The French national network dedicated to rare gynecological cancers diagnosis and management could improve the quality of surgery in daily practice of granulosa cell tumors. A TMRG and GINECO group Study.

OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs). METHODS: This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines. RESULTS: Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery. CONCLUSION: Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.

A tracking algorithm for cell motility assays in CMOS systems.

This work proposes a method for the study and real-time monitoring of a single cell on a 2D electrode matrix, of great interest in cell motility assays and in the characterization of cancer cell metastasis. A CMOS system proposal for cell location based on occupation maps data generated from Electrical Cell-substrate Impedance Spectroscopy (ECIS) has been developed. From experimental assays data, an algorithm based on the analysis of the eight nearest neighbours has been implemented to find the cell center of mass. The path followed by a cell, proposing a Brownian route, has been simulated with the proposed algorithm. The presented results give an accuracy over 95% in the determination of the coordinates (x, y) from the expected cell center of mass.

Delta-aminolevulinic acid dehydratase activity (ALA-D) in red mullet (Mullus barbatus) from Mediterranean waters as biomarker of lead exposure.

The enzyme delta-aminolevulinic acid dehydratase (ALA-D) has been investigated as biomarker of lead (Pb) exposure in red mullet (Mullus barbatus) from the Spanish continental shelf. Concentrations of Pb and Zn in muscle and organosomatic indices were also measured to explore causality. Blood ALA-D assay conditions were optimized; the optimum pH for this species has been set to 6.5. Results showed that ALA-D activity ranged from 3.2 to 16.9 nmol PBGmin(-1)mg(-1). No significant differences on ALA-D levels between genders have been detected. ALA-D Baseline level and Background Assessment Criteria (BAC) for this species have been set to 9.1 and 6.6 nmol PBGmin(-1)mg(-1), respectively. There have been detected significant differences on ALA-D activity levels among areas, though the markedly low levels of Pb measured in fish muscle seemed not to be able to produce a relevant suppression on ALA-D. In spite of this, a weak inverse relationship detected between ALA-D and Pb concentrations pointed out the potential of this biomarker in red mullet to reflect Pb bioavailability in marine environment. Nevertheless, subsequent research on ALA-D in marine fish species is recommended to be limited to areas where environmental Pb is effectively accumulated by fish.

Expression of epithelial markers by human umbilical cord stem cells. A topographical analysis.

INTRODUCTION: Human umbilical cord stem cells have inherent differentiation capabilities and potential usefulness in regenerative medicine. However, the epithelial differentiation capability and the heterogeneity of these cells have not been fully explored to the date. METHODS: We analyzed the expression of several undifferentiation and epithelial markers in cells located in situ in different zones of the umbilical cord -in situ analysis- and in primary ex vivo cell cultures of Wharton's jelly stem cells by microarray and immunofluorescence. RESULTS: Our results demonstrated that umbilical cord cells were heterogeneous and had intrinsic capability to express in situ stem cell markers, CD90 and CD105 and the epithelial markers cytokeratins 3, 4, 7, 8, 12, 13, 19, desmoplakin and zonula occludens 1 as determined by microarray and immunofluorescence, and most of these markers remained expressed after transferring the cells from the in situ to the ex vivo cell culture conditions. However, important differences were detected among some cell types in the umbilical cord, with subvascular zone cells showing less expression of stem cell markers and cells in Wharton's jelly and the amnioblastic zones showing the highest expression of stem cells and epithelial markers. CONCLUSIONS: These results suggest that umbilical cord mesenchymal cells have intrinsic potential to express relevant epithelial markers, and support the idea that they could be used as alternative cell sources for epithelial tissue engineering.

Heterogeneous distribution of polycyclic aromatic hydrocarbons in surface sediments and red mullet along the Spanish Mediterranean coast.

The spatial distribution of polycyclic aromatic hydrocarbon (PAH) concentrations was characterised in surface sediments and red mullet from eleven Iberian Mediterranean coastal areas. Mean PAH concentrations ranged from 28 to 1006 and from 3 to 40 µg kg(-1)d.w. in sediment and red mullet muscle, respectively. The highest PAH concentrations in sediments were detected close to main ports and urban nuclei. However, concentrations of PAHs in red mullet showed little correspondence with PAH concentrations of the sediments due to its metabolic capacity. Phenanthrene was the predominant homologue in red mullet, whereas fluoranthene, pyrene and benzo(b)fluoranthene were the most abundant ones in sediments. Significant correlations between PAHs and organic carbon or fine fraction in sediments were only found in some areas. PAH concentrations in sediments were lower than environmental criteria in the majority of cases, except for benzo(g,h,i)perylene in 25% of samples from the Barcelona coastal area and for several homologues close to the port of Sagunto.

Effects of water accommodated fractions of crude oils and diesel on a suite of biomarkers in Atlantic cod (Gadus morhua).

The aim of this study was to characterize concentration- and time-dependent responses in juvenile Atlantic cod (Gadus morhua) following exposure for one and three weeks to the water-soluble fraction (WAF) of three weathered oils: Arabian Light crude oil (ALC), North Sea crude oil (NSC) and ship-diesel. The sum of polycyclic aromatic hydrocarbons (PAH) in water was highest after one week of exposure and within environmentally relevant concentrations. PAH metabolites in bile confirmed exposure to and uptake of PAHs. Hepatic cytochrome P450 1A (CYP1A) gene expression (mRNA quantification) increased dramatically following exposure to all three oil types (fold-change up to 165) and there was a time lag between gene and protein expression. Hepatic CYP1A protein concentration and ethoxyresorufin-O-deethylase (EROD) activity were more variable among individuals and treatments than gene expression. EROD activity in liver and gills increased in fish exposed to WAF from the two crude oils, but not in fish exposed to WAF from diesel. Exposure to diesel appeared to induce oxidative stress to a greater extent than exposure to crude oils. Other biomarkers (glutathione S-transferases, acetylcholine esterase, vitellogenin) did not appear to respond to the exposure and hence did not discriminate among oils. Biomarker responses in cod after exposure to weathered crude oils and diesel suggested that the CYP1A system and oxidative stress markers have the highest potential for discriminating among different oil types and to monitor the environmental consequences of spills.

Spatial distribution and temporal trends of polycyclic aromatic hydrocarbons in Mytilus galloprovincialis from the Iberian Mediterranean coast.

Polycyclic aromatic hydrocarbons (PAHs) have been determined in blue mussels (Mytilus galloprovincialis) from several Iberian Mediterranean coastal areas through the implementation of a monitoring programme from Spain in the framework of the Mediterranean Pollution Programme (MED POL). The selected areas correspond to sites with differing degrees of exposure to the main pollution sources (hot spots, coastal and reference areas). The sampling campaigns were performed from 2004 to 2009, with samples being taken from May to June, the non-spawning period for mussels in this area. Thirteen PAHs were determined by high-performance liquid chromatography with specific fluorescence detection. In general, total PAHs concentration was lower than 50 µg kg(-1) d.w., except in areas close to the principal ports and cities (Barcelona, Tarragona, Valencia and Algeciras) where it varies from 75 to 390 µg kg(-1) d.w. Background concentrations have been proposed for PAHs in mussels (23.8 µg kg(-1) d.w.) from Western Mediterranean area. Temporal trends were not statistically significant for PAHs concentrations from 2004 to 2009. Longer monitoring periods would be required to detect a continuous tendency, especially for PAHs because although the efficiency of combustion engines has reduced PAHs emissions, their increasing use could alter this potential reduction. The predominant PAHs were three and four ring congeners in all cases, with the predominance of phenanthrene in mussels sited far from the main PAHs sources. The phenanthrene/anthracene (lower than 10) and fluoranthene/pyrene (higher than 1) ratios indicate that PAHs detected in Spanish Mediterranean coastal mussels are mainly of pyrolytic origin.

Antioxidant responses in gills of mussel (Mytilus galloprovincialis) as biomarkers of environmental stress along the Spanish Mediterranean coast.

Antioxidant response was used to assess the effects of the main pollutants in wild mussels (Mytilus galloprovincialis) along the Mediterranean coast of Spain. Antioxidant enzyme activities - those of catalase, superoxide dismutase, glutathione peroxidases, glutathione reductase, glutathione S-transferase and DT-diaphorase - as well as lipid peroxidation and metallothionein concentrations were measured in gills of mussels from 16 selected sites. Furthermore, concentrations of the main contaminants (Hg, Pb, Cd, Cu, Zn, As, PAH, PCB, and DDT) were quantified in mussel tissue, and environmental parameters were measured in water samples collected at each site. Results showed that the glutathione-dependent antioxidant enzymes offered an increased and coordinated response against metal (Hg, Pb and Cd) contamination. These enzymatic activities correlated positively to temperature, suggesting the influence of this environmental parameter on antioxidant responses in gill tissues. Furthermore, although temperature did not reach stressful levels in the study area, it seemed to add a synergistic effect to that produced by metals to induce antioxidant enzymes in the most metal-polluted sites. Catalase activity appeared to be involved in a different antioxidant pathway, more related to organic pollutant bioaccumulation, offering an efficient protection mechanism against reactive oxygen species generation due both to organic exposure and high physiological activity, reflected by high condition indices. In general terms, increased levels of antioxidant enzymes at some sites suffering from metal and organic pollution indicated a situation of oxidative stress that nevertheless did not appear to be harmful, since lipid peroxidation levels showed no peroxidative damage in gill tissues of mussels collected from even the most heavily polluted sites. On the other hand, metallothionein and DT-diaphorase did not reflect pollutant exposure and seemed to be more influenced by environmental variables than by the pollutants.

Evaluation of three-year monitoring with biomarkers in fish following the Prestige oil spill (N Spain).

A previous study using a suite of hepatic enzymatic biomarker in two demersal fish species (Lepidorhombus boscii and Callionymus lyra) indicated exposure of the fish to the hydrocarbons in the oil spilled by the Prestige five months after the accident. The main objective of this follow-up study is to determine whether the same biomarkers in both fish species show any significant variations in responses over the years following the Prestige oil spill. Detoxification and antioxidant enzyme measurements--of ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), glutathione reductase (GR) and catalase (CAT)--were taken from immature specimens. The results show significant lowering of biomarker activity two and three-years after the oil spill, indicating a decreasing level of exposure of the fish to residual hydrocarbons associated with the spillage (p < 0.01) and a recovery to baseline levels existing before the accident. Overall, spatial biomarker patterns over time are in agreement with the oil slick trajectories and the spatial distribution of tar aggregates found on the bottom shelf after the accident. The results also indicate that the Prestige oil spill had an impact on sublethal responses in fish not only in inshore areas, but also in offshore areas along the middle/outer northern Iberian shelf. In both species, EROD activity was found to be the most discriminating biomarker.

Síndrome metabólico en pacientes tratados con antipsicóticos de segunda generación en monoterapia / Metabolic syndrome in patients treated with second-generation antipsychotic medication monotherapy

Introducción: El objetivo de este trabajo es determinarla presencia de síndrome metabólico en pacientes atratamiento con nuevos antipsicóticos y comprobar quétratamiento reciben con el fin de corregir estas alteracionesmetabólicas.Métodos: Son seleccionados 44 pacientes en una unidadde salud mental, con diagnósticos de patologíasmentales diversos. Se diagnostican de síndrome metabólicosegún los criterios de la ATP-III.Resultados: Cumple criterios diagnósticos para síndromemetabólico un 25% de los pacientes incluidos enel estudio. Al menos el 80% de los pacientes con algunaalteración metabólica no recibe el tratamiento adecuado.Conclusiones: En caso de evidenciarse datos similaresen muestras de este tipo de población, implicaría lanecesidad de aplicar protocolos de tratamiento paramejorar la salud física de pacientes

Introduction: The aim of this study is to clarify thepresence of metabolic syndrome in patients treated withsecond-generation antipsychotic medication and tocheck what therapy they are having for these metabolicabnormalities.Methods: 44 patients at a mental health unit areincluded, with different mental disorders diagnosis.They are diagnosed with metabolic syndrome accordingto ATP-III diagnostic criteria.Results: Among the patients included in the study25% conform to the metabolic syndrome diagnostic criteria.At least 80% of the patients with some metabolicabnormality are not being appropriately treated.Conclusions: These data would imply the need toapply treatment guidelines In case of evidence of similardata in the same kind of population samples toimprove patients’ physic health (AU)

Monitoring biomarkers in fish (Lepidorhombus boscii and Callionymus lyra) from the northern Iberian shelf after the Prestige oil spill.

Hepatic biomarker responses were measured in two demersal fish species (Lepidorhombus boscii and Callionymus lyra) from the northern Iberian shelf associated with the massive Prestige oil spill (POS), five months after the accident. The biomarkers selected were 7-ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT), and DNA integrity. Interspecies differences and spatial variations in biomarker responses were observed along the shelf. GST, GR and CAT activities were significantly elevated in L. boscii in the most oil impacted area (Finisterre) and positively correlated (p<0.05) with POS tar aggregate densities. The lack of previous data from the area together with the existence of chronic background pollution of the shelf implies that the observed biomarker responses cannot be solely attributed to the petroleum hydrocarbon components of the spilled oil. This first biological effect assessment showed that L. boscii is a potentially suitable target species to be used in future biomonitoring programmes along the northern Iberian shelf.

Psiquiatría en la comunidad: teoría y práctica / Community psychiatry: theory and practice

Se hace una breve revisión histórica del desarrollo de la psiquiatría que termina con las modernas cocepciones de una práctica psiquiátrica estrechamente vinculada a la comunidad, en la que se aplican los últimos adelantos de la ciencia en la especialidad. Se hace un análisis crítico de los diferentes modelos de psiquiatría en la comunidad. Se describe a grandes rasgos la evolución de la psiquiatría en Cuba, y se enfatiza en las etapas posteriores a 1959; se concluye con la descripción de los diferentes modelos de psiquiatría en la comunidad aplicados actualmente en Cuba, y se analizan las posibilidades de su aplicación por el sistema nacional de salud dentro de los marcos de la medicina en la comunidad (AU)