Normal Disc Research Articles

Stress-Activated Protein Kinases in Intervertebral Disc Degeneration: Unraveling the Impact of JNK and p38 MAPK.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The pathophysiological development of IDD is closely related to the stimulation of various stressors, including proinflammatory cytokines, abnormal mechanical stress, oxidative stress, metabolic abnormalities, and DNA damage, among others. These factors prevent normal intervertebral disc (IVD) development, reduce the number of IVD cells, and induce senescence and apoptosis. Stress-activated protein kinases (SAPKs), particularly, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), control cell signaling in response to cellular stress. Previous studies have shown that these proteins are highly expressed in degenerated IVD tissues and are involved in complex biological signal-regulated processes. Therefore, we summarize the research reports on IDD related to JNK and p38 MAPK. Their structure, function, and signal regulation mechanisms are comprehensively and systematically described and potential therapeutic targets are proposed. This work could provide a reference for future research and help improve molecular therapeutic strategies for IDD.

EFFECTS OF ANTICOAGULANTS ON BLOOD CELLS MORPHOLOGY AND BIOCHEMISTRY

Blood is a particular type of connective tissue that majorly contains red blood cells (RBCs), white blood cells (WBCs), and platelets (Plts). Anticoagulants are used to preserve the fluidity of blood and retard morphological changes in blood cells. Anticoagulants like EDTA, heparin, sodium citrate, and CPDA-1 are used. However, these anticoagulants also have some disadvantages, summarized in this review. This chemical causes the lysis of many cells, including RBCs, and some of them, like EDTA, cause agglutination of platelets, which not only causes a decrease in platelet count but also causes a spurious increase in WBC count. These substances also alter the shapes of various cells present in blood. RBCs and platelets may become spherical from the normal biconcave disc and plate-like structures. Commonly used anticoagulants contribute to alterations of many hematological parameters, including hematocrit, hemoglobin concentration, and packed cell volume of RBCs. Certain chemicals used in anticoagulant solutions, such as potassium and sodium in EDTA solution, make the blood unsuitable for determining these electrolytes in the sample. They also induce many changes in the biochemical composition of the sample. The most affected biochemical changes are observed in 2,3-DPG, D-dimer concentration, blood gas estimation, and cytokine levels. As they contain different chemicals, they have varying pH, so they alter blood pH.

Systemic steroids in pediatric pseudotumor cerebri - A case report

Study design: Case report. Purpose: To study the efficacy of systemic steroids in pediatric pseudotumor cerebri. Introduction: Pseudotumor cerebri is a condition caused by elevated intracranial pressure presenting most commonly with headache. It is a diagnosis of exclusion. Methods: A 15-year-old girl presented in our outpatient department with a headache for 3 months, more in the posterior aspect, continuous type with severe intensity, non-radiating. On examination, the best corrected visual acuity in her right eye was 6/9, and her left eye was 6/6 parts. She had a normal anterior segment and normal Intraocular Pressure (IOP). Fundoscopy showed both optic discs edematous, pink in color with blurry disc margins, tortuous disc vessels, and edematous peripapillary area. The rest of the retina was normal. Lumbar puncture showed elevated opening CSF pressure and normal CSF composition. Hence she was diagnosed with IIH. She was started on oral prednisolone 1mg/kgbw once a day dosage, oral acetazolamide 250 mg once a day, topical nepafenac 0.1% one drop thrice a day and timolol 0.5% eye drops twice a day. Discussion: The main goals of treatment are alleviation of symptoms, including headache, and preservation of vision. Steroids were commonly used for treating IIH in the past, but cause significant long-term side effects, such as weight gain, that are undesirable in IIH patients. Furthermore, withdrawal of steroids can cause rebound intracranial hypertension. Thus, steroids should not be used routinely for IIH treatment. Results: By the end of one month, the patient was relieved of symptoms, best corrected visual acuity was 6/6 in both eyes with normal IOP, normal optic disc in both eyes. Conclusion: Steroids are an effective way of managing idiopathic intracranial hypertension in pediatric patients.

Comparative study of clinical and MRI features of TMD patients with or without joint effusion: a retrospective study

BackgroundThe relationship between joint effusion and temporomandibular disorders (TMD) remains unclear. The purpose of this study was to investigate the correlation among joint effusion, clinical features and MRI imaging features of TMD.MethodsA total of 1532 temporomandibular joints (TMJs) from 766 patients (605 females and 161 males) with the mean age of 31.68 ± 13.71 years from January 2022 to June 2023 were included in the study. Clinical and MRI features were collected and analyzed. Chi-Square test, Spearman correlation coefficient and binary logistic regression analysis were performed.ResultsPatients with joint effusion were significantly older and had smaller value of MIO (p < 0.001). There were significant differences in the distribution of joint sounds (with or without), joint pain (with or without), disc morphology (biconcave, contracture, irregular and lengthened) and disc position between joint effusion group (JE) and non-joint effusion group (NA) (P < 0.05).The odds of having joint effusion were 1.726 higher in patients with joint sounds when compared to those without joint sounds. The odds of having joint effusion were 8.463 higher in patients with joint pain when compared to those without joint pain. The odds of having joint effusion were 2.277 higher in patients with contracture when compared to those with biconcave. The odds of having joint effusion were 1.740 higher in patients with anterior disc displacement with reduction (ADDWR) when compared to those with normal disc position. The prediction accuracy of this model is 74.9%, and the area under curve (AUC) is 79.5%, indicating that it can be used for the prediction and the judgment effect is average.ConclusionsThe results demonstrated that joint sounds, joint pain, contracture, and ADDWR are high risk factors for joint effusion, especially joint pain.Trial registrationThis study was retrospectively registered on 28/03/2022 and endorsed by the Ethics Committee of Affiliated Stomatology Hospital of Guangzhou Medical University (LCYJ2022014).

Tribo‐performance assessment of brake friction composites prepared from agro‐industrial‐sea wastes using pin‐on‐disc

AbstractIn this work, eco‐friendly brake friction composites were developed using walnut shell powder‐fly ash‐white ark shell powder (agro‐industrial‐sea waste). The waste materials content in the friction composites varied from 33 to 53 wt% including a fixed content of fly ash (30 wt%) and walnut shell powder (3 wt%) and a varying amount of white ark shell powder (WASP) from 0 to 20 wt% with a step of 5 wt%. The fabricated specimens were characterized for tribo‐performance and compared with commercial brake lining specimen (CBLS) in compliance with ASTM G99 standards using pin‐on‐disc test setup under dry conditions. The specimens were tested for the disc speed varying from 500 to 2000 rpm under 50 and 150 N of normal loads. The friction coefficients and volume loss of the fabricated specimens were found insensitive to the compositional changes and highly sensitive to the normal load and disc speeds. SEM‐EDS analysis showed the frequent formation of friction films at higher disc speed and integration and disintegration of contact plateaus responsible for the changes in the friction and wear behavior. The direct comparison between the friction coefficient and volume loss indicated that 10 wt% of WASP in compensation with BaSO4 may be used to develop the brake friction composite.Highlights Brake friction composites prepared from the waste materials offered μ‐values from 0.31 to 0.6 in comparison with the CBLS. Friction coefficient dropped significantly at higher disc speed. Morphological and elemental analysis supported in estimating the probable friction and wear mechanisms.

Association Between Articular Eminence Structure and Joint Spaces in Temporomandibular Joints with Anterior Disc Displacement.

The association among the joint spaces, articular eminence morphology, and disc displacement is not well documented in the literature. This study aims to evaluate and compare the joint spaces and the articular eminence structure (eminence height [Eh] and inclination [Ei]) using cone-beam computed tomography (CBCT) of temporomandibular joints (TMJs) with anterior disc displacements and joints with normal disc position. The study groups consisted of 75 TMJs of 39 patients. The disc status of TMJs was diagnosed with magnetic resonance imaging, and the measurements were performed on CBCT. Three groups, that is, normal disc position (NDP) group, anterior disc displacement with reduction (ADDWR) group, and anterior disc displacement without reduction (ADDWoR) group, were established. Anterior, superior, posterior joint spaces (AJS, SJS, and PJS, respectively), articular Eh, and articular Ei were measured. Statistical Package for the Social Sciences version 22 was used for statistical analysis. Shapiro-Wilk test was used to check the normality of data. Intergroup comparisons of categorical variables were assessed with Fisher-Freeman-Halton test. For comparison of continuous variables parameters, Mann-Whitney U test and Kruskal-Wallis test were used. Statistical significance level was determined as P < 0.05. Significant differences were not found in intergroup comparisons for PJS. However, the difference between groups was found to be significant for AJS, SJS, Eh, and Ei. Intergroup comparisons were performed for these parameters. No significant difference was found between the NDP group and the ADDWR group for AJS, SJS, Eh, and Eİ. The mean AJS, SJS, Eh, and Ei values in ADDWoR were found to be significantly lower compared to the corresponding values in both NDP and ADDWR groups. Decreased AJS and SJS when TMJ is evaluated with CBCT may be an indicator of ADDWoR. Authors suggest that narrowed articular Ei and reduced articular Eh can be one of the predisposing factors for anterior disc displacement.

Bilateral Ocular Ischaemic Syndrome due to Carotid Artery and Cardiovascular Disease: A Case Report

Introduction : Ocular ischemic syndrome (OIS) is a rare but potentially blinding and fatal condition caused by carotid artery disease or other systemic condition results in ocular hypoperfusion.&#x0D; Case Illustration : A 62-year-old male with sudden bilateral vision loss, swelling, redness and pain of both eye for 7 days. There were dilated conjunctival and episcleral vessels, visual acuity of the right eye was hand movement and 0.05 for left eye, intraocular pressure (IOP) was 33 mmHg in right eye and 37 mmHgfor left eye. Anterior segment evaluation revealed rubeosis iris, mild anterior chamber reaction, and temporal angle neovascularization on gonioscopy. Both direct and consensual light reflexes were sluggish. Fundus examination showed normal optic disc, minimal hemorrhages at mid-periphery, narrowed arterioles, and minimal cotton wool spot. Macular OCT demonstrated discrete hyperreflectivity of inner retinal layers. From Macular Angiography OCT, ETDRS Central vessel density were 11.2% and 17.6% for the right eye and left eye, respectively. In both eyes, paracentesisof anterior chamber, intravitreal and intracameral injections of anti-VEGF were performed. Brain Magnetic Resonance Angiography Imaging revealed moderate stenosis of both distal carotid artery circulation. Percutaneous Coronary Angiography showed extensive stenosis in coronary artery, with low Ejection Fraction.&#x0D; Discussion : For the cardiovascular management, a pacemaker was implanted. One week after procedure, BCVA were 1/60 and 0.15, and IOPs of 17 and 18 mmHg, for the right and left eye, respectively. The patient was scheduled to have laser retinal photocoagulation.&#x0D; Conclusion : Quick clinical diagnosis, targeted workup for systemic associations, and prompt treatment might preserve life and sight in OIS.

A three-dimensional imaging study of the effect of anterior disc displacement on the bony structural relationship of the temporomandibular joint

Objective: To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further. Methods: Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results: CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm3]>ADDWR group [(1 747.34±369.42) mm3]>ADDWoR group [(1 256.29±418.27) mm3] [t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm2]>ADDWR group [(838.23±118.82) mm2]>ADDWoR group [(669.14±150.26) mm2] [t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUCCV=0.77, AUCCSA=0.76; AUCSJS=0.76) for the NADP and ADDWoR groups, and (AUCCV=0.80; AUCCSA=0.80; AUCSJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC(NADP-ADDWR)=0.73, and AUC(ADDWR-ADDWoR)=0.69. Conclusions: CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.

Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms

Intervertebral disc degeneration is closely related to abnormal phenotypic changes in disc cells. However, the mechanism by which disc cell phenotypes are maintained remains poorly understood. Here, Hedgehog-responsive cells were found to be specifically localized in the inner annulus fibrosus and cartilaginous endplate of postnatal discs, likely activated by Indian Hedgehog. Global inhibition of Hedgehog signaling using a pharmacological inhibitor or Agc1-CreERT2-mediated deletion of Smo in disc cells of juvenile mice led to spontaneous degenerative changes in annulus fibrosus and cartilaginous endplate accompanied by aberrant disc cell differentiation in adult mice. In contrast, Krt19-CreER-mediated deletion of Smo specifically in nucleus pulposus cells led to healthy discs and normal disc cell phenotypes. Similarly, age-related degeneration of nucleus pulposus was accelerated by genetic inactivation of Hedgehog signaling in all disc cells, but not in nucleus pulposus cells. Furthermore, inactivation of Gli2 in disc cells resulted in partial loss of the vertebral growth plate but otherwise healthy discs, whereas deletion of Gli3 in disc cells largely corrected disc defects caused by Smo ablation in mice. Taken together, our findings not only revealed for the first time a direct role of Hedgehog-Gli3 signaling in maintaining homeostasis and cell phenotypes of annuls fibrosus and cartilaginous endplate, but also identified disc-intrinsic Hedgehog signaling as a novel non-cell-autonomous mechanism to regulate nucleus pulposus cell phenotype and protect mice from age-dependent nucleus pulposus degeneration. Thus, targeting Hedgehog signaling may represent a potential therapeutic strategy for the prevention and treatment of intervertebral disc degeneration.

Analysis of joint protein expression profile in anterior disc displacement of TMJ with or without OA.

Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the invitro and invivo results are consistent with protein changes detected in MS profile. This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets.

The BONSAI (Brain and Optic Nerve Study with Artificial Intelligence) deep learning system can accurately identify pediatric papilledema on standard ocular fundus photographs

BackgroundPediatric papilledema often reflects an underlying severe neurologic disorder and may be difficult to appreciate, especially in young children. Ocular fundus photographs are easy to obtain even in young children and in nonophthalmology settings. The aim of our study was to ascertain whether an improved deep-learning system (DLS), previously validated in adults, can accurately identify papilledema and other optic disk abnormalities in children. MethodsThe DLS was tested on mydriatic fundus photographs obtained in a multiethnic pediatric population (<17 years) from three centers (Atlanta-USA; Bucharest-Romania; Singapore). The DLS’s multiclass classification accuracy (ie, normal optic disk, papilledema, disks with other abnormality) was calculated, and the DLS’s performance to specifically detect papilledema and normal disks was evaluated in a one-vs-rest strategy using the AUC, sensitivity and specificity, with reference to expert neuro-ophthalmologists. ResultsExternal testing was performed on 898 fundus photographs:447 patients; mean age, 10.33 (231 patients ≤10 years of age; 216, 11-16 years); 558 normal disks, 254 papilledema, 86 other disk abnormalities. Overall multiclass accuracy of the DLS was 89.6% (range, 87.8%-91.6%). The DLS successfully distinguished “normal” from “abnormal” optic disks (AUC 0.99 [0.98-0.99]; sensitivity, 87.3% [84.9%-89.8%]; specificity, 98.5% [97.6%-99.6%]), and “papilledema” from “normal and other” (AUC 0.99 [0.98-1.0]; sensitivity, 98.0% [96.8%-99.4%]; specificity, 94.1% (92.4%-95.9%)]. ConclusionsOur DLS reliably distinguished papilledema from normal optic disks and other disk abnormalities in children, suggesting it could be utilized as a diagnostic aid for the assessment of optic nerve head appearance in the pediatric age group.

Scanning Laser Ophthalmoscopy Demonstrates Pediatric Optic Disc and Peripapillary Strain During Horizontal Eye Rotation

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults. Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed. Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults, 1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p < .001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels. Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy.

Correlation between TMJ Space Alteration and Disc Displacement: A Retrospective CBCT and MRI Study.

This study aims to determine if a large anterior and reduced posterior/superior joint space is highly predictable for disc displacement. From patients with temporomandibular disorders symptoms, fifty-two experimental joints and fourteen control joints were included. The cone beam computed tomography (CBCT) images were used to calculate posterior-to-anterior (P-A) and superior-to-anterior (S-A) joint space ratios, while disc position was determined using magnetic resonance imaging (MRI). One-way analysis of covariance test and receiver operating characteristics analysis were carried out. The results showed that among the 52 experimental joints, 45 were diagnosed as disc displacement and 7 as normal disc positions (N). All 14 control joints showed normal disc positions. The P-A ratio was 1.46 ± 0.21, 0.99 ± 0.23, and 0.86 ± 0.30 in the control, N, and DD groups, respectively (p < 0.001). The S-A ratio was 1.80 ± 0.27, 1.44 ± 0.33, and 1.08 ± 0.35 in the control, N, and DD groups, respectively (p < 0.001). When an altered P-A ratio and/or S-A ratio are observed on the CBCT, the diagnosis of disc displacement is quite predictable with high sensitivity and specificity.

Artificial intelligence in glaucoma detection using color fundus photographs.

To explore the potential of artificial intelligence (AI) for glaucoma detection using deep learning algorithm and evaluate its accuracy for image classification of glaucomatous optic neuropathy (GON) from color fundus photographs. A total of 1375 color fundus photographs, 735 normal optic nerve head and 640 GON, were uploaded on the AI software for training, validation, and testing using deep learning model, which is based on Residual Network (Res Net) 50V2. For initial training and validation, 400 fundus images (200 normal and 200 GON) were uploaded and for the final training and testing 975 (535 normal and 440 GON) were uploaded later. Accuracy, sensitivity, and specificity were used to evaluate the image classification performance of the algorithm. Also, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated. The model used in the study showed an image classification accuracy of 81.3%, sensitivity of 83%, and specificity of 80% for the detection of GON. The false-negative grading was 17% and false-positive grading was 20% for the image classification of GON. Coexistence of glaucoma in patients with high myopia, early glaucoma in a small disc, and software misclassification of GON were the reasons for false-negative results. Physiological large cupping in a large disc, myopic or titled disc, and software misclassification of normal optic disc were the reasons for false-positive results. The model employed in this study achieved a good accuracy, and hence has a good potential in detection of GON using color fundus photographs.

Prevalence of serum MOG antibody and AQP4 antibody in optic neuritis after SARS-CoV-2 infection.

To evaluate the prevalence of serum myelin oligodendrocyte glycoprotein antibody (MOG-Ab) and aquaporin-4 antibody (AQP4-Ab) in optic neuritis (ON) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by cell-based indirect immunofluorescence assay (CBA). In this prospective case series study, 35 patients clinically diagnosed as ON and laboratory-confirmed SARS-CoV-2 infection from 8 December 2022 to 8 February 2023 were included. All patients' clinical and laboratory data were collected and analyzed. The mean age of the 35 patients (46 eyes) was 38.2 years (ranging from 6 to 69 years), and 17 cases were female patients. Thirty-three and two cases showed positive SARS-CoV-2 RNA test results before or shortly after ON onset, respectively. ON occurred unilaterally in 24 cases and bilaterally in 11 cases. Ophthalmic examination revealed swollen optic disc in 37 eyes, normal optic disc in 6 eyes, and temporally or wholly paled optic disc in 3 eyes. CBA revealed seropositive MOG-Ab in 10 cases and AQP4-Ab in 2 cases, respectively, of which 2 AQP4-Ab-seropositive cases and 1 MOG-Ab-seropositive case had a past medical history of ON. Most ON patients showed a rapid and dramatic response to pulse steroid therapy. The median of BCVA at the onset and at the last follow-up was 20/500 (ranging from light perception to 20/20) and 20/67 (ranging from counting fingers to 20/20), respectively. Serum MOG-Ab and AQP4-Ab were detected in 28.6% (10/35) and 5.7% (2/35) ON cases after SARS-CoV-2 infection. SARS-CoV-2 infection may trigger an onset or a relapse of ON, as well as the production of MOG-Ab.

Mesenchymal stem cell exosomes inhibit nucleus pulposus cell apoptosis via the miR-125b-5p/TRAF6/NF-κB pathway axis.

Intervertebral disc degeneration (IVDD) is the pathological basis of a range of degenerative spinal diseases and is the primary cause of lower back pain. Mesenchymal stem cell (MSC) transplantation inhibits IVDD progression. However, the specific mechanisms that underlie these effects remain unclear. In this study, candidate microRNAs (miRNAs) are screened using bioinformatics and high-throughput sequencing. TNF-α is used to induce nucleus pulposus cell (NPC) degeneration. MSC-derived exosomes (MSC-exosomes) are obtained using high-speed centrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot analysis. Cell viability is determined by CCK-8 assay. Flow cytometry and TUNEL assays are used to detect cell apoptosis. The expression levels of miR-125b-5p are detected by RT-qPCR, and a dual-luciferase gene reporter assay confirms the downstream target genes of miR-125b-5p. Protein expression is determined by western blot analysis. Rat models are used to validate the function of miR-125b-5p in MSC-exosomes. The results show that miR-125b-5p is expressed at low levels in degenerated disc tissues compared with that in normal disc tissues; however, it is highly expressed in MSC-exosomes. Furthermore, MSC-exosomes are efficiently taken up by NPCs while miR-125b-5p is delivered into NPCs; thus, MSC-exosomes act as inhibitors of apoptosis in NPCs. Overexpression of miR-125b-5p downregulates TRAF6 expression and inhibits NF-κB activation. However, TRAF6 overexpression reverses these effects of miR-125b-5p. We demonstrate that MSC-exosomes attenuate IVDD in vivo by delivering miR-125b-5p. MSC-exosomes can deliver miR-125b-5p to target TRAF6, inhibit NF-κB activation, and attenuate the progression of IVDD.

Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.

A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin-3-gallate-coated hydroxyapatite nanorods in O-carboxymethyl chitosan cross-linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin-3-gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1-related pathway) in vitro and in vivo.

The Second Case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Background: Bardet-Biedl syndrome and Laurence-Moon syndrome are rare autosomal recessive disorders with a similar phenotype. They are characterized by the gradual development of phenotype which includes cone-rod retinal dystrophy, obesity, and hypogonadism in males. Other associated abnormalities include learning disability and renal abnormalities. The two conditions are differentiated clinically by the presence of spasticity and the absence of polydactyly in Laurence-Moon syndrome. In 2002, we reported the first patient with Bardet-Biedl syndrome. The boy had polydactyly, obesity, retinal degeneration, and was hospitalized at the University Hospital in Al-Kadhimiyia because of the development of chronic renal failure. Patients and methods: The case of a 9-year-old obese Kurdish girl who had polydactyly of the hands and feet associated with reduced visual acuity is described.Results: A 9-year-old obese Kurdish girl had polydactyly of the hand and feet associated with reduced visual acuity that was attributed to myopia which was partially corrected with eye glasses. The parents were unrelated, and her younger 5-year sister had polydactyly of the feet only. No other family member known to have polydactyly. Both sisters had their extra-digits removed surgically. The girl was studying at fourth grade primary school and the parents reported no learning disability. Fundoscopy showed normal optic disc and periphery of the retina. The presence of retinitis pigmentosa was excluded. However, the foveal reflex was reported to be abnormal by the oophthalmologist. Electroretinography showed evidence of cone-rod dystrophy.Conclusion: The second case of Bardet-Biedl syndrome from Iraq is reported. The current evidence-based expert opinion suggests the use of long tem supplementation of citicoline, co-enzyme Q10 and lutein with hope of retarding the progression to blindness.

Application of a Deep Learning System to Detect Papilledema on Nonmydriatic Ocular Fundus Photographs in an Emergency Department

The Fundus photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) studies showed that ED providers poorly recognized funduscopic findings in patients in the ED. We tested a modified version of the Brain and Optic Nerve Study Artificial Intelligence (BONSAI) deep learning system on nonmydriatic fundus photographs from the FOTO-ED studies to determine if the deep learning system could have improved the detection of papilledema had it been available to ED providers as a real-time diagnostic aid. Retrospective secondary analysis of a cohort of patients included in the FOTO-ED studies. The testing data set included 1608 photographs obtained from 828 patients in the FOTO-ED studies. Photographs were reclassified according to the optic disc classification system used by the deep learning system ("normal optic discs," "papilledema," and "other optic disc abnormalities"). The system's performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 1-vs-rest strategy, with reference to expert neuro-ophthalmologists. The BONSAI deep learning system successfully distinguished normal from abnormal optic discs (AUC 0.92 [95% confidence interval {CI} 0.90-0.93]; sensitivity 75.6% [73.7%-77.5%] and specificity 89.6% [86.3%-92.8%]), and papilledema from normal and others (AUC 0.97 [0.95-0.99]; sensitivity 84.0% [75.0%-92.6%] and specificity 98.9% [98.5%-99.4%]). Six patients with missed papilledema in 1 eye were correctly identified by the deep learning system as having papilledema in the other eye. The BONSAI deep learning system was able to reliably identify papilledema and normal optic discs on nonmydriatic photographs obtained in the FOTO-ED studies. Our deep learning system has excellent potential as a diagnostic aid in EDs and non-ophthalmology clinics equipped with nonmydriatic fundus cameras. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Does Articular Disc Position Change Following Mandibular Setback Surgery?

BackgroundMaintaining condyle position following bilateral sagittal split ramus osteotomy (BSSO) is crucial to minimizing post-operative relapse. However, the impact of BSSO on the articular disc position remains inconclusive. PurposeThis study aimed to investigate the changes in articular disc position following setback BSSO surgery.Study design, setting, and sampling: In this prospective cohort study, subjects with mandibular prognathism requiring setback BSSO were enrolled between August 2021 and June 2022 at the Oral and Maxillofacial Surgery Clinic, Faculty of Dentistry, Chiang Mai University, Thailand. Patients with surgical complications, loss of follow-up, or significant artifacts in their MR images were excluded.' Predictor/exposure/independent variablesThe predictor variable was time and articular disc position was assessed at 3 time points, preoperatively (T0), three months post-surgery (T1), and six months post-surgery (T2). Main outcomeThe primary and secondary outcome variables were the changes in articular disc position between T0-T2 and T0-T1, respectively. Articular disc position was coded as normal, anterior disc displacement with reduction (ADDwR), anterior disc displacement without reduction (ADDwoR), and anterior disc displacement without reduction and degenerative joint disease (ADDwoR+DJD). CovariatesCovariate variables collected included age (years), sex (male or female), asymmetry (present or absent), surgical procedure (single jaw (BSSO) or bimaxillary surgery), and setback distance (millimeters). AnalysesFriedman’s test with 80% power and a significance level of 0.05 was employed. Pairwise comparisons were performed using the Dunn-Bonferroni post hoc test to identify statistically significant differences. ResultsThe study included 16 subjects, six females and ten males, with a total of 32 TMJs. Subjects had a mean age of 23.75 (4.57) years. The proportion of TMJs with normal disc position postoperatively increased from 3 (9.4%) to 19 (59.4%). Statistically significant differences were found in the changes in disc position over time (P < .001). ConclusionsFollowing setback BSSO, the articular discs underwent changes, with a majority of ADDwR cases transitioning to a normal position. Cases with ADDwoR also demonstrated disc reduction capability after surgery. The combined orthodontic treatment and setback BSSO appear to have an effect on articular disc position in skeleton class III patients.