Intrarater and Interrater Reliability and Agreement of a Method to Quantify Lower-Extremity Kinematics Using Remote Data Collection.

CONTEXT: To assess the reliability of a remote 2D markerless motion tracking method (Kinovea) to quantify knee and hip angles during dynamic tasks. METHODS: Fourteen healthy adults performed body weight squats and lateral lunges while video recording themselves at home. Knee and hip angles were quantified in the sagittal plane for the squats and in the frontal plane for the lateral lunges. Two students each performed the video analysis procedure twice, 2 weeks apart. Intraclass correlation coefficients were used to calculate the intrarater and interrater reliability for angles at maximum depth. The intrarater and interrater agreement over the joint angle-time signals were quantified using a validation metric; an acceptable agreement threshold was set at a validation metric of 0.803 or higher. Standard error of measurement (SEM) was also calculated. RESULTS: Reliability was good to excellent (intraclass correlation coefficients = .80-.98) for all angle comparisons at maximum depth. The agreement over the entire joint angle-time signal was acceptable for all squat variables except for the interrater hip angle comparison (validation metric = 0.797). None of the lateral lunge variables met the threshold of acceptable agreement. The mean SEM across participants for all joint angle-time signal and for maximum depth was acceptable (<5°) for all measurements (SEM = 1.2°-4.9°). CONCLUSIONS: Overall, the reliability, agreement, and SEM quantified in this study support the integration of remote methods to quantify lower-extremity kinematics into research and clinical practice.

Circulating extracellular vesicles from patients with acute chest syndrome disrupt adherens junctions between endothelial cells.

BACKGROUND: Small cell-derived extracellular vesicles (EVs) can affect endothelial function. We previously found that patients with sickle cell disease (SCD) have greater numbers of circulating EVs than subjects without the disease, and the EVs differentially disrupt endothelial integrity in vitro. Because endothelial disruption is a critical component of acute chest syndrome (ACS), we hypothesized that EVs isolated during ACS would induce greater endothelial damage than those isolated at baseline. METHODS: Nine pediatric subjects had plasma isolated at baseline and during ACS from which EVs were isolated. Cultured microvascular endothelial cells were treated with EVs and then studied by immunofluorescence microscopy to localize VE-cadherin and F-actin. RESULTS: The EVs had a diameter of 95 nm. They contained CD63 and flotillin-1, which were increased in SCD patients (5-13-fold compared to control) and further increased between baseline and ACS (24-57%). The EVs contained hemoglobin, glycophorin A, and ferritin. Treatment with baseline EVs caused modest separation of endothelial cells, while ACS EVs caused substantial disruptions of the endothelial cell monolayers. EVs from subjects with ACS also caused a 50% decrease in protein levels of VE-cadherin. CONCLUSIONS: These results suggest that circulating EVs can modulate endothelial integrity contributing to the development of ACS in SCD patients by altering cadherin-containing intercellular junctions. IMPACT: Sickle cell disease patients have circulating extracellular vesicles (EVs) that modulate endothelial integrity by altering cadherin-containing intercellular junctions. Disruption is more severe by EVs obtained during acute chest syndrome (ACS). These results expand our knowledge of the pathophysiology of acute chest syndrome and the vasculopathies of sickle cell disease.

Musculoskeletal modeling and movement simulation for structural hip disorder research: A scoping review of methods, validation, and applications.

Musculoskeletal modeling is a powerful tool to quantify biomechanical factors typically not feasible to measure in vivo, such as hip contact forces and deep muscle activations. While technological advancements in musculoskeletal modeling have increased accessibility, selecting the appropriate modeling approach for a specific research question, particularly when investigating pathological populations, has become more challenging. The purposes of this review were to summarize current modeling and simulation methods in structural hip disorder research, as well as evaluate model validation and study reproducibility. MEDLINE and Web of Science were searched to identify literature relating to the use of musculoskeletal models to investigate structural hip disorders (i.e., involving a bony abnormality of the pelvis, femur, or both). Forty-seven articles were included for analysis, which either compared multiple modeling methods or applied a single modeling workflow to answer a research question. Findings from studies comparing methods were summarized, such as the effect of generic versus patient-specific modeling techniques on model-estimated hip contact forces or muscle forces. The review also discussed limitations in validation practices, as only 11 of the included studies conducted a validation and used qualitative approaches only. Given the lack of information related to model validation, additional details regarding the development and validation of generic models were retrieved from references and modeling software documentation. To address the wide variability and under-reporting of data collection, data processing, and modeling methods highlighted in this review, we developed a template that researchers can complete and include as a table within the methodology section of their manuscripts. The use of this table will help increase transparency and reporting of essential details related to reproducibility and methods without being limited by word count restrictions. Overall, this review provides a comprehensive synthesis of modeling approaches that can help researchers make modeling decisions and evaluate existing literature.

Validation of a musculoskeletal model to investigate hip joint mechanics in response to dynamic multiplanar tasks.

Existing hip-focused musculoskeletal (MSK) models are limited by the hip range of motion, hip musculature detail, or have only been qualitatively validated. The purposes of this study were to: i) modify the existing 2396Hip MSK model to simulate dynamic tasks with multiplanar hip joint motion; and ii) validate the modified MSK model quantitatively against experimental data. Experimental data was collected from five healthy adults (age = 25 [6] years, two females) during eight movement tasks. The motion and ground reaction force data were input into the MSK modeling software OpenSim to calculate muscle activations and hip contact forces (HCFs). The HCFs were compared to experimental HCFs previously measured in total hip arthroplasty (THA) patients using instrumented hip prostheses. A gait simulation was performed using data from one THA patient to directly assess the model's accuracy in estimating HCFs. The young adults' modeled and experimental muscle activations for seven muscles were compared using a cross-correlation function. The model only overestimated the peak resultant HCFs by 0.06-0.08 N/BW compared to the experimentally measured HCFs of the THA patient. The young adults' HCFs were over two standard deviations higher than previously measured in the THA patients, which is likely a result of different movement patterns. The correlation coefficients indicated strong correlations between experimental and modeled muscle activations in 50 of the 56 comparisons. The results of this study suggest the new MSK model is an appropriate method to quantify HCFs and muscle activations in response to dynamic, multiplanar tasks among young, healthy adults.

"Her Heart Matters"-Making Visible the Cardiac Pain Experiences of Women with Physical Disabilities and Heart Disease: A Qualitative Study.

BACKGROUND: Women with physical disabilities are faced with challenges in many aspects of life-education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. METHODS: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. RESULTS: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers' attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. CONCLUSIONS: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants' experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women.

CONTEXTE: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l'éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. MÉTHODOLOGIE: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l'échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d'une approche phénoménologique herméneutique inspirée par Ricœur. RÉSULTATS: Deux grands thèmes ressortent de l'analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu'elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d'attente, les services de transport coûteux et peu fiables, les problèmes d'accessibilité et les obstacles liés à l'attitude des fournisseurs de soins vis-à-vis de l'incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d'avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L'autoprise en charge d'une incapacité physique et d'une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l'autonomie sociale. CONCLUSIONS: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l'équité et l'inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d'améliorer les résultats chez ces femmes.

Light microscopy based approach for mapping connectivity with molecular specificity.

Mapping neuroanatomy is a foundational goal towards understanding brain function. Electron microscopy (EM) has been the gold standard for connectivity analysis because nanoscale resolution is necessary to unambiguously resolve synapses. However, molecular information that specifies cell types is often lost in EM reconstructions. To address this, we devise a light microscopy approach for connectivity analysis of defined cell types called spectral connectomics. We combine multicolor labeling (Brainbow) of neurons with multi-round immunostaining Expansion Microscopy (miriEx) to simultaneously interrogate morphology, molecular markers, and connectivity in the same brain section. We apply this strategy to directly link inhibitory neuron cell types with their morphologies. Furthermore, we show that correlative Brainbow and endogenous synaptic machinery immunostaining can define putative synaptic connections between neurons, as well as map putative inhibitory and excitatory inputs. We envision that spectral connectomics can be applied routinely in neurobiology labs to gain insights into normal and pathophysiological neuroanatomy.

Attitudes toward participation in breast cancer randomized clinical trials in the African American community: a focus group study.

Participation of African Americans in research trials is low. Understanding the perspectives of African American patients toward participation in clinical trials is essential to understanding the disparities in participation rates compared with whites. A qualitative study was conducted to discover attitudes of the African American community regarding willingness to participate in breast cancer screening and randomized clinical trials. Six focus groups consisting of 8 to 11 African American women (N = 58), aged 30 to 65, were recruited from local churches. Focus group sessions involved a 2-hour audio-taped discussion facilitated by 2 moderators. A breast cancer randomized clinical trial involving an experimental breast cancer treatment was discussed to identify the issues related to willingness to participate in such research studies. Six themes surrounding willingness to participate in randomized clinical trials were identified: (1) Significance of the research topic to the individual and/or community; (2) level of trust in the system; (3) understanding of the elements of the trial; (4) preference for "natural treatments" or "religious intervention" over medical care; (5) cost-benefit analysis of incentives and barriers; and (6) openness to risk versus a preference for proven treatments. The majority (80%) expressed willingness or open-mindedness to the idea of participating in the hypothetical trial. Lessons learned from this study support the selection of a culturally diverse research staff and can guide the development of research protocols, recruitment efforts, and clinical procedures that are culturally sensitive and relevant.