BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance.

Bacille Calmette-Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted ∼3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (TH1 cell) responses in the lungs. MyD88 signaling was essential for innate and TH1 cell responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or interferon (IFN)-γ activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4+ T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance.

Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses.

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.

Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.

Circular RNA vaccine induces potent T cell responses.

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.

A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes.

Aberrant activity of cyclin-dependent kinase (Cdk5) has been implicated in various neurodegenerative diseases. This deleterious effect is mediated by pathological cleavage of the Cdk5 activator p35 into the truncated product p25, leading to prolonged Cdk5 activation and altered substrate specificity. Elevated p25 levels have been reported in humans and rodents with neurodegeneration, and the benefit of genetically blocking p25 production has been demonstrated previously in rodent and human neurodegenerative models. Here, we report a 12-amino-acid-long peptide fragment derived from Cdk5 (Cdk5i) that is considerably smaller than existing peptide inhibitors of Cdk5 (P5 and CIP) but shows high binding affinity toward the Cdk5/p25 complex, disrupts the interaction of Cdk5 with p25, and lowers Cdk5/p25 kinase activity. When tagged with a fluorophore (FITC) and the cell-penetrating transactivator of transcription (TAT) sequence, the Cdk5i-FT peptide exhibits cell- and brain-penetrant properties and confers protection against neurodegenerative phenotypes associated with Cdk5 hyperactivity in cell and mouse models of neurodegeneration, highlighting Cdk5i's therapeutic potential.

HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia.

Immune aplastic anemia (AA) features somatic loss of HLA class I allele expression on bone marrow cells, consistent with a mechanism of escape from T-cell-mediated destruction of hematopoietic stem and progenitor cells. The clinical significance of HLA abnormalities has not been well characterized. We examined the somatic loss of HLA class I alleles and correlated HLA loss and mutation-associated HLA genotypes with clinical presentation and outcomes after immunosuppressive therapy in 544 AA patients. HLA class I allele loss was detected in 92 (22%) of the 412 patients tested, in whom there were 393 somatic HLA gene mutations and 40 instances of loss of heterozygosity. Most frequently affected was HLA-B*14:02, followed by HLA-A*02:01, HLA-B*40:02, HLA-B*08:01, and HLA-B*07:02. HLA-B*14:02, HLA-B*40:02, and HLA-B*07:02 were also overrepresented in AA. High-risk clonal evolution was correlated with HLA loss, HLA-B*14:02 genotype, and older age, which yielded a valid prediction model. In 2 patients, we traced monosomy 7 clonal evolution from preexisting clones harboring somatic mutations in HLA-A*02:01 and HLA-B*40:02. Loss of HLA-B*40:02 correlated with higher blood counts. HLA-B*07:02 and HLA-B*40:01 genotypes and their loss correlated with late-onset of AA. Our results suggest the presence of specific immune mechanisms of molecular pathogenesis with clinical implications. HLA genotyping and screening for HLA loss may be of value in the management of immune AA. This study was registered at clinicaltrials.gov as NCT00001964, NCT00061360, NCT00195624, NCT00260689, NCT00944749, NCT01193283, and NCT01623167.

Retrograde Transvenous Obliteration (RTO): A New Treatment Option for Hepatic Encephalopathy.

Hepatic Encephalopathy (HE) is a complication of liver disease, consisting of brain dysfunction often due to portosystemic shunting of blood flow in the liver. HE can range from minimal HE, presenting with normal neurological function, to overt HE, with neurological and neuropsychiatric abnormalities. Various clinical grading systems are used to differentiate HE to provide the appropriate treatments. Traditional treatment of HE aims to identify and resolve precipitating factors through targeting hyperammonemia and administering antibiotics or probiotics. While retrograde transvenous obliteration (RTO), including balloon-occluded retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration or plug-assisted retrograde tranvenous obliteration, is an established procedure to manage gastric varices, little is known about its potential to treat HE. RTO is a procedure to occlude a spontaneous portosystemic shunt, minimizing shunting of portal blood to systemic circulation. Though there is not a large study with HE patients who have undergone RTO; the results appear promising in reducing HE. Side effects, however, should be considered in the treatment of HE such as the transient worsening of portal hypertension and the formation of additional shunts. While additional studies are needed to assess the long-term success, RTO appears to be an effective alternative method to alleviate clinical symptoms of HE when pharmacological therapies and other conservative medical managements have failed.

Cartilage-Targeted IGF-1 Treatment to Promote Longitudinal Bone Growth.

Recombinant human growth hormone (GH) is commonly used to treat short stature in children. However, GH treatment has limited efficacy, particularly in severe, non-GH-deficient conditions such as chondrodysplasias, and potential off-target effects. Because short stature results from decreased growth plate chondrogenesis, we developed a cartilage-targeting single-chain human antibody fragment (CaAb) aiming to deliver therapeutic molecules to the growth plate, thereby increasing treatment efficacy while minimizing adverse effects on other tissues. To this end, we created fusion proteins of these CaAbs conjugated with insulin-like growth factor 1 (IGF-1), an endocrine and/or paracrine factor that positively regulates chondrogenesis. These CaAb-IGF-1 fusion proteins retained both cartilage binding and IGF-1 biological activity, and they were able to stimulate bone growth in an organ culture system. Using a GH-deficient (lit) mouse model, we found that subcutaneous injections of these CaAb-IGF-1 fusion proteins increased overall growth plate height without increasing proliferation in kidney cortical cells, suggesting on-target efficacy at the growth plate and less off-target effect on the kidney than IGF-1 alone. Alternate-day injections of these fusion proteins, unlike IGF-1 alone, were sufficient to produce a therapeutic effect. Our findings provide proof of principle that targeting therapeutics to growth plate cartilage can potentially improve treatment for childhood growth disorders.

QRICH1 mutations cause a chondrodysplasia with developmental delay.

In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in QRICH1. In vitro studies confirmed that the mutation impaired expression of the QRICH1 protein. SiRNA-mediated knockdown of Qrich1 in primary mouse epiphyseal chondrocytes caused downregulation of gene expression associated with hypertrophic differentiation. We then identified an unrelated individual with another heterozygous de novo nonsense mutation in QRICH1 who had a similar phenotype. A recently published study identified QRICH1 mutations in three patients with developmental delay, one of whom had short stature. Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation.

An agenda for assessing and improving conservation impacts of sustainability standards in tropical agriculture.

Sustainability standards and certification serve to differentiate and provide market recognition to goods produced in accordance with social and environmental good practices, typically including practices to protect biodiversity. Such standards have seen rapid growth, including in tropical agricultural commodities such as cocoa, coffee, palm oil, soybeans, and tea. Given the role of sustainability standards in influencing land use in hotspots of biodiversity, deforestation, and agricultural intensification, much could be gained from efforts to evaluate and increase the conservation payoff of these schemes. To this end, we devised a systematic approach for monitoring and evaluating the conservation impacts of agricultural sustainability standards and for using the resulting evidence to improve the effectiveness of such standards over time. The approach is oriented around a set of hypotheses and corresponding research questions about how sustainability standards are predicted to deliver conservation benefits. These questions are addressed through data from multiple sources, including basic common information from certification audits; field monitoring of environmental outcomes at a sample of certified sites; and rigorous impact assessment research based on experimental or quasi-experimental methods. Integration of these sources can generate time-series data that are comparable across sites and regions and provide detailed portraits of the effects of sustainability standards. To implement this approach, we propose new collaborations between the conservation research community and the sustainability standards community to develop common indicators and monitoring protocols, foster data sharing and synthesis, and link research and practice more effectively. As the role of sustainability standards in tropical land-use governance continues to evolve, robust evidence on the factors contributing to effectiveness can help to ensure that such standards are designed and implemented to maximize benefits for biodiversity conservation.

The protein kinase A regulatory subunit R1A (Prkar1a) plays critical roles in peripheral nerve development.

Signaling through cAMP has been implicated in Schwann cell (SC) proliferation and myelination, but the signaling pathway components downstream of cAMP required for SC function remain unknown. Protein kinase A (PKA) is a potential downstream effector of cAMP. Here, we induced loss of Prkar1a, the gene encoding the type 1A regulatory subunit of PKA, in SC to study its role in nerve development; loss of Prkar1a is predicted to elevate PKA activity. Conditional Prkar1a knock-out in mouse SC (Prkar1a-SCKO) resulted in a dramatic and persistent axonal sorting defect, and unexpectedly decreased SC proliferation in Prkar1a-SCKO nerves in vivo. Effects were cell autonomous as they were recapitulated in vitro in Prkar1a-SCKO SC, which showed elevated PKA activity. In the few SCs sorted into 1:1 relationships with axons in vivo, SC myelination was premature in Prkar1a-SCKO nerves, correlating with global increase in the cAMP-regulated transcription factor Oct-6 and expression of myelin basic protein. These data reveal a previously unknown role of PKA in axon sorting, an unexpected inhibitory role of PKA on SC cell proliferation in vivo and define the importance of Prkar1a in peripheral nerve development.

Pregabalin-Associated Heart Failure Decompensation in a Patient With a History of Stage I Heart Failure.

OBJECTIVE: To describe an elderly male patient with a prior history of New York Heart Association (NYHA) class I heart failure (HF) who presented with cardiac decompensation related to pregabalin therapy and to review the literature involving the effects of pregabalin in HF patients. CASE SUMMARY: An 84-year-old man with NYHA class I HF (left-ventricular ejection fraction between 45% and 50%) presented to the emergency department with acute HF decompensation approximately 10 days after initiation of pregabalin for the management of peripheral neuropathy. Discontinuation of pregabalin and administration of furosemide resulted in resolution of symptoms. Shortness of breath; facial, neck, and peripheral edema; and weight gain all improved within 2 days. Three months following discontinuation of furosemide and pregabalin, the patient remained stable without any recurring symptoms or progression in HF. DISCUSSION: Pregabalin is associated with a 10% to 15% prevalence of peripheral edema and weight gain, with cases reported in patients both with and without HF. Whereas most reported HF exacerbations have occurred in patients with NYHA class II to IV HF, this case is one of the first to be reported in a patient with NYHA class I. According to the Naranjo probability scale (score of 4), it was possible that the patient's HF symptoms were related to pregabalin. The mechanism of action of pregabalin-induced HF is unknown, but pregabalin has been shown to act as a calcium channel antagonist. CONCLUSION: Although further studies are needed, this case suggests that close monitoring of patients with NYHA class I HF should be considered when initiating pregabalin therapy.

Value of pharmacist medication interviews on optimizing the electronic medication reconciliation process.

PURPOSE: Few studies have explored the impact of using different methods for obtaining accurate medication histories on medication safety. This study was conducted to compare the accuracy and clinical impact of pharmacist medication histories obtained by electronic medical record review (EMRR) alone with those obtained by direct interviews combined with EMRR. METHOD: This 18-week prospective study included patients who were admitted to the Inpatient Medicine Service at the study institution and who had a pharmacist-conducted medication reconciliation EMRR within 48 hours of hospital admission. A chart review was performed to collect data to determine whether differences existed in the number of discrepancies, recommendations, and medication errors between the EMRR alone group compared to the EMRR combined with the patient interview group. RESULTS: Five hundred thirteen discrepancies were identified with the EMRR group compared to 986 from the combined EMRR and patient interview group (P < .001). Significantly more recommendations were made in the combination interview group compared to the EMRR alone group (260 vs 97; P < .001). Fewer medication errors were identified for the EMRR alone group compared to the combination interview group (55 vs 134; P < .001). The most common errors were omitted medications followed by extra dose/failure to discontinue therapy and wrong dose/frequency errors. CONCLUSION: Pharmacist-conducted admission medication interviews combined with EMRR can potentially identify harmful medication discrepancies and prevent medication errors.

Staphylococcus aureus subcapsular splenic abscess and associated empyema in the setting of tocilizumab therapy: A case report.

We report a case of Staphylococcus aureus subcapsular splenic abscess and associated empyema after recent commencement of tocilizumab, masquerading as musculoskeletal pain. This highlights the importance of considering unusual underlying infections in patients on tocilizumab.

Levels of autonomy in FDA-cleared surgical robots: a systematic review.

The integration of robotics in surgery has increased over the past decade, and advances in the autonomous capabilities of surgical robots have paralleled that of assistive and industrial robots. However, classification and regulatory frameworks have not kept pace with the increasing autonomy of surgical robots. There is a need to modernize our classification to understand technological trends and prepare to regulate and streamline surgical practice around these robotic systems. We present a systematic review of all surgical robots cleared by the United States Food and Drug Administration (FDA) from 2015 to 2023, utilizing a classification system that we call Levels of Autonomy in Surgical Robotics (LASR) to categorize each robot's decision-making and action-taking abilities from Level 1 (Robot Assistance) to Level 5 (Full Autonomy). We searched the 510(k), De Novo, and AccessGUDID databases in December 2023 and included all medical devices fitting our definition of a surgical robot. 37,981 records were screened to identify 49 surgical robots. Most surgical robots were at Level 1 (86%) and some reached Level 3 (Conditional Autonomy) (6%). 2 surgical robots were recognized by the FDA to have machine learning-enabled capabilities, while more were reported to have these capabilities in their marketing materials. Most surgical robots were introduced via the 510(k) pathway, but a growing number via the De Novo pathway. This review highlights trends toward greater autonomy in surgical robotics. Implementing regulatory frameworks that acknowledge varying levels of autonomy in surgical robots may help ensure their safe and effective integration into surgical practice.

Characteristics and outcomes of reversible platypnoea-orthodeoxia syndrome in COVID-19 pneumonia.

INTRODUCTION: Platypnoea-orthodeoxia syndrome (POS) is an uncommon clinical entity characterised by dyspnoea and platypnoea (oxygen desaturation that follows the assumption of an upright position from recumbency). Since the coronavirus disease 2019 (COVID-19) outbreak, increasing reports of COVID-19-related POS and its associated morbidity have been reported around the world. We aimed to study the characteristics of COVID-19-related POS and orthodeoxia (including associations leading to a more prolonged orthodeoxia), and the postdischarge functional outcomes of patients with COVID-19-related POS. METHODS: An observational cohort study was conducted in a tertiary hospital that managed post-COVID-19 patients. Twenty-four participants with severe-to-critical COVID-19 disease/pneumonia and POS, who received inpatient pulmonary rehabilitation, were enrolled. Descriptive analysis of the data was performed to describe POS/orthodeoxia characteristics and functional outcomes in these participants. Correlation analyses were carried out to identify significant factors associated with a prolonged orthodeoxia. RESULTS: The mean duration of POS and orthodeoxia was 12.9 ± 8.3 days and 28.5 ± 14.6 days, respectively. All participants demonstrated resolution of POS and orthodeoxia by hospital discharge. On multivariable analysis, intensive care unit admission and maximal level of respiratory support were significantly associated with a prolonged duration of orthodeoxia. One participant was lost to follow-up. The remaining 23 participants achieved independence in self-care. With the exception of one patient, who was recovering from a hip fracture, the rest achieved independence in ambulation and independent community access. CONCLUSION: Resolution of orthodeoxia was observed in all our participants with COVID-19-related POS. Good functional outcome can be attained with timely and effective rehabilitation interventions.

Flecainide causing elevated capture thresholds on pacemaker implantation.

Flecainide is a Vaughan Williams class 1c antiarrhythmic used to treat supraventricular and ventricular arrhythmias. It has been described as a rare cause for increased pacemaker capture thresholds. We describe a report of a patient, in her early 80s, presenting with tachy-brady syndrome on a background of permanent atrial fibrillation. She was treated with metoprolol and flecainide by her private cardiologist. Permanent right ventricular chamber pacing was recommended for her slow heart rate. At insertion of her single chamber pacemaker, she was noted to have elevated capture thresholds despite appropriate lead positioning. A flecainide level was elevated at 1.1 µg/mL, and it was subsequently ceased. This was associated with a rapid improvement in her capture threshold. Flecainide should be considered as a cause for elevated pacing thresholds at the time of implant. Particular care should be taken for at-risk groups such as the elderly and patients with renal impairment.

Physical Therapists' Acceptance of a Wearable, Fabric-Based Sensor System (Motion Tape) for Use in Clinical Practice: Qualitative Focus Group Study.

BACKGROUND: Low back pain (LBP) is a costly global health condition that affects individuals of all ages and genders. Physical therapy (PT) is a commonly used and effective intervention for the management of LBP and incorporates movement assessment and therapeutic exercise. A newly developed wearable, fabric-based sensor system, Motion Tape, uses novel sensing and data modeling to measure lumbar spine movements unobtrusively and thus offers potential benefits when used in conjunction with PT. However, physical therapists' acceptance of Motion Tape remains unexplored. OBJECTIVE: The primary aim of this research study was to evaluate physical therapists' acceptance of Motion Tape to be used for the management of LBP. The secondary aim was to explore physical therapists' recommendations for future device development. METHODS: Licensed physical therapists from the American Physical Therapy Association Academy of Leadership Technology Special Interest Group participated in this study. Overall, 2 focus groups (FGs; N=8) were conducted, in which participants were presented with Motion Tape samples and examples of app data output on a poster. Informed by the Technology Acceptance Model, we conducted semistructured FGs and explored the wearability, usefulness, and ease of use of and suggestions for improvements in Motion Tape for PT management of LBP. FG data were transcribed and analyzed using rapid qualitative analysis. RESULTS: Regarding wearability, participants perceived that Motion Tape would be able to adhere for several days, with some variability owing to external factors. Feedback was positive for the low-profile and universal fit, but discomfort owing to wires and potential friction with clothing was of concern. Other concerns included difficulty with self-application and potential skin sensitivity. Regarding usefulness, participants expressed that Motion Tape would enhance the efficiency and specificity of assessments and treatment. Regarding ease of use, participants stated that the app would be easy, but data management and challenges with interpretation were of concern. Physical therapists provided several recommendations for future design improvements including having a wireless system or removable wires, customizable sizes for the tape, and output including range of motion data and summary graphs and adding app features that consider patient input and context. CONCLUSIONS: Several themes related to Motion Tape's wearability, usefulness, and ease of use were identified. Overall, physical therapists expressed acceptance of Motion Tape's potential for assessing and monitoring low back posture and movement, both within and outside clinical settings. Participants expressed that Motion Tape would be a valuable tool for the personalized treatment of LBP but highlighted several future improvements needed for Motion Tape to be used in practice.

Preliminary Validity and Acceptability of Motion Tape for Measuring Low Back Movement: Mixed Methods Study.

BACKGROUND: Low back pain (LBP) is a significant public health problem that can result in physical disability and financial burden for the individual and society. Physical therapy is effective for managing LBP and includes evaluation of posture and movement, interventions directed at modifying posture and movement, and prescription of exercises. However, physical therapists have limited tools for objective evaluation of low back posture and movement and monitoring of exercises, and this evaluation is limited to the time frame of a clinical encounter. There is a need for a valid tool that can be used to evaluate low back posture and movement and monitor exercises outside the clinic. To address this need, a fabric-based, wearable sensor, Motion Tape (MT), was developed and adapted for a low back use case. MT is a low-profile, disposable, self-adhesive, skin-strain sensor developed by spray coating piezoresistive graphene nanocomposites directly onto commercial kinesiology tape. OBJECTIVE: The objectives of this study were to (1) validate MT for measuring low back posture and movement and (2) assess the acceptability of MT for users. METHODS: A total of 10 participants without LBP were tested. A 3D optical motion capture system was used as a reference standard to measure low back kinematics. Retroreflective markers and a matrix of MTs were placed on the low back to measure kinematics (motion capture) and strain (MT) simultaneously during low back movements in the sagittal, frontal, and axial planes. Cross-correlation coefficients were calculated to evaluate the concurrent validity of MT strain in reference motion capture kinematics during each movement. The acceptability of MT was assessed using semistructured interviews conducted with each participant after laboratory testing. Interview data were analyzed using rapid qualitative analysis to identify themes and subthemes of user acceptability. RESULTS: Visual inspection of concurrent MT strain and kinematics of the low back indicated that MT can distinguish between different movement directions. Cross-correlation coefficients between MT strain and motion capture kinematics ranged from -0.915 to 0.983, and the strength of the correlations varied across MT placements and low back movement directions. Regarding user acceptability, participants expressed enthusiasm toward MT and believed that it would be helpful for remote interventions for LBP but provided suggestions for improvement. CONCLUSIONS: MT was able to distinguish between different low back movements, and most MTs demonstrated moderate to high correlation with motion capture kinematics. This preliminary laboratory validation of MT provides a basis for future device improvements, which will also involve testing in a free-living environment. Overall, users found MT acceptable for use in physical therapy for managing LBP.