If only they knew! A non‐inferiority randomized controlled trial comparing deceptive and open‐label placebo in healthy individuals

BackgroundPlacebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open‐label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers.MethodsWe conducted a non‐inferiority, parallel, randomized, controlled trial, which also included a nested cross‐over no‐treatment condition. This study was conducted at a university clinic in France.ResultsWe included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]−∞; 5.4], and 97.5% CI of ]−∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time–treatment interaction.ConclusionThe study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects.SignificanceThis study is the first to show non‐inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP

Is virtual reality effective to teach prevention of surgical site infections in the operating room? study protocol for a randomised controlled multicentre trial entitled VIP Room study

INTRODUCTION: Some surgical site infections (SSI) could be prevented by following adequate infection prevention and control (IPC) measures. Poor compliance with IPC measures often occurs due to knowledge gaps and insufficient education of healthcare professionals. The education and training of SSI preventive measures does not usually take place in the operating room (OR), due to safety, and organisational and logistic issues. The proposed study aims to compare virtual reality (VR) as a tool for medical students to learn the SSI prevention measures and adequate behaviours (eg, limit movements…) in the OR, to conventional teaching. METHODS AND ANALYSIS: This protocol describes a randomised controlled multicentre trial comparing an educational intervention based on VR simulation to routine education. This multicentre study will be performed in three universities: Grenoble Alpes University (France), Imperial College London (UK) and University of Heidelberg (Germany). Third-year medical students of each university will be randomised in two groups. The students randomised in the intervention group will follow VR teaching. The students randomised in the control group will follow a conventional education programme. Primary outcome will be the difference between scores obtained at the IPC exam at the end of the year between the two groups. The written exam will be the same in the three countries. Secondary outcomes will be satisfaction and students' progression for the VR group. The data will be analysed with intention-to-treat and per protocol. ETHICS AND DISSEMINATION: This study has been approved by the Medical Education Ethics Committee of the London Imperial College (MEEC1920-172), by the Ethical Committee for the Research of Grenoble Alpes University (CER Grenoble Alpes-Avis-2019-099-24-2) and by the Ethics Committee of the Medical Faculty of Heidelberg University (S-765/2019). Results will be published in peer-reviewed medical journals, communicated to participants, general public and all relevant stakeholders

Apolipoprotein D synthesis progressively increases in frontal cortex during human lifespan

Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. In the other way, apo D expression has been correlated, in some brain regions, with normal aging and neurodegenerative diseases. To elucidate the regional and cellular expression of apo D in normal human brain during aging, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot blot techniques, for protein and mRNA, as well as immunohistochemistry and hybridohistochemistry methods were used. A positive correlation for apo D expression with aging was found; furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic HIS showed that apo D is synthesized in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes but with aging the number of neurons that synthesize apo D is increased. Our results indicate that apo D could play a fundamental role in central nervous system aging and in the reduction of products derivated from lipid peroxidation. The increment in the expression of apo D with aging can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by aging

Assessment of electrophoresis and electroosmosis in construction materials: effect of enhancing electrolytes and heavy metals contamination

Electrokinetic effects are those that take place by application of an electric field to porous materials, with the zeta potential as the key parameter. Specifically, in the case of contaminated construction materials, the generation of an electroosmotic flux, with the corresponding dragging due to water transport, is a crucial mechanism to succeed in the treatment of decontamination. Therefore, it is of great interest trying to optimize the treatment by the addition of specific electrolytes enhancing the electrokinetic phenomena. Most of the data of zeta potential found in literature for construction materials are based in micro-electrophoresis measurements, which are quite far of the real conditions of application of the remediation treatments. In this paper, electrophoretic and electroosmotic experiments, with monolithic and powdered material respectively, have been carried out for mortar, brick and granite clean and contaminated with Cs, Sr, Co, Cd, Cu and Pb. The electrolytes tested have been distilled water (DW), Na2–EDTA, oxalic acid, acetic acid and citric acid. The zeta potential values have been determined through the two different techniques and the results compared and critically analysed

Molecular Dynamics Analysis of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism for Selective Oxidation of Met-93

Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown. Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus providing a plausible mechanism by which eicosatetraenoic acids bearing hydroperoxides on different carbon atoms can interact with Met93 to yield Met93 sulfoxide (Met93SO). Simulations of glycosylated apoD indicated that a second solvent exposed Met at position 49 was shielded by a triantennerary N-glycan attached to Asn45 thereby precluding lipid interactions. MD simulations of apoD showed B-factors of the loop containing Met93SO were higher in the oxidized protein, indicating increased flexibility that is predicted to destabilize the protein and promote self-association. Conclusions/Significance: These studies provide novel insights into the mechanisms that may contribute to the antioxidant function of apoD and the structural consequences that result if Met93SO is not redox-cycled back to its native state

Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Background To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg). Methodology Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well. Conclusion and significance SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting Cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Gene expression in human alcoholism: Microarray analysis of frontal cortex

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were downregulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol