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7a-(Methoxycarbonyl)- N -methyl-1,3a,5,6,7,7a-hexahydro-4 H -1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn - and anti -alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn -stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process. Additionally, several functional 2,8-ethanonoradamantane derivatives have been prepared., Competing Interests: The authors declare no conflict of interest.

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes., Competing Interests: Conflicts of interest: None declared.

The gas phase atmospheric degradation of pirimiphos-methyl (a widely used organophosphate insecticide and acaricide in many European regions) has been investigated at the large outdoor European Photoreactor (EUPHORE) in Valencia, Spain. Its photolysis has been studied under sunlight conditions and its reaction rate constant with OH radicals was measured by the relative rate method. The reaction with ozone was also investigated. The tropospheric degradation of pirimiphos-methyl is controlled mainly by the OH radical reaction. The rate coefficient of the OH reaction with pirimiphos-methyl, k, was measured by a conventional relative rate technique, where aniline was taken as a reference. The resulting value of the OH reaction rate constant with pirimiphos-methyl was k=(1.14±0.2)×10 -10 cm 3 molecule -1 s -1 . The tropospheric lifetime of pirimiphos-methyl with respect to the reaction with OH radicals was estimated to be around 1.6h (283±10) K and atmospheric pressure. Significant aerosol formation was observed in the OH reaction with yields that ranged from 25 to 37%, and with particle diameters below 550nm. This therefore reveals a high human risk due to PM<1, without taking into account the chemical composition of the degradation products. SO 2 , glyoxal and other oxygenated and nitrogenated compounds were the main degradation products detected., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Knowledge of ovine mesenchymal stromal cells (oMSCs) is currently expanding. Tissue engineering combining scaffolding with oMSCs provides promising therapies for the treatment of osteochondral diseases., Purpose: The aim was to isolate and characterize oMSCs from bone marrow aspirates (oBMSCs) and to assess their usefulness for osteochondral repair using β-tricalcium phosphate (bTCP) and type I collagen (Col I) scaffolds., Methods: Cells isolated from ovine bone marrow were characterized morphologically, phenotypically, and functionally. oBMSCs were cultured with osteogenic medium on bTCP and Col I scaffolds. The resulting constructs were evaluated by histology, immunohistochemistry and electron microscopy studies. Furthermore, oBMSCs were cultured on Col I scaffolds to develop an in vitro cartilage repair model that was assessed using a modified International Cartilage Research Society (ICRS) II scale., Results: oBMSCs presented morphology, surface marker pattern and multipotent capacities similar to those of human BMSCs. oBMSCs seeded on Col I gave rise to osteogenic neotissue. Assessment by the modified ICRS II scale revealed that fibrocartilage/hyaline cartilage was obtained in the in vitro repair model., Conclusions: The isolated ovine cells were demonstrated to be oBMSCs. oBMSCs cultured on Col I sponges successfully synthesized osteochondral tissue. The data suggest that oBMSCs have potential for use in preclinical models prior to human clinical studies., Competing Interests: The authors have declared that no competing interests exist.

We have analyzed the effects of different native membrane lipid composition on the thermodynamic properties of the Na + -K + -ATPase in different epithelia from the gilthead seabream Sparus aurata . Thermodynamic parameters of activation for the Na + -K + -ATPase, as well as contents of lipid classes and fatty acids from polar lipids were determined for gill epithelia and enterocytes isolated from pyloric caeca, anterior intestine and posterior intestine. Arrhenius analyses of control animals revealed differences in thermal discontinuity values ( Td ) and activation energies determined at both sides of Td between intestinal and gill epithelia. Eyring plots disclosed important differences in enthalpy of activation (Δ H ‡ ) and entropy of activation (Δ S ‡ ) between enterocytes and branchial cells. Induction of n-3 LCPUFA deficiency dramatically altered membrane lipid composition in enterocytes, being the most dramatic changes the increase in 18:1n-9 (oleic acid) and the reduction of n-3 LCPUFA (mainly DHA, docosahexaenoic acid). Strikingly, branchial cells were much more resistant to diet-induced lipid alterations than enterocytes, indicating the existence of potent lipostatic mechanisms preserving membrane lipid matrix in gill epithelia. Paralleling lipid alterations, values of Ea 1 , Δ H ‡ and Δ S ‡ for the Na + -K + -ATPase were all increased, while Td values vanished, in LCPUFA deficient enterocytes. In turn, Differences in thermodynamic parameters were highly correlated with specific changes in fatty acids, but not with individual lipid classes including cholesterol in vivo . Thus, Td was positively related to 18:1n-9 and negatively to DHA. Td, Ea 1 and Δ H ‡ were exponentially related to DHA/18:1n-9 ratio. The exponential nature of these relationships highlights the strong impact of subtle changes in the contents of oleic acid and DHA in setting the thermodynamic properties of epithelial Na + -K + -ATPase in vivo . The effects are consistent with physical effects on the lipid membrane surrounding the enzyme as well as with direct interactions with the Na + -K + -ATPase.

Aim: The aim of this study was to evaluate proliferation and chondrogenic differentiation of human bone-marrow mesenchymal stromal cells (hBMSCs) cultured on collagen biomaterials., Materials and Methods: hBMSCs were seeded on five different collagen (Col) sponges: C1C2 (types I and II Col), C1C2HS (types I and II Col plus heparan sulphate (HS)), C1C2CHS (types I and II Col plus chondroitin sulphate (CHS)), C1-OLH3 (type I Col plus low molecular weight heparin) and C1CHS (type I Col plus CHS). The resulting constructs were analyzed by histological and immunohistochemical staining, molecular biology and electron microscopy. Col released into culture media was measured by a dye-binding method Results: hBMSCs on biomaterials C1C2, C1C2HS and C1C2CHS had more capacity to attach, proliferate and synthesize Col II and proteoglycans in the extracellular matrix (ECM) than on C1-OLH3 and C1CHS. The presence of aggrecan was detected only at the gene level. Total Col liberated by the cells in the supernatants in all scaffold cultures was detected. The level of Col I in the ECM was lower in C1-OLH3 and that of Col II was highest in C1C2 and C1C2HS. Electron microscopy showed differently shaped cells, from rounded to flattened, in all constructs. Col fibers in bundles were observed in C1C2CHS by transmission electron microscopy., Conclusions: The results show that Col I and Col II (C1C2, C1C2HS and C1C2CHS) biomaterials allowed cell proliferation and chondrogenic-like differentiation of hBMSCs at an early stage. Constructs cultured on C1C2HS and C1C2CHS showed better cartilage-like phenotype than the other ones.

Introduction: The generation of Rho-0 cells requires the use of an immortalization process, or tumor cell selection, followed by culture in the presence of ethidium bromide (EtBr), incurring the drawbacks its use entails. The purpose of this work was to generate Rho-0 cells using human mesenchymal stem cells (hMSCs) with reagents having the ability to remove mitochondrial DNA (mtDNA) more safely than by using EtBr., Methodology: Two immortalized hMSC lines (3a6 and KP) were used; 143B.TK-Rho-0 cells were used as reference control. For generation of Rho-0 hMSCs, cells were cultured in medium supplemented with each tested reagent. Total DNA was isolated and mtDNA content was measured by real-time polymerase chain reaction (PCR). Phenotypic characterization and gene expression assays were performed to determine whether 3a6 Rho-0 hMSCs maintain the same stem properties as untreated 3a6 hMSCs. To evaluate whether 3a6 Rho-0 hMSCs had a phenotype similar to that of 143B.TK-Rho-0 cells, in terms of reactive oxygen species (ROS) production, apoptotic levels and mitochondrial membrane potential (Δψm) were measured by flow cytometry and mitochondrial respiration was evaluated using a SeaHorse XFp Extracellular Flux Analyzer. The differentiation capacity of 3a6 and 3a6 Rho-0 hMSCs was evaluated using real-time PCR, comparing the relative expression of genes involved in osteogenesis, adipogenesis and chondrogenesis., Results: The results showed the capacity of the 3a6 cell line to deplete its mtDNA and to survive in culture with uridine. Of all tested drugs, Stavudine (dt4) was the most effective in producing 3a6-Rho cells. The data indicate that hMSC Rho-0 cells continue to express the characteristic MSC cell surface receptor pattern. Phenotypic characterization showed that 3a6 Rho-0 cells resembled 143B.TK-Rho-0 cells, indicating that hMSC Rho-0 cells are Rho-0 cells. While the adipogenic capability was higher in 3a6 Rho-0 cells than in 3a6 cells, the osteogenic and chondrogenic capacities were lower., Conclusion: Among the drugs and conditions tested, the use of d4t was the best option for producing Rho-0 cells from hMSCs. Rho-0 cells are useful for studying the role of mitochondria in hMSC differentiation., Competing Interests: The authors have declared that no competing interests exist.

Assessment of the flavanol composition of 41 commercial chocolates was by HPLC-DAD. Among individual flavonols ranged from 0.095 to 3.264mgg(-1), epicatechin was the predominant flavanol accounting for 32.9%. Contrary to catechin, epicatechin was a reliable predictive value of the polyphenol content. Conversely the percentage of theobromine used as a proxy measure for nonfat cocoa solids (NFCS) was not a good predictor of epicatechin or flavanol content. In a further chiral analysis, the naturally occurring forms of cocoa flavanols, (-)-epicatechin and (+)-catechin, was determined joint the occurrence of (+)-epicatechin and (-)-catechin due to the epimerization reactions produced in chocolate manufacture. (-)-Epicatechin, the most bioactive compound and predominant form accounted of 93%. However, no positive correlation was found with% cocoa solids, the most significant quality parameter., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: The use of experimental models is essential to study the pathophysiological mechanisms of diabetes. , Objectives: To compare in adult Wistar rats the diabetogenic action of streptozotocin according to the moment and route of administration during the neonatal period by evaluating biochemical, metabolic and histological variables. , Materials and Methods: Eight groups of neonatal female Wistar rats (n=10) were formed. We evaluated the induction with streptozotocin (100 mg/kg of body weight) on days 2 and 5 after birth, as well as the administration routes (subcutaneous or intraperitoneal). Controls were injected with sodium citrate buffer. Blood glucose level, body weight, food and water intake were monitored for 12 weeks. We also performed tolerance tests for oral glucose and glycosylated hemoglobin, and a histopathological pancreas morphometric study. , Results: The mortality rate was about 100% among rats given streptozotocin on their fifth day of life. All rats receiving the drug on day 2 of life survived, and they showed a marked hyperglycemia, polyphagia, polydipsia and decreased body weight gain in addition to increased glycosylated hemoglobin rates and impaired results in the oral glucose tolerance test. Histopathological lesions of the pancreas as well as a decreased number of islets were significantly more frequent in rats receiving the drug subcutaneously on day 2, which confirms that streptozotocin administered subcutaneously produces greater damage. , Conclusions: Subcutaneous injection of streptozotocin in a dose of 100 mg/kg of body weight in the second day after birth induced moderate diabetes in adult Wistar rats more effectively.

Improving the efficiency of management in protected areas is imperative in a generalized context of limited conservation budgets. However, this is overlooked due to flaws in problem definition, general disregard for cost information, and a lack of suitable tools for measuring costs and management quality. This study describes an innovative methodological framework, implemented in the web application SIGEIN, focused on maximizing the quality of management against its costs, establishing an explicit justification for any decision. The tool integrates, with this aim, a procedure for prioritizing management objects according to a conservation value, modified by a functional criterion; a project management module; and a module for management of continuous assessment. This appraisal associates the relevance of the conservation targets, the efficacy of the methods employed, both resource and personnel investments, and the resulting costs. Preliminary results of a prototypical SIGEIN application on the Site of Community Importance Chafarinas Islands are included., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Current evidence suggests that lipid homeostasis in the hippocampus is affected by different genetic, dietary, and hormonal factors, and that its deregulation may be associated with the onset and progression of Alzheimer's disease (AD). However, the precise levels of influence of each of these factors and their potential interactions remain largely unknown, particularly during neurodegenerative processes. In the present study, we have performed multifactorial analyses of the combined effects of diets containing different doses of docosahexaenoic acid (DHA), estrogen status (ovariectomized animals receiving vehicle or 17β-estradiol), and genotype (wild-type or transgenic APP/PS1 mice) in hippocampal lipid profiles. We have observed that the three factors affect lipid classes and fatty acid composition to different extents, and that strong interactions between these factors exist. The most aberrant lipid profiles were observed in APP/PS1 animals receiving DHA-poor diets and deprived of estrogens. Conversely, wild-type animals under a high-DHA diet and receiving estradiol exhibited a lipid profile that closely resembled that of the hippocampus of control animals. Interestingly, though the lipid signatures of APP/PS1 hippocampi markedly differed from wild-type, administration of a high-DHA diet in the presence of estrogens gave rise to a lipid profile that approached that of control animals. Paralleling changes in lipid composition, patterns of gene expression of enzymes involved in lipid biosynthesis were also altered and affected by combination of experimental factors. Overall, these results indicate that hippocampal lipid homeostasis is strongly affected by hormonal and dietary conditions, and that manipulation of these factors might be incorporated in AD therapeutics.

The selection of the most appropriate wastewater treatment (WWT) technology is a complex problem since many alternatives are available and many criteria are involved in the decision-making process. To deal with this challenge, the analytic network process (ANP) is applied for the first time to rank a set of seven WWT technology set-ups for secondary treatment in small communities. A major advantage of ANP is that it incorporates interdependent relationships between elements. Results illustrated that extensive technologies, constructed wetlands and pond systems are the most preferred alternatives by WWT experts. The sensitivity analysis performed verified that the ranking of WWT alternatives is very stable since constructed wetlands are almost always placed in the first position. This paper showed that ANP analysis is suitable to deal with complex decision-making problems, such as the selection of the most appropriate WWT system contributing to better understand the multiple interdependences among elements involved in the assessment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: Of the numerous instruments available to detect nutritional risk, the most widely used is the Mini Nutritional Assessment (MNA), but it takes 15-20 min to complete and its systematic administration in primary care units is not feasible in practice. We developed a tool to evaluate malnutrition risk that can be completed more rapidly using just clinical variables. Between 2008 and 2013, we conducted a cross-sectional study of 418 women aged ≥60 years from Mexico. Our outcome was positive MNA and our secondary variables included were: physical activity, diabetes mellitus, hypertension, educational level, dentition, psychological problems, living arrangements, history of falls, age and the number of tablets taken daily. The sample was divided randomly into two groups: construction and validation. Construction: a risk table was constructed to estimate the likelihood of the outcome, and risk groups were formed., Validation: the area under the ROC curve (AUC) was calculated and we compared the expected and the observed outcomes. The following risk factors were identified: physical activity, hypertension, diabetes, dentition, psychological problems and living with the family. The AUC was 0.77 (95% CI [0.68-0.86], p < 0.001). No differences were found between the expected and the observed outcomes (p = 0.902). This study presents a new malnutrition screening test for use in elderly women. The test is based on six very simple, quick and easy-to-evaluate questions, enabling the MNA to be reserved for confirmation. However, it should be used with caution until validation studies have been performed in other geographical areas.

Two domino Diels-Alder adducts were obtained from 3,7-bis(cyclopenta-2,4-dien-1-ylidene)-cis-bicyclo[3.3.0]octane and dimethyl acetylenedicarboxylate or N-methylmaleimide under microwave irradiation. From the first adduct, a C20H24 diene with C2v symmetry was obtained by Zn/AcOH reduction, hydrolysis, oxidative decarboxylation, and selective hydrogenation. Photochemical [2+2] cycloaddition of this diene gave a thermally unstable cyclobutane derivative, which reverts to the diene. However, both the diene and the cyclobutane derivatives could be identified by X-ray diffraction analysis upon irradiation of the diene crystal. New six-membered rings are formed upon the transannular addition of bromine or iodine to the diene. The N-type selectivity of the addition was examined by theoretical calculations, which revealed the distinct susceptibility of the doubly bonded carbon atoms to the bromine attack., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

From 1941 to 1978, Franco's regime in Spain banned all contraceptive methods. The pill started circulating in Spain from the 1960s, officially as a drug used in gynaecological therapy. However, in the following decade it was also increasingly used and prescribed as a contraceptive. This paper analyses debates about the contraceptive pill in the Spanish daily newspaper ABC and in two magazines, Blanco y Negro and Triunfo, in the 1960s and 1970s. It concludes that the debate on this contraceptive method was much more heterogeneous than might be expected given the Catholic-conservative character of the dictatorship. The daily press focused on the adverse effects of the drug and magazines concentrated on the ethical and religious aspects of the pill and discussed it in a generally positive light. Male doctors and Catholic authors dominated the debate., (© The Author(s) 2013.)

Mesenchymal stem cells (MSCs) are an accepted candidate for cell-based therapy of multiple diseases. The interest in MSCs and their possible application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently, like aggregation and transforming growth factor beta (TGFβ) delivery, hypoxia has been indicated as crucial for complete chondrogenesis. The aim of this study was to test different culture conditions for directing stem cell differentiation into the chondrogenic lineage in vitro by testing different TGFβ superfamily members into the culture media under normoxic conditions. All chondrogenic culture conditions used allowed the differentiation of bone marrow-MSCs (BM-MSCs) into chondrogenic lineage. Chondrogenic induction capacity depended on the growth factor added to the culture media. In particular, the chondrogenic culture condition that better induced chondrogenesis was the medium that included the combination of three growth factors: bone morphogenetic protein-2 (BMP-2), BMP-7 and TGFβ-3. In this culture media, differentiated cells showed the highest levels expression of two markers of chondrogenesis, SOX9 and COL2A1, compared to the control points (p < 0.05, two-tailed t test). In our experimental conditions, the combination of BMP-2, BMP-7 and TGFβ-3 was the most effective in promoting chondrogenesis of BM-MSCs. These results underline the importance of determining in each experimental design the best protocol for in vitro directing stem cell differentiation into the chondrogenic lineage.

Introduction: We can find in Spain several university studies concerning diet and lifestyle, showing them as an effective strategy to prevent chronic diseases., Objectives: To evaluate the energy and nutrient intake and adherence to the Mediterranean Diet (DM) in a group of college students with different academic profile and to compare the quality of the diet among students attending degrees in Health Science (HS) and those attending other degree courses (not HS)., Methods: 77 students (80.3% female) from the Campus of Soria, 37 HS students and 40 not HS (mean age 21.2 ± 2.1 years), completed a questionnaire on socio-biographical data, the test KIDMED of adhesion to Mediterranean diet and recorded food intake for seven days. The amount of energy and nutrients was estimated using the software Nutriber (version 1.1.1.3r). Student t test or U Mann-Whitney were used to compare means of independent samples and the criterion of significance was set at p <0,05., Results and Discussion: The respondent students, regardless of their academic profile, follow a low calorie diet with more protein and fat consumption than the recommended amount, and less carbohydrate and fiber, which is reflected in the insufficient intake of some vitamins and minerals. However, we observed a higher percentage of respondents with high adhesion to the parameters of the DM in the HS group (51.4%) than in the No HS group (30.8%)., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background: Zn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results., Objective: To compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age., Material and Methods: 123 newborns divided in "study group" (n=50) with <2500g birth weight neonates and "control group" (n=73) with ≥2500g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann-Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations)., Results: Statistically significant low positive correlation between Zn-levels and birth weight (ρ=0.283; p=0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00±0.43 vs. 18.16±0.32 (p=0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ=0.351; p=0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33±0.42 vs. 18.43±0.93 (p=0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p=0.001)., Conclusions: Despite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer's disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.

Objective: To explore the scientific output on transsexuality in the Spanish biomedical literature between 1973 and 2011, through bibliometric and content analyses., Methods: We carried out a descriptive, cross-sectional study of Spanish biomedical articles on transsexuality published between 1973 and 2011. The data sources consisted of Índice Médico Español and ISOC-Ciencias Sociales y Humanidades. Bibliometric and content analyses were performed., Results: A total of 65 papers were analyzed. Knowledge on transsexuality in Spain began to appear in medical journals between 1973 and 1984. A decade of intense productivity began in 1996 and the number of journals publishing articles on transsexuality multiplied in the following years. Until 2006, the year with the most biomedical productivity, biomedical discourses reproduced representations of transsexuality anchored in biological determinism. From 2008-2011, professionals writing on the topic incorporated feminist theories and social perspectives in their discourses., Conclusions: In the last quarter of the twentieth century, the dominant medical discourse considered manifestations of transsexual people from a biologist perspective that conceives transsexuality as a configuration mismatch between sex and gender. The emergence of new identity categories and medical reflection from non-essentialist and non-normative gender perspectives has improved the clinical management of transsexuality., (Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.)

Introduction: Pressure ulcer (PU) infection is a significant clinical problem in many elderly patients., Material and Methods: To determine the microbiology of PU and vascular ulcer (VU) infections by conducting a cross-sectional study of outpatients treated in a chronic wounds unit over an 18 month period., Results: Sixty six patients with PU infection and 159 patients with an infected VU were identified. The PUs were located below the knee in 36 patients (52%). Patients with pressure ulcers had a higher proportion of institutionalization, cognitive impairment, inability to walk, and sphincter incontinence. There was a greater number of infections caused by Enterobacteriaceae (52%, P=.002) and fewer S. aureus infections (24%, P<.001) in patients with a PU compared to those with those with a VU. Forty-one percent of S. aureus strains isolated in all the patients were resistant to methicillin (MRSA). The proportion of Enterobacteriaceae infections was similar in patients with infection of pelvic girdle PU and in those located below the knee., Conclusions: PU patients suffer a higher rate of infection by enterobacteria. The most common pathogen in UV infections is S. aureus. The proportion of MRSA infection in patients with chronic wounds is high. The microbiology of the infection in the pelvic girdle PU is similar to those located below the knee., (Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.)

In the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent probes, we demonstrate that lipid rafts from cerebellum, and frontal and entorhinal cortices, exhibit different biophysical behaviors depending on the stage of the disease. Thus, while membrane anisotropies were similar in the cerebellum along stages, lipid rafts from frontal and entorhinal cortices at AD stages I/II and AD III were significantly more liquid-ordered than in control subjects, both at the aqueous interface and hydrophobic core of the raft membrane. Thermotropic analyses demonstrated the presence of Arrhenius breakpoints between 28.3-32.0 °C, which were not influenced by the disease stage. However, analyses of membrane microviscosity (ηapp) demonstrate that frontal and entorhinal lipid rafts are notably more viscous and liquid-ordered all across the membrane from early stages of the disease. These physicochemical alterations in lipid rafts do not correlate with changes in cholesterol or sphingomyelin levels, but to reduced unsaturation index and increased saturate/polyunsaturated ratios in phospholipid acyl chains. Moreover, we demonstrate that β-secretase/AβPP (amyloid-β protein precursor) interaction and lipid raft microviscosity are strongly, and positively, correlated in AD frontal and entorhinal cortices. These observations strengthens the hypothesis that physical properties of these microdomains modulate the convergence of amyloidogenic machinery toward lipid rafts, and also points to a critical role of polyunsaturated fatty acids in amyloidogenic processing of AβPP.

The purpose of this article was to study, from a feminist perspective, the diversity and homogeneity in the career paths of female primary care physicians from Andalusia, Spain in the early 21st century, by analyzing the meanings they give to their careers and the influence of personal, family and professional factors. We conducted a qualitative study with six discussion groups. Thirty-two female primary care physicians working in urban health centers of the public health system of Andalusia participated in the study. The discourse analysis revealed that most of the female physicians did not plan for professional goals and, when they did plan for them, the goals were intertwined with family needs. Consequently, their career paths were discontinuous. In contrast, career paths oriented towards professional development and the conscious planning of goals were more common among the female doctors acting as directors of health care centers.

In recent years, researchers in social cognition have found the "perceptual crossing paradigm" to be both a theoretical and practical advance toward meeting particular challenges. This paradigm has been used to analyze the type of interactive processes that emerge in minimal interactions and it has allowed progress toward understanding of the principles of social cognition processes. In this paper, we analyze whether some critical aspects of these interactions could not have been observed by previous studies. We consider alternative indicators that could complete, or even lead us to rethink, the current interpretation of the results obtained from both experimental and simulated modeling in the fields of social interactions and minimal perceptual crossing. In particular, we discuss the possibility that previous experiments have been analytically constrained to a short-term dynamic type of player response. Additionally, we propose the possibility of considering these experiments from a more suitable framework based on the use and analysis of long-range correlations and fractal dynamics. We will also reveal evidence supporting the idea that social interactions are deployed along many scales of activity. Specifically, we propose that the fractal structure of the interactions could be a more adequate framework to understand the type of social interaction patterns generated in a social engagement.

The assessment of the sustainability of wastewater treatment (WWT) systems has gained interest in recent years. However, most previous studies have focused on environmental and/or economic dimensions ignoring social aspects. Moreover, they tend to be based on sets of indicators rather than providing a holistic assessment. To overcome this limitation, this paper proposes an innovative methodology to assess the sustainability of WWT systems based on the development of a composite indicator embracing economic, environmental and social issues. Subsequently, the global sustainability of seven WWT technologies for secondary treatment in small communities is compared. The joint application of the analytical hierarchical process (AHP) to assign weights to each indicator allows the incorporation of the preferences of experts. Initially, the global sustainability of the WWT technologies evaluated is quite similar. However, a scenario analysis illustrates that constructed wetlands technology is the most sustainable in five out of the seven scenarios evaluated. Moreover, extended aeration and rotating biological contactors are identified as the technologies with the lowest variability in their sustainability. Hence, in an uncertain context, they might be considered the preferred options. The proposed approach contributes to ease of interpretation of a complex problem such as the selection of the most sustainable WWT alternative., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Pancreatic surgeons try to find the best technique for reconstruction after pancreatoduodenectomy (PD) in order to decrease postoperative complications, mainly pancreatic fistulas (PF). In this work, we compare the two most frequent techniques of reconstruction after PD, pancreatojejunostomy (PJ) and pancreatogastrostomy (PG), in order to determine which of the two is better. A systematic review of the literature was performed, including major meta-analysis articles, clinical randomized trials, systematic reviews, and retrospective studies. A total of 64 articles were finally included. PJ and PG are usually responsible for most of the postoperative morbidity, mainly due to the onset of PF, being considered a major trigger of life-threatening complications such as intra-abdominal abscess and hemorrhagia. The included systematic reviews reported a significant difference only in the incidence of intraabdominal collections favouring PG. PF, delayed gastric emptying and mortality were not different. Although there was heterogeneity between these studies, all were conducted in specialized centers by highly experienced surgeons, and the surgical care was likely to be similar for all the studies. The disadvantages of PG include an increased incidence of delayed gastric emptying and of main pancreatic duct obstruction due to overgrowth by the gastric mucosa. Exocrine function appears to be worse after PG than after PJ, resulting in severe atrophic changes in the remnant pancreas. Depending on the type of PJ or PG used, the PF rate and other complications can also be different. The best method to deal with the pancreatic stump after PD remains questionable. The choice of method of pancreatic anastomosis could be based on individual experience and on the surgeon's preference and adherence to basic principles such as good exposure and visualization. In conclusion, up to now none of the techniques can be considered superior or be recommended as standard for reconstruction after PD.

Study Question: Are there any proteomic differences between receptive (R) and non-receptive (NR) endometrial receptivity array (ERA)-diagnosed endometria obtained on the same day of a hormonal replacement therapy (HRT) treatment cycle?, Summary Answer: There is a different proteomic signature between R and NR ERA-diagnosed endometrium obtained on the same day of HRT cycles., What Is Known Already: The human endometrial transcriptome has been extensively investigated in the last decade resulting in the development of a new diagnostic test based on the transcriptomic signature of the window of implantation (WOI). Much less is known about the proteomics derived from the transcripts present during the WOI., Study Design, Size, and Duration: This study was a basic proteomic analysis of human endometrial biopsies taken from twelve IVF patients., Participants/materials, Setting, and Methods: Human endometrial biopsies were collected during HRT cycles after 5 days of progesterone (P) administration, and diagnosed as receptive (R; n = 6) or non-receptive (NR; n = 6) by the ERA test. Endometrial proteins were extracted, labelled and separated using differential in-gel electrophoresis (DIGE). Proteins were identified using mass spectrometry, followed up by in silico analysis. Validation studies using western blots and immunolocalization were performed for the progesterone receptor membrane component 1 (PGRMC1) and annexin A6 (ANXA6) proteins., Main Results and the Role of Chance: DIGE analysis followed by protein identification by MALDI-MS and database searches revealed 24 differentially expressed proteins in R versus NR samples. In silico analysis showed two pathways which were significantly different between R and NR samples. Expression of PGRMC1 and ANXA6 was validated and localized by western blots and immunohistochemistry. These results highlight these proteins as key targets likely to be important in the comprehension of human endometrial receptivity., Limitations, Reasons for Caution: This was mainly a descriptive study with no functional studies on the proteins found. We also used a low number of human endometrial samples for the DIGE analysis., Wider Implications of the Findings: This study identified the proteomic profile associated with receptive or non-receptive human endometria. Our findings suggest that although histological dating indicates a putative 'receptive' status within the WOI, a different transcriptomic and proteomic profile is observed in these samples. We should move towards using more personalized WOIs, where identification of the correct endometrial receptivity status, and consequently the success of IVF, relies on individual molecular signatures rather than traditional endometrial dating., Study Funding/competing Interests: F.D.'s participation in this work was supported by the Spanish Ministry of Economy and Competitiveness, through the Miguel Servet Programme (CP13/00075) co-founded by FEDER. The project was also supported by a grant from the Spanish Ministry of Economy and Competitiveness, through the FIS Programme (PI12/00450). The authors have no financial/commercial conflicts of interest to declare., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim was to analyze the prevalence of latent tuberculosis infection and associated risk factors in healthcare personnel at the Hospital de Tortosa Verge de la Cinta (Tarragona, Spain). This was a cross-sectional study of 398 workers at this hospital who underwent tuberculin skin testing for latent tuberculosis infection (LTBI) between 2001 and 2012.We also analyzed the relationship between LTBI and age, sex, job and work area according to their risk of exposure to tuberculosis(high, low, uncertain). The total prevalence of LTBI in our sample was 11.1% (95%CI 8.3%-14.5%). LBTI was associated with age and work area. Multivariate analysis showed that the risk of LTBI increased by 6.4% per 1 year increase in age. The prevalence of LTBI in this population approximates that of the general population in Spain., (Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.)

Objective: Internet addiction (IA) has been described as an emerging behavior related to the development of new technologies, with scarce studies on the subject and none involving medical students. The Internet Addiction Test (IAT) is a screening instrument used to detect IA worldwide, which was published in 1998 and inspired by the DSM-IV criteria for pathologic gambling. The objective of this study aims to measure the prevalence of IA in Chilean medical students and its possible association with demographic variables and depressive symptoms., Methods: First- to fifth-year undergraduate medical students at a medical school in Santiago de Chile answered a self-administered survey that included demographic data, the IAT scale, and the Goldberg's General Health Questionnaire (GHQ-12) to screen for IA and depressive symptoms, respectively., Results: Three hundred eighty-four students participated, achieving a response rate of 69.8 %, of which 11.5 % were classified as problematic users according to the IAT. The authors found a statistical association between positive results on the IAT and positive scores on the GHQ-12, as well as with the male gender., Conclusion: In this first study of IA in medical students, the authors found a rate of incidence similar to what has been published in the literature focusing on college students. Additionally, there was a positive association between emotional symptoms and other abuse behaviors.

Background: The diabetic cardiomyopathy occurs in both type 1 and type 2 diabetes mellitus. Hyperglycemia and associated metabolic changes participate in the pathogenesis of this disease., Objective: To characterizes various pathological changes occurring during the development of diabetic cardiomyopathy in rats., Methods: Diabetic rats were used for streptozotocin administration. At 7, 14, 21 and 30 days after toxic administration, the heart was obtained and placed in a Hartman solution and 4% p-formaldehyde. Five-micrometer thick sections were stained with hematoxylin-eosin, Masson trichrome and immunocytochemistry using anti-β-tubulin antibody., Results: At 14 days after application of streptozotocin, dilated sinusoids with endothelial lining in the myocardium and collagen deposits in the cardiac interstitium and between the Purkinje fibers were observed. At 21 days there was a slight decrease of the arteriolar lumen due to hyperplasia of the medial layer. It is important to note that cardiac sinusoids as well as collagen deposits became more evident at 30 day of the study, as well as a major derangement of the microtubular system of the cardiomyocytes., Conclusions: Cardiac sinusoids representing fetal vascular pattern and interstitial fibrosis in the myocardium and the microtubular derangement of cardiomyocytes support the fact that the pathophysiological mechanism of diabetic cardiomyopathy begins in the coronary microcirculation due to changes in cardiac metabolism, contributing to the development of myocardial dysfunction in diabetes.

Tamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor α (ERα). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ERα-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Androgens regulate body development and differentiation through a variety of genotropic mechanisms, mostly in reproductive organs. In recent years a different scenario for sex hormone actions has emerged: the intestinal muscle. Thus, although estrogens relax intestinal muscle, androgens are powerful inducers of mechanical potentiation. This effect of androgens was intriguing because it is observed at physiological concentrations, is mediated by nongenomic mechanisms, and involves a phenomenon of calcium sensitization of contractile machinery by stimulating phosphorylation of 20 kDa myosin light chain by Rho-associated kinase. Here we have deciphered the molecular mechanisms underlying calcium sensitization and mechanical potentiation by androgens in male intestinal muscle as well as its tight relationship to polyamine metabolism. Thus, androgens stimulate polyamine synthesis, and the inhibition of polyamine synthesis abolishes androgen-induced calcium sensitization and 20 kDa myosin light chain phosphorylation. We demonstrate that the first molecular step in the induction of calcium sensitization is a nonconventional activation of the adaptor protein RhoA, triggered by a transglutaminase-catalyzed polyamination of RhoA, which is then targeted to the membrane to activate Rho-associated kinase. Altogether, these results demonstrate that the physiological levels of androgens, through the modulation of polyamine metabolism and posttanslational modification of RhoA, activate a new signal transduction pathway in the intestinal smooth muscle to induce calcium sensitization. Furthermore, apart from being one of the few physiologically relevant nongenomic effects of androgens, these results might underlie the well-known gender differences in intestinal transits, thus expanding the nature's inventory of sex hormones effects.

Background: Difficult airway (DA), including difficult bag-mask ventilation (DBMV), and difficult intubation (DI) is an important challenge for the pediatric anesthesiologist. While expected DBMV can be successfully managed with appropriate equipment and personnel, unexpected DBMV relies on the resources available and the experience of the anesthesiologist at the time of the emergency. The incidence and risk factors of unexpected DA in otherwise healthy children, including DBMV among pediatric patients are not known. The aim of this study was to expand the scientific knowledge of unexpected DBMV among pediatric patients., Methods: Patients between the ages of 0 and 8 years, undergoing elective surgery requiring bag-mask ventilation BMV and intubation at the Montreal Children's Hospital were recruited in this prospective observational study. Data on the incidence of DBMV and risk factors were collected over a 3-year period., Results: In a sample of 484 children, the incidence of unexpected difficult BMV was 6.6% (95% CI [4.6, 9.2]). The incidence of expected DA among the screened patients (N = 4865) was 0.5% (95% CI [0.3, 0.7]). In a logistic regression analysis, age (OR 0.98; 95%CI [0.97, 0.99]), undergoing otolaryngology (ENT) surgery (OR 2.92; 95% CI [1.08, 7.95]) and use of neuromuscular blocking agents (OR 3.49; 95%CI [1.50-8.11]) were independently associated with DBMV. The incidence of DI was 1.2%. No association between DBMV and DI was found (Fisher's exact test, P = 1.0)., Conclusions: This is the first published report of the incidence of unexpected DBMV among healthy pediatric patients., (© 2013 John Wiley & Sons Ltd.)

We report new indene derivatives that are good fluorogenic probes for the cyanide anion, one of which is a highly selective and sensitive fluorogenic probe for the fluorescent detection--as well as reliable quantification--of the cyanide anion in water or buffer, with a 10(3)-fold increase of fluorescence and low detection limit. It is therefore useful for the quantification of natural cyanide from aqueous extracts of green almond seeds, thus proving that the system is suitable for fast detection and quantification of cyanide from natural sources., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The concept of achievement is important to study the professional development. In medicine there are gender inequalities in career. The purpose was to know and compare the professional achievement's perceptions and attributions of female and male primary care physicians in Andalusia., Method: Qualitative study with 12 focus groups (October 2009 to November 2010)., Population: primary care physicians., Sample: intentionally segmented by age, sex and health care management. Were conducted by sex: two groups with young physicians, two groups with middle aged and two with health care management. TOTAL: 32 female physician and 33 male physicians. Qualitative content analysis with Nuddist Vivo., Results: Female and male physicians agree to perceive internal achievements and to consider aspects inherent to the profession as external achievements. The most important difference is that female physician related professional achievement with affective bond and male physician with institutional merit. Internal attributions are more important for female physician who also highlight the importance of family, the organization of working time and work-family balance. Patients, continuing education, institutional resources and computer system are the most important attributions for male physician., Conclusions: There are similarities and differences between female and male physicians both in the understanding and the attributions of achievement. The differences are explained by the gender system. The perception of achievement of the female physicians questions the dominant professional culture and incorporates new values in defining achievement. The attributions reflect the unequal impact of family and organizational variables and suggest that the female physicians would be changing gender socialization.

This article highlights the need for methods to objectively diagnose endometrial receptivity as a factor contributing to infertility in female patients. The correct identification of the appropriate window of implantation in a given patient, by using endometrial receptivity biomarkers, can help to prevent reproductive failure resulting from misplaced timing of the endometrial window of implantation (WOI). Although to date no single, clinically relevant morphologic, molecular, or histologic marker capable of indicating endometrial receptivity status has been identified, global transcriptomic analysis of human endometria performed in the last decade has given us insights into a genomic signature that is capable of identifying endometrial receptivity. As a consequence, a genomic tool named the Endometrial Receptivity Array (ERA), based on a customized microarray, was developed, and along with it a specially trained bioinformatic prediction computer algorithm was created to identify WOI timing in the endometrium. This tool has proven more accurate and consistent than histologic (Noyes) dating at identifying the personalized WOI day, thus leading to the new clinical concept of personalized ET on the optimum day of endometrial receptivity, identified individually case by case., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions. Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS). Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures. Conclusions. In our experimental conditions, severe hypoxia affects the in vitro differentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

The synthesis of a functionalized derivative containing the 2,8-ethanonoradamantane carbocyclic skeleton, whose key-step consists of an intramolecular Diels-Alder reaction, is described. Chemoselective reduction of an intermediate enone required protection of the maleimide function through their Diels-Alder adducts with furan.

Injuries to the Lisfranc joint have a high potential for chronic disability. Posttraumatic arthritis remains the most common complication but not all patients who develop degenerative radiographic changes are symptomatic. A cohort of 32 patients with a Lisfranc fracture dislocation was reviewed. Initial reduction and secondary displacement were measured by the Myerson scale. Radiographic evidence of osteoarthritis (OA) was also investigated. Long-term radiographical data were classified as good, fair or poor results. Functional outcome was measured using several different scales. Mean follow up was 14 years. Seventeen patients with anatomic close reduction but instability were treated with closed reduction and K-wire fixation followed by cast immobilisation. Eight patients with stable anatomic close reduction were treated with closed reduction and cast. Seven patients with unacceptable closed reduction were treated with open reduction and K-wire stabilisation. The analysis of radiological long-term data showed 15 patients with good results, 8 with fair results and 9 with poor results. Final mean AOFAS score was 91.7/100. There was no statistically significant difference between overall PFS scores and different type of treatment, Hardcastle long-term radiological scores or Hardcastle type of fracture (p >0.05). Overall, there was a poor association between the extent of radiological arthritis and clinical scores. We advocate that for the evaluation of long-term outcome of these injuries functional parameters should be the focus of assessment, instead of radiological changes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Achieving accurate measurements of inflammation levels in tissues or thickness changes in biological membranes (e.g., amniotic sac, parietal pleura) and thin biological walls (e.g., blood vessels) from outside the human body, is a promising research line in the medical area. It would provide a technical basis to study the options for early diagnosis of some serious diseases such as hypertension, atherosclerosis or tuberculosis. Nevertheless, achieving the aim of non-invasive measurement of those scarcely-accessible parameters on patient internal tissues, currently presents many difficulties. The use of high-frequency ultrasonic transducer systems appears to offer a possible solution. Previous studies using conventional ultrasonic imaging have shown this, but the spatial resolution was not sufficient so as to permit a thickness evaluation with clinical significance, which requires an accuracy of a few microns. In this paper a broadband ultrasonic technique, that was recently developed by the authors to address other non-invasive medical detection problems (by integrating a piezoelectric transducer into a spectral measuring system), is extended to our new objective; the aim is its application to the thickness measurement of sub-millimeter membranes or layers made of materials similar to some biological tissues (phantoms). The modeling and design rules of such a transducer system are described, and various methods of estimating overtones location in the power spectral density (PSD) are quantitatively assessed with transducer signals acquired using piezoelectric systems and also generated from a multi-echo model. Their effects on the potential resolution of the proposed thickness measuring tool, and their capability to provide accuracies around the micron are studied in detail. Comparisons are made with typical tools for extracting spatial parameters in laminar samples from echo-waveforms acquired with ultrasonic transducers. Results of this advanced measurement spectral tool are found to improve the performance of typical cross-correlation methods and provide reliable and high-resolution estimations.

Chronic wounds represent a drain on the Spanish health system, nowdays is necessary an optimization of the resources used and that is for this that is necessary justify the use of the products over others through cost-effective studies for to show the economic benefit to professionals and the life quality of patient. This article compares the use of a new technology for format polyurethane foam, TLC-NOSF, with the most commonly used products for treating wounds. This comparison is made using a cost-effectiveness model (Markov Model). The results demonstrate that treatment with polyurethane foam dressing with TLC-NOSF are cost-effective versus treatments with polyurethane foams most commonly used in Spain.

The treatment of chronic wounds requires the use of highly specific products for different phases of the healing process. This article raises a number of clinical cases with chronic wounds of vascular origin and pressure ulcers. Such cases required a initial debridement because of the large content of fibrin covering the wound bed at this stage was used dressing hidrodetersive polyacrylate fibers with TLC. Once the debridement is continued treatment with a polyurethane foam dressing with TLC-NOSF.

Annexin A2 (ANXA2) is present in vivo in the mid- and late-secretory endometria and is mainly localized in the luminal epithelium. Our aim was to evaluate its function in regulating the human implantation process. With an in vitro adhesion model, constructed to evaluate how the mouse embryo and JEG-3 spheroids attach to human endometrial epithelial cells, we demonstrated that ANXA2 inhibition significantly diminishes embryo adhesiveness. ANXA2 is also implicated in endometrial epithelial cell migration and trophoblast outgrowth. ANXA2 was seen to be linked to the RhoA/ROCK pathway and to regulate cell adhesion. We noted that ANXA2 inhibition significantly reduces active RhoA, although RhoA inactivation does not alter the ANXA2 levels. RhoA inactivation and ROCK inhibition also moderate embryo adhesiveness to endometrial epithelial cells. We corroborated that the induction of constitutively active RhoA partially reverses the effects of ANXA2 inhibition on endometrial adhesiveness. These molecules colocalize on the plasma membrane of endometrial epithelial cells, and a large proportion of ANXA2 and RhoA are colocalized in the F-actin networks. The functional effects of ANXA2 inhibition and RhoA/ROCK inactivation are associated with significant alterations in F-actin organization and its depolymerization. ANXA2 may act upstream of the RhoA/ROCK pathway by regulating F-actin remodeling and is a key factor in human endometrial adhesiveness.

Background: Osteoarthritis (OA) is a multifactorial disease characterized by destruction of the articular cartilage due to environmental, mechanical and genetic components. The genetics of OA is complex and is not completely understood. Recent works have demonstrated the importance of microRNAs (miRNAs) in cartilage function. MiRNAs are a class of small noncoding RNAs that regulate gene expression and are involved in different cellular process: apoptosis, proliferation, development, glucose and lipid metabolism. The aim of this study was to identify and characterize the expression profile of miRNAs in normal and OA chondrocytes and to determine their role in the OA., Methods: Chondrocytes were moved to aggregate culture and evaluated using histological and qPCR techniques. miRNAs were isolated and analyzed using the Agilent Human miRNA Microarray., Results: Of the 723 miRNAs analyzed, 7 miRNAs showed a statistically significant differential expression. Amongst these 7 human miRNAs, 1 was up-regulated in OA chondrocytes (hsa-miR-483-5p) and 6 were up-regulated in normal chondrocytes (hsa-miR-149*, hsa-miR-582-3p, hsa-miR-1227, hsa-miR-634, hsa-miR-576-5p and hsa-miR-641). These profiling results were validated by the detection of some selected miRNAs by qPCR. In silico analyses predicted that key molecular pathways potentially altered by the miRNAs differentially expressed in normal and OA chondrocytes include TGF-beta, Wnt, Erb and mTOR signalling; all of them implicated in the development, maintenance and destruction of articular cartilage., Conclusions: We have identified 7 miRNAs differentially expressed in OA and normal chondrocytes. Our potential miRNA target predictions and the signalling cascades altered by the differentially expressed miRNAs supports the potential involvement of the detected miRNAs in OA pathology. Due to the importance of miRNA in mediating the translation of target mRNA into protein, the identification of these miRNAs differentially expressed in normal and OA chondrocyte micropellets could have important diagnostic and therapeutic potential. Further studies are needed to know the function of these miRNAs, including the search of their target mRNA genes, which could lead to the development of novel therapeutic strategies for the OA treatment.

Reaction of 1,3-diphenylisobenzofuran (DPIBF) with 2-(iodoethynyl)(phenyl)-iodonium triflate at room temperature gave the expected Diels-Alder adduct, but using an excess of DFIBF (2 equiv.) and performing the reaction at 55 °C or heating at this temperature during the concentration stage, the initial orange solution or product mixture became dark brown and the products 1,2-phenylene-1,2-bis(phenylmethanone) and 2-(3-iodo-1,4-diphenylnaphthyl)(phenyl)iodonium triflate were obtained, which suggests an oxygen transfer between DPIBF and the initial adduct.

Multiple symmetric lipomatosis is an alteration in the neck, upper trunk and upper extremities fat deposits. It produces an aesthetic problem and sometimes upper airway obstruction when the larynx is infiltrated by the mass. We report the case of a male with Madelung's disease, which began with acute dyspnea caused by laryngeal fat deposits and obstructive lipoma., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Objectives: To compare the proliferative and chondrogenic potential of fresh and frozen chondrocytes isolated from superficial and deep articular cartilage biopsies., Materials and Methodology: The study included 12 samples of fresh and frozen healthy human knee articular cartilage. Cell proliferation was tested at 3, 6 and 9 days. Studies of mRNA quantification, protein expression and immunofluorescence for proliferation and chondrogenic markers were performed., Results: Stimulation of fresh and frozen chondrocytes from both superficial and deep cartilage with fetal bovine serum produced an increase in the proliferative capacity compared to the non-stimulated control group. In the stimulated fresh cells group, the proliferative capacity of cells from the deep biopsy was greater than that from cells from the superficial biopsy (0.046 vs 0.028, respectively, p<0.05). There was also a significant difference between the proliferative capacity of superficial zone fresh (0.028) and frozen (0.051) chondrocytes (p<0.05). CCND1 mRNA and protein expression levels, and immunopositivity for Ki67 revealed a higher proliferative capacity for fresh articular chondrocytes from deep cartilage. Regarding the chondrogenic potential, stimulated fresh cells showed higher SOX9 and Col II expression in chondrocytes from deep than from superficial zone (p<0.05, T student test)., Conclusions: The highest rate of cell proliferation and chondrogenic potential of fresh chondrocytes was found in cells obtained from deep cartilage biopsies, whereas there were no statistically significant differences in proliferative and chondrogenic capacity between biopsy origins with frozen chondrocytes. These results indicate that both origin and cryopreservation affect the proliferative and chondrogenic potential of chondrocytes.

Hormone replacement therapy (HRT) may be prescribed to prevent the symptoms of menopause. This therapy may include estrogenic and/or progestin components and may increase the incidence of endometrial and breast cancers. Tibolone (TIB), which is also made up of estrogen and progestin components, is often used to reduce the impact of HRT. However, the effect of TIB on the processes of learning, memory and anxiety has yet to be fully elucidated. The aim of this study was to evaluate the long-term effect on learning, memory processes and anxiety in ovariectomized rats caused by different doses of TIB (0 mg/kg, 0.01 mg/kg, 0.1 mg/kg 1.0 mg/kg and 10 mg/kg, administered daily via the oral route for 18 weeks). Two behavioral animal models, the autoshaping and T maze models were employed. The concentrations of acetyl choline transferase (ChAT) and tryptophan hydroxylase (TPH) in the hippocampus were directly measured by Western blot. No significant changes were observed in the autoshaping model and spontaneous activity test. In the T maze, increased latency was observed with TIB doses of 1 and 10 mg/kg compared to the vehicle. We observed that the ChAT content decreased with increasing doses of TIB, whereas TPH content increased with doses of 1 and 10 mg/kg of TIB. These data indicate that high doses of TIB improved emotional learning, which may be related to the modulation of the cholinergic and serotonergic systems by TIB., (Copyright © 2011 Elsevier Inc. All rights reserved.)