Sequenziamento e studi di associazione su tutto il genoma per svelare i geni di suscettibilità al diabete di tipo 1.

During my third doctoral year, I worked in the Genome-Wide Association (GWA) and sequencing study of type 1 diabetes (T1D), directed by Prof. Francesco Cucca. The project aims to find type 1 diabetes risk loci using a large collection of Sardinian patients and controls. T1D is a multifactorial autoimmune disease, common in Sardinia, so the population is an appropriate cohort for the study. The GWA study design was a scan of 1,377 patients and 1,917 healthy unrelated controls genotyped with the Affymetrix 6.0 chip that contains over 900K single nucleotide polymorphisms (SNPs) across the genome. These data are then imputed with whole genome sequencing data from reference panels: our 508 sequenced Sardinian individuals, or 280 Europeans (of the 1000 genomes project), respectively. This let us test more than 13 million variants per person. Our analysis confirmed (P=1x10-5) several known associations outside the HLA region (PTPN22, CTLA4, IL2RA and INS gene). Imputation quality improved with the Sardinian reference panel. For instance, the INS gene association p-value increased from 7.3*10-8 (1000 Genomes) to 5.5* 10-13 (Sardinian), suggesting that DNA sequencing data from a specific population improves accuracy of imputation in that population. To increase the chance to find new T1D susceptibility loci, we are expanding the dataset (to > 2,000 cases) and sequencing 1,200 Sardinian individuals for the reference panel

Clinical pitfalls of leishmaniasis and Whipple’s disease hidden behind systemic lupus erythematosus: A case series

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple’s disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases

The Impressive Anti-Inflammatory Activity of Cerium Oxide Nanoparticles: More than Redox?

Cerium oxide nanoparticles (CNPs) are biocompatible nanozymes exerting multifunctional biomimetic activities, including superoxide dismutase (SOD), catalase, glutathione peroxidase, photolyase, and phosphatase. SOD- and catalase-mimesis depend on Ce3+/Ce4+ redox switch on nanoparticle surface, which allows scavenging the most noxious reactive oxygen species in a self-regenerating, energy-free manner. As oxidative stress plays pivotal roles in the pathogenesis of inflammatory disorders, CNPs have recently attracted attention as potential anti-inflammatory agents. A careful survey of the literature reveals that CNPs, alone or as constituents of implants and scaffolds, strongly contrast chronic inflammation (including neurodegenerative and autoimmune diseases, liver steatosis, gastrointestinal disorders), infections, and trauma, thereby ameliorating/restoring organ function. By general consensus, CNPs inhibit inflammation cues while boosting the pro-resolving anti-inflammatory signaling pathways. The mechanism of CNPs' anti-inflammatory effects has hardly been investigated, being rather deductively attributed to CNP-induced ROS scavenging. However, CNPs are multi-functional nanozymes that exert additional bioactivities independent from the Ce3+/Ce4+ redox switch, such as phosphatase activity, which could conceivably mediate some of the anti-inflammatory effects reported, suggesting that CNPs fight inflammation via pleiotropic actions. Since CNP anti-inflammatory activity is potentially a pharmacological breakthrough, it is important to precisely attribute the described effects to one or another of their nanozyme functions, thus achieving therapeutic credibility

L’analisi LCA a supporto della sostenibilità delle imprese: prodotti edilizi in laterizio

Capacità di innovare e prodotti ad alta sostenibilità ambientale saranno fondamentali per superare le difficoltà che stanno interessando il settore delle costruzioni negli ultimi anni. Lo studio presentato in questo articolo rappresenta un esempio di come il Life Cycle Assessment costituisca uno strumento essenziale a supporto della valorizzazione delle risorse e delle filiere locali nel campo dell’edilizia sostenibile. L’analisi condotta su alcuni prodotti edilizi in laterizio, ha portato a risultati interessanti sullo stato attuale: le aziende stanno infatti acquisendo una maggiore consapevolezza sia per quanto riguarda il miglioramento della filiera produttiva sia per quanto riguarda l’implementazione della competitività e la comunicazione degli aspetti ambientali rivolti all’utente finale

Un romanzo in un endecasillabo?

Durante il corso di Letteratura italiana (anno 2017/18), dedicato alla Commedia di Dante, gli studenti sono stati invitati a cimentarsi nell’impresa di concentrare un romanzo nello spazio conchiuso di un endecasillabo o più terzine dantesche – o, in alternativa, nella misura di un tweet: si trattava (in un certo senso) di emulare la capacità del sommo poeta di distillare un’intera esistenza (Paolo e Francesca, Ulisse, Conte Ugolino…) nel volgere di poche terzine. Una giuria di ‘addetti ai lavori’ ha selezionato i migliori componimenti – sorvolando, di tanto in tanto, su alcune infrazioni creative rispetto alle misure canoniche

In-process real-time probiotic phenotypic strain identity tracking: The use of Fourier transform infrared spectroscopy

Probiotic bacteria, capable of conferring benefits to the host, can present challenges in design, development, scale-up, manufacturing, commercialization, and life cycle management. Strain identification is one of the main quality parameters; nevertheless, this task can be challenging since established methodologies can lack resolution at the strain level for some microorganisms and\or are labor-intensive and time-consuming. Fourier transform infrared spectroscopy (FTIRS) has been largely used for the investigation of pathogenic species in the clinical field, whereas only recently has been proposed for the identification of probiotic strains. Within the probiotic industrial production, bacterial strains can be subjected to stressful conditions that may affect genomic and phenotypic characteristics; therefore, real-time monitoring of all the sequential growth steps is requested. Considering the fast, low-cost, and high-throughput features, FTIRS is an innovative and functional technology for typing probiotic strains from bench-top experiments to large-scale industrial production, allowing the monitoring of stability and identity of probiotic strains. In this study, the discriminatory power of FTIRS was assessed for four Lactiplantibacillus plantarum probiotic strains grown under different conditions, including temperatures (30 and 37°C) and medium (broth and agar), after consecutive sub-culturing steps. A comparison between the generated spectra with pulsed-field gel electrophoresis (PFGE) profiles was also performed. FTIRS was not only able to distinguish the strains of L. plantarum under different growth conditions but also to prove the phenotypic stability of L. plantarum type strain LP-CT after six growing steps. Regardless of the growth conditions, FTIRS spectra related to LP-CT constituted a unique hierarchical cluster, separated from the other L. plantarum strains. These results were confirmed by a PFGE analysis. In addition, based on FTIRS data, broth cultures demonstrated a higher reproducibility and discriminatory power with respect to agar ones. These results support the introduction of FTIRS in the probiotic industry, allowing for the step-by-step monitoring of massive microbial production while also guaranteeing the stability and purity of the probiotic strain. The proposed novel approach can constitute an impressive improvement in the probiotic manufacturing process

Cardiac function in borderline hypothyroidism: a study by pulsed wave tissue Doppler imaging

Objective: In subclinical hypothyroidism (SH), impaired diastolic function has been documented at rest and on effort, while systolic dysfunction has only been assessed on effort. Design: The aim of the present study was: (a) to further assess systolic function at rest in SH; and (b) to ascertain whether cardiac dysfunction could precede TSH increase in euthyroid patients with a high risk of developing SH. Methods: We studied 32 patients with classical Hashimoto's thyroiditis (22 with increased serum TSH (> 3 mU/ml – group A), and 10 with normal serum TSH (< 3 mU/ml – group B)); a third group (C), which included 13 healthy controls. All subjects underwent pulsed wave tissue Doppler imaging (PWTDI) to accurately quantify the global and regional left ventricular function. Results: When compared with group C, PWTDI indices showed that in both groups A and B there was a significant impairment of systolic ejection (P < 0.001 and P < 0.05, respectively), a delay in diastolic relaxation (P < 0.001 and P < 0.05, respectively) and a decrease in the compliance to the ventricular filling (P < 0.05). Several significant correlations were found between PWTDI parameters and serum-free T3 and T4 and TSH concentrations. Conclusion: PWTDI is a sensitive technique that allows detection of both diastolic and systolic abnormalities, not only in patients with SH, but also in euthyroid subjects with a high risk of developing thyroid failure. Futhermore, the significant correlations of several PWTDI indices with serum FT3 and TSH concentrations strongly support the concept of a continuum spectrum of a slight thyroid failure in autoimmune thyroiditis extending to subjects with serum TSH still within the normal range

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging

Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30&nbsp;days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD

National variations in perioperative assessment and surgical management of Crohn's disease: a multicentre study

Aim: Crohn's disease (CD) requires a multidisciplinary approach and surgery should be undertaken by dedicated colorectal surgeons with audited outcomes. We present a national, multicentre study, with the aim to collect benchmark data on key performance indicators in CD surgery, to highlight areas where standards of CD surgery excel and to facilitate targeted quality improvement where indicated. Methods: All patients undergoing ileocaecal or redo ileocolic resection in the participating centres for primary and recurrent CD from June 2018 to May 2019 were included. The main objective was to collect national data on hospital volume and practice variations. Postoperative morbidity was the primary outcome. Laparoscopic surgery and stoma rate were the secondary outcomes. Results: In all, 715 patients were included: 457 primary CD and 258 recurrent CD with a postoperative morbidity of 21.6% and 34.7%, respectively. Laparoscopy was used in 83.8% of primary CD compared to 31% of recurrent CD. Twenty-five hospitals participated and the total number of patients per hospital ranged from 2 to 169. Hospitals performing more than 10 primary CD procedures per year showed a higher adoption of laparoscopy and bowel sparing surgery. Conclusions: There is significant heterogeneity in the number of CD surgeries performed per year nationally in Italy. Our data suggest that high-volume hospitals perform more complex procedures, with a higher adoption of bowel sparing surgery. The rate of laparoscopy in high-volume hospitals is higher for primary CD but not for recurrent CD compared with low-volume hospitals