Upper body balance control strategy during continuous 3D postural perturbation in young adults

We explored how changes in vision and perturbation frequency impacted upright postural control in healthy adults exposed to continuous multiaxial support-surface perturbation. Ten subjects were asked to maintain equilibrium in standing stance with eyes open (EO) and eyes closed (EC) during sinusoidal 3D rotations at 0.25 (L) and 0.50 Hz (H). We measured upper-body kinematics – head, trunk, and pelvis – and analyzed differences in horizontal displacements and roll, pitch, and yaw sways. The presence of vision significantly decreased upper-body displacements in the horizontal plane, especially at the head level, while in EC the head was the most unstable segment. H trials produced a greater segment stabilization compared to L ones in EO and EC. Analysis of sways showed that in EO participants stabilized their posture by reducing the variability of trunk angles; in H trials a sway decrease for the examined segments was observed in the yaw plane and, for the pelvis only, in the pitch plane. Our results suggest that, during continuous multiaxial perturbations, visual information induced: (i) in L condition, a continuous reconfiguration of multi-body-segments orientation to follow the perturbation; (ii) in H condition, a compensation for the ongoing perturbation. These findings were not confirmed in EC where the same strategy – that is, the use of the pelvis as a reference frame for the body balance was adopted both in L and H

Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed. After general disappointment around CVOTs assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1 receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non-fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause mortality. While available mechanistic studies largely support a cardioprotective effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular death was unexpected and deserves future investigation. We herein review the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate CVOT findings into clinical practice

clinical conundrums in antithrombotic therapy management a delphi consensus panel

Abstract Background Anticoagulants are recommended for the prevention of stroke/systemic embolism for most patients with atrial fibrillation (AF) and for the treatment of patients with venous thromboembolism (VTE). Regulatory-driven randomized trials, however, typically exclude extreme patient scenarios involving, for instance, severe bleeding, ischaemic risk, frailty or renal impairment, despite their common occurrence in clinical practice. Uncertainty in the management of such cases leads to a high degree of variability in therapeutic approaches. Consensus conferences or panels may provide insights and help bridge the gaps that separate clinical guidelines from real-world practice. In the present study, a description of challenging AF and VTE patients was submitted to a large panel of experts to investigate areas of common or divergent management. Method A modified-Delphi method was used to obtain consensus among 178 Italian AF and VTE specialists. A questionnaire was sent on the appropriateness of anticoagulant therapy in AF and VTE cases, including CHA 2 DS 2 -VASc=1, comorbid coronary artery disease, frailty, advanced age, risk of falling, prior haemorrhagic stroke, and low- or intermediate-risk pulmonary embolism. Strategies to improve guideline adherence were also investigated. Results All participants completed the questionnaire. Consensus was reached on many, but not all cases, leaving uncertainty on some debated topics (conundrums) where decisions are unsupported by clinical studies or driven by controversial results. Conclusions The indications emerging from this large panel of experts may help guide the management of challenging AF or VTE cases. Studies are needed addressing treatment options in those cases for whom no consensus was reached

Angiogenic potential of human dental pulp stromal (stem) cells.

Dental pulp is a heterogeneous microenviroment where unipotent progenitor and pluripotent mesenchymal stem cells cohabit. In this study we investigated whether human Dental Pulp Stromal (Stem) Cells (DP-SCs) committed to the angiogenic fate. DP-SCs showed the specific mesenchymal immunophenotypical profile positive for CD29, CD44, CD73, CD105, CD166 and negative for CD14, CD34, CD45, in accordance with that reported for bone marrow-derived SCs. The Oct-4 expression in DP-SCs, evaluated through RT-PCR analysis, increased in relation with the number of the passages in cell culture and decreased after angiogenic induction. In agreement with their multipotency, DP-SCs differentiated toward osteogenic and adipogenic commitments. In angiogenic experiments, differentiation of DP-SCs, through Vascular Endothelial Growth Factor (VEGF) induction, was evaluated by in vitro matrigel assay and by cytometric analysis. Accordingly, endothelial-specific markers like Flt-1 and KDR were basally expressed and they increased after exposure to VEGF together with the occurrence of ICAM-1 and von Willebrand Factor positive cells. In addition, VEGF-induced DP-SCs maintained endothelial cell-like features when cultured in a 3-D fibrin mesh, displaying focal organization into capillary-like structures. The DP-SC angiogenic potential may prove a remarkable tool for novel approaches to developing tissue-engineered vascular grafts which are useful when vascularization of ischemic tissues is required

Paediatric HIV infection in the 'omics era: defining transcriptional signatures of viral control and vaccine responses

Modern technologies and their increased accessibility have shifted 'benchtop' medical research to the larger dimension of 'omics. The huge amount of data derived from gene expression and sequencing experiments has propelled physicians, basic scientists and bioinformaticians towards a common goal to transform 'big data' into predictive constructs that are readily available and will offer clinical utility. Although most of the studies available in the literature have been performed on healthy subjects and in peripheral blood mononuclear cells (PBMC), which are a heterogenous and extremely variable pool of cells, scientists are now trying to address mechanistic questions in purified cell subsets in pathological conditions. In the field of HIV, few attempts have been made to comprehensively evaluate gene-expression profiles of infected patients with different disease status. With the view of discovering a path towards remission or viral eradication, perinatally HIV-infected children represent a unique model. In fact the well-defined time of infection and the resulting opportunity to start early treatment, thereby generating a smaller size of viral reservoir and a more intact immune system, allow for investigation of therapeutic strategies to defeat the virus. In this scenario, 'transcriptomic' or gene expression technologies and supporting bioinformatics applications need to be strategically integrated to provide novel information about immune correlates of virus control following treatment interruption. Here we review modern techniques for gene expression analysis and discuss the best transcriptomic strategies applicable to the field of functional cure in paediatric HIV infection

Decoding the role of the lncRNA HOTAIRM1 in human motor neurons

The mammalian genome produces thousands of long non-coding RNAs (lncRNAs), which have been demonstrated to be fundamental in the control of many biological processes. These molecules play a crucial role in the multilayered regulation of physiological and disease-related gene expression programs, having significant implications in shaping central nervous system (CNS) complexity. Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The coordinated activity of transcription factors and non-coding RNAs (ncRNAs), organized in intricate regulatory networks, drives cell fate specification ensuring correct and specific neuronal functions. We previously described,1 at both the molecular and functional level, the lncRNA nHOTAIRM1 as a neuronal-enriched transcript, which is upregulated during in vitro neuronal differentiation and highly expressed in post-mitotic motor neurons (MNs). We demonstrated that the nuclear nHOTAIRM1, even if much less abundant than its cytoplasmic counterpart, it is involved in the achievement of correct neuronal differentiation timing as an epigenetic regulator of NEUROG2 expression.1 Remarkably, among all human brain tissues, nHOTAIRM1 is specifically expressed in the spinal cord. Consistently, we found that nHOTAIRM1 accumulates in MN-enriched ventral spinal cord lineages differentiated from human induced pluripotent stem cells (iPSCs).1 All this evidence prompted us to further investigate the role of the highly expressed nHOTAIRM1 specifically on MN generation and/or function, to ultimately determine whether its deregulation affects MN differentiation and activity. To experimentally address these questions, here we applied a genome editing-based loss-of-function approach to a model system that efficiently recapitulates spinal MN differentiation, and we identified key nHOTAIRM1 target genes implicated in MN maturation, morphology and activity. Our findings allowed us to conclude that nHOTAIRM1 directs multiple crucial aspects of MN physiology, from their development to the acquisition of appropriate morphological features and motor function

Possible Impacts of C-ITS on Supply-Chain Logistics System

The purpose of this research is to introduce an analysis, which is qualitative and whenever possible quantitative, on how Cooperative Intelligent Transport Systems (C-ITS) can affect a Supply-Chain Logistics System by adopting a three-level approach. Considerations are made on the role and importance of Logistics within a company, its cost structure and the strategic relevance it assumes within the Supply-Chain, while considering its evolution from a Physical Distribution Management to a Supply-Chain Management. The increasing importance of logistics requires more sophisticated solutions to reduce or optimize its costs, as well as to find new opportunities to redesign the network configuration and the value-chain. These applications require a careful evaluation method in order to assess their effective adoption. The research is based on a literature review of the most relevant European Road ITS and C-ITS projects evaluation methods and benefits. The result of the investigation is an analysis that classifies the impact of C-ITS on the structure of the Supply-Chain according to different levels. Firstly, the paper reports the different impacts of a large-scale C-ITS deployment on the Logistics cost structure of a company and more in general, on the expected costs. After that, a second level of analysis deals with a possible redesign of the Distribution Network, oriented to the optimization of transportation costs over long distances. Finally, the third step of the analysis investigates a possible impact of C-ITS on the value-chain from several perspectives within the different roles of the subjects involved in the Supply Chain

Francesca da Rimini : un libretto di Felice Romani, tra Dante e Mazzini

Analizzando tre testi di autori teatrali italiani a cavallo tra XVIII e XIX secolo, che scelsero la tragedia di Paolo e Francesca come dramma di prosa, si indagheranno in questo studio le modifiche che porteranno alla scrittura, ad opera di Felice Romani, di uno dei suoi libretti meno famosi: Francesca da RiminiThrough an analysis of three texts by Italian playwrights at the turn of the eighteenth and nineteenth century, who chose the tragedy of Paolo and Francesca as a prose drama, this article will study the adaptations in the writing of one of Felice Romani's lesser-known librettos: Francesca da Rimini