Decision-making in advanced heart failure patients requiring LVAD insertion: can preoperative simulation become the way forward? A case study

Clinical practice heavily relies on results from randomized controlled trials, which may not reflect completely individual patients. Patient-specific modelling has received increasing attention in recent years. Although still far from clinical application on a daily basis, the potential of this approach is significant. The treatment of advanced heart failure may benefit from a modelling framework to guide device treatment and predict outcome. The role of mechanical circulatory support as a long-term solution is increasing in view of the evolving technology and worsening heart failure patient population. Therefore, a preoperative strategy with the ability to predict the course of events in a simulation setting may be justified. Here we present a heart failure patient discussed at a multidisciplinary team meeting whose outcome was compared with simulations carried out with CARDIOSIM (C) software to investigate the role of this approach as a planning strategy to guide intervention and predict outcome. The clinical decision process is complex and many factors are involved. Patient-specific modelling may have a role to play as part of a preoperative planning strategy with more quantitative evaluation to smooth decision-making

Simulation as a preoperative planning approach in advanced heart failure patients. A retrospective clinical analysis

Background: Modelling and simulation may become clinically applicable tools for detailed evaluation of the cardiovascular system and clinical decision-making to guide therapeutic intervention. Models based on pressure-volume relationship and zero-dimensional representation of the cardiovascular system may be a suitable choice given their simplicity and versatility. This approach has great potential for application in heart failure where the impact of left ventricular assist devices has played a significant role as a bridge to transplant and more recently as a long-term solution for non eligible candidates. Results: We sought to investigate the value of simulation in the context of three heart failure patients with a view to predict or guide further management. CARDIOSIM© was the software used for this purpose. The study was based on retrospective analysis of haemodynamic data previously discussed at a multidisciplinary meeting. The outcome of the simulations addressed the value of a more quantitative approach in the clinical decision process. Conclusions: Although previous experience, co-morbidities and the risk of potentially fatal complications play a role in clinical decision-making, patient-specific modelling may become a daily approach for selection and optimisation of device-based treatment for heart failure patients. Willingness to adopt this integrated approach may be the key to further progress

Enteric glia: A new player in inflammatory bowel diseases

In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases

The Effect of Manual Therapy on Muscle Stiffness in Healthy Individuals

The purpose of this study was to evaluate the immediate and delayed changes in muscle stiffness (in a resting and contracted state) related to DN of the gastrocnemius compared to a sham DN condition. To further investigate this relationship, we investigated these changes at the site of the TP, as well as at a standard site (medial head of the gastrocnemius). We hypothesize that gastrocnemius DN reduces muscle stiffness in individuals with TP

An evidence map and synthesis review with meta-analysis on the risk of incisional hernia in colorectal surgery with standard closure.

Purpose To assess the incidence of incisional hernia (IH) across various type of incisions in colorectal surgery (CS) creating a map of evidence to define research trends, gaps and areas of future interest. Methods Systematic review of PubMed and Scopus from 2010 onwards. Studies included both open (OS) and laparoscopic (LS). The primary outcome was incidence of IH 12 months after index procedure, secondary outcomes were the study features and their influence on reported proportion of IH. Random effects models were used to calculate pooled proportions. Meta-regression models were performed to explore heterogeneity. Results Ninetyone studies were included reporting 6473 IH. The pooled proportions of IH for OS were 0.35 (95% CI 0.27–0.44) I2 0% in midline laparotomies and 0.02 (95% CI 0.00–0.07), I2 52% for off-midline. In case of LS the pooled proportion of IH for midline extraction sites were 0.10 (95% CI 0.07–0.16), I2 58% and 0.04 (95% CI 0.03–0.06), I2 86% in case of off-midline. In Port-site IH was 0.02 (95% CI 0.01–0.04), I2 82%, and for single incision surgery (SILS) of 0.06—95% CI 0.02–0.15, I2 81%. In case of stoma reversal sites was 0.20 (95% CI 0.16–0.24). Conclusion Midline laparotomies and stoma reversal sites are at high risk for IH and should be considered in research of preventive strategies of closure. After laparoscopic approach IH happens mainly by extraction sites incisions specially midline and also represent an important area of analysis.pre-print3102 K

A 1 m3^3 Gas Time Projection Chamber with Optical Readout for Directional Dark Matter Searches: the CYGNO Experiment

The aim of the CYGNO project is the construction and operation of a 1~m$^3$ gas TPC for directional dark matter searches and coherent neutrino scattering measurements, as a prototype toward the 100-1000~m$^3$ (0.15-1.5 tons) CYGNUS network of underground experiments. In such a TPC, electrons produced by dark-matter- or neutrino-induced nuclear recoils will drift toward and will be multiplied by a three-layer GEM structure, and the light produced in the avalanche processes will be readout by a sCMOS camera, providing a 2D image of the event with a resolution of a few hundred micrometers. Photomultipliers will also provide a simultaneous fast readout of the time profile of the light production, giving information about the third coordinate and hence allowing a 3D reconstruction of the event, from which the direction of the nuclear recoil and consequently the direction of the incoming particle can be inferred. Such a detailed reconstruction of the event topology will also allow a pure and efficient signal to background discrimination. These two features are the key to reach and overcome the solar neutrino background that will ultimately limit non-directional dark matter searches.Comment: 5 page, 7 figures, contribution to the Conference Records of 2018 IEEE NSS/MI

S100B‑p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin‑4 and metalloproteinase‑2 inhibition in C6 glioma cells

S100 calcium‑binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B‑p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5 diphenyltetrazolium bromide‑formazan assay. Significant dose‑dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 μM (58.5±5%; P<0.05), 0.5 μM (40.6±7%; P<0.01) and 5 μM (13±4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 μM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl‑2 (‑60%, P<0.001; ‑80.13%, P<0.001; ‑95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 μM pentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, P<0.05; 1244±94.3%, P<0.01; and 2244±111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase‑2 (42±2.3%, P<0.05; 71±2.5%, P<0.01; and 95.8±3.3%, P<0.001, respectively) and aquaporin 4 (38±2.5%, P<0.05; 69±2.6%, P<0.01; and 88±3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 μM pentamidine compared with untreated cells (88±4.2%, P<0.05; 64±2%, P<0.01; and 42±3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B‑p53 inhibitors may represent a novel approach for the treatment of glioma

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

Long-term sex-dependent vulnerability to metabolic challenges in prenatally stressed rats

Prenatal stress (PNS) might affect the developmental programming of adult chronic diseases such as metabolic and mood disorders. The molecular mechanisms underlying such regulations may rely upon long-term changes in stress-responsive effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect neuronal plasticity underlying mood disorders and may also play a role in metabolic regulation. Based upon previous data, we hypothesized that PNS might lead to greater vulnerability to an obesogenic challenge experienced at adulthood. In order to investigate our hypothesis, pregnant Sprague-Dawley female rats underwent a chronic procedure of restraint stress during the last week of gestation. The adult offspring were then challenged with a high fat diet (HFD) over 8 weeks and tested for metabolic and emotional endpoints. Moreover, brain specific changes in Bdnf expression levels were also assessed. Overall, HFD resulted in increased caloric intake, insulin resistance, impaired glucose tolerance and higher circulating levels of leptin, while PNS increased the leptin/adiponectin ratio, an index of metabolic risk in adult male subjects. Interestingly, HFD consumption increased anxiety-like behaviors in the Elevated Plus Maze, particularly in males, and this effect was buffered by PNS. Levels of Bdnf were finely modulated by PNS and HFD in a region- and sex-dependent fashion: female offspring overall showed greater plasticity, possibly mediated through increased total Bdnf mRNA expression both in the hippocampus and in the hypothalamus. In conclusion, while the experience of maternal stress during intrauterine life promotes metabolic dysfunction induced by a HFD at adulthood, the interaction between PNS and HFD is positive in male subjects, and in agreement with the match-mismatch hypothesis, resulting in a reduction of anxious behaviors

Party system closure and openness: conceptualization, operationalization and validation

The degree of closure of the governmental arena is a central aspect of the stabilization of party systems, and yet little systematic effort has been devoted to its operationalization. The article proposes a new index, examines its reliability and validity, and reports the ranking of 60 party systems. By redefining the units of measurement we suggest new indicators that are uniform and transparent in their logic of construction, can be applied both to specific government-changes and to time periods, and are sensitive to the degree of change. The article finds a hierarchy among the components of party system closure, dominated by coalition formula. While new and established democracies can both produced closed patterns, the analysis of inter-war European party systems shows that closed systems are less prone to authoritarian takeover. The article demonstrates the power of inertia: the completely closed configurations stand out as the most durable ones