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.

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.

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.

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.

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.

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.

YAC/BAC contig spanning the MHC class III region of cattle.

A contig of the class III region of the bovine major histocompatibility complex (MHC) was established from bacterial and yeast artificial chromosomes using PCR and BAC-end sequencing. The marker content of individual clones was determined by gene and BAC-end specific PCR, and the location of genes and BAC-ends was confirmed analyzing somatic hybrid cells. A comparative analysis indicated that the content and order of MHC class III genes is strongly conserved between cattle and other mammalian species. Fluorescence in situ hybridization localized the bovine class III region to BTA23q21-->q22. The results show that the collection of sequenced BAC-ends is a powerful resource for generating high-resolution comparative chromosome maps.

Sparing of cognitive function in mild hypoglycemia: dissociation from the neuroendocrine response.

Central nervous system function during insulin-induced reductions in plasma glucose was studied by measuring plasma epinephrine concentrations and testing cognitive function. Mild glucose reduction [mean plasma glucose, 62 +/- 3 (+/- SEM) mg/dL (3.4 +/- 0.2 mmol/L)] was induced with an iv insulin infusion at the rate of 40 mU/kg.h for 180 min in 7 normal subjects. Despite a marked increase in mean plasma epinephrine concentrations, which peaked at 426 +/- 68 pm/mL (2325 +/- 371 pmol/mL; P less than 0.001), no significant differences in cognitive function occurred as determined by a series of trail-making tests compared with the results of serial tests in a group of 17 control subjects. In contrast, when hypoglycemia was induced (plasma glucose, less than 42 mg/dL; 2.3 mmol/L) by bolus injection of insulin in 4 normal subjects, cognitive function was impaired in every subject, as demonstrated by a delay in completion of the trail-making test. The mean completion time was prolonged to 107 +/- 16% of the baseline at the time of hypoglycemia vs. 74 +/- 4% in control subjects (P less than 0.01). These findings suggest that cognitive function may be spared during mild plasma glucose reductions and is dissociated from the neuroendocrine adrenergic response that is activated under these conditions. This dissociation may be part of a homeostatic process in which overall brain function is maintained during glucoprivation, although counterregulation has already been triggered to prevent a further decrease in plasma glucose.

Calcitonin in nonthyroidal cancer.

A blind prospective study was undertaken to determine the use of calcitonin (CT) as a tumor marker. After final diagnosis, results revealed elevated plasma CT (greater than 150 pg/ml) in common cancers as follows: lung, 38%; colon, 24%; breast, 38%; pancreas, 42%; and gastric, 30%. Fifty-eight percent of oat cell carcinomas were associated with elevated plasma CT. CT immunoreactivity was detected in 14% of tumor extracts and was not detectable in normal tissue other than thyroid. Hypercalcemia was not the cause of hypercalcitonemia. Incubation studies of [125I]human CT in cancer plasma and tumor extracts demonstrated that measurements were not an artifact of label degradation. In a survey of control patients with nonneoplastic disease, elevated CT was noted in renal failure, acute gastrointestinal bleeding, and in some patients with chronic obstructive lung disease. In conclusion, plasma CT is elevated in a substantial proportion of common neoplasms and is useful as a tumor marker.

A glucose reduction challenge in the differential diagnosis of fasting hypoglycemia: a two-center study.

Investigation of patients with suspected or proven hypoglycemia is often a time-consuming and expensive process. We describe a glucose reduction challenge test which may be useful as an out-patient screening procedure. Insulin is infused for 3 h at 40 mU/kg.h. Plasma glucose was monitored at the bedside during the test, and blood samples were collected for measurement of C-peptide. Responses were examined in 17 normal controls, and 6 patients with insulinomas. In normal subjects, mean plasma glucose fell to a plateau value of 3.2 +/- 0.2 mmol/L (57 +/- 2.6 mg/dL) and remained at that level with few symptoms. In contrast, five of six patients with insulinomas developed severe hypoglycemia, with plasma glucose levels between 1.9 (34 mg/dL) and 2.2 mmol/L (39 mg/dL). Plasma C-peptide concentrations were suppressed to 0.08 pmol/mL or less in normal subjects, but in insulinoma patients remained at 0.32-1.6 pmol/mL i.e. outside the normal range, and diagnostic of nonsuppressible insulin secretion. These data demonstrate that moderate reduction of serum glucose maintained for a prolonged period results in marked suppression of plasma C-peptide, permitting improved discrimination between normal subjects and patients with insulinomas. This glucose reduction challenge can, therefore, be used as a test of glucose-regulating ability, where failure (hypoglycemia) per se represents a measurable abnormality. C-Peptide measurements will determine whether the cause of hypoglycemia is due to hyperinsulinemia.

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging.

BACKGROUND: Psychopathy is a complex personality disorder of unknown etiology. Central to the disorder are anomalies or difficulties in affective processing. METHODS: Functional magnetic resonance imaging was used to elucidate the neurobiological correlates of these anomalies in criminal psychopaths during performance of an affective memory task. RESULTS: Compared with criminal nonpsychopaths and noncriminal control participants, criminal psychopaths showed significantly less affect-related activity in the amygdala/hippocampal formation, parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate gyri. Psychopathic criminals also showed evidence of overactivation in the bilateral fronto-temporal cortex for processing affective stimuli. CONCLUSIONS: These data suggest that the affective abnormalities so often observed in psychopathic offenders may be linked to deficient or weakened input from limbic structures.

Injected inositol 1,4,5-trisphosphate activates Ca2(+)-sensitive K+ channels in the plasmalemma of Eremosphaera viridis.

InsP3, and established mediator of intracellular Ca2+ signals in animal cells, is microinjected into the cytoplasm of Eremosphaera viridis. InsP3, but not Ins, InsP1, InsP2 or F2,6-P2 induce a transient opening of Ca2(+)-dependent K+ channels in the plasmalemma of this alga. This effect is indicated by a transient polarization (TP) with a simultaneous increase of membrane conductance. The TP is inhibited by TMB8 (2 mM), an intracellular Ca2+ antagonist or by BAPTA (20 mM), microinjected together with InsP3. The results suggest that InsP3 initiates an increase in the cytoplasmic Ca2+ activity and an activation of Ca2(+)-dependent membrane currents, hence, opening of K+ channels.