Immunogenicity of a secreted, C-terminally truncated, form of bovine viral diarrhea virus E2 glycoprotein as a potential candidate in subunit vaccine development.

Both current live, attenuated, and killed virus vaccines for bovine viral diarrhea virus (BVDV) have their limitations. Here, we report the development of a BVDV subunit vaccine by (i) the expression of a secreted form of a recombinant E2 glycoprotein using BHK21 cells and (ii) determination of the immune responses in mice. The E2 glycoprotein was modified by deletion of the C-terminal transmembrane anchor domain and fusion to a V5 epitope tag. This allowed detection using anti-V5 monoclonal antibodies together with simple purification of the expressed, secreted, form of E2 from the cell media. Furthermore, we genetically fused green fluorescent protein (GFP) linked to E2 via a Thosea asigna virus 2A (T2A) ribosome skipping sequence thereby creating a self-processing polyprotein [GFP-T2A-BVDV-E2trunk-V5], producing discrete [GFP-T2A] and [E2trunk-V5] translation products: GFP fluorescence acts, therefore, as a surrogate marker of E2 expression, BALB/c mice were inoculated with [E2trunk-V5] purified from cell media and both humoral and cellular immune responses were observed. Our antigen expression system provides, therefore, both (i) a simple antigen purification protocol together with (ii) a feasible strategy for further, large-scale, production of vaccines.

Magnesium implants in orthopaedic surgery create a diagnostic conundrum: A radiology case series and literature review.

During a routine post-operative orthopaedic radiograph reading session, repeated unusual radiographic soft tissue and bone appearances became evident. It was discovered that these patients had received biodegradable magnesium implants which have recently been introduced into orthopaedic clinical practice. To the untrained eye, the combination of peri-metallic bone resorption with associated soft tissue gas, could easily be mistaken for post-operative infection. The aim of this study is to properly characterise the radiographic post-operative appearances of biodegradable magnesium orthopaedic hardware. We retrospectively evaluated radiographs of all patients who underwent magnesium screw implantation for fractures over a 6 month period. Four patients, mean age of 9.75 (range: 6-15) years who underwent magnesium screw fixation following fracture were included in the study. Follow up duration was 100 days (range: 75-122) with a mean of 2.5 postoperative radiographs being performed per patient during this period. All cases demonstrated post-operative peri-metallic radiolucency which developed around the magnesium screws on x-ray, which subsequently resorbed over time. Peri-metallic soft tissue gas was observed in all patients. In two cases, magnesium implants fractured. As the use of biodegradable metal implants becomes more common, it is important for radiologists to be aware of their imaging characteristics. Prior to reporting a case, it would be prudent to know if biodegradable screws have been utilised and whether there exists a clinical concern for post-operative infection in patients with these particular implants, in which case it would be critical not to dismiss peri-prosthetic radiolucencies and soft tissue gas as merely a sequela of the natural metal degradation process.

Colorectal Cancer Screening with Mailed Fecal Immunochemical Tests and Telephone Outreach at a Community Health Center during the COVID-19 Pandemic.

Colorectal cancer (CRC) is a common cause of cancer death and disproportionately affects non-Hispanic Black patients. Routine screening with the fecal immunochemical test (FIT) decreases CRC incidence and mortality, and previous literature suggests pairing FIT with live outreach. Screening delays due to the COVID-19 pandemic will likely increase CRC incidence and mortality, especially in underserved communities. We implemented a quality improvement (QI) project at an urban community health center (CHC) in which FIT was paired with live telephone outreach. The intervention increased CRC screening at the CHC by five percentage points. Fecal immunochemical test completion rates significantly increased with successful contact (24.6% for at least one vs. 3.0% for none, p < .0001) and ordering a FIT kit during a patient interaction (28.4% vs. 15.7%, p < .001). This intervention addressed disparities in CRC screening, and the report may have general implications for addressing systemic racism in preventive medicine.

Co-Amoxiclav as empiric treatment of UTI in children: importance of surveillance in ensuring optimal empiric treatment choice.

Background Urinary tract infections are common and require prompt treatment. Objective To examine the resistance rates of co-amoxiclav in children with urinary tract infection and whether antimicrobial resistance is influenced by other variables. Methods The records and antibiotic susceptibility data of 209 patients admitted with symptomatic urinary tract infection between January 2018 and December 2019 were reviewed. Results We examined 209 patients [mean (SD) age 23.73 (32.86) months], of whom 176 (84.2%) had first urinary tract infection. Escherichia coli was isolated in 190 (90.1%). Uropathogens were sensitive to co-amoxiclav in 47.8% of patients and gentamicin in 95.2%. Combined co-amoxiclav with gentamicin demonstrated antimicrobial sensitivity in 96.2%. Antimicrobial resistance was associated with longer hospital stay (p-value < 0.02). An association was identified between co-amoxiclav resistance and recurrent urinary tract infections. Uropathogens were resistant to co-amoxiclav in 80/176 (45.5%) and 29/33 (87.9%) patients with first and recurrent urinary tract infections, respectively (p-value 0.001). No link was observed between antimicrobial resistance and atypical urinary tract infection. Conclusion Approximately half of children in this cohort had urinary tract infection due to uropathogens resistant to co-amoxiclav. Co-amoxiclav resistance is associate with recurrent infections and longer hospital stays. A combination of co-amoxiclav and gentamicin demonstrates > 96% susceptibility.

Neck circumference – Height ratio cut-off as a predictor of obstructive sleep apnea severity among adult patients diagnosed with obstructive sleep apnea at the Lung Center of the Philippines

Introduction@#Obstructive sleep apnea (OSA) is the most common breathing-related sleep disorder. OSA is mainly characterized by a set of symptoms resulting from apnea events that have negative outcomes on health, such as excessive daytime sleepiness, cardiovascular impairment, and increased morbidity and mortality. It is important to develop simple, reliable, cost-effective methods to predict obstructive sleep apnea. Neck circumference - height ratio has limited studies in its relation to obstructive sleep apnea compared to neck circumference. @*Method@#This is a retrospective cross-sectional study using chart review of all patients who had been diagnosed with obstructive sleep apnea by polysomnogram at the Lung Center of the Philippines from January 2019 to December 2019. Demographic characteristics like age, gender, weight, height, neck circumference, BMI, neck circumference - height ratio [NHR], and apnea-hypopnea index were determined. Accuracy of the neck circumference - height radio cutoff had been determined in predicting obstructive sleep apnea and its severity by comparing neck - circumference - height ratio cut-off with a polysomnogram. @*Results@#Among the 384 charts collected and reviewed, this study had a total of 194 participants were included. Most participants were male (72.68%) and the age range was between 35 to 60 years old. There were 12 (6%) participants in the Mild OSA group, 19 (10%) in the Moderate OSA group, and 163 (84%) were categorized as Severe. Median Neck Circumference -Height Ratio was 0.23 to 0.26. A cutoff of > 0.23 NHR was used to predict Mild OSA showed PPV of 46.15% (24.47 to 65.98), NPV was 66.67% (50.78 to 79.49), AUC of 0.5307 (0.30 to 0.76), and accuracy of 58.06% (39.08 to 75.45). A cutoff of > 0.23 NH was used to predict Moderate OSA showed positive predictive value (PPV) was 15.94% (10.91 to 22.7), NPV of 93.6% (89.52 to 96.16), AUC of 0.6421 (0.52 to 0.77), and accuracy of 65.98% (58.85 to 72.61). A cutoff of > 0.23 HR was used to predict Severe OSA showed PPV of 15.94% (10.91 to 22.7), NPV of 93.6% (89.52 to 96.16), AUC of 0.6421 (0.52 to 0.77), and accuracy of 65.98% (58.85 to 72.61).@*Conclusion@#The HR cut-off demonstrated a moderate positive correlation with OSA, and NH increases as the apnea-hypopnea index are increased. NH cut-off of 0.23 is sufficient to predict severe OSA but has poor diagnostic accuracy for mild and moderate OSA. Moreover, the HR cut-off may also be an integral tool to predict severe OSA.

Mutagenesis Mapping of RNA Structures within the Foot-and-Mouth Disease Virus Genome Reveals Functional Elements Localized in the Polymerase (3Dpol)-Encoding Region.

RNA structures can form functional elements that play crucial roles in the replication of positive-sense RNA viruses. While RNA structures in the untranslated regions (UTRs) of several picornaviruses have been functionally characterized, the roles of putative RNA structures predicted for protein coding sequences (or open reading frames [ORFs]) remain largely undefined. Here, we have undertaken a bioinformatic analysis of the foot-and-mouth disease virus (FMDV) genome to predict 53 conserved RNA structures within the ORF. Forty-six of these structures were located in the regions encoding the nonstructural proteins (nsps). To investigate whether structures located in the regions encoding the nsps are required for FMDV replication, we used a mutagenesis method, CDLR mapping, where sequential coding segments were shuffled to minimize RNA secondary structures while preserving protein coding, native dinucleotide frequencies, and codon usage. To examine the impact of these changes on replicative fitness, mutated sequences were inserted into an FMDV subgenomic replicon. We found that three of the RNA structures, all at the 3' termini of the FMDV ORF, were critical for replicon replication. In contrast, disruption of the other 43 conserved RNA structures that lie within the regions encoding the nsps had no effect on replicon replication, suggesting that these structures are not required for initiating translation or replication of viral RNA. Conserved RNA structures that are not essential for virus replication could provide ideal targets for the rational attenuation of a wide range of FMDV strains. IMPORTANCE Some RNA structures formed by the genomes of RNA viruses are critical for viral replication. Our study shows that of 46 conserved RNA structures located within the regions of the foot-and-mouth disease virus (FMDV) genome that encode the nonstructural proteins, only three are essential for replication of an FMDV subgenomic replicon. Replicon replication is dependent on RNA translation and synthesis; thus, our results suggest that the three RNA structures are critical for either initiation of viral RNA translation and/or viral RNA synthesis. Although further studies are required to identify whether the remaining 43 RNA structures have other roles in virus replication, they may provide targets for the rational large-scale attenuation of a wide range of FMDV strains. FMDV causes a highly contagious disease, posing a constant threat to global livestock industries. Such weakened FMDV strains could be investigated as live-attenuated vaccines or could enhance biosecurity of conventional inactivated vaccine production.

Design Authorship: an intrinsic driver of designer-entrepreneurs.

This paper describes the entrepreneurial journey of product designers and the driver that makes them take an idea into the market. Following a Constructivist Grounded Theory approach, a multiple-phase data generation method explored the entrepreneurial journey of eleven designer-entrepreneurs (D-entrepreneurs). The paper describes the driver named design authorship (D-authorship) and why it is essential in the entrepreneurial journey of designers. The study identified two types of D-authorship: a) the inside-out, where D-entrepreneurs spent considerable time obtaining perfection in the product without any user feedback involved, and b) the outside-in, where D-entrepreneurs build their product as a result of a systematic user-centric approach.

Product designers are equipped with the right skills and knowledge to create new products. This paper describes the entrepreneurial journey of eleven designer-entrepreneurs starting their product-based companies. However, most of these products never reach the market because of the gap between invention and product launch. This research has identified a critical driver that meant these designers did finally launch products. We call it Design Authorship (D-authorship). The study identified two types of D-authorship: a) the inside-out, where D-entrepreneurs spent considerable time perfecting the product without any user feedback, b) the outside-in, where D-entrepreneurs build their product as a result of a systematic user-centric approach.

A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System.

The proliferation, differentiation, and survival of cells of the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, and classical dendritic cells) are controlled by signals from the M-CSF receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters, but none is both universal and lineage restricted. In this article, we report the development and characterization of a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with the C terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells, arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly expressed in marrow monocytes and common myeloid progenitors but significantly lower in granulocyte-macrophage progenitors. In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages, and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations, including classical dendritic cells. Whole mount imaging of nonlymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells, including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.

Acceleration Profile of Elite Gaelic Football With Special Reference to Position of Play.

Ryan, M, Malone, S, Donnellan, A, and Collins, K. Acceleration profile of elite Gaelic football with special reference to position of play. J Strength Cond Res 34(6): 1750-1758, 2020-The current study aimed to characterize the positional match-play demands of elite Gaelic football players with special reference to acceleration using predetermined 5-minute periods (epochs). Thirty-five male Gaelic players (mean ± SD, age: 24 ± 6 years; height: 180 ± 7 cm; mass: 81 ± 7 kg) across 5 playing positions (full-back, half-back, midfield, half-forward, and full-forward) were monitored during the investigation. Player movement was recorded during 19 matches using 4-Hz global positioning system technology (VXSport, New Zealand) resulting in 154 player observations. Global positioning system was used to record total distance (m), (high-speed running; m; ≥17 km·h), (very high-speed running distance; m; ≥22 km·h), the number of accelerations (n), duration of accelerations (s), peak acceleration (m), and distance of accelerations (m). Acceleration profiles were position dependent with midfielders found to have a high accumulation of acceleration movements when compared with all other positions (p ≤ 0.05). Declines of -2 to -32% for acceleration distance (m) depending on positional line of play were observed during match-play. Less high-speed running and very high-speed running distance was performed by the full-back line (high-speed running; -39% and very high-speed running; -36%) and full-forward line (-35%; -29%) when compared with half-back, midfielders, and half-forwards (p = 0.01, d = 1.35-1.77). Similar trends were reported for peak acceleration distance (p = 0.01, d = 1.15-1.93). The current investigation provides a greater understanding of temporal differences in acceleration profiles of playing position. We show that half-back, midfield, and half-forwards have the highest acceleration movements; these data can assist coaches in appropriately preparing players for the required acceleration distances required during match-play.

Seasonal Changes in Gaelic Football Match-Play Running Performance.

Mangan, S, Ryan, M, Shovlin, A, McGahan, J, Malone, S, O'Neill, C, Burns, C, and Collins, K. Seasonal changes in Gaelic football match-play running performance. J Strength Cond Res 33(6): 1686-1692, 2019-Time of season influences performance in many team sports; however, the anomaly has not yet been examined with regards to elite Gaelic football. Global positioning systems (4 Hz; VX Sport, Lower Hutt, New Zealand) were used to monitor 5 elite Gaelic football teams over a period of 5 years (2012-2016). In total, 95 matches equated to 780 full player data sets. Running performance was characterized by total distance (m) and high-speed distance (≥17 km·h; m). High-speed distance was further categorized into 4 match quarters. Time of season was determined by month of the year. Time of season had a significant effect on total distance (p ≤ 0.001 partial η = 0.148) and high-speed distance (p ≤ 0.001 partial η = 0.105). August and September were significantly different from every other month for total distance (p ≤ 0.001) and high-speed distance (p ≤ 0.002). Month of season and match quarter had a significant interaction with high-speed distance (p ≤ 0.001 partial η = 0.106). High-speed distances run in the fourth quarter in August (478 ± 237 m) and in September (500 ± 219 m) were higher than any other quarter in any other month. This is the first study to show that time of season influences running performance in Gaelic football. The findings have major implications for training practices in Gaelic football.

Quality Risk Management Framework: Guidance for Successful Implementation of Risk Management in Clinical Development.

Effective quality risk management is fundamental to ensuring the protection of human subjects and reliability of clinical trial results during the conduct of clinical trials. Quality risk management supports effective delivery of clinical development programs and ultimately delivery of treatments to patients. Thus, risk management is a core element of an effective quality management system (QMS) as described in the TransCelerate Clinical Quality Management System (CQMS) conceptual framework. In addition, the landscape of quality risk management in clinical development evolves as regulatory authorities adopt elements of risk management to promote proactive quality management. This paper's goal is to provide a conceptual framework for quality risk management as part of a CQMS. The components of a quality risk management program are explored including foundational elements and quality risk management methods appropriate for clinical development.

"Therapeutic applications of the 'NPGP' family of viral 2As".

Oligopeptide "2A" and "2A-like" sequences ("2As"; 18-25aa) are found in a range of RNA virus genomes controlling protein biogenesis through "recoding" of the host-cell translational apparatus. Insertion of multiple 2As within a single open reading frame (ORF) produces multiple proteins; hence, 2As have been used in a very wide range of biotechnological and biomedical applications. During translation, these 2A peptide sequences mediate a eukaryote-specific, self-"cleaving" event, termed "ribosome skipping" with very high efficiency. A particular advantage of using 2As is the ability to simultaneously translate a number of proteins at an equal level in all eukaryotic systems although, naturally, final steady-state levels depend upon other factors-notably protein stability. By contrast, the use of internal ribosome entry site elements for co-expression results in an unbalanced expression due to the relative inefficiency of internal initiation. For example, a 1:1 ratio is of particular importance for the biosynthesis of the heavy-chain and light-chain components of antibodies: highly valuable as therapeutic proteins. Furthermore, each component of these "artificial polyprotein" systems can be independently targeted to different sub-cellular sites. The potential of this system was vividly demonstrated by concatenating multiple gene sequences, linked via 2A sequences, into a single, long, ORF-a polycistronic construct. Here, ORFs comprising the biosynthetic pathways for violacein (five gene sequences) and ß-carotene (four gene sequences) were concatenated into a single cistron such that all components were co-expressed in the yeast Pichia pastoris. In this review, we provide useful information on 2As to serve as a guide for future utilities of this co-expression technology in basic research, biotechnology, and clinical applications.

Using the 2A Protein Coexpression System: Multicistronic 2A Vectors Expressing Gene(s) of Interest and Reporter Proteins.

To date, a huge range of different proteins-many with cotranslational and posttranslational subcellular localization signals-have been coexpressed together with various reporter proteins in vitro and in vivo using 2A peptides. The pros and cons of 2A co-expression technology are considered below, followed by a simple example of a "how to" protocol to concatenate multiple genes of interest, together with a reporter gene, into a single gene linked via 2As for easy identification or selection of transduced cells.

Acceleration Profile of Elite Gaelic Football Match Play.

Ryan, M, Malone, S, and Collins, K. An acceleration profile of elite Gaelic football match play. J Strength Cond Res 32(3): 812-820, 2018-The use of global positioning system (GPS) technology in Gaelic football is the primary source of quantifying game demands. The aim of this study was to quantify the acceleration profile of elite Gaelic football. Thirty-six elite male Gaelic football players (mean ± SD, age: 24 ± 6 years; height: 180 ± 7 cm; mass: 81 ± 7 kg) across 5 playing positions took part in a multiple study (n = 154 observations). Player movement was recorded during 19 (n = 19) competitive games over 2 seasons using 4-Hz GPS (VXSport, New Zealand). The average total distance (m), high-speed running distance (m; ≥17 km·h), and very high-speed running distance (m; ≥22 km·h) were recorded. In addition, the number (n), distance (m), and the duration of accelerations were quantified. Accelerations were subdivided into 14 equal parts of 5-minute epochs (E1 = 0-5 minutes, E2 = 5-10 minutes, E3 = 10-15 minutes etc). Players performed 166 ± 41 accelerations. High-speed running distance and very high-speed running distance was 1563 ± 605 and 524 ± 190 m, respectively. The mean acceleration distance was 267 ± 45 m distributed between 12 ± 5 accelerations per 5-minute epoch. The maximum acceleration epoch classified as the greatest distance covered accelerating during a predetermined 5-minute epoch was 296 ± 134 m. The PEAK epoch resulted in a significant reduction of acceleration distance covered in the period before and in the subsequent epoch. An understanding of the acceleration profile in Gaelic football can inform the prescription of appropriate training regimen.

Systematic review and meta-analysis of the effectiveness of pharmacist-led medication reconciliation in the community after hospital discharge.

BACKGROUND: Pharmacists' completion of medication reconciliation in the community after hospital discharge is intended to reduce harm due to prescribed or omitted medication and increase healthcare efficiency, but the effectiveness of this approach is not clear. We systematically review the literature to evaluate intervention effectiveness in terms of discrepancy identification and resolution, clinical relevance of resolved discrepancies and healthcare utilisation, including readmission rates, emergency department attendance and primary care workload. METHODS: This is a systematic literature review and meta-analysis of extracted data. Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Allied and Complementary Medicine Database (AMED),Education Resources Information Center (ERIC), Scopus, NHS Evidence and the Cochrane databases were searched using a combination of medical subject heading terms and free-text search terms. Controlled studies evaluating pharmacist-led medication reconciliation in the community after hospital discharge were included. Study quality was appraised using the Critical Appraisal Skills Programme. Evidence was assessed through meta-analysis of readmission rates. Discrepancy identification rates, emergency department attendance and primary care workload were assessed narratively. RESULTS: Fourteen studies were included, comprising five randomised controlled trials, six cohort studies and three pre-post intervention studies. Twelve studies had a moderate or high risk of bias. Increased identification and resolution of discrepancies was demonstrated in the four studies where this was evaluated. Reduction in clinically relevant discrepancies was reported in two studies. Meta-analysis did not demonstrate a significant reduction in readmission rate. There was no consistent evidence of reduction in emergency department attendance or primary care workload. CONCLUSIONS: Pharmacists can identify and resolve discrepancies when completing medication reconciliation after hospital discharge, but patient outcome or care workload improvements were not consistently seen. Future research should examine the clinical relevance of discrepancies and potential benefits on reducing healthcare team workload.

Influence of Team Rating on Running Performance in Elite Gaelic Football.

Mangan, S, Malone, S, Ryan, M, Mc Gahan, J, Warne, J, Martin, D, O'Neill, C, Burns, C, and Collins, K. Influence of team rating on running performance in elite Gaelic football. J Strength Cond Res 32(9): 2584-2591, 2017-It is currently unknown how team rating influences running performance in Gaelic football. Global positioning system technologies were used to quantify match-running performance within 5 elite Gaelic football teams over a period of 5 years (2012-2016). In total 780 player data sets were collected over 95 matches. Running performance variables included total distance, high-speed distance (≥17 km·h), and the percentage of high-speed distance. Team ratings were determined objectively using the Elo rating system for Gaelic football. Reference team rating had trivial effects on total distance (p = 0.011, partial η = 0.008) and high-speed distance (p = 0.011, partial η = 0.008). Opposition team rating had small effects on total distance (p = 0.005, partial η = 0.016) and high-speed distance (p = 0.001, partial η = 0.020). Top-tier teams cover greater total distances and high-speed distance than lower tier teams. Players cover considerably less total distance and high-speed distance against tier-3 and tier-4 teams. Tier-1 players ran a significantly higher percentage of distance at high speed than players who played for tier-2 teams (p = 0.020). The competitive advantage of top-tier Gaelic football teams is closely linked with their ability to demonstrate a higher physical intensity than lower tier teams.

A Retrospective Comparative Analysis of the Use of Implantable Bone Stimulators in Nonunions.

This study details the use of implantable bone stimulators in the setting of nonunion. A retrospective comparative analysis was used to evaluate the efficacy of implantable bone stimulators in achieving union in the setting of atrophic or oligotrophic nonunion by two fellowship-trained orthopaedic trauma surgeons. Initially, 72 patients underwent surgical intervention for nonunion. Twenty-one patients had an implantable bone stimulator placed at the time of nonunion surgery. Thirty-eight patients had a minimum of 1-year follow-up. An implantable bone stimulator was used in 13 patients and 25 patients did not have a bone stimulator. The use of implantable bone stimulators was found to be significantly associated with increased union rates (p = .042). (Journal of Surgical Orthopaedic Advances.

'2A-Like' Signal Sequences Mediating Translational Recoding: A Novel Form of Dual Protein Targeting.

We report the initial characterization of an N-terminal oligopeptide '2A-like' sequence that is able to function both as a signal sequence and as a translational recoding element. Owing to this translational recoding activity, two forms of nascent polypeptide are synthesized: (i) when 2A-mediated translational recoding has not occurred: the nascent polypeptide is fused to the 2A-like N-terminal signal sequence and the fusion translation product is targeted to the exocytic pathway, and, (ii) a translation product where 2A-mediated translational recoding has occurred: the 2A-like signal sequence is synthesized as a separate translation product and, therefore, the nascent (downstream) polypeptide lacks the 2A-like signal sequence and is localized to the cytoplasm. This type of dual-functional signal sequence results, therefore, in the partitioning of the translation products between the two sub-cellular sites and represents a newly described form of dual protein targeting.

Primary total knee arthroplasty in a patient with a chronic extensor mechanism deficiency.

A 44-year-old female presented with a chief complaint of left knee pain and dysfunction. The patient had a complex surgical history including patellar fracture repair, subsequent patellar ligament repair, and ultimately allograft reconstruction which was complicated by septic arthritis requiring graft resection. On presentation to our clinic, she was noted to have significant degenerative disease in addition to chronic extensor mechanism deficiency. She underwent primary total knee arthroplasty with concomitant tibial tubercle osteotomy and advancement. The patient has had an excellent result postoperatively including return of full range of motion without residual extensor lag.