Trattamento preoperatorio dei Pazienti obesi candidati a chirurgia bariatrica: dieta chetogenica vs dieta ipocalorica

Background L'obesità ha un ruolo fisiopatologico rilevante per i problemi di salute che si presentano a seguito dell' interazione complessa di fattori genetici, nutrizionali e metabolici. Dal punto di vista scientifico, in Italia le prime Sperimentazioni del trattamento dietetico chetogenico risalgono al 1996 (Az. Osp. Moscati di Avellino), a partire dagli studi di Blackburn GL degli anni 70(14,15). Nel corso degli anni le peculiarità della metodologia sono state analizzate, finalizzandole in uno studio pilota come preparazione del paziente candidato a Chirurgia Bariatrica. Tale metodica è stata analizzata paragonandola ad una dieta ipocalorica, con l' intento di confermarne l' efficacia nel rapido calo ponderale e, soprattutto, nell' approccio al Paziente candidato a Chirurgia, la risposta del tessuto adiposo viscerale e degli organi interni quali milza e fegato. Sono stati inoltre valutati parametri ematobiochimici, la cui riduzione predispone il Paziente ad un migliore outcome in vista dell' intervento chirurgico. A corollario di tale Studio Clinico, sono stati citati tre ulteriori e successivi Studi clinici(19,20,21), i quali hanno confermato l' efficacia della dieta proteica chetogenica nel confronto con l' ipocalorica, analizzando la sua efficacia e sicurezza a priori, non limitandosi al suo utilizzo propedeutico alla Chirurgia Bariatrica, così da rendere tale trattamento dietetico ancor più standardizzato e validato scientificamente per l' intento proposto. Materiali e metodi Sono stati analizzati 56 Pazienti candidati a Chirurgia Bariatrica, la metà dei quali trattati con dieta proteico-aminoacidica chetogenica, metà con dieta ipocalorica bilanciata. Criterio di inclusione: BMI> 50 kg/m2 o altri parametri di alto rischio operatorio. Adesione volontaria al protocollo. Risultati Rispetto allo scopo iniziale dello studio, ossia valutare l’impiego in termini di maggiore efficacia ed efficienza, del trattamento dietetico proteico-aminoacidico rispetto ad alcuni parametri presi in considerazione, è possibile affermare che nel complesso i pazienti trattati hanno avuto un outcome migliore rispetto al controllo. I parametri ecografici, clinici ed ematobiochimici sono variati nel campione che ha sostenuto il trattamento dietetico proteico- aminoacidico in modo assai più rilevante rispetto al controllo. Parallelamente, negli studi esposti a corollario dello Studio clinico iniziale, il trattamento chetogenico ha mostrato efficacia e sicurezza paragonabile ad una dieta ipocalorica, fatto questo che lo propone con più consapevolezza come idoneo alla preparazione del paziente grande obeso alla Chirurgia bariatrica. Conclusioni A fronte di risultati soddisfacenti nei Pazienti candidati a Chirurgia Bariatrica, lo scetticismo della Comunità Scientifica verso un trattamento dietetico ritenuto molto “aggressivo” e non privo di controindicazioni ed effetti collaterali(16), può essere ragionevolmente mitigato dagli Studi Clinici che sono seguiti a quello oggetto di questa Tesi, che sono stati dovutamente citati, rendendo questo protocollo dietetico ancor più conosciuto anche nelle dinamiche biochimiche che presuppone, ottenute in condizioni di efficacia e sicurezza, così da proporlo con meno remore per lo scopo dello studio Clinico iniziale. A livello più strettamente chirurgico, le modificazioni rese evidenti dalla ecografia e che presentano indubbi vantaggi al tavolo operatorio, dovranno essere statisticamente quantificate, rendendole quanto più possibile oggettive e indipendenti dalle variabili dell' atto chirurgico stesso, così da validare ancor meglio tale approccio dietoterapico preoperatorio

Musées et accessibilité: de la sélection de l'information à la médiation, quelles approches pour les publics en situation de handicap visuel ?

L’accès aux musées pour les publics en situation de handicap visuel constitue un défi considérable, que de plus en plus d’institutions s’attellent à relever. Au-delà des difficultés liées aux déplacements physiques et à l’orientation dans l’espace, la complexité réside aussi dans la transmission de l’objet muséal, de ses contenus informatifs et de son ressenti. Alors que, traditionnellement, l’exposition sollicite de manière quasi exclusive la vue, comment s’adresser à un public privé de ce sens ? Ce travail traite donc de la problématique de l’accessibilité informationnelle et émotionnelle. Il a pour objectifs de dresser un état des lieux de la théorie et de la pratique dans ce domaine en Suisse et à l’étranger, de recueillir les besoins des handicapés de la vue et d’explorer les différents moyens permettant de communiquer des informations et de générer des émotions lors d’une visite. Il s’adresse aux musées souhaitant développer l’accueil des publics aveugles et malvoyants, en leur offrant l’occasion de mieux comprendre les attentes spécifiques de cette catégorie de visiteurs et en leur fournissant un panel d’exemples de médiations, réalisées ou non. Dans la première partie de ce travail, l’état de l’art regroupe d’abord des données contextuelles sur la définition du handicap visuel, qui s’avère être fort varié suivant les déficiences et les vécus des personnes atteintes, et les aspects juridiques traitant de l’égalité d’accès à la culture. Il rassemble ensuite les éléments touchant à la médiation, allant de l’éducation à l’art à la formation du personnel, en passant par les dispositifs eux-mêmes, classés en fonction des sens qu’ils stimulent. Enfin, il présente des exemples de médiations en Suisse et dans le monde. Sur la base cette première recherche, nous avons mené une enquête qualitative sur le territoire genevois, sous la forme d’un entretien avec des médiateurs culturels et d’un focus group avec des visiteurs de musées ayant une déficience visuelle, recrutés par le biais d’associations d’aide aux aveugles. Les résultats de ces entrevues sont présentés dans la deuxième partie de ce dossier. Ils permettent de mieux cerner la nature de l’offre et de la demande en matière de médiation pour les handicapés de la vue. L’une et l’autre sont également comparées pour évaluer leur degré d’adéquation. Dans la troisième partie de cette étude, la confrontation des résultats de notre enquête avec l’état de l’art fait ressortir les similitudes et les décalages entre la théorie et les pratiques actuelles à Genève. Parmi les éléments mis en évidence, nous pouvons notamment citer la prépondérance de la médiation humaine par rapport à la médiation technologique, l’importance de la stimulation de l’ensemble des sens dans la transmission des émotions et la nécessité de développer des dispositifs adaptés à tous les types de handicaps visuels. Enfin, notre réflexion débouche sur une série de recommandations à l’attention des institutions culturelles

Undesired monetary policy effects in a bubbly world

Stock market bubbles arise as a joint monetary and financial phenomenon. We assess the potential of monetary policy in mitigating the onset of bubbles by means of a Markov-switching Bayesian Vector Autoregression model estimated on US 1960-2019 data. Bubbles are detected and dated from the regime-specific interplay among asset prices, fundamental values, and monetary policy shocks. We rationalize the empirical evidence with an Overlapping Generations model, able to generate a bubbly scenario with shifts in monetary policy, and where agents form beliefs over transition dynamics. By matching the VAR impulse responses, we find that procyclicality and financial instability align with high equity premia and the presence of asset price bubbles. Monetary policy tightening, by increasing real rates, is ineffective in deflating bubble episodes

Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. METHODS: Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann-Whitney test. RESULTS: Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (< 3 months) to nivolumab treatment. The median value of kyn/trp ratio was 0.06 µg/ml and the median value of quinolinic acid was 68.45 ng/ml. A significant correlation between early progression and higher kyn/trp ratio and quinolinic acid concentration was observed (p = 0.017 and p = 0.005, respectively). Patients presenting lower values of kyn/trp ratio and quinolinic acid levels showed longer PFS (median PFS not reached versus 3 months; HR: 0.3; p = 0.018) and OS (median OS not reached vs 3 months; HR: 0.18; p = 0.0005). CONCLUSION: IDO activity, expressed as kyn/trp ratio, is associated with response to immunotherapy; in particular, higher kyn/trp ratio could predict resistance to anti-PD-1 treatment. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio

Biomarkers of Chronic Inflammatory State in Uremia and Cardiovascular Disease

Cardiovascular disease is the leading cause of death in the general population; traditional risk factors seem inadequate to explain completely the remarkable prevalence of cardiovascular mortality and morbidity observed in the uremic population. A role for chronic inflammation has been well established in the development of atherosclerotic disease, and, on the basis of these observations, atherosclerosis might be considered an inflammatory disease. Inflammation has been implicated in the etiology of coronary artery disease in the general population, and traditional inflammatory biomarkers such as C-reactive protein (CRP) and interleukin-6 (IL-6) have been shown to predict cardiovascular events in both symptomatic and asymptomatic individuals as well as those in the uremic population. Later on, new nontraditional markers were related to the risk of cardiovascular morbidity and mortality in general and in uremic population. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for cardiovascular disease (CVD) risk prediction has grown rapidly and several commercial assays have become available. So, up to now we can consider that several new nontraditional markers as CD40-CD40 ligand system and pentraxin-3 seem to be significant features of cardiovascular disease in general and in ESRD population

Dioxomolybdenum(VI) compounds with α-amino acid donor ligands as catalytic precursors for the selective oxyfunctionalization of olefins

A series of cis-dioxomolybdenum(VI) α-amino acid containing compounds I–V has been investigated as potential catalyst precursors for the mild and selective oxyfunctionalization of conjugated or unconjugated olefins like styrene, α-methylstyrene, cis-β-methylstyrene, cyclohexene and cyclooctene, using tert-butyl hydroperoxide (TBHP) as main oxidant. All the I–V complexes behaved as active heterogeneous and recyclable catalysts, showing good to quantitative conversion values of the substrate. In all cases, high selectivity toward the corresponding epoxide formation was detected. No substantial difference in terms of efficiency has been observed among the different catalysts I–V, thus confirming that the different nature of the amino acidic side-chain does not strictly affect the catalytic process. Insights into mechanistic details and reaction free energy profile of catalytic oxidations by means of quantum chemical calculations have been discussed

Receptive music interventions improve apathy and depression in elderly patients with dementia

Individuals with dementia and their families often experience poor quality of life due to patient's behavioral and psychological symptoms. Increasing evidence has mounted on the potential role of music in improving social, emotional and cognitive skills. In the present study we aim to investigate whether a receptive music intervention might reduce apathy and depression in elderly patients with Alzheimer's disease (AD) or vascular dementia (VaD) and improve their caregivers' burden. Among patients attending to a Memory Clinic, we have enrolled 48 AD or VaD elderly subjects. They were divided into two groups on the basis of family agreement to musictherapy. The experimental group (n=15) was asked to listen to a 80-minute audio CD, for at least 15 minutes per day, at least once a week, for three months. The overall sample was evaluated at baseline, at week 4 and at week 12 through the Mini Mental State Examination (MMSE), the Cornel- Brown Scale QoL in Dementia (CBSQoLD) and the Apathy Evaluation Scale (AES); caregiver stress was assessed using the Caregiver Burden Inventory (CBI). Apathy and depression were significantly improved among patients treated with music interventions compared to control group (treatment effect =43.667; P<0.001 and treatment effect =61.238; P<0.001 respectively). Caregiver burden was significantly reduced after three months of receptive music approach (treatment effect =15.759; P<0.001). The results of this study are consistent with the efficacy of receptive music interventions on improving apathy and depression in AD or VaD elderly patients and lowering associated caregiver's burden

Musical hallucinations in elderly patients with visuospatial impairment: two case reports

Musical hallucinations are an uncommon type of auditory hallucinations, they widely occur in elderly. Our group analyzed medical history, pharmacological therapy, neuropsychological pattern, audiometric testing, electroencephalogram, cerebral magnetic resonance and cerebral fludeoxyglucose-positron emission tomography (FDG-PET) of two patients. FDGPET showed in both patients hypometabolism pronounced in posterior regions. In particular the medial-inferior temporal cortex and the occipital associative areas were affected. Moreover, neuropsychological pattern suggested a visuospatial-executive deficit, conformed to the occipital involvement. Our reported cases might suggest that musical hallucinations have been arisen from a combination of peripheral and central dysfunction. A further explanation might be that musical hallucinations result from multiple white matter lacunar lesions due to small vascular events. A question is whether musical hallucinations might be primarily associated with occipital areas hypometabolism and visuospatial alterations typically associated with Levy body dementia (LBD)

Leaning against the bubble. Can theoretical models match the empirical evidence?

By estimating a Markov-switching model, we provide new evidence on the nonlinear effects of monetary policy shocks on asset prices and on their bubble component. We show that regime-dependence is mainly driven by the states affecting the interest rate equation. We also show that, following a positive interest rate shock, an OLG model of asset price bubbles with credit frictions and sticky prices may predict an increase in the real rate, a recession/deflation and an increase in the bubble value. This result, which is new to the theoretical literature, matches both the previously existing and our empirical evidence

Leaning against the bubble. Can theoretical models match the empirical evidence?

By estimating a Markov-switching model, we provide new evidence on the nonlinear effects of monetary policy shocks on asset prices and on their bubble component. We show that regime-dependence is mainly driven by the states affecting the interest rate equation. We also show that, following a positive interest rate shock, an OLG model of asset price bubbles with credit frictions and sticky prices may predict an increase in the real rate, a recession/deflation and an increase in the bubble value. This result, which is new to the theoretical literature, matches both the previously existing and our empirical evidence