142 research outputs found
Possibile interazione tra i livelli plasmatici dell'omocisteina e le abitudini alimentari come fattori di rischio per lo sviluppo di patologie nell’uomo umana: Il ruolo nutraceutico dei supplementi vitaminici
No full textValutare il ruolo nutraceutico di integratori vitaminici nella patologia umana associata a disturbi metabolici dell'omocisteina. L'omocisteina è un aminoacido che si forma nel corpo a partire dalla metionina. Il metabolismo dell'omocisteina è regolato dalle vitamine B6, B12, acido folico e betaine. I fattori che determinano l'iperomocisteinemia sono: genetica, dieta, disturbi renali e altre condizioni mediche. Questo lavoro descrive 4 soggetti italiani con grave iperomocisteinemia.
Lo screening genetico è stato eseguito mediante Next Generation Sequencing (NGS). Questa tecnologia innovativa consente di poter sequenziare l’interol genoma. Questo approccio è particolarmente promettente per la diagnosi di malattie neuromuscolari pediatriche, endocrine, disturbi metabolici, ecc., caratterizzati da una forte eterogeneità clinica e genetica. Utilizzando NGS è possibile eseguire una diagnosi genetica senza limitare l’attenzione a un singolo gene candidato.
Combinando i dati clinici con il report derivante dalla sequenza dell’ esoma, individuiamo le mutazioni potenzialmente causative dei fenotipi osservati. Lo screening genetico ha consentito una corretta diagnosi e terapia con integratori vitaminici B6 (supplementazione orale), B12 (integratore parenterale), acido folico (supplemento orale) e betaina (supplemento orale), ciascuna somministrata individualmente. La terapia ha interamente corretto le anomalie metaboliche ei segni clinici (tabella 1).
La terapia con integrazione complessa di vitamina B è stata efficace in molte forme di iperomocisteinemia ed anche in queste forme di iperomocisteinaemia. Oggi la terapia con vitamina B12 consiste in integratori parenterali. Nel prossimo futuro, sarebbe opportuno avere una formulazione utile per la terapia orale sia per il cianocobalamina che per l'idrossicobalamina. Inoltre, sarebbe auspicabile avere un pool unico di complesso vitamina B (B6, B12, acido folico, betaino) sperimentato complessivamente con il cibo, per una terapia orale più facile per i pazienti.Objective of the work. To evaluate the role of vitamins supplementation in human pathology associated with metabolic disorders of homocysteine. Homocysteine is an amino acid that is formed in the body starting from the methionine. The metabolism of homocysteine is regulated by vitamins B6, B12, folic acid and betaine. The factors determining hyperhomocysteinemia are: genetic, diet, kidney disorders and other medical conditions. This report describes 4 italian subjects with severe hyperhomocysteinemia.
Methodological Detail. The genetic screening was carried out by Next Generation Sequencing (NGS). These innovative technologies allow a complete genome sequences. This approach is particularly promising for the diagnosis of pediatric neuromuscular diseases, endocrine, metabolic disorders, etc. that are characterized by a strong clinical and genetic heterogeneity. Using NGS it is possible to perform a genetic diagnosis without limiting to a single candidate gene.
Main Results of the study. Combining clinical data with the report resulting from exome sequencing we identify site specific mutations in each subject. The genetic screening allowed a correct diagnosis and therapy with vitamin supplements B6 (oral supplementation), B12 (parenteral supplementation), folic acid (oral supplementation) and betaine (oral supplementation) each one administered individually. The therapy fully corrected metabolic abnormalities and clinical signs (table 1).
Implications, meanings, conclusion that can be drawn from the data. The therapy with vitamin B complex supplementation has been effective in many forms of hyperhomocysteinemia as well as in these forms of severe hyperhomocysteinemia. Nowdays the therapy with vitamin B12 consists in parenteral supplementations. In the next future, it would be desiderable to have a formulation useful for oral therapy for both cianocobalamin and hydroxycobalamin. In addition, it would be desirable to have a unique pool of vitamin B complex (B6, B12, folic acid, betaine) hopefully complexed with food, for an oral therapy easier for patients
C0268 Higher risk of idiopathic small for gestational age newborns in Italian women carrying the annexin A5 M2 haplotype
No full textClinical utility of screening for CALR gene exon 9 mutations in patients with splanchnic venous thrombosis
No full textFever of unknown origin and splenomegaly: A case report of blood culture negative endocarditis.
No full textRATIONALE: Fever of unknown origin (FUO) can be determined by different conditions among which infectious diseases represent the main cause.
PATIENT CONCERNS: A young woman, with a history of aortic stenosis, was admitted to our unit for a month of intermittent fever associated with a new diastolic heart murmur and splenomegaly. Laboratory tests were negative for infectious screening. The total body computed tomography (CT) scan excluded abscesses, occulted neoplasia, or lymphadenopathy.
DIAGNOSES: The transthoracic and transesophageal echocardiogram showed an aortic valve vegetation. Three sets of blood cultures were negative for all microorganisms tested. According to these findings, Bartonella endocarditis was suspected and the serology tests performed were positive. Finally, real-time polymerase chain reaction (RT-PCR) detected Bartonella henselae DNA on tissue valve.
INTERVENTIONS: The patient underwent heart valve surgery and a treatment of Ampicillin, Gentamicin, and oral Doxycycline was prescribed for 16 days and, successively, with Doxycycline and Ceftriaxone for 6 weeks.
OUTCOMES: After surgery and antibiotic therapy, patient continued to do well.
LESSONS: Bartonella species are frequently the cause of negative blood culture endocarditis. Molecular biology techniques are the only useful tool for diagnosis. Valvular replacement is often necessary and antibiotic regimen with Gentamicin and either Ceftriaxone or Doxycycline is suggested as treatment.Echocardiogram and blood cultures must be performed in all cases of FUO. When blood cultures are negative and echocardiographic tools are indicative, early use of Bartonella serology is recommended
A novel congenital dysprothrombinemia leading to defective prothrombin maturation
No full textProthrombin deficiency is a very rare disorder caused by mutations in the F2 gene that generate hypoprothrombinemia or dysprothrombinemia and is characterized by bleeding manifestations that can vary from clinically irrelevant to life-threatening
A Sardinian Family with Factor XI Deficiency
No full textIntroduction Factor XI (FXI) deficiency is a bleeding disorder which causes a bleeding tendency after trauma or surgery. An inhibitor may be acquired secondary to replacement therapy. Aim To study on genetical and functional grounds a family admitted to our Haemostasis and Thrombosis Centre for an incidental finding of a prolonged activated partial thromboplastin time (aPTT) in three members. Methods aPTT mixing test, dosage of FXI activity and antigen, FXI inhibitor titration, DNA analysis and clot waveform analysis (CWA) were performed. Results Patients II.1, II.3 and II.4 showed a severe FXI deficiency (0.7, 0.7 and 1.8%, respectively) and low antigen level. Since the proposita was already treated with plasma, the dosage of the inhibitor was determined to be 6.4 Bethesda units. They were homozygous for the p.Glu117Stop mutation. The other family members were heterozygous. The velocity and the maximum acceleration of the clot formation were lower than those of the other family members and the normal subjects but higher than those of patients with acquired haemophilia A. Conclusion A mixing test of a prolonged aPTT should be performed because it will be present both in patients with or without the inhibitor. A molecular analysis in severe FXI deficiency is warranted as it may have prognostic significance. CWA may be helpful for better understanding the pathophysiology of this kind of defect
Factor XI gene variants in factor XI-deficient patients of Southern Italy: identification of a novel mutation and genotype-phenotype relationship
No full textCongenital Factor XI (FXI) deficiency shows a high variability in clinical phenotype. To date, many allele variants have been shown to cause this bleeding disorder. However, the genotype-phenotype relationship is difficult to establish. This report provides insights into this bleeding disorder. Sixteen unrelated Italian index cases with congenital FXI deficiency and their relatives were investigated. After the identification of the deficiency, we obtained DNA from each subject and analyzed the FXI gene using direct sequencing. We identified 5 and 11 individuals with severe and moderate deficiency of FXI activity, respectively. Most patients (8/16) carried mutations in the Apple 2 domain and 4 patients showed c.403G>T (p.Glu135*; type II mutation). Four novel compound heterozygosities were identified. Bleeding symptoms were present in two severely deficient subjects carrying the combinations c.901T>C (p.Phe301Leu)/c.1556G>A (p.Trp519*) and c.943G>A (p.Glu315)/c.1556G>A (p.Trp519*), respectively. Bleeding episodes were also observed in the presence of a moderate deficiency in two individuals heterozygous for c.449C>T (p.Thr150Met) and c.1253G>T (p.Gly418Val), respectively. One novel mutation, c.1682C>A (p.Ala561Asp), was identified as potentially deleterious in an asymptomatic individual. We confirm an unclear prediction of phenotype from mutational data. The FXI levels should be coupled with FXI analysis for a more comprehensive prediction of the bleeding phenotype in FXI deficiency
Deep-fake review detection
No full textLAUREA MAGISTRALENell'Era del Deep Learning è possibile fare un uso malevolo delle tecniche di Machine Learning per produrre audio e video tali da ingannare sia macchine che umani. Questo lavoro si focalizza sull'identificazione di recensioni deep-fake tramite un Autoencoder Variazionale basato sul meccanismo dell'Attenzione. L'Autoencoder Variazionale è allenato, validato e testato su tree partizioni dell'Amazon Product Dataset ed è paragonato all'architettura dello stato dell'arte Transformer, su moderazione di linguaggio naturale. L'Encoder dell'Autoencoder Variazionale rende possibile separare recensioni deep-fake da recensioni reali.In the Deep Learning Era it is possible to misuse machine learning techniques to produce audios and videos that can easily deceive humans and machines. This work deals with identifying deep-fake reviews by means of a Variational Autoencoder based on the Attention mechanism. The Varia- tional Autoencoder is trained, validated and tested on three partitions of the Amazon Product Data dataset, then it is compared against the state-of-the-art architecture, the Transformer, on natural language modelling tasks. The Encoder of the Variational Autoencoder produces review embeddings that make possible disentangling deep-fake reviews from legit ones
Structural analysis of protein Z gene variants in patients with foetal losses
No full textThe role of protein Z (PZ) in the etiology of human disorders is unclear. A number of PZ gene variants, sporadic or polymorphic and found exclusively in the serine protease domain, have been observed. Crystal structures of PZ in complex with the PZ-dependent inhibitor (PZI) have been recently obtained. The aim of this study was a structural investigation of the serine protease PZ domain, aiming at finding common traits across disease-linked mutations. We performed 10-20 ns molecular dynamics for each of the observed PZ mutants to investigate their structure in aqueous solution. Simulation data were processed by novel tools to analyse the residue-by-residue backbone flexibility. Results showed that sporadic mutations are associated with anomalous flexibility of residues belonging to specific regions. Among them, the most important is a loop region which is in contact with the longest helix of PZI. Other regions have been identified, which hold anomalous flexibility associated with potentially protective gene variants. In conclusion, a possible interpretation of effects associated with observed gene variants is provided. The exploration of PZ/PZI interactions seems essential in explaining these effects
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