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Drawing from fieldwork I conducted in Brussels with a group of drag kings in which I experience myself to perform a male character, and from my practice of dance and performance, I will focus my analysis on what I call “losing the self”. By “losing the self”, I mean a moment in which social actors, in the framework of a gendered and embodied transformational activity, experience to come out from the self and to welcome into one’s own body a desired self, and to becoming something/someone new. The analysis of this moment I experienced in the field, in which the transition from observer to participant status took place, and in which I experienced the transition from an assigned at birth masculinity to a king masculinity, allows me to highlight some central points for gender studies and performance studies, in particular, and for the social sciences, in general: How to think of transformational processes through a multidimensional perspective (i.e. verbal, tactile, visual, material) taking into account its public, reflexive, multimodal and indexical dimensions? Finally, how can we rethink the boundaries between observation and participation, art and life, and to think of science through the lens of experience and becoming?

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease., Methods: We evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH., Results: Bivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice., Conclusion: By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells., Competing Interests: NV. TG and HV own LAVA Therapeutics NV shares. DH, PY, VI-G, PH and HV are/were employed by LAVA Therapeutics NV. TG is scientific advisor to LAVA Therapeutics NV. The authors declare that this study received funding from Lava Therapeutics NV. LK, MJ and MV were funded by LAVA Therapeutics NV., (Copyright © 2024 King, de Jong, Veth, Lutje Hulsik, Yousefi, Iglesias-Guimarais, van Helden, de Gruijl and van der Vliet.)

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model., Materials and Methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days., Results: Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP - counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential., Conclusions: This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy., (© 2024 The Author(s).)

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an enveloped DNA virus of the Baculoviridae family. This baculovirus is widely exploited for the biological control of insect pest species and as an expression platform to produce recombinant proteins in insect cells. Extracellular vesicles (EVs) are secreted by all cells and are involved in key roles in many biological processes through their cargo consisting of proteins, RNA or DNA. In viral infections, EVs have been found to transfer both viral and cellular cargo that can elicit either a pro- or antiviral response in recipient cells. Here, small EVs (sEVs) released by Spodoptera frugiperda (Sf) insect cells were characterised for the first time. Using S. frugiperda (SfC1B5) cells stably expressing the baculovirus gp64 , the viral envelope protein GP64 was shown to be incorporated into sEVs. Sf9 cells were also transfected with a bacmid AcMNPV genome lacking p6.9 (AcΔP6.9) to prevent budded virus production. The protein content of sEVs from both mock- and AcΔP6.9-transfected cells were analysed by mass spectrometry. In addition to GP64, viral proteins Ac-F, ME-53 and viral ubiquitin were identified, as well as many host proteins including TSG101-which may be useful as a protein marker for sEVs., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

The design and development of supported catalysts for the oxygen evolution reaction (OER) is a promising pathway to reducing iridium loading in proton exchange membrane water electrolysers. However, supported catalysts often suffer from poor activity and durability, particularly when deployed in membrane electrode assemblies. In this work, we deploy iridium coated hollow titanium dioxide particles as OER catalysts to achieve higher Ir mass activities than the leading commercial catalysts. Critically, we demonstrate state-of-the-art durabilities for supported iridium catalysts when compared against the previously reported values for analogous device architectures, operating conditions and accelerated stress test profiles. Through extensive materials characterisations alongside rotating disk electrode measurements, we investigate the role of conductivity, morphology, oxidation state and crystallinity on the OER electrochemical performance. Our work highlights a new supported catalyst design that unlocks high-performance OER activity and durability in commercially relevant testing configurations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Purpose: The Functional Gait Assessment (FGA) and High Level Mobility Assessment Tool (HiMAT) are clinical batteries used to assess people with mild traumatic brain injury (mTBI). However, neither assessment was specifically developed for people with mTBI; the FGA was developed to evaluate vestibular deficits, and the HiMAT was developed for individuals with more severe TBI. To maximize the sensitivity and reduce the time burden of these assessments, the purpose of this study was to determine the combination of FGA and HiMAT items that best discriminates persons with persistent symptoms from mTBI from healthy controls., Methods: Fifty-three symptomatic civilians with persistent symptoms from mTBI (21% male, aged 31 (9.5) years, 328 [267] days since concussion) and 57 healthy adults (28% male, aged 32 (9.6) years) participated across 3 sites. The FGA and HiMAT were evaluated sequentially as part of a larger study. To determine the best combination of items, a lasso-based generalized linear model (glm) was fit to all data., Results: The area under the curve (AUC) for FGA and HiMAT total scores was 0.68 and 0.66, respectively. Lasso regression selected 4 items, including FGA Gait with Horizontal Head Turns and with Pivot Turn, and HiMAT Fast Forward and Backward Walk, and yielded an AUC (95% confidence interval) of 0.71 (0.61-0.79) using standard scoring., Discussion and Conclusions: The results provide initial evidence supporting a reduced, 4-Item Hybrid Assessment of Mobility for mTBI (HAM-4-mTBI) for monitoring individuals with mTBI. Future work should validate the HAM-4-mTBI and investigate its utility for tracking progression throughout rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A409 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Although supervised and real-time telerehabilitation by videoconferencing is now becoming common for people with Parkinson's disease (PD), its efficacy for balance and gait is still unclear. This paper uses a scoping approach to review the current evidence on the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD. We also explored whether studies have used wearable technology during telerehabilitation to assess and treat balance and gait via videoconferencing. Literature searches were conducted using PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. The data were extracted for study design, treatment, and outcomes. Fourteen studies were included in this review. Of these, seven studies investigated the effects of telerehabilitation (e.g., tele-yoga and adapted physiotherapy exercises) on balance and gait measures (e.g., self-reported balance, balance scale, walking speed, mobility, and motor symptoms) using videoconferencing in both assessment and treatment. The telerehabilitation programs by videoconferencing were feasible and safe for people with PD; however, the efficacy still needs to be determined, as only four studies had a parallel group. In addition, no study used wearable technology. Robust evidence of the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD was not found, suggesting that future powered, prospective, and robust clinical trials are needed.

Background: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics., Methods: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO 2 ]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group., Results: Average NSI total score was 26.4 (13.2). HbO 2 was significantly higher ( P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO 2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion ( r = .79; P = .001), and stride time variability ( r = -.54; P = .046)., Conclusion: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study ( n  = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.

γδ T cells are important components of the immune system due to their ability to elicit a fast and strong response against infected and transformed cells. Because they can specifically and effectively kill target cells in an MHC independent fashion, there is great interest to utilize these cells in anti-tumor therapies where antigen presentation may be hampered. Since only a small fraction of T cells in the blood or tumor tissue are γδ T cells, they require extensive expansion to allow for fundamental, preclinical and ex vivo research. Although expansion protocols can be successful, most are based on depletion of other cell types rather than γδ T cell specific isolation, resulting in unpredictable purity of the isolated fraction. Moreover, the primary focus only lies with expansion of Vδ2 + T cells, while Vδ1 + T cells likewise have anti-tumor potential. Here, we investigated whether γδ T cells directly isolated from blood could be efficiently expanded while maintaining function. γδ T cell subsets were isolated using MACS separation, followed by FACS sorting, yielding >99% pure γδ T cells. Isolated Vδ1 + and Vδ2 + T cells could effectively expand immediately after isolation or upon freeze/thawing and reached expansion ratios between 200 to 2000-fold starting from varying numbers using cytokine supported feeder stimulations. MACS/FACS isolated and PHA stimulated γδ T cells expanded as good as immobilized antibody mediated stimulated cells in PBMCs, but delivered purer cells. After expansion, potential effector functions of γδ T cells were demonstrated by IFN-γ, TNF-α and granzyme B production upon PMA/ionomycin stimulation and effective killing capacity of multiple tumor cell lines was confirmed in killing assays. In conclusion, pure γδ T cells can productively be expanded while maintaining their anti-tumor effector functions against tumor cells. Moreover, γδ T cells could be expanded from low starting numbers suggesting that this protocol may even allow for expansion of cells extracted from tumor biopsies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Verkerk, Pappot, Jorritsma, King, Duurland, Spaapen and van Ham.)

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Background: Balance impairments, that lead to falls, are one of the main symptoms of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days., Methods: The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period., Conclusion: The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments., Trial Registration: This trial was prospectively registered on ClinicalTrials.gov (NCT05680597)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Imbalance is common following mild Traumatic Brain Injury (mTBI) and can persist months after the initial injury. To determine if mTBI subjects with chronic imbalance differed from healthy age- and sex-matched controls (HCs) we used both the Central SensoriMotor Integration (CSMI) test, which evaluates sensory integration, time delay, and motor activation properties and the standard Sensory Organization Test (SOT). Four CSMI conditions evoked center-of-mass sway in response to: surface tilts with eyes closed (SS/EC), surface tilts with eyes open viewing a fixed visual surround (SS/EO), visual surround tilts with eyes open standing on a fixed surface (VS/EO), and combined surface and visual tilts with eyes open (SS+VS/EO). The mTBI participants relied significantly more on visual cues during the VS/EO condition compared to HCs but had similar reliance on combinations of vestibular, visual, and proprioceptive cues for balance during SS/EC, SS/EO, and SS+VS/EO conditions. The mTBI participants had significantly longer time delays across all conditions and significantly decreased motor activation relative to HCs across conditions that included surface-tilt stimuli with a sizeable subgroup having a prominent increase in time delay coupled with reduced motor activation while demonstrating no vestibular sensory weighting deficits. Decreased motor activation compensates for increased time delay to maintain stability of the balance system but has the adverse consequence that sensitivity to both internal (e.g., sensory noise) and external disturbances is increased. Consistent with this increased sensitivity, SOT results for mTBI subjects showed increased sway across all SOT conditions relative to HCs with about 45% of mTBI subjects classified as having an "Aphysiologic" pattern based on published criteria. Thus, CSMI results provided a plausible physiological explanation for the aphysiologic SOT pattern. Overall results suggest that rehabilitation that focuses solely on sensory systems may be incomplete and may benefit from therapy aimed at enhancing rapid and vigorous responses to balance perturbations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campbell, King, Parrington, Fino, Antonellis and Peterka.)

Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants ( n = 31; females = 22; mean age = 40.9 ± 11 y) with chronic (>3 months) mTBI symptoms of self-reported imbalance were randomized into vestibular rehabilitation with ABF ( n = 16) or without ABF ( n = 15). The intervention was a standard vestibular rehabilitation, with or without ABF, for 45 min biweekly for 6 weeks. The ABF intervention involved a smartphone that provided auditory feedback when postural sway was outside of predetermined equilibrium parameters. Participant's completed the Post-Concussion Symptom Scale (PCSS). Balance was assessed with the sensory organization test (SOT) and the Central Sensorimotor Integration test which measured sensory weighting, motor activation, and time delay with sway evoked by surface and/or visual surround tilts. Effect sizes (Hedge's G) were calculated on the change between pre-and post-rehabilitation scores. Both groups demonstrated similar medium effect-sized decreases in PCSS and large increases in SOT composite scores after rehabilitation. Effect sizes were minimal for increasing sensory weighting for both groups. The with ABF group showed a trend of larger effect sizes in increasing motor activation (with ABF = 0.75, without ABF = 0.22) and in decreasing time delay (with ABF = -0.77, without ABF = -0.52) relative to the without ABF group. Current clinical practice focuses primarily on sensory weighting. However, the evaluation and utilization of motor activation factors in vestibular rehabilitation, potentially with ABF, may provide a more complete assessment of recovery and improve outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campbell, Peterka, Fino, Parrington, Wilhelm, Pettigrew and King.)

Background and Purpose: Multimodal physical therapy for mild traumatic brain injury (mTBI) has been shown to improve recovery. Due to the coronavirus disease-2019 (COVID-19) pandemic, a clinical trial assessing the timing of multimodal intervention was adapted for telerehabilitation. This pilot study explored feasibility and adoption of an in-person rehabilitation program for subacute mTBI delivered through telerehabilitation., Methods: Fifty-six in-person participants-9 males; mean (SD) age 34.3 (12.2); 67 (31) days post-injury-and 17 telerehabilitation participants-8 males; age 38.3 (12.7); 61 (37) days post-injury-with subacute mTBI (between 2 and 12 weeks from injury) were enrolled. Intervention included 8, 60-minute visits over 6 weeks and included subcategories that targeted cervical spine, cardiovascular, static balance, and dynamic balance impairments. Telerehabilitation was modified to be safely performed at home with minimal equipment. Outcome measures included feasibility (the number that withdrew from the study, session attendance, home exercise program adherence, adverse events, telerehabilitation satisfaction, and progression of exercises performed), and changes in mTBI symptoms pre- and post-rehabilitation were estimated with Hedges' g effect sizes., Results: In-person and telerehabilitation had a similar study withdrawal rate (13% vs 12%), high session attendance (92% vs 97%), and no adverse events. The telerehabilitation group found the program easy to use (4.2/5), were satisfied with care (4.7/5), and thought it helped recovery (4.7/5). The telerehabilitation intervention was adapted by removing manual therapy and cardiovascular portions and decreasing dynamic balance exercises compared with the in-person group. The in-person group had a large effect size (-0.94) in decreases in symptoms following rehabilitation, while the telerehabilitation group had a moderate effect size (-0.73)., Discussion and Conclusions: Telerehabilitation may be feasible for subacute mTBI. Limited ability to address cervical spine, cardiovascular, and dynamic balance domains along with underdosage of exercise progression may explain group differences in symptom resolution.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A392 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Background and Aim: Individuals with Parkinson's disease (PD) with and without freezing of Gait (FoG) may respond differently to exercise interventions for several reasons, including disease duration. This study aimed to determine whether both people with and without FoG benefit from the Agility Boot Camp with Cognitive Challenges (ABC-C) program., Methods: This secondary analysis of our ABC-C trial included 86 PD subjects: 44 without FoG (PD-FoG) and 42 with FoG (PD + FoG). We collected measures of standing sway balance, anticipatory postural adjustments, postural responses, and a 2-minute walk with and without a cognitive task. Two-way repeated analysis of variance, with disease duration as covariate, was used to investigate the effects of ABC-C program. Effect sizes were calculated using standardized response mean (SRM) for PD-FoG and PD + FoG, separately., Results: The ABC-C program was effective in improving gait performance in both PD-FoG and PD + FoG, even after controlling for disease duration. Specifically, dual-task gait speed ( P  < .0001), dual-cost stride length ( P  = .012), and these single-task measures: arm range of motion ( P  < .0001), toe-off angle ( P  = .005), gait cycle duration variability ( P  = .019), trunk coronal range of motion ( P  = .042), and stance time ( P  = .046) improved in both PD-FoG and PD + FoG. There was no interaction effect between time (before and after exercise) and group (PD-FoG/PD + FoG) in all 24 objective measures of balance and gait. Dual-task gait speed improved the most in PD + FoG (SRM = 1.01), whereas single-task arm range of motion improved the most in PD-FoG (SRM = 1.01)., Conclusion: The ABC-C program was similarly effective in improving gait (and not balance) performance in both PD-FoG and PD + FoG.

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors ( i.e. Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential. Vδ2 T-cells, in contrast, are enriched in circulation and consist of a large, relatively homogeneous, pro-inflammatory effector T-cell subset. Healthy individuals typically harbor in the order of 50-500 million Vγ9Vδ2 T-cells in the peripheral blood alone (1-10% of the total CD3 + T-cell population), which can rapidly expand upon stimulation. The Vγ9Vδ2 T-cell receptor senses intracellular phosphorylated metabolites, which accumulate in cancer cells as a result of mevalonate pathway dysregulation or upon pharmaceutical intervention. Early clinical studies investigating the therapeutic potential of Vγ9Vδ2 T-cells were based on either ex vivo expansion and adoptive transfer or their systemic activation with aminobisphosphonates or synthetic phosphoantigens, either alone or combined with low dose IL-2. Immune-related adverse events (irAE) were generally \mild, but the clinical efficacy of these approaches provided overall limited benefit. In recent years, critical advances have renewed the excitement for the potential of Vγ9Vδ2 T-cells in cancer immunotherapy. Here, we review γδ T-cell-based therapeutic strategies and discuss the prospects of those currently evaluated in clinical studies in cancer patients as well as future therapies that might arise from current promising pre-clinical results., Competing Interests: JS-E, MJ and LK are funded by Lava therapeutics. HV, PP, EE, BW are employed by and hold stock of LAVA Therapeutics. TG holds stock of LAVA Therapeutics., (Copyright © 2022 Saura-Esteller, de Jong, King, Ensing, Winograd, de Gruijl, Parren and van der Vliet.)

Background: Physical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to detect subtle deficits post-injury, which can impact a patient's quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an opportunity for objective assessment of physical function and can be used in any environment. A single waist worn IMU has the potential to provide broad/macro quantity characteristics to estimate gait mobility, as well as more high-resolution micro spatial or temporal gait characteristics (herein, we refer to these as measures of quality). Our recent work showed that quantity measures of mobility were less sensitive than measures of turning quality when comparing the free-living physical function of chronic mTBI patients and healthy controls. However, no studies have examined whether measures of gait quality in free-living conditions can differentiate chronic mTBI patients and healthy controls. This study aimed to determine whether measures of free-living gait quality can differentiate chronic mTBI patients from controls., Methods: Thirty-two patients with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post-injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~ 7 days using a single IMU at the waist on a belt. Free-living gait quality metrics were evaluated for chronic mTBI patients and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI., Results: Free-living gait quality metrics were not different between chronic mTBI patients and controls (all p > 0.05) whilst controlling for age and sex. ROC and AUC analysis showed stride length (0.63) was the most sensitive measure for differentiating chronic mTBI patients from controls., Conclusions: Our results show that gait quality metrics determined through a free-living assessment were not significantly different between chronic mTBI patients and controls. These results suggest that measures of free-living gait quality were not impaired in our chronic mTBI patients, and/or, that the metrics chosen were not sensitive enough to detect subtle impairments in our sample., (© 2022. The Author(s).)

Objective: To explore patterns of postconcussion care at a level 1 trauma center., Design: Retrospective cohort study., Setting: U.S. level 1 trauma center and local satellite units., Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417)., Intervention: Not applicable., Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis., Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR] unadjusted =75.05, P <.001), primary care providers (OR unadjusted =7.98, P <.001), and specialty care departments (OR unadjusted =7.62, P <.001) than from the emergency department. Women were more likely to receive a referral (OR unadjusted =1.92, P <.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (OR adjusted =2.12, P <.001) to get a rehabilitation referral than patients without a comorbidity., Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion., (© 2022 The Authors.)

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.

Five studies tested the effect of exposure to authoritarian values on positive affect (PA), negative affect (NA), and meaning in life (MIL). Study 1 (N = 1,053) showed that simply completing a measure of right-wing authoritarianism (vs. not) prior to rating MIL led to higher MIL. Preregistered Study 2 (N = 1,904) showed that reading speeches by real-world authoritarians (e.g., Adolf Hitler) led to lower PA, higher NA, and higher MIL than a control passage. In preregistered Studies 3 (N = 1,573) and 4 (N = 1,512), Americans read authoritarian, egalitarian, or control messages and rated mood, MIL, and evaluated the passages. Both studies showed that egalitarian messages led to better mood and authoritarian messages led to higher MIL. Study 5 (N = 148) directly replicated these results with Canadians. Aggregating across studies (N = 3,401), moderational analyses showed that meaning in life, post manipulation, was associated with more favorable evaluations of the authoritarian passage. In addition, PA was a stronger predictor of MIL in the egalitarian and control conditions than in the authoritarian condition. Further results showed no evidence that negative mood (or disagreement) spurred the boost in MIL. Implications and future directions are discussed., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Although considerable progress has been made with autologous T cell-based therapy in B-cell malignancies, application in chronic lymphocytic leukemia (CLL) lags behind due to disappointing response rates as well as substantial toxicity that is of particular concern in the elderly CLL population. Vγ9Vδ2-T cells form a conserved T-cell subset with strong intrinsic immunotherapeutic potential, largely because of their capacity to be triggered by phosphoantigens that can be overproduced by CLL and other malignant cells. Specific activation of Vγ9Vδ2-T cells by a bispecific antibody may improve the efficacy and toxicity of autologous T-cell-based therapy in CLL., Experimental Design: We evaluated CD1d expression in a cohort of 78 untreated patients with CLL and generated and functionally characterized a CD1d-specific Vγ9Vδ2-T cell engager based on single-domain antibodies (VHH)., Results: CD1d was expressed by CLL in the majority of patients, particularly in patients with advanced disease. The CD1d-specific Vγ9Vδ2-T cell engager induced robust activation and degranulation of Vγ9Vδ2-T cells, enabling Vγ9Vδ2-T cells from patients with CLL to lyse autologous leukemic cells at low effector-to-target ratios. Expression of CD1d on CLL cells is upregulated by all-trans retinoic acid, and sensitizes the malignant cells to bispecific VHH-induced lysis. Furthermore, we provide evidence that the Vγ9Vδ2-T cell receptor retains responsiveness to phosphoantigens when the bispecific VHH is bound, and aminobisphosphonates can therefore enhance bispecific Vγ9Vδ2-T cell engager-mediated tumor-specific killing., Conclusions: Collectively, our data demonstrate the immunotherapeutic potential of this novel CD1d-specific Vγ9Vδ2-T cell engager in CLL., (©2021 American Association for Cancer Research.)

There is a dearth of knowledge about how symptom severity affects gait in the chronic (>3 months) mild traumatic brain injury (mTBI) population despite up to 53% of people reporting persisting symptoms after mTBI. The aim of this investigation was to determine whether gait is affected in a symptomatic, chronic mTBI group and to assess the relationship between gait performance and symptom severity on the Neurobehavioral Symptom Inventory (NSI). Gait was assessed under single- and dual-task conditions using five inertial sensors in 57 control subjects and 65 persons with chronic mTBI (1.0 year from mTBI). The single- and dual-task gait domains of Pace, Rhythm, Variability, and Turning were calculated from individual gait characteristics. Dual-task cost (DTC) was calculated for each domain. The mTBI group walked (domain z-score mean difference, single-task = 0.70; dual-task = 0.71) and turned (z-score mean difference, single-task = 0.69; dual-task = 0.70) slower ( p  < 0.001) under both gait conditions, with less rhythm under dual-task gait (z-score difference = 0.21; p  = 0.001). DTC was not different between groups. Higher NSI somatic subscore was related to higher single- and dual-task gait variability as well as slower dual-task pace and turning ( p  < 0.01). Persons with chronic mTBI and persistent symptoms exhibited altered gait, particularly under dual-task, and worse gait performance related to greater symptom severity. Future gait research in chronic mTBI should assess the possible underlying physiological mechanisms for persistent symptoms and gait deficits.

Determining readiness for duty after mild traumatic brain injury (mTBI) is essential for the safety of service members and their unit. Currently, these decisions are primarily based on self-reported symptoms, objective measures that assess a single system, or standardized physical or cognitive tests that may be insensitive or lack ecological validity for warrior tasks. While significant technological advancements have been made in a variety of assessments of these individual systems, assessments of isolated tasks are neither diagnostically accurate nor representative of the demands imposed by daily life and military activities. Emerging evidence suggests that complex tasks, such as dual-task paradigms or turning, have utility in probing functional deficits after mTBI. Objective measures from turning tasks in single- or dual-task conditions, therefore, may be highly valuable for clinical assessments and return-to-duty decisions after mTBI. The goals of this study are to assess the diagnostic accuracy, predictive capacity, and responsiveness to rehabilitation of objective, dual-task turning measures within an mTBI population. These goals will be accomplished over two phases. Phase 1 will enroll civilians at three sites and active-duty service members at one site to examine the diagnostic accuracy and predictive capacity of dual-task turning outcomes. Phase 1 participants will complete a series of turning tasks while wearing inertial sensors and a battery of clinical questionnaires, neurocognitive testing, and standard clinical assessments of function. Phase 2 will enroll active-duty service members referred for rehabilitation from two military medical treatment facilities to investigate the responsiveness to rehabilitation of objective dual-task turning measures. Phase 2 participants will complete two assessments of turning while wearing inertial sensors: a baseline assessment prior to the first rehabilitation session and a post-rehabilitation assessment after the physical therapist determines the participant has completed his/her rehabilitation course. A variable selection procedure will then be implemented to determine the best task and outcome measure for return-to-duty decisions based on diagnostic accuracy, predictive capacity, and responsiveness to rehabilitation. Overall, the results of this study will provide guidance and potential new tools for clinical decisions in individuals with mTBI. Clinical Trial Registration : clinicaltrials.gov, Identifier NCT03892291., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fino, Weightman, Dibble, Lester, Hoppes, Parrington, Arango, Souvignier, Roberts and King.)

Augmented sensory biofeedback training is often used to improve postural control. Our previous study showed that continuous auditory biofeedback was more effective than continuous visual biofeedback to improve postural sway while standing. However, it has also been reported that both discrete visual and auditory biofeedback training, presented intermittently, improves bimanual task performance more than continuous visual biofeedback training. Therefore, this study aimed to investigate the relative effectiveness of discrete visual biofeedback versus discrete auditory biofeedback to improve postural control. Twenty-two healthy young adults were randomly assigned to either a visual or auditory biofeedback group. Participants were asked to shift their center of pressure (COP) by voluntary postural sway forward and backward in line with a hidden target, which moved in a sinusoidal manner and was displayed intermittently. Participants were asked to decrease the diameter of a visual circle (visual biofeedback) or the volume of a sound (auditory biofeedback) based on the distance between the COP and the target in the training session. The feedback and the target were given only when the target reached the inflection points of the sine curves. In addition, the perceptual magnitudes of visual and auditory biofeedback were equalized using Stevens' power law. Results showed that the mean and standard deviation of the distance between COP and the target were reduced int the test session, removing the augmented sensory biofeedback, in both biofeedback training groups. However, the temporal domain of the performance improved in the test session in the auditory biofeedback training group, but not in the visual biofeedback training group. In conclusion, discrete auditory biofeedback training was more effective for the motor learning of voluntarily postural swaying compared to discrete visual biofeedback training, especially in the temporal domain., Competing Interests: The authors have declared that no competing interests exist.

Few exercise interventions practice both gait and balance tasks with cognitive tasks to improve functional mobility in people with PD. We aimed to investigate whether the Agility Boot Camp with Cognitive Challenge (ABC-C), that simultaneously targets both mobility and cognitive function, improves dynamic balance and dual-task gait in individuals with Parkinson's disease (PD). We used a cross-over, single-blind, randomized controlled trial to determine efficacy of the exercise intervention. Eighty-six people with idiopathic PD were randomized into either an exercise (ABC-C)-first or an active, placebo, education-first intervention and then crossed over to the other intervention. Both interventions were carried out in small groups led by a certified exercise trainer (90-min sessions, 3 times a week, for 6 weeks). Outcome measures were assessed Off levodopa at baseline and after the first and second interventions. A linear mixed-effects model tested the treatment effects on the Mini-BESTest for balance, dual-task cost on gait speed, SCOPA-COG, the UPDRS Parts II and III and the PDQ-39. Although no significant treatment effects were observed for the Mini-BESTest, SCOPA-COG or MDS-UPDRS Part III, the ABC-C intervention significantly improved the following outcomes: anticipatory postural adjustment sub-score of the Mini-BESTest (p = 0.004), dual-task cost on gait speed (p = 0.001), MDS-UPDRS Part II score (p = 0.01), PIGD sub-score of MDS-UPDRS Part III (p = 0.02), and the activities of daily living domain of the PDQ-39 (p = 0.003). Participants with more severe motor impairment or more severe cognitive dysfunction improved their total Mini-BESTest scores after exercise. The ABC-C exercise intervention can improve specific balance deficits, cognitive-gait interference, and perceived functional independence and quality of life, especially in participants with more severe PD, but a longer period of intervention may be required to improve global cognitive and motor function.

The provision of elective clinical services has decreased during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic to enable hospitals to focus on acute illness. Any end to the pandemic through widespread vaccination, effective treatment or development of herd immunity may be years away. Until then, hospitals will need to resume treating other diseases while also attempting to eradicate transmission of COVID-19 within the healthcare setting. In this article we suggest six major themes which could affect the design and delivery of elective clinical services: hospital avoidance, separation of high- and low-risk groups, screening, maintenance of adequate infection control, and new ways of working., (© Royal College of Physicians 2020. All rights reserved.)

Background: Balance deficits in people with Parkinson's disease (PD) are often not helped by pharmacological or surgical treatment. Although balance exercise intervention has been shown to improve clinical measures of balance, the efficacy of exercise on different, objective balance domains is still unknown. Objective: To compare the sensitivity to change in objective and clinical measures of several different domains of balance and gait following an Agility Boot Camp with Cognitive Challenges (ABC-C) intervention. Methods: In this cross-over, randomized design, 86 individuals with PD participated in 6-week (3×/week) ABC-C exercise classes and 6-week education classes, consisting of 3-6 individuals. Blinded examiners tested people in their practical off state. Objective outcome measures from wearable sensors quantified four domains of balance: sway in standing balance, anticipatory postural adjustments (APAs) during step initiation, postural responses to the push-and-release test, and a 2-min natural speed walk with and without a cognitive task. Clinical outcome measures included the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, the Mini Balance Evaluation Systems Test (Mini-BESTest), the Activities of Balance Confidence (ABC), and the Parkinson's Disease Questionnaire (PDQ-39). The standardized response means (SRM) of the differences between before and after each intervention compared responsiveness of outcomes to intervention. A linear mixed model compared effects of exercise with the active control-education intervention. Results: The most responsive outcome measures to exercise intervention with an SRM > 0.5 were objective measures of gait and APAs, specifically arm range of motion, gait speed during a dual-task walk, trunk coronal range of motion, foot strike angle, and first-step length at step initiation. The most responsive clinical outcome measure was the patient-reported PDQ-39 activities daily living subscore, but all clinical measures had SRMs <0.5. Conclusions: The objective measures were more sensitive to change after exercise intervention compared to the clinical measures. Spatiotemporal parameters of gait, including gait speed with a dual task, and APAs were the most sensitive objective measures, and perceived functional independence was the most sensitive clinical measure to change after the ABC-C exercise intervention. Future exercise intervention to improve gait and balance in PD should include objective outcome measures., (Copyright © 2020 Hasegawa, Shah, Harker, Carlson-Kuhta, Nutt, Lapidus, Jung, Barlow, King, Horak and Mancini.)

Background: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation., Methods: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine., Results: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported., Conclusions: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

Three studies addressed two research questions. First, does accounting for meaning in life (MIL) wipe out the association between narcissism and other aspects of well-being? Second, among the three facets of MIL (significance, purpose, and coherence), does significance explain the association between narcissism and MIL? All studies measured narcissism and MIL. Study 1 was a re-analysis of cross-sectional data, including measures of subjective well-being (SWB) and self-deceptive enhancement ( N = 415; Womick et al., 2019). Study 2, N = 300, measured the facets of MIL in a sample of adults. Study 3, N = 295, included MIL facets and self-esteem in a sample of students. In Studies 1 and 3, MIL fully mediated the relationship between narcissism and SWB. SWB did not fully mediate the association between narcissism and MIL. Studies 2 and 3 showed that all MIL facets accounted for the association between narcissism and MIL. Self-esteem partially mediated the association between narcissism and MIL, but self-esteem and MIL, both, independently wiped out the link between narcissism and SWB. Narcissism contributes to SWB through MIL, and the paths from narcissism to SWB through MIL and self-esteem are independent. Implications are discussed., (© 2020 The Author(s).)

Introduction . It is well documented that freezing of gait (FoG) episodes occur in situations that are mentally challenging, such as dual tasks, consistent with less automatic control of gait in people with Parkinson disease (PD) and FoG. However, most physical rehabilitation does not include such challenges. The purpose was to determine (1) feasibility of a cognitively challenging Agility Boot Camp-Cognitive (ABC-C) program and (2) effects of this intervention on FoG, dual-task cost, balance, executive function, and functional connectivity. Methods . A total of 46 people with PD and FoG enrolled in this randomized crossover trial. Each participant had 6 weeks of ABC-C and Education interventions. Outcome measures were the following: FoG, perceived and objective measures; dual-task cost on gait; balance; executive function; and right supplementary motor area (SMA)-pedunculopontine nucleus (PPN) functional connectivity. Effect sizes were calculated. Results . ABC-C had high compliance (90%), with a 24% dropout rate. Improvements after exercise, revealed by moderate and large effect sizes, were observed for subject perception of FoG after exercise, dual-task cost on gait speed, balance, cognition (Scales for Outcomes in Parkinson's disease-Cognition), and SMA-PPN connectivity. Conclusions . The ABC-C for people with PD and FoG is a feasible exercise program that has potential to improve FoG, balance, dual-task cost, executive function, and brain connectivity. The study provided effect sizes to help design future studies with more participants and longer duration to fully determine the potential to improve FoG.

Background: Clinical practice for rehabilitation after mild traumatic brain injury (mTBI) is variable, and guidance on when to initiate physical therapy is lacking. Wearable sensor technology may aid clinical assessment, performance monitoring, and exercise adherence, potentially improving rehabilitation outcomes during unsupervised home exercise programs., Objective: The objectives of this study were to: (1) determine whether initiating rehabilitation earlier than typical will improve outcomes after mTBI, and (2) examine whether using wearable sensors during a home-exercise program will improve outcomes in participants with mTBI., Design: This was a randomized controlled trial., Setting: This study will take place within an academic hospital setting at Oregon Health & Science University and Veterans Affairs Portland Health Care System, and in the home environment., Participants: This study will include 160 individuals with mTBI., Intervention: The early intervention group (n = 80) will receive one-on-one physical therapy 8 times over 6 weeks and complete daily home exercises. The standard care group (n = 80) will complete the same intervention after a 6- to 8-week wait period. One-half of each group will receive wearable sensors for therapist monitoring of patient adherence and quality of movements during their home exercise program., Measurements: The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will include symptomatology, static and dynamic postural control, central sensorimotor integration posturography, and vestibular-ocular-motor function., Limitations: Potential limitations include variable onset of care, a wide range of ages, possible low adherence and/or withdrawal from the study in the standard of care group, and low Dizziness Handicap Inventory scores effecting ceiling for change after rehabilitation., Conclusions: If initiating rehabilitation earlier improves primary and secondary outcomes post-mTBI, this could help shape current clinical care guidelines for rehabilitation. Additionally, using wearable sensors to monitor performance and adherence may improve home exercise outcomes., (© 2020 American Physical Therapy Association.)

Many steps in the baculovirus life cycle, from initial ingestion to the subsequent infection of all larval cells, remain largely unknown; primarily because it has hitherto not been possible to follow individual genomes and their lineages. Use of ANCHOR TM technology allows a high intensity fluorescent labelling of DNA. When applied to a virus genome, it is possible to follow individual particles, and the overall course of infection. This technology has been adapted to enable labelling of the baculovirus Autographa californica Multiple NucleoPolyhedroVirus genome, as a first step to its application to other baculoviruses. AcMNPV was modified by inserting the two components of ANCHOR TM : a specific DNA-binding protein fused to a fluorescent reporter, and the corresponding DNA recognition sequence. The resulting modified virus was stable, infectious, and replicated correctly in Spodoptera frugiperda 9 (Sf9) cells and in vivo. Both budded viruses and occlusion bodies were clearly distinguishable, and infecting cells or larvae allowed the infection process to be monitored in living cells or tissues. The level of fluorescence in the culture medium of infected cells in vitro showed a good correlation with the number of infectious budded viruses. A cassette that can be used in other baculoviruses has been designed. Altogether our results introduce for the first time the generation of autofluorescent baculovirus and their application to follow infection dynamics directly in living cells or tissues.

Over 35 years since it was established to make recombinant proteins, the baculovirus expression vector system continues to develop and improve. Early systems for recombinant virus selection were laborious, but better methods were rapidly devised that enabled non-virologists to use baculovirus vectors successfully in a wide range of applications. These applications include multiple gene expression for complex molecules, production of adeno-associated virus-like particles for gene therapy, the use of baculovirus budded virus for the same purpose, numerous potential human and animal vaccines, and for other therapeutic proteins. A number of products for human and veterinary use are now on the market, which attests to the utility of the systems. Despite these successes, baculovirus vectors essentially remain in a relatively primitive state of development. Many proteins, particularly membrane-bound or secreted products, continue to be difficult to produce. Various research groups are working to identify potential areas of improvement, which if combined into an ideal vector might offer considerable advances to the system. This chapter will review some of the most recent reports and highlight those that might have generic application for recombinant protein synthesis in insect cells. We also summarize parallel developments in host cells used for baculovirus expression and how culture conditions can influence protein production.

Balance and mobility issues are common non-resolving symptoms following mild traumatic brain injury (mTBI). Current approaches for evaluating balance and mobility following an mTBI can be subjective and suboptimal as they may not be sensitive to subtle deficits, particularly in those with chronic mTBI. Wearable inertial measurement units (IMU) allow objective quantification of continuous mobility outcomes in natural free-living environments. This study aimed to explore free-living mobility (physical activity and turning) of healthy and chronic mild traumatic brain injury (mTBI) participants using a single IMU. Free-living mobility was examined in 23 healthy control (48.56 ± 23.07 years) and 29 symptomatic mTBI (40.2 ± 12.1 years) participants (average 419 days post-injury, persistent balance complaints) over 1 week, using a single IMU placed at the waist. Free-living mobility was characterized in terms of macro (physical activity volume, pattern and variability) and micro-level (discrete measures of turning) features. Macro-level outcomes showed those with chronic mTBI had similar quantities of mobility compared with controls. Micro-level outcomes within walking bouts showed that chronic mTBI participants had impaired quality of mobility. Specifically, people with chronic mTBI made larger turns, had longer turning durations, slower average and peak velocities (all p  < 0.001), and greater turn variability compared with controls. Results highlighted that the quality rather than quantity of mobility differentiated chronic mTBI from controls. Our findings support the use of free-living IMU continuous monitoring to enhance understanding of specific chronic mTBI-related mobility deficits. Future work is required to develop an optimal battery of free-living measures across the mTBI spectrum to aid application within clinical practice.

P10 is a small, abundant baculovirus protein that accumulates to high levels in the very late stages of the infection cycle. It is associated with a number of intracellular structures and implicated in diverse processes from occlusion body maturation to nuclear stability and lysis. However, studies have also shown that it is non-essential for virus replication, at least in cell culture. Here, we describe the use of serial block-face scanning electron microscopy to achieve high-resolution 3D characterisation of P10 structures within Trichoplusia ni TN-368 cells infected with Autographa californica multiple nucleopolyhedrovirus. This has enabled unparalleled visualisation of P10 and determined the independent formation of dynamic perinuclear and nuclear vermiform fibrous structures. Our 3D data confirm the sequence of ultrastructural changes that create a perinuclear cage from thin angular fibrils within the cytoplasm. Over the course of infection in cultured cells, the cage remodels to form a large polarised P10 mass and we suggest that these changes are critical for nuclear lysis to release occlusion bodies. In contrast, nuclear P10 forms a discrete vermiform structure that was observed in close spatial association with both electron dense spacers and occlusion bodies; supporting a previously suggested role for P10 and electron dense spacers in the maturation of occlusion bodies. We also demonstrate that P10 hyper-expression is critical for function. Decreasing levels of p10 expression, achieved by manipulation of promoter length, correlated with reduced P10 production, a lack of formation of P10 structures and a concomitant decrease in nuclear lysis., Competing Interests: The authors have declared that no competing interests exist.

Context: In longitudinal studies tracking recovery after concussion, researchers often have not considered the timing of return to play (RTP) as a factor in their designs, which can limit the understanding of how RTP may affect the analysis and resulting conclusions., Objective: To evaluate the recovery of balance and gait in concussed athletes using a novel linear mixed-model design that allows an inflection point to account for changes in trend that may occur after RTP., Design: Cohort study., Setting: University athletics departments, applied field setting., Patients or Other Participants: Twenty-three concussed (5 women, 18 men; age = 20.1 ± 1.3 years) and 25 healthy control (6 women, 19 men; age = 20.9 ± 1.4 years) participants were studied. Participants were referred by their team athletic trainers., Main Outcome Measure(s): Measures consisted of the Balance Error Scoring System (BESS) total score, sway (instrumented root mean square of mediolateral sway), single-task gait speed, gait speed while simultaneously reading a handheld article (dual-task gait speed), dual-task cost of reading on gait speed, and dual-task cost of walking on reading., Results: We observed no significant effects or interactions for the BESS. Instrumented sway was worse in concussed participants, and a change in the recovery trend occurred after RTP. We observed group and time effects and group × time and group × RTP change interactions ( P ≤ .046). No initial between-groups differences were found for single-task or dual-task gait. Both groups increased gait speed initially and then leveled off after the average RTP date. We noted time and RTP change effects and positive group × time interactions for both conditions ( P ≤ .042) and a group × RTP change interaction for single-task gait speed ( P = .005). No significant effects or interactions were present for the dual-task cost of reading on gait speed or the dual-task cost of walking on reading., Conclusions: Changes in the rate of recovery were coincident with the timing of RTP. Although we cannot suggest these changes were a result of the athletes returning to play, these findings demonstrate the need for further research to evaluate the effects of RTP on concussion recovery.

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing Escherichia coli (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016.MethodsA voluntary nationwide network of 32 paediatric departments notifies cases. Two national reference centres perform microbiological STEC confirmation.ResultsOver the study period, the paediatric HUS incidence rate (IR) was 1.0 per 100,000 children-years, with a median of 116 cases/year. In 2011, IR peaked at 1.3 per 100,000 children-years, and decreased to 1.0 per 100,000 children-years in 2016. STEC O157 associated HUS peaked at 37 cases in 2011 and decreased to seven cases in 2016. Cases of STEC O26-associated HUS have increased since 2010 and STEC O80 associated HUS has emerged since 2012, with 28 and 18 cases respectively reported in 2016. Four STEC-HUS food-borne outbreaks were detected (three STEC O157 linked to ground beef and raw-milk cheese and one STEC O104 linked to fenugreek sprouts). In addition, two outbreaks related to person-to-person transmission occurred in distinct kindergartens (STEC O111 and O26).ConclusionsNo major changes in HUS IRs were observed over the study period of 10 years. However, changes in the STEC serogroups over time and the outbreaks detected argue for continuing epidemiological and microbiological surveillance.

Wearable inertial measurement units (IMUs) may provide useful, objective information to clinicians interested in quantifying head movements as patients' progress through vestibular rehabilitation. The purpose of this study was to validate an IMU-based algorithm against criterion data (motion capture) to estimate average head and trunk range of motion (ROM) and average peak velocity. Ten participants completed two trials of standing and walking tasks while moving the head with and without moving the trunk. Validity was assessed using a combination of Intra-class Correlation Coefficients (ICC), root mean square error (RMSE), and percent error. Bland-Altman plots were used to assess bias. Excellent agreement was found between the IMU and criterion data for head ROM and peak rotational velocity (average ICC > 0.9). The trunk showed good agreement for most conditions (average ICC > 0.8). Average RMSE for both ROM (head = 2.64°; trunk = 2.48°) and peak rotational velocity (head = 11.76 °/s; trunk = 7.37 °/s) was low. The average percent error was below 5% for head and trunk ROM and peak rotational velocity. No clear pattern of bias was found for any measure across conditions. Findings suggest IMUs may provide a promising solution for estimating head and trunk movement, and a practical solution for tracking progression throughout rehabilitation or home exercise monitoring.