Indagine immunologica in una coorte di pazienti pediatrici affetti da sindrome di DiGeorge: correlazioni con lo stato vitaminico D.

La sindrome di DiGeorge (SDG) è causata da una microdelezione del braccio lungo del cromosoma 22. E’ stata inizialmente osservata dall’endocrinologo italo-americano Angelo DiGeorge in un gruppo di bambini che presentavano un quadro clinico comune, caratterizzato da malformazioni cardiache, dismorfismi facciali, convulsioni neonatali dovute ad ipocalcemia conseguente all’ipoparatiroidismo, infezioni ricorrenti dovute all’aplasia del timo e delle paratiroidi. L'ipocalcemia, osservata frequentemente nel periodo neonatale, di solito scompare, ma alcuni bambini possono presentare una persistenza dell'ipoparatiroidismo, che rende necessario un trattamento con calcio e vitamina D. E’ anche descritta recentemente un’incrementata incidenza di malattie autoimmuni, la cui eziopatogenesi ad oggi non acclarata, sembra essere di natura multifattoriale. Il quadro delle anomalie immunologiche è molto ampio e può variare da un normale profilo immunologico ad una completa assenza di linfociti tale da necessitare di un trapianto di timo o di midollo osseo. A causa di questa variabilità, i pazienti vengono classificati come “SDG completi”, quando presentano aplasia timica associata a severa o completa linfopenia T (≤ 1,5% dei pazienti) e “SDG parziali” quando mostrano invece ipoplasia timica. In questo gruppo di pazienti il difetto immunologico è lieve/moderato e può includere difetti numerici e/o funzionali dei linfociti T, come pure difetti dell’immunità umorale. Alterazioni quantitative e/o funzionali delle cellule dendritiche (DC) sono state identificate in diverse condizioni patologiche (allergie, patologie autoimmuni, tumori, ecc.) tuttavia il loro coinvolgimento nella SDG non è ancora stato studiato. Le DC per le loro proprietà funzionali svolgono un ruolo fondamentale nella comunicazione tra immunità innata e adattativa. Esse rappresentano la più importante famiglia di cellule presentanti l’antigene, capaci di innescare efficientemente la risposta di cellule T naive, memory ed effettrici; sono inoltre coinvolte nel mantenimento della tolleranza. Le DC circolanti possono essere distinte, sulla base di un diverso profilo fenotipico e funzionale, in due sottotipi, mieloidi (mDCs) e plasmacitoidi (pDCs), capaci di esercitare effetti complementari sulle cellule T; infatti, mentre le mDCs sono efficienti APCs, le pDCs sono implicate nella tolleranza immunitaria. Recentemente sono stati riconosciuti molteplici effetti extra-scheletrici della vitamina D ed in particolare quelli sul sistema immunitario in considerazione della presenza del suo recettore (VDR) su molte cellule del sistema immunitario (linfociti T attivati CD4 e CD8, linfociti B, neutrofili, DC, macrofagi). La 1,25-diidrossivitamina D (1,25(OH)2D3) agisce sulle cellule T, sia direttamente che indirettamente andando a regolare la produzione di citochine determinanti per il differenziamento linfocitario. Gli effetti inibitori diretti della 1,25(OH)2D3 sono più pronunciati a livello delle cellule T della memoria ed effettrici, in quanto queste cellule hanno un maggior numero di VDR sulla loro superficie rispetto alle cellule naive. La 1,25(OH)2D3 diminuisce la proliferazione, differenziazione e produzione aniticorpale dei linfociti B e ne aumenta l’apoptosi. Relativamente agli effetti sulle DC, studi in vitro hanno dimostrato che la 1,25(OH)2D3 ne inibisce la maturazione e differenziazione, portando alla formazione di cellule coinvolte in meccanismi di tolleranza ed inibendo la formazione di cellule coinvolte in meccanismi di difesa. L’effetto della 1,25(OH)2D3 su i due sottotipi di DC (mieloidi e plasmacitoidi) non è equivalente poiché essa regola, in modo preferenziale, il sottotipo delle mDCs, con conseguente soppressione dell’attivazione delle cellule T naive. Numerosi studi hanno riscontrato una correlazione inversa fra i livelli di vitamina D e l’incidenza di alcune malattie come: patologie infettive (tubercolosi, influenza, HIV), malattie autoimmuni (sclerosi multipla, diabete mellito tipo I, malattie reumatiche, psoriasi, malattie infiammatorie croniche intestinali), asma, patologie cardiovascolari e neoplasie. Scopi dello studio: Poichè l’immunodeficienza riscontrata nella SDG è causata dall’ipoplasia timica, la maggior parte degli studi ha focalizzato l’attenzione sul numero e funzione dei linfociti T. Tuttavia lo studio di questi parametri dell’immunità cellulo-mediata non si è rivelato esaustivo e non ha permesso di identificare i pazienti con SDG a maggior rischio di sviluppare infezioni severe e/o complicanze autoimmuni. Pertanto questo studio ha avuto come obiettivo un approfondimento di indagine immunologica dei pazienti con SDG, con particolare attenzione alla valutazione delle cellule dendritiche. In considerazione dei riconosciuti effetti immunomodulanti della vitamina D, la determinazione della vitamina D è stata effettuata in tutta la coorte dei pazienti studiati; essi sono stati inoltre suddivisi in gruppi, sulla base dello stato vitaminico e della presenza di ipoparatiroidismo, al fine di valutare se fosse possibile identificare correlazioni tra livelli sierici di vitamina D e deficit immune. Infine, il gruppo dei pazienti deficitari è stato sottoposto a supplementazione e successiva rivalutazione immunologica, al fine di evidenziare gli eventuali effetti della vitamina D sul sistema immunitario

Magistracy in a province of the argentine interior (Mendoza, 1872-1890)

Este trabajo busca realizar un aporte a la historia social de la justicia a través de enfoques y metodologías sujetos a la actual agenda de investigación sobre las instituciones estatales. Puntualmente, se propone presentar un análisis sobre cómo estaba organizada la justicia de paz en el territorio mendocino entre 1872-1890, un periodo en el que se dictaron las primeras leyes que regularon la administración de la justicia baja en la provincia. En efecto, durante esos años la fisonomía del poder judicial local adquirió mayor cohesión como resultado del desarrollo político e institucional del poder central y provincial. Asimismo, el trabajo centra su atención en quiénes fueron los actores que ejercieron los fueros de paz en la provincia, atendiendo principalmente, a sus perfiles socioocupacionales.This article seeks to contribute to the social history of justice through approaches and methodologies linked to the current research agenda on state institutions. Specifically, it attempts to analyze the way magistracy in Mendoza was organized between 1872-1890, the period when the first laws regulating the administration of low justice in the province were enacted. Indeed, during those years, the local judiciary acquired greater cohesion because of the political and institutional development of the central and provincial power. The article also focuses on the actors who exercised magistracy in the province, mainly exploring their sociooccupational profiles.Fil: Fucili, Eliana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Terranova, David German. Universidad Nacional de Cuyo. Facultad de Derecho; Argentina. Universidad "juan Agustin Maza". Facultad de Ciencias Empresariales y Juridicas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentin

Nanodiamond-mediated crystallization in fibers of PANI nanocomposites produced by template-free polymerization : conductive and thermal properties of the fibrillar networks

The detonation nanodiamond is a novel versatile nanomaterial with tunable properties and surface chemistry. In this work, we report on a template-free method to synthesize polyaniline based nanocomposite fibers during a chemical oxidative precipitation polymerization where the cooperative interactions between nanodiamond and polyaniline nucleates trigger the final morphology of the nanocomposite. FE–SEM and TEM observations evidence the prominent growth of fibril-like structures assembled in 2-D networks of tightly woven, partially oriented fibers. Optical and Raman spectroscopy and X-ray diffraction analyses reveal that the polymer chains are in a protonated emeraldine form and organize themselves in a highly ordered 3-D spatial arrangement. Conductivity measurements performed on isolated fibers by a conductive tip of an AFM apparatus highlight that the diamond filler does not affect the conductive properties of the polyaniline matrix while increases the thermal stability of the polymer as confirmed by TGA studies

CVD-based techniques for the synthesis of nanographites and nanodiamonds

We report about some Chemical Vapor Deposition approaches used to produce a variety of C-sp2 and C-sp3 crystalline nanostructures. The methodologies developed in our laboratories provide custom-made solutions for the fabrication of specific carbon nanomaterials with properties tailored for applications in the field of nanotechnology

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population