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Background: Sitting-related pain is a common feature of patellofemoral pain (PFP). However, little is known regarding features associated with sitting-related PFP. The aim of this study was to determine whether sitting-related PFP is associated with patellofemoral alignment, morphology and structural magnetic resonance imaging (MRI) features of the patellofemoral joint (cartilage lesions, bone marrow lesions, fat pad synovitis)., Methods: 133 individuals with PFP were included from two unique but similar cohorts. Participants were classified into one of three groups based on their response to item 8 of the Anterior Knee Pain Scale: (i) problems with sitting; (ii) sitting pain after exercise; and (iii) no difficulty with sitting. All participants underwent 3T Magnetic Resonance Imaging (MRI) to enable: (i) scoring of structural features of the patellofemoral joint with MRI Osteoarthritis Knee Score (MOAKS); and (ii) patellofemoral alignment and morphology measurements using standardised methods. The association of sitting pain to bony alignment, morphology and MOAKS features were evaluated using multinomial logistic regression (adjusted for age, sex, BMI; reference group = no difficulty with sitting)., Results: 82 (61.7%) participants reported problems with sitting, and 24 (18%) participants reported sitting pain after exercise. There were no significant associations between the presence of sitting pain and any morphology, alignment or structural characteristics., Conclusions: Findings indicate that PFP related to sitting is not associated with patellofemoral alignment, morphology, or structural MRI features of the patellofemoral joint. Further research to determine mechanisms of sitting-related PFP, and inform targeted treatments, are required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.) more...

Objective: To describe the prevalence of radiographic features of patellofemoral (PF) osteoarthritis (OA) in adults with persistent PF pain, to describe the prevalence of magnetic resonance imaging (MRI)-defined PF OA and compare it to that in age- and sex-matched controls, and to explore the prevalence of radiographic and MRI-defined PF OA across age, sex, and body mass index (BMI) groups., Methods: This cross-sectional study included 84 individuals with PF pain ≥3 months duration and 26 age- and sex-matched controls. In participants with PF pain, posteroanterior, lateral, and skyline radiographs were obtained. Radiographic OA features were scored using Kellgren/Lawrence (K/L) criteria and a radiographic atlas, with K/L grade ≥2 defined as OA, and K/L grade 1 as early OA. Both groups underwent 3.0 Tesla MRI scans, scored using the MRI Osteoarthritis Knee Score criteria. Compartmental prevalence of MRI OA features was based on cartilage lesions, bone marrow lesions (BMLs), and osteophytes., Results: Overall, 20 participants (24%) with PF pain had radiographic PF OA (K/L grade ≥2), and 36 participants (43%) had early PF OA (K/L grade 1). MRI-defined PF OA was more prevalent in participants with PF pain (16-29%) than in controls (4-12%), irrespective of how PF OA was defined. Within the PF pain group, the prevalence of PF OA on radiographs and MRI was greater in participants who were older or female or who had a higher BMI., Conclusion: Features of radiographic and MRI-defined PF OA were evident in 20-30% of adults ages 26-50 years with persistent PF pain, with greater prevalence observed in those who were older, or female, or who had a higher BMI. MRI-defined PF OA was more prevalent in individuals with PF pain than in pain-free controls, especially when defined as a full-thickness cartilage lesion with BML., (© 2018, American College of Rheumatology.) more...

Background: Patellofemoral malalignment has been observed among people with patellofemoral pain (PFP) and may be associated with the presence of imaging features of osteoarthritis, symptoms, and function., Purpose: To determine whether patellofemoral joint alignment and bony shape are associated with (1) cartilage, bone, and soft tissue morphological abnormalities defined on magnetic resonance imaging (MRI) and (2) reported symptoms and function among people with PFP., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Participants (mean ± SD age, 30.2 ± 9.5 years; range, 14-50 years; 78 females, 58.6%) completed questionnaires regarding demographics, pain, symptoms, and function and underwent a 3-T MRI scan of their more symptomatic eligible knee. Structural MRI abnormalities were scored with the MOAKS (Magnetic Resonance Imaging Osteoarthritis Knee Score), and MRI alignment and shape were measured with standardized methods. Associations among MOAKS features, PFP symptoms, and alignment and shape measures were evaluated with regression analyses (α = .05)., Results: Minor cartilage defects were present in 22 (16.5%) participants, patellar osteophytes in 83 (62.4%), anterior femur osteophytes in 29 (21.8%), Hoffa synovitis in 81 (60.9%), and prefemoral fat pad synovitis in 49 (36.8%). A larger Insall-Salvati ratio was significantly associated with the presence of patellar osteophytes (odds ratio [OR], 51.82; 95% CI, 4.20-640.01), Hoffa synovitis (OR, 60.37; 95% CI, 4.66-782.61), and prefemoral fat pad synovitis (OR, 43.31; 95% CI, 4.28-438.72) in the patellofemoral joint. A larger patellar tilt angle was significantly associated with the presence of minor cartilage defects (OR, 1.10; 95% CI, 1.00-1.20), the presence of patellar osteophytes (OR 1.12; 95%CI 1.02-1.22), and prefemoral fat pad synovitis (OR, 1.11; 95% CI, 1.03-1.20) in the patellofemoral joint. Finally, a larger bisect offset was significantly associated with the presence of minor cartilage defects (OR, 1.05; 95% CI, 1.00-1.11) and patellar osteophytes (OR, 1.07; 95% CI, 1.01-1.14) in the patellofemoral joint. The majority of patellofemoral alignment measures were not associated with symptoms or function., Conclusion: For people with PFP, the presence of morphological abnormalities defined on MRI appears to be related to particular patellofemoral alignment measures, including higher Insall-Salvati ratio (indicating patella alta), larger patellar tilt angle (indicating greater lateral tilt), and larger bisect offset (indicating greater lateral displacement). Hardly any associations were found with symptoms or function. So there might be a distinct subgroup of PFP that is more prone to developing patellofemoral osteoarthritis later in life, as particular alignment measures seem to be associated with the presence of patellar osteophytes. Prospective studies are required to investigate the longitudinal relationship between alignment or bony shape and morphological abnormalities defined on MRI in this patient population. more...

Background: Structural abnormalities of the patellofemoral joint might play a role in the pathogenesis of patellofemoral pain (PFP), a common knee problem among young and physically active individuals. No previous study has investigated if PFP is associated with structural abnormalities of the patellofemoral joint using high-resolution magnetic resonance imaging (MRI)., Purpose: To investigate the presence of structural abnormalities of the patellofemoral joint on high-resolution MRI in patients with PFP compared with healthy control subjects., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Patients with PFP and healthy control subjects between 14 and 40 years of age underwent high-resolution 3-T MRI. All images were scored using the Magnetic Resonance Imaging Osteoarthritis Knee Score with the addition of specific patellofemoral features. Associations between PFP and the presence of structural abnormalities were analyzed using logistic regression analyses adjusted for age, body mass index (BMI), sex, and sports participation., Results: A total of 64 patients and 70 control subjects were included in the study. Mean ± SD age was 23.2 ± 6.4 years, mean BMI ± SD was 22.9 ± 3.4 kg/m(2), and 56.7% were female. Full-thickness cartilage loss was not present. Minor patellar cartilage defects, patellar bone marrow lesions, and high signal intensity of the Hoffa fat pad were frequently seen in both patients (23%, 53%, and 58%, respectively) and control subjects (21%, 51%, and 51%, respectively). After adjustment for age, BMI, sex, and sports participation, none of the structural abnormalities were statistically significantly associated with PFP., Conclusion: Structural abnormalities of the patellofemoral joint have been hypothesized as a factor in the pathogenesis of PFP, but the study findings suggest that structural abnormalities of the patellofemoral joint on MRI are not associated with PFP., (© 2016 The Author(s).) more...

Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as therapeutics for MS. more...

Background: Prolonged exposure to ketamine results in accelerated neurodegeneration and neurocognitive deficits in the neonatal rats. Experimental models of neurodegeneration have implicated reentry of postmitotic neurons into the cell cycle, leading to cell death. The authors hypothesize that the ketamine-induced neuroapoptosis is partially due to aberrant cycle cell reentry. To explore this hypothesis, the authors characterized the effect of ketamine on the cell cycle signaling pathway in the developing rodent brain in vivo and in vitro., Methods: Postnatal day 7 rat pups and primary neurons were used for the experiments. Each rat pup received five intraperitoneal doses of either saline or ketamine (5, 10, and 20 mg/kg/dose) at 90-min intervals over 6 h. Primary neurons were exposed to varying concentrations of ketamine to determine the dose and duration effects. The expression of cell cycle proteins (cyclin D1, cyclin-dependent kinase 4, and E2F1), Bcl2-interacting mediator of cell death (Bim), and activated caspase-3 was determined. The effect of cyclin D1 knockdown by small interfering RNA was also examined in primary neurons incubated in ketamine., Results: Ketamine mediated a dose- and time-dependent increase in expression of cell cycle proteins and activated caspase-3. Cyclin D1, cyclin-dependent kinase 4, E2F1, Bim, and cleaved caspase-3 expression increased at 12 h and peaked at 24 h in vitro. Knockdown of cyclin D1 by small interfering RNA attenuated Bim and cleaved caspase-3 expression., Conclusion: These findings support a model in which ketamine induces aberrant cell cycle reentry, leading to apoptotic cell death in the developing rat brain. more...

How axon regeneration is controlled in both PNS and CNS remains elusive. Mechanistic studies of axon growth during development and axon regeneration after injury reveal the PTEN dependent molecular mechanism as a commonality. This pathway could impact the processes occurring in the neuronal soma, such as mTOR-regulated protein translation, and in the axons, such as cytoskeleton assembly. In this review, we will discuss the current understanding of the involvement of these processes in the regulation of axon growth and the potential implication in promoting axon regeneration after injury., (Copyright 2010 Elsevier Inc. All rights reserved.) more...

Introduction: Anti-citrullinated protein antibodies have a diagnostic role in rheumatoid arthritis (RA); however, little is known about their origins and contribution to pathogenesis. Citrullination is the post-translational conversion of arginine to citrulline by peptidyl arginine deiminase, and increased citrullination of proteins is observed in the joint tissue in RA and in brain tissue in multiple sclerosis (MS)., Methods: We applied synovial and myelin protein arrays to examine epitope spreading of B cell responses to citrullinated epitopes in both the collagen-induced arthritis (CIA) model for RA and the experimental autoimmune encephalomyelitis (EAE) model for MS. Synovial and myelin protein arrays contain a spectrum of proteins and peptides, including native and citrullinated forms, representing candidate autoantigens in RA and MS, respectively. We applied these arrays to characterise the specificity of autoantibodies in serial serum samples derived from mice with acute and chronic stages of CIA and EAE., Results: In samples from pre-disease CIA and acute-disease EAE, we observed autoantibody targeting of the immunising antigen and responses to a limited set of citrullinated epitopes. Over the course of diseases, the autoantibody responses expanded to target multiple citrullinated epitopes in both CIA and EAE. Using immunoblotting and mass spectrometry analysis, we identified citrullination of multiple polypeptides in CIA joint and EAE brain tissue that have not previously been described as citrullinated., Conclusions: Our results suggest that anti-citrulline antibody responses develop in the early stages of CIA and EAE, and that autoimmune inflammation results in citrullination of joint proteins in CIA and brain proteins in EAE, thereby creating neoantigens that become additional targets in epitope spreading of autoimmune responses. more...

In an effort to use model fluid membranes for immunological studies, we compared the formation of planar phospholipid bilayers supported on silicon dioxide surfaces with and without incorporation of glycolipids as the antigen for in situ antibody binding. Dynamic light scattering measurements did not differentiate the hydrodynamic volumes of extruded small unilamellar vesicles (E-SUVs) containing physiologically relevant concentrations (0.5-5 mol%) of monosialoganglioside GM1 (GM1) from exclusive egg yolk L-alpha-phosphatidylcholine (egg PC) E-SUVs. However, quantifiable differences in deposition mass and dissipative energy loss emerged in the transformation of 5 mol% GM1/95 mol% egg PC E-SUVs to planar supported lipid bilayers (PSLBs) by vesicle fusion on thermally evaporated SiO2, as monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. Compared to the 100 mol% egg PC bilayers on the same surface, E-SUVs containing 5 mol% GM1 reached a approximately 12% higher mass and a lower dissipative energy loss during bilayer transformation. PSLBs with 5 mol% GM1 are approximately 18% heavier than 100 mol% egg PC and approximately 11% smaller in projected area per lipid, indicating an increased rigidity and a tighter packing. Subsequent binding of polyclonal immunoglobulin G anti-GM1 to the PSLBs was performed in situ and showed specificity. The anti-GM1 to GM1 ratios at equilibrium were roughly proportional to the concentrations of anti-GM1 administered in the solution. Fluorescence recovery after photobleaching was utilized to verify the retained, albeit reduced lateral fluidity of the supported membranes. Five moles percentage of GM1 membranes (GM1 to PC ratio approximately 1:19) decorated with 1 mol% N-(Texas Red sulfonyl)-1,2-dihexadecanoyl-sn-glycerol-3-phosphoethanolamine (Texas Red DHPE) exhibited an approximately 16% lower diffusion coefficient of 1.32+/-0.06 microm2/s, compared to 1.58+/-0.04 microm2/s for egg PC membranes without GM1 (p<0.01). The changes in vesicle properties and membrane lateral fluidity are attributed to the interactions of GM1 with itself and GM1 with other membrane lipids. This system allows for molecules of interest such as GM1 to exist on a more biologically relevant surface than those used in conventional methods such as ELISA. Our analysis of rabbit serum antibodies binding to GM1 demonstrates this platform can be used to test for the presence of anti-lipid antibodies in serum. more...

Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination. more...

In his or her life-long career, the physician will eventually encounter a patient with factitious disorder, or Munchausen's syndrome. We discuss two patients complaining of renal colic that were identified as having Munchausen's syndrome. We review the literature to identify certain aspects of the disease and to discuss the medical and legal implications for the treating physician and hospital. more...