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Dissolved organic matter: Unraveling the role of organic carbon from the hypogeal cadaver decomposition island
No full textThe biogeochemical processes occurring in soils beneath buried cadavers, here defined as hypogeal cadaver decomposition islands (HCDIs), remain poorly understood, particularly with respect to the role of organic carbon. This study investigated temporal variations in dissolved organic matter (DOM) within HCDI to evaluate its potential as a time-dependent decomposition marker. Twenty piglets were buried under controlled conditions at the non-human Forensic Taphonomy Facility Ticino-LEAF(s) (University of Milan, Italy), using four different concealment scenarios: unclothed, wounded, clothed in cotton, and covered with quicklime prior burial. Soil samples collected at successive post-burial intervals (PBIs) up to 467 days were analyzed for pH, DOM concentration, and molecular composition through Fourier Transform Infrared (FT-IR) spectroscopy. Results revealed consistent correlations between decomposition stage, soil pH, and DOM dynamics. In most groups, pH increased during early decay and declined in advanced stages, while DOM concentrations peaked at intermediate intervals before returning to baseline levels. FT-IR spectra highlighted molecular markers of lipids, fatty acids, and protein degradation, with adipocere-associated signals detectable at later stages. Quicklime-treated burials exhibited atypical chemical patterns, though DOM analyses remained informative. Other burial conditions, such as the presence of lesions or clothing, significantly influenced both decomposition processes and the expression of biochemical markers. This pilot study suggests that combined monitoring of DOM concentration and molecular characterization, supported by pH measurements, may contribute to a better understanding of decomposition processes. The approach shows potential for estimating the post-burial interval, suggesting a potentially rapid, cost-effective, and context-sensitive support tool for forensic investigations
Health-Related Quality of Life and Mobility Levels in ICU Survivors with Heel Pressure Ulcer: An Observational Study
No full textBackground/Objectives: Heel pressure ulcers are a relevant complication in critically ill patients and may negatively affect recovery after ICU discharge. This study investigated health-related quality of life (HRQoL) and mobility levels one year after ICU discharge in survivors who developed heel pressure ulcers. Methods: A prospective observational study was conducted in the ICU of an academic tertiary-level hospital in Milan (Italy) from 1 January 2023 to 31 December 2024. Adult survivors were enrolled, and HRQoL was assessed using the EQ-5D-5L questionnaire. Functional status at ICU discharge was evaluated using the Manchester Mobility Score and Barthel Index. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: Among 3144 ICU admissions, 52 survivors were enrolled. At ICU discharge, functional status was markedly impaired: only 15 patients (28.9%) were able to stand upright according to the Manchester Mobility Score, and none achieved even moderate levels of independence. At one year, 47 patients (90.4%) completed the follow-up, and 15 of them (31.9%) continued to report moderate-to-severe mobility limitations. The mean EQ-5D index value was 0.75 (SD 0.27), representing a significant reduction compared with Italian population norms (p < 0.001). Conclusions: ICU survivors who developed heel pressure ulcers exhibit reduced HRQoL at one year after discharge. These findings emphasize the need for structured post-ICU rehabilitation and targeted follow-up
Development and field testing of a system for non-contact estimation of weight in dairy calves using a low-cost 3D camera
No full textOptimal growth and management of replacement animals are crucial for the economic and environmental sustainability of the dairy sector, as it ensures long-term herd size and productivity.
Calf body growth is typically monitored using mechanical or electronic scales, however such manual measurements are labor-intensive and can cause stress to young animals. Despite the advances in precision technologies and research focussed on adult cattle, there is a significant gap in solutions specifically designed to estimate the weight and the growth rate of young calves.
Hence, this study aimed to develop a system for non-contact evaluation of the calf body weight, using a low-cost 3D camera and an associated algorithm to enable fully automated weight estimate. A total of 230 measurements were carried out on 110 female Italian Holstein calves, aged between 1 to 121 days. Depth (3D) images of each calf’s back were acquired from a top-view configuration, using a Kinect V2 sensor mounted at a height of 1.7 m above the ground.
3D images were analysed using custom-developed software to extract two key morphological parameters for each individual calf, namely the maximum width of the abdomen (WA) and the height (HM) measured at the same position,. Simultaneously, each imaged calf was weighed on a mechanical scale with a resolution of ± 1 kg. In addition, its abdomen width and height at the withers were manually measured with a resolution of ± 5 mm, for further validation of the system accuracy.
The two image-extracted morphological parameters were finally used to train a simple prediction model for calf body weight. The resulting equation demonstrated a fairly good prediction capability (R2 = 0.87, RMSE = 3.52 kg, mean relative error = 6.6 %) when applied to a validation set of calves weighing between 24 and 88 kg. These results, combined with the simplicity of the measurement setup and the low cost of the device used, highlight the potential of implementing daily monitoring of individual calf growth using such a system, with significant advantages over traditional, labor-intensive weighing method based on scales
NOVEL THERAPEUTIC APPROACHES EMERGING FROM HCN CHANNELS STRUCTURAL AND FUNCTIONAL STUDIES
No full textHyperpolarization-activated cyclic-nucleotide gated 1 (HCN1) channels are the molecular determinants of the cationic Ih current that regulates spontaneous electrical activity and synaptic integration in neurons. Mutations in the HCN1 gene have been linked to Early Infantile Epileptic Encephalopathy (EIEE) and a spectrum of neurodevelopmental disorders (ND). Despite the growing number of identified HCN1 variants, the mechanisms by which they alter channel function and contribute to pathogenesis remain poorly understood. Here, we combine molecular, cellular, and system-level neuroscience approaches to functionally characterize HCN1 mutations and explore targeted strategies for therapeutic rescue. Using in vitro electrophysiology in HEK293 cells, we analyze a panel of patient-derived variants, and we propose a systematic classification of HCN1 mutations into four distinct classes (I-IV) according to their functional properties. This framework reveals correlations between mutation location, channel dysfunction, and clinical phenotype. Interestingly, we identify a novel correlation between loss-of-function mutations in the pore-helix / selectivity filter domain of HCN1 that are associated with ND and no history of seizures. We further explore the use of pore blockers and allosteric modulators to restore wild-type-like function in mutant HCN1 channels in vitro, highlighting the potential of precision medicine approaches tailored to mutation-specific phenotypes. Extending these studies ex vivo, we demonstrate that the allosteric modulator J&J12e effectively rescues altered intrinsic properties and excitability in hippocampal CA1 pyramidal neurons from a knock-in mouse model carrying the HCN1 M153I mutation. Additionally, we show that NB6 can modulate native Ih currents in native brain tissue, underscoring its promise as a peptide-based therapeutic tool. At the system level, in vivo electrophysiological recordings reveal increased interictal spike activity in knock-in mice, which is further amplified following lamotrigine administration. Sleep architecture is also disrupted in these animals, suggesting that HCN1 dysfunction impacts broader aspects of brain function beyond seizure susceptibility. Together, these findings provide a comprehensive understanding of the functional impact of HCN1 dysfunction and lay the basis for the development of targeted, mutation-specific therapies aimed at restoring normal channel function and improving clinical outcomes in patients with HCN1-related disorders
Clinical characteristics of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
No full textRationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by diffuse bronchial hyperplasia of pulmonary neuroendocrine cells, which are situated within the walls of bronchi and bronchioles. Presenting symptoms are nonspecific and the clinical course varies, making diagnosis challenging. We sought to describe the clinical characteristics of patients with DIPNECH in a large multinational case series to guide and inform future care and research. Methods: Data were collated from 18 international centres. Information collected included disease presentation, pulmonary function testing, histopathology, radiological patterns and outcomes. The relationship between clinical features, radiology and symptoms were explored in parametric and nonparametric group-wise analyses, univariate linear regressions, and multivariate binomial logistic regression. Results: The mean±sd age of the 258 patients in this study was 63.3±10.6 years and 93.4% were female. Diffuse pulmonary nodules (98.8%) and mosaic attenuation (59.1%) were the most common radiological findings and 29.5% had obstructive spirometry with a mean±sdforced expiratory volume in 1 s (FEV1) % pred of 69.0±23.7%. There was a significant association between the number of nodules and a reduction in FEV1 % pred (p<0.001), while the presence of bronchial wall thickening on imaging was most closely associated with cough (OR 4.97, p=0.001) dyspnoea (OR 3.14, p=0.003) and bronchodilator responsiveness (OR 3.09, p=0.013). Approximately half of patients treated with inhaled beta agonist and corticosteroids (46.3%) or somatostatin analogue (54.1%) reported improvement in symptoms. Conclusions: The presence of radiological bronchial wall thickening is associated with the presence of symptoms, while mosaic attenuation is correlated with airflow obstruction; hence, the presence of these radiological findings has the potential to guide possible treatment decisions
The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities
No full textUnlabelled: The B-cell receptor (BCR) is central to normal and malignant B-cell biology, integrating intrinsic programs with microenvironmental cues to shape cell fate. Across mature B-cell lymphomas, differences in BCR expression, class, and signaling mode define distinct pathogenetic routes and therapeutic vulnerabilities, ranging from BCR-dependent to BCR-silent states. We propose a BCR blueprint that positions these tumors along a continuum of signaling modes and class-imposed functions, emphasizing germinal center-derived lymphomas. This framework links specific BCR states to genetic lesions and microenvironmental niches, underscoring the value of routinely monitoring BCR features to track tumor evolution and inform therapy. Significance: B-cell lymphomas exploit diverse BCR expression levels, classes, and signaling modes that span BCR-addicted to BCR-silent states and shape their genetic programs and therapeutic dependencies. A unified BCR blueprint reframes these diseases along a continuum of BCR signaling and isotype-driven biology, particularly in germinal center-derived entities. Embedding this blueprint into routine clinical testing has the potential to improve prediction of response or resistance to BCR-targeted and other mechanism-based therapies
The rise of transplant oncology in primary liver cancer and metastatic disease
No full textBackground aims: Liver transplantation has evolved from a treatment restricted to patients with end-stage liver disease to a therapeutic option for selected patients with primary and metastatic liver malignancies. This review explores the rapidly expanding field of transplant oncology, highlighting its role in hepatocellular carcinoma, colorectal liver metastasis, neuroendocrine liver metastasis, and intra-hepatic and perihilar cholangiocarcinoma. Emphasis is placed on strategies to broaden eligibility, optimize donor organ use, and improve oncologic outcomes. Approach results: We synthesized current evidence from clinical series, registries, and experimental protocols to evaluate patient selection criteria, outcomes, and peri-transplant management. Key topics include downstaging approaches to meet transplant criteria such as locoregional therapies and systemic regimens, and their prognostic implications. Advances in donor utilization have been analyzed for their capacity to expand the graft pool. Additionally, the review addresses the integration of oncologic principles into immunosuppression regimens, balancing graft protection with cancer control. Collectively, the reported studies demonstrate improved survival and reduced recurrence when stringent selection and multimodal therapy were applied. Conclusions: Transplant oncology reshapes the therapeutic landscape of liver malignancies, with growing evidence supporting liver transplantation in carefully selected patients beyond traditional indications. Optimized downstaging, innovative donor strategies, and tailored immunosuppression are pivotal for safe expansion. Continued collaboration between the transplant and oncology disciplines, along with prospective trials, is essential to further define standardized protocols and solidify transplantation as a cornerstone of multidisciplinary cancer care
Internal considerations: Provisional identity, precarity and opportunism among French professional interns
No full textInternships are an increasingly ubiquitous temporary work category, positioned between educational and market spheres. Based on emerging discussions around the precarity and ambiguity of internships, we focus on how interns use provisional identifications to navigate this ambiguity. An in-depth qualitative study was conducted in the context of professional internships in the French business school context, examining how interns navigate the tensions between educational and workplace roles, making sense of their own identities alternatively as students and as precarious workers. Based on how the interns understood their intern positions, as that of organizational members, career-building entrepreneurs, or students-in-training, they built specific conceptions of themselves at work that oriented their coping behaviours, as well as their possibilities for engaging in workplace critique. We discuss the implications of these results in terms of understanding the heterogeneous identities of interns and their ramifications for workplace critiqu
La giustizia amministrativa come servizio pubblico tra efficienza e adeguatezza
No full textRagionare della giustizia come di un servizio pubblico necessita di considerare i caratteri generali qualificanti dei servizi pubblici e saggiarne la tenuta con riferimento alla giustizia. Nel servizio pubblico contano, per un verso, la dimensione organizzativa, e, per altro verso, il risultato finale dell’attività materiale. Il piano organizzativo e il piano dell’attività sono sì separati, ma al tempo stesso coordinati tra loro. L’organizzazione del servizio pubblico giudiziario abbraccia in sé tante tematiche, che spaziano dall’allocazione di persone, di risorse e di mezzi all’informatizzazione degli uffici, con il suo corollario del processo telematico, dall’accesso universale alla giustizia a tempistiche all’insegna della ragionevolezza. Invece il risultato finale dell’attività materiale si risolve in quel bene prezioso che è dato dalla effettività e dalla pienezza della tutela giurisdizionale
Le persone anziane tra vulnerabilità, vita attiva e inclusione sociale: quale tutela giuridica?
No full textl volume raccoglie le riflessioni emerse dal Convegno “Le persone anziane tra vulnerabilità, vita attiva e inclusione sociale: quale tutela giuridica?” (Università degli Studi di Perugia, Aula Dessau, 26 e 27 giugno 2025) nel corso del quale sono stati discussi i risultati della ricerca realizzata nell’ambito del progetto Prin 2022 intitolato “Elderly People, Vulnerability, Inclusive Society. Ageing and Law (ELVIS)”. I saggi ricostruiscono le coordinate costituzionali dell’invecchiamento in una società longeva approfondendo il rapporto tra gli obiettivi prioritari della legislazione nazionale sulle politiche per le persone anziane e il tessuto normativo in cui quelle riforme sono destinate ad operare. Dall’analisi svolta su specifici aspetti della vulnerabilità dell’anziano (condizioni precarie di natura personale e/o sociale e criticità legate al digital divide) emerge la necessità di rivedere alcune scelte di natura normativa e/o giurisprudenziale, per renderle coerenti con le effettive esigenze di una società che invecchia e che deve al contempo confrontarsi con il costante calo delle nascite