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RSA as a reconstructive procedure improved function at the time of short-term follow-up in our young patients with glenohumeral arthritis and rotator cuff deficiency. Objective outcomes in our patient cohort were similar to those in previously reported studies. However, overall satisfaction was much lower in this patient population (81%) compared with that in the older patient population as reported in the literature (90% to 96%).

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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.

Alternative splicing of fibroblast growth factor receptor 2 (FGFR2) mutually exclusive exons IIIb and IIIc represents a tightly regulated and functionally relevant example of post-transcriptional gene regulation. Rat prostate cancer DT3 and AT3 cell lines demonstrate exclusive selection of either exon IIIb or exon IIIc, respectively, and have been used to characterize regulatory FGFR2 RNA cis-elements that are required for splicing regulation. Two sequences termed ISE-2 and ISAR are located in the intron between exons IIIb and IIIc and are required for cell-type specific exon IIIb. Previous studies suggest that the function of these elements involves formation of an RNA stem structure, even though they are separated by more than 700 nucleotides. Using transfected minigenes, we performed a systematic analysis of the sequence and structural components of ISE-2 and ISAR that are required for their ability to regulate FGFR2 splicing. We found that the primary sequence of these elements can be replaced by completely unrelated sequences, provided that they are also predicted to form an RNA stem structure. Thus, a nonsequence-specific double stranded RNA stem constitutes a functional element required for FGFR2 splicing; suggesting that a double-stranded RNA binding protein is a component of the splicing regulatory machinery.Alternative splicing represents an important mechanism of modulating the expression of gene transcripts (1-5). It is estimated that at least 35% of human genes are alternatively spliced, although this is based on conservative estimates and it may be that alternative splicing is more the rule than the exception in the post-transcriptional processing of pre-mRNA transcripts (6, 7). Studies of the mechanisms employed by mammalian cells to differentially regulate splicing indicate that the selection of splice sites is influenced by proteins that bind to non-splice site RNA cis-elements and recruit or block spliceosome assembly. Such RNA cis-elements include exonic and intronic splicing enhancers (ESEs 1 or ISEs) as well as exonic and intronic splicing silencers (ESSs or ISSs) that enhance or block splicing to neighboring splice sites. A number of ubiquitous RNA-binding proteins have been demonstrated to alter alternative splice site choice. Examples include the SR proteins (8 -11), heterogeneous nuclear ribonucleoproteins (hnRNPs) (12-26), KSRP (KH-type splicing regulatory protein) (27), and TIA-1 (28,29). While most proteins demonstrated to modulate splicing of mammalian transcripts are not differentially expressed, several mammalian tissue-specific RNA-binding proteins that function as splicing regulators have recently emerged (30 -33). Alternatively spliced mammalian transcripts generally contain several cis-elements in introns and exons with positive or negative functions (enhancers and silencers) that modulate splicing. Such observations have led to models of combinatorial control, whereby regulation of alternatively spliced mammalian transcripts is achieved through the net influence of several pro...

Background:Challenges exist in routinely collecting patient-reported outcomes (PROs) from patients at a busy ambulatory clinic. A number of validated Patient-Reported Outcomes Measurement Information System (PROMIS) subdomains allow for efficient PRO administration.Purpose:To determine the time to completion (TTC) of 3 PROMIS computer adaptive test (CAT) scores. CAT questionnaires were administered at the ambulatory clinic with the following PROMIS subdomains: Pain Interference (PI), Depression, and Physical Function for lower extremity (PF) or for upper extremity (UE). The secondary purpose was to determine the influence of patient demographic factors on TTC.Study Design:Cross-sectional study; Level of evidence, 3.Methods:Patients were recruited from 3 fellowship-trained upper extremity and sports medicine orthopaedic surgery clinics. PROMIS CAT questionnaires were administered to consecutive patients during the study period (July 2017–September 2017). The start and completion times of each CAT were recorded. The primary outcome of interest was TTC of the questionnaires. Patients were stratified into age quartiles to determine the impact of age on TTC. Patient demographic information, such as sex, race, and ethnicity, was determined retroactively.Results:A total of 1178 questionnaire sets consisting of 3658 individual PROMIS forms were analyzed. The mean TTC was 3.29 minutes for all 4 forms in aggregate, with PROMIS PI, PF, UE, and Depression taking on average 1.05, 0.74, 0.96, and 0.57 minutes to complete, respectively. Patients from the oldest age quartile (mean ± SD, 70.3 ± 7.5 years) had a statistically significant longer TTC as compared with the second quartile (41.2 ± 4.7 years) (3.70 vs 2.87 minutes; P < .05). Asian patients had the longest PROMIS PF TTC, while white patients completed PF with the shortest TTC (1.28 vs 0.68 minutes; P < .05). Patients of unstated ethnicity had a longer TTC for PF as compared with their Hispanic/Latino and non-Hispanic/Latino counterparts (0.91 vs 0.30 and 0.70 minutes; P < .05).Conclusion:PROMIS CAT forms are efficient tools for collecting patient-reported outcomes in the ambulatory orthopaedic surgery clinic. Older patients, Asian patients, and patients of unstated ethnicity took longer to complete the forms.

The purpose of this form is to provide readers of your manuscript with information about your other interests that could influence how they receive and understand your work. The form is designed to be completed electronically and stored electronically. It contains programming that allows appropriate data display. Each author should submit a separate form and is responsible for the accuracy and completeness of the submitted information. The form is in six parts. Identifying information. The work under consideration for publication. This section asks for information about the work that you have submitted for publication. The time frame for this reporting is that of the work itself, from the initial conception and planning to the present. The requested information is about resources that you received, either directly or indirectly (via your institution), to enable you to complete the work. Checking "No" means that you did the work without receiving any financial support from any third party-that is, the work was supported by funds from the same institution that pays your salary and that institution did not receive third-party funds with which to pay you. If you or your institution received funds from a third party to support the work, such as a government granting agency, charitable foundation or commercial sponsor, check "Yes". Relevant financial activities outside the submitted work. This section asks about your financial relationships with entities in the bio-medical arena that could be perceived to influence, or that give the appearance of potentially influencing, what you wrote in the submitted work. You should disclose interactions with ANY entity that could be considered broadly relevant to the work. For example, if your article is about testing an epidermal growth factor receptor (EGFR) antagonist in lung cancer, you should report all associations with entities pursuing diagnostic or therapeutic strategies in cancer in general, not just in the area of EGFR or lung cancer. Report all sources of revenue paid (or promised to be paid) directly to you or your institution on your behalf over the 36 months prior to submission of the work. This should include all monies from sources with relevance to the submitted work, not just monies from the entity that sponsored the research. Please note that your interactions with the work's sponsor that are outside the submitted work should also be listed here. If there is any question, it is usually better to disclose a relationship than not to do so. For grants you have received for work outside the submitted work, you should disclose support ONLY from entities that could be perceived to be affected financially by the published work, such as drug companies, or foundations supported by entities that could be perceived to have a financial stake in the outcome. Public funding sources, such as government agencies, charitable foundations or academic institutions, need not be disclosed. For example, if a government agency sponsored a study in which you have been involved and drugs...

We have developed a series of fluorescent splicing reporter minigenes for the establishment of cell-based screens to identify splicing regulatory proteins. A key technical advance in the application of these reporters was the use of two different fluorescent proteins: EGFP and monomeric Red Fluorescent Protein (mRFP). Through establishment of stable cell lines expressing such dual color fluorescent reporters, these minigenes can be used to perform enhanced screens for splicing regulatory proteins. As an example of such applications we generated fluorescent minigenes that can be used to determine the splicing of mutually exclusive FGFR2 exons IIIb and IIIc by flow cytometry. One minigene contained a coding sequence for EGFP whose translation was dependent on splicing of exon IIIb, whereas a second minigene required exon IIIc splicing for translation of an mRFP coding sequence. Stable incorporation of both minigenes into cells that express endogenous FGFR2-IIIb or FGFR2-IIIc resulted in EGFP or mRFP fluorescence, respectively. Cells stably transfected with both minigenes were used to screen a panel of cDNAs encoding known splicing regulatory proteins, and several were identified that induced a switch in splicing that could be detected specifically by an increase in green, but not red, fluorescence. We further demonstrated additional minigenes that can be used in dual color fluorescent screens for identification of splicing regulatory proteins that function through specific intronic splicing enhancer elements (ISEs). The methods and minigene designs described here should be adaptable for broader applications in identification of factors and mechanisms involved in alternative splicing of numerous other gene transcripts.