Vicarious experiences and detection accuracy while observing pain and touch: the effect of perspective taking

In this study, we investigated the effects of observing pain and touch in others on vicarious somatosensory experiences and the detection of subtle somatosensory stimuli. Furthermore, the effect of taking a first- versus a third-person perspective was investigated. Undergraduates (N = 57) viewed videos depicting hands being pricked (pain), hands being touched by a cotton swab (touch), and control scenes (same approaching movement of a hand as in the other video categories, but without the painful/touching object) while experiencing vibrotactile stimuli themselves on the left, on the right, or on both hands. Participants reported the location at which they felt a somatosensory stimulus. The vibrotactile stimuli and visual scenes were applied in a spatially congruent or incongruent way, and other trials were presented without vibrotactile stimuli. The videos were depicted in first-person perspective and third-person perspective (i.e., the videos were shown upside down). We calculated the proportions of correct responses and false alarms (i.e., numbers of trials on which a vicarious somatosensory experience was reported congruent or incongruent to the site of the visual information). Pain-related scenes facilitated the detection of tactile stimuli and augmented the number of vicarious somatosensory experiences, as compared with observing the touch or control videos. Detection accuracy was higher for videos depicted in first-person perspective than for those in third-person perspective. Perspective had no effect on the number of vicarious somatosensory experiences. This study indicates that somatosensory detection is particularly enhanced during the observation of pain-related scenes, as compared to the observation of touch or control videos. These research findings further demonstrate that perspective taking impacts somatosensory detection, but not the report of vicarious experiences

The role of the right tempoparietal junction in the elicitation of vicarious experiences and detection accuracy while observing pain and touch

This study investigated the effects of observing pain and touch in others upon vicarious somatosensory experiences and the detection of subtle somatosensory stimuli. Furthermore, transcranial direct current stimulation (tDCS) was used to assess the role of the right temporoparietal junction (rTPJ), as this brain region has been suggested to be involved in perspective taking and self-other distinction. Undergraduates (N = 22) viewed videos depicting hands being touched, hands being pricked, and control scenes (same approaching movement as in the other video categories but without the painful/touching object), while experiencing vibrotactile stimuli themselves on the left, right, or both hands. Participants reported the location at which they felt a somatosensory stimulus. Vibrotactile stimuli and visual scenes were applied in a congruent or incongruent way. During three separate testing sessions, excitability of the rTPJ was modulated with tDCS (cathodal, anodal, or sham). We calculated the proportion of correct responses and false alarms (i.e., number of trials in which a vicarious somatosensory experience was reported congruent to the site of the visual information). Pain-related scenes facilitated the correct detection of tactile stimuli and augmented the number of vicarious somatosensory experiences compared with observing touch or control videos. Stimulation of the rTPJ had no reliable influence upon detection accuracy or the number of vicarious errors. This study indicates that the observation of pain-related scenes compared to the observation of touch or control videos increases the likelihood that a somatosensory stimulus is detected. Contrary to our expectations, the rTPJ did not modulate detection accuracy

Observing another in pain facilitates vicarious experiences and modulates somatosensory experiences

Objective: This study investigated whether individuals reporting vicarious pain in daily life (e.g., the self-reported vicarious pain group) display vicarious experiences during an experimental paradigm, and also show an improved detection of somatosensory stimuli while observing another in pain. Furthermore, this study investigated the stability of these phenomena. Finally, this study explored the putative modulating role of dispositional empathy and hypervigilance for pain. Methods: Vicarious pain responders (i.e., reporting vicarious pain in daily life; N = 16) and controls (N = 19) were selected from a large sample, and viewed videos depicting pain-related (hands being pricked) and non-pain related scenes, whilst occasionally experiencing vibrotactile stimuli themselves on the left, right or both hands. Participants reported the location at which they felt a somatosensory stimulus. We calculated the number of vicarious errors (i.e., the number of trials in which an illusionary sensation was reported while observing pain-related scenes) and detection accuracy. Thirty-three participants (94.29%) took part in the same experiment 5 months later to investigate the temporal stability of the outcomes. Results: The vicarious pain group reported more vicarious errors compared with controls and this effect proved to be stable over time. Detection was facilitated while observing pain-related scenes compared with non-pain related scenes. Observers' characteristics, i.e., dispositional empathy and hypervigilance for pain, did not modulate the effects. Conclusion: Observing pain facilitates the detection of tactile stimuli, both in vicarious pain responders and controls. Interestingly, vicarious pain responders reported more vicarious errors during the experimental paradigm compared to controls and this effect remained stable over time

A new venue of TNF targeting

The first Food and Drug Administration-(FDA)-approved drugs were small, chemically-manufactured and highly active molecules with possible off-target effects, followed by protein-based medicines such as antibodies. Conventional antibodies bind a specific protein and are becoming increasingly important in the therapeutic landscape. A very prominent class of biologicals are the anti-tumor necrosis factor (TNF) drugs that are applied in several inflammatory diseases that are characterized by dysregulated TNF levels. Marketing of TNF inhibitors revolutionized the treatment of diseases such as Crohn's disease. However, these inhibitors also have undesired effects, some of them directly associated with the inherent nature of this drug class, whereas others are linked with their mechanism of action, being pan-TNF inhibition. The effects of TNF can diverge at the level of TNF format or receptor, and we discuss the consequences of this in sepsis, autoimmunity and neurodegeneration. Recently, researchers tried to design drugs with reduced side effects. These include molecules with more specificity targeting one specific TNF format or receptor, or that neutralize TNF in specific cells. Alternatively, TNF-directed biologicals without the typical antibody structure are manufactured. Here, we review the complications related to the use of conventional TNF inhibitors, together with the anti-TNF alternatives and the benefits of selective approaches in different diseases

Laypersons' perception of common cold and influenza prevention : a qualitative study in Austria, Belgium and Croatia

Background: Common cold and influenza result in an increased number of primary care consultations, significant work/school absences and cause a socio-economic burden. Laypeople's perceptions and knowledge regarding common cold and influenza prevention is poorly understood and under-researched. Objectives: Our study explores laypeople's knowledge of prevention of common cold and influenza across three European countries. Furthermore, it investigates if there is any distinction between prevention activities focussing on reasons impacting the attitude towards influenza vaccination as well as investigating cross-country variation. Methods: In total, 85 semi-structured individual interviews were performed across three European countries (Austria n = 31, Belgium n = 30, Croatia n = 24). Qualitative thematic content analysis was performed. Results: Most participants across all three countries made no distinction between the prevention of the common cold and influenza and referenced the same preventative measures for both conditions. They mainly expressed negative attitudes towards influenza vaccination possibly effective but only intended for high-risk groups (bedridden/older people, chronic patients or health workers). There were very few cross-country differences in results. Conclusion: The perception of health risk of contracting influenza and a primary healthcare physicians' recommendation played an important role in shaping participants' decisions towards vaccination. Primary healthcare physicians are invited to assess and if necessary adjust inappropriate prevention behaviour through their everyday patient consultations as well as add to the knowledge about influenza severity and influenza vaccination benefits to their patients

Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1

TNF is a central actor during inflammation and a well-recognized drug target for inflammatory diseases. We found that the mouse strain SPRET/Ei, known for extreme and dominant resistance against TNF-induced shock, displays weak expression of TNF receptor 1 protein (TNFR1) but normal mRNA expression, a trait genetically linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in cells. In mice, overexpression of miR-511 down-regulates TNFR1 and protects against TNF, while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF, breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia and experimental hepatitis and that this miR is strongly induced by glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR. Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity, we believe that at least part of the anti-inflammatory effects of glucocorti-coids are mediated by induction of this miR, resulting in reduced TNFR1 expression

A study of cecal ligation and puncture-induced sepsis in tissue-specific tumor necrosis factor receptor 1-deficient mice

Sepsis is a complex syndrome resulting from a dysregulated immune response to an infection. Due to the high prevalence, morbidity, and mortality, there is a lot of interest in understanding pathways that play a role in sepsis, with a focus on the immune system. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine and a master regulator of the immune system but clinical trials with TNF blockers in sepsis have failed to demonstrate significant protection. Since TNF stimulates two different receptors, TNF receptor 1 (TNFR1) and TNFR2, pan-TNF inhibition might be suboptimal since both receptors have opposite functions in polymicrobial sepsis. Therefore, we hypothesized that TNF has a dual role in sepsis, namely a mediating and a protective role, and that protection might be obtained by TNFR1-specific inhibition. We here confirmed that TNFR1(-/-) mice are protected in the sterile endotoxemia model, whereas TNFR1 deficiency did not protect in the cecal ligation and puncture (CLP)-induced polymicrobial sepsis model. Since whole body TNFR1 blockage might be deleterious because of the antibacterial function of TNF/TNFR1 signaling, we focused on the potential devastating role of TNF/TNFR1 signaling in specific cell types. We were interested in the gut epithelium, the endothelium, and hepatocytes using conditional TNFR1(-/-) mice, as these cell types have been shown to play a role in sepsis. However, none of these conditional knockout mice showed improved survival in the CLP model. We conclude that cell-specific targeting of TNFR1 to these cell types has no therapeutic future in septic peritonitis

Correction to: The interplay between self-esteem, expectancy, cognitive control, rumination, and the experience of stress: A network analysis

The original version of this article unfortunately contained a mistake. In Table 1 of this article, bulleted data in the column 1 were incorrectly aligned. Thus, this erratum is presented to fix this error. The original article has been correcte

Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting

The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating protein antagonist against induced myeloid leukemia cell differentiation protein MCL-1, an intracellular target in cancer, by grafting the critical B-cell lymphoma 2 homology 3 helix of MCL-1 onto the Alphabody and tagging the scaffold’s termini with designed cell-penetration polypeptides. Introduction of an albumin-binding moiety extended the serum half-life of the engineered Alphabody to therapeutically relevant levels, and administration thereof in mouse tumor xenografts based on myeloma cell lines reduced tumor burden. Crystal structures of such a designed Alphabody in complex with MCL-1 and serum albumin provided the structural blueprint of the applied design principles. Collectively, we provide proof of concept for the use of Alphabodies against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics