Management of Extensive Talar Osteolysis with Agility™ Total Ankle Replacement Systems Using Geometric Metal-reinforced Polymethylmethacrylate Cement Augmentation

The Agility™ Total Ankle Replacement System, almost exclusively without polymethylmethacrylate cement fixation, was the most commonly used implant in the United States from 1998 to 2007. Much attention has been given to the intraoperative complications and incision healing-related problems. However, it is the intermediate- and long-term complications, specifically, aseptic osteolysis, talar component loosening, subsidence, and progressive malalignment, that require careful consideration, because the revision options are limited. We describe a technique for management of extensive talar aseptic osteolysis for revision of Agility™ total ankle replacement systems with use of geometric metal-reinforced polymethylmethacrylate cement augmentation. This technique preserves the subtalar joint, provides immediate component stability and restoration of component alignment and height, and is a cost-effective alternative to other available options and still allows for additional revision should late failure occur.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

The effect of extensive reading and paired-associate learning on long-term vocabulary retention: An event-related potential study

We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d = 1.35). Evidence from the N400 effects (d = 1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL.     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

(iii) Bearing surfaces

Alternative bearings surfaces to polyethylene have reduced wear and have led to improved patient outcomes, allowing younger and more active patients to be considered for joint replacements. These bearing surfaces have been developed largely as a response to osteolysis and loosening associated with polyethylene particulate debris. This has led to the evolution of various forms of cross-linked polyethylene and to the greater use of hard-on-hard bearings. The use of metal-on-metal led to resurfacing hip replacements and to the use of large head metal-on-metal hip replacements. Although metal-on-metal bearings have a number of theoretical advantages, the release of metal debris and ions from some designs has been catastrophic. In the future new bearing surfaces must be more thoroughly tested pre-clinically and in well-designed clinical series.     

Interaction between the photosensitizer lumichrome and human serum albumin: effect of excipients

Lumichrome (Lc) is a photodegradation product of riboflavin that can be used as a photosensitizer (PS) in antibacterial photodynamic therapy (aPDT). The binding of Lc with plasma proteins such as human serum albumin (HSA) could affect its efficiency as PS. Excipients are necessary to prepare stable formulations to be used in aPDT and they may affect the PS-HSA binding. Hydroxypropyl (HP)-α, β, γ-cyclodextrin (CD), polyethylene glycol 400 (PEG400) and Pluronic^® F-127 (PF127) were selected as model excipients in this study. The intrinsic HSA fluorescence quenching and absorption and fluorescence spectroscopy were used to evaluate the Lc-HSA interaction in the absence and presence of excipients. Nano-differential scanning calorimetry (DSC) was used to determine the effect of excipients on HSA. The photostability of the samples was also evaluated. The combined results showed a modest interaction between Lc and HSA which was reduced mainly by HPβCD. No major alterations of the HSA nano-DSC thermogram were observed after addition of excipients. HSA did enhance Lc photodegradation. The presence of PF127 did also induce photochemical destabilization of Lc independent of HSA. In conclusion, HPαCD, HPγCD and PEG400 seemed to be the excipients more suitable for use in topical preparations containing Lc.