An immersive virtual reality exergame as a patient education approach in fibromyalgia: Pilot study.

Background: Immersive Virtual Reality (VR) has been applied in pain management for various conditions, but its use in fibromyalgia (FM) remains underexplored. While physical activity plays a role in treating FM, patients' low tolerance often limits its effectiveness. After reviewing the literature on VR and games for FM, we designed a novel VR exergame to assist FM patients in performing physical activity, and evaluate its feasibility.

Inference on COVID-19 Epidemiological Parameters Using Bayesian Survival Analysis.

The need to provide accurate predictions in the evolution of the COVID-19 epidemic has motivated the development of different epidemiological models. These models require a careful calibration of their parameters to capture the dynamics of the phenomena and the uncertainty in the data. This work analyzes different parameters related to the personal evolution of COVID-19 (i.

Social contacts, epidemic spreading and health system. Mathematical modeling and applications to COVID-19 infection.

Lockdown and social distancing, as well as testing and contact tracing, are the main measures assumed by the governments to control and limit the spread of COVID-19 infection. In reason of that, special attention was recently paid by the scientific community to the mathematical modeling of infection spreading by including in classical models the effects of the distribution of contacts between individuals. Among other approaches, the coupling of the classical SIR model with a statistical study of the distribution of social contacts among the population, led some of the present authors to build a Social SIR model, able to accurately follow the effect of the decrease in contacts resulting from the lockdown measures adopted in various European countries in the first phase of the epidemic.

Novel targets to cure primary myelofibrosis from studies on Gata1 mice.

In 2002, we discovered that mice carrying the hypomorphic Gata1 mutation that reduces expression of the transcription factor GATA1 in megakaryocytes (Gata1 mice) develop myelofibrosis, a phenotype that recapitulates the features of primary myelofibrosis (PMF), the most severe of the Philadelphia-negative myeloproliferative neoplasms (MPNs). At that time, this discovery had a great impact on the field because mutations driving the development of PMF had yet to be discovered. Later studies identified that PMF, as the others MPNs, is associated with mutations activating the thrombopoietin/JAK2 axis raising great hope that JAK inhibitors may be effective to treat the disease.

Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology.

Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease.

Dexamethasone Predisposes Human Erythroblasts Toward Impaired Lipid Metabolism and Renders Their Expansion Highly Dependent on Plasma Lipoproteins.

Cultures of stem cells from discarded sources supplemented with dexamethasone, a synthetic glucocorticoid receptor agonist, generate cultured red blood cells (cRBCs) in numbers sufficient for transfusion. According to the literature, however, erythroblasts generated with dexamethasone exhibit low enucleation rates giving rise to cRBCs that survive poorly . The knowledge that the glucocorticoid receptor regulates lipid metabolism and that lipid composition dictates the fragility of the plasma membrane suggests that insufficient lipid bioavailability restrains generation of cRBCs.

Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes.

The physiological effects of acetylcholine on keratinocytes depend on the presence of nicotinic and muscarinic receptors. The role of nonneuronal acetylcholine in keratinocytes could have important clinical implications for patients with various skin disorders such as nonhealing wounds. In order to evaluate the efficacy of highly diluted acetylcholine solutions obtained by sequential kinetic activation, we aimed to investigate the effects of these solutions on normal human keratinocytes.

Role of vitamin D combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells.

Background: Gastric diseases are a worldwide problem in modern society, as reported in the USA, in the range of 0.5-2 episodes/year/person and an incidence of 5-100 episodes/1000/week according to seasons and age. There is convincing evidence that oxidative stress is involved in the pathogenesis of acute gastric injury.

Protective effects of 1α,25-Dihydroxyvitamin D3 on cultured neural cells exposed to catalytic iron.

Recent studies have postulated a role for vitamin D and its receptor on cerebral function, and anti-inflammatory, immunomodulatory and neuroprotective effects have been described; vitamin D can inhibit proinflammatory cytokines and nitric oxide synthesis during various neurodegenerative insults, and may be considered as a potential drug for the treatment of these disorders. In addition, iron is crucial for neuronal development and neurotransmitter production in the brain, but its accumulation as catalytic form (Fe(3+)) impairs brain function and causes the dysregulation of iron metabolism leading to tissue damage due to the formation of toxic free radicals (ROS). This research was planned to study the role of vitamin D to prevent iron damage in neuroblastoma BE(2)M17 cells.

Neurokinin (NK)-1 receptor expression in monocytes from bipolar disorder patients: a pilot study.

Background: Neurokinin 1 receptors (NK-1R) have been involved in several psychiatric disorders including major depression, but less is known for bipolar disorder (BD).

Method: We compared NK-1R expression and Substance P (SP) ability to induce NF-κB activation in monocytes from BD patients and healthy donors (HD), also looking for the effects of tobacco smoke. After informed written consent, 20 euthymic BD patients, either bipolar type 1 (BDI) or type 2 (BDII), and 14 age-matched healthy donors (HD) were enrolled.

Characterization of the anti-inflammatory properties of NCX 429, a dual-acting compound releasing nitric oxide and naproxen.

Aims: Cyclooxygenase (COX)-inhibiting nitric oxide donors (CINODs) are a new class of drugs that structurally combine a COX inhibitor with a nitric oxide (NO) donating moiety. This combination reduces potential toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) whilst maintaining the analgesic and anti-inflammatory effects. The present study was undertaken to investigate the anti-inflammatory effects of NCX 429, a naproxen-based CINOD, and to assess the additional properties of NO donation beyond those related to naproxen.

Montelukast prevents microparticle-induced inflammatory and functional alterations in human bronchial smooth muscle cells.

Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation.

Recurrent major depressive disorder: Imbalance of neurokinin (NK)-1 and NK-2 receptor expression in monocytes.

Increasing evidence suggests that tachykinins are involved in the control of different pathological conditions, including psychiatric disorders. In this study we evaluated the expression of NK(1) and NK(2) receptors (NK-1R and NK-2R), as well as the effects of substance P (SP) and neurokinin A (NKA), in monocytes isolated from 15 healthy subjects and 15 patients with recurrent major depressive disorder (RMDD), under stable antidepressant therapy. NK-1R expression in monocytes from RMDD patients was significantly decreased as compared to healthy subjects, whereas NK-2R expression was markedly increased.

Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation.

Background And Purpose: An important objective in asthma therapy is to prevent the accelerated growth of airway smooth muscle cells which leads to hyperplasia and bronchial hyperreactivity. We investigated the effect of combination of salbutamol and PPARγ agonists on growth factor-stimulated human bronchial smooth muscle cell (BSMC) proliferation.

Experimental Approach: Synergism was quantified by the combination index-isobologram method.

Functional SNPs within the intron 1 of the PROP1 gene contribute to combined growth hormone deficiency (CPHD).

Context: Mutations within the PROP1 gene represent one of the main causes of familial combined pituitary hormone deficiency (CPHD). However, most of the cases are sporadic with an unknown genetic cause.

Objective: The aim of this study was the search for low penetrance variations within and around a conserved regulatory element in the intron 1 of PROP1, contributing to a multifactorial form of the disease in sporadic patients.

Autocrine activation of human monocyte/macrophages by monocyte-derived microparticles and modulation by PPARγ ligands.

Background And Purpose: Microparticles (MPs), small membrane-bound particles originating from different cell types during activation or apoptosis, mediate intercellular communication, exert pro-coagulant activity and affect inflammation and other pathophysiological conditions. Monocyte-derived MPs have undergone little investigation and, to our knowledge, have never been evaluated for their possible autocrine effects. Therefore, we assessed the ability of monocyte-derived MPs to stimulate human monocytes and monocyte-derived macrophages (MDM).

Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison.

Role of NF-kappaB and PPAR-gamma in lung inflammation induced by monocyte-derived microparticles.

Microparticles (MP) are phospholipid vesicles shed by cells upon activation or apoptosis. Monocyte-derived MP upregulate the synthesis of proinflammatory mediators by lung epithelial cells; the molecular bases of such activity are unknown. Peroxisome proliferator-activated receptors (PPAR) have been demonstrated to be involved in the modulation of nuclear factor (NF)-κB transcriptional activity and inflammation.

Rosiglitazone reverses salbutamol-induced β(2) -adrenoceptor tolerance in airway smooth muscle.

Background And Purpose: β₂-Adrenoceptor agonists are important therapeutic agents in the treatment of asthma and chronic obstructive pulmonary disease. The regular use of these drugs has been associated with proasthmatic-like changes that limit their efficacy and increase the risk of severe adverse reactions. We investigated whether the peroxisome-proliferator-activated receptor (PPAR)γ agonist rosiglitazone modulated salbutamol-induced β₂-adrenoceptor desensitization in vivo and in vitro.

The nitric oxide-donating pravastatin, NCX 6550, inhibits cytokine release and NF-κB activation while enhancing PPARγ expression in human monocyte/macrophages.

Previous studies have shown that NCX 6550 (NCX), a nitric oxide (NO)-donating pravastatin, induces anti-inflammatory effects in murine macrophage cell lines. Here, we have studied its activity in human monocyte/macrophages, by investigating cytokine release, NF-κB translocation and peroxisome proliferator-activated receptor γ (PPARγ) expression and function. For comparison, pravastatin, isosorbide-5-mononitrate (ISMN), sodium nitroprusside (SNP) and the PPARγ ligand 15-deoxy-Δ(12,14)-prostaglandin J(2) (PGJ) were also tested.

Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans.

Objective: Atherosclerosis and restenosis are largely ruled by inflammation. The aim of this study was to test the effects of a short-course, high-dose oral prednisone on the release of interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha from circulating monocytes and on the neointimal growth that follows bare metal stent (BMS) implantation. In a sub-group of patients activated NF-kappaB was also evaluated.

The 423Q polymorphism of the X-linked inhibitor of apoptosis gene influences monocyte function and is associated with periodic fever.

Objective: Hereditary periodic fever syndromes (HPFs) develop as a result of uncontrolled activation of the inflammatory response, with a substantial contribution from interleukin-1beta or tumor necrosis factor alpha (TNFalpha). The HPFs include familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), TNF receptor-associated syndrome (TRAPS), and cryopyrinopathies, which are attributable to mutations of the MEFV, MVK, TNFRSF1A, and CIAS1 genes, respectively. However, in many patients, the mutated gene has not been determined; therefore, the condition in these patients with an HPF-like clinical picture is referred to as idiopathic periodic fever (IPF).

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.

Background And Purpose: Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPARgamma in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARgamma.

Enhanced peroxisome proliferator-activated receptor-gamma expression in monocyte/macrophages from coronary artery disease patients and possible gender differences.

Peroxisome proliferator-activated receptor (PPAR) activation reduces inflammation and atherosclerosis, but recent evidence raised concerns about its beneficial clinical effects. However, the effects of gender on PPAR expression and basal cytokine release have not been investigated. In the present study, we evaluated PPAR-gamma and -alpha expression, as well as cytokine release, in monocyte/macrophages from 15 male and 15 female patients with coronary artery disease (CAD) in comparison with healthy controls.

A recurrent signal peptide mutation in the growth hormone releasing hormone receptor with defective translocation to the cell surface and isolated growth hormone deficiency.

Context: Mutations in the GHRH receptor (GHRHR) have been detected in the familial type-IB isolated GH deficiency (IGHD-IB) inherited as an autosomal recessive disorder and characterized by a low but detectable serum GH level and good response to substitutive GH therapy.

Objective: The aim of our study was the identification of mutations in sporadic patients with a IGHD-IB phenotype.

Subjects And Methods: The GHRHR gene was systematically screened by DHPLC in 134 IGHD patients with no family history of the disorder or declared parental consanguinity.