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Maledetti e discriminati. Lavoratori "pericolosi" nel Basso Medioevo italiano
No full textNel Medioevo italiano dei secoli XIII-XV, alcune tipologie di lavoratori sono “discriminate”, infamate e oggetto di attenzioni speciali. Macellai, tavernieri, mugnai, tintori e sarti godono di una cattiva fama. Perché? Muovendo da fonti di vario tipo – letterarie, cronachistiche, giuridiche, giudiziarie, notarili e iconografiche –, questo libro vuole fornire nuove risposte rispetto alla storiografia che si è occupata di questo tema
Tumor biology versus nodal stage in predicting survival after resection of pulmonary atypical carcinoids
No full textPulmonary atypical carcinoid (AC) demonstrates a variable prognosis influenced by both tumor biology and anatomic
staging. It remains unclear whether histopathologic markers such as mitotic count, necrosis, and Ki-67 more effectively
predict overall survival (OS) than nodal involvement (pN). This study aims to determine whether OS after surgical
resection of pulmonary AC is more strongly associated with pathologic markers or with nodal involvement, by directly
comparing their prognostic performance within a single institutional cohort. We retrospectively analyzed 111 patients
with resected AC and complete OS data, comparing prognostic performance between a biologic model (mitoses>2 per 2
mm2
, necrosis present, Ki-67>10%), an anatomic model (pN>0), and a combined model. Survival curves were estimated
by Kaplan–Meier analysis. Model discrimination was evaluated using Harrell’s C-index; nested models were compared
via likelihood-ratio testing. Restricted mean survival time (RMST) at 60 months was used to quantify absolute survival differences by category. Median follow-up was 88 months (IQR 46–136 months). Proportions of high-risk features
were: mitoses>2 mm2
, 66%; necrosis, 31%; Ki-67>10%, 42%; nodal involvement, 36%. The biologic model achieved
a higher C-index (0.748) than the anatomic model (0.559), and the combined model showed minimal incremental gain
(C-index=0.755, p=0.97 vs. biologic model). Only 11 deaths occurred during follow-up, which limits the precision of
effect estimates. RMST analysis showed that the presence of necrosis was associated with the largest absolute difference
in 60-month survival, followed by high mitotic count, elevated Ki-67, and nodal involvement. Histopathologic indicators
of tumor biology, particularly necrosis and mitotic activity, were more strongly associated with OS than nodal stage. These
findings support the potential value of pathology-anchored prognostic stratification in AC. Validation in larger multicenter
cohorts is required before implications for clinical decision-making can be fully defined. These results may help refine
postoperative counselling and surveillance strategies if prospectively confirmed
Organizzare la solidarietà: il sostegno degli anarchici tedeschi ai rifugiati anarchici russi negli anni Venti
No full textIl saggio intende analizzare la rete di solidarietà organizzata dal movimento anarchico tedesco per sostenere le attività dei rifugiati anarchici russi presenti a Berlino nella prima metà degli anni Venti. Nella prima parte viene presa in esame la rottura con il bolscevismo, rottura alimentata dalla denuncia delle persecuzioni politiche subite dagli anarchici in Russia. La seconda parte è dedicata allo sviluppo e al funzionamento della rete di solidarietà organizzata dagli anarchici tedeschi per accogliere i profughi anarchici, in fuga o espulsi dal regime bolscevico. La terza e ultima parte analizza l’attività degli anarchici russi a Berlino, concentrandosi sullo sforzo propagandistico e sul supporto ai prigionieri politici rimasti nelle carceri bolsceviche.This paper aims to analyse the solidarity network organised by the German anarchist movement to support the activities of Russian anarchist refugees in Berlin in the first half of the 1920s. The first part examines the split with Bolshevism, a split fuelled by the reporting of political persecution suffered by anarchists in Russia. The second part is dedicated to the development and functioning of the solidarity network organised by German anarchists to support anarchist refugees who had fled or been expelled by the Bolshevik regime. The third and final part discusses the activities of Russian anarchists in Berlin, focusing on their propaganda efforts and support for political prisoners remaining in Bolshevik prisons
Microscopic Findings in Primary Teeth Associated with Vitamin D Deficiency
No full textBACKGROUND: Rickets is a medical condition caused by vitamin D deficiency, typically caused by inadequate dietary intake, limited sun exposure, or, less commonly, genetic disorders. While skeletal abnormalities are the hallmark of rickets in children, oral manifestations, such as recurrent dental abscesses occurring in the absence of carious lesions, can also be observed. This report describes the case of a child presenting with oral features suggestive of hereditary rickets, despite the lack of skeletal abnormalities and without a confirmed genetic aetiology. Histological and microstructural analyses of dental tissues played a key role in guiding the diagnosis, ultimately leading to referral to a paediatrician and confirmation of vitamin D deficiency. CASE REPORT: A 4-year-old male presented to the Emergency Dental Department of a paediatric clinic with a history of spontaneous dental abscesses. Three affected primary teeth, extracted for clinical reasons, were comprehensively analysed using micro-computed tomography, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and optical microscopy. Investigations revealed an enlarged pulp chamber, pulpal calcifications, extensive interglobular dentine, and porous, hypomineralised enamel. Additionally, an irregular and poorly defined dentino-enamel junction was observed, along with abrupt spatial variations in mineral composition. The findings are consistent with defective biomineralisation. Subsequent biochemical testing confirmed vitamin D deficiency in the absence of a detectable genetic cause. The patient was supplemented with vitamin D and calcium, resulting in clinical improvement. CONCLUSION: Vitamin D deficiency profoundly impairs the development and mineralisation of dental hard tissues, including both enamel and dentine. These alterations compromise the structural integrity of teeth and may increase the risk of spontaneous dental abscesses. Early identification of such oral manifestations is critical for prompt diagnosis and appropriate management
Early mechanical reperfusion in high-risk pulmonary embolism supported by V-A ECMO: a multicenter international cohort study
No full textObjectives: To explore how early mechanical reperfusion impacts outcomes in high-risk pulmonary embolism (PE) patients supported by veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Methods: This retrospective international study included adult patients treated with V-A ECMO for high-risk PE at 39 ECMO centers (2014-2024). Early mechanical reperfusion was defined as catheter-directed therapy or surgical embolectomy within 48 hours of ECMO initiation. Patients dying within 12 hours or receiving delayed reperfusion were excluded. The primary outcome was 90-day mortality, assessed using propensity-matched groups. Measurements and main results: Among 492 patients on V-A ECMO (median age 53), 69% had cardiac arrest, and 28% received early mechanical reperfusion. After propensity matching, 137 patients were compared in each group. Ninety-day mortality was 32% with early mechanical reperfusion on ECMO versus 39% with ECMO stand-alone (HR 0.68; 95% CI, 0.45-1.03; p = 0.07). Overall, ECMO duration and weaning rates were similar; however, early mechanical reperfusion improved ECMO weaning in patients without prior thrombolysis (sHR 1.56; 95% CI, 1.03-2.36; p = 0.04). Bleeding occurred in 50% of patients, with no significant difference between groups. Conclusion: In this large international cohort of patients with high-risk PE on V-A ECMO, early mechanical reperfusion therapy was not associated with a reduction in 90-day mortality or ECMO duration. These findings may support a stepwise, individualized approach favoring initial ECMO stand-alone support, although a certain clinical benefit from early mechanical reperfusion in selected patients cannot be excluded
Systemic inflammation and CAR-T specific toxicities as major drivers of non-relapse mortality: analysis from the Italian prospective observational CART-SIE Study
No full textBackground: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized outcomes in relapsed/refractory lymphomas, yet non-relapse mortality (NRM) has emerged as a notable concern, with older age and infections identified as major determinants of NRM in real-life studies. Objective: The aim of the present study was to describe the rate and causes of NRM after CAR-T cells and identify risk factors. Study design: Within the framework of the prospective, multicenter, observational CART‐SIE study, we analyzed causes and determinants of NRM in a large real-world cohort of lymphoma patients receiving CAR‐T cells from 2019 to 2025. Associations between NRM and clinical or biological factors were assessed using Fine and Gray subdistribution hazard models. Results: From 2019 to 2025, 1132 patients were enrolled in the CART-SIE Study; among those, 932 were evaluable for outcomes, with a median follow-up of 17.8 months (IQR 6.3-25.4). In this cohort, 305 deaths were observed, mainly occurring after disease progression (n=258); overall, 47 deaths were solely attributable to NRM (5%), either early (≤28 days, 40.4%), late (29-90 days, 23.4%) or very late (>90 days, 36.2%). The 1- and 2-year cumulative incidence of NRM were 5.5% and 8.8%. Infections were the leading cause (51%), followed by CAR-T acute toxicities (CRS, ICANS, and HLH/MAS; 30%), and secondary malignancies (11%). In univariable analysis, age > 60 years, diabetes, atrial fibrillation, high CAR-HEMATOTOX score, elevated ferritin, baseline cytopenias, CRS grade ≥3, any-grade or grade ≥3 ICANS and infectious events were risk factors for NRM. Multivariable models revealed that, among pre-infusion factors, only high ferritin levels (HR 3.23, 95%CI 1.37-7.62, p=0.007) and diabetes (HR 3.93, 95%CI 1.28-12.1, p=0.017) independently predicted NRM, while only severe CRS, ICANS, and infections remained strong post-infusion predictors. Conclusions: These findings emphasize the role of host-related factors and inflammation in shaping CAR-T outcomes. Optimised patient selection, rigorous management of acute toxicities, tailored infectious prophylaxis and long-term oncologic surveillance are essential components of long-term survivorship care, aiming to mitigate NRM and sustain long-term benefits of CAR-T cells. Clinical trial registration ClinicalTrials.gov ID: NCT06339255
Urate urolithiasis in a 5‐week‐old Dalmatian with confirmed hereditary hyperuricosuria
No full textA 5-week-old male Dalmatian was referred for suspected urethral obstruction. Imaging revealed multiple urinary bladder and urethral uroliths composed predominantly of ammonium urate. Genetic testing confirmed homozygosity for the SLC2A9 mutation associated with hereditary hyperuricosuria in this breed. The patient was managed conservatively with medical therapy, a balanced low-purine diet formulated for growth, and regular monitoring. This case highlights the importance of including hereditary hyperuricosuria among the differential diagnoses for urate urolithiasis, even in very young dogs
Socio-economic institutions for the green transition. Comparing labour strategies in Italy and the Netherlands
No full textSocial actors face an eco-social-growth trilemma when addressing the ecological transition. This comparative analysis discusses the strategies adopted by metalworkers’ unions to tackle this trilemma in Taranto and IJmuiden. While the transition promises both environmental and public health benefits, it also poses challenges, including job cuts and uncertainties concerning profitability. In the Italian case, the unions prioritise job preservation, with most opposing the transition. In contrast, the Dutch trade unions have adopted an innovative approach, proposing the ‘Groene Staal’ plan that openly accepts redundancies to achieve ecological goals. We explain the difference in terms of socio-economic institutions: IJmuiden’s dynamic economic geography, strong social dialogue mechanisms (for example, the Polder Model) and age-heterogeneous workforce lower the social costs of transition, making ecological benefits more attainable. The article aims to elaborate on the labour market effects of the ecological transition, trade union positions and their determinants, in a dialogue with labour environmentalism
REGENERATIVE MEDICINE STRATEGIES FOR ENDOMETRITIS IN REPRODUCTIVE MARES:IN VITRO AND IN VIVO STUDIES
No full textEndometritis is a fertility-impairing pathology frequent in reproductive mares. Persistent post-breeding induced endometritis (PPBIE) is caused by a uterine inflammatory imbalance, while chronic degenerative endometritis (CDE) involves endometrial fibrotic alterations and has been associated with advanced age. Causing a considerate alteration of uterine environment, endometritis is believed also to impair fetal-maternal communication. Since conventional therapies often fail to achieve a resolutive endometrial regeneration, this project aimed at identifying novel alternative approaches based on the employment of secretome (conditioned medium: CM) and extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) isolated extra-foetal adnexa as sources of regenerative medicine. Platelet rich plasma (PRP) was also examined as further alternative approach.
The initial phase of research involved in vitro studies:
1) Wharton’s jelly-derived conditioned medium (WJ-CM) and PRP were investigated in counteracting in vitro LPS-induced inflammation on equine endometrial cells (ECs). Unexpectedly, PRP did not exert an anti-inflammatory effect on stressed ECs, causing cytotoxicity and increasing ROS levels. Contrarily, WJ-CM showed a significant decrease in PGE-2 release after 24 hours of incubation, confirming its anti-inflammatory activity.
Both these regenerative products contain soluble factors and EVs. Therefore, the attention of this thesis was directed on EVs, but specifically those obtained from amniotic mesenchymal stromal/stem cells (AMCs), which are isolated from another extra-foetal tissue, namely the amniotic membrane.
2) The literature provide evidence for the anti-inflammatory and pro-regenerative properties of amniotic-derived extracellular vesicles (AMC-EVs), even in reproductive disorders. However, the mechanism of interaction between AMC-EVs and recipient ECs and the modality of EV-uptake remain to be fully elucidated. Therefore, in vitro analyses were performed to characterize the glycoprofile of ECs and AMC-EVs using a panel of FITC-conjugated lectins. Results show that ECs and AMC-EVs express fucosylated and sialylated glycans on their surface, which are actively involved in the internalization of AMC-EVs by ECs.
3) Given the potential future application of AMCs and EVs in regenerative medicine, a comparative proteomic analysis was conducted to assess the specific functional features of AMCs and their EVs. The results show that AMCs and EVs are characterized by a distinct proteomic profile, showing the expression of different sets of proteins involved in regenerative processes and thus diversified therapeutic properties. Proteins promoting anti-inflammatory activity, oxidative stress resistance and angiogenesis exhibited increased expression levels in AMCs, while ECM organization and deposition are predominantly upregulated in EVs. This emphasizes their important complementary roles in the fine regulation of the main processes involved in tissue regeneration, proposing AMCs and EVs as a dynamic and effective “couple” rather than separated actors with similar effects. Consequently, to date, we are still unable to definitively elect cells over EVs (or vice versa) as better therapeutic candidate.
4) Extracellular vesicles are internalized by ECs and exerted a functional effect in a mare treated via intrauterine infusion, which resulted in a successful pregnancy. But which bioactive molecules are transferred from EVs to target cells? The miRNA cargo of AMCs and their EVs was previously characterized by the research group under which the present project was conducted. However, most of the intercellular communication is likely mediated also by the proteomic cargo of these vesicles. In this context, the proteins involved in AMC-EV effects were evaluated in vitro assessing the effect of their incorporation into equine ECs challenged with LPS to induce inflammation. Treatment with AMC-EVs resulted in the upregulation of several proteins implicated in the modulation of the inflammatory response, components of the extracellular matrix, antioxidant enzymes and mediators, as well as various transcription factors and regulatory molecules. In contrast, a subset of pro-inflammatory mediators—including specific cytokines, oxidative stress-related factors, and inhibitors of matrix metalloproteinases—were found to be downregulated. These findings indicate that AMC-EVs may exert anti-inflammatory effects on LPS-stimulated endothelial cells through a multifaceted mechanism involving cytokine modulation, enhancement of antioxidant defenses, regulation of gene transcription, remodeling of the extracellular matrix, and modulation of key signaling pathways associated with inflammation, confirming the regenerative properties of AMC-EVs and their possible employment as cell-free therapy.
Alongside the in vitro experiments, also in vivo studies were performed.
5) Previous studies showed that AMC-EVs decrease pro-inflammatory cytokine levels and improve endometrial cell proliferation in vitro. Moreover, also the in vitro studies performed during this PhD reinforce the potential role of AMC-EVs for endometrial regeneration. Therefore, mare reproductive diseases were approached, including two kinds of endometritis.
Among the various forms of endometritis that negatively impact fertility, PPBIE represents a major cause of subfertility in mares. In the present project, stallion semen was supplemented with AMC-EVs at the time of insemination in the attempt of preventing or limiting the development of PPBIE after artificial insemination. Before administration in mares, the effect of AMC-EVs on sperm mobility parameters was assessed to exclude sperm toxicity. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with AMC-EVs (n = 8; EV group). The supplementation of AMC-EVs to the inseminating dose resulted in a reduction in polymorphonuclear neutrophil infiltration as well as intrauterine fluid accumulation. Intrauterine levels of IL-6 were significantly decreased, while anti-inflammatory IL-10 was up-regulated, suggesting successful modulation of the post-insemination inflammatory response and possible future use of this procedure in mares susceptible to PPBIE.
6) Considering the efficacy of AMC-EVs in preventing the onset of PPBIE, an additional in vivo study evaluated AMC-EV treatment in mares affected by CDE.
The aim of this project was to attempt restoring embryo-maternal communication and improving endometrial histological conditions by intrauterine administrations of AMC-EVs in twelve mares. These animals were divided into Group 1 (n=7), receiving a single treatment cycle (two administrations), and Group 2 (n=5) receiving two treatment cycles (four administrations). Each administration consisted of 2×1010 AMC-EVs diluted in 50 ml of sterile saline solution. Eleven mares were able to conceive after the treatment with AMC-EVs without significant difference in pregnancy outcomes between one or two treatment cycles. However, no improvement in endometrial histology was observed, suggesting that under the adopted therapeutical protocol AMC-EVs did not induce a complete tissue regeneration, but likely contributed to restoring functional paracrine interaction between embryo and maternal tissues
Performance of the BioFire FilmArray Pneumonia Panel Plus Compared to Standard Microbiology in Lung Transplant Donor and Recipient Samples: A Prospective Cohort Study
No full textBackground: Lung transplantation (LuTx) is hampered by infectious risks. Perioperative antibiotic prophylaxis (PAP) is widely used; however, real-time adjustment is hindered by the timing of standard microbiology. Syndromic molecular panels offer rapid results, yet their integration into PAP strategies remains unclear. Methods: We conducted a prospective cohort study comparing the BioFire FilmArray Pneumonia Panel Plus (PNplus) with standard of care (SOC) on bronchoalveolar lavage (BAL) samples obtained from donors at procurement and from recipients 72 h after LuTx. Concordance between PNplus and SOC was assessed for bacterial species and antimicrobial resistance genes. Results: Fifty-three donor-recipient pairs were analyzed. In donor BAL, PNplus identified at least one pathogen in 67.9% (36/53) of cases versus 63.5% (33/53) by SOC, with a markedly shorter time to result (221 min vs. 5.3 days). Concordance between PNplus and SOC for bacterial species was substantial (Cohen's κ = 0.654), particularly for Staphylococcus aureus (Cohen's κ = 0.689), Streptococcus pneumoniae (Cohen's κ = 0.658), and Pseudomonas aeruginosa (Cohen's κ = 0.731). In recipient BAL, PNplus detected pathogens in 61.5% (32/53) compared to 47.2% (25/53) with SOC, but overall concordance was only moderate (κ = 0.365). Resistance gene concordance was minimal, with PNplus often identifying additional determinants not confirmed by SOC. Viruses were detected exclusively by PNplus, while fungi were identified only by SOC. Conclusion: PNplus provides rapid, clinically relevant pathogen detection in LuTx, showing substantial agreement with SOC in donor samples and offering potential to support PAP adjustment. In early post-transplant recipient BAL, interpretation requires caution, and SOC remains indispensable, particularly for detecting fungi and confirming phenotypic resistance. (Figure presented.)