Effects of Lockdown Restrictions and Impact of Anxiety and Depression Symptoms in People With Chronic Pain During the Covid-19 Pandemic: A 13-Wave Longitudinal Study.

In early 2020, countries across the world imposed lockdown restrictions to curb the spread of the Covid-19 coronavirus. Lockdown conditions, including social and physical distancing measures and recommended self-isolation for clinically vulnerable groups, were proposed to disproportionately affect those living with chronic pain, who already report reduced access to social support and increased isolation. Yet, empirical evidence from longitudinal studies tracking the effects of prolonged and fluctuating lockdown conditions, and potential psychological factors mediating the effects of such restrictions on outcomes in chronic pain populations, is lacking. Accordingly, in the present 13-wave longitudinal study, we surveyed pain intensity, pain interference, and tiredness in people with chronic pain over the course of 11 months of the Covid-19 pandemic (April 2020-March 2021). Of N = 431 participants at baseline, average completion rate was ∼50% of time points, and all available data points were included in linear mixed models. We examined the impact of varying levels of lockdown restrictions on these outcomes and investigated whether psychological distress levels mediated effects. We found that a full national lockdown was related to greater pain intensity, and these effects were partially mediated by depressive symptoms. No effects of lockdown level were found for pain interference and tiredness, which were instead predicted by higher levels of depression, anxiety, pain catastrophising, and reduced exercise. Our findings are relevant for improving patient care in current and future crises. Offering remote management options for low mood could be particularly beneficial for this vulnerable population in the event of future implementation of lockdown restrictions. PERSPECTIVE: This longitudinal study demonstrates the impact of Covid-19 lockdown restrictions on people with chronic pain. Findings suggest a complex interaction of psychosocial factors that impacted various aspects of pain experience in patients, which offer the potential to inform clinical strategies for remote medicine and future crises.

The neural correlates of texture perception: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

INTRODUCTION: Humans use discriminative touch to perceive texture through dynamic interactions with surfaces, activating low-threshold mechanoreceptors in the skin. It was largely assumed that texture was processed in primary somatosensory regions in the brain; however, imaging studies indicate heterogeneous patterns of brain activity associated with texture processing. METHODS: To address this, we conducted a coordinate-based activation likelihood estimation meta-analysis of 13 functional magnetic resonance imaging studies (comprising 15 experiments contributing 228 participants and 275 foci) selected by a systematic review. RESULTS: Concordant activations for texture perception occurred in the left primary somatosensory and motor regions, with bilateral activations in the secondary somatosensory, posterior insula, and premotor and supplementary motor cortices. We also evaluated differences between studies that compared touch processing to non-haptic control (e.g., rest or visual control) or those that used haptic control (e.g., shape or orientation perception) to specifically investigate texture encoding. Studies employing a haptic control revealed concordance for texture processing only in the left secondary somatosensory cortex. Contrast analyses demonstrated greater concordance of activations in the left primary somatosensory regions and inferior parietal cortex for studies with a non-haptic control, compared to experiments accounting for other haptic aspects. CONCLUSION: These findings suggest that texture processing may recruit higher order integrative structures, and the secondary somatosensory cortex may play a key role in encoding textural properties. The present study provides unique insight into the neural correlates of texture-related processing by assessing the influence of non-textural haptic elements and identifies opportunities for a future research design to understand the neural processing of texture.

Machine learning and EEG can classify passive viewing of discrete categories of visual stimuli but not the observation of pain.

Previous studies have demonstrated the potential of machine learning (ML) in classifying physical pain from non-pain states using electroencephalographic (EEG) data. However, the application of ML to EEG data to categorise the observation of pain versus non-pain images of human facial expressions or scenes depicting pain being inflicted has not been explored. The present study aimed to address this by training Random Forest (RF) models on cortical event-related potentials (ERPs) recorded while participants passively viewed faces displaying either pain or neutral expressions, as well as action scenes depicting pain or matched non-pain (neutral) scenarios. Ninety-one participants were recruited across three samples, which included a model development group (n = 40) and a cross-subject validation group (n = 51). Additionally, 25 participants from the model development group completed a second experimental session, providing a within-subject temporal validation sample. The analysis of ERPs revealed an enhanced N170 component in response to faces compared to action scenes. Moreover, an increased late positive potential (LPP) was observed during the viewing of pain scenes compared to neutral scenes. Additionally, an enhanced P3 response was found when participants viewed faces displaying pain expressions compared to neutral expressions. Subsequently, three RF models were developed to classify images into faces and scenes, neutral and pain scenes, and neutral and pain expressions. The RF model achieved classification accuracies of 75%, 64%, and 69% for cross-validation, cross-subject, and within-subject classifications, respectively, along with reasonably calibrated predictions for the classification of face versus scene images. However, the RF model was unable to classify pain versus neutral stimuli above chance levels when presented with subsequent tasks involving images from either category. These results expand upon previous findings by externally validating the use of ML in classifying ERPs related to different categories of visual images, namely faces and scenes. The results also indicate the limitations of ML in distinguishing pain and non-pain connotations using ERP responses to the passive viewing of visually similar images.

No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, cross-over trial (ENERGIZE).

AIM: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). RESULTS: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. CONCLUSIONS: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.

Neural correlates of naturalistic single-trial appetitive conditioning.

BACKGROUND: Prior research suggests naturalistic single-trial appetitive conditioning may be a potent phenomenon in humans, capable of modulating both motivation and attention. In this study, we aimed to characterise the neural correlates of this phenomenon using functional Magnetic Resonance Imaging (fMRI) paradigms METHODS: Twenty-three healthy adults (12 males) underwent conditioning during which they ate a novel 3D object made from white chocolate (CS+) and handled a similar object made from plastic (CS-). Brain activity was recorded before and after conditioning during a passive viewing paradigm RESULTS: A naturalistic CS+ was rated as more highly craved, better-liked and elicited greater expectancies for chocolate than the CS- after conditioning. An exploration of the interaction between time (pre- and post-conditioning) and CS type (CS+, CS-) during the passive viewing task suggested enhanced activation from pre- to post-conditioning in the right superior frontal gyrus (R.SFG) in response to the CS-. CONCLUSION: Results reveal neural correlates of single-trial appetitive conditioning and highlight a possible role of response inhibition during learning about non-rewards, perhaps optimizing motivated behaviour. These findings contribute to our understanding of the neural mechanisms underpinning rapid reward and non-reward learning, and may inform development of behavioural interventions for reward-driven overeating.

Tactile estimation of hedonic and sensory properties during active touch: An electroencephalography study.

Perceptual judgements about our physical environment are informed by somatosensory information. In real-world exploration, this often involves dynamic hand movements to contact surfaces, termed active touch. The current study investigated cortical oscillatory changes during active exploration to inform the estimation of surface properties and hedonic preferences of two textured stimuli: smooth silk and rough hessian. A purpose-built touch sensor quantified active touch, and oscillatory brain activity was recorded from 129-channel electroencephalography. By fusing these data streams at a single trial level, oscillatory changes within the brain were examined while controlling for objective touch parameters (i.e., friction). Time-frequency analysis was used to quantify changes in cortical oscillatory activity in alpha (8-12 Hz) and beta (16-24 Hz) frequency bands. Results reproduce findings from our lab, whereby active exploration of rough textures increased alpha-band event-related desynchronisation in contralateral sensorimotor areas. Hedonic processing of less preferred textures resulted in an increase in temporoparietal beta-band and frontal alpha-band event-related desynchronisation relative to most preferred textures, suggesting that higher order brain regions are involved in the hedonic processing of texture. Overall, the current study provides novel insight into the neural mechanisms underlying texture perception during active touch and how this process is influenced by cognitive tasks.

Economic value in the Brain: A meta-analysis of willingness-to-pay using the Becker-DeGroot-Marschak auction.

Forming and comparing subjective values (SVs) of choice options is a critical stage of decision-making. Previous studies have highlighted a complex network of brain regions involved in this process by utilising a diverse range of tasks and stimuli, varying in economic, hedonic and sensory qualities. However, the heterogeneity of tasks and sensory modalities may systematically confound the set of regions mediating the SVs of goods. To identify and delineate the core brain valuation system involved in processing SV, we utilised the Becker-DeGroot-Marschak (BDM) auction, an incentivised demand-revealing mechanism which quantifies SV through the economic metric of willingness-to-pay (WTP). A coordinate-based activation likelihood estimation meta-analysis analysed twenty-four fMRI studies employing a BDM task (731 participants; 190 foci). Using an additional contrast analysis, we also investigated whether this encoding of SV would be invariant to the concurrency of auction task and fMRI recordings. A fail-safe number analysis was conducted to explore potential publication bias. WTP positively correlated with fMRI-BOLD activations in the left ventromedial prefrontal cortex with a sub-cluster extending into anterior cingulate cortex, bilateral ventral striatum, right dorsolateral prefrontal cortex, right inferior frontal gyrus, and right anterior insula. Contrast analysis identified preferential engagement of the mentalizing-related structures in response to concurrent scanning. Together, our findings offer succinct empirical support for the core structures participating in the formation of SV, separate from the hedonic aspects of reward and evaluated in terms of WTP using BDM, and show the selective involvement of inhibition-related brain structures during active valuation.

Neural correlates of perceptual texture change during active touch.

Introduction: Texture changes occur frequently during real-world haptic explorations, but the neural processes that encode perceptual texture change remain relatively unknown. The present study examines cortical oscillatory changes during transitions between different surface textures during active touch. Methods: Participants explored two differing textures whilst oscillatory brain activity and finger position data were recorded using 129-channel electroencephalography and a purpose-built touch sensor. These data streams were fused to calculate epochs relative to the time when the moving finger crossed the textural boundary on a 3D-printed sample. Changes in oscillatory band power in alpha (8-12 Hz), beta (16-24 Hz) and theta (4-7 Hz) frequency bands were investigated. Results: Alpha-band power reduced over bilateral sensorimotor areas during the transition period relative to ongoing texture processing, indicating that alpha-band activity is modulated by perceptual texture change during complex ongoing tactile exploration. Further, reduced beta-band power was observed in central sensorimotor areas when participants transitioned from rough to smooth relative to transitioning from smooth to rough textures, supporting previous research that beta-band activity is mediated by high-frequency vibrotactile cues. Discussion: The present findings suggest that perceptual texture change is encoded in the brain in alpha-band oscillatory activity whilst completing continuous naturalistic movements across textures.

External validation of binary machine learning models for pain intensity perception classification from EEG in healthy individuals.

Discrimination of pain intensity using machine learning (ML) and electroencephalography (EEG) has significant potential for clinical applications, especially in scenarios where self-report is unsuitable. However, existing research is limited due to a lack of external validation (assessing performance using novel data). We aimed for the first external validation study for pain intensity classification with EEG. Pneumatic pressure stimuli were delivered to the fingernail bed at high and low pain intensities during two independent EEG experiments with healthy participants. Study one (n = 25) was utilised for training and cross-validation. Study two (n = 15) was used for external validation one (identical stimulation parameters to study one) and external validation two (new stimulation parameters). Time-frequency features of peri-stimulus EEG were computed on a single-trial basis for all electrodes. ML training and analysis were performed on a subset of features, identified through feature selection, which were distributed across scalp electrodes and included frontal, central, and parietal regions. Results demonstrated that ML models outperformed chance. The Random Forest (RF) achieved the greatest accuracies of 73.18, 68.32 and 60.42% for cross-validation, external validation one and two, respectively. Importantly, this research is the first to externally validate ML and EEG for the classification of intensity during experimental pain, demonstrating promising performance which generalises to novel samples and paradigms. These findings offer the most rigorous estimates of ML's clinical potential for pain classification.

Pulse Intensity Effects of Burst and Tonic Spinal Cord Stimulation on Neural Responses to Brushing in Patients With Neuropathic Pain.

OBJECTIVES: Tonic spinal cord stimulation (SCS) is accompanied by paresthesia in affected body regions. Comparatively, the absence of paresthesia with burst SCS suggests different involvement of the dorsal column system conveying afferent impulses from low-threshold mechanoreceptors. This study evaluated cortical activation changes during gentle brushing of a pain-free leg during four SCS pulse intensities to assess the effect of intensity on recruitment of dorsal column system fibers during burst and tonic SCS. MATERIALS AND METHODS: Twenty patients using SCS (11 burst, nine tonic) for neuropathic leg pain participated. Brushing was administered to a pain-free area of the leg during four SCS intensities: therapeutic (100%), medium (66%), low (33%), and no stimulation. Whole-brain electroencephalography was continuously recorded. Changes in spectral power during brushing were evaluated using the event-related desynchronization (ERD) method in theta (4-7 Hz), alpha (8-13 Hz), and beta (16-24 Hz) frequency bands. RESULTS: Brushing was accompanied by a suppression of cortical oscillations in the range 4-24 Hz. Stronger intensities of burst and tonic SCS led to less suppression of 4-7 Hz and 8-13 Hz bands in parietal electrodes, and in central electrodes in the 16-24 Hz band, with the strongest, statistically significant suppression at medium intensity. Tonic SCS showed a stronger reduction in 4-7 Hz oscillations over right sensorimotor electrodes, and over right frontal and left sensorimotor electrodes in the 8-13 Hz band, compared to burst SCS. CONCLUSIONS: Results suggest that burst and tonic SCS are mediated by both different and shared mechanisms. Attenuated brushing-related ERD with tonic SCS suggests a gating of cortical activation by afferent impulses in the dorsal column, whereas burst may engage different pathways. Diminished brushing-related ERD at medium and therapeutic intensities of burst and tonic SCS points towards a nonlinear effect of SCS on somatosensory processing.

Predictors of radiographic outcomes of conservative and surgical treatment of Legg-Calvé-Perthes disease.

PURPOSE: Treatment outcomes of conservative and surgical treatment of Legg-Calvé-Perthes disease (LCPD) have been shown to be conditioned by a number of factors that may vary across different populations. This retrospective study aimed to evaluate factors affecting radiographically assessed treatment outcomes in patients treated surgically or conservatively for LCPD at Faculty Hospital Motol, Prague, Czech Republic, between the years 2006 and 2019. METHODS: Data of forty-seven children comprising 52 hips were analysed. Treatment outcomes were evaluated according to Stulberg classification. Predictors included the initial stage of fragmentation of the hip joint according to Herring classification, type of treatment (conservative or surgical), age at the time of diagnosis and sex. RESULTS: Older age and severity of LCPD according to Herring classification but not the type of treatment were the strongest factors determining treatment outcomes. Treatment outcomes were comparable in patients treated conservatively or surgically both across the whole cohort of patients and a group of young children < six years of age. CONCLUSIONS: Results strengthen the roles of severity of the LCPD at onset of treatment and age of the patient in predicting treatment outcomes in patients with LCPD. Conservative and surgical treatments appear to yield similar treatment outcomes irrespective of age of patients.

Bid outcome processing in Vickrey auctions: An ERP study.

Online retailers often sell products using a socially competitive second-price sealed-bid auction known as a Vickrey auction (VA), an incentivized demand-revealing mechanism used to elicit players' subjective values. The VA presents a situation of risky decision-making, which typically implements value processing and a loss aversion mechanism. Neural outcome processing of VA bids are not known; this study explores this for the first time using EEG. Twenty-eight healthy participants bid on household items against an anonymous, computerized opponent. Bid outcome event-related potentials were predicted to differentiate between three conditions: outbid (no-win), large margin win (bargain), and small margin win (snatch). Individual loss aversion values were evaluated in a separate behavioral experiment offering gains or losses of variable amounts but equal chances against an assured gain. Processing outcomes of VA bids were associated with a feedback-related negativity (FRN) potential with a spatial maximum at the vertex (251-271 ms), where bargain win trials resulted in greater FRN amplitudes than snatch win trials. Additionally, a P300 potential was sensitive to win versus no-win outcomes and to retail price. Individual loss aversion level did not correlate with the strength of FRN or P300. Results show that outcome processing in a VA is associated with FRN that differentiates between relatively advantageous and less advantageous gains, and a P300 that distinguishes between the more and less expensive auction items. Our findings pave the way to an objective exploration of economic decision-making and purchasing behavior involving a widely popular auction.

Neural correlates of texture perception during active touch.

Previous studies have shown attenuation of cortical oscillations over bilateral sensorimotor cortex areas during passive perception of smooth textures applied to the skin. However, humans typically explore surfaces using dynamic hand movements. As movements may both modulate texture-related cortical activity and induce movement-related cortical activation, data from passive texture perception cannot be extrapolated to active texture perception. In the present study, we used electroencephalography to investigate cortical oscillatory changes during texture perception throughout active touch exploration. Three natural textured stimuli were selected: smooth silk, soft brushed cotton, and rough hessian. Texture samples were mounted on a purpose-built touch sensor which measured the load and position of the index finger, whilst electroencephalography from 129 channels recorded oscillatory brain activity. The data were fused to investigate oscillatory changes relating to active touch. Changes in oscillatory band power, event-related desynchronisation/synchronisation (ERD/ERS), were investigated in alpha (8-12 Hz) and beta (16-24 Hz) frequency bands. Active texture exploration revealed bilateral activation patterns over sensorimotor cortical areas. Beta-band ERD increased over contralateral sensorimotor regions for soft and smooth textures, and over ipsilateral sensorimotor areas for the smoothest texture. Analysis of covariance revealed that individual differences in perception of softness and smoothness were related to variations in cortical oscillatory activity. Differences may be due to increased high frequency vibrations for smooth and soft textures compared to rough. For the first time, active touch was quantified and fused with electroencephalography data streams, contributing to the understanding of the neural correlates of texture perception during active touch.

Intensity-dependent modulation of cortical somatosensory processing during external, low-frequency peripheral nerve stimulation in humans.

External low-frequency peripheral nerve stimulation (LFS) has been proposed as a novel method for neuropathic pain relief. Previous studies have reported that LFS elicits long-term depression-like effects on human pain perception when delivered at noxious intensities, whereas lower intensities are ineffective. To shed light on cortical regions mediating the effects of LFS, we investigated changes in somatosensory-evoked potentials (SEPs) during four LFS intensities. LFS was applied to the radial nerve (600 pulses, 1 Hz) of 24 healthy participants at perception (1 times), low (5 times), medium (10 times), and high intensities (15 times detection threshold). SEPs were recorded during LFS, and averaged SEPs in 10 consecutive 1-min epochs of LFS were analyzed using source dipole modeling. Changes in resting electroencephalography (EEG) were investigated after each LFS block. Source activity in the midcingulate cortex (MCC) decreased linearly during LFS, with greater attenuation at stronger LFS intensities, and in the ipsilateral operculo-insular cortex during the two lowest LFS stimulus intensities. Increased LFS intensities resulted in greater augmentation of contralateral primary sensorimotor cortex (SI/MI) activity. Stronger LFS intensities were followed by increased α (alpha, 9-11 Hz) band power in SI/MI and decreased θ (theta, 3-5 Hz) band power in MCC. Intensity-dependent attenuation of MCC activity with LFS is consistent with a state of long-term depression. Sustained increases in contralateral SI/MI activity suggests that effects of LFS on somatosensory processing may also be dependent on satiation of SI/MI. Further research could clarify if the activation of SI/MI during LFS competes with nociceptive processing in neuropathic pain.NEW & NOTEWORTHY Somatosensory-evoked potentials during low-frequency stimulation of peripheral nerves were examined at graded stimulus intensities. Low-frequency stimulation was associated with decreased responsiveness in the midcingulate cortex and increased responsiveness in primary sensorimotor cortex. Greater intensities were associated with increased midcingulate cortex θ band power and decreased sensorimotor cortex α band power. Results further previous evidence of an inhibition of somatosensory processing during and after low-frequency stimulation and point toward a potential augmentation of activity in somatosensory processing regions.

Investigating the effect of losses and gains on effortful engagement during an incentivized Go/NoGo task through anticipatory cortical oscillatory changes.

Losses usually have greater subjective value (SV) than gains of equal nominal value but often cause a relative deterioration in effortful performance. Since losses and gains induce differing approach/avoidance behavioral tendencies, we explored whether incentive type interacted with approach/avoidance motor-sets. Alpha- and beta-band event-related desynchronization (ERD) was hypothesized to be weakest when participants expected a loss and prepared an inhibitory motor-set, and strongest when participants expected a gain and prepared an active motor-set. It was also hypothesized that effort would modulate reward and motor-set-related cortical activation patterns. Participants completed a cued Go/NoGo task while expecting a reward (+10p), avoiding a loss (-10p), or receiving no incentive (0p); and while expecting a NoGo cue with a probability of either .75 or .25. Pre-movement alpha- and beta-band EEG power was analyzed using the ERD method, and the SV of effort was evaluated using a cognitive effort discounting task. Gains incentivized faster RTs and stronger preparatory alpha band ERD compared to loss and no incentive conditions, while inhibitory motor-sets resulted in significantly weaker alpha-band ERD. However, there was no interaction between incentive and motor-sets. Participants were more willing to expend effort in losses compared to gain trials, although the SV of effort was not associated with ERD patterns or RTs. Results suggest that incentive and approach/avoidance motor tendencies modulate cortical activations prior to a speeded RT movement independently, and are not associated with the economic value of effort. The present results favor attentional explanations of the effect of incentive modality on effort.

Adverse effects of COVID-19-related lockdown on pain, physical activity and psychological well-being in people with chronic pain.

Countries across the world imposed lockdown restrictions during the COVID-19 pandemic. It has been proposed that lockdown conditions, including social and physical distancing measures, may disproportionately impact those living with chronic pain and require rapid adaptation to treatment and care strategies. Using an online methodology, we investigated how lockdown restrictions in the United Kingdom impacted individuals with chronic pain (N = 431) relative to a healthy control group (N = 88). Data were collected during the most stringent period of lockdown in the United Kingdom (mid-April to early-May 2020). In accordance with the fear-avoidance model, we hypothesised lockdown-related increases in pain and psychological distress, which would be mediated by levels of pain catastrophising. Responses indicated that people with chronic pain perceived increased pain severity, compared to their estimation of typical pain levels prior to lockdown (p < .001). They were also more adversely affected by lockdown conditions compared to pain-free individuals, demonstrating greater self-perceived increases in anxiety and depressed mood, increased loneliness and reduced levels of physical exercise (p ⩽ .001). Hierarchical regression analysis revealed that pain catastrophising was an important factor relating to the extent of self-perceived increases in pain severity during lockdown (ß = .27, p < .001) and also mediated the relationship between decreased mood and pain. Perceived decreases in levels of physical exercise also related to perceptions of increased pain (ß = .15, p < .001). Interestingly, levels of pain intensity (measured at two time points at pre and during lockdown) in a subgroup (N = 85) did not demonstrate a significant change. However, individuals in this subgroup still reported self-perceived pain increases during lockdown, which were also predicted by baseline levels of pain catastrophising. Overall, the findings indicate that people with chronic pain suffer adverse effects of lockdown including self-perceived increases in their pain. Remote pain management provision to target reduction of pain catastrophising and increase health behaviours including physical activity could be beneficial for this vulnerable population.

Paediatric pelvic injuries: a retrospective epidemiological study from four level 1 trauma centers.

AIM OF THE STUDY: Epidemiologic evaluation of pelvic ring injuries in children. METHODS: Retrospective analysis over a period of 13 years, excluding pathological fractures. AO/OTA type, epidemiological data, type of treatment, and complications were recorded. Data were assessed using Fisher's exact test and Wilcoxon test. RESULTS: 243 boys, 115 girls, mean age (SD) 14.1 ± 3.0 years, AO/OTA types: 281 A, 52 B, 25 C. Multiple trauma: 62, combined trauma: 59, mono-trauma: 237. 281 patients were treated non-operatively, 97 surgically. ETIOLOGY: traffic accidents 88, falls from a great height 37, crushing injuries four, and sports injuries 192, simple falls 30, others seven. High-energy mechanisms prevailed in types B and C. Low-energy mechanism in type A (p < 0.0001). Similar differences were found between type A (p = 0.0009) and in case type C requiring surgery and cases treated non-operatively (p < 0.0001). Twenty-six patients (7.3%) had complications (pelvic asymmetry 5, neurological deficits 5, non-union 1, ectopic calcification 4, others 7). Higher complication rates were associated with types B and C (p = 0.0015), with surgically treated cases (p < 0.0001) and multiple trauma (p = 0.0305). DISCUSSION: Results of this trial were comparable with other studies. CONCLUSION: Sports injuries accounted for most type A injuries, while types B and C tended to be associated with high-energy trauma. Complications were associated with the severity of pelvic trauma, more common in surgically treated group of patients; this is primarily linked to the surgical cases being more serious as well as the associated injuries.

A randomised, controlled, double blind study to assess mechanistic effects of combination therapy of dapagliflozin with exenatide QW versus dapagliflozin alone in obese patients with type 2 diabetes mellitus (RESILIENT): study protocol.

INTRODUCTION: The newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity. METHODS AND ANALYSIS: 110 obese patients with diagnosed T2D (glycated haemoglobin, HbA1c ≥48 mmol/mol) will be treated for 32 weeks with dapagliflozin (10 mg once daily either alone or in combination with exenatide QW (2 mg once weekly); active treatments will be compared with a control group (placebo tablet and sham injection). The primary objective of the study is to compare the adjusted mean reduction in total body fat mass (determined by dual-energy X-ray absorptiometry, DEXA) from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo). Secondary outcome measures include changes in (1) energy balance (energy intake and energy expenditure measured by indirect calorimetry); (2) appetite (between and within meals) and satiety quotient; (3) body composition including visceral adipose tissue, subcutaneous adipose tissue, liver and pancreatic fat. Exploratory outcome measures include metabolic changes in hepatic and peripheral insulin sensitivity (using a two-stage hyperinsulinaemic, euglycaemic clamp), central nervous system responses to food images using blood oxygen level-dependent (BOLD) functional MRI (fMRI) and changes in cardiovascular function (using transthoracic echocardiography, cardiac MR and duplex ultrasonography). ETHICS AND DISSEMINATION: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1147) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice. Results from the study will be published in peer-reviewed scientific and open access journals and/or presented at scientific conferences and summarised for distribution to the participants. TRIAL SPONSOR: University of Liverpool. TRIAL REGISTRATION NUMBER: ISRCTN 52028580; EUDRACT number 2015-005242-60.

Inhibition of cortical somatosensory processing during and after low frequency peripheral nerve stimulation in humans.

OBJECTIVE: Transcutaneous low-frequency stimulation (LFS) elicits long-term depression-like effects on human pain perception. However, the neural mechanisms underlying LFS are poorly understood. We investigated cortical activation changes occurring during LFS and if changes were associated with reduced nociceptive processing and increased amplitude of spontaneous cortical oscillations post-treatment. METHODS: LFS was applied to the radial nerve of 25 healthy volunteers over two sessions using active (1 Hz) or sham (0.02 Hz) frequencies. Changes in resting electroencephalography (EEG) and laser-evoked potentials (LEPs) were investigated before and after LFS. Somatosensory-evoked potentials were recorded during LFS and source analysis was carried out. RESULTS: Ipsilateral midcingulate and operculo-insular cortex source activity declined linearly during LFS. Active LFS was associated with attenuated long-latency LEP amplitude in ipsilateral frontocentral electrodes and increased resting alpha (8-12 Hz) and beta (16-24 Hz) band power in electrodes overlying operculo-insular, sensorimotor and frontal cortical regions. Reduced ipsilateral operculo-insular cortex source activity during LFS correlated with a smaller post-treatment alpha-band power increase. CONCLUSIONS: LFS attenuated somatosensory processing both during and after stimulation. SIGNIFICANCE: Results further our understanding of the attenuation of somatosensory processing both during and after LFS.

A Behavioral and Electrophysiological Investigation of Effects of Visual Congruence on Olfactory Sensitivity During Habituation to Prolonged Odors.

Congruent visual cues augment sensitivity to brief olfactory presentations and habituation of odor perception is modulated by central-cognitive processing including context. However, it is not known whether habituation to odors could interact with cross-modal congruent stimuli. The present research investigated the effect of visual congruence on odor detection sensitivity during continuous odor exposures. We utilized a multimethod approach, including subjective behavioral responses and reaction times (RTs; study 1) and electroencephalography (EEG, study 2). Study 1: 25 participants received 2-min presentations of moderate-intensity floral odor delivered via olfactometer with congruent (flower) and incongruent (object) image presentations. Participants indicated odor perception after each image. Detection sensitivity and RTs were analyzed in epochs covering the period of habituation. Study 2: 25 new participants underwent EEG recordings during 145-s blocks of odor presentations with congruent or incongruent images. Participants passively observed images and intermittently rated the perceived intensity of odor. Event-related potential analysis was utilized to evaluate brain processing related to odor-visual pairs across the period of habituation. Odor detection sensitivity and RTs were improved by congruent visual cues. Results highlighted a diminishing influence of visual congruence on odor detection sensitivity as habituation occurred. Event-related potential analysis revealed an effect of congruency on electrophysiological processing in the N400 component. This was only evident in early periods of odor exposure when perception was strong. For the first time, this demonstrates the modulation of central processing of odor-visual pairs by habituation. Frontal negativity (N400) responses encode the aspects of cross-modal congruence for odor-vision cross-modal tasks.