1,491 research outputs found
Green Fluorescent Protein-Based Chloride Ion Sensors for In Vivo Imaging
No full textcapitolo di libro: in: G. Jung (Ed.), Fluorescent Proteins II, Springer Berlin Heidelber
Replication Data for: Muscle proteome analysis of facioscapulohumeral dystrophy patients reveals a metabolic rewiring promoting oxidative/reductive stress contributing to the loss of muscle function
No full textThis dataverse include the 2-D DIGE and LC-MS/MS proteomics datasets of changed proteins generated in the study: “muscle proteome analysis of facioscapulohumeral dystrophy patients reveals a metabolic rewiring promoting oxidative/reductive stress contributing to the loss of muscle function” by Manuela Moriggi, Lucia Ruggiero, Enrica Torretta, Dario Zoppi, Beatrice Arosio, Evelyn Ferri, Alessandra Castegna, Chiara Fiorillo, Cecilia Gelfi and Daniele Capitanio. Data were generated by LC-ESI-MS/MS with label-free quantitation. Mass spectra were analyzed using MaxQuant software (Max-Planck-Institute of Biochemistry, Munich, Germany, version 1.6.17.0). Statistical analyses were performed using the Perseus software (Max Planck Institute of Biochemistry, Munich, Germany, version 1.6.15.0). For statistical analysis, Student's t-test with a p-value threshold of 0.05 was applied. To exclude the presence of false positives from the analysis, Benjamini–Hochberg false discovery rate test was applied
Profilo molecolare e genetico negli adenocarcinomi nasosinusali di tipo intestinale (ITAC)
No full textINTRODUZIONE. Il valore dei parametri istopatologici convenzionali nel predire la prognosi è dibattuto per quanto riguarda gli adenocarcinomi nasali di tipo intestinale (ITAC), richiedendo la scoperta di nuovi fattori prognostici. Il lavoro ha studiato il valore prognostico delle caratteristiche del microambiente tumorale (TME) e il panorama genetico in questo istotipo tumorale.
METODI. È stata effettuata un’analisi retrospettiva di 178 pazienti affetti da ITAC trattati presso l’Università dell’Insubria di Varese, tra il 2002 e il 2020. Le densità di linfociti intraepiteliali (EIL) e intratumorali (TIL) CD3+, CD4+, CD8+, l'espressione di MHC di classe I e II e gli score di espressione di PD-L1 sono stati valutati e correlati con la prognosi. Lo studio genetico ha incluso l'analisi NGS in 21 casi e l'analisi SALSA MLPA per delezioni/duplicazioni in 19 casi.
RISULTATI. L'analisi del TME è stata eseguita in 42 su 178 pazienti totali. PD-L1 è risultato espresso principalmente dalle cellule infiammatorie, con PD-L1 TPS>0 nel 2,4% e PD-L1 CPS>1 nel 31% degli ITAC. Gli ITAC mucinosi hanno mostrato valori di PD-L1 CPS e infiltrati intratumorali CD4+ inferiori rispetto agli altri sottotipi. Una relazione non lineare è emersa per TIL CD4+ e CD3+ nei confronti di OS e DFS, rispettivamente. Associazioni significative con OS e DFS sono state osservate per TIL CD3+, CD4+, CD8+ e PD-L1 CPS nell'analisi univariata. Tutti gli infiltrati intratumorali e l’espressione di MHC-I sulle cellule tumorali sono risultati associati ad OS in modelli multivariati. I TIL CD4+ e l'infiltrazione dei margini sono risultati associati a peggiore OS nell'analisi multivariata. I geni frequentemente mutati nella serie sono risultati essere ERBB2, KRAS, PIK3CA, HRAS e NRAS. La duplicazione/amplificazione di EGFR è stata osservata nel 73,7% dei casi.
CONCLUSIONE. La densità dei TIL, soprattutto considerando i TIL CD4+, sembra essere un fattore prognostico indipendente in questo istotipo tumorale. Il panorama genetico degli ITAC si dimostra essere eterogeneo, con l'amplificazione dell'EGFR come alterazione di più frequente riscontro. Per convalidare i risultati di questa analisi preliminare saranno necessari studi multicentrici su casistiche più ampie.INTRODUCTION. The prognostic value of conventional histopathological parameters in sinonasal Intestinal Type Adenocarcinoma (ITAC) is debated, demanding for exploration of new factors. This study assessed Tumor Microenvironment (TME) features and their prognostic impact in ITAC, along with a description of the genetic landscape.
METHODS. A retrospective analysis of 178 ITAC patients treated at the University of Insubria, Varese, between 2002 and 2020 was performed. CD3+, CD4+, CD8+ EILs/TILs densities, MHC-I, MHC-II, and PD-L1 expression were evaluated and correlated with prognosis. The genetic study included NGS analysis in 21 ITACs and SALSA MLPA analysis for deletions/duplications in 19 ITACs.
RESULTS. TME analysis was performed in 42 of the 178 patients. PD-L1 was mainly expressed by inflammatory cells, with PD-L1 TPS>0 in 2.4% and PD-L1 CPS1 in 31% of ITACs. Mucinous ITACs showed lower PD-L1 CPS and CD4+ TILs. Non-linear associations were observed between CD4+ and CD3+ TILs with OS and DFS, respectively. Significant associations with OS and DFS were noted for CD3+, CD4+, CD8+ TILs, and PD-L1 CPS in univariate analysis. All TILs and MHC-I tumor expression were associated with OS in multivariate models. CD4+ TILs and positive margins were associated with worse OS in a comprehensive multivariate model. Frequently mutated genes included ERBB2, KRAS, PIK3CA, HRAS, and NRAS. EGFR duplication/amplification occurred in 73.7% of cases.
CONCLUSION. TIL density, especially considering CD4+ TILs, appears to be an independent prognostic factor for ITACs. The genetic landscape of ITACs was heterogeneous, with EGFR amplification being the most common alteration. Larger multicentric studies are needed to validate these findings
Clenbuterol-sensitive delayed outward potassium currents in a cell model of spinal and bulbar muscular atrophy
No full textSpinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. SBMA is characterized by selective dysfunction and degeneration of motor neurons in the brainstem and spinal cord through still unclear mechanisms in which ion channel modulation might play a central role as for other neurodegenerative diseases. The beta2-adrenergic agonist clenbuterol was observed to ameliorate the SBMA phenotype in mice and patient-derived myotubes. However, the underlying molecular mechanism has yet to be clarified. Here, we unveil that ionic current alterations induced by the expression of polyQ-expanded AR in motor neuron-derived MN-1 cells are attenuated by the administration of clenbuterol. Our combined electrophysiological and pharmacological approach allowed us to reveal that clenbuterol modifies delayed outward potassium currents. Overall, we demonstrated that the protection provided by clenbuterol restores the normal function through the modulation of K(V)2-type outward potassium currents, possibly contributing to the protective effect on motor neuron toxicity in SBMA
Skull base osteoradionecrosis: from pathogenesis to treatment
No full textPurpose of review This review aims to provide a comprehensive analysis of skull base osteoradionecrosis (ORN), a severe and rare complication of radiotherapy for head and neck malignancies. It explores pathogenesis, clinical presentation, diagnostic strategies, and management approaches, emphasizing the importance of multidisciplinary care in addressing this challenging condition. Recent findings Skull base ORN results from radiotherapy-induced tissue damage, characterized by hypovascularity, hypoxia, and necrosis, often compounded by secondary infections. Advances in radiotherapy techniques, such as intensity-modulated radiotherapy and heavy particles, have reduced ORN incidence, though cases persist, particularly in high-dose radiotherapy fields. Emerging treatments, including hyperbaric oxygen therapy and the pentoxifylline-tocopherol protocol, show promise but lack robust evidence for standardized use. Surgical interventions, especially those incorporating vascularized tissue reconstruction, have demonstrated favorable outcomes in refractory cases. Recent studies underscore the utility of multimodal imaging techniques, including MRI and PET/CT, for distinguishing ORN from tumor recurrence. Summary Skull base ORN represents a complex and potentially life-threatening condition requiring tailored, multidisciplinary management. Although advancements in diagnostics and therapeutics have improved outcomes, significant challenges remain, particularly in developing standardized protocols. Further research is needed to refine treatment strategies and improve evidence-based practices for this entity
Sinonasal non-intestinal type adenocarcinoma: a retrospective review of 22 patients
No full textOBJECTIVE: To analyze outcomes and prognostic factors of sinonasal nonsalivary non-intestinal-type adenocarcinoma (n-ITAC.)METHODS: A retrospective review of 22 consecutive patients with n-ITAC was performed.RESULTS: Average follow-up time was 77 months. The 5-year overall survival and disease-specific survival were 95.2%. The 5-year overall survival and disease-specific survival were 100% for pT1, pT2, and pT3 tumors and 83.3% for pT4a and pT4b tumors; 100% for G1 tumors and 87.5% for G3 tumors; and 100% for tumors with negative surgical margin and 50% for tumors with positive surgical margin. Stage, grade, and surgical margins were independent prognostic factors. Adjuvant radiotherapy was performed for high-grade and high-stage tumors.CONCLUSIONS: Surgery followed by radiotherapy has remained a mainstay for management of n-ITAC, and the endoscopic transnasal approach, when correctly planned and indicated, is the surgery of choice. Adjuvant radiotherapy is recommended in cases of high-stage (T3 and T4) and high-grade tumors. n-ITAC is associated with a favorable outcome. High grade, pT4 stage, and positive surgical margins are independent negative prognostic factors
Perspettiva ridotta a perfezione: Glimpses of Daniele Barbaro’s Perspective Theory
No full textThis contribution is intended to identify some textual elements, apparently
secondary in Daniele Barbaro’s treatise on perspective, which either foreshadow
unprecedented developments in the discipline of representation or have
constituted complex critical nodes in the field of perspective. The first of these
is introduced in part V: anamorphosis (though never so called by the author, since
the term was not yet in use), suggesting a quick method to deform any flat image
by means of shadows. Finally, the author mentions two other ‘eccentric’ elements
of interest for the future developments of perspective that originated in Daniele
Barbaro’s text: an optical-projective device first introduced by Giovanni Battista
Vimercato, later developed by Jean François Niceron in his Thaumaturgus
opticus (1646), and the camera obscura
INTRUSION AND PRESENCE OF THE AUTHOR IN SAMUEL BECKETT’S “THE UNNAMABLE” AND B. S. JOHNSON’S “ALBERT ANGELO”
No full textThis article explores the intricate relationship between B.S. Johnson’s novel “Albert Angelo” and Beckett’s “The Unnamable”, both dealing with the issue of the possible presence of the author in his own text. The point of departure for such comparison is Johnson’s incorporation, as an epigraph, of a passage taken from Beckett’s novel. Such passage, intended rather literally by the British author, is employed as a justification not only for the central device at the heart of his novel, but also in support of a larger aesthetic project which will characterise a great part of his oeuvre – which famously stresses the importance of ‘truth’, as opposed to fabulation, and the necessity of the author’s direct presence in his texts. This contribution, in particular, tries to reconstruct the history of Johnson’s involvement with Beckett’s work, demonstrating how Johnson has in fact distorted the master’s message – perhaps intentionally – in order to produce a rather different model of literature, despite moving from very similar premises
A Surgical Variant of the Pre-Lacrimal Approach to the Maxillary Sinus
No full textWhen dealing with maxillary sinus pathology, some areas of the sinus remain difficult to examine. In this regard, the pre-lacrimal approach is a minimally invasive technique to reach anterolateral areas of the maxillary sinus while preserving the physiological nasal function
Recensione di Daniele Vecchiato: Versi per dopodomani. Percorsi di lettura nell’opera di Durs Grünbein
No full textDaniele Vecchiato offers a clear excursus on the reception of Durs Grünbein. This is the first study in Italy about this famous contemporary author that was also influenced greatly by Italian culture and literature
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