Effects of long term application of compost and poultry manure on soil quality of citrus orchards in Southern Italy.

A six-year study was carried out in an organically managed orange orchard located in Sicily (Southern Italy) to assess the effect of compost and organic fertilizers utilisation on soil quality. Adopting a randomized-block experimental design with three replicates, four treatments were carried out. In treatments 1 and 2, two different composts (C1 from distillery by products and C2 from livestock wastes) were applied. The plots of treatment 3 were fertilized using dried poultry manure. The control treatment was fertilized with mineral/synthetic fertilizers. In order to verify the hypothesis that composts and organic fertilizers improve soil fertility, soil quality was evaluated by selecting dynamic soil parameters, as indicators linked to C and N cycles. Total organic C, total N, C/N ratio, humified fraction, isoelectric focusing (IEF) of extracted organic matter, microbial biomass C, potentially mineralisable N under anaerobic conditions, potenzially mineralizable C, C mineralization quotient and metabolic quotient were determined for each sample. Furthermore, the Comunity level Physiological Profile (by Biolog tecnique) was defined, calculating derived functional biodiversity and versatility indexes. Parameters related to IEF and potentially mineralizable C showed significant differences among the treatments. Moreover, total C, total N and humification parameters tended to increase, while no differences were observed in biodiversity indexes. On these findings, it was concluded that composts and poultry manure only weakly affected soil properties, though they increased soil nutritive elements potentially available to crops

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

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

COVID-19 related lockdown: a trigger from the pre-melancholic phase to catatonia and depression, a case report of a 59 year-old man

Background: The pre-melancholic model described by Tellenbach may provide a common model for understanding the psychological implications of the lockdown. In this case report, we describe a rare catatonic status as a psychological implication linked to the COVID-19 pandemic, a really unique global situation. Case presentation: B is a 59 year-old man with mute psychiatric anamnesis whose mother suffered from a major depressive disorder. As the lockdown began, he started to develop concerns about his family’s economic condition. According to his wife, he could see no end to the epidemic and no future at all. Moving from this, he started to show a severe and rapidly progressive depression and to develop mood congruent delusions. In addition, he had increasing anhedonia, apathy, starvation and insomnia. This turned in the end into a catatonic-like state, along with a deep desire to die. Admitted to the psychiatry ward in a state of mutism, he was discharged after 15 days with a diagnosis of “Major depressive disorder, single severe episode with no psychotic behavior”. He was treated with Sertraline, Olanzapine and Lorazepam. Conclusions: Our aim is to draw attention to the effect of the lockdown upon a Tellenbach-like personality structure. Identifying this type of pre-morbid personality structure could help clinicians understand and treat some cases of patients with severe major depressive disorders elicited by the COVID-19 pandemic

Autophagy in trimethyltin-induced neurodegeneration

Autophagy is a degradative process playing an important role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria and endoplasmic reticulum, as well as eliminating intracellular pathogens. The autophagic process is important for balancing sources of energy at critical developmental stages and in response to nutrient stress. Recently, autophagy has been involved in the pathophysiology of neurodegenerative diseases although its beneficial (pro-survival) or detrimental (pro-death) role remains controversial. In the present review, we discuss the role of autophagy following intoxication with trimethyltin (TMT), an organotin compound that induces severe hippocampal neurodegeneration associated with astrocyte and microglia activation. TMT is considered a useful tool to study the molecular mechanisms occurring in human neurodegenerative diseases such as Alzheimer’s disease and temporal lobe epilepsy. This is also relevant in the field of environmental safety, since organotin compounds are used as heat stabilizers in polyvinyl chloride polymers, industrial and agricultural biocides, and as industrial chemical catalysts

The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease

The role of new technologies to prevent suicide in adolescence. a systematic review of the literature

Background and objectives: Suicide in adolescents represents a major public health concern. To date, a growing number of suicide preventive strategies based on the use of new technologies are emerging. We aimed to provide an overview of the present literature on the use of new technologies in adolescent suicide prevention. Materials and methods: An electronic search was run using the following keywords: Technology OR Technologies OR APP OR Application OR mobile application) AND (Adolescent OR youth OR puberty) AND (Suicid* OR Self-harm OR self-destruction). Inclusion criteria were: English language, published in a peer-reviewed journal, suicide prevention with the use of new technologies among adolescents. Results: Our search strategy yielded a total of 12 studies on the use of telemedicine, 7 on mobile applications, and 3 on language detection. We also found heterogeneity regarding the study design: 3 are randomized controlled trials (RCT), 13 are open-label single group trials, 2 are randomized studies, and 1 is a cross-sectional study. Telemedicine was the most adopted tool, especially web-based approaches. Mobile applications mostly focused on screening of depressive symptoms and suicidal ideation, and for clinical monitoring through the use of text messages. Although telepsychiatry and mobile applications can provide a fast and safe tool, supporting and preceding a face-to-face clinical assessment, only a few studies demonstrated efficacy in preventing suicide among adolescents through the use of these interventions. Some studies suggested algorithms able to recognize people at risk of suicide from the exploration of the language on social media posts. Conclusions: New technologies were found to be well accepted and tolerated supports for suicide prevention in adolescents. However, to date, few data support the use of such interventions in clinical practice and preventive strategies. Further studies are needed to test their efficacy in suicide prevention among adolescents and young adults

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