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The Journal of Veterinary Medical... Jun 2024Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere...
Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan.
PubMed: 38925932
DOI: 10.1292/jvms.24-0069 -
International Journal of Spine Surgery Jun 2024Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and...
Allogeneic Disc Progenitor Cells Safely Increase Disc Volume and Improve Pain, Disability, and Quality of Life in Patients With Lumbar Disc Degeneration-Results of an FDA-Approved Biologic Therapy Randomized Clinical Trial.
BACKGROUND
Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease.
METHODS
Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells ( = 20), high-dose cells ( = 20), vehicle alone ( = 10), or placebo ( = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment.
RESULTS
At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm ( = 0.028) at 52 weeks and 402.1 mm ( = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle ( = 1) or placebo ( = 3) groups, none treatment related.
CONCLUSIONS
High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection.
CLINICAL TRIAL REGISTRATION
NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.
PubMed: 38925869
DOI: 10.14444/8609 -
Advanced Healthcare Materials Jun 2024Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease affecting degenerative joints, and there is currently no...
Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease affecting degenerative joints, and there is currently no disease-modifying treatment for OA. The pathogenesis of OA is significantly linked with oxidative stress and the process of pyroptosis. Astaxanthin (Ast) is a natural keto-carotenoid pigment with potent antioxidant activity and has been shown to effectively alleviate cartilage damage in OA. However, its poor water solubility and high sensitivity to light, temperature, and pH greatly limit its bioavailability. In this study, we developed Ast-loaded tetrahedral framework nucleic acids (tFNAs) for Ast delivery (TAC). Compared with free Ast and tFNAs, TAC exhibited improved drug stability and cellular uptake. Most importantly, TAC effectively protected chondrocytes against oxidative stress-induced pyroptosis, promoted extracellular matrix anabolism by chondrocytes, and ultimately alleviated cartilage damage in a rat DMM model. Thus, we believe that TACs hold great promise for the treatment of OA. This article is protected by copyright. All rights reserved.
PubMed: 38923865
DOI: 10.1002/adhm.202401452 -
Environmental Toxicology Jun 2024Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in...
Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA.
PubMed: 38923690
DOI: 10.1002/tox.24367 -
Journal of Cardiovascular Development... May 2024Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the... (Review)
Review
Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients.
PubMed: 38921662
DOI: 10.3390/jcdd11060162 -
Nature Aging Jun 2024Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to...
Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data from humans and mice with metabolic dysfunction-associated liver disease, validated findings with functional studies in mice and applied the signature to transcriptomic data from other organs to determine whether aging-sensitive degenerative mechanisms are conserved. We discovered that the signature enriches in diseased livers in parallel with degeneration. It is also enriched in failing human hearts, diseased kidneys and pancreatic islets from individuals with diabetes. The signature includes genes that control ferroptosis. Aged mice develop more hepatocyte ferroptosis and liver degeneration than young mice when fed diets that induce metabolic stress. Inhibiting ferroptosis shifts the liver transcriptome of old mice toward that of young mice and reverses aging-exacerbated liver damage, identifying ferroptosis as a tractable, conserved mechanism for aging-related tissue degeneration.
PubMed: 38918603
DOI: 10.1038/s43587-024-00652-w -
European Spine Journal : Official... Jun 2024Intervertebral disc degeneration (IDD) is a common degenerative disease associated with ageing. Additionally, IDD is recognized as one of the leading causes of low back...
PURPOSE
Intervertebral disc degeneration (IDD) is a common degenerative disease associated with ageing. Additionally, IDD is recognized as one of the leading causes of low back pain and disability in the working-age population and is the first step in the process leading to degenerative spinal changes. However, the genetic factors and regulatory mechanisms of IDD remain unknown. Therefore, we selected eight single nucleotide polymorphisms of genes to reveal the progression of IDD in a 7-year longitudinal study of the general population in Japan.
METHODS
IDD was evaluated in the Wakayama Spine Study (WSS), which is a population-based cohort study. Overall, 574 participants from the general population cohort who underwent whole spine magnetic resonance imaging and provided clinical information were included in this longitudinal survey.
RESULTS
The progression of IDD was affected only by THBS2 at the lumbar region, T12-L1 (p = 0.0044) and L3-4 (p = 0.0045). The significant interaction between THBS2 and age with IDD negatively affected the thoracic spines and passively influenced both the thoracolumbar junction and thoracic spines. The higher progression per year of Pfirrmann's score was rapid in young people with age; however, this decelerated the IDD progression per year in different ages.
CONCLUSION
Our longitudinal study found the genes associated with IDD progression and that genetic factors' impact on IDD differs depending on disc level and age.
PubMed: 38918228
DOI: 10.1007/s00586-024-08152-6 -
Asian Spine Journal Jun 2024A retrospective case-control propensity score-matching study.
Association between ligamentous stenosis at spondylolisthetic segments before fusion surgery and symptomatic adjacent canal stenosis at follow-up in patients with degenerative spondylolisthesis.
STUDY DESIGN
A retrospective case-control propensity score-matching study.
PURPOSE
This study aimed to longitudinally evaluate whether preoperative ligamentous stenosis at the spondylolisthetic segments could affect the incidence of symptomatic adjacent canal stenosis following one-segment fusion surgery.
OVERVIEW OF LITERATURE
Several risk factors for symptomatic adjacent canal stenosis following fusion surgery have been assessed. Patients with lumbar canal stenosis mainly due to ligamentum flavum (LF) hypertrophy (ligamentous stenosis) also have LF hypertrophy in other segments.
METHODS
In total, 76 patients participated in this case-control study (neurologically symptomatic adjacent canal stenosis, n=33; neurologically asymptomatic cases at follow-up, n=43). Their risk factors during surgery and magnetic resonance (MR) images before the surgery and at follow-up were evaluated. Data from the two groups (n=25 each) were matched using propensity scores for age, sex, time to MR imaging at follow-up, surgical procedure, and LF hypertrophy in adjacent segments before the surgery and analyzed.
RESULTS
Compared with the asymptomatic group, the symptomatic adjacent canal stenosis group had a significantly larger LF area/spinal canal area in the spondylolisthetic segments before the surgery. During the follow-up periods (in months), they had a larger LF area/ spinal canal area in the adjacent segments: the two values were significantly correlated. The sensitivity, specificity, and positive and negative predictive values for determining symptomatic adjacent canal stenosis were high compared with on the cutoff value for the LF area/spinal canal area at the spondylolisthetic segments before the surgery. These results were the same after matching.
CONCLUSIONS
Symptomatic adjacent canal stenosis is mainly caused by LF hypertrophy. Ligamentous stenosis at the spondylolisthetic segments before fusion surgery might be strongly associated with symptomatic adjacent canal stenosis at follow-up.
PubMed: 38917859
DOI: 10.31616/asj.2023.0064 -
Asian Spine Journal Jun 2024A retrospective cohort study using the Kaplan-Meier method with propensity-score matching.
Prevalent morphometric vertebral fractures as a risk factor for subsequent clinical vertebral fractures after shortfusion surgery in older Japanese women with degenerative spondylolisthesis.
STUDY DESIGN
A retrospective cohort study using the Kaplan-Meier method with propensity-score matching.
PURPOSE
To evaluate whether the presence of prevalent morphometric vertebral fractures (VFs) poses a risk for subsequent clinical VFs after short-fusion surgery in women aged ≥60 years with degenerative spondylolisthesis.
OVERVIEW OF LITERATURE
VFs are common osteoporotic fractures and are associated with a low quality of life. Subsequent VFs are a complication of instrumented fusion in patients with degenerative lumbar disorders. Thus, risk factors for subsequent VFs after fusion surgery must be analyzed. Population-based studies have suggested that prevalent morphometric VFs led to a higher incidence of subsequent VFs in postmenopausal women; however, no studies have investigated whether prevalent morphometric VFs are a risk factor for subsequent VFs after fusion surgery in patients with degenerative spondylolisthesis.
METHODS
The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [-] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (-) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis.
RESULTS
Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (-) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching.
CONCLUSIONS
The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery.
PubMed: 38917857
DOI: 10.31616/asj.2023.0327 -
JCI Insight Jun 2024Autosomal dominant optic atrophy plus (ADOA+) is characterized by primary optic nerve atrophy accompanied by a spectrum of degenerative neurological symptoms. Despite...
Autosomal dominant optic atrophy plus (ADOA+) is characterized by primary optic nerve atrophy accompanied by a spectrum of degenerative neurological symptoms. Despite ongoing research, no effective treatments are currently available for this condition. Our study provided evidence for the pathogenicity of an unreported c.1780T>C variant in the OPA1 gene through patient-derived skin fibroblasts and an engineered HEK293T cell line with OPA1 downregulation. We demonstrated that OPA1 insufficiency promoted mitochondrial fragmentation and increased DRP1 expression, disrupting mitochondrial dynamics. Consequently, this disruption enhanced mitophagy and caused mitochondrial dysfunction, contributing to the ADOA+ phenotype. Notably, the Drp1 inhibitor, mitochondrial division inhibitor-1 (Mdivi-1), effectively mitigated the adverse effects of OPA1 impairment. These effects included reduced Drp1 phosphorylation, decreased mitochondrial fragmentation, and balanced mitophagy. Thus, we propose that intervening in DRP1 with Mdivi-1 could correct mitochondrial abnormalities, offering a promising therapeutic approach for managing ADOA+.
PubMed: 38916953
DOI: 10.1172/jci.insight.180582