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We develop an electrochemical sensor by using 2D-transition metal dichalcogenides (TMD), specifically MoS2, and nanoparticles stabilized with cucurbit[8]uril (CB[8]) incorporated together with them. Two different nanoparticles are assayed: diamond nanoparticles (DNPs) and gold nanoparticles (AuNp). 0D materials, together with TMD, provide increased conductivity and active surface while the macrocycle CB[8] affords selectivity towards the guest methyl viologen (MV2+), also named paraquat. Glassy Carbon (GC) electrodes are modified by drop-casting of suspensions of MoS2, followed by either a CB[8]-DNPs hybrid dispersion or a CB[8]-AuNp suspension. Atomic force microscopy is employed for the morphological characterization of the electrochemical sensor surface while cyclic voltammetry and electrochemical impedance spectroscopy techniques allow the electrochemical characterization of the sensor. The well-stablished signals of CB[8]-encapsulated MV2+ arise in voltammetric measurements when the macrocycle modifies the 0D-materials. Once the sensor construction and differential pulse voltammetry parameters have been optimized for quantification purposes, calibration procedures are performed with the platform GC/MoS2/CB[8]-DNPs. This sensing platform shows linear relations between peak intensity and the MV2+ concentration in the linear concentration range of (0.73–8.0) · 10−6 M with a limit of detection of 2.2 · 10−7 M. Analyses of river water samples fortified with MV2+ at the μM level shows recoveries of 100% with RSD values of 6.4% (n = 3).

This work presents an on-line fluorescence method for the allura red (AR) determination. The method is based on the fluorescence quenching of dots of MoS because of their interaction with the non-fluorescence dye. MoS-dots were synthetized and characterized by spectroscopic techniques and High Resolution Transmission Electronic Microscopy (HR-TEM). The simultaneous injection of the nanomaterial and the dye in a flow injection analysis system allows the determination of allura red at 1.7 × 10 M concentration level with a very good accuracy and precision (Er minor than 10% and RSD lower than 8%) and a sampling frequency of 180 samples per hour. Moreover, the interaction fluorophore-quencher results a dynamic inhibition mechanism. The proposed methodology was applied to the AR analysis in soft beverages and powders for gelatine preparation. Colourant concentrations of 63 ± 2 mg/L (n = 3) and 0.30 ± 0.01 mg/g (n = 3) were found, respectively. These results were validated by high performance liquid chromatography technique., The authors acknowledge financial support from the Spanish MICINN (MAT2017-85089-C2-2-R), the Comunidad Autónoma de Madrid (P2018/NMT-4349, TRANSNANOAVANSENS-CM).

We employ chevron-like graphene nanoribbons (GNRs) synthesized by a solution-based chemical route to develop a novel electrochemical sensor for determination of the neurotransmitter epinephrine (EPI). The sensor surface, a glassy carbon electrode modified with GNRs, is characterized by atomic force microscopy, scanning electron microscopy and Raman spectroscopy, which show that the electrode surface modification comprises of bi-dimensional multilayer-stacked GNRs that retain their molecular structure. The charge transfer process occurring at the electrode interface is evaluated by electrochemical impedance spectroscopy. The sensor is applied to the determination of EPI, employing as an analytical signal the reduction peak corresponding to the epinephrinechrome–leucoepinephrinechrome transition (E = − 0.25 V) instead of the oxidation peak usually employed in the literature (E = + 0.6 V) in order to minimize interferences. The results obtained demonstrate that chevron-like nanoribbons synthesized by solution methods exhibit reliable electrocatalytic activity for EPI determination. Using differential pulse voltammetry, we obtain a linear concentration range from 6.4 × 10 to 1.0 × 10 M and a detection limit of 2.1 × 10 M. The applicability of the sensor was evaluated by determining EPI in pharmaceutical samples with satisfactory results., Te authors acknowledge fnancial support from the Spanish MICINN (MAT2017-85089-C2-1-R, MAT2017- 85089-C2-2-R), MINECO (MAT2016-78293-C6-3-R), the Comunidad Autónoma de Madrid (P2018/NMT-4349 TRANSNANOAVANSENS-CM, S2013/MIT-3029, PEJD-2017/IND4130), the Xunta de Galicia (Centro singular de investigación de Galicia, accreditation 2016–2019, ED431G/09) and Fondo Europeo de Desarrollo Regional (FEDER). We thank I. Ballesteros for the SEM measurements.

Since December 2019, severe acute respiratory syndrome coronavirus 2 infection has spread worldwide. We all are concerned about immunocompromised children, especially hematologic and oncologic pediatric patients. We want to share our experience with 2 pediatric cancer patients with severe acute respiratory syndrome coronavirus 2 infection. Both presented mild disease and good outcome. No respiratory symptoms were identified, but both developed diarrhea, one probably secondary to lopinavir/ritonavir. Pediatric cancer patients may have milder disease than adults, but larger studies are needed to make conclusions.

This work presents an on-line fluorescence method for the allura red (AR) determination. The method is based on the fluorescence quenching of dots of MoS

This study investigates the still uncertain association between serum phospholipid fatty acids (PL-FA), and anthropometric and adiposity variables. A cross-sectional study was conducted with 1443 Spanish premenopausal women. Participants answered an epidemiological and a food frequency questionnaire. Anthropometric variables were measured using a bioimpedance scale. Serum PL-FAs levels were determined by gas chromatography&ndash, mass spectrometry. The association between body mass index (BMI), weight gain, body fat percentage, visceral fat index, and waist circumference with serum PL-FAs and desaturation indices was evaluated using multivariable linear regression models. BMI was positively associated with the relative concentration of saturated fatty acids (SFAs) (&beta, = 0.94, q-val = 0.001), and with palmitoleic, dihomo-&gamma, linolenic (DGLA), arachidonic (AA) and &alpha, linolenic acids, and was inversely associated with oleic, gondoic, trans-vaccenic, linoleic and &gamma, linolenic acids. Total fat percentage was positively associated with DGLA and AA, and inversely with linoleic and &gamma, linolenic acids. Low relative concentrations of some SFAs and high levels of n-6 PUFAs were associated with greater waist circumference. While the oleic/stearic and AA/DGLA acid ratios were inversely associated with BMI, DGLA/linoleic acid ratio was positively related to almost all variables. In addition to BMI, total fat percentage and waist circumference were also associated with certain individual fatty acids.

INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

We have developed electrochemical sensors for the determination of H2O2 in a complex matrix such as human semen as a method to evaluate oxidative stress related to male infertility. Our sensors are based on the modification of conventional electrode surfaces with nanoparticles. We used diamond nanoparticles (DNp) either on glassy carbon or gold surfaces (GC/DNp and Au/DNp sensors, respectively), and copper nanoparticles electrochemically generated directly on glassy carbon surfaces (GC/CuNp). The morphology of the modified electrode surfaces was characterized by Atomic Force Microscopy (AFM), and the H2O2 determination performance evaluated by chronoamperometric measurements at different applied potentials. The best results are obtained for GC/DNp at +1.0 V, Au/DNp at −0.6 V and GC/CuNp at +0.2 V with detection limits (LD) of 1.1 μM, 2.4 μM and 2.6 μM, respectively. The analysis of H2O2 in doped synthetic semen using the GC/CuNp sensor shows the best recoveries, reaching a mean value of 103%. The GC/CuNp sensor was successfully applied to H2O2 analysis in real human semen. In this case, a H2O2 concentration of 1.42 ± 0.05 mM is found and recoveries of 102% on average are obtained.

In this paper, a new 2D lactate electrochemical biosensor was developed. It was based on the incorporation of molybdenum disulfide (MoS2) nanosheets, obtained by an exfoliation method, onto the surface of a glassy carbon (GC) electrode, together with lactate oxidase enzyme (LOx). For the sensor construction, conditions regarding the exfoliation solvent type, as well as both the size and amount of MoS2, were optimized. The biosensor platform (GC/MoS2/LOx) was topographically characterized by atomic force microscopy (AFM) and the charge transfer process occurring at the electrode interface was studied by electrochemical impedance spectroscopy (EIS). The GC/MoS2/LOx biosensor was applied to the determination of lactate in presence of hydroxymethylferrocene (HMF) as a redox mediator. Electrocatalytic effect of the system MoS2/LOx was evaluated by comparing the cyclic voltammetric biosensor response with those obtained for biosensors incorporating only one of the components (MoS2 or LOx) onto the electrode surface. Biosensors containing both components exhibit the best electrocatalytic response. From the calibration curve obtained at +0.30 V, the following analytical parameters were obtained: linear concentration range from 0.056 to 0.77 mM, high sensitivity (6.2 μA mM−1), good detection limit (17 μM) and reproducibility (RSD = 4.7%).

Gold nanoparticles (AuNPs) were capped with cucurbit [6, 7]urils or α- and β-cyclodextrins. The resulting macrocycle-coated AuNPs are shown to enable the visual and spectrophotometric determination of cadaverine. The morphology of the modified AuNPs was characterized by transmission electron microscopy (TEM), which revealed the formation of spherical nanosystems with a narrow size distribution. The macrocycle-coated AuNPs are stable under storage conditions for at least 3 months and well dispersible in water. The cadaverine assay is based on the ability of cucurbiturils and cyclodextrins to recognize diamines. This leads to changes in the UV-vis absorption spectra due to particle aggregation, accompanied by a colour change from red to blue. By using the α-cyclodextrin-coated AuNPs, cadaverine can be quantified by spectrophotometry with a 3.9 μM detection limit.

[EN] Background: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. Objectives: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. Methods: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. Results: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (beta(T3vsT1) = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (beta(T3vsT1) = 3.12; 95% CI: 0.99, 5.25) and gondoic (beta(T3vsT1) = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (beta(T3vsT1) = 5.22; 95% CI: 3.15, 7.29) and elaidic (beta(T3vsT1) = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (omega-6) linoleic (beta(T3vsT1) = -5.49; 95% CI; -7.62, -3.35) and arachidonic (beta(T3vsT1) = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo. gamma-linolenic acids were associated with higher MD. Conclusions: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually., This study was funded by the Carlos III Institute of Health (AESI PI15CIII/0029). The article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health.

We present the development of an electrochemical sensor towards the simultaneous analysis of a mixture of food additives: sunset yellow (SY) and quinoline yellow (QY) dyes. The sensor is based on the synergetic effect observed between diamond nanoparticles (DNPs) and WS nanosheets obtained by liquid exfoliation. The prepared TMDs were characterized using Raman spectroscopy, X-Ray Diffraction (XRD) and Atomic Force Microscopy (AFM). The AFM characterization showed isolated WS flakes with different lateral dimensions scattered over the flat background. The combination of WS and DNPs allows resolution of the oxidation signals of the analytes, which overlap working with the bare glassy carbon (GC) electrode. The best electroanalytical response was obtained with a sensor containing both nanomaterials deposited employing the drop-casting method in a sequential manner, a first layer of WS and a second layer of DNPs (GC/WS/DNPs). Electrochemical impedance spectroscopy experiments showed that for the GC/WS/DNPs system the charge transfer is clearly improved. Under optimized differential pulse voltammetry conditions, the GC/WS/DNPs sensor allows the determination of SY at +100 mV and QY at +850 mV with detection limits of 0.086 and 3.4 μM respectively, with relative errors ≤ 8.40 % and a relative standard deviation ≤ 12.6 %. The proposed methodology was applied to the determination of SY and QY in commercial throat lozenge samples with very good recoveries on average: 93 %, for QY and 106 % for SY., The authors acknowledge financial support from the Spanish MINECO (MAT2017-85089-C2-1-R, MAT2017-85089-C2-2-R) and the Comunidad Autónoma de Madrid (P2018/NMT-4349, TRANSNANOAVANSENS-CM). Authors thank Patricia Reyero from the Interdepartmental Research Service (SIDI) of the Universidad Autónoma de Madrid for the XRD measure

An electrochemical sensor for the carcinogen 4,4′-oxydianiline (Oxy) is described. The method is based on the ability of MoS2 nanosheets to preconcentrate Oxy. A glassy carbon electrode (GCE) was covered, by drop-casting, with MoS2 nanosheets that were obtained by exfoliation. X-Ray photoemission spectroscopy indicates that Oxy accumulates on the MoS2 nanosheets through an electropolymerization process similar to that reported for aniline. Both electrochemical impedance spectroscopy and atomic force microscopy were used to characterize the electrode surface at the different stages of device fabrication. Employing the current measured at +0.27 V vs. Ag/AgCl after Oxy adsorption, the modified GCE enables the voltammetric detection of Oxy at 80 nM levels with relative errors and relative standard deviations of

We report on the development of an electrochemical sensor for the simultaneous determination of ponceau 4R (P4R) and tartrazine (TR) dyes in non-alcoholic beverages. The sensor is based on the sequential modification of a glassy carbon (GC) electrode with WS2 and diamond nanoparticles (DNP). First, we have performed a computational study to select, among several eco-friendly solvents, the most adequate for exfoliating the 2D nanomaterial from bulk WS2. From this study, four solvents (triacetin, triethyl citrate, dimethylisosorbide and ethanol/water) were preselected for obtaining WS2 dispersions that were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. The sensors obtained with these WS2 dispersions and DNP were tested for the determination of both dyes, finding the best results for ethanol/water. We have verified that the presence of both nanomaterials gives rise to an enhancement in the response with respect to both the bare GC and the sensor containing only one of them. The response consists of a pair of peaks corresponding to P4R (+0.69 V) and TR (+0.96 V) and a peak at around +0.2 V, coming from both dyes. After optimizing the initial potential in differential pulse voltammetric (DPV) measurements, we found that when −0.30 V is applied, the peak at +0.2 V is only due to P4R. This lower potential value is more adequate than that at +0.69 V to perform the determination of P4R. As a result of the capability to determine P4R at a low potential together with the synergistic effect between both nanomaterials, which leads to improved sensitivities, our methodology allows the simultaneous determination of both dyes with good analytical properties.

[EN] A novel optical sensor, based on the use of the macrocyclic receptor cucurbit[7]uril as molecular selector taking part of a sensing poly(vinyl chloride)-based membrane immobilized onto a quartz slide surface, has been developed and tested to thiabendazole analysis. The method is built upon the increase of the thiabendazole fluorescence as a result of the supramolecular recognition event. Variables involved in the membrane construction and fluorescence measurements have been evaluated and optimized. The sensing membrane is prepared by a spin-coating procedure (1 min at 800 r.p.m.). An increase of more than 2 fold in the fluorescence signal is observed when the supramolecular complex is immobilized into the membrane respect to that observed for the free guest. Under optimized conditions, the dispositive responds in a few seconds to thiabendazole concentrations at 10(-7) M level. In addition, the characterization of the supramolecular complex together with lifetime measurements is included., The authors would like to thank the Comunidad Autonoma de Madrid (P2018/NMT-4349, TRANSNANOAVANSENS-CM) for financial support.

The authors describe an electrochemical sensor based on the use of diamond nanoparticles (DNPs) and molybdenum disulfide (MoS2) platelets. The sensor was applied to the voltammetric determination of the anticonvulsant valproic acid which was previously derivatized with ferrocene. The MoS2 platelets were obtained by an exfoliation method, and the DNPs were directly dispersed in water and subsequently deposited on a glassy carbon electrode (GCE). The sensor response was optimized in terms of the solvent employed for dispersing the MoS2 nanomaterial and the method for modifying the GCE. Sensors consisting of a first layer of MoS2 dispersed in ethanol/water and a second layer of DNPs give better response. The single steps of sensor construction were characterized by atomic force microscopy and electrochemical impedance spectroscopy. The differential pulse voltammetric response of the GCE (measured at +0.18 V vs. Ag/AgCl) was compared to that of sensors incorporating only one of the nanomateriales (DNPs or MoS2). The formation of a hybrid MoS2-DNP structure clearly improves performance. The GCE containing both nanomaterials exhibits high sensitivity (740 µA ⋅ mM−1 ⋅ cm−2), a 0.27 μM detection limit, and an 8% reproducibility (RSD). The sensor retained 99% of its initial response after 45 days of storage.

In this work, different macrocyclic systems, belonging to cucurbit[n]urils and cyclodextrins families, were employed as stabilizers of gold nanoparticles and their performance as catalysts in the reduction reaction of the toxic 4-nitrophenol to produce the valuable 4-aminophenol, was evaluated. To this goal, six nanosystems were prepared and compared under identical experimental conditions. The influence that (i) differences in shape, (ii) nature of chemical groups constituting the receptor entrances and (iii) differences in the portal sizes of those stabilizing agents have in the activity of these nanoparticles as catalysts in a nitro compound reduction reaction is evaluated and discussed. The TEM characterization of the nanocatalysts prepared is included. From these data, nanoparticles ranging from 3.7–10.7 nm in diameter, depending on the stabilizer employed, were obtained. The evaluation of kinetic rate constants normalized respect to gold concentration and catalyst surface for each system is included and discussed. In addition, the stability of the different nanocatalyst depending on the capping agent employed is also evaluated.

The results of the development of cucurbit[8]uril (CB[8]) electrochemical sensors and their performance as electrochemical transducers in a flow injection analysis (FIA) system are described. Two electrodes were designed, using either PVC or Nafion, to immobilise the macrocyclic receptor on a glassy carbon electrode (GCE) surface and used for dopamine (Dop) determination. 1 H NMR and MS experiments were conducted to corroborate the formation of the CB[8]–Dop complex formation. Once all of the experimental variables were optimised, the developed methodologies achieved Dop detection limits of as low as 9.9 × 10 −8 M in the case of the Nafion-CB[8] based electrode and 2.6 × 10 −8 M for the case of the PVC-CB[8] electrode. For both sensors, the relative error values, E r (%), were lower than 13.9% and the relative standard deviation, RSD (%), ranged from 1.0% to 9.3% across the concentration range assayed, indicating that the methods proposed under flow conditions were of acceptable accuracy and precision. The electrodes were sufficiently durable to be used under flow conditions with no loss of reproducibility for approx. 85 successive analyses. Under optimised conditions, we were able to obtain sampling frequencies of 55 and 72 samples h −1 for the Nafion-CB[8] and PVC-CB[8]-modified electrodes, respectively. The elimination of any interference from ascorbic acid (Asc) in the Dop analysis demonstrates that the use of CB[8] leads to an additional selectivity in the method.

ObjectiveTo report the presence of a new neuronal surface antibody against the metabotropic glutamate receptor 2 antibody (mGluR2-Ab) in 2 patients with paraneoplastic cerebellar ataxia.MethodsmGluR2-Abs were initially characterized by immunohistochemistry on the rat brain and confirmed by immunofluorescence on HEK293 cells transfected with mGluR2. Additional studies included analysis of potential cross-reactivity with other mGluRs, expression of mGluR2 in patients' tumors, and the effects of mGluR2-Abs on cultures of rat hippocampal neurons.ResultsPatient 1 was a 78-year-old woman with progressive cerebellar ataxia with an initial relapsing-remitting course who developed a small-cell tumor of unknown origin. Patient 2 was a 3-year-old girl who presented a steroid-responsive acute cerebellitis preceding the diagnosis of an alveolar rhabdomyosarcoma. Patients' serum and CSF showed a characteristic immunostaining of the hippocampus and cerebellum in rat brain sections and immunolabeled the cell surface of live rat hippocampal neurons. HEK293 cells transfected with mGluR1, 2, 3, and 5 confirmed that patients' antibodies only recognized mGluR2. mGluR2-Abs were not detected in 160 controls, 120 with paraneoplastic, autoimmune, or degenerative ataxias, and 40 with autoimmune encephalitis and antibodies against mGluR5 or unknown antigens. Expression of mGluR2 in tumors was confirmed by immunohistochemistry using a commercial mGluR2-Ab. Incubation of live rat hippocampal neurons with CSF of patient 2 did not modify the density of surface mGluR2 clusters.ConclusionsmGluR2-Abs are a novel biomarker of paraneoplastic cerebellar ataxia. The potential pathogenic effect of the antibodies is not mediated by downregulation or internalization of neuronal surface mGluR2.

This work presents the electrochemical behaviour of the supramolecular complex formed between the macrocyclic receptor cucurbit[7]uril and the fungicide carbendazim. Moreover, this host molecule is used to develop a selective and sensitive differential pulse voltammetric method for the determination of carbendazim through its cucurbit[7]uril inclusion complex, allowing the detection of the analyte at 4.25×10−9 M. The method was applied to the determination of the fungicide in untreated apple peel samples after a matrix solid-phase dispersion sample preparation procedure. The detection limit calculated for this real sample was 0.17 mg kg−1, which is below the legally allowed limit of 0.20 mg kg−1.

Ts65Dn mouse is the most widely accepted model for Down syndrome. We previously showed that environmental enrichment improved spatial learning in female but deteriorated it in male Ts65Dn mice. This study analyzed the factors contributing to the disturbed cognition of male Ts65Dn mice after enriched housing, by allocating male control and Ts65Dn mice in four conditions after weaning: small (n = 2-3) and large group (n = 8-10) housing, and enriched housing in small (2-3) and large groups (8-10). Learning, aggressive behavior, anxiety-like behavior and biochemical correlates of stress were evaluated when Ts65Dn and control mice were 4-5 months old. Environmental enrichment in large mixed colonies of Ts65Dn and diploid littermates disturbed behavioral and learning skills of Ts65Dn mice in the Morris water maze. ACTH and testosterone levels were not modified in any group of mice. Ts65Dn and control mice subjected to enriched housing in large groups and Ts65Dn mice housed in large groups showed higher corticosterone levels. Aggressive behavior was evaluated by measuring the number of attacks performed in the presence of an intruder. Ts65Dn mice performed less attacks than controls in all conditions, especially after enriched housing, indicating subordination. In the plus maze, cognitive aspects (i.e. risk assessment) and motor components (open arm avoidance) of anxiety behavior were evaluated; no difference in any condition was found. It is suggested that an excess of social and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the emotional and behavioral components of the learning process.

The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology., This work was supported through grants from the Instituto de Formación e Investigación Marqués de Valdecilla (FMV-API 10/19), the Jerome Lejeune Foundation and the Spanish Ministry of Economy and Competitiveness (PSI2012-33652).

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age-related cholinergic degeneration, and increased brain expression of β-amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long-term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β-amyloid levels of TS mice. Melatonin was administered for 5 months to 5- to 6-month-old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)-positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β-amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age-related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age-related progression of cognitive deterioration found in DS.

Three different strategies for cucurbit[8]uril immobilization on a glassy carbon electrode have been assayed. The electrochemical properties of the resulting modified electrodes in solutions containing neutral, positively and negatively charged potential cucurbit[8]uril guests were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The comparison of the electrochemical behaviour exhibited by the unmodified electrodes against various probes, with respect to that of each modified electrode, resulted in an appropriate method to choose among different strategies for the development of electrochemical sensors. These sensors are based on the incorporation of the cucurbit[8]uril molecular selection properties that depend on the chemical characteristics of the potential analytes. Furthermore, atomic force microscopy was employed for the characterization of the different surfaces developed.

Hyperactivity is a feature frequently reported in behavioral studies on the Ts65Dn (TS) mouse, the most widely accepted model of Down syndrome, when tested in anxiety-provoking situations such as the plus-maze and the open-field tests. Although this behavior could be considered as an expression of reduced anxiety, it has been considered as a consequence of a lack of behavioral inhibition and/or reduced attention. This study addressed anxiety and panic behavior of male and female TS mice by evaluating serum biochemical parameters and behavioral responses to a predator in the Mouse Defense Test Battery. Flight, risk assessment, defensive threat/attack and escape attempts were measured during and after rat confrontation. When confronted to a rat, male TS mice showed similar biochemical and behavioral responses as control mice. However, female control and TS mice presented lower serum adrenocorticotropic hormone (ACTH) levels under basal conditions and higher corticosterone levels after predator exposure than male mice. Thus, there was a larger increase in ACTH and corticosterone levels after predator exposure with respect to the undisturbed condition in females than in males. In addition, TS females showed some alterations in defensive behaviors after predator exposure. The results emphasize the need to consider gender as a confounding factor in the behavioral assessment of TS mice.

Un principio fundamental de las finanzas es que el valor de cualquier activo es igual al valor actual de sus flujos de caja. Como los contratos de seguros implican flujos de caja en diferentes momentos del tiempo, el método del descuento de flujos de caja proporciona un planteamiento natural para la valoración del seguro. Aunque los principios del descuento de flujos de caja han formado las bases para la ciencia actuarial de vida, es relativamente reciente la introducción para el uso en seguros de no-vida. Tanto los modelos de tiempo discreto como los de tiempo continuo han sido aplicados a problemas del seguro, a ellos se refiere este artículo.

Se tratan las modalidades de reaseguro, centrándonse en las no proporcionales, excess loss (XL) y stop loss, estudiando la variación de la distribución de la siniestralidad antes y después del reaseguro. También se trata de la aplicación de la teoría de opciones al contrato de reaseguro, para finalmente, mediante la aplicación de esta teoría obtener la prima de un contrato de reaseguro.

El negocio asegurador se caracteriza por la variable aleatoria siniestralidad ampliamente estudiada en la Teoría de Riesgo Clásica cuyos dos objetivos fundamentales son estudiar la distribución de la siniestralidad a partir de las variables básicas (número de siniestros y la cuantía de un siniestro) y la estabilidad del negocio asegurador, analizando el efecto que las fluctuaciones de la siniestralidad producen en el mismo y las medidas para evitar que estas conduzcan a la empresa a la ruina.

Este artículo trata el estudio y aplicación de la Teoría financiera al campo del seguro. A este normalmente le han sido aplicados los modelos estadísticos y actuariales, pero gracias a la moderna Teoría financiera se le pueden aplicar, entre otros, modelos financieros tales como el Insurance CAPM, el modelo de valoración de opciones y el modelo de descuentos de flujos de caja. Se estudia del modelo de valoración de opciones aplicado a la valoración de una empresa aseguradora.

Se trata en primer lugar de las características fundamentales que debería tener un modelo de control de la solvencia de las empresas aseguradoras. En segundo lugar el fundamento científico y metodología del mismo. En tercer lugar las condiciones de acceso y ejercicio que deben cumplir las empresas de seguros así como las medidas a tomar en caso de incumplimiento. Para finalmente, realizar un estudio crítico del modelo de control vigente actualmente en la Unión Europea.

The host–guest properties of cucurbit[8]uril have been employed to modify a conventional electrode surface in order to increase its analytical performance. The new electrode surface has been characterized, and the influence of different experimental parameters on complex formation has been investigated in detail using different electrochemical techniques. The results of electrochemical spectroscopic impedance studies are in good agreement with the electrochemical behaviour shown by this electrode material in terms of the molecular-recognition properties of this nanosize receptor to positively or negatively charged guests. The electrode developed herein has enhanced sensitivity and selectivity, as demonstrated by its application to the determination of tryptophan in real samples, with a good accuracy and precision and no need for any additional sample treatment.

El artículo detalla las funciones del Centro de Intervención en el patrimonio histórico del IAPH, como unidad administrativa responsable de la formulación y ejecución de los programas de conservación y actuación sobre el patrimonio histórico que ejecuta el Instituto, de la investigación de las fuentes, métodos y técnicas que contribuyen al conocimiento completo de los bienes sobre los que se proyecta la intervención, y de la prestación de los ser vicios técnicos y científicos necesarios para las mismas.