding protein-binding protein (CBP) in skeletal muscle transcriptional homeostasis and physiology in adult mice. METHODS: Mice with skeletal muscle-specific and inducible knockout of p300 and CBP (PCKO) were generated by crossing mice with a tamoxifen-inducible Cre recombinase expressed under the human α-skeletal actin promoter with mice having LoxP sites flanking exon 9 of the Ep300 and Crebbp genes. Knockout of PCKO was induced at 13-15 weeks of age via oral gavage of tamoxifen for 5 days to both PCKO and littermate control [wildtype (WT)] mice. Body composition, food intake, and muscle function were assessed on day 0 (D0) through 5 (D5). Microarray and...

Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report

Fri, 30 Aug 2024 00:00:00 +0000

While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity...

Exercise and high-fat feeding remodel transcript-metabolite interactive networks in mouse skeletal muscle

Fri, 30 Aug 2024 00:00:00 +0000

Enhanced coverage and sensitivity of next-generation ‘omic’ platforms has allowed the characterization of gene, metabolite and protein responses in highly metabolic tissues, such as, skeletal muscle. A limitation, however, is the capability to determine interaction between dynamic biological networks. To address this limitation, we applied Weighted Analyte Correlation Network Analysis (WACNA) to RNA-seq and metabolomic datasets to identify correlated subnetworks of transcripts and metabolites in response to a high-fat diet (HFD)-induced obesity and/or exercise. HFD altered skeletal muscle lipid profiles and up-regulated genes involved in lipid catabolism, while decreasing 241 exercise-responsive genes related to skeletal muscle plasticity. WACNA identified the interplay between transcript and metabolite subnetworks linked to lipid metabolism, inflammation and glycerophospholipid metabolism that were associated with IL6, AMPK and PPAR signal pathways. Collectively, this novel experimental...

SIRT1 regulates nuclear number and domain size in skeletal muscle fibers

Fri, 30 Aug 2024 00:00:00 +0000

Skeletal muscle fibers are giant multinucleated cells wherein individual nuclei govern the protein synthesis in a finite volume of cytoplasm; this is termed the myonuclear domain (MND). The factors that control MND size remain to be defined. In the present study, we studied the contribution of the NAD⁺ -dependent deacetylase, sirtuin 1 (SIRT1), to the regulation of nuclear number and MND size. For this, we isolated myofibers from mice with tissue-specific inactivation (mKO) or inducible overexpression (imOX) of SIRT1 and analyzed the 3D organisation of myonuclei. In imOX mice, the number of nuclei was increased whilst the average MND size was decreased as compared to littermate controls. Our findings were the opposite in mKO mice. Muscle stem cell (satellite cell) numbers were reduced in mKO muscles, a possible explanation for the lower density of myonuclei in these mice; however, no change was observed in imOX mice, suggesting that other factors might also be involved,...

Assessment of fitting methods and variability of IVIM parameters in muscles of the lumbar spine at rest

Wed, 21 Aug 2024 00:00:00 +0000

Intravoxel incoherent motion (IVIM) MRI provides insight into tissue diffusion and perfusion. Here, estimates of perfusion fraction ( ), pseudo-diffusion coefficient ( ), and diffusion coefficient ( ) obtained via different fitting methods are compared to ascertain (1) the optimal analysis strategy for muscles of the lumbar spine and (2) repeatability of IVIM parameters in skeletal muscle at rest. Diffusion-weighted images were acquired in the lumbar spine at rest in 15 healthy participants. Data were fit to the bi-exponential IVIM model to estimate and using three variably segmented approaches based on non-linear least squares fitting, and a Bayesian fitting method. Assuming that perfusion and diffusion are temporally stable in skeletal muscle at rest, and spatially uniform within a spinal segment, the optimal analysis strategy was determined as the approach with the lowest temporal or spatial variation and smallest residual between measured and fit data. Inter-session repeatability...

Osteochondral lesions in Wilson’s disease: case report and literature review

Thu, 15 Aug 2024 00:00:00 +0000

Background: Wilson's disease (WD) is a rare genetic disorder characterized by copper accumulation in the body, leading to a spectrum of health issues, such as liver disease, neurological disturbances, and psychiatric disorders. In recent years, there has been increasing recognition that WD can also result in osteoarticular defects. Research has shed light on the potential of WD to cause these findings, which in some instances, can progress to osteoarthritis and persistent pain. However, the exact pathophysiological process through which WD leads to osteochondral defects remains unclear. Case Description: We present a case of a 30-year-old male diagnosed with WD exhibiting musculoskeletal symptoms. The patient's medical history revealed chronic intermittent knee pain. Radiographic and magnetic resonance imaging (MRI) studies revealed a substantial osteochondral lesion with high-grade chondral fissuring. This report reviews the proposed pathophysiology of orthopedic pathology in...

Golf Swing-Induced Pacemaker Atrial Noise and Extraction: A Case Report and Literature Review.

Fri, 9 Aug 2024 00:00:00 +0000

Implantable medical devices, such as pacemakers, have significantly improved the quality of life for patients with cardiac conditions, allowing them to maintain active lifestyles. Nonetheless, these devices can present unique challenges when interacting with the wearers physical activities, potentially leading to unforeseen complications. Here, we present a case of an 81-year-old male golfer, with a history of atrial fibrillation, congestive heart failure, and sick sinus syndrome, who experienced atrial lead noise from his pacemaker, exclusively triggered by his golf swing. This incident, which led to multiple interventions including lead extraction, reimplantation, and eventually a switch to a unipolar lead configuration, represents the first documented case of its kind. It underscores the intricate relationship between the biomechanical forces of certain sports and the functionality of implanted cardiac devices. Through detailed electrophysiology testing, this case demonstrates...

Comparison of brace to observation in stable, radiological developmental dysplasia of the hip: a protocol for a global multicentre non-inferiority randomised trial

Thu, 8 Aug 2024 00:00:00 +0000

INTRODUCTION: Brace treatment is common to address radiological dysplasia in infants with developmental dysplasia of the hip (DDH); however, it is unclear whether bracing provides significant benefit above careful observation by ultrasound. If observation alone is non-inferior to bracing for radiological dysplasia, unnecessary treatment may be avoided. Therefore, the purpose of this study is to determine whether observation is non-inferior to bracing for infants with radiological dysplasia. METHODS AND ANALYSIS: This will be a multicentre, global, randomised, non-inferiority trial performed under the auspices of a global prospective registry for infants and children diagnosed with DDH. Patients will be included if they present with radiological dysplasia (centred hip, alpha angle 43-60°, percent femoral head coverage greater than 35% measured on ultrasound) of a clinically stable hip under 3 months old. Patients will be excluded if they present with clinical hip instability, have...

Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues

Tue, 30 Jul 2024 00:00:00 +0000

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation. Here, we analyzed single-cell transcriptomes, proteomes, and flow cytometry profiles from paired clinical-grade BMAC and ADSVF. This comparative transcriptional atlas challenges the prevalent notion that there is one therapeutic cell type present in both tissues. We also provide data of surface markers that may enable isolation and investigation of cell (sub)populations. Furthermore, the proteome atlas highlights intertissue and interpatient heterogeneity of injected...

Cancer‐cell‐secreted extracellular vesicles target p53 to impair mitochondrial function in muscle

Tue, 16 Jul 2024 00:00:00 +0000

Skeletal muscle loss and weakness are associated with bad prognosis and poorer quality of life in cancer patients. Tumor‐derived factors have been implicated in muscle dysregulation by inducing cachexia and apoptosis. Here, we show that extracellular vesicles secreted by breast cancer cells impair mitochondrial homeostasis and function in skeletal muscle, leading to decreased mitochondrial content and energy production and increased oxidative stress. Mechanistically, miR‐122‐5p in cancer‐cell‐secreted EVs is transferred to myocytes, where it targets the tumor suppressor TP53 to decrease the expression of TP53 target genes involved in mitochondrial regulation, including Tfam, Pgc‐1α, Sco2, and 16S rRNA. Restoration of Tp53 in muscle abolishes mitochondrial myopathology in mice carrying breast tumors and partially rescues their impaired running capacity without significantly affecting muscle mass. We conclude that extracellular vesicles from breast cancer cells mediate skeletal...

Single-event multilevel surgery in cerebral palsy

Tue, 18 Jun 2024 00:00:00 +0000

ABSTRACT: The aim of this study was to compare outcomes for single-event multilevel surgery (SEMLS) in cerebral palsy (CP) performed by 1 or 2 attending surgeons.A retrospective review of patients with CP undergoing SEMLS was performed. Patients undergoing SEMLS performed by a single senior surgeon were compared with patients undergoing SEMLS by the same senior surgeon and a consistent second attending surgeon. Due to heterogeneity of the type and quantity of SEMLS procedures included in this study, a scoring system was utilized to stratify patients to low and high surgical burden. The SEMLS events scoring less than 18 points were categorized as low burden surgery and SEMLS scoring 18 or more points were categorized as high burden surgery. Operative time, estimated blood loss, hospital length of stay, and operating room (OR) utilization costs were compared.In low burden SEMLS, 10 patients had SEMLS performed by a single surgeon and 8 patients had SEMLS performed by 2 surgeons....

Modifiable and non-modifiable risk factors for failure of non-operative treatment of pediatric forearm fractures: Where can we do better?

Tue, 18 Jun 2024 00:00:00 +0000

Introduction: Distal third forearm fractures are common fractures in children. While outcomes are generally excellent, some patients fail initial non-operative management and require intervention. The purpose of this study is to identify independent risk factors associated with failure of closed reduction. Methods: We conducted a retrospective review of distal third forearm fractures in children treated with closed reduction and casting. Patients were divided into two cohorts-those who were successfully closed reduced and those who failed initial non-operative management. Demographic characteristics, cast type, cast index, radiographic fracture, soft tissue characteristics, and quality of reduction were analyzed between groups. Results: A total of 207 children treated for distal third forearm fractures were included for analysis. A total of 190 (91.8%) children maintained their reduction while 17 (8.2%) failed initial non-operative management. Modifiable risk factors associated...

The Utility of Routine Radiographic Monitoring in Pediatric Osteoarticular Infections

Tue, 18 Jun 2024 00:00:00 +0000

BACKGROUND: Pediatric musculoskeletal (MSK) infections broadly include isolated osteomyelitis (OM), septic arthritis (SA), and combined infections (OM+SA). These diagnoses are often monitored with serum inflammatory markers and serial radiographs to monitor treatment response and development of negative sequelae, despite limited data supporting these practices. The purpose of this study is to evaluate the utility of obtaining serial radiographic follow-up for pediatric osteoarticular infections. METHODS: An institutional review board-approved retrospective review was completed. Children 18 years and below admitted to a single institution with a culture/biopsy-proven diagnosis of OM, SA, or OM+SA. All postdischarge radiographs were reviewed and retrospectively categorized as either routine (scheduled) or reactive. Routine radiographs were obtained regardless of clinical presentation. Reactive radiographs were obtained in patients presenting with the sign of an altered clinical...

National Trends in Total Hip Arthroplasty Bearing Surface Usage in Extremely Young Patients Between 2006 and 2016

Tue, 18 Jun 2024 00:00:00 +0000

BACKGROUND: Long-term implant durability is a key concern when considering total hip arthroplasty (THA) in young patients. The ideal bearing surface used in these patients remains unknown. The purpose of this study was to analyze trends in THA bearing surface use from 2006 to 2016 using a large, pediatric national database. METHODS: This was a retrospective review from January 1, 2006, to December 31, 2016, using the Kids' Inpatient Database. International Classification of Diseases, 9^th revision and 10^th revision codes were used to identify patients who underwent THA and create cohorts based on bearing surfaces: metal-on-metal, metal-on-polyethylene, ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC). Annual utilization of each bearing surface and associated patient and hospital demographics were analyzed. RESULTS: A total of 1004 THAs were identified during the 11-year study period. The annual number of THAs performed increased by 169% from 2006...

When Should Instrumentation to the Pelvis be Considered in Minimally Ambulatory Adolescents With Neuromuscular Scoliosis?

Tue, 18 Jun 2024 00:00:00 +0000

INTRODUCTION: The goal of neuromuscular scoliosis (NMS) surgery is to improve sitting balance, facilitate daily care, and alleviate pain. In nonambulatory patients, where sitting balance is key, fusion to the pelvis is usually required. However, in minimally ambulatory patients, fusion to the pelvis remains controversial, and there is considerable practice variability in this patient population. The purpose of this study is to evaluate and summarize the available evidence regarding fusion constructs in minimally ambulatory patients with NMS and to provide expert opinion regarding when fusion to the pelvis should be considered. METHODS: A search of the English literature was performed using PubMed to identify papers pertaining to patients with NMS treated with instrumented posterior spinal fusion. Papers published before 2000, case reports, and level V evidence were excluded. RESULTS: The authors identified 8 studies for review. The majority included both nonambulatory and minimally...

Temporal dynamics of the multi-omic response to endurance exercise training

Fri, 14 Jun 2024 00:00:00 +0000

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1–3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to...

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Sat, 8 Jun 2024 00:00:00 +0000

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose...

Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training

Fri, 7 Jun 2024 00:00:00 +0000

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training...

An evidence based conceptual framework for the multifactorial understanding of proximal junctional kyphosis.

Fri, 17 May 2024 00:00:00 +0000

INTRODUCTION: Adult spinal deformity (ASD) is a debilitating pathology that arises from a variety of etiologies. Spinal fusion surgery is the mainstay of treatment for those who do not achieve symptom relief with conservative interventions. Fusion surgery can be complicated by a secondary deformity termed proximal junctional kyphosis (PJK). RESEARCH QUESTION: This scoping review evaluates the modern body of literature analyzing risk factors for PJK development and organizes these factors according to a multifactorial framework based on mechanical, tissue or demographic components. MATERIALS AND METHODS: An extensive search of the literature was performed in PubMed and Embase back to the year 2010. Articles were assessed for quality. All risk factors that were evaluated and those that significantly predicted the development of PJK were compiled. The frequency that a risk factor was predictive compared to the number of times it was evaluated was calculated. RESULTS: 150 articles...

Functional Radiographic Diagnosis of the Lumbar Spine

Thu, 9 May 2024 00:00:00 +0000

Several attempts have been made to measure the segmental range of motion in the lumbar spine during flexion-extension with the purpose of gathering additional data for the diagnosis of instability. The previous studies were performed in vitro or in vivo during active motion. The aim of this study was to obtain normal values of passively performed segmental motions. Forty-one healthy adults were examined by means of functional radiographs during flexion-extension and lateral bending. A graphic construction method and a computer-assisted method were used to measure rotations. Comparing with recent in vivo studies, the values obtained for normal angles of rotation were predominately larger. This might be due to the passive examination used in the study. The graphic construction method and computer-assisted method techniques are equally reliable, but the computer-assisted method method yields other important kinematic data, such as translations. It is proposed that passive motion...

An Analysis of Errors in Kinematic Parameters Associated with in Vivo Functional Radiographs

Thu, 9 May 2024 00:00:00 +0000

A pair of functional radiographs, taken at each end of the range of motion, are used to determine spinal motions. Graphic construction and computer-assisted methods are available for the radiographic analysis. The later provides many more motion parameters. A study of lumbar spine lateral radiographs was conducted to determine errors in the motion parameters due to spinal level, radiographic quality, and errors in the two digitizing instruments. Significant differences were found in the errors due to the two digitizers when the same radiographic pair was redigitized several times. There were only minimal differences, however, between the digitizers when the radiographic films were remarked and redigitized. The error ranges (2 x SD) for the motion parameters were 1) rotation = +/- 1.25 degrees; 2) translation of the inferior posterior vertebral body corner = +/- 0.86 degrees; and 3) coordinates for the center of rotation = +/- 4.3 mm. Both the spinal level and radiographic quality...

Clinical Validation of Functional Flexion-Extension Roentgenograms of the Lumbar Spine

Thu, 9 May 2024 00:00:00 +0000

The purpose of this study was to determine the clinical validity of functional flexion-extension roentgenograms of the lumbar spine in a defined patient population. One hundred and one adults with low-back pain or functional disorders underwent passive functional flexion-extension examinations. Their roentgenograms were analyzed using a computer-assisted method to determine segmental motion parameters such as rotation and translation of the lumbar vertebrae. The patient population was broken down into five groups with similar pathologies or physical conditions, and their motion parameters compared to a normal population and to each other. It was found that all of the patient groups exhibited significantly hypomobile motion, spread equally among all levels, in comparison to the normal population, except for the group of high-performance athletes, who had significant hypermobility. The uniform spread of hypomobility limits the ability to distinguish with any confidence between the...

Quantitation and localization of cartilage degeneration following the induction of osteoarthritis in the rabbit knee

Thu, 9 May 2024 00:00:00 +0000

OBJECTIVE: To develop and apply a new video imaging technique to quantify and localize Indian ink staining of cartilage of the rabbit femorotibial joint after the induction of osteoarthritis by unilateral transection of the anterior cruciate ligament (ACLT). METHODS: Nine weeks after surgery, femora and tibiae from 11 ACLT and contralateral control knees were harvested and positioned to obtain calibrated gray-scale images of the ink-painted articular cartilage surfaces that are opposed with the knee in 90 degrees flexion. Images were processed so that areas of normal cartilage gave a relatively high reflectance score, whereas ink-stained fibrillated cartilage and exposed bone gave low scores. RESULTS: Comparison of the medial and lateral femoral condyles and tibial plateaus (MFC, LFC, MTP, LTP) of control and ACLT knees showed that the area of the MTP not covered by the meniscus had a significantly lower reflectance score (P < 0.001) than other areas. ACLT led to an 11% decrease...

Body position and backpack loading: an upright magnetic resonance imaging study of the adult lumbar spine

Thu, 9 May 2024 00:00:00 +0000

The human lumbar spine is uniquely adapted to the gravitational stress of upright posture. Using upright magnetic resonance imaging (uMRI), we characterized the adult lumbar spine's response to upright gravitational loading. We hypothesized that a gravitational load would compress the intervertebral discs (IVDs). Five volunteers underwent T2 weighted sagittal 0.6T uMRI scans of the lumbar spine while supine, upright, and upright with a 10% body weight (BW) backpack. While upright, the 10% BW load significantly compressed the L4‐L5 and L5‐S1 IVDs by about 10% relative to supine (p < 0.05). Upright posture and the 10% BW load significantly compressed the anterior L5‐S1 IVD relative to supine (p < 0.05). Gravitational loading of the lumbar spine plus an added 10% BW load compresses the caudal IVDs (L4‐L5 and L5‐S1), suggesting that these discs are either bearing more of the load or are more compliant than the other IVDs. This study is the first radiographic analysis to describe...

Geometric Changes in the Cervical Spinal Canal During Impact

Thu, 9 May 2024 00:00:00 +0000

SUMMARY OF BACKGROUND DATA: Although the extent of injury after cervical spine fracture can be visualized by imaging, the deformations that occur in the spinal canal during injury are unknown. STUDY DESIGN: This study compared spinal canal occlusion and axial length changes occurring during a simulated compressive burst fracture with the residual deformations after the injury. METHODS: Canal occlusion was measured from changes in pressure in a flexible tube with fluid flowing through it, placed in the canal space after removal of the cord in cadaver specimens. To measure canal axial length, cables were fixed in C1 and led through the foramen transversarium from C2-T1, then out through the base, where they were connected to the core rods of linearly variable differential transformers (LVDT). Axial compressive burst fractures were created in each of ten cadaveric cervical spine specimens using a drop-weight, while force, distraction, and occlusion were monitored throughout the injury...

Ultrashort time-to-echo MR morphology of cartilaginous endplate correlates with disc degeneration in the lumbar spine

Wed, 1 May 2024 00:00:00 +0000

PurposeUsing ultrashort echo time (UTE) MRI, we determined prevalence of abnormal cartilaginous endplate (CEP), and the relationship between CEP and disc degeneration in human lumbar spines.Materials and methodsLumbar spines from 71 cadavers (age 14–74 years) were imaged at 3 T using sagittal UTE and spin echo T2 map sequences. On UTE images, CEP morphology was defined as “normal” with linear high signal intensity or “abnormal” with focal signal loss and/or irregularity. On spin echo images, disc grade and T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) were determined. 547 CEPs and 284 discs were analysed. Effects of age, sex, and level on CEP morphology, disc grade, and T2 values were determined. Effects of CEP abnormality on disc grade, T2 of NP, and T2 of AF were also determined.ResultsOverall prevalence of CEP abnormality was 33% and it tended to increase with older ages (p = 0.08) and at lower spinal levels of L5 than L2 or L3 (p = 0.001). Disc...

T1rho MR properties of human patellar cartilage: correlation with indentation stiffness and biochemical contents

Wed, 1 May 2024 00:00:00 +0000

ObjectiveCartilage degeneration involves structural, compositional, and biomechanical alterations that may be detected non-invasively using quantitative MRI. The goal of this study was to determine if topographical variation in T1rho values correlates with indentation stiffness and biochemical contents of human patellar cartilage.DesignCadaveric patellae from unilateral knees of 5 donors with moderate degeneration were imaged at 3-Telsa with spiral chopped magnetization preparation T1rho sequence. Indentation testing was performed, followed by biochemical analyses to determine water and sulfated glycosaminoglycan contents. T1rho values were compared to indentation stiffness, using semi-circular regions of interest (ROIs) of varying sizes at each indentation site. ROIs matching the resected tissues were analyzed, and univariate and multivariate regression analyses were performed to compare T1rho values to biochemical contents.ResultsGrossly, superficial degenerative change of the...

Periarticular blast wounds without fracture a prospective case series

Tue, 30 Apr 2024 00:00:00 +0000

BackgroundDuring the wars in Afghanistan and Iraq most injuries to service members involved the musculoskeletal system. These wounds often occurred around joints, and in some cases result in traumatic arthrotomy—a diagnosis that is not always clear, especially when there is no concomitant articular fracture. The aim of the present study is to evaluate the diagnosis and treatment of peri-articular blast injuries without fracture.MethodsThe study cohort included 12 consecutive patients (12 involved extremities) who sustained peri-articular blast wounds of the extremities without fractures. The diagnosis of penetrating articular injury was based on clinical examination, radiographic findings, or aspiration. A peri-articular wound was defined as any wound, or radio-opaque blast fragment, within 5 cm of a joint. The New Injury Severity Score (NISS) was calculated for each patient. Four patients had upper, and 8 patients had lower extremity injuries. Nine of 12 patients had joint...

Management and treatment of musculoskeletal problems in adults with cerebral palsy: Experience gained from two lifespan clinics

Fri, 12 Apr 2024 00:00:00 +0000

Management and treatment of musculoskeletal problems in adults with cerebral palsy: Experience gained from two lifespan clinics

Are our actions matching our words? A review of trainee ethnic and gender diversity in orthopaedic surgery

Sat, 23 Mar 2024 00:00:00 +0000

Background: There is a lack of physician ethnic and gender diversity amongst surgical specialties. This study analyzes the literature that promotes diversity amongst surgical trainees. Specifically, this study sought to answer (i) how the number of publications regarding diversity in orthopaedic surgery compares to other surgical specialties, (ii) how the number of publications amongst all surgical subspecialties trends over time and (iii) which specific topics regarding diversity are discussed in the surgical literature. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to query articles from PubMed, Web of Science, Embase and the Cumulative Index to Nursing and Allied Health Literature. Broad inclusion criteria for both ethnic and gender diversity of any surgical specialty were utilized. Results: Our query resulted 1429 publications, of which 408 duplicates were removed, and 701 were excluded on title and abstract screening,...

Serum reactivity to citrullinated protein/peptide antigens and left ventricular structure and function in the Multi-Ethnic Study of Atherosclerosis (MESA)

Thu, 29 Feb 2024 00:00:00 +0000

BACKGROUND: Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF. METHODS: Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each...

Intervertebral disc kinematics in active duty Marines with and without lumbar spine pathology

Sun, 25 Feb 2024 00:00:00 +0000

Military members are required to carry heavy loads frequently during training and active duty combat. We investigated if operationally relevant axial loads affect lumbar disc kinematics in forty-one male active duty Marines with no previous clinically diagnosed pathology. Marines were imaged standing upright with and without load. From T2-weighted magnetic resonance images, intervertebral disc (IVD) health and kinematic changes between loading conditions and across lumbar levels were evaluated using two-way repeated measures analysis of variance tests. IVD kinematics with loading were compared between individuals with and without signs of degeneration on imaging. Linear regression analyses were performed to determine associations between IVD position and kinematic changes with loading. Fifty-eight percent (118/205) of IVDs showed evidence of degeneration and 3% (7/205) demonstrated a disc bulge. IVD degeneration was not related to posterior annular position (P > .205)....

Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury

Sun, 25 Feb 2024 00:00:00 +0000

OBJECTIVE: To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures. SETTING: Marine Corps Base and VA Healthcare System. PARTICIPANTS: A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89). DESIGN: Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer. MAIN MEASURES: Amygdala volumes with/without normalizations to ICV. RESULTS: The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes...

NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia

Sun, 25 Feb 2024 00:00:00 +0000

Progression of chronic lymphocytic leukemia (CLL) and resistance to therapy are affected by tumor microenvironmental factors. One such factor is B-cell activating factor (BAFF), a cytokine that is produced mainly by nurse-like cells (NLC) and enhances CLL cells survival and modulates response to therapy. In CLL cells, BAFF activates NF-κB signaling, but how NF-κB supports CLL survival is not entirely clear. In this study we show that BAFF induces accumulation of the signaling and autophagy adaptor p62/SQSTM1 in a manner dependent on NF-κB activation. p62 potentiates mTORC1 signaling and activates NRF2, the master regulator of the anti-oxidant response. We found that expression of NRF2 target genes, such as NAD(P)H quinone oxidoreductase 1 (NQO1), is particularly enriched in CLL cells with high ROR1 surface expression (ROR1Hi). ROR1Hi CLL cells with elevated NQO1 expression exhibit resistance to drugs that induce ROS accumulation, such venetoclax. However, such cells are more...

Nuclear Factor-κB Decoy Oligodeoxynucleotide Attenuates Cartilage Resorption In Vitro

Sat, 3 Feb 2024 00:00:00 +0000

BACKGROUND: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-κB (NF-κB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-κB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-κB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. MATERIALS AND METHODS: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage...

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise

Sat, 20 Jan 2024 00:00:00 +0000

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated...

Yoga and Low Back Pain: No Fool's Tool.

Thu, 18 Jan 2024 00:00:00 +0000

Yoga and Low Back Pain: No Fool's Tool.

Yoga for veterans with chronic low back pain: Design and methods of a randomized clinical trial

Thu, 18 Jan 2024 00:00:00 +0000

Chronic low back pain (CLBP) afflicts millions of people worldwide, with particularly high prevalence in military veterans. Many treatment options exist for CLBP, but most have limited effectiveness and some have significant side effects. In general populations with CLBP, yoga has been shown to improve health outcomes with few side effects. However, yoga has not been adequately studied in military veteran populations. In the current paper we will describe the design and methods of a randomized clinical trial aimed at examining whether yoga can effectively reduce disability and pain in US military veterans with CLBP. A total of 144 US military veterans with CLBP will be randomized to either yoga or a delayed treatment comparison group. The yoga intervention will consist of 2× weekly yoga classes for 12weeks, complemented by regular home practice guided by a manual. The delayed treatment group will receive the same intervention after six months. The primary outcome is the change...

Secondary Outcomes from a Randomized Controlled Trial of Yoga for Veterans with Chronic Low-Back Pain

Thu, 18 Jan 2024 00:00:00 +0000

Chronic low-back pain (cLBP) is a prevalent condition, and rates are higher among military veterans. cLBP is a persistent condition, and treatment options have either modest effects or a significant risk of side-effects, which has led to recent efforts to explore mind-body intervention options and reduce opioid medication use. Prior studies of yoga for cLBP in community samples, and the main results of a recent trial with military veterans, indicate that yoga can reduce back-related disability and pain intensity. Secondary outcomes from the trial of yoga with military veterans are presented here. In the study, 150 military veterans (Veterans Administration patients) with cLBP were randomized to either yoga or a delayed-treatment group receiving usual care between 2013 and 2015. Assessments occurred at baseline, 6 weeks, 12 weeks, and 6 months. Intent-to-treat analyses were conducted. Yoga classes lasting 60 minutes each were offered twice weekly for 12 weeks. Yoga sessions consisted...

Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury

Thu, 18 Jan 2024 00:00:00 +0000

Objective

To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures.

Setting

Marine Corps Base and VA Healthcare System.

Participants

A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89).

Design

Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer.

Main measures

Amygdala volumes with/without normalizations to ICV.

Results

The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only...

Anatomic Evaluation of the Sacroiliac Joint: A Radiographic Study with Implications for Procedures.

Thu, 18 Jan 2024 00:00:00 +0000

BACKGROUND: Sacroiliac joint (SI) pain is increasingly being recognized as a source of low back pain. Injections and percutaneous type procedures are performed to treat symptomatic joints. However, there are limited studies available assessing the anatomy of the SI joint in vivo among patients with pain. OBJECTIVES: The purpose of this study was to provide more precise information on the dimensions and orientation of the SI joint using a new technique for the radiographic evaluation of this joint. STUDY DESIGN: Observational study. SETTING: Emergency department METHODS: Three dimensional computed tomographic (CT) reconstructions of the pelvis were formatted from 100 SI joints in 50 patients who had clinically indicated abdominal/pelvic scans. These images were manipulated to evaluate the SI joint in multiple planes and measure its dimensions, area, and relationship to anatomic landmarks such as the anterior superior iliac spine (ASIS) and posterior superior iliac spine (PSIS). RESULTS:...

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation

Thu, 18 Jan 2024 00:00:00 +0000

BACKGROUND CONTEXT: For chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight. PURPOSE: To examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the...

Intraligamentous synovial chondromatosis of the anterior cruciate ligament

Thu, 18 Jan 2024 00:00:00 +0000

Synovial chondromatosis is a rare disease that causes disability and dysfunction of the involved synovial joint. We describe the second case in the literature of intraligamentous synovial chondromatosis involving the anterior cruciate ligament, confirmed by pathology after arthroscopic removal of the chondral bodies. We also describe associated magnetic resonance imaging findings which may be helpful for diagnosis of this very rare entity.

Comparing Types of Yoga for Chronic Low Back and Neck Pain in Military Personnel: A Feasibility Randomized Controlled Trial

Thu, 18 Jan 2024 00:00:00 +0000

Background: Chronic low back pain (cLBP) and chronic neck pain (cNP) are highly prevalent conditions and common reasons for disability among military personnel. Yoga and other mind-body interventions have been shown to safely decrease pain and disability in persons with cLBP and/or cNP but have not been adequately studied in active duty military personnel. The objective of this study was to examine the feasibility and acceptability of delivering 2 types of yoga (hatha and restorative) to a sample of active-duty military personnel with cLBP/cNP. Methods: Military personnel with cLBP and/or cNP (n = 49; 59% men) were randomized to either hatha or restorative yoga interventions. Interventions consisted of in-person yoga 1-2x weekly for 12 weeks. Feasibility and acceptability were measured by rates of recruitment, intervention attendance, attrition, adverse events, and satisfaction ratings. Health outcomes including pain and disability were measured at baseline, 12 weeks,...

From the International Space Station to the Clinic: How Prolonged Unloading May Disrupt Lumbar Stability

Thu, 18 Jan 2024 00:00:00 +0000

From the International Space Station to the Clinic: How Prolonged Unloading May Disrupt Lumbar Stability

Yoga as a treatment for chronic low back pain: A systematic review of the literature.

Thu, 18 Jan 2024 00:00:00 +0000

OBJECTIVES: Chronic low back pain (CLBP) affects millions of people worldwide, and appears to be increasing in prevalence. It is associated not only with pain, but also with increased disability, psychological symptoms, and reduced quality of life. There are various treatment options for CLBP, but no single therapy stands out as being the most effective. In the past 10 years, yoga interventions have been studied as a CLBP treatment approach. The objective of this paper is to review the current literature supporting the efficacy of yoga for CLBP. METHODS: A literature search through the beginning of 2015 was conducted in Pub Med for randomized control trials addressing treatment of CLBP with yoga. RESULTS: In this review we evaluate the use of yoga as a treatment for CLBP. Specifically we evaluate how yoga impacts physical functioning and disability, pain, and associated psychological symptoms. We also evaluate possible mediators of the effect of yoga and the safety of yoga. DISCUSSION:...

Yoga Plus Mantram Repetition to Reduce Chronic Pain in Veterans With Post-Traumatic Stress Disorder: A Feasibility Trial

Thu, 18 Jan 2024 00:00:00 +0000

Background: Veterans with post-traumatic stress disorder (PTSD) are more likely to report chronic pain than veterans without PTSD. Yoga has been shown to reduce both chronic pain and PTSD symptoms in clinical trials. The goal of our study was to assess the feasibility and acceptability of conducting a randomized controlled trial (RCT) that combined yoga and mantram repetition (Yoga + MR) into one program for military veterans with both chronic pain and PTSD. Methods: In this feasibility RCT, 27 veterans were randomized to either Yoga + MR or a relaxation intervention. Due to the COVID-19 pandemic, in-person recruitment, assessments, and intervention attendance were re-evaluated. Although remote delivery of aspects of the study were utilized, interventions were delivered in-person. Feasibility benchmarks met included full recruitment in 12 months or less, 75%+ retention at initial follow-up assessment, 50%+ attendance rate, and 75%+ of participants satisfied with the interventions. Results:...

Lower Macromolecular Content in Tendons of Female Patients with Osteoporosis versus Patients with Osteopenia Detected by Ultrashort Echo Time (UTE) MRI

Thu, 18 Jan 2024 00:00:00 +0000

Tendons and bones comprise a special interacting unit where mechanical, biochemical, and metabolic interplays are continuously in effect. Bone loss in osteoporosis (OPo) and its earlier stage disease, osteopenia (OPe), may be coupled with a reduction in tendon quality. Noninvasive means for quantitatively evaluating tendon quality during disease progression may be critically important for the improvement of characterization and treatment optimization in patients with bone mineral density disorders. Though clinical magnetic resonance imaging (MRI) sequences are not typically capable of directly visualizing tendons, ultrashort echo time MRI (UTE-MRI) is able to acquire a high signal from tendons. Magnetization transfer (MT) modeling combined with UTE-MRI (i.e., UTE-MT-modeling) can indirectly assess macromolecular proton content in tendons. This study aimed to determine whether UTE-MT-modeling could detect differences in tendon quality across a spectrum of bone health. The lower...

Poster 180 Rectus Femoris Avulsion of the Direct and Reflected Heads in a Kickball Player: MRI Diagnosis and Nonoperative Outcome

Thu, 18 Jan 2024 00:00:00 +0000

Poster 180 Rectus Femoris Avulsion of the Direct and Reflected Heads in a Kickball Player: MRI Diagnosis and Nonoperative Outcome

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-day bed rest in women

Thu, 18 Jan 2024 00:00:00 +0000

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle...

An Update in Qualitative Imaging of Bone Using Ultrashort Echo Time Magnetic Resonance

Thu, 18 Jan 2024 00:00:00 +0000

Bone is comprised of mineral, collagenous organic matrix, and water. X-ray-based techniques are the standard approach for bone evaluation in clinics, but they are unable to detect the organic matrix and water components in bone. Magnetic resonance imaging (MRI) is being used increasingly for bone evaluation. While MRI can non-invasively assess the proton pools in soft tissues, cortical bone typically appears as a signal void with clinical MR techniques because of its short T2*. New MRI techniques have been recently developed to image bone while avoiding the ionizing radiation present in x-ray-based methods. Qualitative bone imaging can be achieved using ultrashort echo time (UTE), single inversion recovery UTE (IR-UTE), dual-inversion recovery UTE (Dual-IR-UTE), double-inversion recovery UTE (Double-IR-UTE), and zero echo time (ZTE) sequences. The contrast mechanisms as well as the advantages and disadvantages of each technique are discussed.

Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone: An Update

Thu, 18 Jan 2024 00:00:00 +0000

Bone possesses a highly complex hierarchical structure comprised of mineral (~45% by volume), organic matrix (~35%) and water (~20%). Water exists in bone in two forms: as bound water (BW), which is bound to bone mineral and organic matrix, or as pore water (PW), which resides in Haversian canals as well as in lacunae and canaliculi. Magnetic resonance (MR) imaging has been increasingly used for assessment of cortical and trabecular bone. However, bone appears as a signal void on conventional MR sequences because of its short T2^*. Ultrashort echo time (UTE) sequences with echo times (TEs) 100-1,000 times shorter than those of conventional sequences allow direct imaging of BW and PW in bone. A series of quantitative UTE MRI techniques has been developed for bone evaluation. UTE and adiabatic inversion recovery prepared UTE (IR-UTE) sequences have been developed to quantify BW and PW. UTE magnetization transfer (UTE-MT) sequences have been developed to quantify collagen...

The Impact of Spine Pathology on Posterior Ligamentous Complex Structure and Function

Sat, 6 Jan 2024 00:00:00 +0000

Purpose of ReviewSpinal ligament is an important component of the spinal column in mitigating biomechanical stress. Particularly the posterior ligamentous complex, which is composed of the ligamentum flavum, interspinous, and supraspinous ligaments. However, research characterizing the biomechanics and role of ligament health in spinal pathology and clinical context are scarce. This article provides a comprehensive review of the implications of spinal pathology on the structure, function, and biomechanical properties of the posterior ligamentous complex.Recent FindingsCurrent research characterizing biomechanical properties of the posterior ligamentous complex is primarily composed of cadaveric studies and finite element modeling, and more recently incorporating patient-specific anatomy into finite element models. The ultimate goal of current research is to understand the relative contributions of these ligamentous structures in healthy and pathological spine, and whether preserving...

Sleep Architecture and Mental Health Among Community-Dwelling Older Men

Sun, 24 Dec 2023 00:00:00 +0000

OBJECTIVES: To investigate the association of mood and anxiety symptoms with sleep architecture (the distribution of sleep stages) in community-dwelling older men. METHOD: We used in-home unattended polysomnography to measure sleep architecture in older men. Men were categorized into 4 mental health categories: (a) significant depressive symptoms only (DEP+ only, Geriatric Depression Scale ≥ 6), (b) significant anxiety symptoms only (ANX+ only, Goldberg Anxiety Scale ≥ 5), (c) significant depressive and anxiety symptoms (DEP+/ANX+), or (d) no significant depressive or anxiety symptoms (DEP-/ANX-). RESULTS: Compared with men without clinically significant symptomology, men with depressive symptoms spent a higher percentage of time in Stage 2 sleep (65.42% DEP+ only vs 62.47% DEP-/ANX-, p = .003) and a lower percentage of time in rapid eye movement sleep (17.05% DEP+ only vs 19.44% DEP-/ANX-, p = .0005). These differences persisted after adjustment for demographic/lifestyle characteristics,...

Bilateral Hand Salvage With Simultaneous Pedicled Groin Flaps in an Immunocompromised Patient.

Tue, 12 Dec 2023 00:00:00 +0000

Bilateral Hand Salvage With Simultaneous Pedicled Groin Flaps in an Immunocompromised Patient.

A Simple and Versatile Test for Elbow Posterolateral Rotatory Instability

Mon, 11 Dec 2023 00:00:00 +0000

BACKGROUND: Posterolateral rotatory instability (PLRI) results from lateral ulnar collateral ligament (LCL) deficiency. The lateral pivot shift test is used to diagnose PLRI but can be difficult to perform and is poorly tolerated. We present a new maneuver, the Posterior Radiocapitellar Subluxation Test (PRST), that we believe is easier to perform. The purpose of this study was to compare the efficacy and reproducibility of the PRST with the lateral pivot shift test. METHODS: We obtained 10 cadaveric upper extremity specimens, performed a Kocher approach on each, released the LCL origin in 5, then closed. The specimens were randomized, and 3 attending orthopedic surgeons and 1 resident blindly performed the PRST then the lateral pivot shift test after re-randomization and assessed presence or absence of PLRI. This process was repeated the following day. The data for each test were analyzed for sensitivity, specificity, and accuracy. RESULTS: For the blinded testing when comparing...

A three-dimensional computed tomography study of the palmar ulnar corner fragment in distal radial fractures

Mon, 11 Dec 2023 00:00:00 +0000

Fixing palmar ulnar corner fragments of distal radial fractures can be challenging. We described the palmar ulnar corner fragment morphology in a retrospective cohort study of 40 patients who underwent preoperative wrist computed tomography scans. Palmar ulnar corner fractures were categorized based on articular cross-sectional area, sagittal angulation relative to the radius long axis, palmar cortical length, radioulnar width and associated palmar radiocarpal subluxation. Three types emerged: type 1 fragments involved 37% (SD 10) of the radiocarpal articular surface and were extended in the sagittal plane; type 2 fragments involved 28% (SD 10) of the articular surface and had a long palmar cortex, of which 57% had palmar carpal subluxation; and type 3 fragments involved 13% (SD 2) of the articular surface, had a short palmar cortex and all had palmar carpal subluxation. Understanding palmar ulnar corner fragment morphology may guide optimal reduction and fixation strategy and...

Opioid Analgesia Compared with Non-Opioid Analgesia After Operative Treatment for Pediatric Supracondylar Humeral Fractures

Sat, 9 Dec 2023 00:00:00 +0000

BACKGROUND: Minimal pain and opioid use after operative treatment for pediatric supracondylar humeral fractures have been previously described; however, opioid-prescribing practices in the United States remain variable. We hypothesized that children without an opioid prescription would report similar postoperative pain compared with children prescribed opioids following closed reduction and percutaneous pinning (CRPP) of supracondylar humeral fractures. METHODS: Children who were 3 to 12 years of age and were undergoing CRPP for a closed supracondylar humeral fracture were prospectively enrolled in a multicenter, comparative study. Following a standardized dosing protocol, oxycodone, ibuprofen, and acetaminophen were prescribed at 2 hospitals (opioid cohort), and 2 other hospitals prescribed ibuprofen and acetaminophen alone (non-opioid cohort). The children's medication use and the daily pain that they experienced (scored on the Wong-Baker FACES Scale) were recorded at postoperative...

The influence of ligament biomechanics on proximal junctional kyphosis and failure in patients with adult spinal deformity

Wed, 11 Oct 2023 00:00:00 +0000

Purpose: It is unknown whether the biomechanics of the posterior ligamentous complex (PLC) are impaired in individuals undergoing surgery for adult spinal deformity (ASD). Characterizing these properties may improve our understanding of proximal junctional kyphosis (PJK; defined as proximal junctional angle [PJA] of >10 deg from UIV-1 to UIV + 2), as well as proximal junctional failure (PJF; symptomatic PJK requiring revision). The purpose of this prospective observational study is to compare biomechanical properties of the PLC in individuals with ASD who do, and do not develop PJK or PJF within 1 year of spinal fusion surgery. Methods: Intraoperative biopsies of PLC were obtained from 32 consecutive patients undergoing spinal fusions for ASD (>4 levels). Ligament peak force, tensile stress, tensile strain, and elastic modulus (EM) were measured with a materials testing system. Biomechanical properties and tissue dimensions were correlated with age, gender, BMI, vitamin...

Do associated proximal fibula fractures help predict the severity of tibial plateau fractures?

Tue, 26 Sep 2023 00:00:00 +0000

PurposeProximal fibula fractures are often associated with tibial plateau fractures, but their relationship is poorly characterized. The purpose of this study was to better define the relationship between tibial plateau injury severity and presence of associated soft tissue injuries.MethodsA retrospective review was performed on all operatively treated tibial plateau fractures at a Level 1 trauma center over a 5-year period. Patient demographics, injury radiographs, CT scans, operative reports and follow-up were reviewed.ResultsQueried tibial plateau fractures from 2014 to 2019 totaled 217 fractures in 215 patients. Fifty-two percent were classified as AO/OTA 41B and 48% were AO/OTA 41C. Thirty-nine percent had an associated proximal fibula fracture. The presence of a proximal fibula fracture had significant correlation with AO/OTA 41C fractures, as compared with AO/OTA 41B fractures (chi-square, p < 0.001). Of the patients with a lateral split depression type tibial plateau...

Anterior-Posterior Transcranial Ultrasound to Measure Cranial Oscillations

Sun, 17 Sep 2023 00:00:00 +0000

BACKGROUND: We aimed to provide information on whether or not the correlation between body tilt and the pulse amplitude of transcranial ultrasonic time-of-flight waveform can be observed in the anterior-posterior skull direction. Also, we asked the question whether or not the skull pulsation can be detected since the cranial bones involved are thicker. METHODS: The experimental model of body tilt that alters intracranial pressure by shifting body fluid headward was employed. Transcranial ultrasound waveforms were examined in 15 healthy volunteers positioned at five tilt angles of +30 degrees, 0 degrees, -30 degrees, -60 degrees, and -90 degrees from the horizontal body position. A pulse-echo transducer was placed on the middle forehead and ultrasound waveforms were recorded. Synchronized variations in the ultrasonic time-of-flight with heartbeats were monitored using the pulsed phase locked loop technique for the output voltage of the ultrasound transducer. Simultaneous effects...

Transcriptional time course after rotator cuff repair in 6 month old female rabbits

Fri, 15 Sep 2023 00:00:00 +0000

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that...

Intramuscular Degloving Injury of the Rectus Femoris From Kickball: A Case Report and Review

Fri, 15 Sep 2023 00:00:00 +0000

Intramuscular degloving injuries (IDIs) are a rare and unique type of muscle injury where there is a dissociation between the inner and outer components of a particular muscle. This type of injury is seen exclusively within the rectus femoris (RF) muscle due to its unique muscle-within-a-muscle anatomy and represents 9% of RF injuries. Despite the significance of this injury, limited knowledge exists regarding the mechanism, management, and prognosis of IDIs, and IDIs are not currently included among the various muscle injury classifications. We present a 38-year-old active male with a one-week history of acute onset right anterior mid-thigh pain and palpable lump after playing kickball. Right thigh MRI revealed an IDI of the RF muscle, edema within the inner and outer muscular portions of the muscle, and a retraction of the torn inner indirect myotendinous complex of the RF. He was managed with physical therapy while being advised to avoid aggressive quadriceps contractions,...

Slow-motion smartphone video improves interobserver reliability of gait assessment in ambulatory cerebral palsy

Thu, 14 Sep 2023 00:00:00 +0000

Purpose: Structured visual gait assessment is essential for the evaluation of pediatric patients with neuromuscular conditions. The purpose of this study was to evaluate the benefit of slow-motion video recorded on a standard smartphone to augment visual gait assessment. Methods: Coronal and sagittal plane videos of the gait of five pediatric subjects were recorded on a smartphone, including four subjects with ambulatory cerebral palsy and one subject without gait pathology. Twenty-one video scorers were recruited and randomized to evaluate slow-motion or normal-speed videos utilizing the Edinburgh Visual Gait Score. The slow-motion group (N = 11) evaluated the videos at one-eighth speed, and the normal-speed group (N = 10) evaluated the same videos at normal speed. Interrater reliabilities were determined by calculating intraclass correlation coefficients for each group as a whole, for each Edinburgh Visual Gait Score item, and after stratification by evaluator experience level. Results:...

Quantitative assessment of articular cartilage degeneration using 3D ultrashort echo time cones adiabatic T1ρ (3D UTE-Cones-AdiabT1ρ) imaging

Tue, 5 Sep 2023 00:00:00 +0000

ObjectivesTo evaluate articular cartilage degeneration using quantitative three-dimensional ultrashort-echo-time cones adiabatic-T1ρ (3D UTE-Cones-AdiabT1ρ) imaging.MethodsSixty-six human subjects were recruited for this study. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic-Resonance-Imaging Score (WORMS) were evaluated by two musculoskeletal radiologists. The human subjects were categorized into three groups, namely normal controls (KL0), doubtful-minimal osteoarthritis (OA) (KL1–2), and moderate–severe OA (KL3–4). WORMS were regrouped to encompass the extent of lesions and the depth of lesions. The UTE-Cones-AdiabT1ρ values were obtained using 3D UTE-Cones data acquisitions preceded by seven paired adiabatic full passage pulses that corresponded to seven spin-locking times (TSLs) of 0, 12, 24, 36, 48, 72, and 96 ms. The performance of the UTE-Cones-AdiabT1ρ technique in evaluating the degeneration of knee cartilage was assessed via the ANOVA comparisons with subregional...

Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures

Mon, 4 Sep 2023 00:00:00 +0000

We investigated the effects of the cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor-1 (sTNFR1) on the extracellular matrix metabolism of human intervertebral discs (IVDs) and the roles of IL-1β and TNF in the homeostasis of IVD cells. The 1.2% alginate beads and the explants obtained from 35 human lumbar discs were treated with cytokine inhibitors. Extracellular matrix metabolism was evaluated by proteoglycan (PG) and collagen syntheses and IL-1β, TNF, and IL-6 expressions after three days of culture in the presence or absence of IL-1Ra, sTNFR1, and cycloheximide. Simultaneous treatment with IL-1Ra and sTNFR1 stimulated PG and collagen syntheses in the NP and AF cells and explants. The IL-1β concentration was significantly correlated to the relative increase in PG synthesis in AF explants after simultaneous cytokine inhibitor treatment. The relative increase in PG synthesis induced by simultaneous cytokine treatment was significantly...

Role of mitochondria-bound HK2 in rheumatoid arthritis fibroblast-like synoviocytes

Sat, 2 Sep 2023 00:00:00 +0000

Background: Glucose metabolism, specifically, hexokinase 2 (HK2), has a critical role in rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) phenotype. HK2 localizes not only in the cytosol but also in the mitochondria, where it protects mitochondria against stress. We hypothesize that mitochondria-bound HK2 is a key regulator of RA FLS phenotype. Methods: HK2 localization was evaluated by confocal microscopy after FLS stimulation. RA FLSs were infected with Green fluorescent protein (GFP), full-length (FL)-HK2, or HK2 lacking its mitochondrial binding motif (HK2ΔN) expressing adenovirus (Ad). RA FLS was also incubated with methyl jasmonate (MJ; 2.5 mM), tofacitinib (1 µM), or methotrexate (1 µM). RA FLS was tested for migration and invasion and gene expression. Gene associations with HK2 expression were identified by examining single-cell RNA sequencing (scRNA-seq) data from murine models of arthritis. Mice were injected with K/BxN serum and given MJ. Ad-FLHK2 or Ad-HK2ΔN...

Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling

Fri, 1 Sep 2023 00:00:00 +0000

Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation. Within mitochondria, Ox-mtDNA was either repaired by DNA glycosylase OGG1 or cleaved by the endonuclease FEN1 to 500-650 bp fragments that exited mitochondria via mPTP- and VDAC-dependent channels to initiate cytosolic NLRP3 inflammasome activation. Ox-mtDNA fragments also activated cGAS-STING signaling and gave rise to pro-inflammatory extracellular DNA. Understanding...

The Utility of Virtual Reality in Orthopedic Surgical Training

Fri, 1 Sep 2023 00:00:00 +0000

OBJECTIVE: To examine the efficacy of virtual reality (VR) to prepare surgical trainees for a pediatric orthopedic surgery procedure: pinning of a slipped capital femoral epiphysis (SCFE). DESIGN: Participants were randomly assigned to a standard, study guide (SG) group or to a VR training group. All participants were provided a technique video and SG; the VR group additionally trained via an Osso VR surgical trainer (ossovr.com) with real-time feedback and coaching from an attending pediatric orthopedic surgeon. Following training, participants performed a SCFE guidewire placement on a SawBones model embedded in a soft-tissue envelope (SawBones model 1161). Participants were asked to achieve "ideal placement" based on the training provided. Participants were evaluated on time, number of pin "in-and outs," penetration of the articular surface, angle between the pin and the physis, distance from pin tip to subchondral bone and distance from the center-center point of the epiphysis. SETTING:...

Knock-Down of IL-1Ra in Obese Mice Decreases Liver Inflammation and Improves Insulin Sensitivity

Fri, 1 Sep 2023 00:00:00 +0000

Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet-...

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology

Fri, 1 Sep 2023 00:00:00 +0000

PurposeThe purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis.MethodsMultifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini–Hochberg) and for between-group post hoc comparisons (Sidak) were applied.ResultsAdipogenic gene (ADIPOQ) expression was higher...

Selective Fatty Replacement of Paraspinal Muscles in Facioscapulohumeral Muscular Dystrophy.

Fri, 1 Sep 2023 00:00:00 +0000

A 65-year-old man with a history of facioscapulohumeral muscular dystrophy presented to his physician with a complaint of new-onset low back pain, bilateral foot numbness, and left lower extremity radicular symptoms with foot drop. He subsequently underwent magnetic resonance imaging of the lumbar spine, which revealed complete fatty replacement of the erector spinae musculature throughout the lumbar spine. Preservation of the lumbar multifidus muscles above the L4 level was observed, which has not previously been reported in patients with this condition. The patient's lower extremity symptoms were consistent with left L5-S1 radiculopathy, and the magnetic resonance images indicated mild to moderate central canal stenosis at L2-L3 with severe bilateral L5-S1 foraminal narrowing. J Orthop Sports Phys Ther 2019;49(6):483. doi:10.2519/jospt.2019.8815.

The effect of fatty infiltration, revision surgery, and sex on lumbar multifidus passive mechanical properties

Fri, 4 Aug 2023 00:00:00 +0000

Purpose: Previous research has demonstrated increased stiffness in the multifidus muscle compared to other paraspinal muscles at the fiber bundle level. We aimed to compare single fiber and fiber bundle passive mechanical properties of multifidus muscle: (1) in 40 patients undergoing primary versus revision surgery and (2) in muscle with mild versus severe fatty infiltration. Methods: The degree of muscle fatty infiltration was graded using the patients' spine magnetic resonance images. Average single fiber and fiber bundle passive mechanical properties across three tests were compared between primary (N = 30) and revision (N = 10) surgery status, between mild and severe fatty infiltration levels, between sexes, and with age from passive stress-strain tests of excised multifidus muscle intraoperative biopsies. Results: At the single fiber level, elastic modulus was unaffected by degree of fatty infiltration or surgery status. Female sex (p = 0.001) and younger...

Return to Sport Using Corticosteroid Injections for Knee Pain in Triathletes

Thu, 3 Aug 2023 00:00:00 +0000

Introduction Despite the prevalence of corticosteroid injections in athletes, little is known about their efficacy in triathletes. We aim to assess attitudes, use, subjective effectiveness, and time to return to sport with corticosteroid injections compared to alternative methods in triathletes with knee pain. Methods This is an observational study during the COVID-19 pandemic. Triathletes answered a 13-question survey posted to three triathlon-specific websites. Results Sixty-one triathletes responded, 97% of whom experienced knee pain at some point in their triathlete career; 63% with knee pain received a corticosteroid injection as treatment (average age 51 years old). The most popular attitude (44.3%) regarding corticosteroid injections was "tried them, with good improvement". Most found the cortisone injection helpful for two to three months (28.6%), or more than one year (28.6%); of individuals who found the injections useful for more than one year, four-eight...