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Il capitolo evidenzia il rapporto che dovrebbe instaurarsi tra imprenditore e manager per assicurare che l'impresa funzioni. La ricerca evidenzia come nelle imprese eccellenti il manager sia considerato uno di famiglia ma allo stesso tempo sia una persona alla quale si lascia lo spazio di vita, familiare e professionale. inoltre il manager è libero di sperimentare le proprie competenze senza la paura di sbagliare ed essere licenziato.

Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.

Recent clinical and experimental studies have highlighted the involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons for the early pathogenesis of Alzheimer’s Disease (AD). We have previously described a progressive and selective degeneration of these neurons in the Tg2576 mouse model of AD, long before amyloid-beta plaque formation. The degenerative process in DA neurons is associated with an autophagy flux impairment, whose rescue can prevent neuronal loss. Impairments in autophagy can be the basis for accumulation of damaged mitochondria, leading to disturbance in calcium (Ca2+) homeostasis, and to functional and structural deterioration of DA neurons. Methods In Tg2576 mice, we performed amperometric recordings of DA levels and analysis of dopaminergic fibers in the Nucleus Accumbens – a major component of the ventral striatum precociously affected in AD patients – together with retrograde tracing, to identify the most vulnerable DA neuron subpopulations in the VTA. Then, we focused on these neurons to analyze mitochondrial integrity and Apoptosis-inducing factor (AIF) localization by electron and confocal microscopy, respectively. Stereological cell count was also used to evaluate degeneration of DA neuron subpopulations containing the Ca2+-binding proteins Calbindin-D28K and Calretinin. The expression levels for these proteins were analyzed by western blot and confocal microscopy. Lastly, using electrophysiology and microfluorometry we analyzed VTA DA neuron intrinsic properties and cytosolic free Ca2+ levels. Results We found a progressive degeneration of mesolimbic DA neurons projecting to the ventral striatum, located in the paranigral nucleus and parabrachial pigmented subnucleus of the VTA. At the onset of degeneration (3 months of age), the vulnerable DA neurons in the Tg2576 accumulate damaged mitochondria, while AIF translocates from the mitochondria to the nucleus. Although we describe an age-dependent loss of the DA neurons expressing Calb

Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.

Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.

Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the past years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato, the Società Italiana di Diabetologia and the Società Italiana dell’Obesità reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l’Eccellenza delle cure and Istituto Superiore di Sanità. Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence Level of evidence of recommendations for each PICO question were reported according to available evidence.

Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available evidences on the impact of patient preferences for therapy on adherence to a prescribed treatment in chronic diseases requiring long-term treatment. A search on PubMed retrieved 699 publications, leading to a selection of 12 publications: 6 on osteoporosis, 2 on moderate-to-severe asthma, 1 on type 1 diabetes, 1 on type 2 diabetes, 1 on kidney transplantation, and 1 on atrial fibrillation. Overall, 8 studies found a positive association between patient preference and adherence to therapy, while the others found no association. In general, overall adherence was considered to be high in the published studies. The reasons for a positive association included reduced dosing frequency, route of administration, lower costs, and favorable safety profile, which is related to the diverse nature of the pathology and its type and duration of treatment. A literature review suggests that achieving good adherence and persistence to therapy requires evaluation of patient preferences. In a period of increasingly limited resources, more effort is warranted to promote better adherence to therapy, especially when patients must self-manage their disease in the long term. Our results further highlight that insufficient attention has been given to the relationship between patient preference and adherence and point out the complex nature of adherence and the need for adequate patient education. More efforts are also needed to better understand the entity of cost savings for payers for specific treatments and the link with patient preference.

Aim: This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis: Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions: The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.