What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

The jury on trial: Guilty or not guilty? Investigating jury trial issues through a comparative approach

In response to the democratic principle ‘justice by the people and for the people’, many jurisdictions worldwide choose to use the jury trial. European juries differ from Anglo-American juries and from one another in several aspects. However, despite the differences, none of the jurisdictions that uses juries seems to have found the ‘perfect recipe’ for a well-functioning jury system. The occurrence of miscarriages of justice involving incorrect jury verdicts demonstrates that the jury trial as a whole may be failing to respond to those democratic needs that constituted the foundations of its introduction. Nevertheless, the jury system appears to be ineradicably rooted in those jurisdictions that chose to introduce it. Clearly, the current situation calls for reform. This chapter, looking at juries from an international standpoint, proposes a critical comparative analysis of some of the most worrying issues occurring in jury decision-making contexts. As the chapter will show, in the search for solutions, comparisons at the international level can offer fruitful insights on how to promote improvement and reform of the jury trial worldwide. </p

Naming the threat: lay prototypes of organized crime in Italy and the US

Aims. Our goal is to detail the development of RS Ophiuchi and the other Galactic symbiotic-like recurrent novae throughout their outburst and quiescence, with a particular emphasis on the propagation of the shock wave during the outburst of the binaries. Methods. The spectral analysis has been performed using archival data according to the features of the individual datasets. Swift grism spectra were reduced and extracted using a combination of the pre-existing UVOTPY Python routine and newly written pipelines in Matlab. Other datasets were directly available in reduced form, already corrected for instrumental or background contamination, and calibrated in wavelength and flux or intensity. The work on these was done through pipelines suited for reading the data and elaborating them to extract quantities of interest for the analysis. Results. We find striking similarities in different outbursts of the same object and for different novae. For example, RS Oph 2021 was almost identical to the 2006 outburst, despite having occurred at a different orbital phase with the observations made from a different line of sight through the red giant wind. Despite the intrinsically different properties of the binaries, striking similarities are found for different systems of the same class, for instance, the trend of the electron density over time during outburst appears to follow a general temporal development.</p

Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics

Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior; however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate. L-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe+2/αKG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymes’ subcellular localization. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons. In the nucleus, VitC enhances the activity of DNA and histone demethylases, improving somatic cell reprogramming and pushing embryonic stem cell towards the naive pluripotent state. The broad spectrum of actions of VitC highlights its relevance for stem cell biology in both physiology and disease

The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus-Baf60c axis in embryonic stem cell cardiomyogenesis

Mammalian cardiomyogenesis occurs through a multistep process that requires a complex network of tightly regulated extracellular signals, which integrate with the genetic and epigenetic machinery to maintain, expand, and regulate the differentiation of cardiac progenitor cells. Pluripotent embryonic stem cells (ESCs) recapitulate many aspects of development, and have provided an excellent opportunity to dissect the molecular mechanisms underlying cardiomyogenesis, which is still incompletely defined

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

3D embryonic stem cell (ESC) aggregates self-organize into embryo-like structures named gastruloids that recapitulate the axial organization of post-implantation embryos. Crucial in this process is the symmetry-breaking event that leads to the emergence of asymmetry and spatially ordered structures from homogeneous cell aggregates. Here, we show that budesonide, a glucocorticoid drug widely used to treat asthma, prevents ESC aggregates to break symmetry. Mechanistically, the effect of budesonide is glucocorticoid receptor independent. RNA sequencing and lineage fate analysis reveal that budesonide counteracts exit from pluripotency and modifies the expression of a large set of genes associated with cell migration, A-P axis formation, and WNT signaling. This correlates with reduced phenotypic and molecular cell heterogeneity, persistence of E-CADHERIN at the cell-cell interface, and cell aggregate compaction. Our findings reveal that cell-cell adhesion properties control symmetry breaking and cell fate transition in 3D gastruloids and suggest a potential adverse effect of budesonide on embryo development