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SommarioLa chirurgia rappresenta la terapia di elezione della Sindrome di Cushing (SC). Quando è controindicata o rifiutata dal paziente, o quando non si dimostra un trattamento di successo perché associato a recidiva o persistenza di malattia, si può ricorrere alla terapia medica che include principalmente tre categorie farmacologiche: i farmaci ad azione centrale, quali gli analoghi della somatostatina e gli agonisti della dopamina; i farmaci ad azione surrenalica, ossia gli inibitori della steroidogenesi surrenalica; e i bloccanti dei recettori dei glucocorticoidi (GC). Recentemente, anche in Italia sono disponibili nuove molecole con diversi target terapeutici e altre sono tuttora oggetto di studi preclinici e clinici.

Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy rarely relieves bothersome symptoms for all patients. The objective of this study was to analyze the approaches and solutions that address the social and health unmet needs of patients with IBS. A qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the "Blueprint on Digital Transformation in Health and Care in an Ageing Society" persona methodology. A Survey was administered to a group of patients in anonymous form. The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management. Three main needs were identified to be met to improve IBS patient's lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and homebased digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway. Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life. KEY WORDS: Digital Health, Irritable bowel syndrome, mHealth, Nutrition, Physical activity, Psychological support.La sindrome dell’intestino irritabile (IBS) è una condizione multifattoriale comune che colpisce l’intestino crasso ed è caratterizzata da dolore addominale cronico e recidivante e alterazione delle abitudini intestinali. L’IBS è dovuta a una combinazione di fattori genetici, ambientali e dietetici. Di solito è un problema che permane per tutta la vita, molto frustrante per conviverci e può avere un grande impatto negativo sulla qualità della vita, poiché la terapia con un solo farmaco raramente allevia i sintomi fastidiosi per tutti i pazienti. L’obiettivo di questo studio era di analizzare gli approcci e le soluzioni che affrontano i bisogni sociali e sanitari insoddisfatti dei pazienti con IBS. Nel presente studio è stato adottato un approccio qualitativo per identificare e specificare la soluzione digitale chiave e gli scenari utente ad alto impatto applicati ai pazienti con IBS, attraverso un adattamento al singolo della metodologia “Blueprint on Digital Transformation in Health and Care in an Aging Society”. Un sondaggio è stato somministrato a un gruppo di pazienti in forma anonima. L’elaborazione teorica IBS personale è stata sviluppata attraverso un Focus Group interdisciplinare, che ha anche tracciato il percorso per la gestione del paziente. Sono state identificate tre esigenze principali da soddisfare per migliorare lo stile di vita dei pazienti affetti da IBS: accesso al supporto psicologico, soluzioni di mHealth a supporto della dieta e dell’attività fisica adattata e supporto sanitario digitale domiciliare. L’intervento mHealth è stato identificato per l’aderenza alla dieta, l’esercizio fisico e il benessere psicologico. Il processo è stato mappato e adattato per integrare le nuove soluzioni nel percorso assistenziale. Sono necessarie ulteriori ricerche per valutare in che modo i servizi di mHealth consentano ai pazienti con IBS di gestire le loro condizioni e migliorare la loro qualità di vita.

Background : Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy ra: Objective to analyze the approaches and solutions that address the social and health unmet needs of patients with IBS. Design: A quantitative-qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the “Blueprint on Digital Transformation in Health and Care in an Ageing Society” persona methodology. Settings: Digital health solutions bring the potential of supporting health interventions through mobile apps, wearable devices, telemedicine. Patients: A Survey was administered to a group of patients in an anonymous form, and no need for Medical Ethical Committee approval was identified. Interventions. The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management. Main Outcome : Three main needs were identified to be met to improve IBS patient’s lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and home-based digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway. Limitation: Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life. Conclusion The person-centered approach was implemented through a multidisciplinary Focus group that enabled the identification of the need for a mHealth intervention

Obesity is a chronic condition whose management is a critical challenge for physicians. The scientific community has increased its focus on the molecular mechanisms involved in obesity etiopathogenesis to better manage patients with obesity and its associated complications. The tight connection between adipose tissue and the immune system has been demonstrated to play a crucial role in inflammation, and melatonin is important for circadian rhythm regulation and metabolic homeostasis, in which it orchestrates several molecular mechanisms involved in obesity and associated inflammation. Melatonin also regulates innate and adaptive immunity; its antioxidant properties are linked to reduced predisposition to infection and weight gain in patients with obesity through the modulation of the immune response, which has a significant beneficial effect on inflammation and, consequently, on the metabolic state. Low melatonin levels have been linked to obesity, and melatonin supplementation can reduce body weight, improve metabolic profile, and ameliorate immune responses and pro-inflammatory stimuli. The role of melatonin in obesity is mainly related to improved oxidative stress signaling, modulation of adipokine secretion, and a switching from white-to-brown adipose tissue phenotype and activity. Moreover, the role of melatonin in obesity modulation by controlling circadian rhythm has recently emerged as a pivotal mechanism for lipid and glucose metabolism dysfunction in adipose, muscle, and liver tissues. Melatonin may also regulate the immune system by acting directly on thymus morphology and activity as well as by modulating oxidative stress and inflammatory states during infections. The tight association between melatonin and immune response regulation is coordinated by Toll-like receptors, which are rhythmically expressed during the day. Their expression may be strongly modulated by melatonin as their signaling is highly inhibited by melatonin. The current review summarizes studies of melatonin-induced mechanisms involved in infection regulation, particularly the modulation of obesity-associated inflammation and systemic complications.

Frailty is a complex interplay between several factors, including physiological changes in ageing, multimorbidities, malnutrition, living environment, genetics, and lifestyle. Early screening for frailty risk factors in community-dwelling older people allows for preventive interventions on the clinical and social determinants of frailty, which allows adverse events to be avoided. By conducting a narrative review of the literature employing the International Narrative Systematic Assessment tool, the authors aimed to develop an updated framework for the main measurement tools to assess frailty risks in older adults, paying attention to use in the community and primary care settings. This search focused on the biopsychosocial domains of frailty that are covered in the SUNFRAIL tool. The study selected 178 reviews (polypharmacy: 20; nutrition: 13; physical activity: 74; medical visits: 0; falls: 39; cognitive decline: 12; loneliness: 15; social support: 5; economic constraints: 0) published between January 2010 and December 2021. Within the selected reviews, 123 assessment tools were identified (polypharmacy: 15; nutrition: 15; physical activity: 25; medical visits: 0; falls: 26; cognitive decline: 18; loneliness: 9; social support: 15; economic constraints: 0). The narrative review allowed us to evaluate assessment tools of frailty domains to be adopted for multidimensional health promotion and prevention interventions in community and primary care.

Demographic change represents the most significant challenge of the 21st century. The aging population around the world will foster a consequent change in labor markets, wealth distribution, request of goods and services, as well as social and healthcare needs. The number of survivors to once deadly conditions, as well as the age associated increase in degenerative chronic conditions will represent a severe stress to our systems, that will not be sustainable any longer. At the same time, longevity might become an opportunity for the re-organization of services, leading to a new era of opportunities for economic and social prosperity. These challenges require a strong interdisciplinary approach in the identification of unmet needs, and new social, health and technological solutions, that are demand-driven and user-oriented. ICT is going to be the key to many of these revolutionary services. The European Community has proposed a new grant instrument to foster the collaboration between public administration and ICT industry for purchasing Research and Development services in order to develop a novel Information and Communication Technology solution, called Pre Commercial Procurement. ProEmpower is such a project aimed to enable patients to early diagnosis, daily management, and clinical data collection for people with type 2 diabetes. The project goes through a call for tenders issued by a consortium of four public procurers, that jointly defined a set of requirements and use cases, in collaboration with end-users, for the development of innovative solutions This manuscript describes the process that has led to the selection of two solutions that will be tested by end users in the four regions.

According to the World Health Organization (WHO), the worldwide obesity rate has tripled since 1975. In Europe, more than half of the population is overweight and obese. Around 2.8 million people die each year worldwide as a result of conditions linked to being overweight or obese. This study aimed to analyze the policies, approaches, and solutions that address the social and health unmet needs of obese patients, at different levels, in order to simulate the definition of an integrated approach, and to provide and share examples of innovative solutions supporting health promotion, disease prevention, and integration of services to improve the collaboration between the different health and care stakeholders involved across the country and in the lives of obese patients. A collaborative approach involving various levels of government and regional experts from different European countries was applied to identify, explore, and evaluate different aspects of the topic, from the innovation perspective and focusing on a European and a regional vision. Currently, people prefer more foods rich in fats, sugars, and salt/sodium than fruits, vegetables, and fiber. This behavior leads to a significant negative impact on their health-related quality of life. Changes in healthcare systems, healthy policy, and approaches to patient care and better implementation of the different prevention strategies between all the stakeholders are needed, taking advantage of the digital transformation of health and care. Such changes can support obese patients in their fight against an unhealthy lifestyle and at the same time reduce healthcare costs.

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

Purposes Pasireotide is the first medical therapy officially approved for adult patients with Cushing’s disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center. Methods Fourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis. Results Full or partial disease control was obtained in 85.7% of patients, according to a “per-protocol” methodology analysis, and in 42.9% of patients, according to an “intention-to-treat” methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose. Conclusions The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.

PI3K/Akt/mTOR pathway activation is common in GH-secreting pituitary tumours, and a target for treatment with mTOR inhibitors, including everolimus (EVE). The current study aimed to evaluate the efficacy of two PI3K inhibitors (PI3Ki), NVP-BKM120 and NVP-BYL719, alone and in combination with EVE in rat GH-secreting pituitary tumour cell line (GH3) and human GH-secreting pituitary tumour cell cultures. In GH3 cell line and in six GH-secreting tumour cell cultures, the effects of PI3Ki and EVE, as single agents and in combination, were tested on cell viability and colony survival, by MTT and clonogenic assay, respectively, whereas western blot was performed to evaluate the underlying intracellular signalling pathways. PI3Ki and EVE showed a dose-dependent inhibition of cell viability in GH3 cell line, with PI3Ki displaying a synergistic effect when combined with EVE. PI3Ki and EVE inhibited colony survival in GH3 cell line with no further improvement in combination. In GH-secreting pituitary tumour cell cultures PI3Ki are effective in inhibiting cell viability increasing the slight and non significant inhibition induced by EVE as single agent, generally showing a synergistic effect. Despite in both GH3 cell line and GH-secreting pituitary tumour cell cultures combination of PI3Ki enhanced EVE effect, the study of intracellular signalling pathways revealed a different regulation of PI3K/Akt/mTOR and MAPK between the two models. The results of the current study demonstrated that PI3Ki, especially in combination with EVE, are effective in inhibiting cell proliferation, therefore representing a promising therapeutic tool for the treatment of aggressive GH-secreting pituitary tumours, not responsive to standard medical therapies.

The paper deals with imagination and its failures from a psychoanalytic perspective. We offer a definition of imagination failures and suggest how they can be interpreted as an opportunity to learn from experience. In order to show that the topic has a concrete and not only speculative significance we consider the public report on September 11 as a case study. The report was published by the National Commission on Terrorist Attacks Upon the United States after a long investigation of the facts and circumstances relating to the September 11 attacks. The document has been the object of strong criticisms, as we argue in the paper. Both the document and some of the critiques that it received focus, however, on significant aspects of the debate about imagination, such us the fragility of imaginative thought, its dependence on unconscious desires and its plurality of outcomes: a plethora of imaginaries can in fact be developed at any time, from the same set of information about reality. We comment on these aspects and reinterpret them from a Bionian perspective. The concepts of 'unthinkability', 'imagination failure' and 'depressive position' are used to inform the necessity of dealing with an evolving and conflictual geopolitical scenario. Particular attention is paid to the proposal of 'routinizing, even bureaucratizing, the exercise of imagination' within the institutions that deal with National Defense. This possibility is discussed in depth in order to suggest how it may be concretely implemented. In conclusion, a strong case is made for the usefulness of psychoanalytic reflection in the arena of relationships among countries, with particular emphasis on the new terrorist challenges.

El articulo trata acerca de la imaginacion y sus fallas desde una perspectiva psicoanalitica. Ofrecemos una definicion de la nocion de fallas de la imaginacion y sugerimos como tales fallas pueden ...

Acromegaly is associated with an enhanced mortality, with cardiovascular and respiratory complications representing not only the most frequent comorbidities but also two of the main causes of deaths, whereas a minor role is played by metabolic complications, and particularly diabetes mellitus. The most prevalent cardiovascular complications of acromegaly include a cardiomyopathy, characterized by cardiac hypertrophy and diastolic and systolic dysfunction together with arterial hypertension, cardiac rhythm disorders and valve diseases, as well as vascular endothelial dysfunction. Biochemical control of acromegaly significantly improves cardiovascular disease, albeit completely recovering to normal mainly in young patients with short disease duration. Respiratory complications, represented mainly by sleep-breathing disorders, particularly sleep apnea, and respiratory insufficiency, frequently occur at the early stage of the disease and, although their severity decreases with disease control, this improvement does not often change the indication for a specific therapy directed to improve respiratory function. Metabolic complications, including glucose and lipid disorders, are variably reported in acromegaly. Treatments of acromegaly may influence glucose metabolism, and the presence of diabetes mellitus in acromegaly may affect the choice of treatments, so that glucose homeostasis is worth being monitored during the entire course of the disease. Early diagnosis and prompt treatment of acromegaly, aimed at obtaining a strict control of hormone excess, are the best strategy to limit the development or reverse the complications and prevent the premature mortality.

Primary or acquired resistant mechanisms prevent the employment of individualized therapy with target drugs like the mTOR inhibitor everolimus (EVE) in hepatocellular carcinoma (HCC). The current study evaluated the effect of 1,25(OH)2Vitamin D (VitD) treatment on EVE sensitivity in established models of HCC cell lines resistant to everolimus (EveR). DNA content and colony formation assays, which measure the proliferative index, revealed that VitD pre-treatment re-sensitizes EveR cells to EVE treatment. The evaluation of epithelial and mesenchymal markers by western blot and immunofluorescence showed that VitD restored an epithelial phenotype in EveR cells, in which prolonged EVE treatment induced transition to mesenchymal phenotype. Moreover, VitD treatment prompted hepatic miRNAs regulation, evaluated by liver miRNA finder qPCR array. In particular, miR-375 expression was up-regulated by VitD in EveR cells, in which miR-375 was down-regulated compared to parental cells, with consequent inhibition of oncogenes involved in drug resistance and epithelial-mesenchymal transition (EMT) such as MTDH, YAP-1 and c-MYC. In conclusion, the results of the current study demonstrated that VitD can re-sensitize HCC cells resistant to EVE treatment triggering miR-375 up-regulation and consequently down-regulating several oncogenes responsible of EMT and drug resistance.

In this paper, as-if thinking is addressed as a constitutive component of creativity at the individual and social level. We explore its functions across the life span and envision a fundamental continuity between its use in pretend play during childhood and its involvement in the process of social change. Psychoanalytic theory and its integration with developmental and cultural psychology constitute the background of our contribution and are used to define its starting hypothesis. On the basis of this literature, we also introduce a concept of everyday, ordinary creativity. Two main results are suggested. As-if thinking, that we learn to use in infancy when our capacity to symbolize starts to develop, can add a significant contribution to the process of social evolution. Many children develop creative capacities spontaneously. After childhood, however, the future of creativity is not predetermined and can follow different trajectories, depending on the level of investment in it.

In this paper we aim to conceptualize the involvement of emotion in the processes of institutional emergence and change. The starting point of our proposal is the theory of change that has been developed by Douglass North since the 1990s and has recently culminated in the publication of “Understanding the process of economic change” (2005). We agree with North in considering change as an endogenous process which starts in the individual mind through a modification of mental models and beliefs. However, notwithstanding the value that North attributes to the cognitive components of change, his approach assigns no specific role to emotion. Based on recent findings on emotions and their contribution to the process of thought, we will suggest how North’s approach may be extended in order to explore some basic mechanisms of the interaction between institutions and feelings.

Recent developments in economic literature have pointed out that path-dependence has a cognitive dimension. The paper shows how this result may be analyzed in more depth, by making explicit the links between the properties of path-dependent processes in economics and the functioning of the mind. Through the investigation of memory mechanisms, we explain why human beings might be considered as complex systems whose growth follows a stochastic and non-ergodic dynamic.

The concept of resistance to change made its appearance in the literature more than six decades ago. The paper analyses how the concept was introduced in the 1950s and how it was integrated in economic analysis by Kenneth E. Boulding. Secondly, we discuss the recent literature on the topic in order to identify the multifaceted meanings that the concept has taken on in three main areas of research: problem solving, organizational studies and institutional economics. Finally, we turn to methodological issues; the historical nature of change will be considered in order to clarify the relationship between resistance to change and path dependence.

Since the contributions by D. North [(1990). Institutions, institutional change, and economic performance. New York: CUP] and his Nobel Prize lecture [(1994). Economic performance through time, Nobel Prize Lecture. The American Economic Review, 84(3), 359–368], the relationship between mind and institutions has been increasingly investigated by economists. Mantzavinos, North, and Shariq [(2004). Learning, institutions, and economic performance. Perspectives on Politics, 2(1), 75–84] introduced the expression cognitive institutionalism in order to define this stream of research. In the first part of the paper we discuss some recent findings of the cognitive approach to institutions and its roots in the history of economic ideas. We also claim that in such an approach, no place has yet been found for a crucial faculty of the human mind, imagination. We then explore the concept of radical imaginary developed by Cornelius Castoriadis in his book The Imaginary Institution of Society (1975; 1987). From the perspective of cognitive economics, and on the grounds of Castoriadis’ legacy, we aim at highlighting some basic mechanisms of interaction between imagination, affectivity and institutions.