Sign-tracking modulates reward-related neural activation to reward cues, but not reward feedback.

Research shows cognitive and neurobiological overlap between sign-tracking [value-modulated attentional capture (VMAC) by response-irrelevant, discrete cues] and maladaptive behaviour (e.g. substance abuse). We investigated the neural correlates of sign-tracking in 20 adults using an additional singleton task (AST) and functional magnetic resonance imaging (fMRI). Participants responded to a target to win monetary reward, the amount of which was signalled by singleton type (reward cue: high value vs. low value). Singleton responses resulted in monetary deductions. Sign-tracking-greater distraction by high-value vs. low-value singletons (H > L)-was observed, with high-value singletons producing slower responses to the target than low-value singletons. Controlling for age and sex, analyses revealed no differential brain activity across H > L singletons. Including sign-tracking as a regressor of interest revealed increased activity (H > L singletons) in cortico-subcortical loops, regions associated with Pavlovian conditioning, reward processing, attention shifts and relative value coding. Further analyses investigated responses to reward feedback (H > L). Controlling for age and sex, increased activity (H > L reward feedback) was found in regions associated with reward anticipation, attentional control, success monitoring and emotion regulation. Including sign-tracking as a regressor of interest revealed increased activity in the temporal pole, a region related to value discrimination. Results suggest sign-tracking is associated with activation of the 'attention and salience network' in response to reward cues but not reward feedback, suggesting parcellation between the two at the level of the brain. Results add to the literature showing considerable overlap in neural systems implicated in reward processing, learning, habit formation, emotion regulation and substance craving.

Mapping multidimensional pain experience onto electrophysiological responses to noxious laser heat stimuli.

The origin of the conscious experience of pain in the brain is a continuing enigma in neuroscience. To shed light on the brain representation of a multifaceted pain experience in humans, we combined multivariate analysis of subjective aspects of pain sensations with detailed, single-trial analysis of electrophysiological brain responses. Participants were asked to fully focus on any painful or non-painful sensations occurring in their left hand during an interval surrounding the onset of noxious laser heat stimuli, and to rate their sensations using a set of visual analogue scales. Statistical parametric mapping was used to compute a multivariate regression analysis of subjective responses and single-trial laser evoked potentials (LEPs) at subject and group levels. Standardized Low Resolution Electromagnetic Tomography method was used to reconstruct sources of LEPs. Factor analysis of subjective responses yielded five factors. Factor 1, representing pain, mapped firstly as a negative potential at the vertex and a positive potential at the fronto-temporal region during the 208-260ms interval, and secondly as a strong negative potential in the right lateral frontal and prefrontal scalp regions during the 1292-1340ms interval. Three other factors, labelled "anticipated pain", "stimulus onset time", and "body sensations", represented non-specific aspects of the pain experience, and explained portions of LEPs in the latency range from 200ms to 700ms. The subjective space of pain during noxious laser stimulation is represented by one large factor featuring pain intensity, and by other factors accounting for non-specific parts of the sensory experience. Pain is encoded in two separate latency components with different scalp and brain representations.

Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity.

The insula cortex and hypothalamus are implicated in eating behaviour, and contain receptor sites for peptides and hormones controlling energy balance. The insula encompasses multi-functional subregions, which display differential anatomical and functional connectivities with the rest of the brain. This study aimed to analyse the effect of fasting and satiation on the functional connectivity profiles of left and right anterior, middle, and posterior insula, and left and right hypothalamus. It was hypothesized that the profiles would be altered alongside changes in homeostatic energy balance. Nineteen healthy participants underwent two 7-min resting state functional magnetic resonance imaging scans, one when fasted and one when satiated. Functional connectivity between the left posterior insula and cerebellum/superior frontal gyrus, and between left hypothalamus and inferior frontal gyrus was stronger during fasting. Functional connectivity between the right middle insula and default mode structures (left and right posterior parietal cortex, cingulate cortex), and between right hypothalamus and superior parietal cortex was stronger during satiation. Differences in blood glucose levels between the scans accounted for several of the altered functional connectivities. The insula and hypothalamus appear to form a homeostatic energy balance network related to cognitive control of eating; prompting eating and preventing overeating when energy is depleted, and ending feeding or transferring attention away from food upon satiation. This study provides evidence of a lateralized dissociation of neural responses to energy modulations.

Heightened eating drive and visual food stimuli attenuate central nociceptive processing.

Hunger and pain are basic drives that compete for a behavioral response when experienced together. To investigate the cortical processes underlying hunger-pain interactions, we manipulated participants' hunger and presented photographs of appetizing food or inedible objects in combination with painful laser stimuli. Fourteen healthy participants completed two EEG sessions: one after an overnight fast, the other following a large breakfast. Spatio-temporal patterns of cortical activation underlying the hunger-pain competition were explored with 128-channel EEG recordings and source dipole analysis of laser-evoked potentials (LEPs). We found that initial pain ratings were temporarily reduced when participants were hungry compared with fed. Source activity in parahippocampal gyrus was weaker when participants were hungry, and activations of operculo-insular cortex, anterior cingulate cortex, parahippocampal gyrus, and cerebellum were smaller in the context of appetitive food photographs than in that of inedible object photographs. Cortical processing of noxious stimuli in pain-related brain structures is reduced and pain temporarily attenuated when people are hungry or passively viewing food photographs, suggesting a possible interaction between the opposing motivational forces of the eating drive and pain.

Survival of Single-Unit Porcelain-Fused-to-Metal (PFM) and Metal Crowns Placed by Students at an Australian University Dental Clinic over a Five-Year Period.

The aim of this retrospective study was to determine the survival rate of single-unit porcelain-fused-to-metal (PFM) and metal crowns placed by dental students at an Australian university undergraduate dental clinic over a five-year period. Complications and the incidences of crown failures were recorded. Clinical records pertaining to single-unit PFM and metal crowns inserted over a five-year period were reviewed, including patient-related, tooth-related, and procedural factors for each crown. Crowns were evaluated as surviving, surviving with complications, or failed. Kaplan-Meier statistical analysis was used to estimate survival rate., This study is based on a sample of 232 (78.4%) PFM crowns and 64 (21.6%) metal crowns inserted between 2014 and 2018. Cumulatively, 224 (75.7%) were surviving, 48 (16.2%) were surviving but previously had complications, and 24 (8.1%) failed. The 5-year cumulative survival rate of all PFM and metal crowns was 83.9% (0.839 ± 0.038, Kaplan-Meier). The average survival time for all crowns was 4.432 ± 0.089 years. Comparatively, PFM crowns had a higher survival rate at 1 year (0.972 ± 0.010) and 2 years (0.919 ± 0.017), compared to metal crowns at 1 year (0.964 ± 0.011) and 2 years (0.894± 0.018). The survival rate of metal crowns remained constant from 2 years to 4 years and thereafter, whereas there was a continued decline in the survival rate of PFM crowns to 83.2% (0.832 ± 0.038) at 4 years and thereafter. Crowns placed on premolars had the highest cumulative survival rate whereas those placed on molars exhibited the lowest survival rate for the duration of the study period. Despite single-unit PFM crowns having a higher 1- and 2-year survival rate compared to metal crowns, metal crowns had a higher survival rate at 4 years and thereafter. Survival rates are comparable to previous studies.

Simultaneous odour-face presentation strengthens hedonic evaluations and event-related potential responses influenced by unpleasant odour.

Odours alter evaluations of concurrently presented visual stimuli, such as faces. Stimulus onset asynchrony (SOA) is known to affect evaluative priming in various sensory modalities. However, effects of SOA on odour priming of visual stimuli are not known. The present study aimed to analyse whether subjective and cortical activation changes during odour priming would vary as a function of SOA between odours and faces. Twenty-eight participants rated faces under pleasant, unpleasant, and no-odour conditions using visual analogue scales. In half of trials, faces appeared one-second after odour offset (SOA 1). In the other half of trials, faces appeared during the odour pulse (SOA 2). EEG was recorded continuously using a 128-channel system, and event-related potentials (ERPs) to face stimuli were evaluated using statistical parametric mapping (SPM). Faces presented during unpleasant-odour stimulation were rated significantly less pleasant than the same faces presented one-second after offset of the unpleasant odour. Scalp-time clusters in the late-positive-potential (LPP) time-range showed an interaction between odour and SOA effects, whereby activation was stronger for faces presented simultaneously with the unpleasant odour, compared to the same faces presented after odour offset. Our results highlight stronger unpleasant odour priming with simultaneous, compared to delayed, odour-face presentation. Such effects were represented in both behavioural and neural data. A greater cortical and subjective response during simultaneous presentation of faces and unpleasant odour may have an adaptive role, allowing for a prompt and focused behavioural reaction to a concurrent stimulus if an aversive odour would signal danger, or unwanted social interaction.

Effects of loss aversion on neural responses to loss outcomes: An event-related potential study.

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes.

Ectopic intratracheal thyroid: an illustrative case report and literature review.

A 19-year-old woman was treated with bronchodilators for new-onset dyspnea with exercise. Her symptoms progressively worsened, culminating 4 months later in acute shortness of breath at rest. Flow-volume loops suggested a fixed obstruction and a computed tomography scan of the neck revealed a large subglottic mass. The patient underwent emergent tracheostomy and laryngoscopy and a near-obstructing intratracheal mass was found. Biopsy showed ectopic thyroid tissue. Magnetic resonance imaging of the neck showed a 1.4-cm tracheal lesion and a normally located thyroid gland. The intratracheal mass was resected endoscopically. Pathology revealed hyperplastic ectopic thyroid tissue. The patient has been maintained on thyroid hormone suppression therapy for 2 years without growth of the residual intratracheal thyroid tissue. She recently underwent a surgical palate expansion. We present this case, along with a literature review of ectopic intratracheal thyroid, its epidemiology, possible etiologies, genetic underpinnings, presentation, and treatment. The co-occurrence of an ectopic thyroid, a functioning orthotopic gland, and a high arched palate is also discussed.

Data to support observation of late and ultra-late latency components of cortical laser evoked potentials.

Data are provided to document the presence of late and ultra-late latency components of cortical laser evoked potentials (LEPs) following noxious laser stimulus in Stancak et al. (2015) [3]. The latency components, labeled provisionally as N4, N5, and N6, were observed in 16 healthy human participants who were asked to fully attend their painful and non-painful sensations occurring in association with noxious laser stimulus. Individual laser evoked potential waveforms are provided in support of this observation. Data provided demonstrate the cortical sources of the late and ultra-late laser evoked potentials. The cortical sources of LEPs were reconstructed using the standardized Low Resolution Electromagnetic Tomography (sLORETA) method.

Pleasant and Unpleasant Odors Influence Hedonic Evaluations of Human Faces: An Event-Related Potential Study.

Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs). Healthy, young participants (N = 20) rated neutral faces presented after a 3 s pulse of a pleasant odor (jasmine), unpleasant odor (methylmercaptan), or no-odor control (clean air). Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600-950 ms). In the 620-640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (>600) and ultra-late (>900 ms) latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations.

Identification of the major proteins of an immune modulating fraction from adult Fasciola hepatica released by Nonidet P40.

Fasciola hepatica NP-40 released protein extract (FhNPE) exhibits potent Th1 immunosuppressive properties in vitro and in vivo. However, the protein composition of this active fraction, responsible for Th1 immune modulatory activity, has yet to be resolved. Therefore, FhNPE, a Nonidet P-40 extract, was subjected to a proteomic analysis in order to identify individual protein components. This was performed using an in house F. hepatica EST database following 2D electrophoresis combined with de novo sequencing based mass spectrometry. The identified proteins, a mixture of excretory/secretory and membrane-associated proteins, are associated with stress response and chaperoning, energy metabolism and cytoskeletal components. The immune modulatory properties of these identified protein(s) are discussed and HSP70 from F. hepatica is highlighted as a potential host immune modulator for future study.

Towards delineating functions within the fasciola secreted cathepsin l protease family by integrating in vivo based sub-proteomics and phylogenetics.

BACKGROUND: fasciola hepatica, along with Fasciola gigantica, is the causative agent of fasciolosis, a foodborne zoonotic disease affecting grazing animals and humans worldwide. Pathology is directly related to the release of parasite proteins that facilitate establishment within the host. The dominant components of these excretory-secretory (ES) products are also the most promising vaccine candidates, the cathepsin L (Cat L) protease family. METHODOLOGY/PRINCIPAL FINDINGS: the sub-proteome of Cat L proteases from adult F. hepatica ES products derived from in vitro culture and in vivo from ovine host bile were compared by 2-DE. The individual Cat L proteases were identified by tandem mass spectrometry with the support of an in-house translated liver fluke EST database. The study reveals plasticity within the CL1 clade of Cat L proteases; highlighted by the identification of a novel isoform and CL1 sub-clade, resulting in a new Cat L phylogenetic analysis including representatives from other adult Cat L phylogenetic clades. Additionally, for the first time, mass spectrometry was shown to be sufficiently sensitive to reveal single amino acid polymorphisms in a resolved 2-DE protein spot derived from pooled population samples. CONCLUSIONS/SIGNIFICANCE: we have investigated the sub-proteome at the population level of a vaccine target family using the Cat L proteases from F. hepatica as a case study. We have confirmed that F. hepatica exhibits more plasticity in the expression of the secreted CL1 clade of Cat L proteases at the protein level than previously realised. We recommend that superfamily based vaccine discovery programmes should screen parasite populations from different host populations and, if required, different host species via sub-proteomic assay in order to confirm the relative expression at the protein level prior to the vaccine development phase.

Rewards and challenges of nursing wounded warriors at Landstuhl Regional Medical Center, Germany.

Since the beginning of the Overseas Contingency Operation, more than 45,000 ill and wounded service members have been evacuated from the battlefield to Landstuhl Regional Medical Center (LRMC) in western Europe. LRMC is a stopover for these service members, where they are further assessed, treated, and stabilized before they return to the United States. This process requires coordination between different military services, health care teams, and modes of transportation. These processes can be complicated given the severity of the wounded. Nurses at LRMC have learned how to streamline services, providing efficient, comprehensive care for wounded service members and their families.

Proteomic analysis of embryonic Fasciola hepatica: characterization and antigenic potential of a developmentally regulated heat shock protein.

Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. We report the first post-genomic investigation of cellular proteins expressed by embryonic F. hepatica via two-dimensional electrophoresis, image analysis and tandem mass spectrometry. Antioxidant proteins and protein chaperones are prominently expressed by embryonic F. hepatica. Molecular differences between the egg and other characterized F. hepatica lifecycle stages were noted. Furthermore, proteins expressed within liver fluke eggs differ to those isolated from the well-characterized eggs of the human blood flatworm Schistosoma mansoni were revealed. Plasticity in expression of major proteins, particularly a prominently expressed 65kDa protein cluster was seen between natural populations of embryonating F. hepatica eggs suggesting that liver fluke embryogenisis is a plastic process. Immunoblotting revealed that the abundant 65kDa protein cluster is recognised by infection sera from three F. hepatica challenged host species. Mass spectrometry and BLAST analyses demonstrated that the 65kDa antigen shows homology to egg antigens of other flatworm parasites, and is represented in a F. hepatica EST database constructed from adult fluke transcripts. EST clones encoding the egg antigen were re-sequenced, predicting two forms of the protein. Four clones predict a 312 aa polypeptide, three clones encode a putative 110 amino acid extension at the N-terminus which may be involved in protein secretion, although this extension was not expressed by natively extracted proteins. Consistent expression of alpha crystallin domains confirmed the protein to be a member of the alpha crystallin containing small heat shock protein (AC/sHSP) superfamily. AC/sHSPs are ubiquitous in nature, however, this is the first time a member of this protein superfamily has been described from F. hepatica. The antigenic AC/sHSP was named Fh-HSP35alpha based on predictions of molecular weight. Production of recombinant Fh-HSP35alpha reveals considerable mass discrepancy between native and recombinant proteins, although descriptions of other characterized flatworm AC/sHSPs, suggest that the native form is a dimer. Immunoblot analyses confirm that the recombinant protein is recognised by F. hepatica challenged hosts, but does not react with sera from non-infected animals. We discuss the potential of recombinant Fh-HSP35alpha as an egg-based diagnostic marker for liver fluke infection.

Comparative proteomics of excretory-secretory proteins released by the liver fluke Fasciola hepatica in sheep host bile and during in vitro culture ex host.

Livestock infection by the parasitic fluke Fasciola hepatica causes major economic losses worldwide. The excretory-secretory (ES) products produced by F. hepatica are key players in understanding the host-parasite interaction and offer targets for chemo- and immunotherapy. For the first time, subproteomics has been used to compare ES products produced by adult F. hepatica in vivo, within ovine host bile, with classical ex host in vitro ES methods. Only cathepsin L proteases from F. hepatica were identified in our ovine host bile preparations. Several host proteins were also identified including albumin and enolase with host trypsin inhibitor complex identified as a potential biomarker for F. hepatica infection. Time course in vitro analysis confirmed cathepsin L proteases as the major constituents of the in vitro ES proteome. In addition, detoxification proteins (glutathione transferase and fatty acid-binding protein), actin, and the glycolytic enzymes enolase and glyceraldehyde-3-phosphate dehydrogenase were all identified in vitro. Western blotting of in vitro and in vivo ES proteins showed only cathepsin L proteases were recognized by serum pooled from F. hepatica-infected animals. Other liver fluke proteins released during in vitro culture may be released into the host bile environment via natural shedding of the adult fluke tegument. These proteins may not have been detected during our in vivo analysis because of an increased bile turnover rate and may not be recognized by pooled liver fluke infection sera as they are only produced in adults. This study highlights the difficulties identifying authentic ES proteins ex host, and further confirms the potential of the cathepsin L proteases as therapy candidates.