Etiology of Traumatic Causes of Extensor Pollicis Longus Tendon Rupture: A Systematic Review.

Introduction: The extensor pollicis longus (EPL) is a muscle that follows a complex anatomical course in the hand to allow for thumb extension. Almost all manual activities require the use of the EPL; therefore, when ruptured it can be very disabling for patients. The etiologies behind traumatic EPL rupture were mostly attributed to distal radius fracture in the literature. However, EPL rupture remains uncommon, and other traumatic etiologies exist. Therefore, this systematic review aimed to provide a holistic view of the traumatic etiologies behind the EPL rupture and fill the global lack of knowledge regarding this rare injury. Materials and Methods: We searched among Cochrane Central Register of Controlled Trials (CENTRAL) Embase, Medline, and Cochrane Database of systematic review register databases via Ovid, with no restriction on the date, including studies containing data about the etiology of traumatic causes of EPL tendon rupture with available full text, and excluding non-English and animal studies. Results: A total of 37 articles with 371 cases constituted the basis of this review. We classified the etiology of the EPL rupture into three groups according to the affected anatomical structure that caused the EPL rupture (fracture-related, soft tissue-related, and mallet thumb). Conclusion: Distal radius fractures remain the most common cause of EPL rupture; however, other causes, such as lacerations, blunt trauma, and direct cuts to the EPL tendon, should be considered.

Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. METHODS: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire-metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. DISCUSSION: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. TRIAL REGISTRATION: European Union Clinical Trials Register, EudraCT, 2021-006069-39. Registered on March 13, 2022.

Clinical factors associated with subsequent surgical intervention in women undergoing early medical termination of viable or non-viable pregnancies.

Introduction: Mifepristone-misoprostol treatment for medical abortion and miscarriage are safe and effective. This study aimed to assess clinical factors associated with subsequent surgical intervention after medical termination of early viable or non-viable pregnancy. Methods: This retrospective, single-center study included women who underwent medical abortion at Taipei Medical University between January 2010 and December 2019. A total of 1,561 subjects, with 1,080 viable and 481 non-viable pregnancies, who were treated with oral mifepristone 600 mg followed by misoprostol 600 mg 48 h later were included. Data of all pregnancies and medical termination of pregnancy were evaluated using regression analysis. The main outcome was successful termination of pregnancy. Results: The success rate of medical abortion was comparable in women with viable and non-viable (92.13% vs. 92.93%) pregnancies. Besides retained tissue, more existing pregnancies with ultrasonographic findings were found in the non-viable pregnancy group than in the viable pregnancy group (29.4% vs. 14.1%, p = 0.011). Multivariate analysis showed that previous delivery was an independent risk factor for failed medical abortion among all included cases. In women with viable pregnancy, longer gestational age [adjusted odds ratio (aOR): 1.483, 95% confidence interval (CI): 1.224-1.797, p < 0.001] and previous Cesarean delivery (aOR: 2.177, 95% CI: 1.167-40.62, p = 0.014) were independent risk factors for failed medical abortion. Number of Cesarean deliveries (aOR: 1.448, 95% CI: 1.029-2.039, p = 0.034) was an independent risk factor for failed medication abortion in women with non-viable pregnancies. Conclusion: This is the first cohort study to identify risk factors for subsequent surgical intervention in women with viable or non-viable pregnancies who had undergone early medically induced abortions. The success rate of medical abortion is comparable in women with viable and non-viable pregnancies. Previous delivery is an independent risk factor for failed medical abortion. Clinical follow-up may be necessary for women who are at risk of subsequent surgical intervention.

Optimization of Graphical Parameter Extraction Algorithm for Chip-Level CMP Prediction Model Based on Effective Planarization Length.

As a planarization technique, chemical mechanical polishing (CMP) continues to suffer from pattern effects that result in large variations in material thickness, which can influence circuit performance and yield. Therefore, tools for predicting post-CMP chip morphology based on the layout-dependent effect (LDE) have become increasingly critical and widely utilized for design verification and manufacturing development. In order to characterize the impact of patterns on polishing, such models often require the extraction of graphic parameters. However, existing extraction algorithms provide a limited description of the interaction effect between layout patterns. To address this problem, we calculate the average density as a density correction and innovatively use a one-dimensional line contact deformation profile as a weighting function. To verify our hypothesis, the density correction method is applied to a density step-height-based high-K metal gate-CMP prediction model. The surface prediction results before and after optimization are compared with the silicon data. The results show a reduction in mean squared error (MSE) of 40.1% and 35.2% in oxide and Al height predictions, respectively, compared with the preoptimization results, confirming that the optimization method can improve the prediction accuracy of the model.

Extensor tendon transfer for fracture-related extensor pollicis longus rupture: Long-term outcome case series.

BACKGROUND: Spontaneous rupture of the extensor pollicis longus (EPL) tendon following both nonoperative and operative treatment of distal radius fractures has been well described. PURPOSE: The purpose of this study was to assess long-term outcomes of extensor indicis proprius to EPL tendon transfers for patients following distal radius fracture and EPL tendon repair. STUDY DESIGN: Retrospective case series focusing on long-term clinical outcomes. METHODS: A retrospective review was conducted for patients who sustained a distal radius fracture and subsequently underwent extensor tendon transfer from 2005-2015 at a private practice center. Outcome measures including index finger (IF) metacarpophalangeal (MCP) and thumb interphalangeal (IP) active range of motion (ROM), digital extension against resistance, subjective complaints, and QuickDASH scores were recorded at final follow-up. RESULTS: Seven patients were included in the study. There were six females and one male subject, mean age of 54 ± 13 years at injury of EPL, and 5/7 involved the left upper extremity. For isolated function, 7/7 (100%) patients had isolated, active IF MCP extension, 6/7 (86%) could extend IF MCP and thumb IP against resistance. Mean IF MCP extension was 1° ± 2°, mean IF MCP flexion was 89° ± 2°, mean thumb IP extension was -5° ± 4°, and mean thumb IP flexion was 67° ± 15°. Mean QuickDASH score was 16 ± 14. CONCLUSIONS: This series shows good long-term functional and patient reported outcomes in patients following extensor indicis proprius to EPL tendon transfers at a single center.

Accessory Extensor Pollicis Longus Tendon Classification Modification.

Supernumerary extensor pollicis longus (EPL) and extensor indicis proprius tendons are infrequently reported. There are few case reports on more than one accessory tendon in one individual. As a result, they are not represented in previously described classifications for variations in extensors to the thumb. Elective surgery was performed on a 57-year-old right-handed female. Within the fourth compartment, two anomalous accessory tendons were present. These tendons were identified as an accessory EPL tendon and an accessory extensor indicis proprius tendon. The normal EPL tendon occupied the third compartment ulnar to Lister's tubercle, as usual. The previous classification system for anomalous EPL tendons is useful in the organization and description of thumb extensor tendon variations. However, it is not a complete representation of the anomalies identified, including the one in this report. We have proposed an additional category for this classification system to better encompass the variation in anomalous tendon anatomy.

Kinetics Conditioning of (Electro) Chemically Stable Zn Anode with pH Regulation Toward Long-Life Zn-Storage Devices.

The safety, low cost, and high power density of aqueous Zn-based devices (AZDs) appeal to large-scale energy storage. Yet, the presence of hydrogen evolution reaction (HER) and chemical corrosion in the AZDs leads to local OH- concentration increasement and the formation of ZnxSOy(OH)z•nH2O (ZHS) by-products at the Zn/electrolyte interface, causing instability and irreversibility of the Zn-anodes. Here, a strategy is proposed to regulate OH- by introducing a bio-sourced/renewable polypeptide (ɛ-PL) as a pH regulator in electrolyte. The consumption of OH- species is evaluated through in vitro titration and cell in vivo in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy at a macroscopic and molecular level. The introduction of ɛ-PL is found to significantly suppress the formation of ZHS and associated side reactions, and reduce the local coordinated H2O of the Zn2+ solvation shell, widening electrochemical stable window and suppressing OH- generation during HER. As a result, the inclusion of ɛ-PL improves the cycle time of Zn/Zn symmetrical cells from 15 to 225 h and enhances the cycle time of aqueous Zn- I2 cells to 1650 h compared to those with pristine electrolytes. This work highlights the potential of kinetical OH- regulation for by-product and dendrite-free AZDs.

3D-printed bioink loading with stem cells and cellular vesicles for periodontitis-derived bone defect repair.

The suitable microenvironment of bone regeneration is critically important for periodontitis-derived bone defect repair. Three major challenges in achieving a robust osteogenic reaction are the exist of oral inflammation, pathogenic bacteria invasion and unaffluent seed cells. Herein, a customizable and multifunctional 3D-printing module was designed with glycidyl methacrylate (GMA) modified epsilon-poly-L-lysine (EPLGMA) loading periodontal ligament stem cells (PDLSCs) and myeloid-derived suppressive cells membrane vesicles (MDSCs-MV) bioink (EPLGMA/PDLSCs/MDSCs-MVs, abbreviated as EPM) for periodontitis-derived bone defect repair. The EPM showed excellent mechanical properties and physicochemical characteristics, providing a suitable microenvironment for bone regeneration.In vitro, EPMs presented effectively kill the periodontopathic bacteria depend on the natural antibacterial properties of the EPL. Meanwhile, MDSCs-MV was confirmed to inhibit T cells through CD73/CD39/adenosine signal pathway, exerting an anti-inflammatory role. Additionally, seed cells of PDLSCs provide an adequate supply for osteoblasts. Moreover, MDSCs-MV could significantly enhance the mineralizing capacity of PDLSCs-derived osteoblast. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that the EPM scaffold similarly had an excellent anti-inflammatory and bone regeneration efficacyin vivo. This biomimetic and multifunctional 3D-printing bioink opens new avenues for periodontitis-derived bone defect repair and future clinical application.

Employment Protection Legislation, Labour Market Dualism, and Fertility in Europe.

Theoretically, whether a more loosely regulated labour market inhibits or fosters fertility in a society is ambiguous. Empirically, the few studies analysing the relationship between the strictness of employment protection legislation-the norms and procedures regulating labour markets' hiring and firing processes-and fertility have found mixed evidence. This paper reconciles the ambivalent conclusions of previous studies by analysing the impact of employment protection legislation and labour market dualism on total fertility across 19 European countries between 1990 and 2019. Our results indicate that an increase in employment protection for regular workers positively affects total fertility. Nonetheless, an increasing gap between the regulation of regular and temporary employment-that is, labour market dualism-negatively impacts total fertility. These effects, of small-to-moderate intensity, are relatively homogeneous across age groups and geographical areas and are especially pronounced among the lower educated. We conclude that labour market dualism, rather than a "rigid" employment protection legislation, discourages fertility.

Biomechanical Strength of a Novel Tendon Splicing Open Book Technique Compared to the Pulvertaft Method Using Unembalmed Human Cadaveric Tissue.

Background: Extensor pollicis longus (EPL) tendon rupture is a known complication of distal radius fractures. The Pulvertaft graft technique is currently used for tendon transfer of extensor indicis proprious (EIP) to EPL. This technique can produce unwanted tissue bulkiness and cosmetic concerns as well as hinder tendon gliding. A novel "open book" technique has been proposed, but relevant biomechanical data are limited. We designed a study to examine the biomechanical behaviours of the "open book" versus Pulvertaft techniques. Methods: Twenty matched forearm-wrist-hand samples were harvested from 10 fresh frozen cadavers (2 female, 8 male) with a mean age of 61.7 (±19.25) years. The EIP was transferred to EPL using the Pulvertaft versus "open book" techniques for each matched pair (sides randomly assigned). The repaired tendon segments were mechanically loaded using a Materials Testing System to examine graft biomechanical behaviours. Results: Mann-Whitney U test outcomes demonstrated that there was no significant difference between "open book" versus Pulvertaft techniques for peak load, load at yield, elongation at yield, or repair width. The "open book" technique demonstrated a significantly lower elongation at peak load and repair thickness, as well as significantly higher stiffness when compared with the Pulvertaft technique. Conclusions: Our findings support the use of the "open book" technique, producing comparable biomechanical behaviours compared to the Pulvertaft technique. Incorporating the "open book" technique potentially requires smaller repair volume, producing size and appearance that is more anatomic when compared with the Pulvertaft.

Contexte: La rupture du tendon du long extenseur du pouce (EPL - Extensor pollicis longus) est une complication connue des fractures distales du radius. La technique de greffe de Pulvertaft est actuellement utilisée pour un transfert tendineux de l'extenseur propre de l'index (EIP - extensor indicis proprious) à l'EPL. Cette technique peut produire une masse de tissu volumineuse non désirée et des préoccupations cosmétiques, mais aussi gêner le glissement du tendon. Une nouvelle technique en « livre ouvert ¼ a été proposée, mais les données biomécaniques pertinentes sont limitées. Nous avons conçu une étude visant à examiner les comportements biomécaniques de la technique « en livre ouvert ¼ comparativement à la technique de Pulvertaft. Méthodes: Vingt échantillons appariés avant-bras-poignet-main ont été prélevés sur 10 cadavres récemment congelés (2 femmes, 8 hommes) d'âge moyen 61,7 (± 19,25) ans. Les EIP ont été transférés aux EPL en utilisant la technique de Pulvertaft et la technique en livre ouvert pour chaque paire appariée (l'affectation du côté à chaque technique a été faite de manière aléatoire). Les segments tendineux réparés ont été chargés mécaniquement au moyen d'un système pour tester les matériaux afin d'étudier les comportements biomécaniques des greffes. Résultats: Les résultats du test U de Mann-Whitney ont montré qu'il n'y avait pas de différence significative entre la technique « en livre ouvert ¼ et la technique de Pulvertaft pour la charge maximum, la charge à la limite apparente d'élasticité, l'allongement à la limite apparente d'élasticité ou la largeur de réparation. La technique « en livre ouvert ¼ a démontré un allongement à la charge maximum et une épaisseur de réparation significativement moindres, ainsi qu'une significativement plus grande raideur, comparativement à la technique de Pulvertaft. Conclusions: Nos constatations étayent l'utilisation de la technique « en livre ouvert ¼ qui procure des comportements biomécaniques comparables à ceux de la technique de Pulvertaft. L'incorporation de la technique « en livre ouvert ¼ requiert potentiellement un plus petit volume de réparation, aboutissant à des dimensions et à un aspect plus anatomiques par rapport à la technique de Pulvertaft.

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples.

Chromosomal abnormalities are the most common causes of early pregnancy losses (EPLs). In this study, we aimed to evaluate the incidence and spectrum of chromosomal abnormalities in EPLs and correlate them with different clinical characteristics. We performed Quantitative Fluorescent PCR (QF-PCR), followed by subtelomeric Multiplex Ligation Probe Amplification (MLPA) analysis to detect chromosomal abnormalities in 900 products of conceptions (POCs) from EPLs collected over a period of 10 years. Chromosomal abnormalities were present in 56.25% of uncontaminated EPLs, with significantly higher incidence in women ≥36 years (71.37%, p<0.0001) in comparison to women ≤30 years of age (43.40%). Trisomies were also more common in women ≥36 years (79.68%, p<0.0001) than in those ≤30 years of age (48.70%). In contrast, triploidy and monosomies were more prevalent in women ≤30 years of age (26.09%, p<0.0001 and 16.52%, p=0.0066 respectively) than in women ≥36 years of age (6.42% and 6.42% respectively). Trisomy 16 was more common in women ≤30 (39.29%, p=0.0009) than in those ≥36 years of age (16.78%), while trisomy 22 was predominant among women ≥36 (23.49%, p=0.013), and was not present in the group of women ≤30 years of age. The frequency of chromosomal abnormalities in POCs from women with sporadic (61.19%) was higher than in those with recurrent EPLs (55.21%). This difference, however, was not statistically significant (p=0.164). Although some differences in the chromosomal aneuploidy rates among women with different ABO blood groups, as well as among 6-8 and 9-11 gestational week EPLs were observed, further larger studies are required to confirm these findings. In conclusion, our study enriches the knowledge about chromosomal abnormalities as a cause of EPLs and confirms the higher incidence of foetal chromosomal abnormalities in EPLs in women of older reproductive age. Furthermore, it shows that using QF-PCR and MLPA methodologies, a high detection rate of chromosomal abnormalities in EPLs can be reached.

Growing inequality during the Great Recession: Labour market institutions and the education gap in unemployment across Europe and in the United States.

We study how the education gap in unemployment has evolved by gender and age groups across 28 European countries and the United States from 2000 to 2014, using the European Union's Labour Force Surveys and the US Current Population Surveys. During and after the Great Recession, the absolute education gap in unemployment expanded in almost all countries, which was mainly driven by a marked increase in the unemployment risk among low educated men. A two-step multilevel analysis confirmed the negative relationship between the education gap and both (lagged) GDP growth and GDP level. Further, institutional labour market features moderated the impact of the business cycle. A higher share of temporary employment boosted employment for less educated persons, thus flattening the education gradient in unemployment, while a larger public sector somewhat protected more highly educated individuals against unemployment. The gap for young workers was large in settings with strict regular contract regulations.

Radial vs. Dorsal Approach for Elastic Stable Internal Nailing in Pediatric Radius Fractures-A 10 Year Review.

BACKGROUND: Forearm fractures are one of the most common fractures in children. Over the last years, a tendency towards surgical treatment was seen, especially closed reduction and internal fixation with elastic stable internal nailing (ESIN). Despite an overall low complication rate being described, a risk of intraoperative complications remains. MATERIAL AND METHODS: A total of 237 patients (mean age 8.3 ± 3.4 (1-16) years) with forearm or radius fractures treated with ESIN between 2010 and 2020 were included in the study. The retrospective review of 245 focused on fracture pattern, pre- and postoperative fracture angulation, intra- and postoperative complications, and surgical approach for nail implant. The fracture pattern and pre- and postoperative angulation were measured radiographically. Complications such as ruptures of the extensor pollicis longus (EPL) tendon and sensibility disorders of the superficial radial nerve were further analyzed. RESULTS: In 201 cases (82%), we performed a dorsal approach; 44 fractures (17.9%) were treated with a radial approach. In total, we found 25 (10%) surgery-related complications, of which 21 (8.6%) needed further surgical treatment. In total, we had 14 EPL ruptures (5.7%), 4 sensibility disorders of the superficial radial nerve (1.6%), 2 refractures after implant removal (0.8%), 2 superficial wound infections (0.8%), and 1 child with limited range of motion after surgery (0.4%). No statistical significance between pre- and postoperative angulation correlated to fracture patterns or diameter of the elastic nail was seen. As expected, there was a significant improvement of postoperative angulation. Using radial approach in distal radial fractures showed a lower rate of surgical related complications, 2.3% of which need further surgical treatment as well as better postoperative angulations compared to the dorsal approach (8.5%). CONCLUSION: Especially due to the low risk of damaging the EPL tendon, the radial approach showed a lower complication rate which needed further surgical treatment. The risk of lesions of the superficial radial nerve remains.

Spontaneous rupture of the extensor pollicis longus tendon in a lacrosse player.

Spontaneous rupture of the extensor pollicis longus (EPL) tendon at the wrist has been reported with predisposing factors to include distal radius fractures, rheumatoid arthritis, systemic or local steroids, and repetitive abnormal motion of the wrist joint.We present a case of an 18-year-old college lacrosse player without history of known predisposing factors who presented with an acute inability to extend the interphalangeal (IP) joint of his right thumb. Preoperative musculoskeletal ultrasound demonstrated rupture of the EPL tendon proximal to the carpometacarpal (CMC) joint of the thumb. A tendon transfer was therefore performed, where the extensor indicis proprius (EIP) was surgically rerouted to reconstruct the ruptured EPL. The athlete eventually returned to competition without sequela.We suggest that the tendon rupture was secondary to repetitive stick checking during play, causing microtrauma to his exposed dorsal wrist. Lacrosse team physicians, athletic trainers, and equipment managers should be aware of this injury mechanism and ensure that their players, and attackmen in particular, are equipped with gloves which adequately pad the dorsal wrist to decrease the risk of microtrauma to the EPL tendon.

The Arabidopsis NuA4 histone acetyltransferase complex is required for chlorophyll biosynthesis and photosynthesis.

Although two Enhancer of Polycomb-like proteins, EPL1A and EPL1B (EPL1A/B), are known to be conserved and characteristic subunits of the NuA4-type histone acetyltransferase complex in Arabidopsis thaliana, the biological function of EPL1A/B and the mechanism by which EPL1A/B function in the complex remain unknown. Here, we report that EPL1A/B are required for the histone acetyltransferase activity of the NuA4 complex on the nucleosomal histone H4 in vitro and for the enrichment of histone H4K5 acetylation at thousands of protein-coding genes in vivo. Our results suggest that EPL1A/B are required for linking the NuA4 catalytic subunits HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY 1（HAM1) and HAM2 with accessory subunits in the NuA4 complex. EPL1A/B function redundantly in regulating plant development especially in chlorophyll biosynthesis and de-etiolation. The EPL1A/B-dependent transcription and H4K5Ac are enriched at genes involved in chlorophyll biosynthesis and photosynthesis. We also find that EAF6, another characteristic subunit of the NuA4 complex, contributes to de-etiolation. These results suggest that the Arabidopsis NuA4 complex components function as a whole to mediate histone acetylation and transcriptional activation specifically at light-responsive genes and are critical for photomorphogenesis.

The immunogenic reaction and bone defect repair function of ε-poly-L-lysine (EPL)-coated nanoscale PCL/HA scaffold in rabbit calvarial bone defect.

Tissue engineering is a promising strategy for bone tissue defect reconstruction. Immunogenic reaction, which was induced by scaffolds degradation or contaminating microorganism, influence cellular activity, compromise the efficiency of tissue engineering, or eventually lead to the failure of regeneration. Inhibiting excessive immune response through modulating scaffold is critical important to promote tissue regeneration. Our previous study showed that ε-poly-L-lysine (EPL)-coated nanoscale polycaprolactone/hydroxyapatite (EPL/PCL/HA) composite scaffold has enhanced antibacterial and osteogenic properties in vitro. However, the bone defect repair function and immunogenic reaction of EPL/PCL/HA scaffolds in vivo remains unclear. In the present study, three nanoscale scaffolds (EPL/PCL/HA, PCL and PCL/HA) were transplanted into rabbit paraspinal muscle pouches, and T helper type 1 (Th1), T helper type 2 (Th2), T helper type 17 (Th17), and macrophage infiltration were analyzed after 1 week and 2 weeks to detect their immunogenic reaction. Then, the different scaffolds were transplanted into rabbit calvarial bone defect to compare the bone defect repair capacities. The results showed that EPL/PCL/HA composite scaffolds decreased pro-inflammatory Th1, Th17, and type I macrophage infiltration from 1 to 2 weeks, and increased anti-inflammatory Th2 infiltration into the regenerated area at 2 weeks in vivo, when compared to PCL and PCL/HA. In addition, EPL/PCL/HA showed an enhanced bone repair capacity compared to PCL and PCL/HA when transplanted into rabbit calvarial bone defects at both 4 and 8 weeks. Hence, our results suggest that EPL could regulate the immunogenic reaction and promote bone defect repair function of PCL/HA, which is a promising agent for tissue engineering scaffold modulation.

Site-Directed Modification of Yeast-Produced Proteins Using Expressed Protein Ligation.

Expressed protein ligation (EPL), using non-self-cleaving inteins, allows for the site-specific addition of customized chemical moieties to the termini of proteins. In this way, protein activity can be preserved while functionalizing the target protein with a wide range of chemical handles. Here, we describe methods for EPL-based modification of proteins produced by yeast, employing an engineered, non-self-cleaving intein known as 202-08. Methods for EPL modification of both yeast surface displayed and secreted proteins with bioorthogonal chemical groups are described. These methods allow for the site-specific modification of intein-fused proteins produced in yeast.

Gcn5 and Esa1 function as histone crotonyltransferases to regulate crotonylation-dependent transcription.

Histone post-translational modifications (PTMs) are critical for processes such as transcription. The more notable among these are the nonacetyl histone lysine acylation modifications such as crotonylation, butyrylation, and succinylation. However, the biological relevance of these PTMs is not fully understood because their regulation is largely unknown. Here, we set out to investigate whether the main histone acetyltransferases in budding yeast, Gcn5 and Esa1, possess crotonyltransferase activity. In vitro studies revealed that the Gcn5-Ada2-Ada3 (ADA) and Esa1-Yng2-Epl1 (Piccolo NuA4) histone acetyltransferase complexes have the capacity to crotonylate histones. Mass spectrometry analysis revealed that ADA and Piccolo NuA4 crotonylate lysines in the N-terminal tails of histone H3 and H4, respectively. Functionally, we show that crotonylation selectively affects gene transcription in vivo in a manner dependent on Gcn5 and Esa1. Thus, we identify the Gcn5- and Esa1-containing ADA and Piccolo NuA4 complexes as bona fide crotonyltransferases that promote crotonylation-dependent transcription.

Nerve transfers in the upper extremity following cervical spinal cord injury. Part 1: Systematic review of the literature.

OBJECTIVE: Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly being used to treat patients with cervical SCIs. In this study, the authors performed a systematic review summarizing the published literature on nerve transfers to restore upper-extremity function in tetraplegia. METHODS: A systematic literature search was conducted using Ovid MEDLINE 1946-, Embase 1947-, Scopus 1960-, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and clinicaltrials.gov to identify relevant literature published through January 2019. The authors included studies that provided original patient-level data and extracted information on clinical characteristics, operative details, and strength outcomes after nerve transfer procedures. Critical review and synthesis of the articles were performed. RESULTS: Twenty-two unique studies, reporting on 158 nerve transfers in 118 upper limbs of 92 patients (87 males, 94.6%) were included in the systematic review. The mean duration from SCI to nerve transfer surgery was 18.7 months (range 4 months-13 years) and mean postoperative follow-up duration was 19.5 months (range 1 month-4 years). The main goals of reinnervation were the restoration of thumb and finger flexion, elbow extension, and wrist and finger extension. Significant heterogeneity in transfer strategy and postoperative outcomes were noted among the reports. All but one case report demonstrated recovery of at least Medical Research Council grade 3/5 strength in recipient muscle groups; however, there was greater variation in the results of larger case series. The best, most consistent outcomes were demonstrated for restoration of wrist/finger extension and elbow extension. CONCLUSIONS: Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. Flexor reinnervation strategies show variable treatment effect sizes; however, extensor reinnervation may provide more consistent, meaningful recovery. Despite numerous published case reports describing good patient outcomes with nerve transfers, there remains a paucity in the literature regarding optimal timing and long-term clinical outcomes with these procedures.

Nerve transfers in the upper extremity following cervical spinal cord injury. Part 2: Preliminary results of a prospective clinical trial.

OBJECTIVE: Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly used to treat patients with cervical SCIs. In this article, the authors present early results of a prospective clinical trial using nerve transfers to restore upper-extremity function in tetraplegia. METHODS: Participants with American Spinal Injury Association (ASIA) grade A-C cervical SCI/tetraplegia were prospectively enrolled at a single institution, and nerve transfer(s) was performed to improve upper-extremity function. Functional recovery and strength outcomes were independently assessed and prospectively tracked. RESULTS: Seventeen participants (94.1% males) with a median age of 28.4 years (range 18.2-76.3 years) who underwent nerve transfers at a median of 18.2 months (range 5.2-130.8 months) after injury were included in the analysis. Preoperative SCI levels ranged from C2 to C7, most commonly at C4 (35.3%). The median postoperative follow-up duration was 24.9 months (range 12.0-29.1 months). Patients who underwent transfers to median nerve motor branches and completed 18- and 24-month follow-ups achieved finger flexion strength Medical Research Council (MRC) grade ≥ 3/5 in 4 of 15 (26.7%) and 3 of 12 (25.0%) treated upper limbs, respectively. Similarly, patients achieved MRC grade ≥ 3/5 wrist flexion strength in 5 of 15 (33.3%) and 3 of 12 (25.0%) upper limbs. Among patients who underwent transfers to the posterior interosseous nerve (PIN) for wrist/finger extension, MRC grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) upper limbs 18 and 24 months postoperatively, respectively. Similarly, grade ≥ 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) cases for thumb extension. No meaningful donor site deficits were observed. Patients reported significant postoperative improvements from baseline on upper-extremity-specific self-reported outcome measures. CONCLUSIONS: Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. In the authors' experience, nerve transfers for the reinnervation of hand and finger flexors showed variable functional recovery; however, transfers for the reinnervation of arm, hand, and finger extensors showed a more consistent and meaningful return of strength and function.