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In the framework of the OECD/NEA/CSNI/WGAMA, an activity on the “Status report on thermal–hydraulic passive systems design and safety assessment” has been conducted. Within this activity, a benchmark exercise, based on the experimental data developed in the full scale PERSEO (in-Pool Energy Removal System for Emergency Operation) component separate effect test facility, built at SIET (Piacenza, Italy), has been proposed and carried out. An “OPEN” benchmark exercise, hosted by ENEA, has been conducted. Twelve results from eleven Organizations were submitted. PERSEO is a full-scale separate effect test facility designed to study a new passive decay heat removal system operating in natural circulation. Test 7 is a full pressure test (7 MPa) and investigates the system stability and the system operation. The accuracy of the calculated results has been evaluated both qualitatively and quantitatively. The latter has been conducted adopting the Fast Fourier Transform Based Method. The present paper summarizes the main features of the PERSEO facility and Test 7 and discusses the main results and outcome of the benchmark exercise.

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF

Il contributo, muovendo dalle leggi razziali del1939, analizza il tema delle responsabilità italiane nella Shoah

Introduction:Inherited Peripheral Neuropathies.represent a large group of hereditary diseases that comprises the hereditary motor and sensory neuropathy, more known as Charcot-Marie-Tooth (CMT), hereditary sensory and autonomic neuropathy (HSNA) and distal motor neuropathy (dHMN). Typically IPNs are characterized by distal wasting and weakness, decreased deep tendon reflexes, contractures and skeletal deformities. More than 60 nuclear genes are implicated in the pathogenesis.In the last few years, the molecular diagnosis improved with the advent of NGS, which is now the strategy used in routine in many laboratories. Aim of the study We performed genetic tests for 49 genetically un-diagnosed IPNs patients who had been excluded 17p12 (PMP22) duplication by Real Time PCR and microsatellite markers. Materials and Methods: We designed a genes panel using the Ion Ampliseq Designer (Thermo Fisher Scientific) targeting the coding sequence comprising the intron/exon boundaries of 32 genes associated with IPNs phenotype, reaching a target coverage of 99,13%. The amplicon libraries obtained by the Ion AmpliSeq Library Kit 2.0 (Thermo Fisher Scientific), were subsequently barcoded, pool together in equimolar concentrations and enriched using the One Touch 2 instrument. Sequencing was performed on an Ion PGM machine using an Ion 318 sequencing chip. The obtained raw data were analyzed with the Ion Torrent Suite 5.10 for the alignment and variants caller. To annotate the variants ANNOVAR tool was also used. The identified variants were confirmed by Sanger sequencing. Results: By using IPNs genes panel, we are able to detect in 19 out of 49 examined patients pathogenic variants in the following genes: KIF1B, MFN2, MPZ, SETX, SBF2, DCTN1, GARS, GAN, DNM2, WINK1 and FIG4. KIF1B and MFN2 genes result to be, in our study, the most frequent mutated genes. Conclusions: Targeted gene panel sequencing is a power tool to resolve uncertain cases with suspected IPN diagnosis. It strikingly reduces the cost and the time with better detection efficiency; but, because the number of causative genes for IPNs is still growing, it is necessary to have a continuous updating of the involved genes to facilitate the diagnosis of the unsolved cases.

Introduction: Vanishing white matter disease (VWM) is an autosomal recessive leukodystrophy caused by mutations genes encoding the translational initiation factor 2B: EIF2B1-EIFB5. It is a heterogeneous neurological disorder with prominent cerebellar ataxia and spasticity in childhood-onset form and behavioural changes, dementia and seizures in adult-onset form (#15% of cases). The course of the disease is chronic progressive with episodes of stress-provoked rapid neurological deterioration. Purpose of the study: We present the case of a 60 years old patient, MTHFR homozygous, presenting white matter lesions and a subcortical vascular encephalopathy being diagnosed. To investigate a possible genetic cause, suspecting CADASIL, genetic and genomic analysis were performed. Materials and Methods: For genetic and genomic investigations, Sanger sequencing of NOTCH3 gene, linked to CADASIL disease, and Next Generation Sequencing (NGS) analysis were performed on the patient. NOTCH3 sequencing was performed using primer pairs for all 22 exons, while for NGS analysis, we used a genes panel including 753 genes involved in neurological diseases. Libraries were prepared using Ion Ampliseq Library preparation kit 2.0 (Thermo Fisher Scientific) and they were run on Ion Torrent PGM (Thermo Fisher Scientific). We performed the alignment using Torrent Suite v. 5.10 and we used ANNOVAR for annotation step. Results: Sanger sequencing did not reveal any mutation in NOTCH3 gene, excluding CADASIL disease as the genetic cause responsible for the clinical history of our patient. NGS detected a novel heterozygous non- synonimous variant in exon 5 of EIF2B3 gene (c. C554G; p. S185C), whose mutations have been strongly related to leukoencephalopathy and VWM disease. Furthermore, all in silico analysis conducted on this variant predicts its deleterious impact that could affect protein function. Conclusion: S185C variant in EIF2B3 gene was discovered in an atypical condition of adult onset Leukodistrophy, a disease that usually occurs in childhood. It is uncertain if S185C could be responsible for the clinical history of our patient or if the peculiarity of his symptoms could be related to the potential contribution of this new detected variant on the phenotypical spectrum observed in the disease.

Introduction: Mitochondrial DNA (mtDNA) is a 16.6 kb, double-stranded, circular molecule that contains 37 genes coding for 13 subunits of the respiratory chain plus two rRNAs and 22 tRNAs, required to synthetize them. Mutations in these genes have been identified in patients with a variety of disorders affecting every system in the body. Mitochondrial diseases are clinically heterogeneous, so both diagnosis and treatment are extremely difficult. Traditional molecular diagnostic approach was limited to testing the most frequent mtDNA point mutations related to well-known mitochondrial diseases like MELAS, MERRF, NARP, LHON. The advent of next generation sequencing technologies has provided the whole mtDNA sequencing, allowing the identification of disease-causing pathogenic variants in a single platform. Aim of the study: The aim of this study was to develop an NGS strategy, by using an amplicon-based method to sequence the entire mitogenome, in order to identify disease-causing pathogenic variants in patients affected by mitochondrial diseases.Materials and Methods: The whole mtDNA coming from 20 patients was analyzed using an amplicon-based approach (Precision ID mtDNA Whole Genome Panel - ThermoFisher Scientific). The enriched libraries were sequenced on the Personal Genome Machine (PGM) from ThermoFisher Scientific. Primary bioinformatic analysis was carried out using the Ion Torrent suite v. 5.6. Annotation of the variants was made by the Variant Annotation Integrator from the UCSC browser. Results: After bioinformatics analysis and filtering, 100% coverage of the targeted regions was obtained with at least 500-fold mean depth. The size distribution of the amplicons ranged from 118 to 150 bp. The generated reads were 100% on target, with a uniformity of 99.8%. After variant calling, we were able to detect a mean of 35 SNVs for sample. Conclusions: The analysis of the whole mtDNA is a useful strategy for researchers studying human diseases linked to variations present in this type of genome. The NGS approach, compared to the standard methods, is a more reliable and time-cost reducing strategy to detect all the variants present in the mitogenome possibly associated with mitochondrial diseases.

Inguino-scrotal herniation of the ureter is a rare and difficult situation for a surgeon, especially if only recognized during inguinal hernia repair. An 83-year-old gentleman, with a previous history of radiation treatment for squamous anal cancer, presented with a large left inguinoscrotal hernia causing occasional pain at the base of the scrotum. Follow-up, post-radiation therapy CT scan showed a hernia sac containing the bladder and large bowel. Calcifications in the sac were interpreted as bladder stones, in keeping with the history of left renal calculi. During hernia repair careful dissection revealed a herniated portion of the left ureter located alongside a large hernia sac, complicated by ureteral calculi. Following stones extraction and ureteral repair, hernia repair with mesh was successfully accomplished. Pathogenesis of ureteric herniation is reviewed. A herniated ureter is potentially a source of serious renal or ureteral complications. When discovered, ureteric hernias should be surgically repaired. If preoperative detection of a ureter herniation alongside an inguinal hernia is missed, awareness of the existence of this condition may help avoid iatrogenic ureteral damage injury during a complex hernioplasty. Documentation of unexplained, sizeable and distinct calcifications in an inguino-scrotal hernia sac, particularly in a patient with a history of urolithiasis, may suggest the presence of a herniated, calculus-filled ureter. In such cases, retrograde pyelograms may be considered for a definitive diagnosis prior to surgery.

BackgroundSurgical resection remains the treatment of choice for primary and secondary liver cancer. Complications are mainly related to blood loss. Radiofrequency-assisted liver resection (RF-R) has been proposed for parenchymal division as an alternative to clamp crushing in order to reduce blood loss.MethodsFifty patients (median age 62 (range 30–82) years) undergoing hepatectomy were randomized to RF-R (24 patients) or the clamp-crushing method (26). In the RF-R group the resection plane was precoagulated by multiple insertion of a planar triple-cooled radiofrequency ablation needle, and then the parenchyma was sectioned using a scalpel.ResultsThe two groups were well matched in terms of age, sex, liver disease and type of resection. There were no deaths. Eight in the RF-R group developed complications (abscess in six, biliary fistula in three and biliary stenosis in one) compared with none of those who had resection by the crush method (P < 0·001). Two patients with cirrhosis in each group developed decompensation. Blood transfusion was required in eight of 24 patients in the RF-R group and 13 of 26 in the clamp-crushing group (P = 0·079).ConclusionRF-R allows parenchymal resection in a clean surgical field but is associated with a higher rate of postoperative complications than the clamp-crushing technique.

Serum concentrations of soluble human leukocyte class I antigens (sHLA-I) and of the intercellular adhesion molecule-1 (sICAM-1) are increased in the early inflammatory stages of several immune-related diseases. These soluble molecules also exert immunomodulatory activity, including regulation of natural killer (NK) cell cytotoxicity. The aim of this study was to verify whether sHLA-I and sICAM-1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune-related disorder associated with impaired in-vitro NK cell activity. Serum sHLA-I and sICAM-1 concentrations were similar in patients and in healthy donors. However, when evaluated according to disease stage, sHLA-I and sICAM-1 concentrations were higher in patients with endometriosis stage I-II (revised American Fertility Society classification), or with non-pigmented peritoneal lesions. In conclusion, studies on sHLA-I and sICAM-1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome.

The human DRD2 gene is located on chromosome 11q22-q23 and contains one specific functional polymorphism called TaqIA, which characteristically presents two alleles referred to as A1 and A2. Evidence indicates that the A1 allele impacts brain dopaminergic function and may confer an increased risk of developing Parkinson's disease. However, possible morphological changes underlying such genetic variant remain to be clarified. The aim of this study was to provide an in vivo demonstration of changes in brain structures associated with the TaqIA polymorphism of the DRD2 gene. Optimized voxel-based morphometry (VBM) was applied to high-resolution MR brain images of 70 healthy controls divided into two groups according to their DRD2 genotype (A1/A2, n = 15; A2/A2, n = 55). Compared with individuals' homozygous for the A2 allele, the A1 carriers had significantly smaller areas of a specific part of the midbrain, encompassing the substantia nigra bilaterally. Our findings showed an association of the DRD2 TaqIA polymorphism with the changed volumes of a specific subcortical region strongly involved in the dopaminergic system.