Paired Primary and Recurrent Rhabdoid Meningiomas: Cytogenetic Alterations, BAP1 Gene Expression Profile and Patient Outcome.

Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients.

Clinical, Histopathologic and Genetic Features of Rhabdoid Meningiomas.

Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.

Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas.

Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for ≈50% of all recurrent meningiomas. Currently, limited data exist about the mutational profiles of grade 1 meningiomas and patient outcome. We investigated the genetic variants present in 32 WHO grade 1 meningiomas using whole exome sequencing, and correlated gene mutational profiles with tumor cytogenetics and patient outcome. Overall, WHO grade 1 meningiomas harbored numerous and heterogeneous genetic variants, which most frequently affected the NF2 (47%) gene and to a less extent the PNMA6A (22%), TIGD1 (16%), SMO (13%), PTEN (13%), CREG2 (9%), EEF1A1 (6%), POLR2A (6%), ARID1B (3%), and FAIM3 (3%) genes. Notably, non-synonymous genetic variants of SMO and POLR2A were restricted to diploid meningiomas, whereas NF2 mutations were only found among tumors that showed -22/22q─ (with or without a complex karyotype). Based on NF2 mutations and tumor cytogenetics, four genetic profiles were defined with an impact on patient recurrence-free survival (RFS). These included (1) two good-prognosis tumor subgroups-diploid meningiomas (n=9) and isolated -22/22q─ associated with NF2 mutation (n=7)-with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas-isolated -22/22q─ without NF2 mutation (n=3) and tumors with complex karyotypes (n=11)-with a RFS rate at 10 y of 48% (p=0.003). Our results point out the existence of recurrent but heterogeneous mutational profiles in WHO grade 1 meningiomas which have an impact on patient outcome.

[Spanish Norms for Mini-SEA (Mini Social Cognition and Emotional Assessment) in adults in Buenos Aires]. / Baremos en español del Mini-SEA (Mini Social Cognition and Emotional Assessment) en adultos normales de Buenos Aires.

INTRODUCTION AND OBJECTIVE: The Mini-SEA is a quick and brief cognitive assessment test developed to study social cognition. It consists of a modified version of the faux pas Test and an emotional recognition test based on Ekman's faces. The objective of this work was to obtain the first Spanish Speaking norms for the Mini-SEA test. MATERIAL AND METHODS: 64 healthy volunteers, between 35 and 80 years old, were recruited and evaluated with the Mini-SEA by specialized neuropsychologists from the Cities of Buenos Aires and La Plata, both in the Province of Buenos Aires, Argentina. RESULTS: The total mean (M) of the Mini-SEA was 25 +/- 4. The M of the faux pas Score was 12.5 +/- 2.4 and the M of the Emotional Recognition Score was 12.8 +/- 1.5. The sample was divided into 4 age groups: Group 1 (<50 years), Group 2 (50-59 years), Group 3 (60-69 years) and Group 4 (more than 70 years). Differences were found in the age continuum in the Emotional Recognition score between group 1 and 4 (p <0.05) and between group 3 and 4 (p <0.01), but not in the Faux Pas Score. CONCLUSION: This study presents the first normative values of the Mini-SEA Social Cognition test for a Spanish-speaking population. The Mini-SEA, being a quick and easy to administer test, allows the study of social cognition in an adequate and precise way, especially in prodromal stages of neurodegenerative diseases.

Bioconversion by gut microbiota of predigested mango (Mangifera indica L) 'Ataulfo' peel polyphenols assessed in a dynamic (TIM-2) in vitro model of the human colon.

Gut microbiota bioconversion of polyphenols in predigested mango 'Ataulfo' peel was studied using a validated, dynamic in vitro human colon model (TIM-2) with faecal microbial inoculum. Dried peels were predigested with enzymatic treatment, followed by TIM-2 fermentation (72 h). Samples were taken at 0, 24, 48 and 72 h and analyzed by HPLC-QToF. Derivatives of hydroxyphenylpropionic, hydroxyphenylacetic and hydroxybenzoic acids, as well as, pyrogallol were the main polyphenols identified. These metabolites might derivate from flavonoid (flavanols and flavonols), gallate and gallotannin biotransformation. Despite the high content of ellagic acid in mango peel, low amounts were detected in TIM-2 samples due to transformation into urolythins A and C, mainly. Xanthone and benzophenone derivatives, specific to mango, remained after the colonic biotransformation, contrary to flavonoids, which completely disappeared. In conclusion, microbial-derived metabolites, such as xanthone and benzophenone derivatives, among others, are partially stable after colonic fermentation, and thus have the potential to contribute to mango peel bioactivity.

Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome.

The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAP+ CD45- ) tumor and normal astrocytic cells, infiltrating myeloid cells -i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)- and tumor-infiltrating lymphocytes (TIL) -i.e. CD3+ T-cells and their TCD4+ , TCD8+ , TCD4- CD8- , and (CD25+ CD127lo ) regulatory (T-regs) subsets, (CD19+ CD20+ ) B-cells, and (CD16+ ) NK-cells-. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4+ (0.5% ± 0.7%) and TCD8+ cells (0.6% ± 0.7%), together with lower numbers of TCD4- CD8- T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.

Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283.

BACKGROUND: Glioblastoma is the most aggressive primary brain tumour and has a very poor prognosis. Inhibition of c-Src activity in glioblastoma stem cells (GSCs, responsible for glioblastoma lethality) and primary glioblastoma cells by the peptide TAT-Cx43266-283 reduces tumorigenicity, and boosts survival in preclinical models. Because c-Src can modulate cell metabolism and several reports revealed poor clinical efficacy of various antitumoral drugs due to metabolic rewiring in cancer cells, here we explored the inhibition of advantageous GSC metabolic plasticity by the c-Src inhibitor TAT-Cx43266-283. METHODS: Metabolic impairment induced by the c-Src inhibitor TAT-Cx43266-283 in vitro was assessed by fluorometry, western blotting, immunofluorescence, qPCR, enzyme activity assays, electron microscopy, Seahorse analysis, time-lapse imaging, siRNA, and MTT assays. Protein expression in tumours from a xenograft orthotopic glioblastoma mouse model was evaluated by immunofluorescence. FINDINGS: TAT-Cx43266-283 decreased glucose uptake in human GSCs and reduced oxidative phosphorylation without a compensatory increase in glycolysis, with no effect on brain cell metabolism, including rat neurons, human and rat astrocytes, and human neural stem cells. TAT-Cx43266-283 impaired metabolic plasticity, reducing GSC growth and survival under different nutrient environments. Finally, GSCs intracranially implanted with TAT-Cx43266-283 showed decreased levels of important metabolic targets for cancer therapy, such as hexokinase-2 and GLUT-3. INTERPRETATION: The reduced ability of TAT-Cx43266-283-treated GSCs to survive in metabolically challenging settings, such as those with restricted nutrient availability or the ever-changing in vivo environment, allows us to conclude that the advantageous metabolic plasticity of GSCs can be therapeutically exploited through the specific and cell-selective inhibition of c-Src by TAT-Cx43266-283. FUNDING: Spanish Ministerio de Economía y Competitividad (FEDER BFU2015-70040-R and FEDER RTI2018-099873-B-I00), Fundación Ramón Areces. Fellowships from the Junta de Castilla y León, European Social Fund, Ministerio de Ciencia and Asociación Española Contra el Cáncer (AECC).

Multivariate analysis reveals differentially expressed genes among distinct subtypes of diffuse astrocytic gliomas: diagnostic implications.

Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas-33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)-based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II-III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes.

Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival.

BACKGROUND: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. METHODS: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. RESULTS: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). CONCLUSIONS: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.

[Emotional valence effect on prospective memory in relapsing remitting Multiple Sclerosis]. / Efecto de valencia emocional sobre la memoria prospectiva en pacientes con esclerosis múltiple recaídas y remisiones.

INTRODUCTION: prospective memory is the ability to remember to perform actions in the future. Currently there is no consensus about the relationship between prospective memory and emotional processing. OBJECTIVE: The aim of this work is to determine the influence of the emotional valence of prospective memory signals on prospective recall in patients diagnosed with multiple sclerosis. METHOD: 37 patients with multiple sclerosis and 32 healthy volunteers were recruited. An experimental test was made where the concurrent task consisted in a 2-back working memory activity and the prospective component consisted of remembering to press a key on the computer when an image of positive, negative or neutral emotional content appears on the screen. RESULTS: An intra-group comparison was made between the memory of emotional and neutral stimuli, and it was obtained that the differences are significant in both groups in favor of the recall of stimuli with neutral valence (Z = -3.39, p = .001 for the control group and Z = -2.63, p = .008 for multiple sclerosis). DISCUSSION: The results indicate that emotionally neutral target stimuli benefits prospective memory in normal people and in multiple sclerosis patients. The limitations of the implemented method are discussed.

In vitro and in vivo testing of the hypocholesterolemic activity of ergosterol- and ß-glucan-enriched extracts obtained from shiitake mushrooms (Lentinula edodes).

Herein, a supercritical extraction plant (with a 6 L extraction cell) was successfully used to obtain ergosterol-enriched extracts from Lentinula edodes under the following conditions: a temperature of 40 °C, pressure of 225 bar, reaction time of 1-5 h, and the flow rate of 20 L h-1 for recirculated CO2. Moreover, ergosterol (ERG) and the SFE extract (SFE) with highest ergosterol concentration were microemulsified and submitted to in vitro digestion to study their ability to displace cholesterol from dietary mixed micelles (DMMs). ERG was also mixed with a ß-glucan-enriched (33.5%) extract (BGE) obtained from L. edodes to investigate the synergies between them; the results indicated that all these extracts (including BGE without ERG) could reduce the cholesterol levels in the DMMs. However, when ERG and SFE were simultaneously administered to mice with a hypercholesterolemic diet, no significant differences in the serum cholesterol levels were detected as compared to the case of the control. However, when only BGE was administrated to another mice model previously induced with hypercholesterolemia, significant reduction in the cholesterol levels was noticed.

Effect of traditional and modern culinary processing, bioaccessibility, biosafety and bioavailability of eritadenine, a hypocholesterolemic compound from edible mushrooms.

Eritadenine is a hypocholesterolemic compound that is found in several mushroom species such as Lentinula edodes, Marasmius oreades, and Amanita caesarea (1.4, 0.7 and 0.6 mg per g dry weight, respectively). It was synthesized during all developmental stages, being present in higher concentrations in the skin of shiitake fruiting bodies. When subjected to traditional cooking, grilling followed by frying were more adequate methodologies than boiling or microwaving to maintain its levels. Modern culinary processes such as texturization (with agar-agar) and spherification (with alginate) also interfered with its release. Grilling and gelling using gelatin enhanced eritadenine's bioaccessibility in an in vitro digestion model. An animal model (where male and female rats were administered 21 and 10 mg per kg animal per day of eritadenine) indicated that intake of the compound was safe under these concentrations; it reached the liver and reduced the atherogenic index (TC/HDL) in rat sera. Thus, it might be used to design a functional food.

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles.

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.

Relevancia de la escala de Simpson en la resección de meningiomas de grado I de la OMS / Relevance of Simpson's grading system for resections in WHO grade I meningiomas

Objetivo: Evaluar si las tasas de recurrencia y las supervivencias libres de recurrencia/progresión (RFS) son diferentes en meningiomas de grado I de la Organización Mundial de la Salud (OMS) sometidos a resecciones grado I, II, III y IV de la escala de Simpson. Materiales y métodos: Revisamos de manera retrospectiva los datos de los pacientes que se sometieron a tratamiento quirúrgico de meningiomas de grado I de la OMS localizados en la convexidad, hoz/parasagital y base de cráneo entre junio de 1991 y diciembre de 2011. En el caso de las resecciones grado IV de Simpson la cirugía se complementó con radiocirugía o radioterapia sobre el resto tumoral. Comparamos las tasas de recurrencia y las RFS de los diferentes grados de Simpson tanto de manera global como por localización. Resultados: En el estudio se incluyeron 208 meningiomas. No existieron diferencias significativas en las tasas de recurrencia y en las RFS entre los diferentes grados de Simpson. Por localización, tampoco detectamos diferencias entre los grados de resección. En meningiomas de convexidad, las tasas de recurrencia en los grados I y III fueron del 7 y del 33%, respectivamente (p=0,131). Conclusiones: Este estudio sugiere que las tasas de control tumoral son independientes de los grados de Simpson. En meningiomas de hoz/parasagital y de base de cráneo debe valorarse la agresividad quirúrgica frente a los riesgos de lesionar estructuras neurovasculares. En meningiomas de convexidad, el objetivo inicial debería ser una resección grado I

Object: The aim of this study is to assess if the recurrence rates and recurrence/progression-free survivals (RFS) are different after Simpson's grades I, II, III and IV resections in World Health Organization (WHO) grade I meningiomas. Material and methods: A retrospective review was conducted on the data of patients who underwent surgical treatment of WHO grade I meningiomas located in convexity, falx/parasagittal, and skull base (anterior/media/posterior) between June 1991 and December 2011. In Simpson's grade IV resections, surgical treatment was supplemented with radiotherapy/radiosurgery on the tumour remains. A comparison was made on the recurrence rates and RFSs between Simpson's grades I, II, III, and IV resections, both overall and in tumour subsets according to their location. Results: A total of 208 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson's grades I, II, III, and IV. No significant differences were noted between the different degrees of Simpson in any of the location groups. In convexity meningiomas, the recurrence rates were 7% and 33% in Simpson's grades I and III resections, respectively (P=.131). Conclusions: It has been shown that the rates of tumour control in meningiomas are not related to Simpson grades. In falx/parasagittal and skull base meningiomas, more aggressive attempts of tumour resection must be balanced against the risks of damaging critical neurovascular structures. In convexity meningiomas, a Simpson's grade I resection should be attempted first

[Relevance of Simpson's grading system for resections in WHO grade I meningiomas]. / Relevancia de la escala de Simpson en la resección de meningiomas de grado I de la OMS.

OBJECT: The aim of this study is to assess if the recurrence rates and recurrence/progression-free survivals (RFS) are different after Simpson's grades I, II, III and IV resections in World Health Organization (WHO) grade I meningiomas. MATERIAL AND METHODS: A retrospective review was conducted on the data of patients who underwent surgical treatment of WHO grade I meningiomas located in convexity, falx/parasagittal, and skull base (anterior/media/posterior) between June 1991 and December 2011. In Simpson's grade IV resections, surgical treatment was supplemented with radiotherapy/radiosurgery on the tumour remains. A comparison was made on the recurrence rates and RFSs between Simpson's grades I, II, III, and IV resections, both overall and in tumour subsets according to their location. RESULTS: A total of 208 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson's grades I, II, III, and IV. No significant differences were noted between the different degrees of Simpson in any of the location groups. In convexity meningiomas, the recurrence rates were 7% and 33% in Simpson's grades I and III resections, respectively (P=.131). CONCLUSIONS: It has been shown that the rates of tumour control in meningiomas are not related to Simpson grades. In falx/parasagittal and skull base meningiomas, more aggressive attempts of tumour resection must be balanced against the risks of damaging critical neurovascular structures. In convexity meningiomas, a Simpson's grade I resection should be attempted first.

Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries.

Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy.

Re-Evaluating Simpson Grade I, II, and III Resections in Neurosurgical Treatment of World Health Organization Grade I Meningiomas.

BACKGROUND: Since 1957, the Simpson grading system has been considered a predictive system for meningioma recurrence. However, since then, surgical equipment and neurosurgical technique have developed extensively, so this grading system should be re-evaluated. This study aims to assess if the recurrence rate and recurrence-free survival (RFS) are different after Simpson grade I, II, and III resections in World Health Organization (WHO) grade I meningiomas. METHODS: We retrospectively reviewed the data of patients who underwent surgical treatment of WHO grade I meningiomas located in the convexity (group 1), falx/parasagittal (group 2), skull base, and tentorium (group 3) between June 1991 and December 2011. We compared the recurrence rates and RFSs between Simpson grade I, II, and III resections in both overall cases and tumor subsets according to their localization. RESULTS: A total of 224 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson grades I, II, and III. In each of the location groups, no significant differences were noted between the different degrees of Simpson. CONCLUSIONS: We have shown that complete resection of WHO grade I meningiomas achieves excellent tumor control, regardless of Simpson grades. More aggressive attempts at tumor resection (ie, Simpson grade I) must be balanced against the risks of removing dura or damaging critical neurovascular structures.

Solid phase microextraction and gas chromatography-mass spectrometry methods for residual solvent assessment in seized cocaine and heroin.

A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.

Reconocimiento facial de emociones básicas y su relación con la teoría de la mente en la variante conductual de la demencia frontotemporal / Recognition of basic emotion and their relation with theory of mind in the behavioral variant of frontotemporal dementia

Las emociones básicas están biológicamente determinadas y ligadas a conductas fundamentales para la supervivencia. Las emociones secundarias son aquellas que para su reconocimiento, requieren la elaboración cognitiva de un contexto social, por lo tanto, de la Teoría de la Mente (TdM). La TdM fue definida como la habilidad de conceptualizar estados mentales de otros individuos para explicar y predecir gran parte de su comportamiento. No es un concepto unitario, existen disociaciones entre los componentes cognitivo y el emocional de la TdM. Han sido establecidas las alteraciones en el reconocimiento facial de emociones básicas (RFEB) y en las tareas de TdM en la variante conductual de la demencia frontotemporal (DFTvc). El objetivo del trabajo que se informa fue estudiar el reconocimiento de emociones básicas o primarias y su relación con la TdM en pacientes con DFTvc. El 81% de los pacientes mostró alteraciones en por lo menos uno de los tests de RFEB y el 35% en el reconocimiento de la prosodia emocional. El subtest Denominación y el Puntaje Total Emociones mostraron correlaciones con el Test Lectura de la Mente en los Ojos, mientras que todas las tareas de RFEB correlacionaron con la tarea de falsa creencia. Se encontraron dobles disociaciones entre TdM emocional y cognitiva, con mayor afectación del componente emocional. Como conclusión se corrobora la presencia de alteraciones en el RFEB con prosodia emocional conservada en la DFTvc. La ausencia de correlaciones entre emociones básicas y secundarias parecería indicar que se trata de procesos independientes entre sí.

Behavioral variant of frontotemporal dementia (bvFTD) is associated with dramatic changes in personality. The behavioral manifestations that show these patients may be due, to one hand, to abnormal emotional processing as a result of the anatomical regions concerned, and on the other, to alterations in Theory of Mind (ToM). Basic emotions are biologically determined. Joy, sadness, anger, disgust and fear are the emotional states that have received most agreement. ToM allows representing, inferring and interpreting mental and emotional states of others. It has been suggested that it is not a unitary concept. Cognitive Theory of Mind refers to the representations regarding the cognitive status of others. Affective ToM refers to the representation of emotional and motivational states. The objectives were to study the presence of alterations in the recognition of basic emotions in the face and voice in patients with bvFTD, aswell as examine the relation ships that exist between the recognition of basic emotions and TdM, to know if there are, or not, independent processes. To study, finally, the presence of dissociations between emotional and cognitive ToM, to know which one of these types of ToM shows greater alteration in our population. 26 bvFTD patients were assessed, diagnosed on the basis of the criteria proposed by the International Consortium Behavioral Variant FTD Criteria, and 23 control subjects. A battery for facial recognition of basic emotions (FRBE) was administered, selecting 60 photographs of the Pictures of Facial Affect. Three tasks were created, comprising 60 sheets each, 10 forevery basic emotion. A test for recognition of emotional prosody was also administered. Among the ToM tests were Reading the Mind in the Eyes (RME), Faux Pas, and Firs Order False Belief Task (FOFBT). 81% of the patients showed alterations in at least one of the tests RFEB, and 35% in emotional prosody recognition. All RFEB tasks showed a significantly moderate statistical correlation with the emotional prosody task. The Naming subtest and the Total Emotions Score (RFEB) showed correlations with RME test, while all tasks RFEB correlated with FC1ºO. Finally, 10 simple dissociations between altered FRBE and preserved emotional prosody were found, and double dissociations between emotional and cognitive ToM, with greater impairment of the emotional component of ToM Discussion: A decreased performance is corroborated in the bvFTD patients group, relative to a control group, in all FRBE tasks. The recognition of emotional prosody is preserved. The presence of correlations between RME and all FRBE tasks may be explained by the neuropsychological structure of the tasks. The correlations found between RME and under standing of emotional prosody may be due to the fact that both tests assess emotional comprehension. As for the correlations found between FC1ºO and all FRBE tasks, taking into account that there seems to be no bibliographic outcome regarding to this correlation, that the neuropsychological tasks structure is completely different, and that FC1ºO showed no correlations with the emotional prosody task, it seems not possible for us to explain this result, leaving open the possibility for the development of a acceptable conclusion. Because of the absence of significant correlations between all of the recognition of basic and complex emotions tasks, we infer that the basic emotions are a qualitatively different kind of emotional state that secondary emotions, this lasts ones processed through ToM.