Le Digital Humanities per lo studio e la comunicazione di beni culturali architettonici: il caso dei mausolei di Teodorico e Galla Placidia in Ravenna

The paper presents a series of methodological reflections on the following themes: survey, restitution, analysis and communication. The objective of the research was the critical reading of two of the most famous monuments in Ravenna and UNESCO heritage sites: the Mausoleum of Theodoric (ca. 520 AD) and the Mausoleum of Galla Placidia (before 450 AD). From advanced and integrated survey data, 2D graphs and 3D models were elaborated for hypothesis testing and for the multimedia communication of the scientific contents identified during the work. This second topic of the paper is part of the experiments conducted by the research group on new modes of multimedia communication, interactive and not, based on virtual models as an edutainment tool for enjoying monuments and masterpieces of cultural importance

COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome.

COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome. BACKGROUND: Mutations of the type IV collagen COL4A5 gene cause X-linked Alport syndrome (ATS). Mutations of COL4A3 and COL4A4 have been reported both in autosomal-recessive and autosomal-dominant ATS, as well as in benign familial hematuria (BFH). In the latter conditions, however, clinical features are less defined, few mutations have been reported, and other genes and non-genetic factors may be involved. METHODS: We analyzed 36 ATS patients for COL4A3 and COL4A4 mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Sporadic patients who had tested negative for COL4A5 mutations were included with typical cases of autosomal recessive ATS to secure a better definition of the phenotype spectrum. RESULTS: We identified seven previously undescribed COL4A3 mutations: in two genetic compounds and three heterozygotes, and one in COL4A4. In agreement with the literature, some of the mutations of compound heterozygotes were associated with microhematuria in healthy heterozygous relatives. The mutations of heterozygous patients are likely dominant, since no change was identified in the second allele even by sequencing, and they are predicted to result in shortened or abnormal chains with a possible dominant-negative effect. In addition, both genes showed rare variants of unclear pathogenicity, and common polymorphisms that are shared in part with other populations. CONCLUSIONS: This study extends the mutation spectrum of COL4A3 and COL4A4 genes, and suggests a possible relationship between production of abnormal COL IV chains and dominant expression of a continuous spectrum of phenotypes, from ATS to BFH

Survey, archaeoastronomy and communication: the Mausoleum of Galla Placidia in Ravenna (Italy)

The Mausoleum of Galla Placidia (built pre-450), is one of Ravenna‟s UNESCO protected monuments, renowned worldwide for the extraordinary mosaic decorations that cover its internal surfaces. The famous starry vault profoundly engages and inspires the observer. Its accurate representation of the real sky has been analysed and described, as has its mystical and symbolic meaning in relation to the iconographic tradition of the time. Archaeoastronomical research was carried out on the building by Giuliano Romano, who measured its orientation. The azimuth value of 180.2° highlights a north-south bearing, unique among the other Byzantine buildings in Ravenna. This paper also examines other architectural elements beyond the orientation, with particular attention paid to the building‟s small slit windows, investigating their possible archaeoastronomical significance. A functional 3D model was developed from the archaeoastronomical analysis data to display the original morphology of the building (the floor was about 140 cm lower due to subsidence), and astronomical phenomena, and to provide a multimedia way of communicating the scientific content produced. This final part of the contribution forms part of the trials conducted by the research group into interactive and noninteractive multimedia communication based on virtual models as an edutainment tool for the enjoyment of cultural sites and artefacts

NEXT GENERATION SEQUENCING: IMPLICAZIONI NELLA PRATICA CLINICA E NELLA DIAGNOSI DELLA SINDROME NEFROSICA STEROIDO-RESISTENTE

Differenti studi hanno dimostrato che mutazioni in geni della sindrome nefrosica steroido-resistente (SNSR) si associano ad una significativa variabilità, rendendo il test genetico e la consulenza un compito complesso. Sono stati descritti almeno 14 geni espressi nel podocita le cui mutazioni, soprattutto recessive, si associano alla SNSR; la base molecolare in oltre la metà dei casi rimane sconosciuta e spesso anche la terapia è inefficace. Proprio perchè il genotipo dei pazienti si presenta così articolato, abbiamo iniziato ad analizzare, mediante Next Generation Sequencing (NGS), soggetti affetti per i geni che nell’uomo e/o nel topo sono coinvolti nel pathway del podocita. Abbiamo effettuato il targeted resequencing di 47 geni podocitari in 8 pazienti affetti, che precedentemente erano risultati negativi all'analisi dei geni NPHS2 e WT1, le cui mutazioni sono associate con una certa frequenza a questo disordine. Tra i casi analizzati, per es, in una bambina con SNSR e glomerulosclerosi focale-segmentale (GSFS), che ha portato a insufficienza renale e terapia con dialisi da circa 3 anni, abbiamo riscontrato una nuova variante missense in eterozigosi in ACTN4. Il gene codifica per l’α-actinina-4, un proteina del citoscheletro che colocalizza con i fasci di actina e si estende lungo il centro dei processi del piede podocitario. Mutazioni del gene determinano una forma familiare di GSFS ad eredità AD con esordio intorno ai 20 anni; ad oggi in letteratura sono state riportate solo 10 mutazioni e nessuna in età pediatrica. In un altro soggetto, che ha ricevuto diagnosi di SNSR all’età di circa 2+6/12 anni e che attualmente (età 7 anni) esegue dialisi peritoneale, abbiamo rilevato una nuova mutazione nel gene PLCE1, il quale codifica per una proteina che può servire come impalcatura di assemblaggio per l'organizzazione del complesso molecolare coinvolto nello sviluppo glomerulare. Ad oggi le mutazioni (circa 30) si associano soprattutto ad un quadro di sclerosi mesangiale diffusa. Infine abbiamo anche accertato una variante in un nuovo gene, non ancora descritto come gene malattia nell’uomo, un fattore di trascrizione che regola l’espressione genica di diversi geni podocitari, incluso WT1, durante lo sviluppo della sindrome nefrosica

NEXT GENERATION SEQUENCING: IMPLICATIONS IN CLINICAL PRACTICE AND DIAGNOSIS OF STEROID-RESISTANT NEPHROTIC SYNDROME

During recent years, several podocyte genes have been implicated in severe forms of steroid-resistant nephrotic syndrome (SRNS) progressing to renal failure. To date, at least 14 genes highly expressed in the podocyte have been associated with the syndrome and different mutations in these genes have been identified; it is now known that the phenotypes associated with mutations in these genes display significant variability, rendering genetic testing and counselling a more complex task. Due to this large genetic heterogeneity and missing of adequate gene-diagnostic tools, most patients are not genetically characterized, which would be important for individualized patient care. Currently, next-generation sequencing technologies are revolutionizing genetic, since they are capable to produce billions of bases of sequence information in a single experiment. Accordingly, this powerful technology can now also open avenues for genetic diagnostics. The scope of our work is to illustrate clinical applications of the Next Generation Sequencing (NGS) technology to study patients affected by SRNS, in which the previous analysis of NPHS2 and WT1 genes had not shown pathogenetic mutations. We perform in 4 affected subjects a targeted resequencing of 23 genes including those already known as causative of the disorder and several other genes highly expressed in the podocyte. In the case of a young girl with SRNS and focal segmental glomerulosclerosis (FSGS), which quickly led to end stage kidney disease (ESKD) and dialysis treatment, we found a new heterozygous missense mutation in the ACTN4 gene, which encodes for α-actinin-4, a protein of podocyte cytoskeleton. Mutations in this gene are associated with an autosomal dominant form of FSGS characterized by adult-onset of proteinuria. In another patient who had received at 2 years of age the diagnosis of SRNS and Minimal-change disease (MCD) and currently under dialysis treatment, we discovered a new heterozygous missense mutation in the PLCE1 gene. In literature rare mutations reported in this gene are associated with diffuse mesangial sclerosis. We also detected a variation in the ZHX2 gene, that to date has never been associated with SRNS. This gene encode for a transcriptional factor which regulates the expression of several genes in the podocyte, including WT1, during the development of nephrotic syndrome. The combination of the variations in the known genes for SRNS and the identification of this novel gene combined with the extensive clinical investigations provides an exciting opportunity to reveal further insight into the pathogenic mechanisms that underlie this debilitating disorder

Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity

A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis.

Pediatr Nephrol. 2007 May;22(5):727-33. Epub 2007 Feb 3. Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis. Verrina E, Caruso U, Calevo MG, Emma F, Sorino P, De Palo T, Lavoratti G, Turrini Dertenois L, Cassanello M, Cerone R, Perfumo F; Italian Registry of Pediatric Chronic Dialysis. Abstract We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n=16) or hemodialysis (HD; n=8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months. FC levels were measured in plasma and peritoneal dialysate by tandem mass spectrometry. There were no statistically significant changes in lipid levels, hemoglobin, or rhEPO requirements during the course of the study. Fifteen patients (13 PD, 2 HD) had plasma FC levels measured before and after treatment; FC levels increased from 32.1 +/- 14.1 micromol/l to 80.9 +/- 38.7 micromol/l (P<0.001). In PD patients, dialysate FC losses increased from 106 +/- 78 micromol/day at baseline to 178 +/- 119 micromol/day after supplementation. Positive correlations between FC plasma levels and dialysate levels (R=0.507) or daily excretion (R=0.603) were found after treatment. In our case series, an oral dose of 20 mg/kg per day of L-carnitine restored FC levels and produced a positive carnitine balance with no significant effects on hematological parameters or lipid profile over a 3-month period. Prolonged treatment duration may be required to obtain significant results

Clinical experience in the treatment of infants with chronic peritoneal dialysis

Chronic peritoneal dialysis (CPD) is the first treatment modality for most infants with end-stage renal failure; this group of patients shows peculiar clinical and technical problems. We present the data from a National Registry on 22 children starting CPD under one year of age, representing 11.6% of the total population of the Registry (189 patients). Mean weight at start of CPD was 6.1 +/- 1.8 kg and duration of dialysis was 22.1 +/- 15.5 months. During the follow-up period, 9 patients were transplanted, 1 was shifted to hemodialysis, and 4 died. Patient survival was 89.1% and 82.2% at 1 and 2 years (97.9% and 96.5% in the group of 167 older children); technique survival results were 89.1% at 1 year and 77.1% at 2 years (vs 92.5% and 85.7%, respectively). The incidence of peritonitis was 1 episode every 15.6 CPD-months (1:16.1 in the older children). Catheter-related complications occurred more frequently in infants (1:11.8 vs 1:17 episode:CPD-months), even if this difference was not statistically significant. Statural growth was on average -0.29 +/- 0.66 SD/year with a significant improvement between the first (-0.50 +/- 0.79) and the second (+0.23 +/- 0.77) year of CPD. Our data confirm that infants represent a higher risk group and that they can be treated satisfactorily with CPD while awaiting renal transplantation