32 research outputs found

    Intronic Alus Influence Alternative Splicing

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    Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA) formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptom

    Optimal management of glenohumeral osteoarthritis

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    Chase B Ansok, Stephanie J Muh Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit, MI, USA Abstract: Glenohumeral osteoarthritis (OA) is defined as progressive loss of articular cartilage, resulting in bony erosion, pain, and decreased function. This article provides a gross overview of this disease, along with peer-reviewed research by experts in the field. The pathology, diagnosis, and classification of this condition have been well described. Treatment begins with non-operative measures, including oral and topical anti-inflammatory agents, physical therapy, and intra-­articular injections of either a corticosteroid or a viscosupplementation agent. Operative treatment is based on the age and function of the affected patient, and treatment of young individuals with glenohumeral OA remains controversial. Various methods of surgical treatment, ranging from arthroscopy to resurfacing, are being evaluated. The roles of hemiarthroplasty, total shoulder arthroplasty, and reverse shoulder arthroplasty are similarly reviewed with supporting data. Keywords: glenohumeral, osteoarthritis, hyaluronic acid, hemiarthroplasty, total shoulder arthroplast

    Treatment of proximal humeral fractures with reverse shoulder arthroplasty in elderly patients

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    Background. Proximal humeral fractures in 4 or even only 3 parts, with metaphyseal hinge distances of less than 8 mm, represent a serious and widely debated problem. Reduction is complex and plating is often instable, especially in elderly patients. Failures, sometimes involving necrosis of the head, are frequent. Hemiarthroplasty has long been used for 3- or 4-part complex fractures, even in young patients, although often with sub-optimal results, due to reabsorption of tuberosities. This complication has partly been overcome with reverse shoulder prostheses which, although more invasive than partial ones, may lead to less disappointing results, even in cases of reabsorption of tuberosities. We have data on a homogeneous series of patients treated with reverse shoulder arthroplasty for proximal fractures, with a maximum follow-up of 10 years. The aim of this study was mainly to identify which cases can be selected for effective treatment and which technical aspects are best to adopt. Materials and Methods. There were 33 patients in this study, mean age 76.6 years (range 54-85). Fractures were classified according to Neer. Surgery was undertaken on average 4.4 days after trauma. The deltopectoral approach was used. Sutures were hooked over the major and lesser tubercles for later reduction and fixation after the prosthesis had been applied. This passage was sometimes not possible in cases of serious degeneration of the rotator cuff. One day after surgery, a shoulder brace providing an abducted angle of 15° was applied for 30 days. Patients were re-assessed with DASH and Constant (CS) scores, and the ratio between healthy and operated shoulders was calculated. Physical examination was followed by X-rays, mainly to evaluate and classify any infraglenoid scapular notching according to Nerot. Results. Mean follow-up was 42.3 months (range 10-121). According to the CS, mean Pain was 12.6/15 (range 3-15/15), Activities of Daily Living 16.3/20 (range 8-20/20), ROM 21.8 (range 8-32/40) and Power 5.4/25 (range 2-12/25). Total mean CS was 56.4 (range 23-80/100). The mean DASH score was 49.7 (range 32-90). The ratio of the CS parameters between opposite and operated shoulders was on average 72.8 % (range 28-90%). Long-term complications were 8 cases of scapular notching (24.2%) of which 4 of grade 2 (12.1%) and 4 grade 1 (12.1%). Conclusions. Total reverse prostheses are more invasive because they also compromise the glenoid surface of the scapula, but they do offer good stability, even in cases of damage to the rotator cuff. Reverse prostheses have great advantages as regards to ROM, allowing functional recovery, which is good in cases with re-insertion of tuberosities, and acceptable in cases when tuberosities are not re-inserted or resorbed. In our cases, the first 3 reverse prostheses lasted 10, 8.3 and 7.3 years, and we believe that they will become increasingly long-lived, so that applying them in cases of complex fractures becomes more feasible. We prefer the deltopectoral approach because it can reduce and stabilize possible intra-operative diaphyseal fractures. Possible scapular notching must be foreseen when inserting the glenosphere. We had 8 cases (24.2%), of which 4 were Nerot grade 1 and 4 grade 2. Applying the Kirschner wire in an infero-anterior position allows the glenosphere to be lowered with a tilt of 10°. Reverse prostheses are suitable for 3- or 4-part complex proximal humeral fractures in patients over 65. Prolonged physiokinesitherapy is essential
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