Changing the size of a mirror-reflected hand moderates the experience of embodiment but not proprioceptive drift: a repeated measures study on healthy human participants.

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

Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial

Objectives: To conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI). Design: Multicentre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial with an embedded process evaluation. No statistical comparison was performed between the two study groups. Setting: Four neuropsychiatric and neurology outpatient clinics in London and Kent, UK. Participants: Our aim was to recruit 50 patients with TBI over 18 months. Follow-up participants at 12 weeks using a battery of assessment scales to measure changes in aggressive behaviour and irritability (Modified Overt Aggression Scale (MOAS)-primary outcome, Irritability Questionnaire) as well as global functioning (Glasgow Outcome Scale-Extended, Clinical Global impression) and quality of life (EQ-5D-5L, SF-12), mental health (Hospital Anxiety and Depression Scale) and medication adverse effects (Udvalg for Kliniske Undersøgelser). Results: Six participants were randomised to the active arm of the trial and eight to the placebo arm over a 10-month period (28% of our target). Two participants withdrew because of adverse events. Twelve out of 14 (85.7%) patients completed a follow-up assessment at 12 weeks. At follow-up, the scores of all outcome measures improved in both groups. Placebo group showed numerically better score change according to the primary outcome MOAS. No severe adverse events were reported. The overall rate of adverse events remained low. Data from the process evaluation suggest that existence of specialised TBI follow-up clinics, availability of a dedicated database of TBI patients’ clinical details, simple study procedures and regular support to participants would enhance recruitment and retention in the trial. Feedback from participants showed that once in the study, they did not find the trial procedure onerous. Conclusions: It was not feasible to conduct a successful randomised trial of risperidone versus placebo for post-TBI aggression using the methods we deployed in this study. It is not possible to draw any definitive conclusion about risperidone’s efficacy from such a small trial. Trial registration number: ISRCTN3019143

Microbial fuel cells with polychlorinated biphenyls contaminated soil as electrolyte. Energy performance and decontamination potential in presence of compost

The electrical performance of Terrestrial Microbial Fuel Cells (TMFCs) with soil as the electrolyte was tested with two concentrations (150 or 250 ng/g soil) of PCBs (Polychlorinated biphenlys) and compost (3 % w/w) in an experiment lasting 60 -80 days. Energy output levels were recorded daily by varying the external resistance for detecting the best operating conditions. PCB concentrations and microbiological analyses (total microbial abundance and activity) were performed at the start and end of the experiment. The highest power generation (207 +/- 80 mW/m 2 at 112.5 Omega) was recorded in the presence of compost with the lowest PCB concentration, when compared to TMFCs without compost (1.5 +/- 0.2 mW/m 2 at 300.8 Omega). The results demonstrated that the power generation was correlated with a lower internal resistance and a higher microbial activity. Moreover, chemical results indicated a possible threshold of PCB concentration for the concurrently electricity production and PCB degradation. In fact, PCB removal was obtained only in the cells with high PCB concentration, achieving a reduction of 21 % and 16 % with and without compost, respectively. The microbiological results showed that an additional organic carbon source (methanol or compost) promoted microbial activity and abundance. A positive correlation was found between microbial activity and TMFC electrical output only in the case of PCB low concentration, in the presence of compost. No previous studies addressed the performance of TMFCs with different levels of PCBs in terms of soil decontamination and electricity production. Although a longer experiment is needed, considering PCB persistence in soils, this experiment provided useful information and a new insight on the TMFC effectiveness for soil decontamination and electricity production. The results presented here support considerations about soil resilience through microbial communities and orient further research on contaminant degradation by TMFCs

Human hippocampal CA3 damage disrupts both recent and remote episodic memories

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance

CD44: A New Prognostic Marker in Colorectal Cancer?

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications

Evolutionary history of endogenous Human Herpesvirus 6 reflects human migration out of Africa

Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result, ∼70 million people harbor the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if 1) these integrations are ancient, 2) if they still occur, and 3) whether circulating virus strains differ from integrated ones. Here, we used next-generation sequencing and mining of public human genome data sets to generate the largest and most diverse collection of circulating and integrated HHV-6 genomes studied to date. In genomes of geographically dispersed, only distantly related people, we identified clades of integrated viruses that originated from a single ancestral event, confirming this with fluorescent in situ hybridization to directly observe the integration locus. In contrast to HHV-6B, circulating and integrated HHV-6A sequences form distinct clades, arguing against ongoing integration of circulating HHV-6A or “reactivation” of integrated HHV-6A. Taken together, our study provides the first comprehensive picture of the evolution of HHV-6, and reveals that integration of heritable HHV-6 has occurred since the time of, if not before, human migrations out of Africa

The human carotid atherosclerotic plaque: an observational review of histological scoring systems

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (&lt;65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events

The Ethics of Delusional Belief

In this paper we address the ethics of adopting delusional beliefs and we apply consequentialist and deontological considerations to the epistemic evaluation of delusions. Delusions are characterised by their epistemic shortcomings and they are often defined as false and irrational beliefs. Despite this, when agents are overwhelmed by negative emotions due to the effects of trauma or previous adversities, or when they are subject to anxiety and stress as a result of hypersalient experience, the adoption of a delusional belief can prevent a serious epistemic harm from occurring. For instance, delusions can allow agents to remain in touch with their environment overcoming the disruptive effect of negative emotions and anxiety. Moreover, agents are not blameworthy for adopting their delusions if their ability to believe otherwise is compromised. There is evidence suggesting that no evidence-related action that would counterfactually lead them to believe otherwise is typically available to them. The lack of ability to believe otherwise, together with some other conditions, implies that the agents are not blameworthy for their delusions. The examination of the epistemic status of delusions prompts us to acknowledge the complexity and contextual nature of epistemic evaluation, establish connections between consequentialist and deontological frameworks in epistemology, and introduce the notion of epistemic innocence into the vocabulary of epistemic evaluatio

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis

CD44: A New Prognostic Marker in Colorectal Cancer?

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial-mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications