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The influence of food on the pharmacokinetics of telbivudine, a candidate antiviral agent against hepatitis B virus (HBV), was investigated in healthy adult subjects following a 600-mg oral dose administered with and without a high-fat/high-calorie meal. Telbivudine was well tolerated under fasting and fed conditions. Oral absorption of telbivudine as measured by maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC(0-t) and AUC(0-infinity)) was not altered by food intake immediately before oral dosing. Values of Cmax, Tmax, and AUC were comparable when telbivudine was administered under fed and fasting conditions. Results from this study indicated that the absorption of telbivudine was not affected by a high-fat/high-calorie meal; telbivudine can therefore be administered orally with no regard to the timing of meals. [ABSTRACT FROM AUTHOR]

O'Connell DL [Faculty of Mathematics, University of Newcastle, New South Wales, 2308, Australia], Alexander HM, Dobson AJ, Lioyd DM, Hardes GR, Springthorpe HJ and Leeder SR. Cigarette smoking and drug use in school-children. II Factors associated with smoking. 1981, 10: 223–231. In 1979 as the first stage in the evaluation of an educational strategy to discourage children from smoking, we surveyed over 6000 10–12 year old primary school children in the Hunter Health Region (New South Wales, Australia) to assess the prevalence of smoking and to identify some of the social and personal factors associated with this phenomenon. Logistic regression was used to determine the relative importance of the key factors in relation to the proportion of smokers in the ‘recent’ and ‘regular’ smoking categories. Friends' smoking behaviour was the best predictor of the child's smoking status followed in order by approval of advertising, siblings' smoking behaviour, amount of money available to spend weekly, sex, age and finally parents' smoking habits. Other factors such as size of family, position of the child in the family, country of birth of parents, father's occupation, having a single parent and urban or non-urban location of schools were all significantly associated with smoking prevalence in these children. Linear modelling techniques used in the analysis showed girls and non-smokers to have less favouring attitudes to smoking and tobacco advertising than boys and smokers. Significant differences in knowledge occurred between categories of smokers. Most children claiming not to smoke disapproved of advertising and did not intend to smoke in the future. Among current smokers, some with natural or favouring attitudes were ambivalent about future smoking. Our data suggest that intervention in the field of cigarette advertising may be the most direct and effective means of reducting prevalence of smoking in children. [ABSTRACT FROM PUBLISHER]

Angiomyolipoma (AML) are benign tumours composed of varying amounts of thick-walled dysplastic blood vessels, smooth muscle and mature adipose tissue derived from epithelioid cells. We present a previously unreported occurrence of multi-focal pancreatic and hepatic AMLs in a patient and discuss the diagnostic and management difficulties associated with this rare disease. In addition relevant case studies are also reviewed. [ABSTRACT FROM PUBLISHER]

Lay Abstract: Children with autism typically experience difficulties interacting socially with others when compared to their non-autistic peers. Establishing how effective interventions are for improving social functioning is important to help inform what should be offered to children with autism. This study reviewed how effective interventions that involved interaction with a live animal, known as animal-assisted interventions, are in improving social functioning in children with autism. A systematic search of the evidence on this topic found nine studies, which were explored for the effectiveness of animal-assisted interventions and the quality of methods used. Overall, these studies showed improvements in social functioning following equine-assisted or therapeutic horse-riding interventions, with initial evidence showing improvements are sustained in the short and medium term. However, several issues were identified, which limit the strength of any conclusions that can be drawn from this evidence. For example, in many studies people assessing the children were aware that they received the intervention or were in a control group. There was also not enough evidence available to draw conclusions on the effectiveness of other animal-assisted interventions. Future research should address the limitations that were common in the designs of these studies and investigate the potential benefit of other animal populations, such as dogs and cats.

Purpose: The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical pain condition. Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane library and Web of Science. Two reviewers screened reports and extracted the data. A third reviewer acted as an arbiter. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and uncontrolled trials. Crossover and parallel-group designs were included. Risk of bias was assessed for all included studies. Results: Thirteen clinical studies were included. The majority of studies investigated a sample of participants with chronic pain. Six were controlled trials and seven uncontrolled studies. Findings from controlled research suggest that interactive virtual reality may reduce pain associated with ankylosing spondylitis and post-mastectomy, but results are inconsistent for patients with neck pain. Findings from uncontrolled studies suggest that interactive virtual reality may reduce neuropathic limb pain, and phantom limb pain, but had no effect on nonspecific chronic back pain. Conclusions: There is a need for more rigorous randomized control trials in order to conclude on the effectiveness of the use of virtual reality for the management of pain.Implications for rehabilitationInteractive virtual reality has been increasingly used in the rehabilitation of painful conditions.Interactive virtual reality using exergames may promote distraction from painful exercises and reduce pain post-mastectomy and in patients with ankylosing spondylitis.Interactive virtual representation of limbs may reduce neuropathic and phantom limb pain.

Background: Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment., Objective: To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia., Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals., Results: Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made., Conclusions: tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies., Perspective: This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research., (Copyright © 2020 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this systematic review was to assess the effect of virtual representation of body parts on pain perception in patients with pain and in pain-free participants exposed to experimentally induced pain. Methods: Databases searched: Medline, PsycInfo, CINAHL, and Web of Science. Studies investigating participants with clinical pain or those who were pain free and exposed to experimentally induced pain were analysed separately. Results: Eighteen clinical studies and seven experimental studies were included. Randomised controlled clinical trials showed no significant difference between intervention and control groups for pain intensity. Clinical studies with a single group pretest-posttest design showed a reduction in pain after intervention. In the studies including a sample of pain free participants exposed to experimentally induced pain there was an increase in pain threshold when the virtual arm was collocated with the real arm, when it moved in synchrony with the real arm, and when the colour of the stimulated part of the virtual arm became blue. Observing a virtual arm covered with iron armour reduced pain. Conclusions: The use of virtual representations of body parts to reduce pain is promising. However, due to the poor methodological quality and limitations of primary studies, we could not find conclusive evidence.Implications for rehabilitationVirtual reality has been increasingly used in the rehabilitation of painful and dysfunctional limbs.Virtual reality can be used to distract attention away from acute pain and may also provide corrective psychological and physiological environments.Virtual representation of body parts has been used to provide a corrective re-embodiment of painful dysmorphic body parts, and primary research shows promising results.

Alpha activity directly before pain onset has been implicated in pain experience with higher prestimulus alpha associated with lower reported pain. However, expectations about pain intensity also seem to affect prestimulus alpha activity. To date, evidence for a relationship between alpha activity and pain experience has been largely correlational. Transcranial alternating current stimulation at alpha frequency (alpha tACS) permits direct manipulation of alpha activity and therefore an examination of the potential causal relationship between alpha activity and pain. We investigated whether somatosensory alpha tACS could reduce pain experience and whether this was influenced by uncertainty about pain intensity. In a within-subjects design, perceived pain intensity and unpleasantness were assessed in 23 participants during alpha tACS and sham stimulation. Visual cues preceding the pain stimulus were used to manipulate uncertainty. A significant tACS × Uncertainty × Stimulus intensity interaction was found for reported pain intensity (F 2,44  = 4.50, P = .017, partial η 2  = .17) and unpleasantness (F 1,22  = 4.78, P = .040, partial η 2  = .18). Pain experience during the application of somatosensory alpha tACS was significantly lowered compared with sham stimulation, but only when the intensity of an upcoming stimulus was uncertain., Perspective: To our knowledge, this is the first study to suggest that somatosensory alpha tACS might lead to a reduction in pain. Interventions targeting alpha activity may have the potential to alleviate chronic pain. However, a patient's expectation about the intensity of upcoming pain must also be taken into account., (Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.)

The aim of this systematic review was to evaluate the effect of visual feedback techniques on pain perception by analysing the effect of normal-sized, magnified or minified visual feedback of body parts on clinical and experimentally-induced pain. Databases searched: Medline, Embase, PsychInfo, PEDro, CINAHL, CENTRAL and OpenSIGLE. Studies investigating pain patients and pain-free participants exposed to experimentally-induced pain were analysed separately. Risk of bias was assessed and data were meta-analysed. Thirty four studies were included. A meta-analysis of clinical data favoured mirror visual feedback (six trials; mean difference = -13.06 mm; 95% CI = -23.97, -2.16). Subgroup analysis favoured mirror visual feedback when used as a course of treatment (three trials; mean difference = -12.76 mm; 95% CI = -24.11, -1.40) and when used for complex regional pain syndrome for complex regional pain syndrome (three trials; standard mean difference = -1.44; 95% CI = -1.88, -0.99). There is insufficient evidence to determine differences between normal-sized view and a size-distorted view of the limb. Mirror visual feedback was not superior to object view or direct view of the hand for reducing experimental pain in pain-free participants. There were inconsistencies in study findings comparing normal-sized reflection of a body part and a reflection of an object, or a magnified or minified reflection. There is tentative evidence that mirror visual feedback can alleviate pain when delivered as a course of treatment, and for patients with complex regional pain syndrome. It was not possible to determine whether normal-sized, magnified or minified visual feedback of body parts affects pain perception because of contradictory findings in primary studies., Significance: It was not possible to determine whether normal-sized, magnified or minified visual feedback of body parts affected pain perception in clinical or experimental settings because of contradictory findings in primary studies. This emphasizes the need for higher quality studies., (© 2017 European Pain Federation - EFIC®.)

Background: Studies suggest that observing magnified and minified body parts using mirrors, lenses and virtual reality may affect pain perception. However, the direction of effect varies between studies. The aim of the present study was to evaluate the effect of observing a normal-sized, magnified and minified reflection of a hand on perceptual embodiment and contact-heat stimuli., Methods: Participants (n = 46) observed a normal-sized, magnified and minified reflection of the hand and a no-reflection condition while performing synchronized finger movements for 3 min (adaptive phase). Measurements of embodiment were taken before adaptive phase, pre- and post-contact-heat stimuli., Results: There were no differences in pain threshold nor tolerance between reflection and no-reflection conditions. Altering the size of the reflection of the hand did not affect estimates of pain threshold nor tolerance. The temperature for warm detection threshold was lower when participants were observing the magnified reflection of the hand compared with the no-reflection condition. Perceptual embodiment of the reflection of the hand was stronger after an adaptive phase with visuo-motor feedback, and the painful stimuli did not weaken the perceptual experience., Conclusion: Observing a reflection of the hand in front of a mirror did not alter heat pain threshold nor tolerance when compared with a no-reflection condition, and altering the size of the reflection did not affect pain perception. Researchers and clinicians using visual feedback techniques may consider including an adaptive phase with visuo-motor feedback to facilitate embodiment of the viewed body part., Significance: An adaptive phase with visuo-motor feedback enhances the perceptual experience of embodiment of a reflection of a hand and a painful stimulus does not weaken the experience. This should be considered when using visual feedback techniques for pain management., (© 2017 European Pain Federation - EFIC®.)

Following a splenectomy patients are at increased risk of significant infections. In its most severe form, overwhelming post-splenectomy infection (OPSI) has a mortality rate of up to 80%. In this study we aim to establish the adherence to vaccination and antibiotic national guidelines in splenectomised patients. A retrospective study of 100 patients who underwent splenectomy (21 emergency, 79 elective), in two teaching hospitals was undertaken over a five-year period. Patients were followed up for five years. Hospital and GP records were reviewed for adherence to pre, intra and postoperative vaccination, thromboprophylaxis and antibiotic guidance. Eighty-six eligible patients (91.5%) received their Haemophilus influenzae B, meningococcal C and pneumococcus vaccinations peri-operatively. Eighty-one (86%) received post-operative antibiotics. Ninety-nine percent of patients received thromboprophylaxis treatment. Eighty-nine (95%) were treated with long-term antibiotic prophylaxis. Only 20 patients (23%) had an emergency supply of antibiotics. Ninety-five percent of patients were administered an annual influenza vaccination and 84% of eligible patients received a five-year pneumococcal booster vaccination. Improvement in the management of this patient cohort can be achieved by a multidisciplinary approach involving adherence to national guidelines, standardised trust protocols, patient information leaflets and advice detailing risk of infection, standardised GP letters and a splenectomy register to monitor and manage this vulnerable group of patients., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The presence of a light flash near to the body not only increases the ability to detect a weak touch but also increases reports of feeling a weak touch that did not occur. The somatic signal detection task (SSDT) provides a behavioural marker by which to clarify the spatial extent of such visuotactile interactions in peripersonal space. Whilst previous evidence suggests a limit to the spatial extent over which visual input can distort the perception of tactile stimulation during the rubber hand illusion, the spatial boundaries of light-induced tactile sensations are not known. In a repeated measures design, 41 participants completed the SSDT with the light positioned 1 cm (near), 17.5 cm (mid) or 40 cm (far) from the tactile stimulation. In the far condition, the light did not affect hit, or false alarm rates during the SSDT. In the near and mid conditions, the light significantly increased hit rates and led to a more liberal response criterion, that is, participants reported feeling the touch more often regardless of whether or not it actually occurred. Our results demonstrate a spatial boundary over which visual input influences veridical and non-veridical touch perception during the SSDT, and provide further behavioural evidence to show that the boundaries of the receptive fields of visuotactile neurons may be limited to reach space.

Mirror visual feedback is used for reducing pain and visually distorting the size of the reflection may improve efficacy. The findings of studies investigating size distortion are inconsistent. The influence of the size of the reflected hand on embodiment of the mirror reflection is not known. The aim of this study was to compare the effect of magnifying and minifying mirror reflections of the hand on embodiment measured using an eight-item questionnaire and on proprioceptive drift. During the experiment, participants (n = 45) placed their right hand behind a mirror and their left hand in front of a mirror. Participants watched a normal-sized, a magnified and a minified reflection of the left hand while performing synchronised finger movements for 3 min (adaptive phase). Measurements of embodiment were taken before (pre) and after (post) synchronous movements of the fingers of both hands (embodiment adaptive phase). Results revealed larger proprioceptive drift post-adaptive phase (p = 0.001). Participants agreed more strongly with questionnaire items associated with location, ownership and agency of the reflection of the hand post-adaptive phase (p < 0.001) and when looking at the normal-sized reflection (p < 0.001). In conclusion, irrespective of size, watching a reflection of the hand while performing synchronised movements enhances the embodiment of the reflection of the hand. Magnifying and minifying the reflection of the hand has little effect on proprioceptive drift, but it weakens the subjective embodiment experience. Such factors need to be taken into account in future studies using this technique, particularly when assessing mirror visual feedback for pain management.

Fluctuations of pre-stimulus oscillatory activity in the somatosensory alpha band (8-14Hz) observed using human EEG and MEG have been shown to influence the detection of supra- and peri-threshold somatosensory stimuli. However, some reports of touch occur even without a stimulus. We investigated the possibility that pre-stimulus alpha oscillations might also influence these false reports of touch - known as tactile misperceptions. We recorded EEG while participants performed the Somatic Signal Detection Task (SSDT), in which participants must detect brief, peri-threshold somatosensory targets. We found that pre-stimulus oscillatory power in the somatosensory alpha range exhibited a negative linear relationship with reporting of touch at electrode clusters over both contralateral and ipsilateral somatosensory regions. As pre-stimulus alpha power increased, the probability of reporting a touch declined; as it decreased, the probability of reporting a touch increased. This relationship was stronger on trials without a somatosensory stimulus than on trials with a somatosensory stimulus, although was present for both trial types. Spatio-temporal cluster-based permutation analysis also found that pre-stimulus alpha was lower on trials when touch was reported - irrespective of whether it was present - over contralateral and ipsilateral somatosensory cortices, as well as left frontocentral areas. We argue that alpha power may reflect changes in response criterion rather than sensitivity alone. Low alpha power relates to a low barrier to reporting a touch even when one is not present, while high alpha power is linked to less frequent reporting of touch overall., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Despite the need for effective pain communication, pain is difficult to verbalise. Co-speech gestures frequently add information about pain that is not contained in the accompanying speech. We explored whether recipients can obtain additional information from gestures about the pain that is being described., Methods: Participants (n=135) viewed clips of pain descriptions under one of four conditions: 1) Speech Only; 2) Speech and Gesture; 3) Speech, Gesture and Face; and 4) Speech, Gesture and Face plus Instruction (short presentation explaining the pain information that gestures can depict). Participants provided free-text descriptions of the pain that had been described. Responses were scored for the amount of information obtained from the original clips., Findings: Participants in the Instruction condition obtained the most information, while those in the Speech Only condition obtained the least (all comparisons p<0.001)., Conclusions: Gestures produced during pain descriptions provide additional information about pain that recipients are able to pick up without detriment to their uptake of spoken information., Practice Implications: Healthcare professionals may benefit from instruction in gestures to enhance uptake of information about patients' pain experiences., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain-related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states., Perspective: This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

In vitro and pre-clinical studies have suggested that addition of the diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of chemotherapy in models of colorectal cancer. However, the majority of evidence for this currently derives from established cell lines. Here, we utilised patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem cell (CSC) models. Combination of curcumin with FOLFOX chemotherapy was then assessed clinically in a phase I dose escalation study. Curcumin alone and in combination significantly reduced spheroid number in CRLM CSC models, and decreased the number of cells with high aldehyde dehydrogenase activity (ALDH(high)/CD133(-)). Addition of curcumin to oxaliplatin/5-FU enhanced anti-proliferative and pro-apoptotic effects in a proportion of patient-derived explants, whilst reducing expression of stem cell-associated markers ALDH and CD133. The phase I dose escalation study revealed curcumin to be a safe and tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses up to 2 grams daily. Curcumin may provide added benefit in subsets of patients when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The skin senses serve a discriminative function, allowing us to manipulate objects and detect touch and temperature, and an affective/emotional function, manifested as itch or pain when the skin is damaged. Two different classes of nerve fibre mediate these dissociable aspects of cutaneous somatosensation: (i) myelinated A-beta and A-delta afferents that provide rapid information about the location and physical characteristics of skin contact; and (ii) unmyelinated, slow-conducting C-fibre afferents that are typically associated with coding the emotional properties of pain and itch. However, recent research has identified a third class of C-fibre afferents that code for the pleasurable properties of touch - c-tactile afferents or CTs. Clinical application of treatments that target pleasant, CT-mediated touch (such as massage therapy) could, in the future, provide a complementary, non-pharmacological means of treating both the physical and psychological aspects of chronic skin conditions such as itch and eczema., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tumor initiating cells (TIC) are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively) and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent heterogeneity observed in cancer populations is maintained.

Despite the importance of effective pain communication, talking about pain represents a major challenge for patients and clinicians because pain is a private and subjective experience. Focusing primarily on acute pain, this article considers the limitations of current methods of obtaining information about the sensory characteristics of pain and suggests that spontaneously produced "co-speech hand gestures" may constitute an important source of information here. Although this is a relatively new area of research, we present recent empirical evidence that reveals that co-speech gestures contain important information about pain that can both add to and clarify speech. Following this, we discuss how these findings might eventually lead to a greater understanding of the sensory characteristics of pain, and to improvements in treatment and support for pain sufferers. We hope that this article will stimulate further research and discussion of this previously overlooked dimension of pain communication.

Effective pain communication is essential if adequate treatment and support are to be provided. Pain communication is often multimodal, with sufferers utilising speech, nonverbal behaviours (such as facial expressions), and co-speech gestures (bodily movements, primarily of the hands and arms that accompany speech and can convey semantic information) to communicate their experience. Research suggests that the production of nonverbal pain behaviours is positively associated with pain intensity, but it is not known whether this is also the case for speech and co-speech gestures. The present study explored whether increased pain intensity is associated with greater speech and gesture production during face-to-face communication about acute, experimental pain. Participants (N = 26) were exposed to experimentally elicited pressure pain to the fingernail bed at high and low intensities and took part in video-recorded semi-structured interviews. Despite rating more intense pain as more difficult to communicate (t(25)  = 2.21, p =  .037), participants produced significantly longer verbal pain descriptions and more co-speech gestures in the high intensity pain condition (Words: t(25)  = 3.57, p  = .001; Gestures: t(25)  = 3.66, p =  .001). This suggests that spoken and gestural communication about pain is enhanced when pain is more intense. Thus, in addition to conveying detailed semantic information about pain, speech and co-speech gestures may provide a cue to pain intensity, with implications for the treatment and support received by pain sufferers. Future work should consider whether these findings are applicable within the context of clinical interactions about pain.

Introduction: The aim was to produce a multidisciplinary consensus to determine the current position on the nomenclature, definition, diagnosis, imaging modalities and management of Sportsman's groin (SG)., Methods: Experts in the diagnosis and management of SG were invited to participate in a consensus conference held by the British Hernia Society in Manchester, U.K. on 11-12 October 2012. Experts included a physiotherapist, a musculoskeletal radiologist and surgeons with a proven track record of expertise in this field. Presentations detailing scientific as well as outcome data from their own experiences were given. Records were made of the presentations with specific areas debated openly., Results: The term 'inguinal disruption' (ID) was agreed as the preferred nomenclature with the term 'Sportsman's hernia' or 'groin' rejected, as no true hernia exists. There was an overwhelming agreement of opinion that there was abnormal tension in the groin, particularly around the inguinal ligament attachment. Other common findings included the possibility of external oblique disruption with consequent small tears noted as well as some oedema of the tissues. A multidisciplinary approach with tailored physiotherapy as the initial treatment was recommended with any surgery involving releasing the tension in the inguinal canal by various techniques and reinforcing it with a mesh or suture repair. A national registry should be developed for all athletes undergoing surgery., Conclusions: ID is a common condition where no true hernia exists. It should be managed through a multidisciplinary approach to ensure consistent standards and outcomes are achieved., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Patients with chronic low back pain (cLBP) show a range of behavioral patterns that do not correlate with degree of spinal abnormality found in clinical, radiological, neurophysiological, or laboratory investigations. This may indicate an augmented central pain response, consistent with factors that mediate and maintain psychological distress in this group., Methods: Twenty-four cLBP patients were scanned with functional magnetic resonance imaging while receiving noxious thermal stimulation to the right hand. Patients were clinically assessed into those with significant pain-related illness behavior (Waddell signs [WS]-H) or without (WS-L) based on WS., Results: Our findings revealed a significant increase in brain activity in WS-H versus WS-L patients in response to noxious heat in the right amygdala/parahippocampal gyrus and ventrolateral prefrontal and insular cortex (at a VoxelPThreshold = 0.01). We found no difference between groups for heat pain thresholds (t(22) = -1.17, p = .28) or sensory-discriminative pain regions., Conclusions: Patients with cLBP displaying major pain behavior have increased activity in the emotional circuitry of the brain. This study is the first to suggest an association between a specific clinical test in cLBP and neurobiology of the brain. Functional magnetic resonance imaging may provide a tool capable of enhancing diagnostic accuracy and affecting treatment decisions in cases where no structural cause can be identified.

Cardiovascular disease (CVD) remains the leading cause of mortality both in the United States and worldwide. Traditional risk factors are essential to CVD risk prediction and explain a significant portion of the between-population and between-individual variance in CVD. Nonetheless, due to the large size of the group, a substantial portion of cardiovascular events occur in individuals predicted to be at low risk based on traditional risk factor models such as the Framingham risk score. The problem is that by disregarding this low risk group, a significant proportion of events are ignored and deemed 'unpreventable'. As such, it is imperative to find new ways to improve CVD risk prediction and thereby apply preventive measures to persons more likely to develop 'preventable' disease. Focus has consequently shifted towards identification of novel markers to improve cardiovascular risk prediction. We review the role of various risk stratification models, and assess the incorporation of imaging markers to guide treatment for lipids in prevention of CVD., (Copyright © 2014. Published by Elsevier Ltd.)

Membrane emulsification is a promising process for formulating emulsions and particulates. It offers many advantages over conventional 'high-shear' processes with narrower size distribution products, higher batch repeatability and lower energy consumption commonly demonstrated at a small scale. Since the process was first introduced around 25 years ago, understanding of the underlying mechanisms involved during microstructure formation has advanced significantly leading to the development of modelling approaches that predict processing output; e.g. emulsion droplet size and throughput. The accuracy and ease of application of these models is important to allow for the development of design equations which can potentially facilitate scale-up of the process and meet the manufacturer's specific requirements. Part B of this review considers the advantages and disadvantages of a variety of models developed to predict droplet size, flow behaviour and other phenomena (namely droplet-droplet interactions), with presentation of the appropriate formulae where necessary. Furthermore, the advancement of the process towards an industrial scale is also highlighted with additional recommendations by the authors for future work., (© 2013 Society of Chemical Industry.)

Modern emulsion processing technology is strongly influenced by the market demands for products that are microstructure-driven and possess precisely controlled properties. Novel cost-effective processing techniques, such as membrane emulsification, have been explored and customised in the search for better control over the microstructure, and subsequently the quality of the final product. Part A of this review reports on the state of the art in membrane emulsification techniques, focusing on novel membrane materials and proof of concept experimental set-ups. Engineering advantages and limitations of a range of membrane techniques are critically discussed and linked to a variety of simple and complex structures (e.g. foams, particulates, liposomes etc.) produced specifically using those techniques., (© 2013 Society of Chemical Industry.)

Background: The nuclear protein high-mobility group box 1 (HMGB1) is a key trigger for the inflammatory reaction during liver ischemia reperfusion injury (IRI). Hydrogen treatment was recently associated with down-regulation of the expression of HMGB1 and pro-inflammatory cytokines during sepsis and myocardial IRI, but it is not known whether hydrogen has an effect on HMGB1 in liver IRI., Methods: A rat model of 60 minutes 70% partial liver ischemia reperfusion injury was used. Hydrogen enriched saline (2.5, 5 or 10 ml/kg) was injected intraperitoneally 10 minutes before hepatic reperfusion. Liver injury was assessed by serum alanine aminotransferase (ALT) enzyme levels and histological changes. We also measured malondialdehyde (MDA), hydroxynonenal (HNE) and 8-hydroxy-guanosine (8-OH-G) levels as markers of the peroxidation injury induced by reactive oxygen species (ROS). In addition, pro-inflammatory cytokines including TNF-α and IL-6, and high mobility group box B1 protein (HMGB1) were measured as markers of post ischemia-reperfusion inflammation., Results: Hydrogen enriched saline treatment significantly attenuated the severity of liver injury induced by ischemia-reperfusion. The treatment group showed reduced serum ALT activity and markers of lipid peroxidation and post ischemia reperfusion histological changes were reduced. Hydrogen enriched saline treatment inhibited HMGB1 expression and release, reflecting a reduced local and systemic inflammatory response to hepatic ischemia reperfusion., Conclusion: These results suggest that, in our model, hydrogen enriched saline treatment is protective against liver ischemia-reperfusion injury. This effect may be mediated by both the anti-oxidative and anti-inflammatory effects of the solution.

Introduction: A sportsman's groin has no accepted definition or consensus on treatment. The aim of this study was to assess current opinion among a large body of European surgeons using an online survey., Methods: An online questionnaire comprising 16 multiple-choice questions was sent by email to general surgeons in Europe. The survey was live from the 6th to 30th September 2011., Results: In total 143 responses were received. One hundred and six respondents (74 %) expressed experience in managing this condition. The majority (91 %) managed <26 cases per year. Posterior wall weakness (53 %), pubic tendinitis (43 %), nerve entrapment (37 %) and conjoint tendon injury (36 %) were the commonest aetiological factors described. Preferred diagnostic investigations were ultrasound of the groin (44 %) and MRI of the pelvis (29 %). The most common initial treatment (91 % of respondents) was conservative measures (rest and analgesia) for a maximum of 6-month period. When surgery was undertaken, Lichtenstein repair (29 %), TEP (27 %), TAPP (20 %), and posterior wall repair (21 %) were the commonest procedures. The majority (95 %) of respondents would not offer bilateral surgery for those presenting with unilateral groin pain., Conclusions: Most European surgeons see <26 cases of "sportsman's groin" per year, which is in keeping with the low incidence of this condition. There remains wide variation in its investigation and management, which reflects the differences in opinion on its aetiology. The majority of surgeons agree that surgery is not the only treatment option available, but there is little consensus on the optimal management.

Un-myelinated C tactile afferents (CT afferents) are a key finding in affective touch. These fibers, which activate in response to a caress-like touch to hairy skin (CT afferents are not found in palm skin), may have more in common with interoceptive systems encoding body ownership, than afferent systems processing other tactile stimuli. We tested whether subjective embodiment of a rubber hand (measured through questionnaire items) was increased when tactile stimulation was applied to the back of the hand at a rate optimal for CT afferents (3 cm/s) vs. stimulation of glabrous skin (on the palm of the hand) or at a non-optimal rate (30 cm/s), which should not activate these fibers. We also collected ratings of tactile pleasantness and a measure of perceived limb position, proprioceptive drift, which is mediated by different mechanisms of multisensory integration than those responsible for feelings of ownership. The results of a multiple regression analysis revealed that proprioceptive drift was a significant predictor of subjective strength of the illusion when tactile stimuli were applied to the back of the hand, regardless of stroking speed. This relationship was modified by pleasantness, with higher ratings when stimulation was applied to the back of the hand at the slower vs. faster stroking speed. Pleasantness was also a unique predictor of illusion strength when fast stroking was applied to the palm of the hand. However, there were no conditions under which pleasantness was a significant predictor of drift. Since the illusion was demonstrated at a non-optimal stroking speed an integrative role for CT afferents within the illusion cannot be fully supported. Pleasant touch, however, does moderate the subjective aspects of the rubber hand illusion, which under certain tactile conditions may interact with proprioceptive information about the body or have a unique influence on subjective body perception.

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.

Ganglia arising from the hip are rare. Its diagnosis is difficult owing to the anatomic location. A high index of suspicion and high-resolution imaging is essential to make the diagnosis. Treatment depends on the size, location, and symptoms. This report is of 2 patients with ganglia arising from the transverse acetabular ligament.

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.

When painful stimuli are evaluated at the time they are experienced, judgments are made not in isolation but with reference to other experienced stimuli. We tested a specific quantitative model of how such context effects occur. Participants experienced 3 blocks of 11 different pressure pain stimuli, and rated each stimulus on a 0-10 scale of intensity. Stimulus distribution was varied between participants. Study 1 found that that the rating of a stimulus of a particular pressure was higher in the context in which it ranked highest. Study 2 found that pain ratings were higher in a context where most stimuli were relatively intense, even when the mean stimulus was constant. It is suggested that pain judgments are relative, involve the same cognitive processes as are used in other psychophysical and socioemotional judgments, and are well described by range frequency theory. This approach can further inform the existing body of research on context-dependent pain evaluation., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

We have previously found that attention to internal somatic sensations (interoceptive attention) during a heart beat perception task increases the misperception of external touch on a somatic signal detection task (SSDT), during which healthy participants erroneously report feeling near-threshold vibrations presented to their fingertip in the absence of a stimulus. However, it has been suggested that mindful interoceptive attention should result in more accurate somatic perception, due to its non-evaluative and controlled nature. To investigate this possibility, 62 participants completed the SSDT before and after a period of brief body-scan mindfulness meditation training, or a control intervention (listening to a recorded story). The meditation intervention reduced tactile misperception and increased sensitivity during the SSDT. This finding suggests that the perceptual effects of interoceptive attention depend on its particular nature, and raises the possibility that body-scan meditation could reduce the misperception of physical symptoms in individuals with medically unexplained symptoms., (Copyright © 2012 Elsevier Inc. All rights reserved.)