Fragile X syndrome is the most common form of inherited mental retardation and is caused by the absence of expression of the FMR1 gene. The protein encoded by this gene, Fmrp, is an RNA-binding protein that binds a subset of mRNAs and regulates their translation, leading to normal cognitive function. Although the association with RNAs is well established, it is still unknown how Fmrp finds and assembles with its RNA cargoes and how these activities are regulated. We show here that Fmrp is post-translationally methylated, primarily on its arginine-glycine-glycine box. We identify the four arginines that are methylated and show that cellular Fmrp is monomethylated and asymmetrically dimethylated. We also show that the autosomal paralog Fxr1 and the Drosophila ortholog dFmr1 are methylated post-translationally. Recombinant protein arginine methyl transferase 1 (PRMT1) methylates Fmrp on the same arginines in vitro as in cells. In vitro methylation of Fmrp results in reduced binding to the minimal RNA sequence sc1, which encodes a stem loop G-quartet structure. Our data identify an additional mechanism, arginine methylation, for modifying Fmrp function and suggest that methylation occurs to limit or modulate RNA binding by Fmrp.

Purpose: Patello-femoral (PF) cartilage damage can cause severe knee pain and result in increasing disability. The purpose of this study was to identify factors associated with grade 4 defects of the patello-femoral joint. Methods: A cohort of 2601 patients (average age¼45, range, 18 to 83) who underwent knee arthroscopy for knee pathology were studied prospectively. All patients had complete demographic data, surgical data, WOMAC scores, and health status (SF12) collected at initial exam and stored in a data registry. Patients with chondral defects of the knee were included. Patients less than 18 years of age were excluded. Results: Grade 4 PF chondral defects were seen in 23% (586) of knees, with 6% (150) patellar (PAT) defects, 10% (267) trochlear groove (TG) defects and 6% (169) combined PAT and TG defects. 29% of patients with grade 4 PF chondral defects had medial compartment chondral defects, while 14% of patients with no PF chondral defect had medial compartment chondral defects (p<0.001). 20% of patients with PF chondral defects had lateral compartment chondral defects, while 12% of knees with no PF chondral defect had lateral compartment chondral defects. PF chondral defects were 3.0 [95%CI: 2.1 to 4.3] times more likely to be chronic injuries. Knees without PF defects were 20 [95%CI: 15.7 to 26.2] times more likely to have ligament injuries than knees with PF defects. Patients with grade 4 TG defects were older (51 vs 45) and had increased stiffness (how was stiffness determined?) compared to other patients (p<0.001). Patients with grade 4 PAT defects were older (52 vs 45; p<0.001) and had increased pain compared to other patients. Patients with diffuse grade 4 PAT defects had increased age, increased WOMAC (increased disability) and decreased Lysholm scores. Conclusions: This study confirms that grade 4 defects of the PF compartment are common. They often occur with chondral defects in other compartments; however, they are not associated with ligament or meniscus injuries. Patients with PF defects are older than patients with other cartilage damage, and patients with grade 4 diffuse defects of the patella suffer the most disability and loss of function. These data confirm the importance of new treatment strategies for chondral defects of the patellofemoral compartment, especially since patellar resurfacing remains controversial.

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Intro: Primary Sjogren's syndrome is a chronic systemic autoimmune disease. Although ocular and oral dryness are the hallmarks of this syndrome, renal involvement when present most commonly has the histological appearance of tubointerstitial nephritis and less often glomerular involvement. We report, a unique case of renal manifestations of primary Sjogren's syndrome with a proven histological focal proliferative and crescentric necrotizing glomeru-lonephritis. Case: A 30 years old man with Kimura disease presented with four months of subjective fevers, migrating skin erythema, dry mouth, and dry eyes. On further workup the patient was found to have a positive ANA, positive anti-SSA, and was evaluated by ophthalmology who found keratoconjunctivitis sicca. The patient was started on hydroxychloroquine in combination with prednisone. On follow up, the patient was found to be hypertensive with acute kidney injury, a creatinine of 3.65, proteinuria and hematuria. Renal ultrasound was unremarkable. Cytoplasmic ANCA was positive and kidney biopsy was performed revealing non pauci-immune focal proliferative and necrotizing glomerulonephritis with cellular crescents and mesangial dense deposits by electron microscopy. Conclusion: To our knowledge, the association between biopsy proven focal proliferative and necrotizing glomerulonephritis with primary Sjogren's syndrome has never been previously described in the literature, nor has there been a reported case of association between Kimura disease, ANCA serology and primary Sjogren's syndrome.

We have read with interest the article written by Schnatz et al 1 called BOsteoporosis screening and treatment guidelines: are they being followed?[ 1 The conclusion was that the guidelines for dual-energy x-ray absorptiometry screening put forth by The North American Menopause Society are not being followed. In 2005, we looked at the adherence to the 2002 United States Preventive Service Task Force guidelines for osteoporosis screening, BScreening for osteoporosis in postmenopausal women: adherence to the 2002 USPSTF Guidelines.[ 2 Our analysis broke down patients by age groups (G50, 50-59, 60-65, and 965 y) and body mass (more or less than 70 kg). We found that there was an overuse of dual-energy x-ray absorptiometry scanning in women younger than 60 and an underuse in high-risk women (G70 kg) or women older than 65 years. This recent study has reinforced our previous conclusions, with the added analysis of undertreatment of those with indications for therapy and the overuse of therapy for those in which none is indicated. The study by Prairie et al 1 (BA higher sense of purpose in life is associated with sexual enjoyment in midlife women[) is to be commended for its multidisciplinary approach, which yielded multidisciplinary answers. Purpose is noted to be a cognitive variable. In the opinion of the authors, how adequate for understanding the diverse results of this study might a neurological interpretation be? An attempt to summarize it in such terms is given below.MacLean's 2 classic model offers a convenient framework, in which each higher brain level tends to control lower levels, whereas lower levels report continuously to higher. The three major brain levels involved in this model are the cerebrocortical, which involves cognition and is distinctly human; the limbic system, which is emotional, our mammalian heritage; and the thalamic-hypothalamic system, our sensory reptilian inheritance.A sense of purpose is a distinctly human cortical event involving typical frontal lobe action. So massive are the cerebral hemispheres, however, that, as revealed in this study, senses of purpose and of sexual satisfaction can Bcosegregate[ or act as separate variables in different motivational contexts. When integrated with emotional feeling and sexual need, however, the sense of purpose is found to add to overall sexual enjoyment.Sexual enjoyment involves emotional aspects, input from the limbic system, and sensory aspects or impulses from the thalamus and hypothalamus. Although the findings relating to hormone therapy in this study did not quite reach statistical significance, there are strong suggestions that in their reporting of function to higher levels, the hormonal status of peripheral tissues influences sexual pleasure. Vaginal dryness significantly detracts, whereas hormone therapy appears to enhance sexual performance.Although a sense of purpose adds to sexual enjoyment, this higher dimension, in itself, does not lead to more frequent sexual experience. In the results of this study, the rate of sexual activity...