Applicability of 'Toolkit for Safety Assessment' tool to interventional radiology using probabilistic risk assessment techniques.

Interventional radiology brings extensive benefits to patients. Nevertheless, certain procedures may result in high doses of radiation, leading to health risks to occupationally exposed individuals (OEIs). Therefore, a more comprehensive risk analysis is essential to ensuring safety and minimising radiation exposures for all OEIs. The Toolkit for Safety Assessment (TOKSA) tool performs risk assessments based on the concepts described in 'General Safety Requirements' Part 3 (Radiation Protection and Safety of Radiation Sources: International Basic Safety Standards) and Part 4 (Safety Assessment for Facilities and Activities). This tool was developed based on the 'Ibero-American Forum of Radiological and Nuclear Regulatory Agencies' risk models and can promote the use of the risk assessment processes by OEIs. The aim of this study was to experimentally analyse the applicability of the TOKSA tool in interventional radiology with the use/support of probabilistic risk assessment techniques. The results were used to reduce the risks associated with a hemodynamics room in a hospital in Belo Horizonte, Brazil.

Diagnóstico de síndrome de POEMS tras neuropatía de larga evolución / Diagnosis of POEMS syndrome in a patient with long-standing neuropathy

No disponible

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

AIMS: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs. METHODS: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. RESULTS: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002. CONCLUSIONS: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

Whole-genome sequencing as standard practice for the analysis of clonality in outbreaks of meticillin-resistant Staphylococcus aureus in a paediatric setting.

Meticillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital-associated infections. This study investigated the potential use of whole-genome sequencing (WGS) for surveillance purposes by re-examining MRSA strains related to past outbreaks among hospitalized paediatric patients. WGS data ameliorated the genotypic profile previously obtained with Sanger sequencing and pulsed-field gel electrophoresis typing, and discriminated between strains that were related and unrelated to the outbreaks. This allowed strain clonality to be defined with a higher level of resolution than achieved previously. This study demonstrates the potential of WGS to trace hospital outbreaks, which may lead to WGS becoming standard practice in outbreak investigations.

An improved method for HLA-B and -C supratyping.

A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases. We noticed that, using a panel of 184 Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I(80), Bw4T(80), Bw6 and HLA-C1 or -C2 supratype.

Expanding the mutational spectrum associated to neural tube defects: literature revision and description of novel VANGL1 mutations.

BACKGROUND: Neural Tube Defects (NTD) are a common class of birth defects that occur in approximately 1 in 1000 live births. Both genetic and nongenetic factors are involved in the etiology of NTD. Planar cell polarity (PCP) genes plays a critical role in neural tube closure in model organisms. Studies in humans have identified nonsynonymous mutations in PCP pathway genes, including the VANGL genes, that may play a role as risk factors for NTD. METHODS: Here, we present the results of VANGL1 and VANGL2 mutational screening in a series of 53 NTD patients and 27 couples with a previous NTD affected pregnancy. RESULTS: We identified three heterozygous missense variants in VANGL1, p.Ala187Val, p.Asp389His, and p.Arg517His, that are absent in controls and predicted to be detrimental on the protein function and, thus, we expanded the mutational spectrum of VANGL1 in NTD cases. We did not identify any new variants having an evident pathogenic effect on protein function in VANGL2. Moreover, we reviewed all the rare nonsynonymous or synonymous variants of VANGL1 and VANGL2 found in patients and controls so far published and re-evaluated them for their pathogenic role by in silico prediction tools. Association tests were performed to demonstrate the enrichment of deleterious variants in reviewed cases versus controls from Exome Variant Server (EVS). CONCLUSION: We showed a significant (p = 7.0E-5) association between VANGL1 rare genetic variants, especially missense mutations, and NTDs risk.

[Vascular risk factors in patients with ischaemic stroke. Distribution according to age, sex and stroke subtype]. / Factores de riesgo vascular en pacientes con ictus isquémico. Distribución según edad, sexo y subtipo de ictus.

INTRODUCTION: Cardiovascular diseases are one of the leading health problems in developed countries. This term covers conditions such as coronary vascular disease, cerebrovascular diseases and peripheral vascular disease. Ischaemic cerebrovascular disease accounts for 80% of all cerebrovascular diseases. From a clinical point of view it is interesting to distinguish between modifiable and non-modifiable vascular risk factors. AIM: To analyse the prevalence of modifiable vascular risk factors and their different combinations in a case-control study on ischaemic cerebrovascular disease in the Spanish population, and also the differences in the distribution of the risk factors according to the type of stroke (TOAST classification), age and sex. SUBJECTS AND METHODS: The study was conducted on 308 patients with ischaemic stroke who were paired by age (+/- 5 years) and sex, with 307 controls with no prior history of thrombosis. The statistical analysis was performed using the software application SAS v. 9.1. RESULTS: The results suggest that the risk factors are subject to an adding effect, as well as pointing to the presence of a specific profile of these factors depending on the subtype of stroke that is developed. CONCLUSION: The addition of cardiovascular risk factors is associated with an increased risk of vascular events. The distribution of the modifiable vascular risk factors differs according to the type of stroke and the patient's sex and age.

Factores de riesgo vascular en pacientes con ictus isquémico. Distribución según edad, sexo y subtipo de ictus / Vascular risk factors in patients with ischaemic stroke distribution according to age, sex and stroke subtype

Las enfermedades cardiovasculares constituyen uno de los principales problemas de salud en los paísesdesarrollados. Esta entidad engloba la patología vascular coronaria, las enfermedades cerebrovasculares y la patología vascular periférica. La enfermedad cerebrovascular isquémica supone el 80% de las enfermedades cerebrovasculares. Desdeun punto de vista clínico, es interesante diferenciar los factores de riesgo vascular modificables de los no modificables. Objetivo. Analizar la prevalencia de factores de riesgo vascular modificables y sus distintas combinaciones en un estudio de casos y controles en enfermedad cerebrovascular isquémica en población española, así como las diferencias en la distribución de los factores de riesgo según el tipo de ictus (clasificación TOAST), edad y sexo. Sujetos y métodos. El estudio se llevó a cabo en 308 pacientes con ictus isquémico emparejados por edad (± 5 años) y sexo con 307 controles sin historia trombótica previa.El análisis estadístico se realizó con el programa SAS v. 9.1. Resultados. Los resultados sugieren un efecto aditivo de los factores de riesgo, así como la presencia de un determinado perfil de estos factores en función del subtipo de ictus que se desarrolle. Conclusión. La adición de factores de riesgo cardiovascular se asocia a un aumento de riesgo de acontecimientos vasculares. Existen diferencias en la distribución de los factores de riesgo vascular modificables en función del tipo de ictus, el sexo y la edad del paciente

Cardiovascular diseases are one of the leading health problems in developed countries. This termcovers conditions such as coronary vascular disease, cerebrovascular diseases and peripheral vascular disease. Ischaemic cerebrovascular disease accounts for 80% of all cerebrovascular diseases. From a clinical point of view it is interesting to distinguish between modifiable and non-modifiable vascular risk factors. Aim. To analyse the prevalence of modifiablevascular risk factors and their different combinations in a case-control study on ischaemic cerebrovascular disease in the Spanish population, and also the differences in the distribution of the risk factors according to the type of stroke (TOAST classification), age and sex. Subjects and methods. The study was conducted on 308 patients with ischaemic stroke who werepaired by age (± 5 years) and sex, with 307 controls with no prior history of thrombosis. The statistical analysis was performed using the software application SAS v. 9.1. Results. The results suggest that the risk factors are subject to an adding effect, as well as pointing to the presence of a specific profile of these factors depending on the subtype of stroke that isdeveloped. Conclusion. The addition of cardiovascular risk factors is associated with an increased risk of vascular events. The distribution of the modifiable vascular risk factors differs according to the type of stroke and the patient’s sex and age

Successful isolation and long-term establishment of a cell line with stem cell-like features from an anaplastic medulloblastoma.

AIMS: Herein we report on the successful isolation and establishment of a novel, long-term, primary, neurosphere-like cell line called 1603-MED from a 5-year-old boy affected by a highly aggressive anaplastic medulloblastoma. METHODS: Elaboration of the new protocol for neurosphere assay is extensively discussed, together with a complete immuno-histochemical and cytogenetic characterization of 1603-MED. RESULTS: Clinical course and histopathology are briefly discussed. The 1603-MED possesses a high capacity for proliferation, CD133 expression, self-renewal and differentiation, thus indicating that anaplastic medulloblastoma contains a subpopulation of cancer stem cells as observed in classic medulloblastoma. CONCLUSIONS: 1603-MED provides us with the first in vitro model of anaplastic medulloblastoma that may be suitable for studying both tumour progression and the genetic mechanisms related to therapy resistance, and may lead to the development and testing of chemosensitivity and new therapeutic targets.

JAK2 as a molecular marker in myeloproliferative diseases.

The molecular pathogenesis of the myeloproliferative disorders (MPD) is poorly understood, except for chronic myeloid leukemia (CML). Recently, several groups have discovered a novel recurrent unique acquired clonal mutation in a tyrosine-kinase JAK2 in patients with Philadelphia-negative MPD and other myeloid disorders. It consists in a guanine-to-thymine change encoding a valine to phenylalanine at codon 617 (JAK2 V617F). JAK2 and the other members of the Janus kinase family are tyrosine kinases that function as intermediates between membrane receptors and intracellular signalling molecules. The mutation occurs within the enzymatically inactive JH2 pseudo-kinase domain that regulates the active JH1 kinase domain. The JAK2 activation leads to constitutive JAK and STAT (activators of transcription) hyperactivation with induction of growth factor hypersensitivity and cell transformation. Some authors have found a higher risk of vascular thrombosis and higher platelet activation when the mutation is present. Therefore, the JAK2 mutation offers a molecular target for new drugs investigation in a similar way to bcr/abl rearrangement in CML. For all these reasons, several studies related to JAK2 have arisen in the last year. In this report, we will review the literature and discuss its possible clinical and prognostic significance.

Synthesis and mass spectroscopy kinetics of a novel ternary copper(II) complex with cytotoxic activity against cancer cells.

The X-ray structure of the [Cu(I-hip)(phen)2](+).(I-hip-).(H2O)7 complex (1) (where I-hipH is referred to o-iodohippuric acid and phen is 1,10-phenanthroline) and its binary synthetic intermediate [Cu(I-hip)2(H2O)3].(H2O)2 (2) have been solved and characterized by different techniques. This ternary [Cu(I-hip)(phen)2]+.(I-hip-).7H2O complex generates the copper(I) complex [Cu(phen)2]+ in aqueous solution without the addition of any external reductant, possibly by an intramolecular red-ox process in the presence of oxygen; the ESI-HRMS spectra (electrospray ionization-high resolution mass spectroscopy) detect these species and 24h after the solution, [Cu(phen)2]+ is the main product. The complex 1 is capable of cleaving DNA. To evaluate the biological properties, we carried out: cell culture, cell proliferation assays, cell cycle analysis, and electrophoresis (SDS-PAGE) and immunoblotting. Complex 1 induced apoptosis of A549 cells at low nanomolar and induced marked decreases of cancer cells at concentrations that did not change adipocyte survival. These data indicate that the parent complex is a potential anticancer drug.

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter's Syndrome (KS).

OBJECTS: Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter's Syndrome (KS) as co-morbid condition. MATERIALS AND METHODS: The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. CONCLUSION: In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.

Effect of metal complexes of acyclovir and its acetylated derivative on Herpes simplex virus 1 and Herpes simplex virus 2 replication.

The effect of zinc, nickel, cobalt and cadmium complexes of acyclovir (ACV) and its omicron-acetylated derivative (Ac-ACV) on the replication of wild type (wt) and ACV-resistant (ACV(R)) strains of Herpes simplex virus 1 (HSV-1) and Herpes simplex virus 2 (HSV-2) was examined. According to cytotoxicity, these compounds followed the order Ni-ACV chloride > Cd-ACV 3 Ni-ACV nitrate > ACV = Zn-ACV nitrate = Ac-ACV = Zn-Ac-ACV > Zn-ACV chloride > Co-ACV. Besides Ac-ACV, the only active complexes in inhibiting virus replication were Zn-ACV nitrate and Zn-Ac-ACV, which effectively suppressed the growth of both wt and ACVR strains of HSV-1 and HSV-2. The most active and most selective inhibitor of the growth of ACVR strains of HSV-1 and HSV-2 was Ac-ACV; its EC50 and SI were 100 and 10 times higher than those of ACV, respectively. Zn-Ac-ACV was less active than Ac-ACV, obviously due to the stability of the complex. Zn-ACV nitrate was active against both wt and ACVR strains of HSV-1; its activity and selectivity were 100 and 75 times higher than those of ACV, respectively. Ac-ACV and Zn-Ac-ACV suppressed the pre-mitotic arrest caused by HSV-1 infection during the first 2 hrs of infection and later on restored the cell division.

Ternary complexes metal [Co(II), Ni(II), Cu(II) and Zn(II)]--ortho-iodohippurate (I-hip)--acyclovir. X-ray characterization of isostructural [(Co, Ni or Zn)(I-hip)(2)(ACV)(H(2)O)(3)] with stacking as a recognition factor.

Four ternary metal--ortho-iodohippurate (I-hip)--acyclovir (ACV) complexes, [M(I-hip)(2)(ACV)(H(2)O)(3)] where M is Co(II) (1), Ni(II) (2), Cu (3) and Zn(II) have been obtained by reaction between the corresponding binary complexes M(II)(I-hip)(2)xnH(2)O and ACV. Three ternary complexes (M=Co, Ni and Zn) and the corresponding Zn(II)--ortho-iodohippurate binary derivative have been structurally characterized by X-ray diffraction: The studies show these three ternary complexes are isostructural and present, in solid state, an interesting stacking between the nucleobase and the aryl ring of the hippurate moiety, which probably promotes the formation of ternary complexes. Moreover, the two different ligands interact between them by means of ancillary hydrogen bonds with water molecules coordinated to the metal ion. It must be mentioned that these two recognition factors, hydrogen bonds plus stacking, could explain the reason for the isostructurality of these ternary derivatives with so different three metal ions, with diverses trends in coordination numbers and geometries. In solid state, there are two enantiomeric molecules that are related by an inversion center as the crystal-building unit (as a translational motif) for the ternary complexes.

Uracilato and 5-halouracilato complexes of Cu(II), Zn(II) and Ni(II). X-ray structures of [Cu(uracilato-N(1))(2)(NH(3))(2)].2(H(2)O), [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2), [Ni(5-chlorouracilato-N(1))(2)(en)(2)].2H(2)O and [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O).

Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units.

A case of carotid bifurcation anomaly discovered during a thyroidectomy operation.

The anatomic anomalies of the supra-aortic trunks and their branches are comparatively frequent observations. They often remain asymptomatic throughout life although in some cases, especially if nothing is known of them, they may complicate surgical interventions involving that anatomical region. The case of a female patient who, during thyroidectomy, suffered the ligature of her external carotid artery which was taken mistakenly for the thyroid, is reported. Dissection of the area made it possible to identify an anomaly of the vascular structures with a carotid bifurcation which turned out to be very low, a very deep internal carotid artery on the prevertebral fascia and an absent lower thyroid artery. In the postoperative period, the patient was subjected to MR of the neck. This showed an anatomical anomaly of the left carotid bifurcation which was much lower than normal. An attempt was made to reconstruct the external carotid artery with a saphenous vein but unsuccessfully. The incident did not have serious complications for the patient but it might be asked whether, given the low cost and the absolute non-invasiveness of the examination, it might not be worth while to carry out a duplex scan of the supra-aortic trunks before going ahead with any operation in the cervical region, in consideration above all of the dangerous nature of these vascular structures and of the usefulness of studying pathologies that often remain silent until the occurrence of an event which might well be catastrophic.

Cystic adventitial disease of the popliteal artery. Report of 1 case and review of the literature.

Cystic adventitial disease (CAD) of the popliteal artery is a rare but well-known cause of intermittent claudication, especially in young patients. The etiology of the disease is still controversial and the literature reports various hypotheses for its origin. Diagnosis starts with thorough history taking and physical examination; non invasive diagnostic studies comprise color duplex scanner (ECD), computed tomography (CT), better if elicoidal (3D CT) and magnetic resonance imaging (MRI), which can aid in establishing correct recognition of the disease in most cases. A 48-year-old man presented with intermittent right calf claudication that had begun 4 months earlier; the symptom-free interval was about 100 m. MRI and MR angiography of right popliteal fossa revealed the presence of an oval cystic (maximum diameter 45 mm). The caudal aspect of the cyst showed pedicles protruding between the popliteal vein and the popliteal artery that compressed the artery, causing complete occlusion of its lumen. Surgery was performed through the posterior approach using an S-shaped incision; the affected segment of the popliteal artery was successfully excised and replaced with an autogenous external saphenous vein graft. A follow-up is underway, both clinical and with; no cyst recurrence has so far been detected either clinically or by duplex scanner during the 15-month postoperative follow-up period; the graft is patent and the patient is completely symptom free. Severe claudication in young patients, possibly without significant vascular risk factors, should prompt the clinical suspicion of adventitial cystic disease of the popliteal artery. Medical history, clinical examination and non invasive instrumental investigations, such as duplex scanner, elicoidal CT and/or MRI, may aid in establishing the correct diagnosis.

Aneurysms of the hypogastric artery following surgery of the abdominal aorta. A report of two cases and review of the literature.

Isolated aneurysms of the hypogastric artery are very rare and account for between 0.04% and 0.4% of all intra-abdominal aneurysms. In 85% of cases they are monolateral and are present in association with an aneurysm of the infrarenal abdominal aorta and of the common and external iliac arteries, they make up part of a poly-aneurysmal disease. Unless the patient is an extremely poor condition, surgical treatment is generally indicated for aneurysms greater than 3 cm; close monitoring of those with smaller aneurysms is recommended. Two patients presented with isolated aneurysm of an internal iliac artery which had developed several years after aortoiliac surgery. The one received surgical treatment; the other, who was in poor general conditions and at high risk for surgery, underwent endovascular embolization. Both procedures were successful, with a current follow-up between 15 and 18 months. Endovascular embolization, as performed in the 2(nd) patient, provided an alternative to the surgical procedure. After injection in the aneurysmal sac of the Gianturco spirals, a covered stent was placed in the iliac axis to exclude the inflow of the hypogastric artery. According to our experience of 2 patients, the one treated surgically and the other submitted to a less invasive endovascular procedure, we can state that both methods are practicable. The final choice lies with the vascular surgeon, after weighing the multiple factors that each case involves.