Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome represents the most common type of primary glomerular disease in children: glucocorticoids (GCs) are the first-line therapy, even if considerable interindividual differences in thepir efficacy and side effects have been reported. Immunosuppressive and anti-inflammatory effects of these drugs are mainly due to the GC-mediated transcription regulation of pro- and anti-inflammatory genes. This mechanism of action is the result of a complex multistep pathway that involves the glucocorticoid receptor and several other proteins, encoded by polymorphic genes. Aim of this review is to highlight the current knowledge on genetic variants that could affect GC response, particularly focusing on children with idiopathic nephrotic syndrome

Surgical treatment of primitive gastro-intestinal lymphomas: a systematic review

Primitive Gastrointestinal Lymphomas (PGIL) are uncommon tumours, although time-trend analyses have demonstrated an increase. The role of surgery in the management of lymphoproliferative diseases has changed over the past 40 years. Nowadays their management is centred on systemic treatments as chemo-/radio- therapy. Surgery is restricted to very selected indications, always discussed in a multidisciplinary setting. The aim of this systematic review is to evaluate the actual role of surgery in the treatment of PGIL

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Urban Territorialization in Areas of Romagna, Italy

This territorial study elaborated on areas of Romagna, envisions a set of numeric and graphic indicators capable to link characters and phases of the spatial transformations to shifting socio-economic regimes. The study introduces notions such as the 'territorial effect', a quantitative indicator of qualitative change in space production

Río Ciudad Monterrey: Space Production, Ecology and Culture

The book proceeds from the Río Ciudad interdisciplinary study conducted at the CRGS of the Universidad de Monterrey. Directed by Peter G. Rowe, Roberto Pasini and Patricio Ortiz Silva, the study addresses the status of the Santa Catarina River within the metropolitan area of Monterrey, Mexico and the relationship between the two entities. Presenting a characterization of the urban segment of the river through the metropolitan area and four future scenarios of transformation, the study envisions programs aiming to increase sustainability and public space provision, with emphasis on improving the identity of the city

Immigrazione e futuro dell'Europa nel corso del 2017

Le dinamiche del fenomeno migratorio in Italia e in Europa stanno subendo nuove trasformazioni. In questo Ventitreesimo Rapporto Fondazione ISMU stima che la popolazione straniera in Italia abbia raggiunto, al 1° gennaio 2017, 5 milioni e 958mila unità di presenze e analizza i nuovi scenari migratori che vanno configurandosi nel nostro Paese e nel resto d'Europa. Il volume infatti mette in evidenza come ancora una volta, nel 2017, l'emergenza sbarchi abbia costituito uno dei temi più rilevanti nell'agenda politica e nel dibattito pubblico in Italia. Se nel 2016 gli arrivi via mare sono diminuiti drasticamente in seguito all'accordo UE-Turchia, che ha di fatto interrotto il flusso sulla cosiddetta rotta balcanica, l'emergenza migranti non è certo risolta. Le gravi crisi che hanno colpito numerosi Stati del continente africano e di ampie aree del Medio Oriente hanno continuato a determinare un notevole afflusso di migranti in Italia, che è ritornata a essere la principale porta per l'Europa nel Mediterraneo, anche se a partire dall'estate 2017, in controtendenza rispetto al passato, si è registrato un deciso decremento degli arrivi. Oltre alle consuete aree di interesse (demografia, normativa, lavoro, scuola, salute), il volume approfondisce alcune tematiche di grande attualità, quali il radicalismo islamico, il rapporto tra Europa e migrazioni, il fenomeno dei minori non accompagnati. Queste tre ultime tematiche sono state assunte da ISMU quali sue linee strategiche. Il volume dedica inoltre una particolare attenzione allo scenario internazionale, alle recenti elezioni che si sono svolte in Europa, alle politiche di integrazione italiane ed europee, al diritto di asilo. Completa il testo un'analisi sulle migrazioni negli Stati Uniti, in Cina e Australia, nonché sulla situazione politica in Medio Oriente