Adjustable loop ACL suspension devices demonstrate less reliability in terms of reproducibility and irreversible displacement.

PURPOSE The aim of this study was to perform a comprehensive biomechanical examination of frequently applied femoral cortical suspension devices, comparing the properties of both fixed and adjustable fixation mechanisms. It was hypothesized that adjustable loop devices demonstrate less consistent fixation properties with increased variability compared to fixed loop devices. METHODS Nine frequently applied fixation button types were tested, six adjustable and three rigid loop devices. Six samples of each device type were purchased. Each device was installed in a servo-hydraulic mechanical testing machine, running a 2000 cycle loading protocol at force increments between 50 and 500 N. Irreversible displacement in mm was measured for all of the tested samples of each implant. Ultimately, maximum load to failure was applied and measured in Nm. An irreversible displacement of 3 mm was considered failure of the implant. RESULTS Three of the six adjustable devices (GraftMax™, TightRope® ToggleLoc™) demonstrated a median displacement above the threshold of clinical failure before completion of the cycles. All adjustable loop devices showed a wide intragroup variation in terms of irreversible displacement, compared to fixed-loop devices. Fixed-loop devices provided consistent reproducible results with narrow ranges and significantly lower irreversible displacement (p < 0.05), the maximum being 1.4 mm. All devices withstood an ultimate force of more than 500 N. CONCLUSION Adjustable loop devices still show biomechanical inferiority and demonstrate heterogeneity of fixation properties with wide- and less-reproducible displacement ranges resultant to the mechanism of adjustment, denoting less reliability. However, three adjustable devices (RIGIDLOOP™ Adjustable, Ultrabutton ◊, ProCinch™) demonstrate fixation capacities within the margins of clinical acceptance. RIGIDLOOP™ Adjustable provides the most comparable fixation properties to fixed loop devices

Mesenchymal Stromal Cell-Mediated Treatment of Local and Systemic Inflammation through the Triggering of an Anti-Inflammatory Response

AbstractThe emergence of cell‐based therapeutics, specifically the use of mesenchymal stromal/stem cells (MSCs), stands to significantly affect the future of targeted drug delivery technologies. MSCs represent a unique cell type, offering more than only regenerative potential but also site‐specific inflammatory targeting and tissue infiltration. In this study, a versatile multicomponent delivery platform, combining MSC tropism with multistage nanovector (MSV)‐mediated payload delivery, is debuted. It is demonstrated that the incorporation of drug‐loaded MSVs bestows MSCs with the ability to transport anti‐inflammatory payloads, achieving a fivefold increase in payload release without negatively impacting cellular functions, viability, extravasation, and inflammatory homing. When incorporated within MSCs, MSVs avoid rapid sequestration by filtering organs and conserve a 15‐fold increase in local inflammatory targeting compared to healthy ears. Furthermore, this MSC‐mediated MSV platform (M&Ms) rapidly triggers a 4.5‐fold reduction of local inflammation compared to free drug and extends survival to 100% of treated mice in a lethal model of systemic inflammation

Spherical nucleic acids as an infectious disease vaccine platform

Despite recent efforts demonstrating that organization and presentation of vaccine components are just as important as composition in dictating vaccine efficacy, antiviral vaccines have long focused solely on the identification of the immunological target. Herein, we describe a study aimed at exploring how vaccine component presentation in the context of spherical nucleic acids (SNAs) can be used to elicit and maximize an antiviral response. Using COVID-19 as a topical example of an infectious disease with an urgent need for rapid vaccine development, we designed an antiviral SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit into a liposome and decorating the core with a dense shell of CpG motif toll-like receptor 9 agonist oligonucleotides. This vaccine induces memory B cell formation in human cells, and in vivo administration into mice generates robust binding and neutralizing antibody titers. Moreover, the SNA vaccine outperforms multiple simple mixtures incorporating clinically employed adjuvants. Through modular changes to SNA structure, we uncover key relationships and proteomic insights between adjuvant and antigen ratios, concepts potentially translatable across vaccine platforms and disease models. Importantly, when humanized ACE2 transgenic mice were challenged in vivo against a lethal live virus, only mice that received the SNA vaccine had a 100% survival rate and lungs that were clear of virus by plaque analysis. This work underscores the potential for SNAs to be implemented as an easily adaptable and generalizable platform to fight infectious disease and demonstrates the importance of structure and presentation in the design of next-generation antiviral vaccines

Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert® MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.PostprintPeer reviewe

Ultrasound-Guided Electrodes for Conduction Studies of the Saphenous Nerve.

PURPOSE Saphenous nerve conduction studies are difficult, because the nerve is hard to localize and evoked responses are small. Ultrasound imaging may assist in the accurate localization and optimal positioning of surface (SE) and needle electrodes (NE). METHODS The study population included 39 subjects and was divided into two groups. Group A consisted of 20 healthy subjects, whereas group B of 19 patients with polyneuropathies. Orthodromic conduction was measured by distal supramaximal nerve stimulation. Surface electrode and NE recordings were compared. RESULTS In the control group, SEs recorded responses in 17 of 20 healthy subjects, whereas NEs in 19. In the patients' group, SEs recorded responses in 7 of 19 patients, whereas NEs in 16. In all healthy subjects and patients, sensory nerve action potentials recorded by NEs were significantly larger than those obtained by SEs (healthy subjects: 5.85 ± 3.01 μV vs. 1.98 ± 1.37 μV, P < 0.0001; patients 3.05 ± 2.35 μV vs. 0.71 ± 1.14 μV, t-test P < 0.0001). CONCLUSIONS Ultrasound guidance allows precise electrode positioning for saphenous nerve electrophysiological testing. Amplitudes of the recorded sensory nerve action potentials are clearly higher with ultrasound-guided needle than with surface recordings

Trends towards Biomimicry in Theranostics

Over the years, imaging and therapeutic modalities have seen considerable progress as a result of advances in nanotechnology. Theranostics, or the marrying of diagnostics and therapy, has increasingly been employing nano-based approaches to treat cancer. While first-generation nanoparticles offered considerable promise in the imaging and treatment of cancer, toxicity and non-specific distribution hindered their true potential. More recently, multistage nanovectors have been strategically designed to shield and carry a payload to its intended site. However, detection by the immune system and sequestration by filtration organs (i.e., liver and spleen) remains a major obstacle. In an effort to circumvent these biological barriers, recent trends have taken inspiration from biology. These bioinspired approaches often involve the use of biologically-derived cellular components in the design and fabrication of biomimetic nanoparticles. In this review, we provide insight into early nanoparticles and how they have steadily evolved to include bioinspired approaches to increase their theranostic potential