Photoresponsive azobenzene-based materials for smart cell culture applications

The work described in this thesis intends to exploit the photomechanical properties of azobenzene-based materials for the realization of functional photoresponsive cell culture platforms. Up to date, a big variety of photolithographic techniques has been successfully adopted for azopolymer photopatterning and even the possibility of a dynamic modulation of the topographical features of 2D cell culture substrates appeared to be feasible using these materials. In fact, a great biological interest resides in the dynamic modulation of the cell-material crosstalk, in order to recapitulate in vitro the fast remodeling of the natural extracellular microenvironment, in terms of biochemical, topographical and mechanical cues. In this thesis, light-induced topographical and structural modifications of different azobenzene-based materials have been used in many biological applications, either at a single-cell level, or in multicellular systems. In particular, light-based techniques already used for single-cell investigations have been implemented to study more complex biological processes, which involve the cell-cell interactions in their final biological response. At the same time, the realization of novel 3D photoresponsive platforms for smart cell culture has been introduced. Findings discussed in this thesis add a valuable contribution to the field of azobenzene-based matters as novel dynamic cell-instructive materials

Functional Foods for elderly people: new paths for multi "functional" agriculture

AbstractNowadays a growing interest in how agritourism could be able to promote alternative nutrition stands out. The increase in the number of elderly has determined a desire for quality of life improvement; consequently, more attention has been paid to the role of food and their contents. A diet comprising Functional Foods could help not only to improve life quality of an aging population, as these foods are potentially capable to improve health and well-being; but they could also reduce health risks or delay the onset of serious pathologies. Moreover, scientific evidence of the correlation between diet and health for the elderly population, having a sedentary lifestyle and even a constant increase in healthcare costs, have addressed the interest in healthier food products. The aim of this paper was to design new food-based paths for agritourism farms that could promote health, nutritional and cultural values. To define these paths, a two steps analysis was carried out: (1) opinion collection from elderly and agritourism operators and (2) definition of a logical framework.Results highlighted that differentiating what is offered could increase health levels of elderly and create new multi "functional" shapes for agritourism farms aimed at both offering local and Functional Foods for elderly and at spreading social-tradition values

New tricks and emerging applications from contemporary azobenzene research

Azobenzenes have many faces. They are well-known as dyes, but most of all, azobenzenes are versatile photoswitchable molecules with powerful photochemical properties. Azobenzene photochemistry has been extensively studied for decades, but only relatively recently research has taken a steer towards applications, ranging from photonics and robotics to photobiology. In this perspective, after an overview of the recent trends in the molecular design of azobenzenes, we highlight three research areas where the azobenzene photoswitches may bring about promising technological innovations: chemical sensing, organic transistors, and cell signaling. Ingenious molecular designs have enabled versatile control of azobenzene photochemical properties, which has in turn facilitated the development of chemical sensors and photoswitchable organic transistors. Finally, the power of azobenzenes in biology is exemplified by vision restoration and photactivation of neural signaling. Although the selected examples reveal only some of the faces of azobenzenes, we expect the fields presented to develop rapidly in the near future, and that azobenzenes will play a central role in this development.publishedVersionPeer reviewe

Screening high school students in Italy for sudden cardiac death prevention by using a telecardiology device. a retrospective observational study

BACKGROUND: In 2010, an Italian project was launched aimed at using a telecardiology device in order to perform early diagnosis of young students at risk of sudden cardiac death. METHODS: Our retrospective observational study was conducted on a population of 13,016 students, aged between 16 and 19 years, in different Italian regions. It consisted of analysis of data recorded during a telecardiology pilot study. The recorded data were electrocardiograms and data concerning lifestyle habits and family history of cardiovascular diseases. In total, 14 alterations in the electrocardiogram signal have been considered in this study. Some of these alterations are as follows: ventricular ectopic beats, atrioventricular block, Brugada-like electrocardiogram pattern, left anterior/posterior fascicular block, left/right ventricular hypertrophy, long/short QT interval, left atrial enlargement, right atrial enlargement, short PQ interval, and ventricular pre-excitation Wolff-Parkinson-White syndrome. On the basis of the collected data, we implemented this retrospective observational study. RESULTS: The analysed data showed that 13.60% of students had a family history for cardiovascular diseases, 22.43% reported smoking habits, 26.23% reported alcohol consumption, and 7.24% reported abuse of drugs. A total of 24% of students had at least one of the 14 electrocardiogram pathological alterations considered in our study and 32% had electrocardiogram values within the normal range. CONCLUSIONS: This retrospective observational study analysed data registered during our telecardiology activity. This activity permitted to maximise data collection and minimise the costs for collecting such data. This activity of screening is being continued and in the next few years it will allow us to have a greater mass of data

Light-Responsive Bilayer Cell Culture Platform for Reversible Cell Guidance

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Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment

Abstract Aim Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. Methods A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland–Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. Results From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538–0.686), PgR (k0.659; 95% CI, 0580–0.737), Ki-67 (k0.609; 95% CI, 0.534–0.684) and grading (k0.669; 95% CI, 0.569–0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444–0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. Conclusions In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results

The role of life cycle thinking-based methodologies in the development of waste management plans

The aim of this article is to examine how Life Cycle Thinking (LCT) contributes to the development of Waste Management Plans (WMPs). The case of Italy has been deeply investigated. The article first analyses whether and how the LCT methodologies were applied to the 21 regional WMPs; then, it draws indications for using LCT in the preparation of a WMP. Moreover, it outlines why the Life Cycle Assessment (LCA) methodology could be used as a powerful tool for regional planning in the waste field, analysing the indications for preparing a WMP that already exist at the European level and in the Italian National WM Programme. Results reveal that only four of the 21 regional WMPs include comprehensive and site-specific LCA studies. Building on these case study results, insights into the opportunities and benefits associated with incorporating LCT methodologies into WMP development and implementation are provided. This study underscores the critical importance of LCT and LCA in promoting sustainable waste management practices, ensuring compliance with European directives, and offering a foundation for more informed regional planning strategies

Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer\u2019s disease.

Memory loss characterizes several neurodegenerative disorders, including Alzheimer’s disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising therapeutic approach to treat cognitive deficits. However, PDE4 exists in several isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here, we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both in vitro and in vivo using biochemical, electrophysiological and behavioural analyses. GEBR-32a efficiently enhances cAMP in neuronal cultures and hippocampal slices. In vivo pharmacokinetic analysis shows that GEBR-32a is rapidly distributed within the central nervous system with a very favourable brain/blood ratio. Specific behavioural tests (object location and Y-maze continuous alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance memory in AD transgenic mice and concomitantly rescues their hippocampal long-term potentiation deficit. Of great relevance, our preliminary toxicological analysis indicates that GEBR-32a is not cytotoxic and genotoxic, and does not seem to possess emetic-like side effects. In conclusion, GEBR-32a could represent a very promising cognitive-enhancing drug with a great potential for the treatment of Alzheimer’s disease

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study

Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA)

The pivotal role of ECG in cardiomyopathies

Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Recent technological advances in cardiovascular imaging offer an opportunity for deep phenotypic and etiological definition. Electrocardiogram (ECG) is the first-line diagnostic tool in the evaluation of both asymptomatic and symptomatic individuals. Some electrocardiographic signs are pathognomonic or fall within validated diagnostic criteria of individual cardiomyopathy such as the inverted T waves in right precordial leads (V1–V3) or beyond in individuals with complete pubertal development in the absence of complete right bundle branch block for the diagnosis of arrhythmogenic cardiomyopathy of the right ventricle (ARVC) or the presence of low voltages typically seen in more than 60% of patients with amyloidosis. Most other electrocardiographic findings such as the presence of depolarization changes including QRS fragmentation, the presence of epsilon wave, the presence of reduced or increased voltages as well as alterations in the repolarization phase including the negative T waves in the lateral leads, or the profound inversion of the T waves or downsloping of the ST tract are more non-specific signs which can however raise the clinical suspicion of cardiomyopathy in order to initiate a diagnostic procedure especially using imaging techniques for diagnostic confirmation. Such electrocardiographic alterations not only have a counterpart in imaging investigations such as evidence of late gadolinium enhancement on magnetic resonance imaging, but may also have an important prognostic value once a definite diagnosis has been made. In addition, the presence of electrical stimulus conduction disturbances or advanced atrioventricular blocks that can be seen especially in conditions such as cardiac amyloidosis or sarcoidosis, or the presence of left bundle branch block or posterior fascicular block in dilated or arrhythmogenic left ventricular cardiomyopathies are recognized as a possible expression of advanced pathology. Similarly, the presence of ventricular arrhythmias with typical patterns such as non-sustained or sustained ventricular tachycardia of LBBB morphology in ARVC or non-sustained or sustained ventricular tachycardia with an RBBB morphology (excluding the “fascicular pattern”) in arrhythmogenic left ventricle cardiomyopathy could have a significant impact on the course of each disease. It is therefore clear that a learned and careful interpretation of ECG features can raise suspicion of the presence of a cardiomyopathy, identify diagnostic “red flags” useful for orienting the diagnosis toward specific forms, and provide useful tools for risk stratification. The purpose of this review is to emphasize the important role of the ECG in the diagnostic workup, describing the main ECG findings of different cardiomyopathies