Correlation between degeneration of cervical intervertebral disc and degeneration of paravertebral muscle.

Objective: To investigate the relationship between degeneration of cervical intervertebral disc and degeneration of paravertebral muscles[multifidus (MF), cervical semispinalis (SCer), semispinalis capitis (SCap) and splenius capitis (SPL)]. Methods: 82 patients with chronic neck pain were randomly selected, including 43 males and 39 females, with 50.73 0.7.51 years old. All patients were scanned by 3.0T MRI Philips Ingenia performed conventional MRI sequence scanning and fat measurement sequence mDIXON-Quant scanning of cervical. Fat infiltration (FI) and cross-sectional area (CSA) of cervical paravertebral muscle (MF, SCer, SCap and SPL) at central level of C5-6 disc were measured by Philips 3.0T MRI image post-processing workstation. According to Pfirrmann grading system, there was no grade I in the included cases. The number of grade IIr IV cases were n=16, 40, 19 and 7 respectively. CSA and FI of cervical paravertebral muscles were compared with t test or one-way ANOVA, Spearman correlation analysis was used to evaluate the correlation between age, disc degeneration, and CSA, FI of cervical paravertebral muscles, and multiple linear regression analysis was used to analyze the independent influencing factors of CSA and FI. Results: CSA of cervical paravertebral muscles in male patients was significantly higher than that in female patients (all P<0.001), but there was no significant difference in FI (all P>0.05). Age was weakly correlated with CSA of MF+SCer, moderately correlated with CSA of SCap and SPL (r=-0.256, -0.355 and -0.361, P<0.05), weakly correlated with FI of SCap and SPL (r= 0.182 and 0.264, P<0.001), moderately correlated with FI of MF+SCer (r=0.408, P<0.001). There were significant differences in FI with disc degeneration (P<0.001, P=0.028 and P=0.005). Further correlation analysis showed that disc degeneration was strongly correlated with FI of MF+SCer (r=0.629, P<0.001), and moderately correlated with FI of SCap and SPL (r=0.363, P=0.001; r=0.345, P=0.002). Multiple linear regression analysis showed that sex and age were the influencing factors of CSA of SCap and SPL, sex was the independent influencing factor of CSA of MF+SCer, and disc degeneration was the independent influencing factor of FI. Conclusions: Age is negatively correlated with CSA and positively correlated with FI. Disc degeneration was correlated with FI of paravertebral muscles, especially with FI of MF and SCer. Sex and age were the influencing factors of CSA, while disc degeneration was the independent influencing factor of FI.

The impact of 25-hydroxyvitamin D and calcium on the risk of age-related macular degeneration: A Mendelian randomization study.

BACKGROUND: The relationships between 25-hydroxyvitamin D (25(OH)D) and calcium and age-related macular degeneration (AMD) are unclear. OBJECTIVE: This study aimed to investigate the causal role of 25(OH)D concentrations, calcium concentrations, and dietary supplements use of vitamin D and calcium on the risk of AMD and its subtypes. METHODS: Independent genetic variants associated with 25(OH)D and calcium concentrations were used as instrumental variables in published genome-wide association studies (GWASs) of European ancestry. The bidirectional two-sample Mendelian randomization (MR) analyses were performed using summary-level data from the UK Biobank and FinnGen datasets. Sensitivity analyses were conducted to ensure the robustness of the MR results. The meta-analyses were conducted using both fixed-effect and random-effect models to provide comprehensive and reliable estimates. RESULTS: A standard deviation increase in calcium concentrations was linked to a 14%, 17%, and 13% reduction in the likelihood of developing AMD (95% confidence interval [CI] = 0.77, 0.97), wet AMD (95% CI = 0.73, 0.95), and dry AMD (95% CI = 0.75, 1.00), respectively. No significant causal relationships were detected between genetically predicted 25(OH)D concentrations and AMD and its subtypes (all P > 0.05). The combined analyses showed that higher calcium concentrations were associated with a reduced risk of overall AMD, with an OR of 0.89 (95% CI = 0.81, 0.98). CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and the risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

[Genotype-phenotype relationship and genetics study of 115 cases with Wilson's disease].

Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.

Corrigendum: Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

[This corrects the article DOI: 10.3389/fnana.2024.1385932.].

Exploring gellan gum-based hydrogels for regenerating human embryonic stem cells in age-related macular degeneration therapy: A literature review.

Age-related macular degeneration (AMD) is a progressive ocular disease marked by the deterioration of retinal photoreceptor cells, leading to central vision decline, predominantly affecting the elderly population worldwide. Current treatment modalities, such as anti-VEGF agents, laser therapy, and photodynamic therapy, aim to manage the condition, with emerging strategies like stem cell replacement therapy showing promise. However, challenges like immune rejection and cell survival hinder the efficacy of stem cell interventions. Regenerative medicine faces obstacles in maximizing stem cell potential due to limitations in mimicking the dynamic cues of the extracellular matrix (ECM) crucial for guiding stem cell behaviour. Innovative biomaterials like gellan gum hydrogels offer tailored microenvironments conducive to enhancing stem cell culture efficacy and tissue regeneration. Gellan gum-based hydrogels, renowned for biocompatibility and customizable mechanical properties, provide crucial support for cell viability, differentiation, and controlled release of therapeutic factors, making them an ideal platform for culturing human embryonic stem cells (hESCs). These hydrogels mimic native tissue mechanics, promoting optimal hESC differentiation while minimizing immune responses and facilitating localized delivery. This review explores the potential of Gellan Gum-Based Hydrogels in regenerative AMD therapy, emphasizing their role in enhancing hESC regeneration and addressing current status, treatment limitations, and future directions.

Discovering potential mechanisms of intervertebral disc disease using systematic Mendelian randomization of human circulating immunocytomics.

BACKGROUND: Although intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites. METHODS: Based on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms (SNPs) were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables (IVs) for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD. RESULTS: MR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of four metabolite-mediated mediation relationships were revealed (3b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine). CONCLUSION: The findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research.

Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis.

Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis, representing a responsive outcome against neovascularization mediated by epithelial-mesenchymal transition of retinal pigment epithelium (RPE) cells. A failure of the current treatment (anti-vascular endothelial growth factor therapy) has also been attributed to the progression of subretinal fibrosis. Hypoxia-inducible factors (HIFs) increase gene expressions to promote fibrosis and neovascularization. HIFs act as a central pathway in the pathogenesis of AMD. HIF inhibitors may suppress ocular neovascularization. Nonetheless, further investigation is required to unravel the aspects of subretinal fibrosis. In this study, we used RPE-specific HIFs or von Hippel-Lindau (VHL, a regulator of HIFs) conditional knockout (cKO) mice, along with pharmacological HIF inhibitors, to demonstrate the suppression of subretinal fibrosis. Fibrosis was suppressed by treatments of HIF inhibitors, and similar suppressive effects were detected in RPE-specific Hif1a/Hif2a- and Hif1a-cKO mice. Promotive effects were observed in RPE-specific Vhl-cKO mice, where fibrosis-mediated pathologic processes were evident. Marine products' extracts and their component taurine suppressed fibrosis as HIF inhibitors. Our study shows critical roles of HIFs in the progression of fibrosis, linking them to the potential development of therapeutics for AMD.

Long acting delivery and therapies for neovascular age-related macular degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life. AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed. EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.

Emotional awareness in patients with amyotrophic lateral sclerosis.

INTRODUCTION: It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS). METHODS: Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status. RESULTS: Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤ .011), memory (p = .006), state-anxiety (p ≤ .013) and depression measures (p ≤ .010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤ .008). CONCLUSIONS: Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease.

Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome.

PURPOSE: To explore patterns of disease expression in Alagille syndrome (ALGS). METHODS: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry. RESULTS: The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina. CONCLUSION: Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes.

Role of plasma fatty acid in age-related macular degeneration: insights from a mendelian randomization analysis.

BACKGROUND: An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes. METHODS: We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides. RESULTS: Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD. CONCLUSIONS: The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.

Spotlight on necroptosis: Role in pathogenesis and therapeutic potential of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which is one of the major factors leading to disability and severe economic burden. Necroptosis is an important form of programmed cell death (PCD), a highly regulated caspase-independent type of cell death that is regulated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL)-mediated, play a key role in the pathophysiology of various inflammatory, infectious and degenerative diseases. Recent studies have shown that necroptosis plays an important role in the occurrence and development of IDD. In this review, we provide an overview of the initiation and execution of necroptosis and explore in depth its potential mechanisms of action in IDD. The analysis focuses on the connection between NP cell necroptosis and mitochondrial dysfunction-oxidative stress pathway, inflammation, endoplasmic reticulum stress, apoptosis, and autophagy. Finally, we evaluated the possibility of treating IDD by inhibiting necroptosis, and believed that targeting necroptosis may be a new strategy to alleviate the symptoms of IDD.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Biomechanical Analysis of Hybrid Artificial Discs or Zero-Profile Devices for Treating 1-Level Adjacent Segment Degeneration in ACDF Revision Surgery.

OBJECTIVE: Cervical hybrid surgery optimizes the use of cervical disc arthroplasty (CDA) and zero-profile (ZOP) devices in anterior cervical discectomy and fusion (ACDF) but lacks uniform combination and biomechanical standards, especially in revision surgery (RS). This study aimed to investigate the biomechanical characteristics of adjacent segments of the different hybrid RS constructs in ACDF RS. METHODS: An intact 3-dimensional finite element model generated a normal cervical spine (C2-T1). This model was modified to the primary C5-6 ACDF model. Three RS models were created to treat C4-5 adjacent segment degeneration through implanting cages plus plates (Cage-Cage), ZOP devices (ZOP-Cage), or Bryan discs (CDA-Cage). A 1.0-Nm moment was applied to the primary C5-6 ACDF model to generate total C2-T1 range of motions (ROMs). Subsequently, a displacement load was applied to all RS models to match the total C2-T1 ROMs of the primary ACDF model. RESULTS: The ZOP-Cage model showed lower biomechanical responses including ROM, intradiscal pressure, maximum von Mises stress in discs, and facet joint force in adjacent segments compared to the Cage-Cage model. The CDA-Cage model exhibited the lowest biomechanical responses and ROM ratio at adjacent segments among all RS models, closely approached or lower than those in the primary ACDF model in most motion directions. Additionally, the maximum von Mises stress on the C3-4 and C6-7 discs increased in the Cage-Cage and ZOP-Cage models but decreased in the CDA-Cage model when compared to the primary ACDF model. CONCLUSION: The CDA-Cage construct had the lowest biomechanical responses with minimal kinematic change of adjacent segments. ZOP-Cage is the next best choice, especially if CDA is not suitable. This study provides a biomechanical reference for clinical hybrid RS decision-making to reduce the risk of ASD recurrence.

Advances in the interaction between lumbar intervertebral disc degeneration and fat infiltration of paraspinal muscles: critical summarization, classification, and perspectives.

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.

Corneal densitometry changes after femtosecond laser-assisted intracorneal ring segments implantation in keratoconus.

Background: Intrastromal corneal ring segments are commonly implanted in the corneas of eyes with mild-to-moderate keratoconus; however, changes in corneal densitometry (CD) after implantation are a matter of debate in the current literature. We evaluated the changes in CD 1 and 3 months after femtosecond laser-assisted Keraring implantation. Methods: This retrospective, non-comparative, multicenter, case series study included patients with keratoconus who underwent femtosecond laser-assisted implantation of double segments with 90° and 160° arc lengths or two 160° arc length Keraring segments. Demographic and baseline clinical ophthalmic data were recorded. Corneal topography and tomography data acquired using a Pentacam HR Scheimpflug tomography system (Pentacam High Resolution; Oculus, Wetzlar, Germany) with a best-fit sphere were used as a reference surface. Using the Pentacam HR, CD measurements were acquired over a corneal area of 12 mm in total and at four concentric zones (0-2, 2-6, 6-10, and 10-12 mm) of three corneal stromal depths: 120 µm of the anterior corneal stromal layer, 60 µm of the posterior corneal stromal layer, and the central layer of stroma lying between these two layers. Results: We included 40 eyes of 40 patients, including 8 (20%) male and 32 (80%) female individuals, with a mean (standard deviation) age of 21.0 (6.4) years. We observed a significant improvement in the topographic values of steep keratometry (K), flat K, maximum K, and corneal astigmatism (all P < 0.05), but not in the mean K, thinnest corneal pachymetry, corneal thickness at the apex, back elevation, or front elevation (all P > 0.05). The mean total anterior, central, and posterior CD differed significantly among the time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05) and no difference between those of the 1-month and 3-month postoperative visits (all P > 0.05). The mean CD for the anterior layer in the central, paracentral, and mid-peripheral zones, and the central layer in all four zones, differed significantly among time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05), which remained unchanged from the 1-month to the 3-month postoperative visit (all P < 0.05), except for the central 2-6-mm zone, which decreased significantly from the 1-month to the 3-month postoperative visit (P < 0.001). The CD of the central 10-12-mm zone did not differ significantly in each pairwise comparison (all P > 0.05). In contrast, CD for the posterior layer in the paracentral zone decreased significantly from the preoperative to the 1-month and 3-month postoperative visits but increased, to a lesser extent, from the 1-month to the 3-month postoperative visit (all P < 0.05). Conclusions: Femtosecond laser-assisted Keraring implantation significantly changes CD, with improvement in most topography parameters. Further longitudinal studies with larger sample sizes are required to verify these preliminary findings.

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. HIGHLIGHTS: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

The role of ultra-widefield imaging with navigated central and peripheral cross-sectional and three-dimensional swept source optical coherence tomography in ophthalmology: Clinical applications.

PURPOSE: To assess central and peripheral retinal and choroidal diseases using ultra-widefield (UWF) fundus imaging in combination with navigated central and peripheral cross-sectional and three-dimensional (3D) swept source optical coherence tomography (SS-OCT) scans. METHODS: Retrospective study involving 332 consecutive patients, with a nearly equal distribution of males and females. The mean age of patients was 52 years (range 18-92 years). Average refractive error was -3.80 D (range +7.75 to -20.75 D). RESULTS: The observations in this study demonstrate the efficacy of peripheral navigated SS-OCT in assessing various ocular conditions. The technology provides high-quality images of the peripheral vitreous, vitreoretinal interface, retina, and choroid, enabling visualization of vitreous floaters and opacities, retinal holes and tears, pigmented lesions, and peripheral retinal degenerations. 3D OCT scans enhance the visualization of these abnormalities and improve diagnostic and therapeutic decisions. CONCLUSION: Navigated central and peripheral cross-sectional and 3D SS-OCT scans offer significant complementary benefits in the assessment and management of retinal diseases. Their addition to UWF imaging provides a comprehensive view of central and peripheral ocular structures, aiding in early detection, precise anatomical measurements, and objective monitoring of disease progression. In addition, this technology serves as a valuable tool for patient education, a teaching tool for trainees, and documentation for medico-legal purposes.

Association between fatty acid intake and age-related macular degeneration: a meta-analysis.

Objective: The association of age-related macular degeneration (AMD) with the intake of high and low fatty acids (FAs), respectively, remains controversial. To this end, we performed a comprehensive meta-analysis of all the existing studies on the association of various intake levels of FA subtypes with AMD to determine these associations. Methods: A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted from inception to September 2023. To compare the highest and lowest groups, odds ratio (OR) with 95% confidence intervals (CIs) was analyzed with a random-effects model/fixed-effects model. Results: A high intake of omega-3 LCPUFAs (OR:0.67; 95%CI:[0.51, 0.88]; p = 0.004), DHA (OR:0.80; 95%CI:[0.70, 0.90]; p < 0.001), EPA (OR:0.91; 95%CI:[0.86, 0.97]; p = 0.004), and simultaneous intake of DHA and EPA (OR:0.79; 95%CI:[0.67, 0.93]; p = 0.035) significantly reduced the risk of overall AMD. Conversely, a high intake of trans-FAs (OR: 2.05; 95%CI: [1.29, 3.25]; p = 0.002) was significantly related to an increased risk of advanced AMD compared to the low-intake group. The subgroup analysis results are shown in the articles. Conclusion: Increasing dietary intake of omega-3 LCPUFAs, specifically DHA, and EPA, or the simultaneous intake of DHA and EPA, is significantly associated with a reduced risk of overall AMD. Various subtypes of omega-3 also have a significant association with a reduced risk of different stages of AMD. The high intake of trans-fatty acids (TFAs) is significantly and positively correlated with the risk of advanced AMD. This could further support the idea that consuming foods rich in omega-3 LCPUFAs and reducing consumption of foods rich in TFAs may prevent AMD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023467227.