Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus

Introduction. Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. Materials and Methods. The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. Results. The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p<0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p<0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p<0.001). Conclusions. The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1. Clin Ter 2010; 161(1):e1-e1

Downregulation of TFPI in breast cancer cells induces tyrosine phosphorylation signaling and increases metastatic growth by stimulating cell motility

<p>Abstract</p> <p>Background</p> <p>Increased hemostatic activity is common in many cancer types and often causes additional complications and even death. Circumstantial evidence suggests that tissue factor pathway inhibitor-1 (TFPI) plays a role in cancer development. We recently reported that downregulation of TFPI inhibited apoptosis in a breast cancer cell line. In this study, we investigated the effects of TFPI on self-sustained growth and motility of these cells, and of another invasive breast cancer cell type (MDA-MB-231).</p> <p>Methods</p> <p>Stable cell lines with TFPI (both α and β) and only TFPIβ downregulated were created using RNA interference technology. We investigated the ability of the transduced cells to grow, when seeded at low densities, and to form colonies, along with metastatic characteristics such as adhesion, migration and invasion.</p> <p>Results</p> <p>Downregulation of TFPI was associated with increased self-sustained cell growth. An increase in cell attachment and spreading was observed to collagen type I, together with elevated levels of integrin α2. Downregulation of TFPI also stimulated migration and invasion of cells, and elevated MMP activity was involved in the increased invasion observed. Surprisingly, equivalent results were observed when TFPIβ was downregulated, revealing a novel function of this isoform in cancer metastasis.</p> <p>Conclusions</p> <p>Our results suggest an anti-metastatic effect of TFPI and may provide a novel therapeutic approach in cancer.</p

The interaction of Thrombospondins with extracellular matrix proteins

The thrombospondins (TSPs) are a family of five matricellular proteins that appear to function as adapter molecules to guide extracellular matrix synthesis and tissue remodeling in a variety of normal and disease settings. Various TSPs have been shown to bind to fibronectin, laminin, matrilins, collagens and other extracellular matrix (ECM) proteins. The importance of TSP-1 in this context is underscored by the fact that it is rapidly deposited at the sites of tissue damage by platelets. An association of TSPs with collagens has been known for over 25 years. The observation that the disruption of the TSP-2 gene in mice leads to collagen fibril abnormalities provided important in vivo evidence that these interactions are physiologically important. Recent biochemical studies have shown that TSP-5 promotes collagen fibril assembly and structural studies suggest that TSPs may interact with collagens through a highly conserved potential metal ion dependent adhesion site (MIDAS). These interactions are critical for normal tissue homeostasis, tumor progression and the etiology of skeletal dysplasias

Revealing future trajectories in sustainable food production: convergence and openness in the innovation ecosystem

PurposeThis paper aims to explore the evolutionary dynamics of innovation ecosystems in the food industry by adopting both open innovation and convergence approaches to derive practical policy implications to develop impactful innovation ecosystems to promote food production sustainably.Design/methodology/approachStarting from the cutting-edge case of Foodvalley in the Netherlands, the study adopts a backcasting approach to reach a future vision of food ecosystems from a sustainable food production perspective. The authors set the backcasting analysis in four steps: (1) description of the present and trends analysis, (2) selection of trustworthy criteria and goals, (3) development of future images and (4) analysis of how to reach the images.FindingsThe trends analysis has identified three existing innovation fields - protein shift, circular agrifood and food and health - and two strategic directions - convergence and localness decrease. The study reports how a long-term commitment may lead the valley toward a best future scenario.Practical implicationsThe study suggests that policymakers and stakeholders can promote innovation strategies in sustainable food production ecosystems by encouraging collaboration between different sectors, reducing regulatory barriers, attracting innovative actors, and investing in education and training programs. To achieve measurable environmental and social impact outcomes, policies should promote entrepreneurship and create an enabling environment that encourages innovation and risk-taking.Originality/valueThe originality of this paper concerns the backcasting perspective applied to the analysis of the food ecosystem. This approach facilitates the identification of a path direction for successfully managing open innovation and industry convergence toward a desirable future of sustainable food production

Changes in the Market Access Process to Combat COVID-19. An Exploratory Study in Italy

The aim of this article is to extend market access literature about specific changes considering the COVID-19 pandemic and what lessons can be taken to make the patient access more efficient. We explored the Italy case of the market access process during the outbreak. Overall, our results show that in an emergency, as the one due to the COVID-19 crisis, the market access undergoes significant changes because some levels of the process seem to be more affected than others. In sum, there seems to be a trend toward a more digitalized and horizontal process, which reduces the times of bureaucracy and overcomes the traditional hierarchical structure of the market access by downsizing the role of the regions in favor of a more direct dialogue between the national agency and the local hospitals. This article contains some relevant implications for policy making. We attempt to unveil empirically the most important changes that occurred in the market access process during the COVID-19 emergency by performing a comparison with the market access process before and after the outbreak