Correction to: Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia.

The original version of this article unfortunately contained mistake in Fig. 3 image.

Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia.

Nuclear pore complexes (NPCs) are the gateways of the nuclear envelope mediating transport between cytoplasm and nucleus. They form huge complexes of 125 MDa in vertebrates and consist of about 30 different nucleoporins present in multiple copies in each complex. Here, we describe pathogenic variants in the nucleoporin 93 (NUP93) associated with an autosomal recessive form of congenital ataxia. Two rare compound heterozygous variants of NUP93 were identified by whole exome sequencing in two brothers with isolated cerebellar atrophy: one missense variant (p.R537W) results in a protein which does not localize to NPCs and cannot functionally replace the wild type protein, whereas the variant (p.F699L) apparently supports NPC assembly. In addition to its recently described pathological role in steroid-resistant nephrotic syndrome, our work identifies NUP93 as a candidate gene for non-progressive congenital ataxia.

MYCN gene expression is required for the onset of the differentiation programme in neuroblastoma cells.

Neuroblastoma is an embryonic tumour of the sympathetic nervous system and is one of the most common cancers in childhood. A high differentiation stage has been associated with a favourable outcome; however, the mechanisms governing neuroblastoma cell differentiation are not completely understood. The MYCN gene is considered the hallmark of neuroblastoma. Even though it has been reported that MYCN has a role during embryonic development, it is needed its decrease so that differentiation can be completed. We aimed to better define the role of MYCN in the differentiation processes, particularly during the early stages. Considering the ability of MYCN to regulate non-coding RNAs, our hypothesis was that N-Myc protein might be necessary to activate differentiation (mimicking embryonic development events) by regulating miRNAs critical for this process. We show that MYCN expression increased in embryonic cortical neural precursor cells at an early stage after differentiation induction. To investigate our hypothesis, we used human neuroblastoma cell lines. In LAN-5 neuroblastoma cells, MYCN was upregulated after 2 days of differentiation induction before its expected downregulation. Positive modulation of various differentiation markers was associated with the increased MYCN expression. Similarly, MYCN silencing inhibited such differentiation, leading to negative modulation of various differentiation markers. Furthermore, MYCN gene overexpression in the poorly differentiating neuroblastoma cell line SK-N-AS restored the ability of such cells to differentiate. We identified three key miRNAs, which could regulate the onset of differentiation programme in the neuroblastoma cells in which we modulated MYCN. Interestingly, these effects were accompanied by changes in the apoptotic compartment evaluated both as expression of apoptosis-related genes and as fraction of apoptotic cells. Therefore, our idea is that MYCN is necessary during the activation of neuroblastoma differentiation to induce apoptosis in cells that are not committed to differentiate.

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

3D angiography in the evaluation of intracranial aneurysms before and after treatment. Initial experience.

PURPOSE: The aim of the study is to evaluate the advantages of 3D angiography as compared to 2D angiography in assessing intracranial aneurysms before and after treatment and, in particular, in selecting and planning the correct treatment. MATERIALS AND METHODS: Thirty intracranial aneurysms were retrospectively reviewed before and after treatment. The study population consisted of 12 men and 18 women (age range: 35-77 years; mean age: 58 years). Eighteen aneurysms were treated surgically, 10 endovascularly and 2 with combined treatment. The 2D and 3D findings before and after treatment were compared, and the pre-treatment angiographic images were compared with surgical findings. The following parameters were assessed and compared: aneurysmal sac and neck size, vascular involvement and evaluation of post-treatment residual mass. RESULTS: On the 2D DSA images, visualisation of the sac and neck was optimal in 45% and 15% of cases, adequate in 10% and 35% of cases and inadequate in 5% and 50% of cases, respectively. On the 3D DSA images, visualisation of the sac and neck was optimal in 100% of cases. Three-dimensional DSA was able to detect 8 aneurysms with vessel involvement in all cases (100%). Of these, four (50%) went undetected on 2D DSA; in two cases, two-dimensional DSA erroneously detected the presence of vascular involvement (false positive). Three-dimensional angiography proved superior to 2D angiography in the evaluation of the residual aneurysms treated with clipping. Finally, 3D DSA was able to reduce the number of radiographic projections, the quantity of contrast medium, the time and associated risks necessary for a precise evaluation of the aneurysm. CONCLUSIONS: In our first experience, 3D DSA proved useful in reducing the risks and diagnostic time as well as in selecting and planning the treatment. Moreover, it improved the operating conditions of both surgical and endovascular treatment. Technological advances in this field will enable the optimisation of the technique in terms of anatomical detail and reconstruction time.

Prevalence of Salmonella enterica and Listeria monocytogenes contamination in foods of animal origin in Italy.

The present survey collected and analyzed the results of routine testing for Salmonella enterica and Listeria monocytogenes on foods of animal origin submitted for official controls in Italy during 2001 to 2002. Salmonella was detected in 2.2% of 71,643 food samples examined, and the isolation rates ranged from 9.9% for raw poultry meat to less than 0.1% for dairy products. Isolation rates were also high in raw pork (4.9%) and processed meats (5.3%), which often involved pork. Low rates were observed in seafood (0.5%) and in ready-to-eat foods, such as grocery products (0.7%) and ice creams (0.1%). Serotyping showed that approximately 50% of the isolates belonged to the serotypes most commonly isolated from humans in Italy, thus confirming that most cases of human salmonellosis have a foodborne origin. Levels of L. monocytogenes were higher than what is accepted by the current regulation in 2.4% of 42,300 food samples. The positivity rates ranged from 10.3% in raw pork to none in eggs and egg products. Contamination rates were higher in other meat products (between 2 and 5%) and fish (6.5%) than in cheeses (1.1%) and other dairy products (0.6%). Routine control activities on the microbial contamination of foods can generate data with statistical and epidemiological value. Such data can be used as a basis for estimating the exposure of consumers to foodborne pathogens, following the trends of contamination over time, and evaluating the effects of control measures on the contamination of food.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of damage to nontumorous liver tissue-long-term prospective study.

PURPOSE: To evaluate damage to cirrhotic liver tissue after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: TACE was performed in 111 patients with HCC that involved less than 30% of the liver. Baseline liver function was evaluated with Child-Pugh scores and other indicators. Eighty-two patients had Child-Pugh class A disease, 27 had class B disease, and two had class C disease. All patients underwent chemotherapy followed by gelatin sponge particle embolization in the proper ("complete" embolization; n = 69) or right or left main ("partial" embolization; n = 42) hepatic artery. Liver function was assessed 4 months later, and 95 patients underwent a second TACE (complete embolization in 57, partial in 38). Liver function was again assessed 4 months later in 60 patients. RESULTS: No patient died. Child-Pugh scores increased in all patients from a mean 5.96 to 6.28 (not significant) and 6.51 (P =. 05) after first and second TACEs, respectively. In patients with class A disease, scores increased from a mean 5.37 to 5.73 (P =.01) and 5.89 (P =.001) after first and second TACEs, respectively; in patients with class B disease, scores changed from a mean of 7.48 to 7.67 and 7.30 after first and second TACEs, respectively (not significant). CONCLUSION: TACE does not induce significant long-term worsening of liver function in patients with class A or B cirrhosis.

Congenital absence of the internal carotid artery.

We report three cases of congenital absence of an internal carotid artery (ICA), diagnosed incidentally by digital subtraction angiography. The analysis of the cases is based on the classification of segmental ICA agenesis proposed by Lasjaunias and Berenstein. Usually the patients with this rare vascular anomaly are asymptomatic; some may have symptoms related to cerebrovascular insufficiency, compression by enlarged intracranial collateral vessels, or complications associated with cerebral aneurysms. Diagnosis of congenital absence of ICA is made by skull base computed tomography (CT) scan, CT and magnetic resonance angiography, and conventional or digital subtraction angiography.

Congenital intrahepatic portosystemic shunt.

The authors report a congenital intrahepatic portosystemic shunt detected by angiography in a young patient with acute onset of hyperammoniemia and hepatic encephalopathy.

Spiral CT angiography in the study of the carotid stenoses.

PURPOSE: To determine sensitivity, specificity and diagnostic accuracy of spiral CT angiography (S-CTA) compared to Digital Subtraction Angiography (DSA). MATERIALS AND METHODS: We studied 40 patients with suspected cerebro-vascular insufficiency by carotid stenosis. Diagnostic examinations by means of S-CTA and DSA were carried out within 24 hours of each other. Twelve of these patients underwent thromboendoarterectomy (TEA). Prospeed SX GE was used for S-CTA. Post-processing was performed using Maximum Intensity Projection (MIP) after deleting osteo-muscular structures and CT angiograms were displayed in an oblique anterior view at an angle of 10 degrees-15 degrees along the longitudinal axis. For DSA examinations, a Siemens Politron 1000 VR unit was used. RESULTS: In this study S-CTA showed values of sensitivity, specificity and diagnostic accuracy of 88%, 100% and 96%, respectively. CONCLUSIONS: In the future, with the improvement of non-invasive techniques (S-CTA, MRA), DSA should be replaced, as the gold-standard, in the evaluation of stenotic disease of the carotid bifurcation.

Treatment of hepatocellular carcinoma: a single-center experience.

PURPOSE: The comparative efficacy of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated. METHODS: Two hundred and sixty consecutive patients were retrospectively analyzed: 156 had received between one and six chemoembolization sessions at 3-month intervals, 33 had had PEI, and the remaining 71 patients refused any treatment. The follow-up ranged from 3 to 36 months. Survival rates were statistically analyzed by life-table analysis. RESULTS: Patients' survival was affected by the number of nodules and by the Child's and Okuda's classes; no relationship was found between survival rates and the histologic grade or vascular supply of the tumor. In the case of a single lesion of Okuda's class I, TACE was more effective than PEI. In multifocal HCC, TACE was better than no treatment in Okuda's class I and Child's class A. CONCLUSION: We suggest TACE as the treatment of choice in Child A or Okuda I patients with multifocal HCCs; it seems of little help in Child B-C or Okuda II-III patients.

[Interventional radiology in thoracic emergencies]. / La radiologia interventistica nelle emergenze toraciche.

There are numerous clinical situations in which interventional angiography fully reveals its two-fold diagnostic and therapeutic value. The present review focuses attention on the use of such procedures in certain thoracic emergencies. Indications, diagnostic results and therapeutic advantages are examined together with possible complications. Pulmonary embolism is a serious circulatory condition that is often difficult to diagnose because of the lack of specificity of its accompanying symptoms. In these cases the role of the angiographic radiologist is often three-fold: diagnosis, therapy (possibility of carrying out locoregional thrombolysis), and prophylaxis (positioning of caval filters that prevent the migration of thrombi). Haemoptysis may arise from both the pulmonary and bronchial vessels and may be caused by various pathologies (cancer, angiodysplasia, vasculitis, aspergillosis). Angiographic study in such cases is indispensable for identifying the source of bleeding and for arresting, using embolising material, haemorrhage that it is no longer possible to control with other therapeutic modalities. Foreign bodies held in the vascular tree are in the main fragments of catheters detached accidentally or as a result of incorrect manoeuvres or for defects of construction of the material. Their removal is possible today by using, percutaneously, angiographic techniques (snare loop, basket, hook system, balloon catheters) which make it possible to hook up the fragment and remove it.

Preoperative embolization in surgical treatment of spinal thoracic dumbbell schwannoma. A case report.

Schwannoma is the most common intraspinal tumor, which at times goes out of spinal canal and spreads into the paraspinal tissue to produce a dumbbell configuration. A 58-year-old woman is reported, in whom a plain thorax X-rays accidentally disclosed a mass located in the posterior mediastinum. Computerized tomography (CT) revealed a dumbbell lesion, 4.5 cm in diameter, in the right rib-vertebral groove at the T9 level. Spinal angiography showed localization of Adamkievicz artery at the T10 level on the left side. The lesion appeared hypervascular and was embolized by particulate agents (Contour Emboli 150-250 mu) with reduction of its blush. A combined two-team (thoracic and neurosurgeon) approach permitted an uneventful removal of a schwannoma.

[Treatment of primary hepatocarcinoma with chemoembolization and alcohol injection. Personal experience]. / Trattamento dell'epatocarcinoma primitivo mediante chemioembolizzazione e alcolizzazione. Esperienza personale.

The comparative efficacy of transcatheter arterial chemoembolization and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated in a series of 243 consecutive patients: 146 of them were submitted to 1-6 chemoembolization sessions at 1 and 3 months' intervals and 30 to PEI; the remaining 67 patients refused any treatment. The follow-up ranged 3 to 36 months. Survival rates were statistically analyzed with the life table analysis. Patients' survival was affected by the number of nodules and by Child's and Okuda's classes; no relationship was found between survival rates and histologic grade or nodule vascular feeding. In case of single lesions, chemoembolization was more effective than PEI in Okuda's class I. In case of multifocal HCC, chemoembolization was better than no treatment in Okuda's class I and Child's class A. In conclusion, we suggest chemoembolization as the treatment of choice in Child A or Okuda I patients with multifocal HCCs, while its use seems of little help in Child B-C or Okuda II-III patients. In case of unifocal HCC, PEI or surgical resection should be combined with chemoembolization.

[Primary hepatocarcinoma. Diagnostic imaging and chemoembolization]. / Epatocarcinoma primitivo. Diagnostica per immagini e chemioembolizzazione.

The diagnostic and therapeutic approach by means of transcatheter arterial chemoembolization is analyzed in 100 patients affected with hepatocellular carcinoma (HCC): in all patients the HCC had been diagnosed by means of US-guided fine-needle biopsy: 75 of 100 patients were in Child A class, 24 in Child B and 1 in Child C class. The most sensitive imaging technique to identify HCC proved to be angiography (95%); post-Lipiodol CT was also of great value to stage the disease. The authors suggest a diagnostic-therapeutic approach including angiography and simultaneous chemoembolization right after US-guided biopsy, avoiding conventional CT; such a protocol allows high diagnostic accuracy at a lower cost. Chemoembolization proved to be a safe technique, with a low incidence of mortality and complications; the latter were easy to treat by medical therapy. The follow-up data relative to 39 of 100 patients who underwent 2 or more chemoembolization treatments prove the latter to be a valuable technique relative to both the evolution of HCC nodules (in 18/21 patients with single lesions and in 9/18 patients with multiple lesions, lesion size was unchanged or decreased) and to survival rates (70% in 65 patients followed-up 1 year at least); on the whole, 77 of 100 patients are still alive.

[Transluminal therapy of stenosing lesions of the supra-aortic vessels. Personal experience]. / Terapia transluminale delle lesioni stenosanti dei tronchi epiaortici. Esperienza personale.

Percutaneous transluminal angioplasty (PTA) is commonly used to treat peripheral vascular diseases, but its use has recently spread to the treatment of stenotic lesions involving the supra-aortic vessels. The authors report their initial experience in 10 patients with left subclavian artery stenoses--8 of them treated with PTA and 2 with PTA and vascular stenting--and two more patients with fibromuscular stenosis of the internal carotid artery (ICA), which was treated by means of PTA. In the authors' opinion, PTA can be considered the procedure of choice to treat the stenotic lesions of the supra-aortic vessels. Intravascular stents can be extremely useful to prevent post-PTA restenosis, but further experience and probably further technological refinements are needed. To conclude, PTA of ICA is an effective method in selected cases--e.g., in the patients with symptomatic hemodynamic lesions and low risk of embolism, in the patients with difficult surgical access or in the event of high anesthesiological and/or surgical morbidity.

Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets.

Adequacy of nutrient intakes of adolescents with and without phenylketonuria (PKU) and infants and children with and without maple syrup urine disease (MSUD) were assessed using 3-day diet records sorted by disease and by age of the subject. Mean intakes of all nutrients were greater than two-thirds of the Recommended Dietary Allowances (RDA) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDI) for all adolescents studied, with the exception of selenium (Se) in PKU adolescents, which averaged 27.8 micrograms. For adolescents with PKU, > 50% of the RDA or ESADDI for all nutrients was provided by elemental or modified protein hydrolysate medical foods, except for vitamin A in children aged 11-15 years and Se in children 11-18 years. Mean nutrient intakes of all infants and children were greater than two-thirds of the RDA or ESADDI for all nutrients except Se in MSUD children aged 1-11 years, where intakes ranged from 6.4 to 13.2 micrograms (21-66% of the RDA). The medical foods provided for most of the RDA and ESADDI recommendations, with the exception of Se in MSUD children.