Recessive EKV

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Functional Characterization of a Novel TP63 Mutation in a Family With Overlapping Features of Rapp-Hodgkin/AEC/ADULT Syndromes

Heterozygous mutations in TP63 cause a wide spectrum of autosomal dominant developmental disorders variably affecting skin, limbs, and face. TP63 encodes p63, a protein expressed in two main isoforms (Tap63 and ΔNp63) with critical roles in both cell differentiation and development. Some analyses suggest a relationship of the mutation site to the observed clinical picture, although this link is inconsistent. This suggests an appreciable phenotypic continuity within the TP63-related disorders. We report a 3-month-old boy ascertained for congenital scalp erosion and mild features of ectodermal dysplasia. His mother showed full-blown characteristics of Rapp-Hodgkin syndrome plus intense abdominal and popliteal freckling. Molecular investigation identified the novel TP63 mutation c.1697delG. We used a luciferase reporter assay to compare the effects on the p63 transactivation (TA) activity of c.1697delG with that of the p.Arg280Cys and p.Gln634X mutations, associated with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome and isolated split hand/foot malformation, respectively. These results demonstrated complex behavior of c.1697delG in the TA of genes involved in epidermal differentiation and development and shed further light in the physiopathology of TP63-related disorders. © 2011 Wiley Periodicals, Inc

Expression of Transglutaminase 5 in Normal and Pathologic Human Epidermis

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Characterization and Clinical Assessment of a Peculiar Case of Hemolytic Anemia

Thalassemic diseases are characterized by a reduced (beta(+)) or absent (beta(0)) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. beta-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: beta(0)/beta(0), the most severe (Cooley's disease); beta(0)/ beta(+) of intermediate severity; beta(+)/beta(+) associated with beta-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the beta-globin gene. According to these data, a diagnosis of beta-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and disease

Role of miR-9 in Modulating NF-κB Signaling and Cytokine Expression in COVID-19 Patients

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a significant impact on global health, with severe cases often characterized by a worsening cytokine storm. Since it has been described that the NF-kappa B signaling pathway, regulated by microRNAs, could play a pivotal role in the inflammatory response, in this study, the role of miR-9 in modulating NF-kappa B signaling and inflammatory cytokine expression in COVID-19 patients was investigated. This observational retrospective single-center study included 41 COVID-19 patients and 20 healthy controls. Serum samples were analyzed for miR-9, NF-kappa B, and I kappa B alpha expression levels using RT-PCR. The expression levels and production of pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha were measured using RT-PCR and ELISA. Statistical analyses, including correlation and regression, were conducted to explore relationships between these variables. COVID-19 patients, particularly non-survivors, exhibited significantly higher miR-9 and NF-kappa B levels compared to controls. A strong positive correlation was found between miR-9 and NF-kappa B expression (r = 0.813, p < 0.001). NF-kappa B levels were significantly correlated with IL-6 (r = 0.971, p < 0.001), IL-1 beta (r = 0.968, p < 0.001), and TNF-alpha (r = 0.968, p < 0.001). Our findings indicate that miR-9 regulates NF-kappa B signaling and inflammation in COVID-19. Elevated miR-9 levels in non-survivors suggest its potential as a severity biomarker. While COVID-19 cases have decreased, targeting miR-9 and NF-kappa B could improve outcomes for other inflammatory conditions, including autoimmune diseases, highlighting the need for continued research in this area

OTX Genes in Adult Tissues

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets

Correlation between Chest Computed Tomography Score and Laboratory Biomarkers in the Risk Stratification of COVID-19 Patients Admitted to the Emergency Department

background: it has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). during the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. however, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. aim: the main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. methods: epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. results and conclusions: the accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources

Impact of Different Illuminance Typical Years Models on a Climate Based Method for the Calculation of Artificial Lighting Energy Use in Office Buildings

Artificial lighting has a relevant impact on the electricity uses in not residential buildings. The method to assess such uses is based on standards, which hardly take into account the daylighting contribution and the time evolution of the outdoor illuminance conditions. Different models were adopted to build diffuse illuminance reference years, starting from satellite images. These models lead to different daylight availability during the year. The paper explores the impact that these models have on the artificial lighting energy uses by hourly monthly mean calculations. The test was carried out with a climate based method, which takes into account: the outdoor luminous environment, the reference indoor visual task and the building daylight characteristics. A typical office building was used for the test in Rome, Italy. Results allowed to compare the impact of each model and to select the most suitable one to be implemented in the climate based method to predict artificial lighting use in buildings