University of Bari Aldo Moro

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    Diagnosis and treatment of paragangliomas and pheochromocytomas: a survey from the Italian Association for Neuroendocrine Tumors

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    Background: Pheochromocytomas (PCCs) and paragangliomas (PPGLs) are rare neuroendocrine neoplasms (NENs) with heterogeneous clinical presentations. Given the rarity of PCCs/PPGLs and the paucity of high-level evidence, therapeutic decisions and treatment sequences vary across institutions. This survey explored current diagnostic practices and treatment patterns among Italian healthcare professionals (HCPs) dedicated to NENs. Methods: An online survey was conducted among Italian HCPs, members of the Italian Association for Neuroendocrine Tumors (ITANET). The survey included 33 questions covering diagnosis, genetic counseling, imaging, and treatment approaches. Responses were collected from December 15, 2023, to May 30, 2024, and analyzed using descriptive statistics to identify trends in clinical practice. Results: We recorded 80/355 responses from invited HCPs (response rate: 23%). Most HCPs (90%) referred all PCC/PPGL patients for genetic counseling, with 71% adopting gene panels for syndromes like VHL, MEN2, and familial PPGLs. Functional imaging preferences included 68Ga-DOTA-peptide PET/CT (38%), 18F-DOPA PET/CT (26%), and 123I-MIBG scintigraphy (19%). First-line systemic treatments favored somatostatin analogs (39%), clinical trial enrollment (19%), and CVD chemotherapy (15%). Radioligand therapy (RLT) emerged as the preferred second-line treatment (49%). Overall, RLT was perceived as the most effective treatment for achieving objective responses, durable responses, and improving health-related quality of life. Conclusions: Clinical wisdom rather than formal evidence and guidelines recommendations appears to guide the management of PCC/PPGLs among Italian HCPs. International, multi-institutional clinical trials designed to take into account the rarity of PCCs/PPGLs are needed to generate high-level evidence and provide guidance for standard clinical practice

    Multi-target antimicrobial activity and molecular characterization of autochthonous bacteria strains from Vitis vinifera leaves to cope with biotic stresses

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    Il progetto di tesi si proponeva di esplorare e studiare il microbioma autoctono del filloplano di Vitis vinifera al fine di identificare microrganismi con proprietà antimicrobiche ed il potenziale per essere utilizzati come agenti di controllo biologico (BCA) nei confronti di stress biotici. La Peronospora, causata da Plasmopara viticola, è stata scelta come caso studio per l'identificazione di BCA. P. viticola è un oomicete strettamente biotrofico che, nelle giuste condizioni ambientali, può attaccare tutti i tessuti verdi della pianta. Ad oggi, per evitare perdite di produttività, il controllo della malattia viene comunemente effettuato utilizzando prodotti chimici che, tuttavia, risultano dannosi per l'ambiente e per la salute umana e animale. L'identificazione di BCA contro P. viticola potrebbe promuovere pratiche più sostenibili in viticoltura come alternativa ecologica ai pesticidi chimici attualmente utilizzati. La prima fase delle attività di ricerca ha riguardato la selezione delle varietà di V. vinifera da cui isolare i microrganismi. La selezione è stata effettuata valutando il grado di tolleranza/suscettibilità delle diverse varietà alla Peronospora sui grappoli e sulle foglie, con la selezione finale di tre varietà: “Dawn seedless”, “Blush seedless” e “Argentina”. L'attenzione si è concentrata sulla componente batterica del microbioma delle foglie delle varietà scelte con conseguente isolamento, tramite un’analisi microbiologica, dei batteri epifiti ed endofiti. Sono stati eseguiti diversi saggi per identificare i candidati BCA. 16 dei batteri isolati sono stati testati su dischi fogliari per valutare la loro attività antagonista contro P. viticola e sono state definite diverse classi di efficacia in base al rapporto percentuale dell'area del disco fogliare coperta da sporulazione dell'oomicete. Cinque ceppi batterici ('BLG_B1.1.1', 'BLG_B1.3', 'BLG_B2', 'BLG_B4', 'BLG_B5') sono stati selezionati sulla base della loro diversa efficacia nel controllo dell'infezione di Peronospora e sono stati caratterizzati per le loro peculiarità morfologiche con successiva identificazione della specie di appartenenza. I cinque ceppi batterici sono stati poi testati con un saggio in vivo su foglie per studiare un possibile meccanismo d'azione contro P. viticola. In particolare, è stato valutato il loro effetto sull'espressione dei geni effettori di P. viticola PvRxLR28 e PvRxLR67 tramite esecuzione di una Real-Time PCR. Nello specifico, tra i cinque ceppi, si è osservato come tre determinassero una riduzione da moderata a elevata dell'espressione di PvRxLR28. È stata inoltre valutata la loro efficacia contro un'ampia gamma di patogeni fungini e la loro sicurezza per la salute umana. È stata infine eseguita un’analisi bioinformatica comparativa tra i ceppi ‘BLG_B2’ e ‘BLG_B4’, seguita da un saggio volto a valutare la loro capacità di contrastare la crescita di batteri patogeni per l’uomo. Le prospettive future del presente lavoro prevedono che i potenziali BCA identificati siano testati su piante per valutare il loro effetto sulla resistenza di V. vinifera a condizioni patologiche che colpiscono il filloplano e la carposfera. A tal fine, è stata condotta una prova pilota in campo su piante testando una comunità microbica sintetica già caratterizzata per le sue proprietà di biocontrollo. I risultati della prova consentiranno di definire i migliori protocolli per replicare in futuro la prova utilizzando i candidati BCA batterici selezionati.This thesis aimed to explore and study the autochthonous microbiome of Vitis vinifera phylloplane to identify microorganisms with antimicrobial properties and the potential to be used as Biological Control Agents (BCAs) to cope with biotic stresses. Downy Mildew, caused by Plasmopara viticola was selected as a case study for the identification of BCAs. P. viticola is a strictly biotrophic oomycete that can attack all the plant’s green tissues in the right environmental conditions. Nowadays, to avoid yield losses, disease control is commonly carried out by using chemical products that are harmful to the environment and to human and animal health. The identification of BCAs against P. viticola could promote more sustainable practices in viticulture as an eco-friendly alternative to currently used chemical pesticides. The first step of the research activities was the selection of the V. vinifera varieties from which microorganisms would be isolated. The selection was carried out by evaluating the degree of tolerance/susceptibility of the different varieties to Downy Mildew on the bunches and leaves and finally, three varieties were selected: ‘Dawn seedless’, ‘Blush seedless’ and ‘Argentina’. Focus was brought on the bacterial component of the leaves microbiome of the chosen varieties and epiphytic and endophytic bacteria were isolated through a microbiological analysis. Different assays were performed to identify candidate BCAs. Sixteen among the total isolated bacteria were tested on leaf discs to evaluate their antagonistic activity against P. viticola and different classes of efficacy were defined according to the percentage ratio of the leaf disc area covered by the oomycete sporulation. Five bacterial strains (‘BLG_B1.1.1’, ‘BLG_B1.3’, ‘BLG_B2’, ‘BLG_B4’, ‘BLG_B5’) were selected on the basis of their different efficacy in controlling Downy Mildew infection and were characterized for their morphological features and their species was identified. The five bacterial strains were tested through an in vivo assay on leaves to study a possible mechanism of action against P. viticola. In particular, their effect on the expression of P. viticola effector genes PvRxLR28 and PvRxLR67 was assessed by performing a Real-Time PCR. Among the five strains, three determined a moderate to high reduction of PvRxLR28 expression. Moreover, their effectiveness against a wide range of fungal pathogens and their safety to human health was also evaluated. A bioinformatic comparative analysis between the strains ‘BLG_B2’ and ‘BLG_B4’ was performed, followed by an evaluation of their ability to counteract the growth of human pathogenic bacteria. Future perspectives of the present work involve testing the identified potential BCAs on plants to evaluate their effect on V. vinifera resistance against plant diseases affecting the phylloplane and carposphere. A pilot field trial on plants was carried out testing a synthetic microbial community already characterized for its biocontrol properties. Results will allow the definition of the best protocols to replicate the trial using the selected candidate bacterial BCAs

    Peri-Implant Oral Squamous Cell Carcinoma (OSCC): Clinicopathological Features and Staging Issues

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    Background: Eighty-five percent of peri-implant malignancies are oral squamous cell carcinomas (OSCCs), and most of them are misdiagnosed as peri-implantitis because of their clinical and radiological presentation; few studies have focused on addressing and solving the diagnostic issues related to peri-implant OSCCs. Objectives: The study aimed to describe the clinicopathological features of peri-implant OSCCs and to report the staging issues related to the diagnosis of these lesions. Methods: This retrospective cohort study included patients who received a diagnosis of and treatment for peri-implant OSCCs at the Unit of Dentistry of the "Aldo Moro" University of Bari (Italy) from 2018 to 2024. By using descriptive statistics, the authors highlighted the diagnostic issues related to the clinical presentation, radiological features, and histology of peri-implant OSCCs. Results: A total of 13 women and 8 men with a mean age of 70.6 +/- 11.7 years met the inclusion criteria; the medical history of the participants showed potentially malignant disorders (OPMDs) in 52.4% of patients, whereas 14.3% had already developed an OSCC. The patients showed 24 peri-implant OSCCs; the clinical presentation was leuko-erythroplakia-like (41.7%) or erythroplakia-like (58.3%), thus simulating peri-implantitis; in addition, 52.0% of dental implants involved had a probing pocket depth >= 10 mm, further mimicking peri-implantitis. Panoramic radiograms and cone beam computed tomography were of little use in studying bundle bone-implant interfaces; in particular, the tomography showed circumferential bone resorption only in peri-implantitis-like OSCCs. In total, 91.6% of histological examinations of OSCCs showed peri-implantitis-like inflammation; early-stage lesions (pTNM I-II) accounted for 33.3%, whereas late-stage lesions (pTNM III-IV) accounted for 66.7%; lymph nodal metastases occurred in 25.0% and 62.5%, respectively. The mean follow-up was 3.4 +/- 1.0 years; all patients with OPMDs had poorly differentiated tumors and thus showed a worse prognosis than those without OPMDs (mean disease-free survival of 15.5 +/- 7.7 months and 44.7 +/- 12.1 months, respectively). Conclusions: The results of the study showed that peri-implant OSCCs occurred most frequently in patients with OPMDs or previous OSCC; in addition, peri-implant OSCCs required demolition rather than conservative excision, and the prognosis of patients strictly depended on the grade of the cancer. In the authors' experience, the clinical-radiological presentation simulating peri-implantitis was the feature that concurred most in complicating the diagnosis of those tumors

    Prevalence, Species Diversity, and Risk Factors of Tick Infestation in Cattle From District Peshawar, Pakistan

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    This study investigated the prevalence, diversity, and risk factors of tick infestation and Theileria annulata infection in cattle from District Peshawar, Pakistan. A total of 322 cattle of different breeds, ages, and sexes were examined between January and March 2024. The overall prevalence of tick infestation was 35.4%, with females more frequently infested than males. Exotic and crossbred cattle, particularly Holstein Friesian and Jersey, along with calves, showed higher susceptibility compared to indigenous breeds and older cattle. Morphological identification revealed Rhipicephalus microplus as the most prevalent species, followed by Hyalomma anatolicum anatolicum, while other species occurred at lower frequencies. Species distribution varied significantly across breeds, with R. microplus predominating in Sahiwal cattle and H. anatolicum strongly associated with Holstein Friesian. Molecular screening confirmed T. annulata infection, with the highest prevalence detected in female H. anatolicum, whereas R. microplus showed relatively low infection rates. Ecological analysis indicated moderate species diversity overall, with Holstein Friesian cattle exhibiting the greatest richness and dissimilarity in tick fauna compared to indigenous breeds. Tick burden severity was mostly moderate, and co-infestation patterns were dominated by combinations of H. anatolicum and R. microplus. This study is the first to integrate molecular detection of T. annulata with ecological indices of tick diversity in cattle of Peshawar, providing a comprehensive picture of vector–host–pathogen interactions. The identification of breed- and age-specific vulnerabilities highlights the need for targeted tick control strategies. These findings have direct implications for designing sustainable management programs aimed at reducing the economic and health burden of tropical theileriosis in endemic regions

    Il Codice civile cinese e la tradizione romanistica

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    Il contributo si propone di approfondire alcuni aspetti della nuova codificazione civile introdotta pochi anni fa in Cina, in cui si coniugano i princìpi cardine del sistema socialista cinese, caratterizzato da forti spinte verso l’economia di mercato, ed elementi romanistici propri della tradizione europea. Da tale sforzo è sorta una fusione tra discipline eterogenee, da un lato antiche consuetudini nazionali e precetti di ispirazione marxista, dall'altro talune strutture giuridiche di marca occidentale. Cosicché, mentre intere aree del diritto cinese sono espressione di un impianto politico innestato nella cultura tradizionale, come accade nella sfera dei diritti reali, del matrimonio, della famiglia e delle successioni, altre parti invece si ispirano e si rifanno agli assetti giuridici degli ordinamenti europei

    Assess Optimal Penalty Hyperparameters in Nonnegative Matrix Factorization Within Hilbert Spaces Perspective

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    The nonnegative matrix factorization (NMF) model, with additional constraints on one or both the factor matrices, is a promising unsupervised learning approach to extract intrinsic properties from nonnegative data. However, solving the constrained NMF model is a challenging optimization task, that also requires the appropriate choice of penalty hyperparameters, to balance the trade-off between the goodness of the nonnegative approximation and the preservation of the additional constraints. How to choose the optimal hyperparameters in these contexts remains an open issue. Recently, we introduced a bi-level framework to optimize the penalty hyperparameters in the constrained NMF optimization problem. In this study, we extend the bi-level formulation of the hyperparameter optimization task to Hilbert spaces. This more general context allows us to extend the existence and convergence results related to the optimal penalty hyperparameter and, additionally, to apply Ekeland’s variational principle to construct an appropriate stopping criterion for the learning procedure, used to numerically solve the bi-level optimization problem. We also proposed an improved iterative algorithm for solving constrained NMF and finding the optimal penalty hyperparameters. Comparisons with state-of-the-art methods for solving constrained NMF problems are also presented on synthetic and real datasets

    Inside out: Exploring edible biocatalytic biosensors for health monitoring

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    Edible biosensors can measure a wide range of physiological and biochemical parameters, including temperature, pH, gases, gastrointestinal biomarkers, enzymes, hormones, glucose, and drug levels, providing real-time data. Edible biocatalytic biosensors represent a new frontier within healthcare technology available for remote medical diagnosis. The main challenges to develop edible biosensors are: i) finding edible materials (i.e. redox mediators, conductive materials, binders and biorecognition elements such as enzymes) complying with Food and Drug Administration (FDA), European Food Safety Authority (EFSA) and European Medicines Agency (EMEA) regulations; ii) developing bioelectronics able to operate in extreme working conditions such as low pH (∼pH 1.5 gastric fluids etc.), body temperature (between 37 °C and 40 °C) and highly viscous bodily fluids that may cause surface biofouling issues. Nowadays, advanced printing techniques can revolutionize the design and manufacturing of edible biocatalytic biosensors. This review outlines recent research on biomaterials suitable for creating edible biocatalytic biosensors, focusing on their electrochemical properties such as electrical conductivity and redox potential. It also examines biomaterials as substrates for printing and discusses various printing methods, highlighting challenges and perspectives for edible biocatalytic biosensors

    Razzismo e difficult heritage: il ruolo delle memorie coloniali

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    The paper intends to reflect on the racial question in the light of the historiographical debate on the return of race in public discourse (Graziosi, 2025). The thesis discussed in the contribution adopts the methodology of the Public history of education (Bandini, 2019) to analyze the controversial Italian colonial memory, considered as an incubator of the race stereotypes still widespread today. The heuristic suggestions of the Public history of education prove invaluable in dealing with the complex legacy of colonialism, which can be defined as a difficult heritage (Macdonald, 2009) that evokes opposing feelings in public opinion. The aim is to develop a credible and, for this very reason, necessarily complex historical narrative of colonialism (Deplano, 2023b)

    Multifocal intravestibulocochlear and intracranial vestibular schwannomas: illustrative case

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    BACKGROUND Eighth cranial nerve schwannomas represent a rare pathological condition, and their sporadic unilateral multifocal presentation is even more uncommon. Here, the authors present a rare case of multifocal intravestibulocochlear and intracranial vestibular schwannomas (VSs) and review analogous cases in the existing literature. OBSERVATIONS A 54-year-old female patient presented to the authors’ clinic in March 2024 with complaints of left-sided hearing loss, tinnitus, and vertigo. Gadolinium-enhanced MRI revealed a Koos grade III VS localized in the cerebellopontine angle (CPA) with extension in the internal auditory canal and a coexisting intravestibulocochlear schwannoma. CT imaging showed no cochlear fundus dilatation or bone erosion. The patient underwent a left transotic approach with blind sac closure of the external auditory canal. No continuity was observed between the inner ear and intrameatal-CPA VSs, confirming the presence of two distinct lesions. LESSONS This case emphasizes the importance of a preoperative radiological evaluation and the necessity of a multidisciplinary team to ensure optimal surgical treatment and complete tumor resection

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