Injury Patterns in Fencing Athletes - A Retrospective Review.

Background: Fencing is a unique and increasingly popular sport, but limited data exist regarding related injuries. Purpose: To examine the types of injuries incurred by fencing athletes, and to analyze associations between age, sex, and hand dominance with type and location of injury. Study Design: Cross-sectional. Methods: Retrospective chart reviews were performed to evaluate fencing related injuries in athletes evaluated in the sports medicine and orthopedic clinics of a large teaching hospital. Results: One hundred and eighty-six patients (98 male, 88 female) were included. Average age at time of injury was 14.6 years (range 9 - 32 years). 73% of injuries involved the lower extremity, 16% involved the upper extremity and 10% affected the back. In the lower extremity, the knee (49%), ankle (16%) and hip (11%) were most commonly affected. 80% of injuries were treated with physical therapy. Only 5% required surgical intervention. Injuries of both upper and lower extremities were more commonly seen on the athlete's dominant side, and the majority of injuries (77%) occurred in athletes 13 years or older. Conclusion: The majority of injuries in these fencing athletes affected the lower extremity, most commonly the knee. Extensor mechanism dysfunction, primarily patellofemoral pain, was the most common diagnosis. Hand dominance, patient age, and patient sex did affect different injury characteristics. Level of Evidence: 2b.

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((NPhe)4GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague-Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78-1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe)4GGGGk(AZT)y(p)-OH to Sprague-Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC90) range (30-130 ng mL-1) for 35 days.

Stress fracture of the first rib in a hockey goalie.

First rib stress fractures are uncommon in athletes and diagnosis requires a high degree of clinical suspicion. Diagnostic delay may increase risk of poor healing and long-term complications. Case reports and series describe these injuries primarily in overhead athletes; proposed contributing factors include anatomic susceptibility to stress and repetitive opposing muscular forces. We describe an ice hockey goalie with acute-on-chronic thoracic back pain who was found to have a first rib stress fracture, which to our knowledge is the first reported in this sport. We hypothesize that biomechanical stress from new stick positioning contributed to the injury. Our patient recovered symptomatically with conservative treatment; however, imaging suggested nonunion of the fracture site and possible pseudoarthrosis.

Enzyme-Triggered l-α/d-Peptide Hydrogels as a Long-Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs.

Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Patient adherence to complicated dosage regimens remains a key barrier. There is a need for convenient long-acting formulations that deliver drugs over sustained periods. This paper presents an alternative platform, an injectable in situ forming hydrogel implant to deliver a model antiretroviral drug (zidovudine [AZT]) over 28 days. The formulation is a self-assembling ultrashort d or l-α peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), covalently conjugated to zidovudine via an ester linkage. Rheological analysis demonstrates phosphatase enzyme instructed self-assembly, with hydrogels forming within minutes. Small angle neutron scattering data suggest hydrogels form narrow radius (≈2 nm), large length fibers closely fitting the flexible cylinder elliptical model. d-Peptides are particularly promising for long-acting delivery, displaying protease resistance for 28 days. Drug release, via hydrolysis of the ester linkage, progress under physiological conditions (37 °C, pH 7.4, H2 O). Subcutaneous administration of Napffk(AZT)Y[p]G-OH in Sprague Dawley rats demonstrate zidovudine blood plasma concentrations within the half maximal inhibitory concentration (IC50 ) range (30-130 ng mL-1 ) for 35 days. This work is a proof-of-concept for the development of a long-acting combined injectable in situ forming peptide hydrogel implant. These products are imperative given their potential impact on society.

Unravelling the antimicrobial activity of peptide hydrogel systems: current and future perspectives.

The use of hydrogels has garnered significant interest as biomaterial and drug delivery platforms for anti-infective applications. For decades antimicrobial peptides have been heralded as a much needed new class of antimicrobial drugs. Self-assembling peptide hydrogels with inherent antimicrobial ability have recently come to the fore. However, their fundamental antimicrobial properties, selectivity and mechanism of action are relatively undefined. This review attempts to establish a link between antimicrobial efficacy; the self-assembly process; peptide-membrane interactions and mechanical properties by studying several reported peptide systems: ß-hairpin/ß-loop peptides; multidomain peptides; amphiphilic surfactant-like peptides and ultrashort/low molecular weight peptides. We also explore their role in the formation of amyloid plaques and the potential for an infection etiology in diseases such as Alzheimer's. We look briefly at innovative methods of gel characterization. These may provide useful tools for future studies within this increasingly important field.

Forming Low-Molecular-Weight Hydrogels by Electrochemical Methods.

Low-molecular-weight hydrogels (LMWG) can be formed by electrochemical methods. Unique to the electrochemical method, gelation is localized on the electrode surface; therefore, thin hydrogel films can be prepared in seconds while thicker gels can be prepared in minutes. Furthermore, hydrogels are suitable for use in a range of characterization methods. Here, we describe techniques to form hydrogels using cyclic voltammetry and potentiometry.

Tuning the antimicrobial activity of low molecular weight hydrogels using dopamine autoxidation.

We present a method to trigger the formation of dipeptide-based hydrogels by the simple addition of dopamine. Dopamine undergoes oxidation in air, reducing the pH to induce gelation. The production of polydopamine and release of reactive oxygen species such as hydrogen peroxide confers antimicrobial activity. Gel stiffness can be controlled by modulating the initial starting pH of the gelator solution. We can use this method to tune the antimicrobial activity of the gels, with gels that are less stiff demonstrating increased bactericidal efficacy against Gram-positive bacteria.

Annealing Supramolecular Gels by a Reaction Relay.

Supramolecular gels have potential in many areas. In many cases, a major drawback is that the gels are formed at a high rate. As a result, nonoptimal, kinetically trapped self-assembled structures are often formed, leading to gels that can be hard to reproduce and control. One method to get around kinetic trapping is annealing. Thermal annealing is one possibility, but it is not always desirable to heat the gels. Here, we describe a method to anneal pH-triggered gels after they are formed. We employ a reaction relay in a peptide-based hydrogel system to anneal the structures by a controlled and uniform pH change. Our method allows us to prepare gels with more controlled properties. We show that this can be used to enable homogeneous "molding and casting" of the hydrogels. This method of annealing is more effective in improving gel robustness than a conventional heat-cool cycle.

Probing the self-assembled structures and pKa of hydrogels using electrochemical methods.

The surface chemistry of the aggregated structures that form the scaffold in self-assembled hydrogels - their charge, hydrophobicity and ion-binding dynamics - plays an important role in determining the gel properties and the gel's suitability for specific applications. However, there are limited methods available for the study of this surface chemistry. Here, we show that electrochemical techniques can be used to measure the surface chemical properties of the self-assembled aggregate structures and also to determine the pKa of the gelators. We also provide a method to quickly determine whether a functionalised-dipeptide will form a gel or not. This method has scope for use in high-throughput screening and further complex pH-triggered self-assembled gelation systems.

Controlled Tuning of the Properties in Optoelectronic Self-Sorted Gels.

Multicomponent supramolecular gels have great potential for optoelectronics. Ideally, we could control the self-assembly of multiple components across many length scales, from the primary assembled structures to how these are arranged in space. This would allow energy transfer between p-type and n-type fibers to be controlled. Usually, a single network is formed and analyzed. It is not clear how most networks could be modified, and certainly not how these might be differentiated. Here, we address both of these issues. We show how the different components in a multicomponent gel can be differentiated by small-angle neutron scattering using contrast-matching experiments. The rate of self-assembly can be used to vary the networks that are formed, leading directly to changes in the efficiency of electron transfer. The assembly kinetics can therefore be used to prepare different networks from the same primary building blocks and primary self-assembled structures. We expect that these advances will allow multicomponent systems to become effective electronic materials.

Optimising low molecular weight hydrogels for automated 3D printing.

Hydrogels prepared from low molecular weight gelators (LMWGs) are formed as a result of hierarchical intermolecular interactions between gelators to form fibres, and then further interactions between the self-assembled fibres via physical entanglements, as well as potential branching points. These interactions can allow hydrogels to recover quickly after a high shear rate has been applied. There are currently limited design rules describing which types of morphology or rheological properties are required for a LMWG hydrogel to be used as an effective, printable gel. By preparing hydrogels with different types of fibrous network structures, we have been able to understand in more detail the morphological type which gives rise to a 3D-printable hydrogel using a range of techniques, including rheology, small angle scattering and microscopy.

Forkhead box M1 transcription factor is required for macrophage recruitment during liver repair.

Acute liver injury results from exposure to toxins, pharmacological agents, or viral infections, contributing to significant morbidity and mortality worldwide. While hepatic inflammation is critical for liver repair, the transcriptional mechanisms required for the recruitment of inflammatory cells to the liver are not understood. Forkhead box M1 (Foxm1) transcription factor is a master regulator of hepatocyte proliferation, but its role in inflammatory cells remains unknown. In this study, we generated transgenic mice in which Foxm1 was deleted from myeloid-derived cells, including macrophages, monocytes, and neutrophils. Carbon tetrachloride liver injury was used to demonstrate that myeloid-specific Foxm1 deletion caused a delay in liver repair. Although Foxm1 deficiency did not influence neutrophil infiltration into injured livers, the total numbers of mature macrophages were dramatically reduced. Surprisingly, Foxm1 deficiency did not influence the proliferation of macrophages or their monocytic precursors but impaired monocyte recruitment during liver repair. Expression of L-selectin and the CCR2 chemokine receptor, both critical for monocyte recruitment to injured tissues, was decreased. Foxm1 induced transcriptional activity of the mouse CCR2 promoter in cotransfection experiments. Adoptive transfer of monocytes to Foxm1-deficient mice restored liver repair and rescued liver function. Foxm1 is critical for liver repair and is required for the recruitment of monocytes to the injured liver.