16 research outputs found

    An integrated strategy to correlate aggregation state, structure and toxicity of Aß 1–42 oligomers

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    Despite great efforts, it is not known which oligomeric population of amyloid beta (Aß) peptides is the main neurotoxic mediator in Alzheimer's disease. In vitro and in vivo experiments are challenging, mainly because of the high aggregation tendency of Aß (in particular of Aß 1–42 peptide), as well as because of the dynamic and non covalent nature of the prefibrillar aggregates. As a step forward in these studies, an analytical platform is here proposed for the identification and characterization of Aß 1–42 oligomeric populations resulting from three different sample preparation protocols. To preserve the transient nature of aggregates, capillary electrophoresis is employed for monitoring the oligomerization process in solution until fibril precipitation, which is probed by transmission electron microscopy. Based on characterization studies by ultrafiltration and SDS-PAGE/Western Blot, we find that low molecular weight oligomers build up over time and form bigger aggregates (> dodecamers) and that the kinetics strongly depends on sample preparations. The use of phosphate buffer results to be more aggregating, since trimers are the smallest species found in solution, whereas monomers and dimers are obtained by solubilizing Aß 1–42 in a basic mixture. For the first time, attenuated total reflection-Fourier transform infrared spectroscopy is used to assign secondary structure to the separated oligomers. Random coil and/or α-helix are most abundant in smaller species, whereas ß-sheet is the predominant conformation in bigger aggregates, which in turn are demonstrated to be responsible for Aß 1–42 toxicity

    Vascular Air Embolism Complicating Percutaneous Nephrolithotomy: Medical Malpractice or Fatal Unforeseeable Complication?

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    Vascular air embolism (VAE), the entry of gas into the vascular structures, is a mainly iatrogenic clinical problem that can result in serious mor- bidity and even in death. Although this complication has been documented in various urologic procedures,1-5 its occurrence after percutaneous nephrolithotomy (PCNL) has been reported in few cases.6,7 To the best of our knowledge only 1 fatal case of VAE complicating PCNL has been described to date. The cause of death was established only on the basis of the macroscopic finding of the right femoral venous system being filled with air and very abundant segmented air in the meningeal ve- nous structure.8 We present a fatal case of VAE compli- cating PCNL, in which the cause of death was established on the basis of microscopic findings after autopsical examination

    Current Data and Future Perspectives on Patients with Atrial Fibrillation and Cancer

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    Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF to be a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo- and radiotherapy), and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient, should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on the mechanisms linking AF to cancer patients with a particular focus on the therapeutic challenges in this population

    Buffer spaces in healthcare facilities: strategies for managing and designing strategic areas

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    Introduction: The recent covid-19 experience highlighted the difficulty of healthcare facilities in responding promptly to emergencies. hospitals had to reorganize their spaces, suspending the ordinary medical activities for ensuring the emergency management of the patients’ surplus. A working group of the postgraduate training course in healthcare management by Altems school in Rome conducted a survey on the buffer space (bs), which could support, in case of emergency, the hospitals. Methodology: The team elaborated a double questionnaire to be administered respectively to healthcare staff and designers with a series of questions aimed at understanding the features of bss. the questions were divided into general information, activities carried out during the pandemic and specific questions on the features of bss. many questions were the same for the two types of participants, while some differed in relation to the respective organizational and design skills of the users. Results: 102 healthcare professionals and 56 designers took part to the survey. the data analysis permitted to highlight a series of specific inputs that the bs project should take in consideration, such as: a) proximity to the emergency department (ed), intensive care (icu) and inpatient wards (iws); b) location within the hospital but separate from other medical areas; c) independent access; d) organizational and spatial features similar to ed, icu and iws; e) configuration of an operational space ready for whatever type of need; f) the bs should host approximately 12% of the ed stations (40 sqm/per station). Conclusions: The research aims to become a starting milestone for future investigations: in fact it is necessary to carry out a widespread analysis at the international level. Although the research was focused in hospital settings, the covid-19 pandemic referred also to the territorial healthcare facilities and therefore some considerations on that issue need to be improved

    Ripensare l’Ospedale 4.0: il ruolo dello Spazio Polmone.

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    Introduzione: L'esperienza pandemica da COVID-19 ha evidenziato la difficoltà delle strutture sanitarie nel saper rispondere tempestivamente alle emergenze. Proprio durante la pandemia, gli ospedali hanno dovuto riorganizzare i propri spazi con accorpamenti e trasferimenti, sospendendo l’erogazione dei servizi ordinari, al solo fine di garantire la gestione emergenziale del sovrannumero di pazienti. Un gruppo di lavoro, a partire dal project work del Corso di Alta Formazione "Direzione sanitaria di presidio ospedaliero" promosso da ALTEMS, ha condotto un’indagine sul ruolo dello Spazio Polmone (SP) che potrebbe supportare – in caso di emergenza – le strutture ospedaliere. Materiali e Metodi. È stato elaborato un doppio questionario, da somministrare rispettivamente a a) staff sanitario e direzioni mediche di presidio e b) progettisti e referenti di uffici tecnici con una serie di quesiti atti a comprendere le caratteristiche che lo SP dovrebbe avere, sia in un edificio esistente che di nuova realizzazione. Le domande sono state così suddivise: a) informazioni generali, b) attività svolte durante la pandemia e c) quesiti puntuali sulle caratteristiche relative allo SP. Molti quesiti sono i medesimi per le due tipologie di partecipanti, mentre alcuni si differenziano in relazione alle rispettive competenze organizzativo/gestionali e spaziali/dimensionali degli utenti. Risultati. Al questionario hanno risposto 102 professionisti sanitari e 56 progettisti. L’elaborazione dei dati ha permesso di evidenziare una serie di input specifici che il progetto dello SP dovrebbe avere, quali: a) prossimità al Pronto Soccorso (PS), Terapia Intensiva (TI) e Degenze; b) localizzazione all’interno dell’ospedale ma separato dalle altre aree funzioni sanitarie; c) accesso autonomo con camera calda; d) caratteristiche organizzative e spaziale similari a PS, TI e Degenze; e) configurazione di uno spazio già operativo pronto all’esigenza; f) lo SP dovrebbe ospitare indicativamente il 12% delle postazioni del PS con dimensioni di circa 40 mq per postazione, come previsto per le TI. Conclusioni. Il lavoro di ricerca vuole essere uno starting point: infatti risulta necessario portare avanti le considerazioni e le strategie ampliando lo studio, magari anche a livello internazionale. Sebbene il lavoro si è focalizzato in ambito ospedaliero non si può trascurare l’emergenza verificatasi anche in ambito territoriale, ovvero in strutture a regime residenziale ormai sempre più diffuse. Pertanto il lavoro condotto dal gruppo di ricerca ha evidenziato possibili strategie che potrebbero essere attuate anche in questi contesti

    CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort

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    To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort. Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n = 15), atypical adenoma (AA) (n = 14) and typical adenoma (TA) (n = 17), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive. Mutations of CDC73 were observed in 9/15 (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair mutation in exon 7 -- c.679_680delAG -- accounted for half of all identified mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67 %) CA, 2/13 (15 %) AA, and 3/17 (18 %) TA tumors. Median follow up times were 88 months for CA, 76 months for AA, and 104 months for TA patients. One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma. Molecular screening and IHC are both useful tools in the differential diagnosis of parathyroid tumors, but both have limited sensitivity and specificity. CDC73 mutations and negative immunostaining were common in atypical adenomas, but no local recurrence was observed in any case with successful surgical removal after follow-up periods of 27 to 210 months.OBJECTIVE: To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort. METHODS: Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n = 15), atypical adenoma (AA) (n = 14) and typical adenoma (TA) (n = 17), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive. RESULTS: Mutations of CDC73 were observed in 9/15 (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair mutation in exon 7 -- c.679_680delAG -- accounted for half of all identified mutations. Absence of parafibromin nuclear staining was not
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