Evidence of slow and variable choice-stepping reaction time in cancer survivors with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is reported to affect up to 70 % of cancer survivors. Despite evidence that CIPN-related impairments often translate into balance and mobility deficits, the effects on stepping and quality of gait, well-documented risk factors for falls, are unclear. AIMS: (i) Establish choice-stepping reaction time (CSRT) performance in survivors with CIPN compared to young and older healthy controls and people with Parkinson's disease; (ii) document walking stability; (iii) investigate relationships between stepping and gait data to objective and patient-reported outcomes. METHODS: 41 cancer survivors with CIPN (mean (SD) age: 60.8 (9.7) years) who were ≥3months post chemotherapy, performed tests of simple and inhibitory CSRT. Walking stability measures were derived from 3-D accelerometry data during the 6-minute walk test. CIPN was assessed using neurological grading and patient-reported outcome measures (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in CIPN Questionnaire scale EORTC CIPN20). RESULTS: In both stepping tests, CIPN participants performed at the level of adults aged 10 years older and people with mild to moderate Parkinson's disease. Mean (SD) total stepping response times in both CSRT (1160 (190) milliseconds) and inhibitory CSRT (1191 (164) milliseconds) tests were not associated with objective neurological grading but were correlated with increased difficulty feeling the ground. Participants with lower-limb vibration sensation deficit had slower and more variable CSRT times. There were no associations between walking stability and objective measures of CIPN, and limited correlations with the EORTC-CIPN20. CONCLUSIONS: Cancer survivors with CIPN showed deficits in voluntary stepping responses and seemed to compensate for their sensory and motor deficits by walking slower to maintain stability. Objective and patient-reported outcomes of CIPN were correlated with slower and more variable stepping response times. Future studies should aim to identify the causes of the apparent premature decline in cognitive-motor function and develop remediating interventions.

Somatosensory attentional modulations during pain-related movement execution.

Pain serves to protect against bodily threat, and therefore initiates protective responses such as attending toward threat-relevant information. Since pain is often exacerbated by executing movements, these motor actions may serve as cues for pain. Up to date, however, pain-related attention during movement remains largely unexplored. While it has been shown that the preparation of a pain-related movement leads to enhanced processing of somatosensory information, it is unclear how the actual execution of a movement interacts with somatosensory attention. In the current study, we examined whether somatosensory processing is enhanced at a moving body part when the movement is expected to be associated with pain. Participants were asked to execute hand movements which were occasionally followed by a pain stimulus. To measure somatosensory attention, a task-irrelevant, innocuous tactile probe was presented on either hand to evoke a somatosensory evoked potential (SEP). The results showed an elevation of the N120 SEP at the hand performing a potentially painful movement, indicating heightened attention toward tactile information at the threatened moving hand compared to the non-threatened hand. Additionally, the P200 SEP also showed enlarged responses when performing a pain-related movement compared to a no-pain-related movement. These results show that not only the anticipation, but also the execution of pain-related movements, may modulate the processing of somatosensory input, driven by attentional processes.

Development of a sprayable hydrogel formulation for the skin application of therapeutic antibodies.

A formulation of an antibody with antibacterial properties for topical use on Staphylococcal skin infections was developed and characterized. The best formulation was obtained with 1.5% (w/v) sodium carboxymethylcellulose containing 10 mg/ml immunoglobulin. Spraying forces and rheological behavior were measured in order to characterize the hydrogel formulation. The percentage of antibody aggregates in gel as well as the antibody release, folding and target binding properties of the released antibody were analyzed to proof an acceptable shelf life and no significant changes in the activity of the antibody over time. No microbial contamination was observed in the chosen non-airless application container. Functional testing of the topical skin formulation was performed with an ex vivo biopsy culture model of dog skin. Histological analysis indicated efficacy in protection from Staphylococcus mediated skin damage and antibody delivery restricted to the epidermal surface. The results demonstrate that this hydrogel is suitable for cutaneous antibody applications in the medical field.

Searching for bodies: ERP evidence for independent somatosensory processing during visual search for body-related information.

Attention allows us to select relevant information by modulating neural activity within sensory brain areas processing that information. Previous research has shown that visual perception of body stimuli recruits visual cortices together with observer's body representation in somatosensory cortex, which is known for processing body-related information (e.g., haptics, kinematics). However, whether attentional selection of visual body stimuli involves just visual or additional somatosensory areas remains elusive. Here we elicited visual and somatosensory evoked activity during a visual search task, whereby participants searched for target hand images defined by either visual (colour) or bodily (posture) features. In line with previous studies, we found electrophysiological evidence for attentional selection over visual areas (i.e., N2pc) regardless of the feature type. Importantly, after dissociating somatosensory from visual evoked activity, we show that only attentional selection of hand posture - but not hand colour - elicits modulation of somatosensory evoked electrocortical activity over somatosensory cortex. This suggests that attention may not only modulate cortical activity associated with the input-sensory modality (in this case, visual), but, depending on the type of attended information, it may also modulate cortical activity associated with another task-relevant sensory modality (in this case, somatosensory). Overall, our results provide evidence for a flexible attention mechanism that operates according to specific behavioural goals and the information embedded in the percept.

Persistent recruitment of somatosensory cortex during active maintenance of hand images in working memory.

Working memory (WM) supports temporary maintenance of task-relevant information. This process is associated with persistent activity in the sensory cortex processing the information (e.g., visual stimuli activate visual cortex). However, we argue here that more multifaceted stimuli moderate this sensory-locked activity and recruit distinctive cortices. Specifically, perception of bodies recruits somatosensory cortex (SCx) beyond early visual areas (suggesting embodiment processes). Here we explore persistent activation in processing areas beyond the sensory cortex initially relevant to the modality of the stimuli. Using visual and somatosensory evoked-potentials in a visual WM task, we isolated different levels of visual and somatosensory involvement during encoding of body and non-body-related images. Persistent activity increased in SCx only when maintaining body images in WM, whereas visual/posterior regions' activity increased significantly when maintaining non-body images. Our results bridge WM and embodiment frameworks, supporting a dynamic WM process where the nature of the information summons specific processing resources.

Relationship between physical activity and hip pain in persons with and without cam or pincer morphology: a population-based case-control study.

OBJECTIVES: The purpose of the study was to determine if physical activity (PA) is a risk factor for persistent or recurrent hip pain in young and middle-aged persons with and without radiographic findings of cam or pincer morphology (CPM). METHODS: A population sample of persons aged 20-49 with (cases) and without (controls) hip pain in Metro Vancouver, Canada, was selected through random digit dialing (RDD). Self-reported PA was expressed as average energy expenditure (MET-hours) per year, over lifetime. CPM was defined as alpha angle >55°, lateral centre edge angle (LCE) >40°, or positive cross-over sign. RESULTS: Data were obtained for 500 subjects, 269 cases and 231 controls. Prevalence of radiographic CPM was 49% in the cases and 44% in the controls. In a logistic regression model adjusted for age, gender and CPM, total lifetime PA, including occupational, domestic and recreational activities, was significantly associated with hip pain (Odds ratio (OR) 1.30 per 1000 MET-hours, 95% CI 1.15-1.38). The effect of total PA was observed in those with CPM (1.44, 1.17-1.78) and without CPM (1.23, 1.04-1.45). For domestic activities, the association was seen only in those with CPM (significant interaction). When PA was categorized into quartiles, higher levels of PA were associated with a greater risk of pain. CONCLUSIONS: PA, as measured by average energy expenditure over lifetime is a risk factor for hip pain in young and middle-aged persons. For some activities, the risk is likely increased in persons with radiographic evidence of CPM.

The validity of a non-radiologist reader in identifying cam and pincer femoroacetabular impingement (FAI) using plain radiography.

The purpose of this study was to evaluate the validity and reliability of a radiographic diagnosis of femoroacetabular impingement (FAI) by a non-radiologist. Symptomatic FAI is prevalent and thought to be a cause of hip osteoarthritis. However, the diagnosis is often delayed by 1-2 years, in large part because radiographic findings are often subtle and clinicians have been unaware of their significance. The purpose of this study was to evaluate the validity of a radiographic diagnosis of FAI by a non-radiologist. A population-based sample of 701 subjects was recruited in Vancouver, Canada. For the current study, 50 subjects were selected-40 randomly from the population sample and 10 from an orthopedic practice with confirmed FAI. An anterior-posterior pelvis and bilateral Dunn radiographs were acquired and read by a fellowship-trained musculoskeletal radiologist and a third-year medical student who received basic training in radiographic signs of FAI. Three radiographic signs were evaluated: the lateral center edge angle, alpha angle and crossover sign. Validity was assessed using sensitivity and specificity, Bland-Altman limits of agreement and kappa. The sample contained 65% women (n = 31), was 62% Caucasian and 38% Chinese and had a mean age of 38.3 years. For correctly diagnosing FAI, the non-radiologist reader had a sensitivity of 0.83 and specificity of 0.87. Intra-rater κ value was 0.72, and prevalence-adjusted bias-adjusted κ was 0.76. This study provides evidence that a non-radiologist can accurately and reliably identify FAI on plain films.

Transplastomic integration of a cyanobacterial bicarbonate transporter into tobacco chloroplasts.

Improving global yields of agricultural crops is a complex challenge with evidence indicating benefits in productivity are achieved by enhancing photosynthetic carbon assimilation. Towards improving rates of CO2 capture within leaf chloroplasts, this study shows the versatility of plastome transformation for expressing the Synechococcus PCC7002 BicA bicarbonate transporter within tobacco plastids. Fractionation of chloroplast membranes from transplastomic tob(BicA) lines showed that ~75% of the BicA localized to the thylakoid membranes and ~25% to the chloroplast envelope. BicA levels were highest in young emerging tob(BicA) leaves (0.12 µmol m(-2), ≈7mg m(-2)) accounting for ~0.1% (w/w) of the leaf protein. In these leaves, the molar amount of BicA was 16-fold lower than the abundant thylakoid photosystem II D1 protein (~1.9 µmol m(-2)) which was comparable to the 9:1 molar ratio of D1:BicA measured in air-grown Synechococcus PCC7002 cells. The BicA produced had no discernible effect on chloroplast ultrastructure, photosynthetic CO2-assimilation rates, carbon isotope discrimination, or growth of the tob(BicA) plants, implying that the bicarbonate transporter had little or no activity. These findings demonstrate the utility of plastome transformation for targeting bicarbonate transporter proteins into the chloroplast membranes without impeding growth or plastid ultrastructure. This study establishes the span of experimental measurements required to verify heterologous bicarbonate transporter function and location in chloroplasts and underscores the need for more detailed understanding of BicA structure and function to identify solutions for enabling its activation and operation in leaf chloroplasts.

To blink or not to blink: fine cognitive tuning of the defensive peripersonal space.

The blink reflex elicited by the electrical stimulation of the median nerve at the wrist [hand blink reflex (HBR)] is a subcortical, defensive response that is enhanced when the stimulated hand is inside the peripersonal space of the face. Such enhancement results from a tonic, top-down modulation of the excitability of the brainstem interneurons mediating the HBR. Here we aim to (1) characterize the somatotopical specificity of this top-down modulation and investigate its dependence on (2) cognitive expectations and (3) the presence of objects protecting the face, in healthy humans. Experiment 1 showed that the somatotopical specificity of the HBR enhancement is partially homosegmental, i.e., it is greater for the HBR elicited by the stimulation of the hand near the face compared with the other hand, always kept far from the face. Experiment 2 showed that the HBR is enhanced only when participants expect to receive stimuli on the hand close to the face and is thus strongly dependent on cognitive expectations. Experiment 3 showed that the HBR enhancement by hand-face proximity is suppressed when a thin wooden screen is placed between the participants' face and their hand. Thus, the screen reduces the extension of the defensive peripersonal space, so that the hand is never inside the peripersonal space of the face, even in the "near" condition. Together, these findings indicate a fine somatotopical and cognitive tuning of the excitability of brainstem circuits subserving the HBR, whose strength is adjusted depending on the context in a purposeful manner.

Frequency of glenoid chondral lesions on MR arthrography in patients with anterior shoulder instability.

PURPOSE: To describe the frequency of glenoid chondral abnormalities in relation to Hill Sachs (HS) lesions in MR arthrograms of patients with anterior shoulder instability versus controls. Such glenoid lesions can directly impact surgical decision-making and approach, and potentially negatively impact outcome if missed. MATERIALS AND METHODS: Retrospective analysis of direct MR shoulder arthrograms in 165 subjects, (101 with anterior instability/64 controls) was performed independently by 2 blinded musculoskeletal radiologists. Outcome measures were the presence of a HS, anterior labral pathology and glenoid chondral injury. Kappa statistic, Pearson Chi-square and Mann-Whitney analysis were employed for analysis. RESULTS: Inter-observer variability for the presence of HS, labral and chondral lesions was 0.964, 0.965 and 0.858 respectively, with intra-observer variability of 1.0, 0.985 and 0.861 for the principle reader. 58% of patients and 8% of controls had HS (p<0.001). 72% of patients and 25% of controls had anterior labral injury (p<0.001). 36% of instability patients and 10% controls had glenoid chondral lesions (p<0.001). 46% of anterior instability patients with HS defects had chondral injury as opposed to 21% of patients without HS defects (p=0.009). Depth of the HS lesion did not increase the likelihood of a glenoid chondral lesion (p=0.7335). CONCLUSION: In the clinical anterior instability cohort, we demonstrated a statistically significant higher number of HS and glenoid chondral lesions than in controls. In anterior instability patients, the presence of a HS lesion confers a statistically significant greater likelihood of having a glenoid chondral lesion when compared to patients with instability and no HS.

The ABCs of the anterior cruciate ligament: a primer for magnetic resonance imaging assessment of the normal, injured and surgically repaired anterior cruciate ligament.

This article reviews the magnetic resonance imaging (MRI) findings of the native and reconstructed anterior cruciate ligament (ACL). MRI is the most accurate non-invasive modality to evaluate the ACL. Tears of the ACL manifest with direct and indirect signs. The reconstructed ACL has several complications including re-tear and anterior arthrofibrosis, which are also accurately assessed using MRI.

[Aspiration of flexor tendon sheath ganglion guided by ultrasonography. An alternative to blind aspiration or surgery?]. / Die Punktion des Beugesehnenscheidenganglions unter Ultraschallkontrolle. Eine Alternative zur blinden Aspiration oder Operation?

Surgery is generally thought to be the most successful treatment of flexor tendon sheath ganglions. Most previous investigators judge the blind percutaneous aspiration as unreliable. The purpose of this study was to investigate the feasibility and the success rate of percutaneous apiration guided by ultrasonography. We performed percutaneous aspiration under ultrasonographic control in 60 patients with flexor tendon sheath ganglions. Encouraged by our favourable results we can recommend this procedure instead of the blind percutaneous aspiration and even instead of surgery.

Cortical and trabecular bone in the femoral neck both contribute to proximal femur failure load prediction.

UNLABELLED: We examined the contributions of femoral neck cortical and trabecular bone to proximal femur failure load. We found that trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for total bone size and cortical bone mineral content or cortical area. INTRODUCTION: The relative contribution of femoral neck trabecular and cortical bone to proximal femur failure load is unclear. OBJECTIVES: Our primary objective was to determine whether trabecular bone mineral density (TbBMD) contributes to proximal femur failure load after accounting for total bone size and cortical bone content. Our secondary objective was to describe regional differences in the relationship among cortical bone, trabecular bone, and failure load within a cross-section of the femoral neck. MATERIALS AND METHODS: We imaged 36 human cadaveric proximal femora using quantitative computed tomography (QCT). We report total bone area (ToA), cortical area (CoA), cortical bone mineral content (CoBMC), and TbBMD measured in the femoral neck cross-section and eight 45 degrees regions. The femora were loaded to failure. RESULTS AND OBSERVATIONS: Trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for ToA and then either CoBMC or CoA respectively. CoBMC contributed significantly to failure load in all regions of the femoral neck except the posterior region. TbBMD contributed significantly to failure load in all regions of the femoral neck except the inferoanterior, superoposterior, and the posterior regions. CONCLUSION: Both cortical and trabecular bone make significant contributions to failure load in ex vivo measures of bone strength.