A 13th-century cystic echinococcosis from the cemetery of the monastery of Badia Pozzeveri (Lucca, Italy)

Objective: To differentially diagnose a calcified formation recovered from a 13th century AD grave from the Tuscan monastery of Badia Pozzeveri, Lucca, Italy. Materials: A calcified formation from the thoraco-abdominal region of a skeleton buried in the monastery cemetery. Methods: Cone Beam Computed Tomography, Scanning Electron Microscope and Energy Dispersive X-Ray Spectroscopy. Results: A hollow, calcified ovoid formation was identified as typical of a hydatid cyst, permitting the diagnosis of cystic echinococcosis in a 35-45year-old female. Conclusions: The study reveals the circulation of the parasite Echinococcus granulosus in the region of Lucca in late medieval Tuscany. Significance: This finding is the fourth case of cystic echinococcosis from an archaeological context in Italy and provides insight into environmental conditions that appear to have affected members of a community, irrespective of social status. Limitations: Caution and the application of multiple analyses must be exercised in the differential diagnosis to discriminate among calcified formations. Suggestions for further research: Analysis of stable isotopes of the calcified formation, such as 15N and 13C, in order to compare them with isotopic values of the host individual and to further confirm the parasitic origin of the find

Electrical Impedance Tomography: From the Traditional Design to the Novel Frontier of Wearables

Electrical impedance tomography (EIT) is a medical imaging technique based on the injection of a current or voltage pattern through electrodes on the skin of the patient, and on the reconstruction of the internal conductivity distribution from the voltages collected by the electrodes. Compared to other imaging techniques, EIT shows significant advantages: it does not use ionizing radiation, is non-invasive and is characterized by high temporal resolution. Moreover, its low cost and high portability make it suitable for real-time, bedside monitoring. However, EIT is also characterized by some technical limitations that cause poor spatial resolution. The possibility to design wearable devices based on EIT has recently given a boost to this technology. In this paper we reviewed EIT physical principles, hardware design and major clinical applications, from the classical to a wearable setup. A wireless and wearable EIT system seems a promising frontier of this technology, as it can both facilitate making clinical measurements and open novel scenarios to EIT systems, such as home monitoring

High concentration of C-type natriuretic peptide promotes VEGF-dependent vasculogenesis in the remodeled region of infarcted swine heart with preserved left ventricular ejection fraction.

Abstract BACKGROUND: Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic late remodeling is associated with pathology and function worsening. At the same time, neo-vasculogenesis helps function improving and requires the release of vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C-type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP. METHODS AND RESULTS: To this end, infarcted swine hearts were investigated by magnetic resonance imaging (MRI), histological and molecular assays. At the fourth week, MRI showed that transmural myocardial infarction (MI) affected approximately 13% of the LV wall mass without impairing global function (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were localized to the infarct border zone (BZ), and were associated with increased expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker, factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF-dependent vasculogenesis without affecting the cell growth and survival, although CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS: CNP expression is locally increased in infarct remodeled myocardium in the presence of dense capillary network. The vasculogenic response requires the co-exposure to high concentration of CNP and VEGF-A. Our data will be helpful to develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse the remodeling process

Metabolic shift toward oxidative phosphorylation in docetaxel resistant prostate cancer cells

Drug resistance of cancer cells is recognized as the primary cause of failure of chemotherapeutic treatment in most human cancers. Growing evidences support the idea that deregulated cellular metabolism is linked to such resistance. Indeed, both components of the glycolytic and mitochondrial pathways are involved in altered metabolism linked to chemoresistance of several cancers. Here we investigated the drug-induced metabolic adaptations able to confer advantages to docetaxel resistant prostate cancer (PCa) cells. We found that docetaxel-resistant PC3 cells (PC3-DR) acquire a pro-invasive behavior undergoing epithelial-to-mesenchymal-transition (EMT) and a decrease of both intracellular ROS and cell growth. Metabolic analyses revealed that PC3-DR cells have a more efficient respiratory phenotype than sensitive cells, involving utilization of glucose, glutamine and lactate by the mitochondrial oxidative phosphorylation (OXPHOS). Consequently, targeting mitochondrial complex I by metformin administration, impairs proliferation and invasiveness of PC3-DR cells without effects on parental cells. Furthermore, stromal fibroblasts, which cause a "reverse Warburg" phenotype in PCa cells, reduce docetaxel toxicity in both sensitive and resistant PCa cells. However, re-expression of miR-205, a microRNA strongly down-regulated in EMT and associated to docetaxel resistance, is able to shift OXPHOS to a Warburg metabolism, thereby resulting in an elevated docetaxel toxicity in PCa cells. Taken together, these findings suggest that resistance to docetaxel induces a shift from Warburg to OXPHOS, mandatory for conferring a survival advantage to resistant cells, suggesting that impairing such metabolic reprogramming could be a successful therapeutic approach.Associazione Italiana Ricerca sul Cancro (AIRC), Istituto Toscano Tumori and Regione Toscan

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis

BackgroundThe objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).Materials and methodsThis observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson’s comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.ResultsA total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced &gt;G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (&gt; 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox’s regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).ConclusionsThe unexpected results of this analysis could be explained by a “response shift bias” concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches

Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score &lt; 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI &lt; 0) and non-cancer pain (73.1% with PMI &lt; 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients &gt;17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p &lt; 0.001) and be vaccinated (37% vs. 12.7%, p &lt; 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at &lt;20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p &lt; 0.001) and immune suppressed (66.4% vs. 35.2%, p &lt; 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

"Le sepolture anomale in Italia, Gran Bretagna e Francia: la paura dei revenants e le testimonianze archeoantropologiche"

Il tema delle sepolture anomale, definite anche con i termini"devianti, atipiche , inusuali, aberranti etc. ha catturato l'attenzione e la curiosità di molti archeologi e studiosi di tutta Europa, che hanno tentato di interpretare e spiegare scientificamente la natura di tali inumazioni che escono dalle "normali" pratiche di seppellimento. Con questo termine si intendono quei casi in cui il defunto viene volontariamente deposto in modo inusuale ed atipico rispetto alle canoniche pratiche deposizionate di un particolare gruppo umano in una determinata epoca. L'obiettivo di questo lavoro è quello di fornire un quadro aggiornato, completo e chiaro su questo tema, analizzando e confrontando i prinicpali modelli di sepolture anomale (sepolture prone, sepolture con pietre, individui decapitati e con segni di amputazione) rinvenuti nei vari contesti archeologici riferibili ad un arco cronologico compreso fra il I secolo ed il XVIII secolo d.c. In particolare il primo capitolo, di carattere antropologico, si concentra sul tema dei revenants, ovvero i non-morti, delle entità che rimangono sulla terra per tormentare i viventi. La paura dei revenants ha sviluppato numerose credenza folkloriche che hanno avuto un peso importante nella determinazione del seppellimento dei defunti, in particolare di coloro che durante la vita avevano commesso dei reati o degli atti giudicati impuri e che quindi, per evitarne il ritorno fra i vivi, dovevano essere deposti in modi particolari. Il secondo capitolo è dedicato all'aggiornamento dei casi di sepolture anomale rinvenute in Italia, tema già affrontato dalla sottoscritta nella tesi " Le sepolture anomale in Italia:dalla lettura tafonomica all'interpretazione del gesto funerario". Il terzo capitolo è dedicato alla descrizione dei casi rinvenuti in Gran Bretagna, abbondanti soprattutto nei cimiteri di esecuzione del periodo anglosassone e alto medievale; nel quarto capitolo vengono presi in rassegna i casi censiti in Francia ed in Svizzera, con un primo confronto con le testimonianze antropologiche del Regno Unito. Nelle conclusioni, oltre a creare un riassunto dell'intero scritto e delle varie tematiche affrontate nei vari capitoli, viene fornito un confronto fra le varie sepolture anomale rinvenute in Italia, Francia e Gran Bretagna; il tutto è supportato da un database consultabile online che ha l'obittivo di rendere fruibile ad un pubblico più vasto l'intero scritto

"La necropoli longobarda di Salica (GR). Studio bioarcheologico dei resti scheletrici"

L’elaborato presenta i risultati emersi dallo studio tafonomico, antropologico e paleopatologico del materiale scheletrico proveniente dalla necropoli longobarda situata in località Salica, in provincia di Grosseto. Le indagini archeologiche, sotto la direzione scientifica del Prof. Campana (Università di Siena), sono iniziate nel 2017 all'interno di un'area agricola di proprietà privata e, unite a quelle del 2018, hanno portato ad individuare 5 sepolture facenti parte di una necropoli rurale di VII secolo prossima all’antica città di Roselle. A partire dal 2019, i sondaggi in località Salica si sono ampliati e lo scavo, eseguito in collaborazione con la Divisione di Paleopatologia dell’Università di Pisa, ha messo in luce altre 13 tombe, per un totale di 18 sepolture. Lo studio bioarcheologico ha permesso di ricostruire il profilo biologico (diagnosi di sesso, stima dell’età alla morte, statura), lo stato di salute e le attività occupazionali per ogni individuo scheletrico, al fine di delineare la composizione e lo stile di vita di questo piccolo gruppo umano della Maremma di VII secolo. Dallo studio il campione risulta costituto da 13 individui adulti (7 maschi e 6 femmine) e 5 bambini. Fra gli adulti, i meglio preservati sono USK 4433 e 4455, entrambi maschi maturi che evidenziano patologie degenerative come l’artrosi ed entesopatie degli arti inferiori legate a stress biomeccanico prolungato riconducibile all’attività equestre. The purpose of this paper is to present the results of the tafonomic, anthropological and paleopathological study of skeletal remains from the Longobard necropolis located in Salica, in the province of Grosseto. Archaeological investigations began in 2017 and continued in 2018 under the scientific direction of Prof. Campana (University of Siena). The first 5 burials were found in a private area used for agricultural purposes; they are part of a 7th century rural necropolis, located near the ancient site of Roselle. Starting from 2019, the surveys in Salica have expanded and the excavation of 2019, carried out in collaboration with the Division of Paleopathology of the University of Pisa, found 13 more graves, investigating a total of 18 burials. The application of bioarchaeology has allowed to reconstruct the biological profile (diagnosis of sex, estimation of age at death, stature), health status and occupational activities for each skeletal individual, in order to outline the composition and overall lifestyle of this small human group in the Maremma of the 7th century. The sample consists of 13 adults (7 males and 6 females) and 5 juveniles. USK 4433 and 4455 are the best preserved adults. They are both mature males who show degenerative pathologies such as arthrosis and enthesopathy of the lower limbs linked to prolonged biomechanical stress, which can be linked to equestrian activity