We report the first empirical confirmation of the co-occurrence of organophosphate esters (OPEs) additives and microplastics (MPs) in benthic compartments from the Loire estuary. Higher median ...concentrations of MPs (3387 items/kg dw), ∑13tri-OPEs (12.0 ng/g dw) and ∑4di-OPEs (0.7 ng/g dw) were measured in intertidal sediments with predominance of fine particles, and under higher anthropogenic pressures, with a general lack of seasonality. Contrarily, Scrobicularia plana showed up to 4-fold higher ∑tri-OPE concentrations in summer (reaching 37.0 ng/g dw), and similar spatial distribution. Polyethylene predominated in both compartments. Tris(2-ethylhexyl) phosphate (TEHP), its degradation metabolite (BEHP) and tris-(2-chloro, 1-methylethyl) phosphate (TCIPP) were the most abundant OPEs in sediments, while TCIPP predominated in S. plana. The biota-sediment accumulation factors suggest bioaccumulation potential for chlorinated-OPEs, with higher exposure in summer. No significant correlations were generally found between OPEs and MPs in sediments suggesting a limited role of MPs as in-situ source of OPEs.
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•TEHP, BEHP and TCIPP most abundant OPEs in sediments, TCIPP predominated in S. plana.•Different spatial-temporal trends of OPEs in sediments and S. Plana in the estuary.•Limited role of MPs as effective in-situ source of OPEs in estuarine sediments.•No significant role of tri-OPEs as environmental source of di-OPEs in sediments.•BSAFs suggest bioaccumulation of TDCIPP, and higher exposure in summer.
Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of ...tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.
The cognitive deficits associated with schizophrenia are commonly believed to arise from the abnormal temporal integration of information, however a quantitative approach to assess network ...coordination is lacking. Here, we propose to use cross-frequency modulation (cfM), the dependence of local high-frequency activity on the phase of widespread low-frequency oscillations, as an indicator of network coordination and functional integration. In an exploratory analysis based on pre-existing data, we measured cfM from multi-channel EEG recordings acquired while schizophrenia patients (n = 47) and healthy controls (n = 130) performed an auditory oddball task. Novel application of independent component analysis (ICA) to modulation data delineated components with specific spatial and spectral profiles, the weights of which showed covariation with diagnosis. Global cfM was significantly greater in healthy controls (F(1,175) = 9.25, P < 0.005), while modulation at fronto-temporal electrodes was greater in patients (F(1,175) = 17.5, P < 0.0001). We further found that the weights of schizophrenia-relevant components were associated with genetic polymorphisms at previously identified risk loci. Global cfM decreased with copies of 957C allele in the gene for the dopamine D2 receptor (r = -0.20, P < 0.01) across all subjects. Additionally, greater "aberrant" fronto-temporal modulation in schizophrenia patients was correlated with several polymorphisms in the gene for the α2-subunit of the GABA(A) receptor (GABRA2) as well as the total number of risk alleles in GABRA2 (r = 0.45, P < 0.01). Overall, our results indicate great promise for this approach in establishing patterns of cfM in health and disease and elucidating the roles of oscillatory interactions in functional connectivity.
Este informe analiza los acuerdos realizados o programados por los distintos Estados, aclarando los temas que se tratan. En esta forma se tiene una idea de los hechos de negociacion, es decir, de los ...acuerdos que se vienen estableciendo. Los aspectos juridicos e institucionales y los economicos tambien son analizados clarificando en esta forma todos los aspectos relevantes de los acuerdos alcanzados.
It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ), however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, ...which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA), to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs) discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA) images in a cohort consisting of 73 SZ patients and 87 healthy controls (HC). A significant correlation (r = -0.37, p = 1.25 × 10(-6)) was identified between one genetic factor and one FA component after controlling for scanning site, ethnicity, age, and sex. The identified FA-SNP association remained stable in a 10-fold validation. A 5000-run permutation test yielded a p-value of 2.00 × 10(-4). The FA component reflected decreased white matter integrity in the forceps major for SZ patients. The SNP component was overrepresented in genes whose products are involved in corpus callosum morphology (e.g., CNTNAP2, NPAS3, and NFIB) as well as canonical pathways of synaptic long term depression and protein kinase A signaling. Taken together, our finding delineates a part of genetic architecture underlying SZ-related FA reduction, emphasizing the important role of genetic variants involved in neural development.
The authors present a case of brain metastasis from an epithelioid malignant schwannoma. The patient previously had undergone a surgical resection of the primary tumor in the right forearm. The ...neoplasm was composed of nests of cells with an entirely epithelioid appearance without spindle cell areas. Immunohistochemically, the tumor cells stained positive for S100 protein and negative for cytokeratin, neuron-specific enolase, and anti-melanoma antiserum. To our knowledge, this is the first reported case of cerebral metastasis from an epithelioid malignant tumor of the peripheral nerve sheath.
Aneurysms of the vertebro-basilar junction area have been considered the most difficult to be surgically treated because of their deep location, the proximity of the brain stem and the cranial ...nerves. However, at present, new endovascular techniques and new transbasal surgical approaches offer valuable management strategies. This paper concerns six consecutive patients whom we managed either endovascularly or surgically during a period of eighteen months. Direct surgical treatment was offered to two young patients with relatively small aneurysms in good neurological condition, whereas the other four patients initially underwent an endovascular attempt at aneurysm obliteration using the Guglielmi detachable coil system. Unfortunately, interventional neuroradiology failed in three cases, and surgery had to be re-considered. Accordingly, a total of five patients underwent surgical clipping through the combination of a transmastoid retrolabyrinthine approach with the suboccipital lateral approach. This combination of approaches provided a good control of both vertebral arteries and basilar artery, and allowed the aneurysm to be correctly clipped in all cases. Good long-term results were achieved in all cases but one. Based on this preliminary experience, we would stress the importance of multidisciplinary approach with a treatment calibrated for each single case. Furthermore, if surgery is to be performed, the combination of transmastoid-retrolabyrinthine and suboccipital lateral approaches provides a wide exposure of the whole vertebro-basilar junction area and allows good access to the lesion.
Intracranial dermoid cysts are usually reported to be associated with long lasting or waxing-waning symptoms. Computer tomography (CT) scans usually depict such neoplasms as well-defined areas of low ...density. This report is about a case of a dermoid cyst, the acute clinical features and CT hyperdensity of which mimicked a hematoma in the posterior fossa. The association of acute onset with CT hyperdensity makes this case of dermoid cyst very unusual.
Juvenile pilocytic astrocytoma of the cerebellum has a benign course and a good prognosis. We report a case of juvenile cerebellar astrocytoma in a 6-year-old girl that underwent surgical resection ...of the tumor and had two recurrences, 13 and 35 years after first removal. After surgery the patient did not receive any radiation therapy. The last relapse showed histological features of an anaplastic astrocytoma. Six months later the patient died with a diffuse leptomeningeal dissemination. Late malignant transformation of a benign cerebellar astrocytoma is very rare and it is thought to be favored by postsurgical irradiation. The possible pathogenetic mechanisms of this evolution are discussed. This case and the few others reported in the literature emphasize the risk of an unpredictable outcome with the low-grade cerebellar astrocytomas of childhood.
Research on Neurofibromatosis (NF) has been directed at understanding what determines disease quiescence, exacerbation, and the possible malignant evolution. Studies on NF have examined the role of ...genetic oncosuppression in the evolution of the defence against the non-self. Paraffin fixed specimens of benign and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for the presence of p53: a reliable marker of genetic oncosupression. The wild type variant of p53 is expressed in malignant neoplasia, and is usually not expressed in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors and is practically absent in malignant tumors. Evidence of protein p53 in the various malignant neoplasias studied by our group seems to reflect the up-regulation on the oncosuppresive genetic potential that occurs while there is a lack of immunological defence. In the presence of an immunological defence, the expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution of the various neoplastic types here reported was the same as that reported by current clinical and experimental models: the cell's defective genes are no longer suppressed and after activation the genes undergo initiation, promotion, and the cell sustains inflammatory-immune reactions that lead to fibrosis; what follows is a variable period of apparent quiescence. Severe pathogenic stimuli may act on predisposed cells and deteriorate pre-existing genetic damage, casting the cell into a phase of dysplastic or neoplastic proliferation that overcomes the body's defences. Hope for future therapy lies in the development of drugs that can either mimic the immune system or the proteins encoded by the oncosuppressor genes.
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