Adolescent pilonidal disease laser treatment (a-PiLaT): a pilot study.

BACKGROUND: Pilonidal disease (PD) is an acquired condition related to hair-induced mechanical forces on the skin surface of the intergluteal cleft, with subsequent abscess formation with or without a concomitant draining sinus (pit). While surgical management currently is the mainstay of treatment, pilonidal disease laser treatment (PiLaT) has recently been recognized as a promising treatment option for non-inflammatory diseases. Nonetheless, there is a paucity of available data on adolescent pilonidal disease laser treatment (a-PiLaT). METHODS: We describe our preliminary experience with PiLaT performed in adolescents aged 10-17 years at our tertiary paediatric surgical hospital from 2019 to 2023. Data on perioperative characteristics and clinical outcomes at follow-up were retrospectively analysed. RESULTS: A total of 17 consecutive patients (n = 12 female, 71%) underwent a-PiLaT. At the time of treatment, the patients' mean age and body mass index were 13.6 ± 1.6 years and 25.3 ± 5.6 kg m-2, respectively. The mean operative time was 21.5 ± 10.4 min, whereas the mean follow-up period was 24.5 ± 16.8 months, with a complication rate of 24% (n = 4) and recurrence rate of 18% (n = 3). With respect to postsurgical scar assessment, the mean Patient and Observer Scar Assessment Scale scores (score range 6-60, with higher scores indicating worse outcome) were 14.2 ± 6.5 (patients' evaluation) and 11.4 ± 4.7 (observers' evaluation). CONCLUSION: The a-PiLaT represents a novel approach for managing PD in adolescents. Our preliminary data on the outcomes of a small series of patients with pilonidal sinuses after a-PiLaT indicated complication and recurrence rates comparable to those reported in the literature for adults. This new minimally invasive technique has great potential and is therefore worthy of further research on a larger population.

Concurrent Validity of Motion Parameters Measured With an RGB-D Camera-Based Markerless 3D Motion Tracking Method in Children and Young Adults.

OBJECTIVE: Low-cost, portable RGB-D cameras with integrated motion tracking functionality enable easy-to-use 3D motion analysis without requiring expensive facilities and specialized personnel. However, the accuracy of existing systems is insufficient for most clinical applications, particularly when applied to children. In previous work, we developed an RGB-D camera-based motion tracking method and showed that it accurately captures body joint positions of children and young adults in 3D. In this study, the validity and accuracy of clinically relevant motion parameters that were computed from kinematics of our motion tracking method are evaluated in children and young adults. METHODS: Twenty-three typically developing children and healthy young adults (5-29 years, 110-189 cm) performed five movement tasks while being recorded simultaneously with a marker-based Vicon system and an Azure Kinect RGB-D camera. Motion parameters were computed from the extracted kinematics of both methods: time series measurements, i.e., measurements over time, peak measurements, i.e., measurements at a single time instant, and movement smoothness. The agreement of these parameter values was evaluated using Pearson's correlation coefficients r for time series data, and mean absolute error (MAE) and Bland-Altman plots with limits of agreement for peak measurements and smoothness. RESULTS: Time series measurements showed strong to excellent correlations (r-values between 0.8 and 1.0), MAE for angles ranged from 1.5 to 5 degrees and for smoothness parameters (SPARC) from 0.02-0.09, while MAE for distance-related parameters ranged from 9 to 15 mm. CONCLUSION: Extracted motion parameters are valid and accurate for various movement tasks in children and young adults, demonstrating the suitability of our tracking method for clinical motion analysis. CLINICAL IMPACT: The low-cost portable hardware in combination with our tracking method enables motion analysis outside of specialized facilities while providing measurements that are close to those of the clinical gold-standard.

Assessing proprioception in children with upper motor neuron lesions: feasibility, validity, and reliability of the proprioception measurement tool.

Introduction: To investigate the feasibility, discriminative and convergent validity, and reliability of a lower limb sensor-based proprioception measure in children with upper motor neuron (UMN) lesions. Method: We assessed three proprioception modalities (joint movement, joint position, and dynamic position sense) of the lower limbs in 49 children with UMN lesions and 50 typically developing (TD) peers (5-19 years). Forty-three children with UMN lesion had a congenital and six an acquired brain lesion and 82% were able to walk without a walking aid. We evaluated the feasibility, compared the test results between children with UMN lesions and TD peers, and calculated Spearman correlations (rs) between the modalities. We quantified relative reliability with Intra-Class Correlation Coefficients (ICC) and absolute reliability with Smallest Detectable Changes (SDC). Results: Most children with UMN lesions (>88%) found the tests easy to perform. The children with UMN lesions had significantly (p < 0.001) lower proprioceptive function than the TD children. The correlation between the three proprioceptive modalities was moderate to high (0.50 ≤ rs ≤ 0.79). The relative reliability for test-retest and the inter-rater reliability was moderate to high (ICCs = 0.65-0.97), and SDC was between 2° and 15°. Discussion: The three tests are feasible, and discriminative and convergent validity and reliability were confirmed. Further studies should investigate the influence on motor function and performance in children with UMN lesions.

Early-stage health technology assessment of fractional flow reserve coronary computed tomography versus standard diagnostics in patients with stable chest pain in The Netherlands.

OBJECTIVES: The aim of this early-stage Health Technology Assessment (HTA) was to assess the difference in healthcare costs and effects of fractional flow reserve derived from coronary computed tomography (FFRct) compared to standard diagnostics in patients with stable chest pain in The Netherlands. METHODS: A decision-tree model was developed to assess the difference in total costs from the hospital perspective, probability of correct diagnoses, and risk of major adverse cardiovascular events at one year follow-up. One-way sensitivity analyses were conducted to determine the main drivers of the cost difference between the strategies. A threshold analysis on the added price of FFRct analysis (computational analysis only) was conducted. RESULTS: The mean one-year costs were €2,680 per patient for FFRct and €2,915 per patient for standard diagnostics. The one-year probability of correct diagnoses was 0.78 and 0.61, and the probability of major adverse cardiovascular events was 1.92x10-5 and 0.01, respectively. The probability and costs of revascularization and the specificity of coronary computed tomography angiography had the greatest effect on the difference in costs between the strategies. The added price of FFRct analysis should be below €935 per patient to be considered the least costly option. CONCLUSIONS: The early-stage HTA findings suggest that FFRct may reduce total healthcare spending, probability of incorrect diagnoses, and major adverse cardiovascular events compared to current diagnostics for patients with stable chest pain in the Dutch healthcare setting over one year. Future cost-effectiveness studies should determine a value-based pricing for FFRct and quantify the economic value of the anticipated therapeutic impact.

Human atherosclerotic plaque transcriptomics reveals endothelial beta-2 spectrin as a potential regulator a leaky plaque microvasculature phenotype.

The presence of atherosclerotic plaque vessels is a critical factor in plaque destabilization. This may be attributable to the leaky phenotype of these microvessels, although direct proof for this notion is lacking. In this study, we investigated molecular and cellular patterns of stable and hemorrhaged human plaque to identify novel drivers of intraplaque vessel dysfunction. From transcriptome data of a human atherosclerotic lesion cohort, we reconstructed a co-expression network, identifying a gene module strongly and selectively correlated with both plaque microvascular density and inflammation. Spectrin Beta Non-Erythrocytic 1 (sptbn1) was identified as one of the central hubs of this module (along with zeb1 and dock1) and was selected for further study based on its predominant endothelial expression. Silencing of sptbn1 enhanced leukocyte transmigration and vascular permeability in vitro, characterized by an increased number of focal adhesions and reduced junctional VE-cadherin. In vivo, sptbn1 knockdown in zebrafish impaired the development of the caudal vein plexus. Mechanistically, increased substrate stiffness was associated with sptbn1 downregulation in endothelial cells in vitro and in human vessels. Plaque SPTBN1 mRNA and protein expression were found to correlate with an enhanced presence of intraplaque hemorrhage and future cardiovascular disease (CVD) events during follow-up. In conclusion, we identify SPTBN1 as a central hub gene in a gene program correlating with plaque vascularisation. SPTBN1 was regulated by substrate stiffness in vitro while silencing blocked vascular development in vivo, and compromised barrier function in vitro. Together, SPTBN1 is identified as a new potential regulator of the leaky phenotype of atherosclerotic plaque microvessels.

Enhancing walking efficiency of adolescents with neurological impairments using an exosuit for ambulatory activities of daily living.

Introduction: Children and adolescents with neurological impairments face reduced participation and independence in daily life activities due to walking difficulties. Existing assistive devices often offer insufficient support, potentially leading to wheelchair dependence and limiting physical activity and daily life engagement. Mobile wearable robots, such as exoskeletons and exosuits, have shown promise in supporting adults during activities of daily living but are underexplored for children. Methods: We conducted a cross-sectional study to examine the potential of a cable-driven exosuit, the Myosuit, to enhance walking efficiency in adolescents with diverse ambulatory impairments. Each participant walked a course including up-hill, down-hill, level ground walking, and stairs ascending and descending, with and without the exosuit's assistance. We monitored the time and step count to complete the course and the average heart rate and muscle activity. Additionally, we assessed the adolescents' perspective on the exosuit's utility using a visual analog scale. Results: Six adolescents completed the study. Although not statistically significant, five participants completed the course with the exosuit's assistance in reduced time (time reduction range: [-3.87, 17.42]%, p-value: 0.08, effect size: 0.88). The number of steps taken decreased significantly with the Myosuit's assistance (steps reduction range: [1.07, 15.71]%, p-value: 0.04, effect size: 0.90). Heart rate and muscle activity did not differ between Myosuit-assisted and unassisted conditions (p-value: 0.96 and 0.35, effect size: 0.02 and 0.42, respectively). Participants generally perceived reduced effort and increased safety with the Myosuit's assistance, especially during tasks involving concentric contractions (e.g., walking uphill). Three participants expressed a willingness to use the Myosuit in daily life, while the others found it heavy or too conspicuous. Discussion: Increased walking speed without increasing physical effort when performing activities of daily living could lead to higher levels of participation and increased functional independence. Despite perceiving the benefits introduced by the exosuit's assistance, adolescents reported the need for further modification of the device design before using it extensively at home and in the community.

Are tactile function and body awareness of the foot related to motor outcomes in children with upper motor neuron lesions?

Introduction: Somatosensory function can be reduced in children with Upper Motor Neuron (UMN) lesions. Therefore, we investigated relationships between somatosensory functions of the foot and motor outcomes in children with UMN lesions. Method: In this cross-sectional study, we assessed the Tactile Threshold (TT) with monofilaments and body awareness with Tactile Localisation Tasks for spatial-related action (TLTaction) and structural-related perception (TLTperception) body representation at the foot sole. Furthermore, we assessed four motor outcomes: the Selective Control Assessment of the Lower Extremity (SCALE), the modified Timed Up and Go test (mTUG), the Gillette Functional Assessment Questionnaire (FAQ), and the Functional Mobility Scale (FMS). Spearman's correlations (ρ) were applied to assess relationships between the somatosensory function of the foot sole and the applied motor outcomes. Results: Thirty-five children with UMN lesions, on average 11.7 ± 3.4 years old, participated. TLTperception correlated significantly with all lower limb motor outcomes (|ρ|=0.36-0.57; p < 0.05), but TLTaction (|ρ|=0.00-0.27; p = 0.15-0.97, and TT did not (|ρ|=0.01-0.83; p = 0.73-0.94). TLTperception correlated strongly with the Gross Motor Function Classification System (|ρ|=0.62; p = 0.001) in children with cerebral palsy (n = 24). Discussion: Assessing structural body representation of the foot sole should be considered when addressing lower limb motor impairments, including gait, in children with upper motor neuron lesions. Our results suggest that the assessment of tactile function and spatial body representation may be less related to lower limb motor function.

Comparing Walking-Related Everyday Life Tasks of Children with Gait Disorders in a Virtual Reality Setup With a Physical Setup: Cross-Sectional Noninferiority Study.

BACKGROUND: A frequent rehabilitation goal for children with gait disorders is to practice daily-life walking activities. Unfortunately, these are often difficult to practice in a conventional therapeutic setting. Virtual reality (VR) with head-mounted displays (HMDs) could be a promising approach in neurorehabilitation to train such activities in a safe environment. First, however, we must know whether obstacles in VR are indeed mastered as obstacles. OBJECTIVE: This study aimed to provide information on whether VR is feasible and motivating to induce and practice movements needed to master real obstacles in children and adolescents with gait disorders. Furthermore, this project aims to evaluate which kinds of everyday walking activities are appropriate to be practiced in VR. METHODS: In this cross-sectional study, participants stepped over a bar, crossed a gap, balanced over a beam, and circumvented stationary obstructions arranged in a course under real physical and virtual conditions wearing a VR HMD. We recorded the respective primary outcomes (step height, step length, step width, and minimal shoulder-obstacle distance) with motion capture. We then calculated the mean differences and 95% CI of the spatiotemporal parameters between the VR and physical setup and later compared them using noninferiority analysis with margins defined a priori by a clinical expert panel. Additionally, the participants responded to a standardized questionnaire while the therapists observed and evaluated their movement performance. RESULTS: We recruited 20 participants (mean age 12.0, range 6.6-17.8 years) with various diagnoses affecting their walking ability. At 3.77 (95% CI 1.28 to 6.26) cm, the mean difference in step height of the leading foot in the overstepping task did not exceed the predefined margin of -2 cm, thus signifying noninferiority of the VR condition compared to mastering the physical obstacles. The same was true for step length (-1.75, 95% CI -4.91 to 1.41 cm; margin -10 cm), step width (1.05, 95% CI 0.20 to -1.90 cm; margin 3 cm), and the minimal shoulder-obstacle distance (0.25, 95% CI -0.85 to 0.35 cm; margin -2 cm) in the other tasks. Only the trailing foot in the overstepping task yielded inconclusive results. CONCLUSIONS: Children with gait disorders perform everyday walking tasks like overstepping, crossing, balancing, or circumventing similarly in physical and VR environments, suggesting that VR could be a feasible therapeutic tool to practice everyday walking tasks.

Trust in and Acceptance of Artificial Intelligence Applications in Medicine: Mixed Methods Study.

BACKGROUND: Artificial intelligence (AI)-powered technologies are being increasingly used in almost all fields, including medicine. However, to successfully implement medical AI applications, ensuring trust and acceptance toward such technologies is crucial for their successful spread and timely adoption worldwide. Although AI applications in medicine provide advantages to the current health care system, there are also various associated challenges regarding, for instance, data privacy, accountability, and equity and fairness, which could hinder medical AI application implementation. OBJECTIVE: The aim of this study was to identify factors related to trust in and acceptance of novel AI-powered medical technologies and to assess the relevance of those factors among relevant stakeholders. METHODS: This study used a mixed methods design. First, a rapid review of the existing literature was conducted, aiming to identify various factors related to trust in and acceptance of novel AI applications in medicine. Next, an electronic survey including the rapid review-derived factors was disseminated among key stakeholder groups. Participants (N=22) were asked to assess on a 5-point Likert scale (1=irrelevant to 5=relevant) to what extent they thought the various factors (N=19) were relevant to trust in and acceptance of novel AI applications in medicine. RESULTS: The rapid review (N=32 papers) yielded 110 factors related to trust and 77 factors related to acceptance toward AI technology in medicine. Closely related factors were assigned to 1 of the 19 overarching umbrella factors, which were further grouped into 4 categories: human-related (ie, the type of institution AI professionals originate from), technology-related (ie, the explainability and transparency of AI application processes and outcomes), ethical and legal (ie, data use transparency), and additional factors (ie, AI applications being environment friendly). The categorized 19 umbrella factors were presented as survey statements, which were evaluated by relevant stakeholders. Survey participants (N=22) represented researchers (n=18, 82%), technology providers (n=5, 23%), hospital staff (n=3, 14%), and policy makers (n=3, 14%). Of the 19 factors, 16 (84%) human-related, technology-related, ethical and legal, and additional factors were considered to be of high relevance to trust in and acceptance of novel AI applications in medicine. The patient's gender, age, and education level were found to be of low relevance (3/19, 16%). CONCLUSIONS: The results of this study could help the implementers of medical AI applications to understand what drives trust and acceptance toward AI-powered technologies among key stakeholders in medicine. Consequently, this would allow the implementers to identify strategies that facilitate trust in and acceptance of medical AI applications among key stakeholders and potential users.

Reporting Completeness of Intensity-, Dose-, and Dosage-Related Items in Active Pediatric Upper Limb Neurorehabilitation Trials: A Systematic Review.

OBJECTIVE: To analyze the reporting completeness of the TIDieR items 8-12, in particular intensity, dose, and dosage, in active pediatric upper limb neurorehabilitation trials. DATA SOURCES: We searched PubMed Central, Scopus, CINAHL, OTseeker, and Web of Science for eligible publications. STUDY SELECTION: We included publications analyzing active pediatric upper limb neurorehabilitation interventions and assessed the reporting completeness of 11 items for each intervention and control group. DATA EXTRACTION: Two raters independently screened titles and abstracts and selected the publications using the RYYAN platform. We unblinded the results after the raters had completed their selection and resolved the disagreements by discussion. We used the same procedures to review the full texts. DATA SYNTHESIS: We included 52 randomized controlled trials with 65 intervention and 48 control groups. Authors did not report all 11 items in any of the study groups. The overall reporting completeness varied between 1% (intensity) to 95% (length of the intervention). The reporting completeness of the TIDieR items ranged from 2% (modifications) to 64% (when and how much). We found no significant differences in the reporting completeness between the intervention and control groups. CONCLUSIONS: Information essential for dose-response calculations is often missing in randomized controlled trials of pediatric upper limb neurorehabilitation interventions. Reporting completeness should be improved, and new measures to accurately quantify intensity should be discussed and developed.

A Tailorable Robotic Hand Orthosis to Support Children with Neurological Hand Impairments: a Case Study in a Child's Home.

Neurological disorders such as traumatic brain injuries (TBI) can lead to hand impairments in children, negatively impacting their quality of life. Fully wearable robotic hand orthoses (RHO) have been proposed to actively support children and promote the use of the impaired limb in daily life. Here we report a case study on the feasibility of using the pediatric RHO PEXO for assistance at home in a 13- year-old child with hand impairment after TBI. The size and functionalities of the RHO were first fully tailored to the child's needs. We trained the child and their parent on independently using the RHO before taking it home for a period of two weeks. The use of the RHO improved hand ability. Additionally, the tailoring and training benefited the unimanual capacity (Box and Block Test score +2 after tailoring) and bimanual performance (Assisting Hand Assessment score +4) of the child with PEXO. Further, it increased device acceptance by the child and the parent. The child used PEXO at home for 76 minutes distributed over three days during eating and drinking tasks. Personal and environmental factors caused the moderate use. No adverse events or safety-related issues occurred. This study highlights the value of tailoring an assistive RHO and, for the first time, demonstrates the feasibility of home use of a pediatric RHO by children with neurological hand impairments.

Two related families of metal transferases, ZNG1 and ZNG2, are involved in acclimation to poor Zn nutrition in Arabidopsis.

Metal homeostasis has evolved to tightly modulate the availability of metals within the cell, avoiding cytotoxic interactions due to excess and protein inactivity due to deficiency. Even in the presence of homeostatic processes, however, low bioavailability of these essential metal nutrients in soils can negatively impact crop health and yield. While research has largely focused on how plants assimilate metals, acclimation to metal-limited environments requires a suite of strategies that are not necessarily involved in metal transport across membranes. The identification of these mechanisms provides a new opportunity to improve metal-use efficiency and develop plant foodstuffs with increased concentrations of bioavailable metal nutrients. Here, we investigate the function of two distinct subfamilies of the nucleotide-dependent metallochaperones (NMCs), named ZNG1 and ZNG2, that are found in plants, using Arabidopsis thaliana as a reference organism. AtZNG1 (AT1G26520) is an ortholog of human and fungal ZNG1, and like its previously characterized eukaryotic relatives, localizes to the cytosol and physically interacts with methionine aminopeptidase type I (AtMAP1A). Analysis of AtZNG1, AtMAP1A, AtMAP2A, and AtMAP2B transgenic mutants are consistent with the role of Arabidopsis ZNG1 as a Zn transferase for AtMAP1A, as previously described in yeast and zebrafish. Structural modeling reveals a flexible cysteine-rich loop that we hypothesize enables direct transfer of Zn from AtZNG1 to AtMAP1A during GTP hydrolysis. Based on proteomics and transcriptomics, loss of this ancient and conserved mechanism has pleiotropic consequences impacting the expression of hundreds of genes, including those involved in photosynthesis and vesicle transport. Members of the plant-specific family of NMCs, ZNG2A1 (AT1G80480) and ZNG2A2 (AT1G15730), are also required during Zn deficiency, but their target protein(s) remain to be discovered. RNA-seq analyses reveal wide-ranging impacts across the cell when the genes encoding these plastid-localized NMCs are disrupted.

Early modelling of the effects and healthcare costs of the Dutch citizen-rescuer system for out-of-hospital cardiac arrests.

OBJECTIVES: 1) to analyse the total average healthcare costs of a patient with an out-of-hospital cardiac arrest (OHCA), as well as estimating the operational costs of the citizen-rescuer system (CRS); 2) to conduct an early modelling of the effects and healthcare costs of the Dutch CRS in comparison to no CRS. METHODS: A health economic modelling study was conducted. Adult patients with OHCA from cardiac causes in the province of Limburg (the Netherlands) were included. The time horizon was from OHCA occurrence up to one year after hospital discharge. First, the total average healthcare costs of OHCA patients were analysed as well as the yearly operating costs of the CRS. Second, an early modelling was conducted to compare from the healthcare perspective the healthcare costs of OHCA patients with the CRS being activated but no responders attended (CRS-NV) versus the CRS being activated with attendance of ≥1 responder(s) (CRS-V). RESULTS: The total average healthcare costs per patient are €42,533. The yearly operating costs for the CRS are approximately €1.5 million per year in the Netherlands. The early modelling of costs and effects showed that the incremental healthcare costs per patient thus were €4,131 in the CRS-V versus the CRS-NV group (€25,184 in the CRS-V group and €21,053 in the CRS-NV group). Incremental quality-adjusted life years (QALYs) was 5 per 100 patients (16 per 100 patients in the CRS-V group versus 11 per 100 patients in the CRS-NV group). The incremental cost-effectiveness ratio (ICER) was €79,662 per QALY for the CRS-V group. CONCLUSION: This study shows that patients in the CSR-V group had additional health care costs of €4,131 per patient compared to patients in the CRS-NV group. This increase is caused by patients surviving more often, who then continue to utilise health services, which results in a (logic) increase in healthcare costs. For future research, accurate and up-to-date data on effectiveness and costs of the CRS needs to be collected.

Defining, quantifying, and reporting intensity, dose, and dosage of neurorehabilitative interventions focusing on motor outcomes.

Introduction: Determining the minimal amount of therapy needed for positive neurorehabilitative outcomes is important for optimizing active treatment interventions to improve motor outcomes. However, there are various challenges when quantifying these relationships: first, several consensuses on the definition and usage of the terms intensity, dose, and dosage of motor interventions have been proposed, but there seems to be no agreement, and the terms are still used inconsistently. Second, randomized controlled trials frequently underreport items relevant to determining the intensity, dose, and dosage of the interventions. Third, there is no universal measure to quantify therapy intensity accurately. This "perspectives" paper aims to increase awareness of these topics among neurorehabilitation specialists. Defining quantifying and reporting: We searched the literature for definitions of intensity, dose, and dosage and adapted the ones we considered the most appropriate to fit the needs of neurorehabilitative interventions. Furthermore, we suggest refining the template for intervention description and replication (TIDieR) to enhance the reporting of randomized controlled trials. Finally, we performed a systematic literature search to provide a list of intensity measures and complemented these with some novel candidate measures. Discussion: The proposed definitions of intensity, dose, and dosage could improve the communication between neurorehabilitation specialists and the reporting of dose and dosage in interventional studies. Quantifying intensity is necessary to improve our understanding of the minimal intensity, dose, and dosage of therapy needed to improve motor outcomes in neurorehabilitation. We consider the lack of appropriate intensity measures a significant gap in knowledge requiring future research.

Differences in gait parameters when crossing real versus projected everyday life obstacles in healthy children and adolescents.

Practicing complex everyday life walking activities is challenging in paediatric neurorehabilitation, although it would prepare patients more comprehensively for the requirements of daily life. Floor projections allow simulation and training of such situations in therapy. Twenty healthy youths aged 6-18 years stepped over a tree trunk and balanced over kerbstones in a real and projected condition. Spatiotemporal and kinematic parameters of the two conditions were compared by equivalence analysis, using the medians of the differences between the two conditions with their bootstrapped 95% confidence intervals. Velocity, step and stride length, step width, and single support time were generally equivalent between the two conditions. Knee and hip joint angles and toe clearance decreased substantially during the execution phase of the projected tree trunk condition. The largest differences were found at the end of the execution phase in both tasks for the ankle joints. As spatiotemporal parameters were equivalent between the conditions, floor projections seem suitable to train precise foot placement. However, differences in knee and hip joint kinematics and toe clearance revealed that floor projections are not applicable for obstacles with a vertical extension. Therefore, exercises aiming at knee and hip flexion improvement should favourably be trained with real objects.

A novel orthotopic mouse model replicates human lung cancer cachexia.

INTRODUCTION: Cancer cachexia, highly prevalent in lung cancer, is a debilitating syndrome characterized by involuntary loss of skeletal muscle mass and is associated with poor clinical outcome, decreased survival and negative impact on tumour therapy. Various lung tumour-bearing animal models have been used to explore underlying mechanisms of cancer cachexia. However, these models do not simulate anatomical and immunological features key to lung cancer and associated muscle wasting. Overcoming these shortcomings is essential to translate experimental findings into the clinic. We therefore evaluated whether a syngeneic, orthotopic lung cancer mouse model replicates systemic and muscle-specific alterations associated with human lung cancer cachexia. METHODS: Immune competent, 11 weeks old male 129S2/Sv mice, were randomly allocated to either (1) sham control group or (2) tumour-bearing group. Syngeneic lung epithelium-derived adenocarcinoma cells (K-rasG12D ; p53R172HΔG ) were inoculated intrapulmonary into the left lung lobe of the mice. Body weight and food intake were measured daily. At baseline and weekly after surgery, grip strength was measured and tumour growth and muscle volume were assessed using micro cone beam CT imaging. After reaching predefined surrogate survival endpoint, animals were euthanized, and skeletal muscles of the lower hind limbs were collected for biochemical analysis. RESULTS: Two-third of the tumour-bearing mice developed cachexia based on predefined criteria. Final body weight (-13.7 ± 5.7%; P < 0.01), muscle mass (-13.8 ± 8.1%; P < 0.01) and muscle strength (-25.5 ± 10.5%; P < 0.001) were reduced in cachectic mice compared with sham controls and median survival time post-surgery was 33.5 days until humane endpoint. Markers for proteolysis, both ubiquitin proteasome system (Fbxo32 and Trim63) and autophagy-lysosomal pathway (Gabarapl1 and Bnip3), were significantly upregulated, whereas markers for protein synthesis (relative phosphorylation of Akt, S6 and 4E-BP1) were significantly decreased in the skeletal muscle of cachectic mice compared with control. The cachectic mice exhibited increased pentraxin-2 (P < 0.001) and CXCL1/KC (P < 0.01) expression levels in blood plasma and increased mRNA expression of IκBα (P < 0.05) in skeletal muscle, indicative for the presence of systemic inflammation. Strikingly, RNA sequencing, pathway enrichment and miRNA expression analyses of mouse skeletal muscle strongly mirrored alterations observed in muscle biopsies of patients with lung cancer cachexia. CONCLUSIONS: We developed an orthotopic model of lung cancer cachexia in immune competent mice. Because this model simulates key aspects specific to cachexia in lung cancer patients, it is highly suitable to further investigate the underlying mechanisms of lung cancer cachexia and to test the efficacy of novel intervention strategies.

Concurrent Validity of a Custom Method for Markerless 3D Full-Body Motion Tracking of Children and Young Adults Based on a Single RGB-D Camera.

Low-cost, portable RGB-D cameras with integrated body tracking functionality enable easy-to-use 3D motion analysis without requiring expensive facilities and specialized personnel. However, the accuracy of existing systems is insufficient for most clinical applications. In this study, we investigated the concurrent validity of our custom tracking method based on RGB-D images with respect to a gold-standard marker-based system. Additionally, we analyzed the validity of the publicly available Microsoft Azure Kinect Body Tracking (K4ABT). We recorded 23 typically developing children and healthy young adults (aged 5 to 29 years) performing five different movement tasks using a Microsoft Azure Kinect RGB-D camera and a marker-based multi-camera Vicon system simultaneously. Our method achieved a mean per joint position error over all joints of 11.7 mm compared to the Vicon system, and 98.4% of the estimated joint positions had an error of less than 50 mm. Pearson's correlation coefficients r ranged from strong ( r =0.64) to almost perfect ( 0.99). K4ABT demonstrated satisfactory accuracy most of the time but showed short periods of tracking failures in nearly two-thirds of all sequences limiting its use for clinical motion analysis. In conclusion, our tracking method highly agrees with the gold standard system. It paves the way towards a low-cost, easy-to-use, portable 3D motion analysis system for children and young adults.

Person-centred care in the Dutch primary care setting: Refinement of middle-range theory by patients and professionals.

In a previous rapid realist review (RRR) of international literature insight was provided into how, why, and under what circumstances person-centred care (PCC) in primary care works (or not) among others for people with low health literacy skills and for people with a diverse ethnic and socioeconomic background, by establishing a middle-range programme theory (PT), which describes the relationship between context items, mechanisms, and outcomes. Since the application of PCC in primary care in the Dutch setting is expected to differ from other countries, the objective of this study is to validate the items (face validity) resulting from the RRR for the Dutch setting by assessing consensus on the relevance of items. Four focus group discussions with patient representatives and patients with limited health literacy skills (n = 14), and primary care professionals (n = 11) were held partly combined with a Delphi-study. Items were added to refine the middle-range PT for the Dutch primary care setting. These items indicated that in order to optimally align care to the patient tailored supporting material that is developed together with the target group is important, next to providing tailored communication. Healthcare providers (HCPs) and patients need to have a shared vision and set up goals and action plans together. HCPs should stimulate patient's self-efficacy, need to be aware of the patient's (social) circumstances and work in a culturally sensitive way. Better integration between information and communications technology systems, flexible payment models, and patients access to documents, and recorded consultations should be in place. This may result in better alignment of care to the needs of patients, improved accessibility to care, improved patient's self-efficacy, and improved health-related quality of life. On the long-term higher cost-effectiveness and a higher quality of healthcare can be realised. In conclusion, this study shows that for PCC to be effective in Dutch primary care, the PT based on international literature was refined by leaving out items and adding new items for which insufficient or sufficient consensus, respectively, was found.

Feasibility, Validity, and Reliability of Lower Limb Tactile and Body Awareness Assessments in Children With Upper Motor Neuron Lesions.

OBJECTIVE: To investigate the feasibility, discriminative and convergent validity, and inter-rater reliability of a lower limb tactile function and 2 body awareness assessments in children with upper motor neuron (UMN) lesions. DESIGN: Cross-sectional psychometric study. SETTING: Pediatric rehabilitation center. PARTICIPANTS: Forty individuals with UMN lesions (mean age 11.7 years, SD 3.4 years; 27 girls) and 40 neurotypically developing children of the same age participated (N=80). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We assessed the tactile threshold (TT) with monofilaments and body awareness with tactile localization tasks (TLTs) for structural (TLTaction) and spatial (TLTperception) body representation at the foot sole. We compared the test outcomes between children with UMN lesions and neurotypically developing children with the Wilcoxon signed-rank test. Furthermore, we quantified the relations between the 3 tests with Spearman correlations (rs) and the interrater reliability with quadratic weighted kappa (κQW). RESULTS: About 80% of the children with UMN lesions perceived the tests easy to perform. The children with UMN lesions had significantly reduced somatosensory function compared with the neurotypically developing children. For the more affected leg, we found good relations between the TT and the TLTaction (rs=0.71; P<.001) and between the 2 TLTs (rs=0.66; P<.001), and a fair relation between the TT and the TLTperception (rs=0.31; P=.06). The inter-rater reliability analyses for the sum scores showed almost perfect agreement for the TT (κQW more affected leg 0.86; less affected leg 0.81), substantial agreement for TLTaction (κQW more affected leg 0.76; less affected leg 0.63), and almost perfect agreement for TLTperception (κQW more affected leg 0.88; less affected leg 0.74). CONCLUSION: The 3 tests are feasible to assess lower limb somatosensory function in children with UMN lesions. Discriminative and convergent validity and reliability of the 3 tests were confirmed. Further studies should investigate responsiveness and association with motor function of these outcome measures.

The Variable Influence of Orthotic Management on Hip and Pelvic Rotation in Children with Unilateral Neurogenic Equinus Deformity.

BACKGROUND: Equinus deformity with or without concomitant drop foot is a common finding in children with unilateral spastic cerebral palsy and spastic hemiplegia of other causes. Hypothetically, these deformities may lead to pelvic retraction and hip internal rotation during gait. Orthoses are used to reduce pes equinus during gait and to restore hindfoot first contact. OBJECTIVE: We aimed to investigate whether the use of orthotic equinus correction reduces rotational hip and pelvic asymmetries. METHODS: In a retrospective study, 34 children with unilateral spastic cerebral palsy or spastic hemiplegia of other causes underwent standardized instrumented 3D gait analysis with and without orthotic equinus management. We analyzed the differences in the torsional profile during barefoot walking and while wearing orthoses, as well as investigated the influence of ankle dorsiflexion and femoral anteversion on pelvic and hip kinematics and hip kinetics. RESULTS: Wearing orthoses corrected pes equinus and pelvic internal rotation at the end of the stance phase and in the swing phase compared to barefoot walking. Hip rotation and the rotational moment did not significantly change with orthoses. Orthotic management or femoral anteversion did not correlate to pelvic and hip asymmetry. CONCLUSION: The findings indicate that the correction of the equinus by using orthoses had a variable effect on the asymmetry of the hip and pelvis and internal rotation; both appear to have a multifactorial cause that is not primarily driven by the equinus component.