FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated. The nude severe combined immunodeficiency phenotype is indeed characterized by the clinical hallmarks of athymia with severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. In this review, we summarize recent discoveries in the field and give interesting perspective about new and promising therapeutic approaches for disorders of immune system with athymia

Influence of Temperature on the Antibacterial Activity of Sodium Hypochlorite

The aim of this study was to compare the antimicrobial activity of 5.25% NaOCl, Hypoclean and Chlor-Xtra at 20 °C and 45 °C in bovine root dentin. One-hundred-and-seventy dentin tubes prepared from bovine maxillary incisors were infected for 21 days with Enterococcus faecalis. The specimens were divided into the following groups: 1. 5.25% NaOCl 20 °C; 2. Hypoclean 20 °C; 3. Chlor-Xtra 20 °C; 4. 5.25% % NaOCl 45 °C; 5. Hypoclean 45 °C; 6. Chlor-Xtra 45 °C; 7. positive control; 8. negative control. Dentin chips were collected with round burs into Brain Heart Infusion (BHI) broth. After culturing, the number of colony- forming units (CFU) was counted. Statistical analyses were performed using descriptive statistics (mean, standard deviation, median), Shapiro-Wilk test, ANOVA and Tukey test. Significance level was set at p<0.05. In all experimental groups, CFU was minimum after treatment (day 0) and the obtained results were significantly different from each other at any period (p<0.05). After treatment, the Hypoclean and Chlor-Xtra showed the lowest numbers of CFU at 20 °C and 45 °C, whereas 5.25% NaOCl showed the highest number of CFU at both temperatures. In each group, the number of CFUs increased significantly with time (p<0.05). The antibacterial activity of Hypoclean and Chlor-Xtra at 45 °C were significantly greater than other tested solutions

Cosimo De Giorgi, Luigi Pigorini e la paletnologia del Salento

EnCosimo De Giorgi (1842-1922) played a decisive role in the prehistoric investigations of Salento. The contribution of the Apulian scholar is analyzed here in the context of the Italian and European archaeological studies between the end of the nineteenth and the beginning of the twentieth century. De Giorgi had a significant scientific relationship with Luigi Pigorini (1842-1925), the leading scholar in that period, who dominated the investigation of Italian prehistory.ItCosimo De Giorgi (1842-1922) ha rivestito un ruolo determinante nelle indagini sulla preistoria del Salento. Il contributo dello studioso pugliese viene qui analizzato nell'ambito della cultura archeologica italiana ed europea nel periodo fra la fine dell'Ottocento e gli inizi del Novecento, un momento in cui Luigi Pigorini (1842-1925) – con cui De Giorgi ebbe un continuo e significativo rapporto scientifico – dominò incontrastato le ricerche sulla preistoria italiana

Metal finds at the Middle and Late Bronze Age settlement of Scoglio del Tonno (Taranto, Apulia): results of archaeometallurgical analyses

Scoglio del Tonno (Taranto) is a settlement with a strategic location in one of the best natural harbours of the Italian Peninsula. During the Late Bronze Age it was an emporion, a privileged and permanent landing place for ships sailing between the Aegean and Italian Peninsulas. Crucibles and a number of metal artefacts were found during its excavation (1899, Quagliati 1900; Säflund 1939); this work reports the quantitative analysis of these metal artefacts by energy dispersive X-ray fluorescence. All are made of copper alloys except for one piece, an eyelet pin made of a gold-silver-copper alloy. The examination of these objects and the analytical data obtained help reconstruct the functions of this site. Metal was systematically accumulated at Scoglio del Tonno, presumably to be shipped towards the eastern Mediterranean. The site highlights the exponential increase in northern Italian metal production during the Recent Bronze Age (ca. 14th-13th c. BC)

Altered signaling through IL-12 receptor in children with very high serum IgE levels

An alteration of Th1/Th2 homeostasis may lead to diseases in humans. In this study, we investigated whether an impaired IL-12R signaling occurred in children with elevated serum IgE levels divided on the basis of the IgE levels (group A: >2000 kU/l; group B: <2000 kU/l). We evaluated the integrity of the IL-12R signaling through the analysis of phosphorylation/activation of STAT4, and mRNA expression and membrane assembly of the receptor chains. At a functional level, a proliferative defect of lymphocytes from group A patients was observed. In these patients, an abnormal IL-12R signaling was documented, and this finding was associated with abnormal expression of the IL-12Rb2 chain. Our data indicate that in patients with very high IgE levels the generation of Th1 response is impaired, and that this abnormality associates with abnormal IL-12R signaling

From Murine to Human Nude/SCID: The Thymus, T-Cell Development and the Missing Link

Primary immunodeficiencies (PIDs) are disorders of the immune system, which lead to increased susceptibility to infections. T-cell defects, which may affect T-cell development/function, are approximately 11% of reported PIDs. The pathogenic mechanisms are related to molecular alterations not only of genes selectively expressed in hematopoietic cells but also of the stromal component of the thymus that represents the primary lymphoid organ for T-cell differentiation. With this regard, the prototype of athymic disorders due to abnormal stroma is the Nude/SCID syndrome, first described in mice in 1966. In man, the DiGeorge Syndrome (DGS) has long been considered the human prototype of a severe T-cell differentiation defect. More recently, the human equivalent of the murine Nude/SCID has been described, contributing to unravel important issues of the T-cell ontogeny in humans. Both mice and human diseases are due to alterations of the FOXN1, a developmentally regulated transcription factor selectively expressed in skin and thymic epithelia

Severe combined immunodeficiency-an update

Severe combined immunodeficiencies (SCIDs) are a group of inherited disorders responsible for severe dysfunctions of the immune system. These diseases are life-threatening when the diagnosis is made too late; they are the most severe forms of primary immunodeficiency. SCID patients often die during the first two years of life if appropriate treatments to reconstitute their immune system are not undertaken. Conventionally, SCIDs are classified according either to the main pathway affected by the molecular defect or on the basis of the specific immunologic phenotype that reflects the stage where the blockage occurs during the differentiation process. However, during the last few years many new causative gene alterations have been associated with unusual clinical and immunological phenotypes. Many of these novel forms of SCID also show extra-hematopoietic alterations, leading to complex phenotypes characterized by a functional impairment of several organs, which may lead to a considerable delay in the diagnosis. Here we review the biological and clinical features of SCIDs paying particular attention to the most recently identified forms and to their unusual or extra-immunological clinical features

Minute ventilation to carbon dioxide output (V’E/V’CO2 slope) is the strongest death predictor before larger lung resections

The minute ventilation to CO2 production ratio (V’E/V’CO2 slope) was recently identified as a mortality predictor after lung surgery, but the effect of the resection extent was not taken into account.  The aim of this study was to investigate the role of V’E/V’CO2 slope as preoperative mortality predictor depending on the type of surgery performed. Retrospective analysis was performed on 263 consecutive patients evaluated before surgery for lung cancer. Death within 30 days and serious respiratory complications were considered. Univariate and multivariate regression analyses were used to identify independent predictors of death. Lobectomy or bilobectomy were performed in 186 patients with 29/186 (15.6%) serious pulmonary complications and 6/186 (3.2%) deaths. Pneumonectomy was performed in 77 patients with 14/77 (18.2%) serious complications and 5/77 (6.5%) deaths.  Considering the whole group, the peak oxygen consumption (V'02peak, L/ min; z=-2.66, p<0.008, OR 0.007) and V'E/V'C02 slope (z=2.80, p<0.005, OR 1.14) were independent predictors of mortality whereas in pneumonectomies V'E/V'C02 slope (z=2.34, p<0.02, OR 1.22) was the only independent predictor of mortality. High V’E/V’CO2 slope, age and low V'02peak are predictors of death and severe complications after lung surgery. Before larger resections as pneumonectomies an increased V’E/V’CO2 slope represents the best mortality predictor