Degenerative Disease Research Articles

Transcriptome sequencing reveals inflammation and macrophage heterogeneity in subacromial bursa from degenerative shoulder disorders

ABSTRACT Purpose We aimed to investigate the transcriptomic alterations that occur in the subacromial bursa (SAB) following degenerative or traumatic shoulder diseases. Materials and Methods RNA sequencing was employed to evaluate the transcriptomic alterations of the SAB in individuals afflicted with degenerative rotator cuff tear (RCT), traumatic RCT and proximal humerus fracture (PHF). To gain insights into the biological significance of differentially expressed genes (DEGs), we conducted an enrichment analysis utilizing Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We further utilized single-cell RNA sequencing datasets of SAB from a recently published study to explore the associated cellular dynamics and alterations. Results We detected 1,790 up-regulated and 1,964 down-regulated DEGs between degenerative RCT and PHF, 2,085 up-regulated and 1,919 down-regulated DEGs between degenerative RCT and traumatic RCT, and 20 up-regulated and 12 down-regulated DEGs between traumatic RCT and PHF. Given the similar expression pattern between traumatic RCT and PHF, they were integrated as the traumatic group. In comparison with the traumatic group, 1,983 up-regulated and 2,205 down-regulated DEGs were detected in degenerative SAB. Enrichment analysis of up-regulated DEGs uncovered an elevated inflammatory and immunologic responses in degenerative SAB. Single-cell transcriptomic analysis revealed macrophage represented the immune cell with the most DEGs between the degenerative and traumatic RCT. Conclusion Our results revealed that the SAB in degenerative RCT exhibited a different transcriptional signature compared to that in traumatic RCT, and enrichment analysis showed immunologic and inflammatory activations. Macrophages may play a fundamental role in this process.

Technical aspects of rod-insertion forceps (persuader) application in reducing construct failure after lumbar spine fusion surgery: a biomechanical cadaveric study in Germany.

A prospective experimental study. This biomechanical in vitro study aimed to examine the extent to which the use of a rod persuader (RP) leads to additional mechanical stress on the screw-rod system and determine its influence on the bony anchoring of primary pedicle screws. Degenerative spine diseases and deformities are the most common indications for the stabilization and fusion of spinal segments. The pedicle screw-rod system is considered the gold standard for dorsal stabilization, and an RP is also increasingly being considered to fit the spondylodesis material. Ten lumbar spines from body donors were examined. Bisegmental dorsal spinal lumbar interbody fusion of the L3-L5 segments was performed using a pedicle screw-rod system (ROCCIA Multi-LIF Cage; Silony Medical, Germany). In group 1, the titanium rod was inserted without tension, whereas in group 2, the rod was attached to the pedicle screws at the L4 and L5 levels, creating a 5-mm gap. To attach the rod, the RP was used to press the rod into the pedicle screw. The rod was left in place for 30 minutes and then removed. The rod reduction technique significantly increased the mechanical load on the overall construct measured by strain gauges (p<0.05) and resulted in outright implant failure with pedicle screw pullout in 88.9%. In cases where the spondylodesis material is not fully attached within the pedicle screw, an RP can be used with extreme caution, particularly in osteoporotic bones, to avoid pedicle screw avulsion and screw anchor failure.

GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.

Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is an age-related macular degeneration-like (AMD-like) retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production in retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus that enabled simple, sensitive, and high-throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix, reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium-derived factor). In vivo, treatment of 8-month-old R345W+/+ knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is an important demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of retinal degenerative diseases, including potentially AMD itself.

Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases.

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies. The impairment of mitophagy, the selective removal of damaged or dysfunctional mitochondria by autophagy, is relevant to the development and progression of age-related diseases. The molecular mechanisms that regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 is an intrinsically disordered scaffold protein with a unique property of regulating the activity of both proliferation and autophagy core machineries. While the role of AMBRA1 during embryonic development and neoplastic transformation has been extensively investigated, its functions in post-mitotic cells of adult tissues have been limited due to the embryonic lethality caused by AMBRA1 deficiency. Recently, a key role of AMBRA1 in selectively regulating mitophagy in post-mitotic cells has emerged. Here we summarize and discuss these results with the aim of providing a comprehensive view of the mitochondrial roles of AMBRA1, and how defective activity of AMBRA1 has been functionally linked to mitophagy alterations observed in age-related degenerative disorders, including muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases and age-related macular degeneration.

Can pelvic incidence affect changes in sagittal spino-pelvic parameters between standing and sitting positions in individuals with lumbar degenerative disease?

The aim of this study was to explore the correlation between PI and standing-to-sitting changes of the sagittal alignment in patients with lumbar degenerative diseases, and investigate the differences in posture changes among Roussouly types. A total of 209 patients with lumbar degenerative disease were retrospectively included in this study. All the patients received lateral full body imaging in both standing and sitting positions. Sagittal parameters including SVA, OD-HA, PT, PI, PT/PI, SS, LL, TK, Upper LL (L1-L4) and Lower LL (L4-S1) were measured in both standing and sitting position, and the parameters were compared between two positions. The correlations between PI and lumbo-pelvic changes were analyzed. The postural changes were compared among different Roussouly types. From standing to sitting, all the parameters except PI significantly changed, including SVA, OD-HA, PT, PT/PI, SS, LL, TK, Upper LL and Lower LL. The contribution of lower LL was greater to global LL than upper LL. PI had a significant correlation with ΔPT, ΔSS, ΔLL, ΔUpper LL and ΔLower LL. From standing to sitting, type 4 patients had the most pronounced ΔPT, ΔSS and ΔLL, and ΔLower LL of types 3 and 4 were greater than that of types 1 and 2. In patients with degenerative disease, PI plays an important role in determining the extent of lumbo-pelvic changes from standing to sitting. Among different Roussouly types, type 4 patients have the most pronounced changes of PT, SS and LL, suggesting the relatively greater flexibility of pelvis and lumbar spine.

Burden of osteoarthritis in Indonesia: A Global Burden of Disease (GBD) study 2019

Osteoarthritis (OA) is a complex and common condition, especially affecting the knees due to their weight-bearing role. Traditionally seen as a degenerative disease, OA is now understood to have both mechanical and inflammatory causes. Despite its increasing prevalence, there is limited data on OA in Indonesia, resulting in low awareness among clinicians and the public. The aim of this study was to describe the OA burden in Indonesia, focusing on its prevalence, incidence, and years lived with disability (YLD) from 1990 to 2019, using data from the Global Burden of Disease (GBD) study 2019. A descriptive cross-sectional study was conducted to examine the prevalence, incidence, and YLD of OA in Indonesia from the GBD study 2019. OA prevalence and YLD were compared to other countries according to similar social demographics and geographical proximity. OA YLD was also compared to the top causes of death and disability YLD in Indonesia. The study found that OA cases in Indonesia more than doubled from 1990 to 2019, with increases of 153.12% in males and 143.36% in females. Similar trends were observed for knee OA. The age-standardized prevalence rate in Indonesia increased by 10.03% in males and 8.42% in females, and these were higher compared to China, India, Singapore, and the global average. Younger people had a higher OA prevalence rate growth than older groups. The incidence rate for OA also rose significantly, with males seeing a 10.89% increase to 290 per 100,000 people and females with an 8.57% increase to 384 per 100,000 people. Despite lower overall burden rates compared to some countries, Indonesia experienced significant growth in YLD due to OA (12.16% in males and 9.65% in females) since 1990. Although OA was less burdensome than stroke, diabetes, low back pain, and chronic obstructive pulmonary disease (COPD), its YLD growth rate was higher. In conclusion, OA prevalence and incidence in Indonesia significantly increased from 1990 to 2019, with a notable rise among younger populations. OA had a higher YLD growth compared to several other major diseases in Indonesia, highlighting the need for early detection and preventive measures, particularly for the younger population.

Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models and tractometry

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy

AbstractOsteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration.

Outcomes of the Modified Dunn Procedure Versus Delayed Imhauser Osteotomy for Moderate to Severe Stable Slipped Capital Femoral Epiphysis.

Traditional management of moderate to severe stable slipped capital femoral epiphysis (SCFE) has been in situ fixation followed by reconstructive surgery if symptoms arise. This delayed approach may lead to irreversible intra-articular damage of the hip over time. The purpose of this study was to compare radiographic and clinical outcomes of the modified Dunn procedure (MDP) versus in situ fixation followed by delayed Imhauser osteotomy (DIO). This was a retrospective study from a single institution between 2001 and 2021. Among 250 patients diagnosed with SCFE, a total of 18 (18 hips) treated with MDP and 16 (18 hips) treated with DIO for moderate to severe stable SCFE were included. Most patients who underwent DIO either had concomitant (11/18 hips) or subsequent (2/18 hips) open osteochondroplasty. Mean follow up was 4.7 years (range: 1 to 12.8y). Radiographs were reviewed to measure Southwick angle, anteroposterior and lateral alpha (α) angles, and femoral head-neck offset ratio preoperatively and at latest follow up. Charts were reviewed for demographics, subsequent surgeries, complications, and Heyman-Herndon clinical outcomes. The amount of deformity correction was greater in the MDP than DIO group based on anteroposterior α angles (mean: 22.3 vs. 11.9 degrees, P=0.046) and femoral head-neck offset ratios (mean: 0.26 vs. 0.12, P=0.001). There was no significant difference in Heyman-Herndon scores (both 16/18, 88.9% good to excellent outcomes, P>0.999). Less reoperations were performed in the MDP than DIO group (2/18, 11.1% vs. 9/18, 50%; P=0.004). AVN occurred in 2/18 hips (11.1%) in the MDP group with both surgeries performed early in the series and underwent prior in situ screw fixation compared with 0/18 hips (0%) in the DIO group (P=0.486). One patient in the DIO group was later diagnosed with osteoarthritis. MDP resulted in more anatomic coronal and sagittal plane deformity correction, less reoperations, and similar Heyman-Herndon clinical outcomes compared with DIO. AVN occurred in the MDP group whereas osteoarthritis occurred in the DIO group. These complications must be weighed against improved long-term clinical results for patients who would otherwise be at risk for premature degenerative joint disease due to residual proximal femoral deformity. Level III-retrospective comparative study.

Benchmarking Large Language Models for Cervical Spondylosis.

Cervical spondylosis is the most common degenerative spinal disorder in modern societies. Patients require a great deal of medical knowledge, and large language models (LLMs) offer patients a novel and convenient tool for accessing medical advice. In this study, we collected the most frequently asked questions by patients with cervical spondylosis in clinical work and internet consultations. The accuracy of the answers provided by LLMs was evaluated and graded by 3 experienced spinal surgeons. Comparative analysis of responses showed that all LLMs could provide satisfactory results, and that among them, GPT-4 had the highest accuracy rate. Variation across each section in all LLMs revealed their ability boundaries and the development direction of artificial intelligence.

Identification of the Metabolic Signature of Aging Retina.

This study aims to explore the metabolic signature of aging retina and identify the potential metabolic biomarkers for the diagnosis of retinal aging. Retinal samples were collected from both young (two months) and aging (14 months) mice to conduct an unbiased metabolic profiling. Liquid chromatography-tandem mass spectrometry analysis was conducted to screen for the metabolic biomarkers and altered signaling pathways associated with retinal aging. We identified 166 metabolites differentially expressed between young and aged retinas using a threshold of orthogonal projection to latent structures discriminant analysis variable importance in projection >1 and P < 0.05. These metabolites were significantly enriched in several metabolic pathways, including purine metabolism, citrate cycle, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, and alanine, aspartate and glutamate metabolism. Among these significantly enriched pathways, glycerophospholipid metabolites emerged as promising candidates for retinal aging biomarkers. We assessed the potential of these metabolites as biomarkers through an analysis of their sensitivity and specificity, determined by the area under the receiver-operating characteristic (ROC) curves. Notably, the metabolites like PC (15:0/22:6), PC (17:0/14:1), LPC (P-16:0), PE (16:0/20:4), and PS (17:0/16:1) demonstrated superior performance in sensitivity, specificity, and accuracy in predicting retinal aging. This study sheds light on the molecular mechanisms underlying retinal aging by identifying distinct metabolic profiles and pathways. These findings provide a valuable foundation for developing future clinical applications in diagnosing, identifying, and treating age-related retinal degeneration. This study sheds light on novel metabolic profiles and biomarkers in aging retinas, potentially paving the way for targeted interventions in preventing, diagnosing, and treating age-related retinal degeneration and other retinal diseases.

Effectiveness of Injection Strategies on Patients With Patellar Tendonitis (Jumpers' Knee): A Network Meta-analysis of Randomized Controlled Trials.

Patellar tendonitis (PT) is a common degenerative disease of the patellar tendon that seriously affects the sports careers of elite athletes and activities of daily living of sports enthusiasts. Injection therapy is a prevalent invasive treatment for PT. This work comprehensively analyzes various injection treatments for PT that consider agent type and characteristics, frequency, and assessment timepoints by meta-analysis. PubMed, Embase, and the Cochrane Library were sources of data. Randomized controlled trials (RCTs) analyzing the effect of various injection strategies on the treatment of patients with PT were considered. Systematic review and meta-analysis. Level 2. First author, year of publication, research location, registration information, patient type, sample size, age, sex, intervention, control treatment, and follow-up period in each study were extracted. Nineteen RCTs were included in the analysis. In the network meta-analysis of Victorian Institute of Sports Assessment-Patellar (VISA-P) outcomes, polidocanol (standardized mean difference (SMD), 6.52; 95% CI 4.75, 8.30; P < 0.01), tenocyte-like cells (SMD, 4.08; 95% CI 2.92, 5.25; P < 0.01), and leukocyte-poor platelet-rich plasma (LP-PRP) plus high-volume image-guided injection (HVIGI) (SMD, 1.56; 95% CI 0.62, 2.50; P < 0.01) were significantly superior to noninjection conservative treatment, mainly at the 6-month follow-up timepoint. For visual analog scale results, multiple dry needling (DN) (SMD, -1.78; 95% CI -2.56, -1.00; P < 0.01), LP-PRP (SMD, -0.71; 95% CI -1.31, -0.12; P = 0.02), and LP-PRP plus HVIGI (SMD, -1.31; 95% CI -2.22, -0.39; P < 0.01) were significantly superior to blank, which was also mainly at the 6-month timepoint. Injection-related treatments: polidocanol, tenocyte-like cells, LP-PRP, and multiple DN showed potential short (1-3 months) or medium (6 months)-term treatment benefits. There is still no evidence for injection interventions with long-term therapeutic benefit.

Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) in treatment of degenerative diseases of lumbosacral spine compared to modified open TLIF: a prospective randomised controlled study.

The aim of this study was to determine the clinical and radiological outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) compared to modified open TLIF via the Wiltse approach for treatment of degenerative diseases of the lumbosacral region. The results were evaluated over a post-operative period of 48 months. Radiological data and medical records of patients who underwent MIS TLIF and modified open TLIF between May 2017 and May 2021 were reviewed. Parameters monitored to evaluate the surgical results were: clinical status, operation time, blood loss, radiation dose to patient, day of discharge, analgesic consumption, fusion, and complications rate. For functional assessment, the Visual Analogue Scale for back pain (VAS-BP), VAS for leg pain (VAS-LP), Oswestry Disability Index (ODI), Patient Satisfaction Rate (PSR), and the complication rate were used. This study included 57 patients randomly divided into two groups: 30 operated on using the MIS TLIF technique, and 27 operated on using the modified open TLIF technique via the Wiltse approach. 48-month follow-up rates were similar for the two cohorts. Patients did not differ significantly at baseline in terms of ODI, VAS-BP, or VAS-LP. Perioperatively, MIS TLIF was associated with significantly less blood loss (167.3 ± 80.0 vs. 297.9 ± 81.5 ml, p = 1.1E-05), slightly longer procedures (185.7 ± 45.2 vs. 183.1 ± 66.4 minutes, p = 0.76), a lower radiation dose (MIS 16.9 ± 7.1 vs. 22.0 ± 9.7 mGy OPEN p = 0.012), and shorter hospitalisations (MIS 5.9 ± 1.8 vs. 7.7 ± 1.6 days OPEN). The most common complication was radiculitis, which accounted for 33% and 37% in the MIS and the TLIF groups, respectively. The second most common complication was malposition of the fixation material, which accounted for 18.5% in the TLIF group and 20% in the MIS group. The level of fusion achieved was 92.6% in the MIS group versus 92.3% in the TLIF group. There was lower consumption of analgesics in MIS. Patient Satisfaction Rate (PSR) was 90%. Clinical and radiological outcomes after MIS TLIF in patients with degenerative disease of the lumbosacral region are generally favourable. MIS TLIF was associated with decreased blood loss perioperatively, a lower radiation dose and an earlier discharge, but there was no difference between MIS TLIF and modified open TLIF in 48-month outcomes in terms of disability, back pain, leg pain, quality of life, or patient satisfaction rate or complication rate. Although the differences taper off over time, MIS TLIF has undeniable advantages in the perioperative and early postoperative periods.

IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.

Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.

Efficacy Comparison of Osteopathic Muscle Energy Techniques and Cervical Mobilization on Pain, Disability, and Proprioception in Cervical Spondylosis Patients.

BACKGROUND Cervical spondylosis (CS) is a degenerative disease of the cervical spine characterized by persistent neck pain. Cervical facet joint mobilization (CM) and the osteopathic muscle energy technique (MET) are effective manual procedures for the treatment of neck pain. In this study, we compared the efficacy of the MET and CM techniques on pain, disability, and proprioception in 76 patients with CS. MATERIAL AND METHODS A total of 96 participants with a diagnosis of CS were randomized into an electro-thermal therapy (ET) group (control group, n=32), ET+MET group (experiment I, n=32), and ET+CM group (experiment II, n=32). All patients received 3 treatment sessions per week for 4 consecutive weeks. Pain intensity, functional disability and cervical position sense were measured using the visual analog scale (VAS), Copenhagen Neck Functional Disability Scale (CNFDS), and cervical range of motion (CROM) device. RESULTS The study was completed by 76 participants. VAS and CNFDS scores decreased significantly after treatment in all 3 groups (P<0.001); however, there was no significant difference between the groups (P>0.05). Between-group analysis showed a significant difference in extension joint position error in favor of MET (P<0.001), while there was no significant difference between the groups in other movement directions (P>0.05). CONCLUSIONS MET and CM have similar effects on improving pain and disability in individuals with CS and chronic neck pain. However, the results of this study show that MET combined with ET is a more effective method for improving cervical position sense.

Significant overlap of inflammatory and degenerative features on imaging among patients with degenerative disc disease, diffuse idiopathic skeletal hyperostosis and axial spondyloarthritis: a real-life cohort study

BackgroundDifferentiating between degenerative disc disease (DDD), diffuse idiopathic skeletal hyperostosis (DISH), and axial spondyloarthritis (axSpA) represents a diagnostic challenge in patients with low back pain (LBP). We aimed to evaluate the distribution of inflammatory and degenerative imaging features in a real-life cohort of LBP patients referred to a tertiary university rheumatology center.MethodsIn a retrospective cross-sectional analysis of patients referred for LBP, demographics, symptom information, and available imaging were collected. SpA-like changes were considered in the spine in the presence of one of the following lesions typically related to SpA: erosions, sclerosis, squaring, and syndesmophytes on conventional radiographs (CR) and bone marrow oedema (BMO), erosions, sclerosis, and fat lesions (FL) on MRI. SIJ CR were graded per New York criteria; on MRIs, SIJs were evaluated by quadrant for BMO, erosions, FL, sclerosis and ankylosis, similar to the approach used by the Berlin SIJ MRI scoring system. The final diagnosis made by the rheumatologist was the gold standard. Data were presented descriptively, by patient and by quadrant, and compared among the three diagnosis groups.ResultsAmong 136 referred patients, 71 had DDD, 38 DISH, and 27 axSpA; median age 62 years [IQR55-73], 63% males. On CR, SpA-like changes were significantly higher in axSpA in the lumbar (50%, vs. DDD 23%, DISH 22%), in DISH in the thoracic (28%, vs. DDD 8%, axSpA 12%), and in DDD in the cervical spine (67% vs. DISH 0%, axSpA 33%). On MRI, BMO was significantly higher in DISH in the thoracic (37%, vs. DDD 22%, axSpA 5%) and equally distributed in the lumbar spine (35-42%). FL were significantly more frequently identified in DISH and axSpA in the thoracic (56% and 52%) and DDD and axSpA in the lumbar spine (65% and 74%, respectively). Degenerative changes were frequent in the three groups. Sacroiliitis (NY criteria) was identified in 49% (axSpA 76%, DDD 48%, DISH 29%).ConclusionA significant overlap was found among DDD, DISH, and axSpA for inflammatory and degenerative imaging features. Particularly, SpA-like spine CR features were found in one-fourth of patients with DISH, and MRI BMO was found in one-third of those patients.

Predicting Knee Joint Contact Force Peaks During Gait Using a Video Camera or Wearable Sensors.

Estimating loading of the knee joint may be helpful in managing degenerative joint diseases. Contemporary methods to estimate loading involve calculating knee joint contact forces using musculoskeletal modeling and simulation from motion capture (MOCAP) data, which must be collected in a specialized environment and analyzed by a trained expert. To make the estimation of knee joint loading more accessible, simple input predictors should be used for predicting knee joint loading using artificial neural networks. We trained feedforward artificial neural networks (ANNs) to predict knee joint loading peaks from the mass, height, age, sex, walking speed, and knee flexion angle (KFA) of subjects using their existing MOCAP data. We also collected an independent MOCAP dataset while recording walking with a video camera (VC) and inertial measurement units (IMUs). We quantified the prediction accuracy of the ANNs using walking speed and KFA estimates from (1) MOCAP data, (2) VC data, and (3) IMU data separately (i.e., we quantified three sets of prediction accuracy metrics). Using portable modalities, we achieved prediction accuracies between 0.13 and 0.37 root mean square error normalized to the mean of the musculoskeletal analysis-based reference values. The correlation between the predicted and reference loading peaks varied between 0.65 and 0.91. This was comparable to the prediction accuracies obtained when obtaining predictors from motion capture data. The prediction results show that both VCs and IMUs can be used to estimate predictors that can be used in estimating knee joint loading outside the motion laboratory. Future studies should investigate the usability of the methods in an out-of-laboratory setting.

Injectable hydrogel encapsulating siMMP13 with anti-ROS and anti-apoptotic functions for osteoarthritis treatment

BackgroundOsteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential.ResultsIn this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers.ConclusionIn summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

Potential of Selected Underutilized Leafy Vegetables Against CCL4 Induced Oxidative Stress on Wistar Rats

Nutritional immunology might become even more important in prevention of disease. Underutilized leafy vegetables are the richest source of many bioactive compounds especially phenolic compounds with excellent antioxidant properties. Increased consumption of diets containing leafy vegetables may give positive results to human health. The underutilized leafy vegetables which includes Indian pennywort, Sessile joyweed, Red amaranth, Red spinach, Asiatic day flower, Indian sorrel, Roselle leaves are quantified for its phenols, flavonoids and vitamins contents by HPLC-LC MS method. The phenols, flavonoids and vitamins ranged from 0.186 – 12014 µg/g, 0.018 – 785.25 µg/g and 0.361 – 18466.56 ng/g in the underutilized leafy vegetables. Based on the bioactive compounds present, herbal preparations are developed and evaluated for hepatoprotective property against CCL4 induced intoxication in wistar rat model. Biochemical estimation in blood serum (AST/SGOT, ALT/SGPT, ALP, Total bilirubin) and antioxidant enzyme estimation in liver homogenate (SOD, GOD, LPO) showed positive results to reduce hepatotoxicity in CCL4 intoxicated wistar rat model. This exploration can helps in addressing importance of bioactive components present in underutilized leafy vegetables in combating various degenerative diseases and also proved the nutraceutical potential of leafy vegetables. Further which can be used for development of functional foods with the present pre-clinical data.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality. As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology-related findings, we conducted a result-evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro-oncology specialists. The MDT identified key determinants impacting decision-making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high-risk nature. From this experience, we developed a decision-making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy-related pathology, genetic disorders and degenerative diseases.