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

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

An MMPI-2 hopelessness scale: Construction, initial validation and implication for suicide risk

This study documents the development of a new MMPI-2 scale, Hopelessness (Hp), designed to identify suicide risk in examinees who, for whatever reason, may be reluctant to endorse items reflecting explicit suicide content. The psychometric and empirical validity characteristics were examined in a sample of 153 Italian psychiatric inpatients, all of whom were administered the MMPI-2, the Beck Hopelessness Scale (BHS), and the Mini International Neuropsychiatric Interview (MINI) shortly following admission.Item analysis suggested that the removal of one of the twelve original Hp items enhanced homogeneity of the scale and Bayesian confirmatory factor analysis (BCFA) indicated the fit of a unidimensional model (PPPs = 0.50 [PPC = -36.42/37.07]) for the 11-item version, with adequate reliability (ordinal alpha = 0.86). A regression analysis, with the MINI scores as criterion, and Hp and BHS scores as independent variables, indicated that only Hp scores (beta = 0.25, t = 2.32, p < 0.05) were independently associated with the MINI suicide risk. These findings indicate that the MMPI-2 Hp scale may be considered a valid and potentially useful measure of pessimistic attitudes toward the future and of potential suicide risk

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)

Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths)

Suicide among Italian adolescents: 1970–2002

The purpose of the present study was to analyze sex and regional differences in the suicide rate of adolescents and the methods they used for suicide in Italy during the period 1970–2002. Temporal trends and regional variations in suicide for Italian adolescents were retrieved from the Italian database on mortality for the period 1970–2002, collected by the Italian Census Bureau and processed by the Italian National Institute of Health-Statistics Unit. In the period 1970–2002, 3,069 adolescent suicides were monitored in Italy. Analyses of these suicides identified significant differences by region of residence and sex. Males were 2.1 times more likely than females to kill themselves. Male and female suicides had inverse trends in the years analyzed, so that the sex difference at the present time is the result of a continuous increase in male suicides and a decrease in female suicides since 1970. The dramatic peaks observed over the time period studied cannot be attributed to a single cause, indicating that further studies are needed to better understand the phenomenon

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

Prenatal genetic counselling: issues and perspectives for pre-conceptional health care in Emilia Romagna (Northern Italy)

Background: there are many reasons why a couple may seek specialist genetic counselling about foetal risk. The referral for prenatal genetic counselling of women with a known risk factor during pregnancy has many disadvantages. Despite this, 10-20% of women seek counselling when already pregnant. Methods: data on 804 pregnant women out of 2 158 (37.3%) referred for genetic counselling in 2010 to three Clinical Genetic Services were retrospectively analysed. Patients referred only for advanced maternal age were analysed in a separate study. Results: the 804 pregnant women were referred for 932 counselling issues. 325 issues (34.9%) were identified during pregnancy and 607 (65.1%) were pre-existing. 81.2% of Italians compared to 41.8% of the non-Italians (P&lt;0.01) had access to counselling before 13 weeks of gestation for risk factors present before pregnancy. An accurate genetic diagnosis was available in 25.0% of cases. In 21.7% of the cases an elevated a priori risk of &gt;10% for the unborn child was established. Conclusions: genetic services provide 37.3% of counselling to pregnant women. Referral for genetic counselling during pregnancy can require considerable resources and pose significant ethical and organizational challenges. New models of pregnancy care in the community need to be developed. General practitioners and gynaecologists have an important role in the referral and in the defence of equity of access and a more structured approach to the participation of medical geneticists to primary practice should be considered

Acute hepatitis caused by a natural lipid-lowering product: When "alternative" medicine is no "alternative" at all

Background/Aims The general public's growing mistrust of the pharmaceutical industry and its perception of the lack of adverse effects of "natural" therapy have lead to the increasing use of "alternative drugs" for hypercholesterolemia. Methods A sixty-three year old woman presented with severe hypertransaminasemia that had developed progressively over a few weeks. For six months she had been taking Equisterol ® , an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract. The product had been prescribed for hypercholesterolemia because the patient had developed hepatotoxicity while on lovastatin. Results Liver biopsy revealed severe lobular necroinflammatory changes with an eosinophilic infiltrate. The episode was regarded as an adverse drug reaction after exclusion of other possible causes of acute liver disease and the prompt normalization of liver function tests after Equisterol ® had been discontinued. Red yeast rice extract's cholesterol-lowering properties are largely due to fungal metabolites known as monacolins, one of which – monacolin K – is identical to lovastatin. Conclusions The choice of an alternative medicine approach in this case subjected the patient to "re-challenge" with the official medicine agent that had previously caused mild hepatotoxicity. Physicians should keep in mind that "alternative" medicine is not always the safest alternative and sometimes it is not even "alternative.

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