Leukaemia hijacks a neural mechanism to invade the central nervous system.

Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.

Chronic nitric oxide exposure induces prostate cell carcinogenesis, involving genetic instability and a pro-tumorigenic secretory phenotype.

Prostate cancer is a leading cause of cancer death in men. Inflammation and overexpression of inducible nitric oxide synthase (NOS2) have been implicated in prostate carcinogenesis. We aimed to explore the hypothesis that nitric oxide NO exerts pro-tumorigenic effects on prostate cells at physiologically relevant levels contributing to carcinogenesis. We investigated the impact of acute exposure of normal immortalised prostate cells (RWPE-1) to NO on cell proliferation and activation of DNA damage repair pathways. Furthermore we investigated the long term effects of chronic NO exposure on RWPE-1 cell migration and invasion potential and hallmarks of transformation. Our results demonstrate that NO induces DNA damage as indicated by γH2AX foci and p53 activation resulting in a G1/S phase block and activation of 53BP1 DNA damage repair protein. Long term adaption to NO results in increased migration and invasion potential, acquisition of anchorage independent growth and increased resistance to chemotherapy. This was recapitulated in PC3 and DU145 prostate cancer cells which upon chronic exposure to NO displayed increased cell migration, colony formation and increased resistance to chemotherapeutics. These findings indicate that NO may play a key role in the development of prostate cancer and the acquisition of an aggressive metastatic phenotype.

Healthcare worker choice and low back force between self-chosen and highest bed height when boosting a patient up in bed.

Healthcare workers have a high rate of low back injury due to patient handling tasks. These workers receive training in patient handling methods such as adjusting bed height, but often ignore them. In this study, 35 healthcare workers completed patient boosts at a self-chosen bed height and again with the bed in a higher standardised position. Motion capture and force data were collected for analysis. Given the choice, less than half of participants adjusted the bed at all and none of them moved the bed to the highest position (99.1 cm). The self-chosen bed position yielded significantly higher low back force than the higher position at L4-L5 and L5-S1 (p = 0.02, p = 0.01 respectively). Low back forces can be reduced by raising the bed prior to engaging in patient handling tasks, which is a simple step that can reduce forces placed on healthcare workers' low backs. Practitioner summary: Healthcare workers experience high rates of low back pain secondary to patient handling tasks. In this cross-sectional crossover study, healthcare workers consistently chose a low bed height when boosting a patient, which resulted in higher low back loads compared to the highest bed height.

Stepping Back to Minimal Footwear: Applications Across the Lifespan.

Minimal footwear has existed for tens of thousands of years and was originally designed to protect the sole of the foot. Over the past 50 yr, most footwear has become increasingly more cushioned and supportive. Here, we review evidence that minimal shoes are a better match to our feet, which may result in a lower risk of musculoskeletal injury.

Ultrasound Imaging Is Reliable for Tibialis Posterior Size Measurements.

OBJECTIVES: The tibialis posterior (TP) is a vital muscle for controlling the medial longitudinal arch of the foot during weight-bearing activities. Dysfunction of this muscle is associated with a variety of pathologic conditions; thus, it is important to reliably assess its morphologic characteristics. Ultrasound (US) has been used to assess characteristics of TP tendons but not the muscle cross-sectional area (CSA). The purpose of this study was to establish a reliable US technique to measure the TP CSA and thickness. METHODS: Twenty-three healthy volunteers participated. We evaluated the CSA and thickness at 4 measurement locations (anterior and posterior views at both 30% and 50% of the shank length). RESULTS: The participants included 12 female and 11 male volunteers (mean age ± SD, 31.23 ± 14.93 years). Excellent reliability was seen for the CSA and thickness at all locations (intraclass correlation coefficients, 0.988-0.998). Limits of agreement (LoA) and standard errors of the measurement (SEMs) were slightly lower at the 30% locations (LoA at 30%, 4.6-9.2; LoA at 50%, 6.4-9.7; SEM at 30%, 0.03-0.05; SEM at 50%, 0.04-0.07). Strong correlations were seen between anterior and posterior measurements of the CSA (30%, r = 0.99; P < .0001; 50%, r = 0.94; P < .0001) and thickness (30%, r = 0.98; P < .0001; 50%, r = 0.95; P = .0001). CONCLUSIONS: Based on these results, the TP can be measured accurately with US at any of the tested locations. Due to the ease of collection and the quality of the data, we recommend the anterior view at 30% of the shank length to measure the CSA. The ability to assess muscle size of the TP will aid in a variety of medical and research applications.

Use of Cine Loops and Structural Landmarks in Ultrasound Image Processing Improves Reliability and Reduces Error in the Assessment of Foot and Leg Muscles.

OBJECTIVES: Foot and leg muscle strength and size are crucial to proper function. It is important to assess these characteristics reliably. Our primary objective was to compare the measurement of still images to cine loops. The secondary purpose was to determine interoperator and intraoperator reliability between operators of different experience levels using video clips and internal and external landmarks. METHODS: Twelve healthy volunteers participated in our study. Internal (navicular tuberosity) and external (lateral leg length at 30% and 50% from the knee joint line) landmarks were used. Two operators each captured and later measured still and cine loop images of selected foot and leg muscles. RESULTS: The 12 participants included 8 male and 4 female volunteers (mean age ± SD, 23.5 ± 1.9 years). Good to excellent intraoperator and interoperator reliability was seen (intraclass correlation coefficient range of 0.946-0.998). The use of cine loops improved the intraclass correlation coefficients for both intraoperator and interoperator reliability (0.5%-4% increases). The use of cine loops decreased the intraoperator standard error of the measurement and limits of agreement of the novice operator (decreases of 45%-73% and 24%-51%, respectively), and these became comparable to those of experienced operators using still images. The interoperator standard errors of the measurement dropped by 42% to 53%, whereas the limits of agreement dropped by 27% to 40%. No substantial changes were noted in the tibialis anterior across reliability metrics. CONCLUSIONS: Improved protocols that take advantage of using internal bony landmarks and cine loops during both the image-gathering and measurement processes improve the reliability of research examining muscle size changes in the lower leg or foot associated with muscle changes due to exercise, injury, disuse, or disease.

IceSense Proof of Concept: Calibrating an Instrumented Figure Skating Blade to Measure On-Ice Forces.

Competitive figure skaters often suffer from overuse injuries, which may be due to the high impact forces endured during jump repetitions performed in practice and competition. However, to date, forces during on-ice figure skating have not been quantified due to technological limitations. The purpose of this study was to determine the optimal calibration procedure for a previously developed instrumented figure skating blade (IceSense). Initial calibration was performed by collecting data from the blade while 11 skaters performed off-ice jumps, landing on a force plate in the lab. However, mean peak force measurements from the blade were greater than the desired error threshold of ±10%. Therefore, we designed a series of controlled experiments which included measuring forces from a load cell rigidly attached to the top of the blade concurrently with strain data from the strain gauges on the blade. Forces were applied to the blade by adding weight to a drop tower or by manually applying force in a quasi-static manner. Both methods showed similar accuracy, though using the drop tower allowed precise standardization. Therefore, calibration was performed using the weighted drop method. This calibration was applied to strain gauge data from out-of-sample drop trials, resulting in acceptable estimates of peak force (less than 10% error). Using this calibration, we collected data on one figure skater and present results from an exemplar on-ice double flip jump. Using the IceSense device to quantify on-ice forces in a research setting may help inform training, technique, and equipment design.

Functional assessments of foot strength: a comparative and repeatability study.

BACKGROUND: Evaluating the strength of the small muscles of the foot may be useful in a variety of clinical applications but is challenging from a methodology standpoint. Previous efforts have focused primarily on the functional movement of toe flexion, but clear methodology guidelines are lacking. A novel foot doming test has also been proposed, but not fully evaluated. The purposes of the present study were to assess the repeatability and comparability of several functional foot strength assessment techniques. METHODS: Forty healthy volunteers were evaluated across two testing days, with a two-week doming motion practice period between them. Seven different measurements were taken using a custom toe flexion dynamometer (seated), custom doming dynamometer (standing), and a pressure mat (standing). Measurements from the doming dynamometer were evaluated for reliability (ICCs) and a learning effect (paired t-tests), while measurements from the toe flexion dynamometer and pressure mat were evaluated for reliability and comparability (correlations). Electromyography was also used to descriptively assess the extent of muscle isolation in all measurements. RESULTS: Doming showed excellent within-session reliability (ICCs > 0.944), but a clear learning effect was present, with strength (p < 0.001) and muscle activity increasing between sessions. Both intrinsic and extrinsic muscles were engaged during this test. All toe flexion tests also showed excellent reliability (ICCs > 0.945). Seated toe flexion tests using the dynamometer were moderately correlated to standing toe flexion tests on a pressure mat (r > 0.54); however, there were some differences in muscle activity. The former may better isolate the toe flexors, while the latter appeared to be more functional for many pathologies. On the pressure mat, reciprocal motion appeared to display slightly greater forces and reliability than isolated toe flexion. CONCLUSIONS: This study further refines potential methodology for foot strength testing. These devices and protocols can be duplicated in the clinic to evaluate and monitor rehabilitation progress in clinical populations associated with foot muscle weakness.

Validity and Reliability of Standing Posture Measurements Using a Mobile Application.

OBJECTIVE: The purpose of this study was to evaluate the validity and reliability of standing posture assessments in asymptomatic men using the PostureScreen Mobile (PSM) iOS application. METHODS: The standing posture of 50 asymptomatic male participants (24.04 ± 1.81 years) was measured during 3 trials on the same day. The following 10 measurements using the PSM app were compared to the criterion VICON 3-dimensional analysis: from the frontal plane, shift and tilt of the head, shoulders, and hips; and from the sagittal plane, shift of the head, shoulders, hips, and knees. We used Bayesian methods to analyze the data. RESULTS: Compared with the VICON measurements, PSM assessments of head tilt, shoulder tilt and shift, and hip tilt and shift in the frontal plane were biased. In the sagittal plane, PSM measurements of shoulder, hip, and knee shift were biased. Only head shift in the frontal and sagittal planes were comparable between the VICON and the PSM. The VICON and PSM had similar intraclass correlations in 6 of 10 measurements. The PSM assessments of head shift and tilt and shoulder tilt in the sagittal plane were significantly less reliable than with VICON. CONCLUSION: The use of the PSM app introduced significant bias in postural measurements in the frontal and sagittal plane. Until further research reports additional validity and reliability data of the PSM app, we suggest caution in the use of PSM app when highly accurate postural assessments are necessary.

Secreted factors from metastatic prostate cancer cells stimulate mesenchymal stem cell transition to a pro-tumourigenic 'activated' state that enhances prostate cancer cell migration.

Mesenchymal stem cells (MSCs) are a heterogeneous population of multipotent cells that are capable of differentiating into osteocytes, chondrocytes and adipocytes. Recently, MSCs have been found to home to the tumour site and engraft in the tumour stroma. However, it is not yet known whether they have a tumour promoting or suppressive function. We investigated the interaction between prostate cancer cell lines 22Rv1, DU145 and PC3, and bone marrow-derived MSCs. MSCs were 'educated' for extended periods in prostate cancer cell conditioned media and PC3-educated MSCs were found to be the most responsive with a secretory profile rich in pro-inflammatory cytokines. PC3-educated MSCs secreted increased osteopontin (OPN), interleukin-8 (IL-8) and fibroblast growth factor-2 (FGF-2) and decreased soluble fms-like tyrosine kinase-1 (sFlt-1) compared to untreated MSCs. PC3-educated MSCs showed a reduced migration and proliferation capacity that was dependent on exposure to PC3-conditioned medium. Vimentin and α-smooth muscle actin (αSMA) expression was decreased in PC3-educated MSCs compared to untreated MSCs. PC3 and DU145 education of healthy donor and prostate cancer patient-derived MSCs led to a reduced proportion of FAP+ αSMA+ cells contrary to characteristics commonly associated with cancer associated fibroblasts (CAFs). The migration of PC3 cells was increased toward both PC3-educated and DU145-educated MSCs compared to untreated MSCs, while DU145 migration was only enhanced toward patient-derived MSCs. In summary, MSCs developed an altered phenotype in response to prostate cancer conditioned medium which resulted in increased secretion of pro-inflammatory cytokines, modified functional activity and the chemoattraction of prostate cancer cells.

Mesenchymal stem cells: key players in cancer progression.

Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour. The key question is how they interact there. MSCs may interact with tumour cells through paracrine signalling. On the other hand, MSCs have the capacity to differentiate to various cell types such as osteocytes, chondrocytes and adipocytes and it is possible that MSCs differentiate at the site of the tumour. More recently it has been shown that cross-talk between tumour cells and MSCs has been shown to increase metastatic potential and promote epithelial-to-mesenchymal transition. This review will focus on the role of MSCs in tumour development at various stages of progression from growth of the primary tumour to the establishment of distant metastasis.

Running decreases knee intra-articular cytokine and cartilage oligomeric matrix concentrations: a pilot study.

INTRODUCTION: Regular exercise protects against degenerative joint disorders, yet the mechanisms that underlie these benefits are poorly understood. Chronic, low-grade inflammation is widely implicated in the onset and progression of degenerative joint disease. PURPOSE: To examine the effect of running on knee intra-articular and circulating markers of inflammation and cartilage turnover in healthy men and women. METHODS: Six recreational runners completed a running (30 min) and control (unloaded for 30 min) session in a counterbalanced order. Synovial fluid (SF) and serum samples were taken before and after each session. Cytokine concentration was measured in SF and serum using a multiplexed cytokine magnetic bead array. Ground reaction forces were measured during the run. RESULTS: There were no changes in serum or SF cytokine concentration in the control condition. The cytokine GM-CSF decreased from 10.7 ± 9.8 to 6.2 ± 5.9 pg/ml pre- to post-run (p = 0.03). IL-15 showed a trend for decreasing concentration pre- (6.7 ± 7.5 pg/ml) to post-run (4.3 ± 2.7 pg/ml) (p = 0.06). Changes in IL-15 concentration negatively correlated with the mean number of foot strikes during the run (r 2 = 0.67; p = 0.047). The control condition induced a decrease in serum COMP and an increase in SF COMP, while conversely the run induced an increase in serum COMP and a decrease in SF COMP. Changes in serum and SF COMP pre- to post-intervention were inversely correlated (r 2 = 0.47; p = 0.01). CONCLUSIONS: Running appears to decrease knee intra-articular pro-inflammatory cytokine concentration and facilitates the movement of COMP from the joint space to the serum.

The Effect of Training in Minimalist Running Shoes on Running Economy.

The purpose of this study was to examine the effect of minimalist running shoes on oxygen uptake during running before and after a 10-week transition from traditional to minimalist running shoes. Twenty-five recreational runners (no previous experience in minimalist running shoes) participated in submaximal VO2 testing at a self-selected pace while wearing traditional and minimalist running shoes. Ten of the 25 runners gradually transitioned to minimalist running shoes over 10 weeks (experimental group), while the other 15 maintained their typical training regimen (control group). All participants repeated submaximal VO2 testing at the end of 10 weeks. Testing included a 3 minute warm-up, 3 minutes of running in the first pair of shoes, and 3 minutes of running in the second pair of shoes. Shoe order was randomized. Average oxygen uptake was calculated during the last minute of running in each condition. The average change from pre- to post-training for the control group during testing in traditional and minimalist shoes was an improvement of 3.1 ± 15.2% and 2.8 ± 16.2%, respectively. The average change from pre- to post-training for the experimental group during testing in traditional and minimalist shoes was an improvement of 8.4 ± 7.2% and 10.4 ± 6.9%, respectively. Data were analyzed using a 2-way repeated measures ANOVA. There were no significant interaction effects, but the overall improvement in running economy across time (6.15%) was significant (p = 0.015). Running in minimalist running shoes improves running economy in experienced, traditionally shod runners, but not significantly more than when running in traditional running shoes. Improvement in running economy in both groups, regardless of shoe type, may have been due to compliance with training over the 10-week study period and/or familiarity with testing procedures. Key pointsRunning in minimalist footwear did not result in a change in running economy compared to running in traditional footwear prior to 10 weeks of training.Both groups (control and experimental) showed an improvement in running economy in both types of shoes after 10 weeks of training.After transitioning to minimalist running shoes, running economy was not significantly different while running in traditional or minimalist footwear.

New Perspectives on Foot Segment Forces and Joint Kinetics-Integrating Plantar Shear Stresses and Pressures with Multi-segment Foot Modeling.

The role of the many small foot articulations and plantar tissues in gait is not well understood. While kinematic multi-segment foot models have increased our knowledge of foot segmental motions, the integration of kinetics with these models could further advance our understanding of foot mechanics and energetics. However, capturing and effectively utilizing segmental ground reaction forces remains challenging. The purposes of this study were to (1) develop methodology to integrate plantar pressures and shear stresses with a multi-segment foot model, and (2) generate and concisely display key normative data from this combined system. Twenty-six young healthy adults walked barefoot (1.3 m/s) across a pressure/shear sensor with markers matching a published 4-segment foot model. A novel anatomical/geometric template-based masking method was developed that successfully separated regions aligned with model segmentation. Directional shear force plots were created to summarize complex plantar shear distributions, showing opposing shear forces both between and within segments. Segment centers of pressure (CoPs) were shown to be primarily stationary within each segment, suggesting that forward progression in healthy gait arises primarily from redistributing weight across relatively fixed contact points as opposed to CoP movement within a segment. Inverse dynamics-based normative foot joint moments and power were presented in the context of these CoPs to aid in interpretation of tissue stresses. Overall, this work represents a successful integration of motion capture with direct plantar pressure and shear measurements for multi-segment foot kinetics. The presented tools are versatile enough to be used with other models and contexts, while the presented normative database may be useful as a baseline comparison for clinical work in gait energetics and efficiency, balance, and motor control. We hope that this work will aid in the advancement and availability of kinetic MSF modeling, increase our knowledge of foot mechanics, and eventually lead to improved clinical diagnosis, rehabilitation, and treatment.

The influence of bed height as a percentage of participant height on low back forces when boosting a patient up in bed.

BACKGROUND: Repositioning patients is a frequent task for healthcare workers causing substantial stress to the low back. Patient handling methodologies that reduce low back load should be used. Some studies have observed the effect of bed height on back forces using a limited range of heights. This study details a wider range. OBJECTIVE: The aim of this study was to discover an optimal bed height for reducing low back force when boosting a patient. METHODS: 11 university students and local residents participated by completing a series of boosts with a 91.6 kg research assistant acting as dependent. The bed was adjusted 3% of participant height and 3 boosts were completed at each height which resulted in 8-10 different bed heights depending on the height of the participant. Motion and force data were collected to estimate low back forces via 3DSSPP. Pearson's R was performed to observe the correlation between caregiver height and low back forces. RESULTS: There were significant negative correlations between bed height and low back compression force at L4-L5 (r = -0.676, p = <0.001) and L5-S1 (r = -0.704, p = <0.001). There were no significant correlations with any shear forces. CONCLUSION: The highest bed height led to decreased low back compression forces regardless of participant height, but there was not a significant difference in shear forces. Thus, healthcare workers may experience less low back stress with the bed at a higher height. There may be a force tradeoff between the low back and other parts of the body that needs further exploration. Healthcare workers need to be made aware of the implications of adjusting the environment when performing patient handling tasks.

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information.

Many of the conditions for the safe and effective use of new molecular entities (NMEs) are understood at the time of initial drug approval. However, some remaining knowledge gaps can be addressed after drug approval through postmarketing requirements (PMRs) or commitments (PMCs) established by the US Food and Drug Administration (FDA). Our objective was to conduct an assessment of clinical pharmacology-related PMRs and PMCs established at the time of approval and evaluate the impact of fulfilled PMRs and PMCs on prescription information (PI). This analysis included clinical pharmacology-related PMRs and PMCs established for NMEs approved between 2009 and 2020. Of the 1171 PMRs and PMCs, over one-third were clinical pharmacology-related. Of these, 46% were to evaluate drug interactions, 16% were to evaluate drug dosing in patients with hepatic impairment, and 10% were related to dose. The majority (57%) of PMRs and PMCs were fulfilled at the time of analysis, with a median time to fulfillment of approximately 2.3 years. The majority (94%) of the fulfilled PMRs and PMCs, either with or without a PI revision, resulted in new or modified instructions for use or supported existing instructions for use. This is the first time that clinical pharmacology-related PMRs and PMCs have been catalogued and analyzed to understand their impact on PI. An understanding of the knowledge gaps that exist at the time of drug approval could inform the most effective and efficient methods for evidence generation prior to and after new drug approval.

Up in the air: the efficacy of weighted gloves in figure skating jumps.

Successful performance of difficult, multi-revolution jumps is a critical aspect of singles and pairs figure skating. Key determinants of quality jumps include jump height, angular momentum at takeoff (L_BodyTO) and total body moment of inertia (I_Body). The purpose of this study was to determine the effect of weighted gloves on L_BodyTO of figure skating jumps. Kinematic data was collected from thirteen skaters during on-ice testing sessions conducted before and after one week of training with weighted gloves. A one-way repeated measures ANOVA was used to compare metrics from jumps performed pre-training without weights (PreNW), post-training without weights (PostNW) and post-training with weights (PostW). No significant differences were found between kinematics in PreNW and PostNW. Skaters did not pull their arms in as tightly while wearing the weighted gloves (distance from the wrists to the axis of rotation were 13.6% and 12.1% greater in PostW than PreNW and PreW, respectively). A post hoc simulation showed that the added mass affected I_Body in the air. While theoretical evidence supports the use of weighted gloves in figure skating jumps, compensations negated their effectiveness in jumps the skaters could already perform well. Optimal implementation may be when skaters are learning new jumps.

Contributions of Intrinsic and Extrinsic Foot Muscles during Functional Standing Postures.

Purpose: Maintaining balance during static standing postures requires the coordination of many neuromuscular mechanisms. The role of the intrinsic and extrinsic foot muscles in this paradigm has yet to be clearly defined. The purpose of this study was to explore foot muscle activation during static phases on common weight-bearing tasks of varying loads and balance demands. Methods: Twenty healthy young adults performed 6 standing postures (single-limb and double-limb stand, squat, and heel raise) with one foot on a force plate. Muscle activity was recorded from the abductor hallucis, flexor hallucis longus and brevis, and tibialis posterior using intramuscular electrodes; surface electrodes were used to record activity from the peroneus longus and tibialis anterior. Two-way repeated measures ANOVA (2 loading conditions × 3 postures) were run to compare muscle activation and center of pressure velocity. Results: Intrinsic foot muscle activity increased as loading and postural demand increased; however, the specific effects varied for each of the extrinsic foot muscles. Conclusions: These results suggest that the intrinsic foot muscles play an important role in maintaining static balance. Strengthening intrinsic and extrinsic foot muscles may help increase stability in people who have weak toe flexors or who suffer from a variety of foot pathologies.

The influence of the windlass mechanism on kinematic and kinetic foot joint coupling.

BACKGROUND: Previous research shows kinematic and kinetic coupling between the metatarsophalangeal (MTP) and midtarsal joints during gait. Studying the effects of MTP position as well as foot structure on this coupling may help determine to what extent foot coupling during dynamic and active movement is due to the windlass mechanism. This study's purpose was to investigate the kinematic and kinetic foot coupling during controlled passive, active, and dynamic movements. METHODS: After arch height and flexibility were measured, participants performed four conditions: Seated Passive MTP Extension, Seated Active MTP Extension, Standing Passive MTP Extension, and Standing Active MTP Extension. Next, participants performed three heel raise conditions that manipulated the starting position of the MTP joint: Neutral, Toe Extension, and Toe Flexion. A multisegment foot model was created in Visual 3D and used to calculate ankle, midtarsal, and MTP joint kinematics and kinetics. RESULTS: Kinematic coupling (ratio of midtarsal to MTP angular displacement) was approximately six times greater in Neutral heel raises compared to Seated Passive MTP Extension, suggesting that the windlass only plays a small kinematic role in dynamic tasks. As the starting position of the MTP joint became increasingly extended during heel raises, the amount of negative work at the MTP joint and positive work at the midtarsal joint increased proportionally, while distal-to-hindfoot work remained unchanged. Correlations suggest that there is not a strong relationship between static arch height/flexibility and kinematic foot coupling. CONCLUSIONS: Our results show that there is kinematic and kinetic coupling within the distal foot, but this coupling is attributed only in small measure to the windlass mechanism. Additional sources of coupling include foot muscles and elastic energy storage and return within ligaments and tendons. Furthermore, our results suggest that the plantar aponeurosis does not function as a rigid cable but likely has extensibility that affects the effectiveness of the windlass mechanism. Arch structure did not affect foot coupling, suggesting that static arch height or arch flexibility alone may not be adequate predictors of dynamic foot function.

Current trends and applications in endoscopy for otology and neurotology.

There has been a rapid increase in endoscopic ear surgery for the management of middle ear and lateral skull base disease in children and adults over the last decade. In this review paper, we discuss the current trends and applications of the endoscope in the field of otology and neurotology. Advantages of the endoscope include excellent ergonomics, compatibility with pediatric anatomy, and improved access to the middle ear through the external auditory canal. Transcanal endoscopic ear surgery has demonstrated comparable outcomes in the management of cholesteatoma, tympanic membrane perforations, and otosclerosis as compared to microscopic approaches, while utilizing less invasive surgical corridors and reducing the need for postauricular incisions. When a postauricular approach is required, the endoscopic-assisted transmastoid approach can avoid a canal wall down mastoidectomy in cases of cholesteatoma. The endoscope also has utility in treatment of superior canal dehiscence and various skull base lesions including glomus tumors, meningiomas, and vestibular schwannomas. Outside of the operating room, the endoscope can be used during examination of the outer and middle ear and for debridement of complex mastoid cavities. For these reasons, the endoscope is currently poised to transform the field of otology and neurotology.