Viability of Structured Gait Retraining for Improving Clinical Outcomes Following Running-related Injury in Active Duty Service Members.

INTRODUCTION: All branches of the U.S. Military have a running component of their physical readiness testing battery. Running-related musculoskeletal injuries affect 20 to 40% of DoD Service Members each year. Running form has not historically been addressed with military running-related injuries. To assess the utility of a structured gait retaining protocol designed to treat the onset of running-related pain and/or injury by correcting identified biomechanical risk factors for injury and improve clinical outcomes. STUDY DESIGN: Case series. MATERIALS AND METHODS: A total of 160 Active Duty Service Members (ADSMs) with running-related lower-body musculoskeletal injuries were referred by a physical therapist for a multisession gait retraining program termed "Run with CLASS" (Cadence, Lean, Alignment, Soft-landing, Strike). Run with CLASS utilized various drills to emphasize impact progression, proximal strengthening, and proprioception and spatial awareness. RESULTS: Results revealed that the implemented gait retraining protocol significantly improved running parameters following lower-body injury as evidenced by increased cadence, improved functional assessment scores, and a marked transition from predominantly heel strike to forefoot strike patterns during running. CONCLUSIONS: A 3-week supervised gait retraining program focused on the gait retraining program termed "Run with CLASS" (Cadence, Lean, Alignment, Soft-landing, Strike) was successful in altering biomechanics of self-selected running gait by increasing cadence and transitioning ADSMs to a forefoot foot strike. Additionally, ADSMs reported significant improvements on the self-reported functional scores on the University of Wisconsin Running Injury and Recovery Index and Single Assessment Numerical Evaluation. LEVEL OF EVIDENCE: 4.

Physical therapist awareness of diagnostic imaging referral jurisdictional scope of practice: an observational study.

OBJECTIVES: To examine physical therapist awareness and utilization of imaging referral privileges in the United States (US) and how it relates to direct access frequency. METHODS: This study utilized survey data collected in 2020-2021 from US physical therapists. Subjects were asked about imaging referral jurisdictional authority in their state. Responses were analyzed for accuracy and compared to the level of jurisdictional authority and its impact on imaging referral. Analysis of imaging skills performance and imaging referral practices were compared to direct access frequency. RESULTS: Only 42.0% of physical therapists practicing in states that allow imaging referral were aware of this privilege. Those practicing where imaging referral was allowed via state legislation were significantly more likely (p < 0.01) to be aware of this privilege (71.4%) compared to those granted by the state board (25.2%). Those aware of their imaging referral scope were more likely (p < 0.01) to practice imaging referral (44.5%) compared to those who were unaware (3.2%). Direct access frequency was positively associated with imaging skill performance and imaging referral practice (p < 0.01). Doctors of Physical Therapy, residency/fellowship-trained physical therapists, and board-certified physical therapists all reported practicing greater frequency of direct access (p < 0.01). DISCUSSION/CONCLUSION: There is a striking lack of awareness of imaging privileges among physical therapists as influenced by the level of jurisdictional scope. These results suggest that the lack of awareness may have a dampening effect on diagnostic imaging referrals. The American Physical Therapy Association should consider engaging with state boards to raise imaging privilege awareness.

The effectiveness of telehealth gait retraining in addition to standard physical therapy treatment for overuse knee injuries in soldiers: a protocol for a randomized clinical trial.

INTRODUCTION: Running is the most common cardiovascular exercise in the military. However, there is a high incidence of running-related overuse injuries that reduces military readiness. Gait retraining is a common intervention to treat running-related injuries, but the high cost of equipment and lack of clinician expertise and availability reduces utilization. Gait retraining intervention in a telehealth format might improve feasibility. The purpose of this randomized clinical trial is to determine the effectiveness of a telehealth gait retraining intervention on pain, self-reported function, and biomechanical risk factors for injury in service members who present to a Military Health System physical therapy clinic with an overuse knee injury. METHODS: This is a parallel, two-arm, single-blind randomized clinical trial. The two independent variables are intervention (2 levels: telehealth gait retraining intervention with standard of care or only standard of care) and time (3 levels: baseline, 10 weeks or post-intervention, 14 weeks). Participants between the ages of 18 to 60 years will be included if they report knee pain during and/or after running to be anywhere from a 3 to a 7 on the numerical pain rating scale and demonstrate a rearfoot strike pattern. The primary dependent variables are as follows: (1) pain (worst pain during and/or after running) and (2) foot strike pattern (conversion rate from rearfoot to non-rearfoot foot strike pattern during running). Secondary outcomes include patient self-reported function and running biomechanics. DISCUSSION: The effectiveness of a telehealth gait retraining intervention to reduce pain and modify foot strike pattern is not known. The results of this study may help determine the effectiveness and feasibility of a telehealth gait retraining intervention to reduce pain, change foot strike, improve function, and improve running gait biomechanics. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04269473 . Registered 05 February 2020.

ST3GAL1 and ßII-spectrin pathways control CAR T cell migration to target tumors.

Adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells is becoming a promising treatment option for hematological malignancies. However, T cell immunotherapies have mostly failed in individuals with solid tumors. Here, with a CRISPR-Cas9 pooled library, we performed an in vivo targeted loss-of-function screen and identified ST3 ß-galactoside α-2,3-sialyltransferase 1 (ST3GAL1) as a negative regulator of the cancer-specific migration of CAR T cells. Analysis of glycosylated proteins revealed that CD18 is a major effector of ST3GAL1 in activated CD8+ T cells. ST3GAL1-mediated glycosylation induces the spontaneous nonspecific tissue sequestration of T cells by altering lymphocyte function-associated antigen-1 (LFA-1) endocytic recycling. Engineered CAR T cells with enhanced expression of ßII-spectrin, a central LFA-1-associated cytoskeleton molecule, reversed ST3GAL1-mediated nonspecific T cell migration and reduced tumor growth in mice by improving tumor-specific homing of CAR T cells. These findings identify the ST3GAL1-ßII-spectrin axis as a major cell-intrinsic program for cancer-targeting CAR T cell migration and as a promising strategy for effective T cell immunotherapy.

Salivary microRNA as a prospective tool for concussion diagnosis and management: A scoping review.

BACKGROUND: Despite increased efforts directed toward research, concussions are a growing concern and can be a complex injury for healthcare professionals to manage. Current practices are largely dependent on patients self-reporting symptoms and a clinical assessment, which uses objective tools that lack effectiveness. With the demonstrated effects of concussions, it is imperative that a more valid or reliable objective tool, like a clinical biomarker, be identified to improve outcomes. One potential biomarker that has shown promise is salivary microRNA. However, there is no objective consensus as to which microRNA offers the most clinical value regarding concussions, hence this review. Therefore, the purpose of this scoping review was to identify salivary miRNAs associated with concussions. METHODS: Two independent reviewers performed a literature search to identify research articles. Studies using human subjects, collected salivary miRNA, and were published in English were included. Data of interest were salivary miRNA, collection timing, and relation to concussion diagnosis or management. RESULTS: This paper reviews nine studies that analyzed salivary miRNA for concussion diagnosis and management. CONCLUSIONS: In total, the studies have identified 49 salivary miRNA that show promise in assisting with concussion practices. With continued research, the use of salivary miRNA may enhance clinicians' abilities to diagnose and manage concussions.

Chronic impairments of static postural stability associated with history of concussion.

Postural stability deficits are commonly observed in cases of concussion. However, the objective duration in which impairments of standing postural stability remain following a concussion is often inconclusive. The present study was conducted to determine if prior history of concussion is associated with deficits in postural stability beyond the clinical determination of recovery. It was hypothesized that concussion history would be associated with decreases in static stability compared to individuals that have never sustained a concussion. Fifty-four healthy adults were recruited based on whether they reported sustaining one or more prior concussions (n = 27) or no history of concussion (n = 27). Participants were instructed to stand on a force platform to track center-of-pressure (CoP) during standing for thirty seconds under four conditions based on stance and number of tasks: (1) bipedal, single-task, (2) bipedal, dual-task, (3) unipedal, single-task, and (4) unipedal, dual-task. Results revealed that individuals with a history of concussion demonstrate significantly reduced postural stability under dual-task conditions as evidenced by increases in average displacements and elliptical area of postural sway as well as reductions in CoP sample entropy. However, there were no significant differences in CoP displacement or elliptical area between groups under single task conditions. Overall, these findings indicate that concussion is associated with impairments of maintaining standing postural stability that remain evident approximately 7 years following clinical resolution of the initial injury. The exacerbation of these impairments under dual-task conditions indicate that concussion can result in a reduced capacity to allocate proper attention resources to multiple concurrent objectives.

CD4+ T Cell Interstitial Migration Controlled by Fibronectin in the Inflamed Skin.

The extracellular matrix (ECM) is extensively remodeled during inflammation providing essential guidance cues for immune cell migration and signals for cell activation and survival. There is increasing interest in the therapeutic targeting of ECM to mitigate chronic inflammatory diseases and enhance access to the tumor microenvironment. T cells utilize the ECM as a scaffold for interstitial migration, dependent on T cell expression of matrix-binding integrins αVß1/αVß3 and tissue display of the respective RGD-containing ligands. The specific ECM components that control T cell migration are unclear. Fibronectin (FN), a canonical RGD-containing matrix component, is heavily upregulated in inflamed tissues and in vitro can serve as a substrate for leukocyte migration. However, limited by lack of tools to intravitally visualize and manipulate FN, the specific role of FN in effector T cell migration in vivo is unknown. Here, we utilize fluorescently-tagged FN to probe for FN deposition, and intravital multiphoton microscopy to visualize T cell migration relative to FN in the inflamed ear dermis. Th1 cells were found to migrate along FN fibers, with T cells appearing to actively push or pull against flexible FN fibers. To determine the importance of T cell interactions with FN, we used a specific inhibitor of FN polymerization, pUR4. Intradermal delivery of pUR4 (but not the control peptide) to the inflamed skin resulted in a local reduction in FN deposition. We also saw a striking attenuation of Th1 effector T cell movement at the pUR4 injection site, suggesting FN plays a key role in T cell interstitial migration. In mechanistic studies, pUR4 incubation with FN in vitro resulted in enhanced tethering of T cells to FN matrix, limiting productive migration. In vivo, such tethering led to increased Th1 accumulation in the inflamed dermis. Enhanced Th1 accumulation exacerbated inflammation with increased Th1 activation and IFNγ cytokine production. Thus, our studies highlight the importance of ECM FN fibrils for T cell migration in inflamed tissues and suggest that manipulating local levels of ECM FN may prove beneficial in promoting T cell accumulation in tissues and enhancing local immunity to infection or cancer.

TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection.

Tissue-resident memory CD8 T (TRM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon reexposure to that pathogen. In the pulmonary system, TRM are identified through S1P antagonist CD69 and expression of integrins CD103/ß7 and CD49a/CD29(ß1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRM cell surface phenotype develops by 2 wk postinfection, with the majority of the population expressing CD49a and a subset that is also positive for CD103. Despite a previously established role in retaining TRM in peripheral tissues, CD49a facilitates locomotion of virus-specific CD8 T cells, both in vitro and in vivo. These results demonstrate that CD49a may contribute to local surveillance mechanisms of the TRM population.

Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis.

Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We find that two actin-dependent molecular motors, class 1 myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we find that without the actin-membrane linkage mediated by these myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a role for class 1 myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.