Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

Psoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3\u201310 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was 65 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance. Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis.What is Known:\u2022 Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.\u2022 Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis.What is New:\u2022 This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.\u2022 In children with psoriasis metabolic syndrome risk factors should be assessed

Is it Possible to Improve the Success Rate of Cellular Therapy Based on Mesenchymal Stem Cells?

Non-clonal stromal cultures, containing a variable amount of Mesenchymal Stem Cells (MSCs), can be easily isolated from a small aspirate of bone marrow and expanded in vitro. As such, these cultures are currently used as a source of putative MSCs for therapeutic purposes. Nowadays, dozens of clinical trials aim to treat a number of diseases, primarily immune system-related diseases, with MSCs. Moreover, several private companies are setting up clinical trials to exploit the immunomodulation and tissue repair properties of MSCs. Nevertheless, besides some successes, specifically in the treatment of immunological diseases, MSC therapies have experienced many failures. There are some issues to be analyses that may improve the success rate of MSC therapy. This editorial will briefly address some concerns associated with MSC transplants

A multi-scale risk assessment for tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part 2: Vulnerability and impact

This is the final version of the article. Available from EGU via the DOI in this record.We perform a multi-scale impact assessment of tephra fallout and dispersal from explosive volcanic activity in Iceland. A companion paper (Biass et al., 2014; "A multi-scale risk assessment of tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part I: hazard assessment") introduces a multi-scale probabilistic assessment of tephra hazard based on selected eruptive scenarios at four Icelandic volcanoes (Hekla, Askja, Eyjafjallajökull and Katla) and presents probabilistic hazard maps for tephra accumulation in Iceland and tephra dispersal across Europe. Here, we present the associated vulnerability and impact assessment that describes the importance of single features at national and European levels and considers several vulnerability indicators for tephra dispersal and deposition. At the national scale, we focus on physical, systemic and economic vulnerability of Iceland to tephra fallout, whereas at the European scale we focus on the systemic vulnerability of the air traffic system to tephra dispersal. This is the first vulnerability and impact assessment analysis of this type and, although it does not include all the aspects of physical and systemic vulnerability, it allows for identifying areas on which further specific analysis should be performed. Results include vulnerability maps for Iceland and European airspace and allow for the qualitative identification of the impacts at both scales in the case of an eruption occurring. Maps produced at the national scale show that tephra accumulation associated with all eruptive scenarios considered can disrupt the main electricity network, in particular in relation to an eruption of Askja. Results also show that several power plants would be affected if an eruption occurred at Hekla, Askja or Katla, causing a substantial systemic impact due to their importance for the Icelandic economy. Moreover, the Askja and Katla eruptive scenarios considered could have substantial impacts on agricultural activities (crops and pastures). At the European scale, eruptive scenarios at Askja and Katla are likely to affect European airspace, having substantial impacts, in particular, in the Keflavík and London flight information regions (FIRs), but also at FIRs above France, Germany and Scandinavia. Impacts would be particularly intense in the case of long-lasting activity at Katla. The occurrence of eruptive scenarios at Hekla is likely to produce high impacts at Keflavík FIR and London FIRs, and, in the case of higher magnitude, can also impact France's FIRs. Results could support land use and emergency planning at the national level and risk management strategies of the European air traffic system. Although we focus on Iceland, the proposed methodology could be applied to other active volcanic areas, enhancing the long-term tephra risk management. Moreover, the outcomes of this work pose the basis for quantitative analyses of expected impacts and their integration in a multi-risk framework.This work has been funded by the Spanish research project “Atmospheric transport models and massive parallelism: applications to volcanic ash clouds and dispersion of pollutants at an urban micro-scale” (ATMOST, CGL2009-10244) and the Fonds National Suisse project “Volcanic-Ash Dispersal from Selected Icelandic Volcanoes: Risk Assessment for the European Region” (IZK0Z2_142343). S. Biass is supported by SNF (#200021-129997) and ESF/MemoVolc (#5193) subsidies

Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells.

Self-renewal, proliferation and differentiation properties of stem cells are controlled by key transcription factors. However, their activity is modulated by chromatin remodeling factors that operate at the highest hierarchical level. Studies on these factors can be especially important to dissect molecular pathways governing the biology of stem cells. SWI/SNF complexes are adenosine triphosphate (ATP)-dependent chromatin remodeling enzymes that have been shown to be required for cell cycle control, apoptosis and cell differentiation in several biological systems. The aim of our research was to investigate the role of these complexes in the biology of mesenchymal stem cells (MSCs). To this end, in MSCs we caused a forced expression of the ATPase subunit of SWI/SNF (Brg1 – also known as Smarca4) by adenoviral transduction. Forced Brg1 expression induced a significant cell cycle arrest of MSCs in culture. This was associated with a huge increase in apoptosis that reached a peak 3 days after transduction. In addition, we observed signs of senescence in cells having ectopic Brg1 expression. At the molecular level these phenomena were associated with activation of Rb- and p53-related pathways. Inhibition of either p53 or Rb with E1A mutated proteins allowed us to hypothesize that both Rb and p53 are indispensable for Brg1-induced senescence, whereas only p53 seems to play a role in triggering programmed cell death. We also looked at the effects of forced Brg1 expression on canonical MSC differentiation in adipocytes, chondrocytes and osteocytes. Brg1 did not induce cell differentiation per se; however, this protein could contribute, at least in part, to the adipocyte differentiation process. In conclusion, our results suggest that whereas some ATP-dependent chromatin remodeling factors, such as ISWI complexes, promote stem cell self-renewal and conservation of an uncommitted state, others cause an escape from ‘stemness’ and induction of differentiation along with senescence and cell death phenomena

Cardiac Autoimmunity as a Novel Biomarker, Mediator, and Therapeutic Target of Heart Disease in Type 1 Diabetes

Patients with type 1 diabetes (T1D) suffer excess mortality from cardiovascular disease (CVD) that has persisted despite substantial reductions in microvascular complications. Although T1D and type 2 diabetes (T2D) are etiologically distinct, it has generally been assumed that CVD in T1D is “the same disease” as that found in T2D. Here, we review the most recent epidemiological and clinical studies on heart disease in T1D, highlighting differences between CVD in T1D and T2D. In addition, we discuss experimental and clinical evidence for a post-myocardial infarction (MI) autoimmune heart syndrome in T1D, including the development of diagnostic assays which we believe can, for the first time, differentiate between heart disease in T1D and T2D. We postulate that a clinically unrecognized form of chronic myocardial inflammation (“myocarditis”) triggered by MI contributes to the poor CVD outcomes in T1D. These findings provide a conceptual shift in our understanding of CVD in T1D and have important diagnostic and therapeutic implications

Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria

Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, untargeted metabolomics of biofluids in metabolic diseases allows the direct investigation of molecular species involved in pathways alterations and their interplay. Here, we present the untargeted metabolomics study of AKU through the nuclear magnetic resonance of urine from a cohort of Italian patients; the study aims to unravel molecular species and mechanisms underlying the AKU metabolic disorder. Dysregulation of metabolic pathways other than the HGD route and new potential biomarkers beyond homogentisate are suggested, contributing to a more comprehensive molecular signature definition for AKU and the development of future adjuvant treatment. © 2022 by the authors

Age as a risk factor in the occurrence of pneumothorax after transthoracic fine needle biopsy: Our experience

Transthoracic needle biopsy (TTNB) of the lung is a well-established technique for diagnosing many thoracic lesions, and is an important alternative to more invasive surgical procedures. Complications of TTNB include pneumothorax, hemoptysis, hemothorax, infection, and air embolism, with the most common complication as pneumothorax. From June 2011 to June 2014 we performed a prospective study of 188 patients who underwent TTNB with CT guidance at University Hospital of Salerno, Italy. Pneumothorax occurred in 14 of 188 biopsies (7.45%). With the respect of age of patients pneumothorax occurred more frequently in patients aged 60-70 years, while it was less frequent in younger (70 years). In conclusion, data of our prospective study documented that CT-guided TTNB is a safe and reliable procedure in elderly patients with suspected chest malignancy and is well tolerated