No differences in tandem gait performance between male and female athletes acutely post-concussion

ObjectivesTo test whether 1) concussed athletes demonstrate slower tandem gait times compared to controls and 2) concussed female athletes display greater post-injury deficits than males.DesignProspective longitudinalMethodFifty concussed collegiate student-athletes (32% female, age = 20.18 ± 1.27 years) completed tandem gait tests during pre-season (Time 1) and acutely (<72 hours) post-concussion (Time 2), and twenty-five controls (52% female, age = 21.08 ± 2.22 years) completed tandem gait at two time points, 1.96 ± 0.46 days apart. Participants completed four single-task (ST) and dual-task (DT) trials. During DT trials, they simultaneously completed a cognitive assessment. The best ST and DT times were recorded, along with cognitive accuracy, and the change score between the two assessments was calculated. A positive change in tandem gait time was indicative of worsening performance. A 2 × 2 (group*sex) ANOVA was used to examine change between pre-injury and post-injury tests for ST/DT tandem gait time and DT cognitive accuracy.ResultsThe change in tandem gait time from Time 1 to Time 2 was significantly higher for the concussion group relative to controls during both ST (Concussion: 1.36 ± 2.6 seconds, Controls: -1.16 ± 0.8 seconds, p < 0.001) and DT (Concussion: 1.70 ± 3.8 seconds, Controls: -0.94 ± 1.7 seconds, p = 0.002) tandem gait. There were no interactions or main effects of sex for tandem gait time or cognitive accuracy.ConclusionsThere were no sex-specific differences in the change in tandem gait performance among concussed collegiate athletes or controls. However, all concussed participants, regardless of sex, performed significantly worse on tandem gait than male and female controls, who both improved between testing time points.     

Single leg stance control in individuals with symptomatic gluteal tendinopathy

BackgroundLateral hip pain during single leg loading, and hip abductor muscle weakness, are associated with gluteal tendinopathy, but it has not been shown how or whether kinematics in single leg stance differ in those with gluteal tendinopathy.PurposeTo compare kinematics in preparation for, and during, single leg stance between individuals with and without gluteal tendinopathy, and the effect of hip abductor muscle strength on kinematics.MethodsTwenty individuals with gluteal tendinopathy and 20 age-matched pain-free controls underwent three-dimensional kinematic analysis of single leg stance and maximum isometric hip abductor strength testing. Maximum values of hip adduction, pelvic obliquity (contralateral pelvis rise/drop), lateral pelvic translation (ipsilateral/contralateral shift) and ipsilateral trunk lean during preparation for leg lift and average values in steady single leg stance, were compared between groups using an analysis of covariance, with and without anthropometric characteristics and strength as covariates.ResultsIndividuals with gluteal tendinopathy demonstrated greater hip adduction (standardized mean difference (SMD) = 0.70, P = 0.04) and ipsilateral pelvic shift (SMD = 1.1, P = 0.002) in preparation for leg lift, and greater hip adduction (SMD = 1.2, P = 0.002) and less contralateral pelvic rise (SMD = 0.86, P = 0.02) in steady single leg stance than controls. When including strength as a covariate, only between-group differences in lateral pelvic shift persisted (SMD = 1.7, P = 0.01).ConclusionIndividuals with gluteal tendinopathy use different frontal plane kinematics of the hip and pelvis during single leg stance than pain-free controls. This finding is not influenced by pelvic dimension or the potentially modifiable factor of body mass index, but is by hip abductor muscle weakness.     

Vision,visuo-cognition and postural control in Parkinson's disease: An associative pilot study

IntroductionImpaired postural control (PC) is common in patients with Parkinson's disease (PD) and is a major contributor to falls, with significant consequences. Mechanisms underpinning PC are complex and include motor and non-motor features. Research has focused predominantly on motor and sensory inputs. Vision and visuo-cognitive function are also integral to PC but have largely been ignored to date. The aim of this observational cross-sectional pilot study was to explore the relationship of vision and visuo-cognition with PC in PD.MethodsTwelve people with PD and ten age-matched healthy controls (HC) underwent detailed assessments for vision, visuo-cognition and postural control. Vision assessments included visual acuity and contrast sensitivity. Visuo-cognition was measured by visuo-perception (object identification), visuo-construction (ability to copy a figure) and visuo-spatial ability (judge distances and location of object within environment). PC was measured by an accelerometer for a range of outcomes during a 2-min static stance. Spearman's correlations identified significant associations.ResultsContrast sensitivity, visuo-spatial ability and postural control (ellipsis) were significantly impaired in PD (p = 0.017; p = 0.001; and p = 0.017, respectively). For PD only, significant correlations were found for higher visuo-spatial function and larger ellipsis (r = 0.64; p = 0.024) and impaired attention and reduced visuo-spatial function (r = −0.62; p = 0.028).ConclusionsVisuo-spatial ability is associated with PC deficit in PD, but in an unexpected direction. This suggests a non-linear pattern of response. Further research is required to examine this novel and important finding.     

Patellar bracing affects sEMG activity of leg and thigh muscles during stance phase in patellofemoral pain syndrome

BackgroundDecreases in patellofemoral pain symptoms with bracing treatment have been established; but, the mechanisms remain unclear. The purpose of this study was to determine the immediate and long-term effects of the patellar bracing on electromyography (EMG) activity of the Vastus Medialis (VM) and Lateralis (VL), Rectus Femoris, lateral Gastrocnemius, Biceps Femoris and Semitendinosus (ST) muscles during level walking.Methods12 eligible women aged 20–30 years with diagnosis of patellofemoral pain participated in the before and after study. Intervention consisted of 8 weeks of patellar bracing. First, patients were tested without brace, then with a brace, and finally eight weeks later without a brace. Surface EMG activation of the selected muscles during level walking was recorded.ResultsAfter eight weeks of patellar bracing, EMG activity of VM muscle was significantly higher when compared to first session without brace (p = 0.011) at mid-stance sub-phase. Additionally, EMG activity of ST muscle during first session with brace was significantly lower when compared to first session without brace at mid-stance sub-phase (without brace) (p = 0.012). EMG activity of VM muscle after eight weeks of patellar bracing was significantly higher than the first session without brace at late stance and preswing sub-phase (p = 0.013).ConclusionLong-term wearing of patellar bracing increases EMG activity of VM during mid-stance and late stance and preswing sub-phases of gait and immediate effect of patellar brace is decrease of EMG activity of ST muscle during mid-stance.     

Impaired postural control in children with developmental coordination disorder is related to less efficient central as well as peripheral control

BackgroundDevelopmental coordination disorder (DCD) is a neurodevelopmental impairment that affects approximately 6% of children in primary school age. Children with DCD are characterized by impaired postural control. It has yet to be determined what effect peripheral and central neuromuscular control has on their balance control.ObjectiveThe aim of this study was to investigate the underlying mechanisms to impaired postural control in children with DCD using the rambling-trembling decomposition of the center of pressure (CoP).MethodNine children with DCD (9.0 ± 0.5 years, 7 boys, 2 girls) and 10 age- and gender-matched typically developing children (TD) with normal motor proficiency (9.1 ± 0.4 years, 7 boys and 3 girls) performed 3 × 30 s bipedal standing on a force plate in six sensory conditions following the sensory organization procedure. Sway length was measured and rambling-trembling decomposition of CoP was calculated in medio-lateral (ML) and anterior-posterior (AP) direction.ResultsBoth rambling and trembling were larger for the children with DCD in AP (p = 0.031; p = 0.050) and ML direction (p = 0.025; p = 0.007), respectively.ML rambling trajectories did not differ in any conditions with fixed support surface. In ML direction children with DCD had a lower relative contribution of rambling to total sway (p = 0.013).ConclusionThis study showed that impaired postural control in children with DCD is associated with less efficient supraspinal control represented by increased rambling, but also by reduced spinal feedback control or peripheral control manifested as increased trembling.     

Whole-body vibration versus proprioceptive training on postural control in post-menopausal osteopenic women

BackgroundTo prevent falls in the elderly, especially those with low bone density, is it necessary to maintain muscle coordination and balance. The aim of this study was to examine the effect of classical balance training (BAL) and whole-body vibration training (VIB) on postural control in post-menopausal women with low bone density.MethodsSixty-eight subjects began the study and 57 completed the nine-month intervention program. All subjects performed resistive exercise and were randomized to either the BAL- (N = 31) or VIB-group (N = 26). The BAL-group performed progressive balance and coordination training and the VIB-group underwent, in total, four minutes of vibration (depending on exercise; 24–26 Hz and 4–8 mm range) on the Galileo Fitness. Every month, the performance of a single leg stance task on a standard unstable surface (Posturomed) was tested. At baseline and end of the study only, single leg stance, Romberg-stance, semi-tandem-stance and tandem-stance were tested on a ground reaction force platform (Leonardo).ResultsThe velocity of movement on the Posturomed improved by 28.3 (36.1%) (p < 0.001) in the VIB-group and 18.5 (31.5%) (p < 0.001) in the BAL-group by the end of the nine-month intervention period, but no differences were seen between the two groups (p = 0.45). Balance tests performed on the Leonardo device did not show any significantly different responses between the two groups after nine months (p ≥ 0.09).ConclusionsStrength training combined with either proprioceptive training or whole-body vibration was associated with improvements in some, but not all, measures of postural control in post-menopausal women with low bone density. The current study could not provide evidence for a significantly different impact of whole-body vibration or balance training on postural control.     

Sensorimotor posture control in the blind: Superior ankle proprioceptive acuity does not compensate for vision loss

To better understand sensorimotor posture control differences between blind and sighted individuals, we examined the role of ankle joint proprioception and ankle muscle strength on postural control in healthy blind (n = 13, 25–58 years) and age- and sex-matched sighted (n = 15, 20–65 years) volunteers. We measured ankle joint proprioceptive acuity and isokinetic muscle strength in plantarflexion and dorsiflexion using an isokinetic dynamometer. We also assessed postural control performance during quiet bipedal stance with and without sudden postural perturbations, and during quiet unipedal stance. We found that while our blind subjects exhibited significantly better proprioceptive acuity than our sighted subjects their postural control performance was significantly poorer than that of the sighted group with eyes open, and no different from that of the sighted group with eyes closed suggesting that their superior proprioceptive acuity does not translate to improved balance control.     

Altered postural control strategies in quiet standing more than 20 years after rupture of the anterior cruciate ligament

AimTo explore long-term consequences of anterior cruciate ligament (ACL) rupture on postural sway and control strategies during bilateral quiet standing, in subjects treated with or without reconstructive surgery compared to uninjured controls.Method70 individuals who had unilateral ACL rupture 23 ± 2.4 years ago (33 received ACL reconstructive surgery, ACL_R, and 37 had physiotherapy only, ACL_PT) and 33 uninjured matched controls (CTRL) (mean age 46 ± 5.3) stood quietly with eyes closed for 3 min on a firm and on a compliant surface, respectively. Center of pressure (CoP) was registered with a force plate and postural sway was calculated from center of mass (CoM) derived from 3D kinematics. Sway density (SD) analyses of CoP assessed distance and duration of stable phases. The torque controlling postural sway was estimated from CoP-CoM.ResultsComparisons across conditions to CTRL revealed larger CoP-CoM-area in ACL_R (p = 0.017, CI: 10.95, 143.10), but not in ACL_PT. Mean distance between SD-peaks was greater for ACL_R (p < 0.001, CI: 1.73, 5.31) than for ACL_PT (p = 0.006, CI: 0.56, 4.12) relative to CTRL. Duration of SD-peaks was smaller for both ACL_R and ACL_PT (p < 0.001, CI: −4.04, −1.23 and −3.82, −1.03, respectively) compared to CTRL. CoM-area in the ACL-groups did not differ from CTRL.ConclusionsACL-injured subjects demonstrated greater postural control efforts than CTRL but without significant differences in postural sway. Control efforts were thus not directly associated with sway and further research should be focused on variance in postural control strategies.     

Haptic feedback from manual contact improves balance control in people with Parkinson's disease

Parkinson's disease (PD) degrades balance control. Haptic (touch and proprioception) feedback from light contact with a stationary surface inadequate to mechanically stabilize balance improves balance control in healthy people. In this study we tested whether PD impairs use of haptic cues independent of mechanical support to control balance. We measured postural sway in thirteen individuals with PD (H&Y 1–3, median = 2, Q₁ = 2, Q₃ = 2) and thirteen age-matched controls balancing in a widened, sharpened Romberg stance in four conditions: eyes-closed, no manual contact; eyes-closed light-touch contact (<1 N), eyes-closed, unrestricted contact; and eyes-open, no contact. To determine whether PD-severity affects any of these balance strategies, PD participants were tested on- and off-medication, and using the more- and less-affected body side in the stance and manual contact.Individuals with PD simultaneously maintained non-supportive fingertip contact and balance in this task without practice. PD participants swayed more than control participants (ML CP p = 0.010; shoulder p < 0.001), but manual contact reduced sway. Non-supportive manual contact stabilized balance more than vision (p < 0.05). PD-severity factors had no significant effect (p > 0.05).We conclude the effect of PD on balance is not specific to vision or haptic feedback. Nevertheless, haptic cues from manual contact, independent of mechanical support, improve balance control in individuals with PD. We discuss the implication that PD or associated dopaminergic pathways do not directly affect haptic feedback balance control mechanisms, including arm/posture coordination and proprioceptive integration.     

Altered joint moment strategy during stair walking in diabetes patients with and without peripheral neuropathy

AimTo investigate lower limb biomechanical strategy during stair walking in patients with diabetes and patients with diabetic peripheral neuropathy, a population known to exhibit lower limb muscular weakness.MethodsThe peak lower limb joint moments of twenty-two patients with diabetic peripheral neuropathy and thirty-nine patients with diabetes and no neuropathy were compared during ascent and descent of a staircase to thirty-two healthy controls. Fifty-nine of the ninety-four participants also performed assessment of their maximum isokinetic ankle and knee joint moment (muscle strength) to assess the level of peak joint moments during the stair task relative to their maximal joint moment-generating capabilities (operating strengths).ResultsBoth patient groups ascended and descended stairs slower than controls (p < 0.05). Peak joint moments in patients with diabetic peripheral neuropathy were lower (p < 0.05) at the ankle and knee during stair ascent, and knee only during stair descent compared to controls. Ankle and knee muscle strength values were lower (p < 0.05) in patients with diabetic peripheral neuropathy compared to controls, and lower at knee only in patients without neuropathy. Operating strengths were higher (p < 0.05) at the ankle and knee in patients with neuropathy during stair descent compared to the controls, but not during stair ascent.ConclusionPatients with diabetic peripheral neuropathy walk slower to alter gait strategy during stair walking and account for lower-limb muscular weakness, but still exhibit heightened operating strengths during stair descent, which may impact upon fatigue and the ability to recover a safe stance following postural instability.     

Functional fatigue of the hip and ankle musculature cause similar alterations in single leg stance postural control

Isokinetic fatigue protocols have been used to determine the relative importance of lower extremity musculature to the maintenance of balance. However, these protocols are not representative of physical activity, thus the recommendations based on these findings may be inappropriate. Therefore, purpose of this investigation was to use a completely within subjects design to examine the effects of a functional ankle and hip fatigue protocol on postural control during single leg stance. All testing was completed in a health and wellness facility where 18 healthy recreationally active university students (nine female, nine male: 21.2 ± 1.96 years, 72.2 ± 17.8 kg, 170.4 ± 10.12 cm) volunteered to participate. Testing consisted of functionally fatiguing the ankle plantar flexors and dorsiflexors as well as the hip flexors and extensors. Postural control was assessed with two pre- and post-fatigue 20 s trials during single leg stance. Three measures of dynamic balance: the overall, medial/lateral, and anterior/posterior stability index were calculated using the Biodex Stability System at stability level 4. Three separate 2-way repeated measure ANOVAs indicated that fatigue of both the ankle (plantar flexors, dorsiflexors) and hip (flexors, extensors) musculature led to postural control impairments for the medial–lateral stability index (p < 0.01), and anterior–posterior stability index (p < 0.01). However, only ankle fatigue resulted in deficits in the overall stability index were (p < 0.01). Furthermore, neither fatigue protocol impaired single leg stance postural control more than the other (p > 0.05). Our results contradict previous isokinetic fatigue protocol findings, which indicate that proximal musculature fatigue results in greater postural control deficits.     

Double-leg stance and dynamic balance in individuals with functional ankle instability

To investigate whether double-leg stance could reveal balance deficits in subjects with functional ankle instability (FAI) and whether such an assessment of static balance would be correlated with measures of dynamic instability, 16 individuals with FAI and 16 healthy controls participated in this study. Static postural control was tested using double-leg stance (either with the eyes open (EO) or closed (EC)) on a dual-plate force platform. Dynamic balance was evaluated using the Multiple Hop Test (MHT) and a weight-shifting task. FAI subjects were significantly less stable in the anteroposterior direction during double-leg stance (as assessed by velocity of centre of pressure, VCP), both for the EO and EC condition. In the mediolateral direction the VCP values were also higher in FAI, but significance was only found for the EC condition (p = .02). FAI subjects made significantly more balance errors compared to healthy controls (p < .001) on both the affected and less affected leg during MHT. There were no significant differences between FAI and healthy subjects during the weight-shifting task. No relationship was found between double-leg stance and MHT measures (all correlations (r_s) less than .30). This study suggests that static postural control during double-leg stance is impaired in FAI subjects. Although dynamic balance during MHT is also affected, no significant relationship was found between static and dynamic measurements, which indicate that they are most probably related to different aspects of postural control.     

The backwards comparability of wrist worn GENEActiv and waist worn ActiGraph accelerometer estimates of sedentary time in children

ObjectivesTo examine the backward comparability of a range of wrist-worn accelerometer estimates of sedentary time (ST) with ActiGraph 100 count min⁻¹ waist ST estimates.DesignCross-sectional, secondary data analysisMethodsOne hundred and eight 10–11-year-old children (65 girls) wore an ActiGraph GT3X+ accelerometer (AG) on their waist and a GENEActiv accelerometer (GA) on their non-dominant wrist for seven days. GA ST data were classified using a range of thresholds from 23 to 56 mg ST estimates were compared to AG ST 100 count min⁻¹ data. Agreement between the AG and GA thresholds was examined using Cronbach’s alpha, intraclass correlation coefficients (ICC), limits of agreement (LOA), Kappa values, percent agreement, mean absolute percent error (MAPE) and equivalency analysis.ResultsMean AG total ST was 492.4 min over the measurement period. Kappa values ranged from 0.31 to 0.39. Percent agreement ranged from 68 to 69.9%. Cronbach’s alpha values ranged from 0.88 to 0.93. ICCs ranged from 0.59 to 0.86. LOA were wide for all comparisons. Only the 34 mg threshold produced estimates that were equivalent at the group level to the AG ST 100 count min⁻¹ data though sensitivity and specificity values of ∼64% and ∼74% respectively were observed.ConclusionsWrist-based estimates of ST generated using the 34 mg threshold are comparable with those derived from the AG waist mounted 100 count min⁻¹ threshold at the group level. The 34 mg threshold could be applied to allow group-level comparisons of ST with evidence generated using the ActiGraph 100 count min⁻¹ method though it is important to consider the observed sensitivity and specificity results when interpreting findings.     

Increased postural sway in persons with multiple sclerosis during short-term exposure to warm ambient temperatures

BackgroundMultiple sclerosis (MS) is a neurological disease marked by demyelination and axonal loss. Individuals with MS experience increases in clinical signs and symptoms during heat exposure.ObjectiveTo test the hypothesis that moderate heat exposure adversely affects postural sway in individuals with MS.MethodsTen individuals with relapsing-remitting MS (50 ± 8y) and nine controls (47 ± 10y) were examined under a Thermal and a Time Control trial. Following a 30 min thermoneutral baseline (25 °C, 30% relative humidity (RH)), stand tests randomized with eyes open and closed, were performed. For Thermal, subjects were first exposed to 60 min of heating (40 °C, 30%RH) followed by 60 min of cooling (20 °C, 30%RH). For Time Control, subjects remained in a thermoneutral environment throughout. Stand tests were repeated at consistent times in both trials.ResultsNo difference in skin and core temperatures between groups were observed for any trial (P > 0.05). During heating, postural sway was higher in MS relative to control subjects (eyes open, P = 0.03; eyes closed, P = 0.011). No differences in postural sway, regardless of eye status, were observed during the Time Control trial for either group (P > 0.05).ConclusionThese data demonstrate that exposure to a moderate heating environment increases postural sway in patients with MS.     

Clustering of screen time behaviours in adolescents and its association with waist circumference and cardiorespiratory fitness

ObjectivesTo identify the association of clusters of screen time (ST) behaviours with waist circumference (WC) and cardiorespiratory fitness (CRF) among adolescents.DesignCross-sectional study of 574 adolescents (53% girls, 13 years), conducted in 2017.MethodsWaist circumference was measured, a shuttle run was performed to assess CRF, and a questionnaire was applied. Sex, age, socioeconomic status was reported, and daily duration of ST indicators for television viewing, computer use, videogame playing, and cellphone use, in weekdays and weekend days. Latent class analysis was performed to identify typologies of ST behaviours. Mixed-effects linear regressions were used to test the association of ST clusters with WC and CRF.ResultsParticipants’ WC was 66.9 ± 8 cm and CRF was 39.5 ± 4 ml O₂/kg/min. Four clusters were identified: “Low ST” (25%); “High ST” (20%); “Gamers” (17%); and “High cellphone” (39%). No significant associations were found between ST clusters and WC. Maximum oxygen uptake was higher in those in the “Low ST” cluster compared to the other clusters. No significant interactions for sex were observed.ConclusionsTypologies of ST behaviours do not seem to be related to WC; however, those in the Low ST cluster had higher CRF compared to their peers in the other clusters, suggesting that total ST may be more important for CRF than specific indicators.     

Drivers of adolescent adiposity: Evidence from the Australian LOOK study

ObjectivesTo contribute to our understanding of the drivers of body composition during adolescence we sought to employ valid and reliable measures to investigate cross-sectional and longitudinal relationships between percentage body fat (%BF) and physical activity (PA), moderate and vigorous PA (MVPA), sedentary time (ST), total energy, sugar and fat intake.DesignLongitudinal cohort study.MethodsWe measured 556 (289 male) participants at age 12.4 (SD 0.4) years, and 269 (123 males) at 16.3 (SD 0.4) years, for %BF (dual energy X-ray absorptiometry); habitual PA, MVPA, ST (accelerometry); and dietary intake (‘multi-pass’ weekday and weekend 24-h recall). Accounting for likely under-reporting of energy intake (Goldberg cut-off), general linear mixed modelling was used to generate relationships with %BF.ResultsCross-sectional analyses indicated that 10 min more MVPA per day was associated with 0.6 lower %BF (95%CI 0.4–0.9, p < 0.001), and 10 min less ST/day with 0.07 lower %BF (95%CI 0.00–0.15, p < 0.001), independently of PA. In contrast, %BF was unrelated to total energy (p = 0.4), sugar intake (p = 0.2) or fat intake (p = 0.9). Longitudinal analysis showed that if PA was increased by 3% (10,000 counts/day) over the 4 years, then %BF was reduced by 0.08 (95%CI 0.05–0.12, p = 0.06).ConclusionsThe independent relationships of %BF with PA and ST, but absence of relationships with energy, sugar or fat intake, suggest that general community campaigns in a developed country directed at reducing adolescent obesity through modifications to energy intake and output would benefit from a more concerted focus on the latter.     

The influence of Mulligan ankle taping during balance performance in subjects with unilateral chronic ankle instability

Objective: To determine whether Mulligan ankle tape influenced the performance in subjects with unilateral chronic ankle instability (CAI) during static balance; postural sway recovery patterns after hopping and dynamic tracking balance tasks.Design: A cross-sectional, within-subjects experimental study design between 4 ankle conditions (taped; untaped: injured and uninjured).Participants: 20 volunteer recreational athletes with unilateral CAI were recruited. Means and standard deviations highlighted the athletes' characteristics: age = 23 ± 1 years; height = 173.1 ± 2.4 cm; weight = 69.3±3 kg; Functional Ankle Disability Index (FADI) = 93.5 ± 5.1% and FADI Sport = 84.2 ± 9.4%.Interventions: Mulligan ankle taping.Main Outcome Measurements: Static balance (10 s); postural sway recovery patterns after a 30 s functional hop test (immediately, 30 and 60 s); dynamic tracking balance tasks (wandering, target overshoot and reaction-time).Results: Between the four conditions, static balance showed no significant differences (p = 0.792); significant changes occurred in postural sway over time (p < 0.001); no significant changes were reported for the dynamic tracking tasks. Wandering was highly correlated with reaction-time and overshooting (p < 0.01).Conclusion: Under resting and fatigued conditions, Mulligan ankle taping did not impact on the neuromuscular control during static and dynamic balance in subjects with healthy and unstable ankles.     

Optimization of precursor synthesis,formulation and stability of 1′-[18 F]fluoroethyl-β-D-lactose ([18 F]FEL) for preclinical studies in detection of pancreatic cancer

Introduction1′-[¹⁸ F]Fluoroethyl-β-d-lactose ([¹⁸ F]FEL) is a new PET imaging agent for early detection of pancreatic cancer and hepatocellular carcinoma. We previously reported the syntheses of [¹⁸ F]FEL using a bromo- and a tosyl- precursor, followed by an improved method using a nosyl-precursor. However, some steps in the synthesis of the precursor appeared to be problematic producing low yields. Here, we report on an optimized method for synthesis of the precursor and production of [¹⁸ F]FEL; we also describe [¹⁸ F]FEL’s formulation and stability.MethodsAcetylation of d-lactose 1 was performed following a literature procedure to obtain 1′,2′,3′,6′,2,3,4,6-d-lactose octa-acetate 2a/2b. Bromination of 2a/2b was performed using HBr/acetic acid to produce 1'-bromo-2′,3′,6′,2,3,4,6-hepta-O-acetyl-α-d-lactose 3. Coupling of 3 with ethylene glycol was performed in the presence of Ag-tosylate and an excess of ethylene glycol to produce 4a. Compound 4a was reacted with p-nitrophenylsulfonyl chloride to produce the nosyl derivative 5. Radiofluorination of 5 was performed using K[¹⁸ F]fluoride/kryptofix to obtain 6, which was purified by HPLC and hydrolyzed with Na-methoxide to produce 7.ResultsCompound 2 (2a/2b) was obtained in 83% yield as a mixture of two anomeric products. Compound 3 was obtained from the 2a/2b mixture in 80% yield as one product. Coupling of 3 with ethylene glycol produced 4a in 90% yield. Compound 5 was obtained in 64% yield, and radiofluorination of 5 produced 6 in 62.5% ± 7.5% yields (n = 8). Hydrolysis of 6 with Na-methoxide produced 7 in 42.0% ± 7.0% yield (n = 8) from the end of bombardment.ConclusionsA simple 4-step synthesis of the precursor, compound 5, has been achieved with improved yields. A new formulation of [¹⁸ F]FEL has been developed that allows the product to remain stable at ambient temperature for use in animal studies. This improved synthesis of the precursor and stable formulation of [¹⁸ F]FEL should be useful for routine production of the radiotracer and its preclinical and, possibly, clinical applications.     

Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait

IntroductionWe asked whether conflicting visual cues influences gait initiation, gait inhibition and postural control in Parkinson’s disease (PD) between freezers, non-freezers and healthy older adults.MethodsTwenty-five PD participants on dopaminergic medication and 17 healthy older adults were asked to initiate or refrain gait depending on visual cues: green GO (GG), green STOP (GS), red GO (RG), red STOP (RS). Center of pressure (CoP) displacement, variability and mean velocity (VCoP) in the anterior-posterior (AP) and medial-lateral (ML) directions and movement time (MT) were measured.ResultsGait initiation: Both freezers and non-freezers were different from controls in GG and GS. In GS, freezers had smaller CoP displacement and velocity in both directions (p < 0.01), while non-freezers had smaller VCoP in AP and ML (p < 0.01). AP CoP displacement in GS was smaller in freezers compared to non-freezers (p < 0.05). Freezers had longer MT compared to controls in GG and compared to both groups in GS (p < 0.01). Gait inhibition: Controls and freezers had larger CoP displacement variability (p < 0.05) and velocity (p < 0.01) in both directions in RG compared to RS. No differences were seen in non-freezers. Three freezers initiated walking during the RG or RS conditions.ConclusionFreezers were in general slower at initiating gait, displayed a more restrictive postural strategy and were more affected by the conflicting conditions compared to both controls and non-freezers. In freezers, the conflicting visual cues may have increased the cognitive load enough to provoke delays in processing the visual information and implementing the appropriate motor program.