The increase of suicide rates: the need for a paradigm shift

Suicide was highlighted as a major public health issue in a recent release of data by the US Centers for Disease Control and Prevention (CDC).1 The CDC reported a 30% increase (1999–2016) in suicide across all age groups up to age 75 years (in half of all US states), and in 2016, 54% of people in 27 US states who died by suicide had no mental health diagnosis.1 Yet most papers and reports on suicide stress that up to 90% of people who die by suicide had a psychiatric disorder. Despite innovative approaches in both psychiatric treatments and suicide prevention, some important shortcomings seem to have a role in impairing effective progress in reducing deaths by suicide. A paradigm shift is needed that should focus the assessment of suicide risk on the centrality of the mental pain in suicidal individual

Critical appraisal of major depression with suicidal ideation

Background: Regardless of its nature, suicidal ideation, in the absence of another diagnosis, is quintessentially associated with major clinical depression. Although for the characteristics of being depressed it is reasonable to have some wish to die, there is no real attempt to understanding the suicidal mind. Clinicians are therefore often inclined to consider suicidal ideation a symptom of major depression. Yet, most depressed patients do not die by suicide, and many of them never experience suicidal ideation even in the most severe depressing scenario. At a closer look, when one works with suicidal individual, suicide appears complex and not line with the obsolete medical model. There are often warning signs for suicide, and suicidal individuals experience mental pain as a common denominator of many adverse events. Case presentation: A case report of an entrepreneur with no previous psychiatric history describes the process of meditating suicide as a dimension overlapping the depressive disorder. Details of how this 63-year-old male developed high suicide risk are reported, and clinicians are guided into the understanding of suicide risk. Conclusions: Nowadays, clinicians are requested to provide an in-depth investigation into the suicidal mind, an assessment adjunctive to the psychiatric evaluation. A phenomenological approach may be the key to unlock the suicidal mind. Clinicians may use such tool in light of the need for the empathic understanding of human suffering as well as a paradigm shift in the care of suicidal individuals

PAR1 activation induces the release by Schwann cells of factors promoting cell survival and neuritogenesis

Protease-activated receptor 1 (PAR1) is a member of a family of four G-protein-coupled receptors which are activated by proteolytic cleavage of their N-terminal extracellular domain. The expression and the role of PAR1 in peripheral nervous system (PNS) is still poorly investigated, although high PAR1 mRNA expression was found in the dorsal root ganglia and in the non-compacted Schwann cell myelin microvilli at the nodes of Ranvier. Schwann cells (SCs) are the principal population of glial cells of the PNS which myelinate axons and play a key role in axonal regeneration and remyelination. Aim of the present study was to determine if the activation of PAR1 affects the neurotrophic properties of SCs. By double immunofluorescence we observed a specific staining for PAR1 in S100ȕ-positive cells of rat sciatic nerve and sciatic teased fibers. Moreover, PAR1 was highly expressed in SC cultures obtained from both neonatal and adult rat sciatic nerves. When PAR1 specific agonists were added to these cultures an increased proliferation rate was observed. Moreover, the conditioned medium obtained from primary SCs treated with PAR1 agonists increased cell survival and neurite outgrowth on PC12 cells respect to controls. By proteomics, western blot and RT-PCR analyses we identified five proteins which are released by SCs following PAR1 stimulation: Macrophage migration inhibitory factor (Mif), Aldose reductase (Akr1b1), Matrix metalloproteinase-2 (Mmp2), Syndecan-4 (Sdc) and Decorin (Dcn). Conversely, a significant decrease in the level of three proteins was observed: Complement C1r subcomponent (C1r) and Complement component 1 Q subcomponent-bindingprotein (C1qbp). When PAR1 expression was silenced by siRNA the observed pro-survival and neurotrophic properties of SCs appear to be reduced respect to controls. References PAR1 activation affects the neurotrophic properties of Schwann cells. Pompili E1, Fabrizi C2, Somma F2, Correani V3, Maras B3, Schininà ME3, Ciraci V2, Artico M4, Fornai F5, Fumagalli L2. 2017 Jan 4;79:23-33. doi: 10.1016/j.mcn.2017.01.001.Schwann cells (SCs) regulate a wide variety of axonal functions in the peripheral nervous system, providing a supportive growth environment following nerve injury (1). Here we show that rat SCs express the protease-activated receptor-1 (PAR1) both in vivo and in vitro. PAR1 is a G-protein coupled receptor eliciting cellular responses to thrombin and other proteases (2). To investigate if PAR1 activation affects the neurotrophic properties of SCs, this receptor was activated by a specific agonist peptide (TFLLR) and the conditioned medium was transferred to PC12 pheocromocytoma cells for assessing cell survival and neurite outgrowth. Culture medium from SCs treated with 10 µM TFLLR reduced significantly the release of LDH and increased the viability of PC12 cells with respect to the medium of the untreated SCs. Furthermore, conditioned medium from TFLLR-treated SCs increased neurite outgrowth on PC12 cells respect to control medium from untreated cells. To identify putative neurotrophic candidates we performed proteomic analysis on SC secretoma and real time PCR experiments after PAR1 activation. Stimulation of SCs with TFLLR increased specifically the release of a subset of five proteins: Macrophage migration inhibitory factor (Mif), Aldose reductase (Akr1b1), Matrix metalloproteinase-2 (Mmp2), Syndecan-4 (Sdc) and Decorin (Dcn). At the same time there was a significant decrease in the level of three proteins: Complement C1r subcomponent (C1r), Complement component 1 Q subcomponent-binding protein (C1qbp) and Angiogenic factor with G patch and FHA domains 1 (Aggf1). These data indicate that PAR1 stimulation does induce the release by SCs of factors promoting cell survival and neuritogenesis. Among these proteins, Mif, Sdc, Dcn and Mmp2 are of particular interest

Degeneration and regeneration of peripheral nerves: role of thrombin and its receptor PAR-1

The peripheral nervous system has a striking regeneration potential and after damage extensive changes in the differentiation state both of the injured neurons and of the Schwann cells are observed. Schwann cells, in particular, undergo a large scale change in gene expression becoming able to support axonal regeneration. Nerve injury is generally associated to inflammation and activation of the coagulation cascade. Thrombin acts as a polyfunctional signalling molecule exerting its physiological function through soluble target proteins and G-protein-coupled receptors, the protease-activated receptors (PARs) [1]. Recently, we have demonstrated that the activation of the main thrombin receptor, PAR-1, in Schwann cells favours their regenerative potential determining the release of factors which promote axonal regrowth [2]. The pro-regenerative potential of thrombin seems to be exerted in a narrow range of concentrations (pM-nM range). In fact, our preliminary data indicate that high levels of thrombin in the micromolar range slow down Schwann cell proliferation and induce cell death. On the contrary, PAR-1 activating peptides mimic the pro-survival but not the pro-apoptotic effects of thrombin. Controlling thrombin concentration may preserve neuronal health during nerve injury and represent a novel target for pharmacologic therapies

Neutron spectrometer for fast nuclear reactors

In this paper we describe the development and first tests of a neutron spectrometer designed for high flux environments, such as the ones found in fast nuclear reactors. The spectrometer is based on the conversion of neutrons impinging on $^6$Li into $\alpha$ and $t$ whose total energy comprises the initial neutron energy and the reaction $Q$-value. The $^6$LiF layer is sandwiched between two CVD diamond detectors, which measure the two reaction products in coincidence. The spectrometer was calibrated at two neutron energies in well known thermal and 3 MeV neutron fluxes. The measured neutron detection efficiency varies from 4.2$\times 10^{-4}$ to 3.5$\times 10^{-8}$ for thermal and 3 MeV neutrons, respectively. These values are in agreement with Geant4 simulations and close to simple estimates based on the knowledge of the $^6$Li(n,$\alpha$)$t$ cross section. The energy resolution of the spectrometer was found to be better than 100 keV when using 5 m cables between the detector and the preamplifiers.Comment: submitted to NI

Questioning on consistency of a stagnation scale in medication overuse headache. one more added to a plea of emperor's clothes?

No abstract availabl

Further insights into the beck hopelessness scale (BHS). Unidimensionality among psychiatric inpatients

Short versions of the Beck Hopelessness Scale have all been created according the Classical Test Theory, but the use and the application of this theory has been repeatedly criticized. In the current study, the Item Response Theory approach was employed to refine and shorten the BHS in order to build a reasonably coherent unidimensional scale whose items/symptoms can be treated as ordinal indicators of the theoretical concept of hopelessness, scaled along a single continuum. In a sample of 492 psychiatrically hospitalized, adult patients (51.2% females), predominantly with a diagnosis of Bipolar Disorder type II, the BHS was submitted to Mokken Scale Analysis. A final set of the nine best-fitting items satisfied the assumptions of local independency, monotonicity, and invariance of the item ordering. Using the ROC curve method, the IRT-based 9-item BHS showed good discriminant validity in categorizing psychiatric inpatients with high/medium suicidal risk and patients with and without suicide attempts. With high sensitivity (>.90), this newly developed scale could be used as a valid screening tool for suicidal risk assessment in psychiatric inpatients

EuPRAXIA@SPARC_LAB: the high-brightness RF photo-injector layout proposal

At EuPRAXIA@SPARC_LAB, the unique combination of an advanced high-brightness RF injector and a plasma-based accelerator will drive a new multi-disciplinary user-facility. The facility, that is currently under study at INFN-LNF Laboratories (Frascati, Italy) in synergy with the EuPRAXIA collaboration, will operate the plasma-based accelerator in the external injection configuration. Since in this configuration the stability and reproducibility of the acceleration process in the plasma stage is strongly influenced by the RF-generated electron beam, the main challenge for the RF injector design is related to generating and handling high quality electron beams. In the last decades of R&D activity, the crucial role of high-brightness RF photo-injectors in the fields of radiation generation and advanced acceleration schemes has been largely established, making them effective candidates to drive plasma-based accelerators as pilots for user facilities. An RF injector consisting in a high-brightness S-band photo-injector followed by an advanced X-band linac has been proposed for the EuPRAXIA@SPARC_LAB project. The electron beam dynamics in the photo-injector has been explored by means of simulations, resulting in high-brightness, ultra-short bunches with up to 3 kA peak current at the entrance of the advanced X-band linac booster. The EuPRAXIA@SPARC_LAB high-brightness photo-injector is described here together with performance optimisation and sensitivity studies aiming to actual check the robustness and reliability of the desired working point.Comment: 5 pages,5 figures, EAAC201

Transcriptional regulation of MdmiR285N microRNA in apple (Malus x domestica) and the heterologous plant system Arabidopsis thaliana

Malus x domestica microRNA MdmiR285N is a potential key regulator of plant immunity, as it has been predicted to target 35 RNA transcripts coding for different disease resistance proteins involved in plant defense to pathogens. In this study, the promoter region of MdmiR285N was isolated from the apple genome and analyzed in silico to detect potential regulatory regions controlling its transcription. A complex network of putative regulatory elements involved in plant growth and development, and in response to different hormones and stress conditions, was identified. Activity of the \u3b2-Glucoronidase (GUS) reporter gene driven by the promoter of MdmiR285N was examined in transgenic apple, demonstrating that MdmiR285N was expressed during the vegetative growth phase. Similarly, in transgenic Arabidopsis thaliana, spatial and temporal patterns of GUS expression revealed that MdmiR285N was differentially regulated during seed germination, vegetative phase change, and reproductive development. To elucidate the role of MdmiR285N in plant immunity, MdmiR285N expression in wild-type apple plants and GUS activity in transgenic apple and Arabidopsis thaliana plants were monitored in response to Erwinia amylovora and Pseudomonas syringae pv. Tomato DC3000. A significant decrease of MdmiR285N levels and GUS expression was observed during host-pathogen infections. Overall, these data suggest that MdmiR285N is involved in the biotic stress response, plant growth, and reproductive development

Characterization of self-injected electron beams from LWFA experiments at SPARC_LAB

The plasma-based acceleration is an encouraging technique to overcome the limits of the accelerating gradient in the conventional RF acceleration. A plasma accelerator is able to provide accelerating fields up to hundreds of $GeV/m$, paving the way to accelerate particles to several MeV over a short distance (below the millimetre range). Here the characteristics of preliminary electron beams obtained with the self-injection mechanism produced with the FLAME high-power laser at the SPARC_LAB test facility are shown. In detail, with an energy laser on focus of $1.5\ J$ and a pulse temporal length (FWHM) of $40\ fs$, we obtained an electron plasma density due to laser ionization of about $6 \times 10^{18}\ cm^{-3}$, electron energy up to $350\ MeV$ and beam charge in the range $(50 - 100)\ pC$.Comment: 6 pages, 11 figures, conference EAAC201