Biomechanical effectiveness of controlled ankle motion boots: A systematic review and narrative synthesis

Introduction Controlled ankle motion (CAM) boots are a below-knee orthotic device prescribed for the management of foot and ankle injuries to reduce ankle range of motion (RoM) and offload the foot and ankle whilst allowing continued ambulation during recovery. There is a lack of clarity within the current literature surrounding the biomechanical understanding and effectiveness of CAM boots. Aims To summarise the biomechanical effects of CAM boot wear as an orthotic for restricting ankle RoM and offloading the foot. Methods A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. All papers were independently screened by two authors for inclusion. Methodological quality was appraised using Joanna Briggs Critical Appraisal checklists. A narrative synthesis of all eligible papers was produced. Results Thirteen studies involving 197 participants (113 male and 84 female) were included. All studies were quasi-randomised and employed a within-study design, of which 12 studies included a control group and a range of CAM boots were investigated. CAM boots can be seen to restrict ankle RoM, however, neighboring joints such as the knee and hip do have kinetic and kinematic compensatory alterations. Plantar pressure of the forefoot is effectively redistributed to the hindfoot by CAM boots. Conclusion The compensatory mechanisms at the hip and knee joint during CAM boot wear could explain the secondary site pain often reported in patients, specifically at the ipsilateral knee and contralateral hip. Although CAM boots can be used to restrict ankle motion, this review has highlighted a lack of in-boot kinematic analyses during CAM boot use, where tracking markers are placed on the anatomical structure rather than on the boot, or through video fluoroscopy, urging the need for a more robust methodological approach to achieve this. There is a need for studies to assess the biomechanical alterations caused by CAM boots in populations living with foot and ankle pathologies. Future research, adopting a longitudinal study design, is required to fully understand the effectiveness of CAM boots for rehabilitation

Walking in a controlled ankle motion (CAM) boot: In-boot measurement of joint kinematics and kinetics

Research investigating ankle function during walking in a controlled ankle motion (CAM) boot has either placed markers on the outside of the boot or made major alterations to the structure of the CAM boot to uncover key landmarks. The aim of this study was to quantify joint kinematics and kinetics using “in-boot” skin markers whilst making only minimal structural alterations. Seventeen healthy participants walked at their preferred walking speed in two conditions: (1) in standard athletic trainers (ASICS patriot 8, ASICS Oceania Pty Ltd, USA), and (2) using a hard-cased CAM boot (Rebound® Air Walker, Össur, Iceland) fitted on the right foot. Kinematic measurements revealed that CAM boots restrict sagittal plane ankle range of motion to less than 5°, and to ∼3° in the frontal plane, which is a reduction of 85% and 73% compared to standard footwear, respectively (p < 0.001). This ankle restriction resulted in a reduction of ankle joint total limb work contribution from 38 ± 5% in normal footwear to 13 ± 4% in the CAM boot (p < 0.001). This study suggests that CAM boots do restrict the ankle joint’s ability to effectively perform work during walking, which leads to compensatory mechanisms at the ipsilateral and contralateral hip and knee joints. Our findings align with previous research that employed “on-boot” kinematic measurements, so we conclude that in-boot approaches do not offer any benefit to the researcher and instead, on-boot measurements are suitable

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

FUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. Our results unravel new pathomechanisms of FUS-ALS and identify a novel paradigm by which mutations in one RBP favor the formation of condensates sequestering other RBPs, affecting crucial biological functions, such as protein translation

Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy.</p> <p>Methods</p> <p>DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean <it>Z</it>-scores, areal BMD (g/cm²), calculated volumetric BMD (g/cm³) and bone mineral content (BMC, g) were determined.</p> <p>Results</p> <p>Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm²(95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm³(95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80.</p> <p>Conclusions</p> <p>The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.</p

Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells:Comparison with human bone marrow and adipose-derived mesenchymal stem cells

We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair

Phase-specific and lifetime costs of cancer care in Ontario, Canada

BACKGROUND: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada. METHODS: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092). Patients were linked to treatment data from Cancer Care Ontario and administrative health care databases at the Institute for Clinical and Evaluative Sciences. Net costs (i.e., cost difference between patients and matched non-cancer control subjects) were estimated by phase of care and sex, and used to estimate 5-year and lifetime costs. RESULTS: Mean net costs of care (2009 CAD) were highest in the initial (6 months post-diagnosis) and terminal (12 months pre-death) phases, and lowest in the (3 months) pre-diagnosis and continuing phases of care. Phase-specific net costs were generally lowest for melanoma and highest for brain cancer. Mean 5-year net costs varied from less than $25,000 for melanoma, thyroid and testicular cancers to more than$60,000 for multiple myeloma and leukemia. Lifetime costs ranged from less than $55,000 for lung and liver cancers to over$110,000 for leukemia, multiple myeloma, lymphoma and breast cancer. CONCLUSIONS: Costs of cancer care are substantial and vary by cancer site, phase of care and time horizon analyzed. These cost estimates are valuable to decision makers to understand the economic burden of cancer care and may be useful inputs to researchers undertaking cancer-related economic evaluations

Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement

BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging. METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung. FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar. CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level