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

Bone marrow haematopoiesis in patients with COVID-19

AIMS Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection broadly affects organ homeostasis, including the haematopoietic system. Autopsy studies are a crucial tool for investigation of organ-specific pathologies. Here we perform an in-depth analysis of the impact of severe coronavirus disease 2019 (COVID-19) on bone marrow haematopoiesis in correlation with clinical and laboratory parameters. METHODS AND RESULTS Twenty-eight autopsy cases and five controls from two academic centres were included in the study. We performed a comprehensive analysis of bone marrow pathology and microenvironment features with clinical and laboratory parameters and assessed SARS-CoV-2 infection of the bone marrow by quantitative polymerase chain reaction (qPCR) analysis. In COVID-19 patients, bone marrow specimens showed a left-shifted myelopoiesis (19 of 28, 64%), increased myeloid-erythroid ratio (eight of 28, 28%), increased megakaryopoiesis (six of 28, 21%) and lymphocytosis (four of 28, 14%). Strikingly, a high proportion of COVID-19 specimens showed erythrophagocytosis (15 of 28, 54%) and the presence of siderophages (11 of 15, 73%) compared to control cases (none of five, 0%). Clinically, erythrophagocytosis correlated with lower haemoglobin levels and was more frequently observed in patients from the second wave. Analysis of the immune environment showed a strong increase in CD68+ macrophages (16 of 28, 57%) and a borderline lymphocytosis (five of 28, 18%). The stromal microenvironment showed oedema (two of 28, 7%) and severe capillary congestion (one of 28, 4%) in isolated cases. No stromal fibrosis or microvascular thrombosis was found. While all cases had confirmed positive testing of SARS-CoV-2 in the respiratory system, SARS-CoV-2 was not detected in the bone marrow by high-sensitivity PCR, suggesting that SARS-CoV-2 does not commonly replicate in the haematopoietic microenvironment. CONCLUSIONS SARS-CoV-2 infection indirectly impacts the haematological compartment and the bone marrow immune environment. Erythrophagocytosis is frequent and associated with lower haemoglobin levels in patients with severe COVID-19

Giant acquired tracheocele in a syndromic child: Case report and review of the literature

We report a case of acquired tracheocele in a child with multiple congenital anomalies of the face, limbs, kidneys, and heart, to share our experience with international scientific community, considering the rarity of the disease especially in the pediatric population. Patientâs history reported a tracheotomy at one month of life that was closed at 3 years old. Ten years later, the patient come to us for an anterior cervical mass swelling during respiratory effort and chronic productive cough. The diagnosis was made by high resolution Computed Tomography scan of the neck and chest and an elective surgical resection of the lesion under general anesthesia was done

Muscle and Systemic Molecular Responses to a Single Flywheel Based Iso-Inertial Training Session in Resistance-Trained Men

Growing evidence points to the effectiveness of flywheel (FW) based iso-inertial resistance training in improving physical performance capacities. However, molecular adaptations induced by FW exercises are largely unknown. Eight resistance-trained men performed 5 sets of 10 maximal squats on a FW device. Muscle biopsies (fine needle aspiration technique) and blood samples were collected before (t0), and 2 h (t1) after FW exercise. Blood samples were additionally drawn after 24 h (t2) and 48 h (t3). Paired samples t-tests revealed significant increases, at t1, of mRNA expression of the genes involved in inflammation, in both muscle (MCP-1, TNF-α, IL-6) and peripheral blood mononuclear cells (IkB-α, MCP-1). Circulating extracellular vesicles (EVs) and EV-encapsulated miRNA levels (miR-206, miR-146a) significantly increased at t1 as well. Conversely, muscle mRNA level of genes associated with muscle growth/remodeling (IGF-1Ea, cyclin D1, myogenin) decreased at t1. One-way repeated measure ANOVAs, with Bonferroni corrected post-hoc pairwise comparisons, revealed significant increases in plasma concentrations of IL-6 (t1; t2; t3) and muscle creatine kinase (t1; t2), while IGF-1 significantly increased at t2 only. Our findings show that, even in experienced resistance trained individuals, a single FW training session modifies local and systemic markers involved in late structural remodeling and functional adaptation of skeletal muscle

New Constraints on the Future Evaporation of the Young Exoplanets in the V1298 Tau System

Transiting planets at young ages are key targets for improving our understanding of the evolution of exo-atmospheres. We present results of a new X-ray observation of V 1298 Tau with XMM-Newton, aimed to determine more accurately the high-energy irradiation of the four planets orbiting this pre-main-sequence star, and the possible variability due to magnetic activity on short and long timescales. Following the first measurements of planetary masses in the V 1298 Tau system, we revise early guesses of the current escape rates from the planetary atmospheres, employing our updated atmospheric evaporation models to predict the future evolution of the system. Contrary to previous expectations, we find that the two outer Jupiter-sized planets will not be affected by any evaporation on Gyr timescales, and the same occurs for the two smaller inner planets, unless their true masses are lower than ~40 Me. These results confirm that relatively massive planets can reach their final position in the mass-radius diagram very early in their evolutionary history

Italian recommendations on enzymatic debridement in burn surgery.

Abstract Introduction Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. Methods The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. Results The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. Discussion The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available