Prevalence of hypertension and correlation with mental health in women with burning mouth syndrome: A case-control study

BackgroundThe relationship between hypertension (HTN) and chronic pain is still a matter of debate, and its prevalence in patients with burning mouth syndrome (BMS) has never been evaluated. This study aimed to assess the prevalence of HTN in women with BMS and to evaluate its relationship with potential predictors such as risk factors for cardiovascular diseases, pain, and mental health status analyzing differences with healthy women.MethodsIn total, 250 women with BMS (WBMS) were prospectively recruited and compared with an equal number of healthy women (HW) matched for age. Education, body mass index, smoke and alcohol consumption, intensity and quality of pain, and psychological profile were further investigated to identify the potential predictors of HTN. Specifically, pain assessment [the Numeric Rating Scale (NRS) and Short-Form McGill Pain Questionnaire (SF-MPQ)] and psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS)] was carried out for the participants.ResultsHTN was found in 128 (51.2%) WBMS and 76 (30.4%) HW (p < 0.001**). The scores of the NRS, SF-MPQ, HAM-D, HAM-A, and PSQI were statistically significantly higher in the WBMS than in the HW (p < 0.001**). A strongly linear correlation between HTN and employment status, systemic diseases, and education level (p < 0.001**) was found in WBMS, while a strong correlation between HTN and employment status, hypercholesterolemia, systemic diseases, and drug consumption was found in HW (p < 0.001**). No statistically significant correlation was found between HTN and pain, anxiety, depression, and sleep disturbances.ConclusionThese results suggest that WBMS showed a higher prevalence of HTN compared with controls. Unemployed WBMS with lower education and other systemic comorbidities are at an increased risk of developing HTN. HTN is associated with alteration in the vascular structure and function of the brain, and these processes accelerate brain aging, which contributes to a reduction in intracortical connectivity, thus affecting the modulatory system of control of pain in patients with BMS, independently of their mental health assessment. Predictors that may underlie this association remain unclear, taking into account the differences found in HW, and should be further elucidated

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

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

Identification and functional characterization of the G-protein coupled receptor APJ and its ligand apelin in embryonic stem cells: a novel pathway regulating mammalian cardiomyogenesis

The commitment of mesodermal precursors to a cardiac fate is one of the first events in embryogenesis. It results from inductive interactions occurring during gastrulation in a temporally and spatially regulated manner. Embryonic Stem Cells (ESCs) are a powerful tool to study the early events of cardiac lineage specification in mammals; in particular, several cardiac cell populations have been generated from differentiating ESCs and studies of gene expression profiles indicate that their development in culture recapitulates cardiogenesis in the early embryo. Thus, ESCs represent a valid model to elucidate the origin and the molecular identity of cardiovascular progenitor populations as well as to identify key regulators of cardiac specification in mammals for which the molecular control is largely unknown. Cripto/ALK4/Smad2 signaling is a key pathway required for the correct cardiac myogenesis, acting in the early phases of ESC differentiation. Here we report the identification of the Angiotensin II Type ReceptorLike I (AGTRL1/ APJ/msr1) and its ligand Apelin as previously unrecognized downstream targets of Cripto/Smad2 signaling both in vivo and in ESCs. Gain of function experiments show that APJ suppresses neuronal differentiation, which spontaneously occurs in cripto/ ESCs, and restore the cardiac program, activating the expression of genes pivotal for cardiac specification and terminal differentiation. Furthermore, lossoffunction experiments reveal, for the first time to our knowledge, a central role for APJ/Apelin signaling in the gene regulatory cascade promoting ESC cardiac specification and differentiation. Most remarkably, we show that Apelin promotes cardiomyogenesis via activation of pERK/p70S6 through coupling to a Go/Gi protein. Together our data point for a previously undescribed functional link between Cripto/Smad2 and APJ/Apelin in the signaling pathways that govern mesoderm patterning and cardiac specification in mammals. Finally, to further investigate the role of APJ/Apelin signaling in the control of ESC differentiation and, in particular, in the specification of cardiovascular progenitors, we have generated an inducible ESC line, which allow overexpression of APJ in a timespecific manner, by using the tetracycline (Tet)regulated transactivator system. Our data reveal that APJ overexpression, in an early time window of wildtype ESC differentiation, promotes the expression of markers of the cardiovascular lineage and markedly increases the number of cardiomyocytes

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

Temporal proteomic profiling of embryonic stem cell secretome during cardiac and neural differentiation

During recent years, increased efforts have focused on elucidating the pluripotency and self-renewal of stem cells. Differentiation towards the different lineages has attracted significant attention given the potential use of stem cells in regenerative medicine. Embryonic stem cell differentiation is a complex process coordinated by strictly regulated extracellular signals that act in an autocrine and/or paracrine manner. Through secreted molecules, stem cells affect local niche biology and influence the cross-talking with the surrounding tissues. Emerging evidence supports the hypothesis that fundamental cell functions, including proliferation and differentiation, are strictly regulated by the complex set of molecules secreted from cells. The understanding of this molecular language could largely increase our knowledge on pathways regulating stem cell differentiation. Here, we have used a proteomics platform to investigate the profile of proteins secreted during differentiation of murine embryonic stem cells. We have followed the dynamics of protein secretion by comparing the secretomes at different time points of murine embryonic stem cell cardiac and neural differentiation. In addition to previously reported molecules, we have identified many secreted proteins not described so far as released from embryonic stem cells nor shown to be differentially released during the process of cardiomyogenesis and neurogenesis

Gastruloid development competence discriminates different states of pluripotency

Floating spheroidal aggregates of mouse embryonic stem cells can develop into polarized/elongated organoids, namely gastruloids. We set up a high-performing assay to measure gastruloid formation efficiency (GFE), and found that GFE decreases as pluripotency progresses from naive (GFE ≥ 95%) to primed (GFE = 0) state. Specifically, we show that primed EpiSCs fail to generate proper cell aggregates, while early-primed EpiLCs aggregate but eventually fail to develop into elongated gastruloids. Moreover, we characterized proline-induced cells (PiCs), a LIF-dependent reversible early-primed state of pluripotency, and show that PiCs are able to generate gastruloids (GFE ∼ 50%) and are also competent to differentiate into primordial germ cell-like cells. Thus, we propose the GFE assay as a valuable functional tool to discriminate different states of the pluripotency continuum.This study was supported by the Associazione Italiana per la Ricerca sul Cancro AIRC (grant IG 20736), Italian Ministry of Education-University-Research (grant CTN01_00177 Cluster ALISEI_IRMI and PRIN 2017XJ38A4), and Project SATIN-POR Campania FESR 2014/2020 to G.M. A.M-A.’s research is funded by an ERC Advanced Investigator award (834580

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