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Amyloidosis: What does pathology offer? The evolving field of tissue biopsy

Since the mid-nineteenth century pathology has followed the convoluted story of amyloidosis, recognized its morphology in tissues and made identification possible using specific staining. Since then, pathology studies have made a significant contribution and advanced knowledge of the disease, so providing valuable information on the pathophysiology of amyloid aggregation and opening the way to clinical studies and non-invasive diagnostic techniques. As amyloidosis is a heterogeneous disease with various organ and tissue deposition patterns, histology evaluation, far from offering a simple yes/no indication of amyloid presence, can provide a wide spectrum of qualitative and quantitative information related to and changing with the etiology of the disease, the comorbidities and the clinical characteristics of patients. With the exception of cardiac transthyretin related amyloidosis cases, which today can be diagnosed using non-biopsy algorithms when stringent clinical criteria are met, tissue biopsy is still an essential tool for a definitive diagnosis in doubtful cases and also to define etiology by typing amyloid fibrils. This review describes the histologic approach to amyloidosis today and the current role of tissue screening biopsy or targeted organ biopsy protocols in the light of present diagnostic algorithms and various clinical situations, with particular focus on endomyocardial and renal biopsies. Special attention is given to techniques for typing amyloid fibril proteins, necessary for the new therapies available today for cardiac transthyretin related amyloidosis and to avoid patients receiving inappropriate chemotherapy in presence of plasma cell dyscrasia unrelated to amyloidosis. As the disease is still burdened with high mortality, the role of tissue biopsy in early diagnosis to assure prompt treatment is also mentioned

Uno spazio per chi non ha dimora

Area 95 è prima di tutto un dispositivo di accoglienza che intercetta una serie di richieste prevalentemente relative all’ambito della salute mentale per persone senza dimora, spesso senza documenti e/o residenza, persone migranti dell’ambito della estrema marginalità. Si tratta di bisogni che, nonostante l’estrema regressione dello stile di vita, sono destinati altrimenti a rimanere inevasi per ragioni di ordine organizzativo/burocratico che mal si conformano al tipo di utenza richiedente. [...

Cancer of unknown primary: challenges and progress in clinical management

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies

Digital Innovation and Sustainable Development: Two Sides of the Same Coin

Digital innovations and sustainable development are key words in the current agenda of worldwide policy makers. There are high expectations that digitalization will lead the world to more sustainable paths so that accomplishing net zero economies by 2050, as envisaged by policy packages, such as the Agenda 2030 by United Nations, and the European Green Deal by the European Commission. However, the scientific evidence reveals that this result is not taken for granted, and digital transformation may worsen and make more difficult the road to sustainable development whether the use of digital devices targets only economic performance. This chapter reviews the major evidence provided by the scientific literature and introduces how policymakers have been acting to make these two key words complementary to each other

Combined Exploitation of Offshore Wind and Wave Energy in the Italian Seas: A Spatial Planning Approach

The opportunity to co-locate wind and wave energy exploitation is analyzed in the Italian seas grounding on the rationale that benefits are greater when un-correlated resources are combined. The study shows that, although waves and winds are generally strongly correlated, in some conditions their correlation is lower and the combined energy harvesting more interesting. As spatial conflicts of sea use and demand for maritime space are increasing, the development of the marine renewable energy sector needs to be evaluated in the perspective of the cumulative pressures deriving from present activities or expected from future developments. The evaluation of areas of potential conflicts among human activities, environmental vulnerabilities and marine renewable developments may facilitate the early development of mitigation actions and negotiations between stakeholders. In this study the opportunity of co-locating offshore wind turbines and wave energy converters is analyzed through a spatial planning approach. Both the potential for combining different renewable technologies, and the impact associated to such development was considered in the context of the existing pressures (e.g., naval traffic; mariculture activities; submarine cables routes; dredge spoils dumping; offshore activities; windfarms and ocean energy projects) and vulnerabilities (Marine Protected Areas, Key habitat presence) through quantitative indicators. The portion of Tyrrhenian coast south of Elba island, the northern-western Sardinian coast, and the southern Adriatic and Ionian coastal waters appear to be the most suitable sites. Moreover, the study presents a spatial quantitative methodology to identify sites of potential interest for the development of the marine renewable energy sector in the perspective of cost-effectiveness and environmental impact minimization

Basal cell carcinoma: A comprehensive review

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge

Rational Design of Photochromic Analogues of Tricyclic Drugs

Tricyclic chemical structures are the core of many important drugs targeting all neurotransmitter pathways. These medicines enable effective therapies to treat from peptic ulcer disease to psychiatric disorders. However, when administered systemically, they cause serious adverse effects that limit their use. To obtain localized and on-demand pharmacological action using light, we have designed photoisomerizable ligands based on azobenzene that mimic the tricyclic chemical structure and display reversibly controlled activity. Pseudo-analogues of the tricyclic antagonist pirenzepine demonstrate that this is an effective strategy in muscarinic acetylcholine receptors, showing stronger inhibition upon illumination both in vitro and in cardiac atria ex vivo. Despite the applied chemical modifications to make pirenzepine derivatives sensitive to light stimuli, the most potent candidate of the set, cryptozepine-2, maintained a moderate but promising M1 vs M2 subtype selectivity. These photoswitchable “crypto-azologs” of tricyclic drugs might open a general way to spatiotemporally target their therapeutic action while reducing their systemic toxicity and adverse effects

Assessment of the hyperspectral data analysis as a tool to diagnose xylella fastidiosa in the asymptomatic leaves of olive plants

Xylella fastidiosa is a bacterial pathogen affecting many plant species worldwide. Recently, the subspecies pauca (Xfp) has been reported as the causal agent of a devastating disease on olive trees in the Salento area (Apulia region, southeastern Italy), where centenarian and millenarian plants constitute a great agronomic, economic, and landscape trait, as well as an important cultural heritage. It is, therefore, important to develop diagnostic tools able to detect the disease early, even when infected plants are still asymptomatic, to reduce the infection risk for the surrounding plants. The reference analysis is the quantitative real time-Polymerase-Chain-Reaction (qPCR) of the bacterial DNA. The aim of this work was to assess whether the analysis of hyperspectral data, using different statistical methods, was able to select with sufficient accuracy, which plants to analyze with PCR, to save time and economic resources. The study area was selected in the Municipality of Oria (Brindisi). Partial Least Square Regression (PLSR) and Canonical Discriminant Analysis (CDA) indicated that the most important bands were those related to the chlorophyll function, water, lignin content, as can also be seen from the wilting symptoms in Xfp-infected plants. The confusion matrix of CDA showed an overall accuracy of 0.67, but with a better capability to discriminate the infected plants. Finally, an unsupervised classification, using only spectral data, was able to discriminate the infected plants at a very early stage of infection. Then, in phase of testing qPCR should be performed only on the plants predicted as infected from hyperspectral data, thus, saving time and financial resources