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)

Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment

Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy bloc

Intense terahertz pulses from SPARC-LAB coherent radiation source

The linac-based Terahertz source at the SPARC_LAB test facility is able to gene rate highly intense Terahertz broadband pulses via coherent transition radiation (CTR) from high brightness electron beams. The THz pulse duration is typically down to 100 fs RMS and can be tuned through the electron bunch duration and shaping. The measured stored energy in a single THz pulse has reached 40 μ J, which corresponds to a peak electric field of 1.6 MV/cm at the THz focus. Here we present the main features, in particular spatial and sp ectral distributions and energy characterizations of the SPARC_LAB THz source, which is very competitive for investigations in Condensed Matter, as well as a valid tool for electron beam longitudinal diagnostics

Short-Term Psychodynamic Psychotherapy in Patients with “Male Depression” Syndrome, Hopelessness, and Suicide Risk: A Pilot Study

Objectives and Methods. This was an observational study of the efficacy of short-term psychodynamic psychotherapy (STPP) in a sample of 35 (30 women and 5 men) patients with moderate-to-severe “male depression” (Gotland Scale for Male Depression (GSMD) ≥ 13) comorbid with unipolar mood disorder (dysthymia and major depression) or anxiety disorder. Outcome measures were GSMD and BHS (Beck Hopelessness Scale) score changes from baseline. Results:. Patients had a strong response to STPP on the GSMD (estimated mean score change (± SE) = −9.08 ± 2.74; P < 0.01; partial eta squared = 0.50), but not on the BHS (estimated mean score change (± SE) = −0.92 ± 1.55; P = 0.57; partial eta squared = 0.03). BHS score changes were significantly associated with GSMD score changes (Pearson's r = 0.56; P < 0.001), even when controlling for the severity of hopelessness at the baseline (partial r = 0.62; P < 0.001). Conclusions:. STPP proved to be effective in patients suffering from “male depression” although hopelessness was only marginally reduced by this treatment which points to the need to better understand how STPP can be involved in the reduction of suicide risk

Antidepressants and Suicide Risk: A Comprehensive Overview

The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment

Beam manipulation for resonant plasma wakefield acceleration

Plasma-based acceleration has already proved the ability to reach ultra-high accelerating gradients. However the step towards the realization of a plasma-based accelerator still requires some e ff ort to guarantee high brightness beams, stability and reliability. A significant improvement in the efficiency of PWFA has been demonstrated so far accelerating a witness bunch in the wake of a higher charge driver bunch. The transformer ratio, therefore the energy transfer from the driver to the witness beam, can be increased by resonantly exciting the plasma with a properly pre-shaped drive electron beam. Theoretical and experimental studies of beam manipulation for resonant PWFA will be presented her

Applicability of the adjusted morbidity groups algorithm for healthcare programming: results of a pilot study in Italy

Background: Population-based Health Risk Assessment (HRA) tools are strategic for the implementation of integrated care. Various HRA algorithms have been developed in the last decades worldwide. Their full adoption being limited by technical, functional, and economical factors. This study aims to apply the Adjusted Morbidity Groups (AMG) algorithm in the context of an Italian Region, and evaluate its performance to support decision-making processes in healthcare programming. Methods: The pilot study used five Healthcare Administrative Databases (HADs) covering the period 2015-2021. An iterative semi-automated procedure was developed to extract, filter, check and merge the data. A technical manual was developed to describe the process, designed to be standardized, reproducible and transferable. AMG algorithm was applied and descriptive analysis performed. A dashboard structure was developed to exploit the results of the tool. Results: AMG produced information on the health status of Marche citizens, highlighting the presence of chronic conditions from age 45 years. Persons with high and very high level of complexity showed elevated mortality rates and an increased use of healthcare resources. A visualization dashboard was intended to provide to relevant stakeholders accessible, updated and ready-to-use aggregated information on the health status of citizens and additional insight on the use of the healthcare services and resources by specific groups of citizens. Conclusion: The flexibility of the AMG, together with its ability to support policymakers and clinical sector, could favour its implementation in different scenarios across Europe. A clear strategy for the adoption of HRA tools and related key elements and lessons learnt for a successful transferability at the EU level were defined. HRA strategies should be considered a pillar of healthcare policies and programming to achieve person-centred care and promote the sustainability of the EU healthcare systems