Glutathione S transferase polymorphisms influence on iron overload in β-thalassemia patients

In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI) in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn't lead to relevant overload. Serum ferritin doesn't appear to be correlated to iron overload instead. 对于β-地中海贫血患者,由于铁过量而造成重要器官受损的情况也在观察之中。谷胱甘肽S转移酶(GST) 酶类在对有毒物质进行解毒的过程中有着抗氧化剂的作用。该作用是由基因决定的。 在这份研究中,我们运用了直接和间接非侵入性的方法对基因型铁过量GSTT1 和GSTM1进行了相关性测量;特别地,我们对42位定期接受螯合和输血治疗的β-地中海贫血患者进行了血清铁蛋白和磁共振强度图像(MRI) 的测试。 多重聚合酶链反应的测试也被运用来确定该基因型。 该两种等位基因的缺失,导致了肝功能减损及心脏磁共振强度的下降,并造成了在这些器官中铁含量的积累;其中一种等位基因的缺失并不会导致过度的铁含量。血清蛋白和铁过量之间,看起来并不存在相关性

Influence of genetic polymorphisms and mutations in the cardiac pathology of iron overload in thalassemia and sickle cell anemia patients: a retrospective study

Cardiac disease in thalassemia is determined by the accumulation of iron in the tissue. Genetic factors could influence the severity and the rapidity of the modifications of the cardiac tissue. Mutations or polymorphisms of genes have already been described as being implicated in cardiac disease. In particular, we studied the polymorphisms C1091T in the Connexin 37 gene (CX 37), 4G -668 5G in the Plasminogen Activator Inhibitor-1 gene (PAI 1) and 5A-1171 6A in the Stromelysin-1 gene (SL) in 193 randomly selected patients affected by hemoglobinopathies and 100 normal subjects randomly selected from the general population. A retrospective analysis based on history, clinical data and imaging studies was carried out to assess the presence and type of heart disease. The results of our study do not demonstrate a close association between polymorphism in these candidate genes and cardiac disease, and in particular with myocardial infarction in a cohort of Sicilian patients affected by hemoglobinopathies. 地中海贫血心脏病的关键诱因是组织中的铁沉积。遗传因子可能影响心脏组织修复的严重程度和速度。基因突变或基因多态性与心脏病有关。尤其是,我们研究了193名随机选择的血红蛋白病患者以及从普通人群中随机选择的100名正常受试者的连接蛋白37基因(CX37)的C1091T、纤溶酶原激活物抑制剂-1基因(PAI1)的4G -668 5G 和基质分解素-1基因(SL)的5A-1171 6A等多态性。根据病史、临床资料和影像研究进行回顾性分析,以评估心脏病的存在情况和类型。我们的研究结果并没有表明这些候选基因的多态性和心脏疾病之间存在密切联系,尤其是与一组西西里岛血红蛋白病患者的心肌梗塞存在密切联系

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

Influence of genetic polymorphisms and mutations in the cardiac pathology of iron overload in thalassemia and sickle cell anemia patients: a retrospective study

Cardiac disease in thalassemia is determined by the accumulation of iron in the tissue. Genetic factors could influence the severity and the rapidity of the modifications of the cardiac tissue. Mutations or polymorphisms of genes have already been described as being implicated in cardiac disease. In particular, we studied the polymorphisms C1091T in the Connexin 37 gene (CX 37), 4G -668 5G in the Plasminogen Activator Inhibitor-1 gene (PAI 1) and 5A-1171 6A in the Stromelysin-1 gene (SL) in 193 randomly selected patients affected by hemoglobinopathies and 100 normal subjects randomly selected from the general population. A retrospective analysis based on history, clinical data and imaging studies was carried out to assess the presence and type of heart disease. The results of our study do not demonstrate a close association between polymorphism in these candidate genes and cardiac disease, and in particular with myocardial infarction in a cohort of Sicilian patients affected by hemoglobinopathies.&nbsp;地中海贫血心脏病的关键诱因是组织中的铁沉积。遗传因子可能影响心脏组织修复的严重程度和速度。基因突变或基因多态性与心脏病有关。尤其是，我们研究了193名随机选择的血红蛋白病患者以及从普通人群中随机选择的100名正常受试者的连接蛋白37基因（CX37）的C1091T、纤溶酶原激活物抑制剂-1基因（PAI1）的4G -668 5G 和基质分解素-1基因（SL）的5A-1171 6A等多态性。根据病史、临床资料和影像研究进行回顾性分析，以评估心脏病的存在情况和类型。我们的研究结果并没有表明这些候选基因的多态性和心脏疾病之间存在密切联系，尤其是与一组西西里岛血红蛋白病患者的心肌梗塞存在密切联系。</p

Glutathione S transferase polymorphisms influence on iron overload in β-thalassemia patients

In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI) in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn’t lead to relevant overload. Serum ferritin doesn’t appear to be correlated to iron overload instead. 对于β-地中海贫血患者，由于铁过量而造成重要器官受损的情况也在观察之中。谷胱甘肽S转移酶(GST) 酶类在对有毒物质进行解毒的过程中有着抗氧化剂的作用。该作用是由基因决定的。 在这份研究中，我们运用了直接和间接非侵入性的方法对基因型铁过量GSTT1 和GSTM1进行了相关性测量；特别地，我们对４２位定期接受螯合和输血治疗的β-地中海贫血患者进行了血清铁蛋白和磁共振强度图像(MRI) 的测试。 多重聚合酶链反应的测试也被运用来确定该基因型。 该两种等位基因的缺失，导致了肝功能减损及心脏磁共振强度的下降，并造成了在这些器官中铁含量的积累；其中一种等位基因的缺失并不会导致过度的铁含量。血清蛋白和铁过量之间，看起来并不存在相关性。</p

Design study of a low-power, low-noise front-end for multianode silicon drift detectors

The read-out for Silicon Drift Detectors in the form of a VLSI chip is presented, with a view to applications in High Energy Physics and space experiments. It is characterised by extremely low power dissipation, small noise and size

NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (&lt;5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML

The Italian project for a proton imaging device

Proton Computed Tomography (or pCT) is a new imaging technique based on the use of high energy proton beams (200–250 MeV) replacing of the commonly adopted X-rays CT. pCT that was firstly proposed in the 1960s but only nowadays, with the continued establishing of new proton therapy centers around the world, the interest in it is growing. The use of protons for tomographic images can represent, in fact, a big enhancement in the quality of a proton therapy treatment either in the patient positioning as well as in the accuracy of the dose calculation for the treatment planning phase. In this paper, after a brief introduction on pCT principles, the main hardware and software characteristics of a first pCT prototype in development by our group (the Italian PRIMA collaboration) will be presented. The role of Monte Carlo simulation in developing will be also emphasized, using the GEANT4 simulation toolkit

Monte Carlo Studies of a proton computed tomography system

Proton therapy is a precise forms of radiation therapy that makes use of high energy proton compared to the conventional, more commonly used and less precise x-ray and electron beams. On the other hand, to fully exploit the proton therapy advantages, very accurate quality controls of the treatments are required. These are mainly related to the dose calculations and treatment planning. Actually dose calculations are routinely performed on the basis of X-ray computed tomography while a big improvement could be obtained with the direct use of protons as the imaging system. In this work we report the results of Monte Carlo simulations for the study of an imaging system based on the use of high energy protons: the proton computed tomography (pCT). The main limitation of the pCT and the current adopted technical solutions, based on the use of the most likely path (MLP) approximation are illustrated. Simulation results are compared with experimental data obtained with a first prototype of pCT system tested with 200 MeV proton beams available at the Loma Linda University Medical Center (LLUMC) (CA)