The development and internal consistency of the comprehensive lower limb amputee socket survey in active lower limb amputees.

BACKGROUND:: Prosthetic socket fit is an important element associated with successful ambulation and use of a prosthesis. Prosthetists and rehabilitation clinicians would benefit from an assessment tool that discriminates between and quantifies the multiple determinants that influence the lower limb amputee's performance and satisfaction of a prosthetic socket. OBJECTIVES:: To determine the internal consistency of the comprehensive lower limb amputee socket survey, a new self-report measure of prosthetic socket satisfaction that quantifies suspension, stability, comfort, and appearance. STUDY DESIGN:: Cross-sectional sample of active amputees. METHODS:: Interviews were conducted with prosthetists, physical therapists, and lower limb amputees to identify clinical concerns and common activities influencing socket fit. An expert panel of five clinicians reviewed the items and constructed the original version of the comprehensive lower limb amputee socket survey which was then administered to a convenience sample of 47 active lower limb amputees. Item analysis and Cronbach's alpha were used to determine the final version of the comprehensive lower limb amputee socket survey. RESULTS:: Following item raw score-to-total score correlation with Cronbach's alpha for comprehensive lower limb amputee socket survey determinants, internal consistency improved when nine questions were eliminated. CONCLUSION:: The comprehensive lower limb amputee socket survey is a self-report measure of prosthetic socket satisfaction with very good internal consistency. CLINICAL RELEVANCE: When socket problems occur, the ability to determine the specific cause can reduce modification time, enhance socket fit, and promote patient satisfaction. A standardized multi-dimensional assessment measure of socket satisfaction enables prosthetists to quantify the multiple determinants of socket satisfaction, improve patient communication, and demonstrate the value of socket interventions.

Nanoparticle-Fusion Protein Complexes Protect against Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA. Mucosal immunization of BCG-primed mice with Nano-FP1 significantly enhanced protection in animals challenged with low-dose, aerosolized Mtb. Bacterial control by Nano-FP1 was associated with dramatically enhanced cellular immunity compared to BCG, including superior CD4+ and CD8+ T cell proliferation, tissue-resident memory T cell (Trm) seeding in the lungs, and cytokine polyfunctionality. Alongside these effects, we also observed potent humoral responses, such as the generation of Ag85B-specific serum IgG and respiratory IgA. Finally, we found that YC-NPs were able to activate antigen-presenting cells via an unconventional IRF-3-associated activation signature, without the production of potentially harmful inflammatory mediators, providing a mechanistic framework for vaccine efficacy and future development.

Mucosal Delivery of Fusion Proteins with Bacillus subtilis Spores Enhances Protection against Tuberculosis by Bacillus Calmette-Guérin.

Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guérin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model. Mice were primed with subcutaneous BCG, followed by mucosal booster immunizations with Spore-FP1. We show that Spore-FP1 enhanced pulmonary control of Mtb, as evidenced by reduced bacterial burdens in the lungs. This was associated with elevated antigen-specific IgG and IgA titers in the serum and lung mucosal surface, respectively. Spore-FP1 immunization generated superior antigen-specific memory T-cell proliferation in both CD4+ and CD8+ compartments, alongside bolstered Th1-, Th17-, and Treg-type cytokine production, compared to BCG immunization alone. CD69+CD103+ tissue resident memory T-cells (Trm) were found within the lung parenchyma after mucosal immunization with Spore-FP1, confirming the advantages of mucosal delivery. Our data show that Spore-FP1 is a promising new TB vaccine that can successfully augment protection and immunogenicity in BCG-primed animals.

Methods and Impact of Correcting Heart Rate Data Errors during Exercise in Older Adults.

Heart rate (HR) by time curves could be useful as a measure of treatment fidelity. The purposes were to describe the frequency of common recording irregularities (e.g. errors) observed during exercise, validate a process to correct those errors, and determine whether there is a clinically meaningful benefit to data correction. 1895 exercise sessions from 69 older adults with hip fracture were inspected for errors in the placement of event markers (duration of exercise) and signal artifacts. Marker errors occurred in 33% of the participants, and corrected in 324 sessions. Signal artifacts occurred in 96% of the participants, and eliminated in 702 sessions. Computer code was 85% accurate in detecting signal artifacts, compared to 97% for investigators. HR was significantly higher after correction, but the average change was only 0.69 + 1.20 beats per minute. A HR monitor showing HR by time curves can be used to evaluate treatment fidelity during exercise.