Collaborative permeation of drug and excipients in transdermal formulations. In vitro scrutiny for ethanol:limonene combinations.

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance. Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them.

Evidence of Partial Seniority Conservation in the πg_{9/2} Shell for the N=50 Isotones.

The reduced transition probabilities for the 4_{1}^{+}→2_{1}^{+} and 2_{1}^{+}→0_{1}^{+} transitions in ^{92}Mo and ^{94}Ru and for the 4_{1}^{+}→2_{1}^{+} and 6_{1}^{+}→4_{1}^{+} transitions in ^{90}Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f_{5/2}, p_{3/2}, p_{1/2}, and g_{9/2} proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N=50 g_{9/2} orbital to be understood. The conclusion is that seniority is largely conserved in the first πg_{9/2} orbital.

Orbital Complexity in Intrinsic Magnetic Topological Insulators MnBi_{4}Te_{7} and MnBi_{6}Te_{10}.

Using angle-resolved photoelectron spectroscopy (ARPES), we investigate the surface electronic structure of the magnetic van der Waals compounds MnBi_{4}Te_{7} and MnBi_{6}Te_{10}, the n=1 and 2 members of a modular (Bi_{2}Te_{3})_{n}(MnBi_{2}Te_{4}) series, which have attracted recent interest as intrinsic magnetic topological insulators. Combining circular dichroic, spin-resolved and photon-energy-dependent ARPES measurements with calculations based on density functional theory, we unveil complex momentum-dependent orbital and spin textures in the surface electronic structure and disentangle topological from trivial surface bands. We find that the Dirac-cone dispersion of the topologial surface state is strongly perturbed by hybridization with valence-band states for Bi_{2}Te_{3}-terminated surfaces but remains preserved for MnBi_{2}Te_{4}-terminated surfaces. Our results firmly establish the topologically nontrivial nature of these magnetic van der Waals materials and indicate that the possibility of realizing a quantized anomalous Hall conductivity depends on surface termination.

[Psychological interventions on fetal alcohol spectrum disorder across the life span]. / Intervenciones psicológicas del trastorno del espectro alcohólico fetal a lo largo del ciclo vital.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is the leading known and preventable cause of intellectual disability in the western world, affecting up to 1-5% of the population. It is considered an underdiagnosed and undertreated disorder, with few psychological interventions with empirical evidence. AIM: To review all the studies published to date on the psychological treatment of FASD throughout life. A bibliographic search was carried out using the MEDLINE, PsychINFO, PubMed and Cochrane Library databases using the terms 'fetal alcohol syndrome disorder' AND 'cognitive behavioral intervention' OR 'psychological intervention' OR 'psychological treatment' OR 'therapy' OR 'psychotherapy'. The review included published works which evaluate the efficacy of psychological treatments for these patients. DEVELOPMENT: Twenty published studies met the inclusion criteria. The treatments were classified according to the type of intervention: emotional and behavioral regulation, social skills training and family interventions for patients with FASD. CONCLUSIONS: The results indicate that psychological treatments focused on emotional and behavioral regulation, social skills training and family interventions are the most evidenced treatments for these patients. These treatments are based on cognitive-behavioral principles and include school-age children. However, more research is needed on psychological interventions for adults with FASD. Despite the progress in psychological interventions for FASD, the research still reflects highlighted limitations.

TITLE: Intervenciones psicológicas del trastorno del espectro alcohólico fetal a lo largo del ciclo vital.Introducción. El trastorno del espectro alcohólico fetal (TEAF) es la principal causa conocida y prevenible de discapacidad intelectual en el mundo occidental y afecta hasta al 1-5% de la población. Se considera un trastorno infradiagnosticado e infratratado, y las intervenciones psicológicas con evidencia empírica son escasas. Objetivo. Revisar los estudios publicados hasta el momento sobre tratamiento psicológico del TEAF a lo largo de la vida. Se realizó una búsqueda bibliográfica mediante las bases de datos de Medline, PsychINFO, PubMed y Cochrane Library usando los términos 'fetal alcohol syndrome disorder' AND 'cognitive behavioral intervention' OR 'psychological intervention' OR 'psychological treatment' OR 'therapy' OR 'psychotherapy'. Se incluyeron los trabajos publicados que evaluaran la eficacia de tratamientos psicológicos para estos pacientes. Desarrollo. Cumplieron los criterios de inclusión 20 estudios publicados. Los tratamientos se clasificaron en función del tipo de intervención: la regulación emocional y conductual, el entrenamiento en habilidades sociales y las intervenciones familiares. Conclusiones. Los resultados indican que los tratamientos psicológicos dirigidos a trabajar la regulación emocional y conductual, el entrenamiento en habilidades sociales y las intervenciones familiares son los que tienen mayor evidencia en el tratamiento para el TEAF. La mayoría se basa en principios cognitivo-conductuales y a niños de edad escolar, y son escasas todavía las investigaciones de tratamientos para adultos con TEAF. A pesar del progreso en las intervenciones psicológicas para el TEAF, la investigación aún refleja marcadas limitaciones.

Increased kynurenine concentration attenuates serotonergic neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats through activation of aryl hydrocarbon receptor.

3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has been shown to produce serotonergic damage in the brains of primates, including humans, and of rats. Tryptophan, the precursor of serotonin, is primarily degraded through the kynurenine (KYN) pathway, producing among others KYN, the main metabolite of this route. KYN has been reported as an endogenous agonist of the aryl hydrocarbon receptor (AhR), a transcription factor involved in several neurological functions. This study aims to determine the effect of MDMA on the KYN pathway and on AhR activity and to establish their role in the long-term serotonergic neurotoxicity induced by the drug in rats. Our results show that MDMA induces the activation of the KYN pathway, mediated by hepatic tryptophan 2,3-dioxygenase (TDO). MDMA also activated AhR as evidenced by increased AhR nuclear translocation and CYP1B1 mRNA expression. Autoradiographic quantification of serotonin transporters showed that both the TDO inhibitor 680C91 and the AhR antagonist CH-223191 potentiated the neurotoxicity induced by MDMA, while administration of exogenous l-kynurenine or of the AhR positive modulator 3,3'-diindolylmethane (DIM) partially prevented the serotonergic damage induced by the drug. The results demonstrate for the first time that MDMA increases KYN levels and AhR activity, and these changes appear to play a role in limiting the neurotoxicity induced by the drug. This work provides a better understanding of the physiological mechanisms that attenuate the brain damage induced by MDMA and identify modulation of the KYN pathway and of AhR as potential therapeutic strategies to limit the negative effects of MDMA.

Prematurity and ADHD in Childhood: An Observational Register-Based Study in Catalonia.

Objective: To evaluate the association between prematurity (by the gestational week [gw]) and ADHD during childhood. Method: Observational, matched cohort study using data from children born in a tertiary-level hospital (Hospital Universitari Vall d'Hebron, Catalonia, Spain) during 1995-2007 and data from the Information System for the Development of Research in Primary Health Care (SIDIAP database, Catalonia, Spain). Results: Prevalence of ADHD increases as gestational age decreases, 12.7% for those born ≤28 gw, compared to 3.2% for those born after the 37 gw. The risk of developing ADHD in the non-premature children tends to increase as the gw decreases (35-36 gw, hazard ratio [HR] = 1.70, 95% confidence interval [CI] [1.19, 2.44]; 33-34 gw, HR = 3.38, 95% CI [2.08, 5.50]; 29-32 gw, HR = 2.37, 95% CI [1.54, 3.63]; and ≤28 gw, HR = 5.57, 95% CI [2.49, 12.46]) Conclusion: Being born preterm is associated with a risk of developing ADHD, also in late preterm children (35-36 gw). Attention when taking care of these infants regarding their mental health must be made.

Relationship between infrared skin radiation and functional tests in patients affected by Emery-Dreifuss muscular dystrophy: Part 2.

HYPOTHESIS: This study represents a second part of a recently published study about a new form of evaluation and development of rare genetic neurodegenerative diseases. The objective is to provide a more global vision of thermography with respect to the Emery-Dreifuss pathology, through the analysis of the data collection carried out for one year. The basic hypothesis is that thermography could become a valid tool for the diagnosis and follow-up of this pathology because is a very specific tool for registering temperature changes produced by a constant degenerative evolution of this muscular dystrophy.

Predictors of a positive oral food challenge to cow's milk in children sensitized to cow's milk

INTRODUCTION AND OBJECTIVES: The diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA. MATERIAL AND METHODS: We retrospectively studied 72 patients [median age, four years; age range 0.75-15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables' discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA. RESULTS: The OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p < 0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by β-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥ 0.95kU/L yielded 88.9% sensitivity and 90.9% specificity. CONCLUSIONS: In our center, casein-specific IgE > 0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history

No disponible

Predictors of a positive oral food challenge to cow's milk in children sensitized to cow's milk.

INTRODUCTION AND OBJECTIVES: The diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA. MATERIAL AND METHODS: We retrospectively studied 72 patients [median age, four years; age range 0.75-15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables' discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA. RESULTS: The OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p<0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by ß-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥0.95kU/L yielded 88.9% sensitivity and 90.9% specificity. CONCLUSIONS: In our center, casein-specific IgE >0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history.

Lactante con distrés respiratorio en invierno. Más allá de las bronquiolitis / Infant with respiratory disters in winter. Beyond bronchiolitis

La dificultad respiratoria en el lactante engloba varias entidades clínicas. Aunque en invierno la más frecuente es la bronquiolitis, no debemos olvidar, entre ellas, las malformaciones pulmonares congénitas (MPC). Se presenta el caso de un lactante de 6 semanas de vida que acudió a Urgencias en invierno por un cuadro de dificultad respiratoria en contexto catarral. Se realizó un diagnóstico inicial de bronquiolitis, pero posteriormente se alcanzó el diagnóstico correcto de enfisema lobar congénito (ELC). Se publica este caso para hacer hincapié en la importancia de revisar un diagnóstico con enfoque analítico, especialmente cuando el curso clínico no es típico. También nos debe servir para recordar que, a pesar de la mejora del diagnóstico prenatal, el diagnóstico de una MPC puede ser en el periodo neonatal o incluso más tardío. Por lo tanto, las MPC deben considerarse en el diagnóstico diferencial de síntomas respiratorios en un niño

Respiratory distress in the infant encompasses several clinical entities. Although bronchiolitis is the most frequent in winter, we should not forget congenital pulmonary malformations (CPMs). We are reporting a case of 6-week-old male presented to pediatric emergency ward during the winter period with respiratory distress in context of a cold. An initial diagnosis of bronchiolitis was made. The authors explore how the correct diagnosis of congenital lobar emphysema (CLE) was reached. This case emphasizes the importance of reviewing a diagnosis through an analytical approach, particularly in non-typical clinical courses. It should also help us to remember that despite the improvement of prenatal diagnosis, we also have CPMs diagnosis in the neonatal period or even later. Therefore, CPMs need to be considered in the differential diagnosis of respiratory symptoms in a child

Prediction and observation of an antiferromagnetic topological insulator.

Magnetic topological insulators are narrow-gap semiconductor materials that combine non-trivial band topology and magnetic order1. Unlike their nonmagnetic counterparts, magnetic topological insulators may have some of the surfaces gapped, which enables a number of exotic phenomena that have potential applications in spintronics1, such as the quantum anomalous Hall effect2 and chiral Majorana fermions3. So far, magnetic topological insulators have only been created by means of doping nonmagnetic topological insulators with 3d transition-metal elements; however, such an approach leads to strongly inhomogeneous magnetic4 and electronic5 properties of these materials, restricting the observation of important effects to very low temperatures2,3. An intrinsic magnetic topological insulator-a stoichiometric well ordered magnetic compound-could be an ideal solution to these problems, but no such material has been observed so far. Here we predict by ab initio calculations and further confirm using various experimental techniques the realization of an antiferromagnetic topological insulator in the layered van der Waals compound MnBi2Te4. The antiferromagnetic ordering  that MnBi2Te4  shows makes it invariant with respect to the combination of the time-reversal and primitive-lattice translation symmetries, giving rise to a ℤ2 topological classification; ℤ2 = 1 for MnBi2Te4, confirming its topologically nontrivial nature. Our experiments indicate that the symmetry-breaking (0001) surface of MnBi2Te4 exhibits a large bandgap in the topological surface state. We expect this property to eventually enable the observation of a number of fundamental phenomena, among them quantized magnetoelectric coupling6-8 and axion electrodynamics9,10. Other exotic phenomena could become accessible at much higher temperatures than those reached so far, such as the quantum anomalous Hall effect2 and chiral Majorana fermions3.

Epidemiological and virological findings during an outbreak of equine influenza in Uruguay in 2018.

Equine influenza is one of the major respiratory infectious diseases in horses. In 2018, equine influenza virus (EIV) was confirmed as the cause of outbreaks of respiratory disease in horses in Chile and Argentina. In the same year, for the first time in Uruguay, EIV infection was confirmed by isolation and molecular analysis to be the cause of respiratory disease among hundreds of clinically affected thoroughbred horses in training and racing facilities. The virus was detected in nasopharyngeal swabs by a pan-reactive influenza type A realtime reverse transcription polymerase chain reaction (rRT-PCR). The partial nucleotide sequence of the haemagglutinin 1 (HA1 ) gene (994 base pairs) was determined and analysed phylogenetically using MEGA X software. Amino acid sequence alignments were constructed, and serum samples were tested by haemagglutination inhibition and single radial haemolysis. The diagnosis of EIV was confirmed by rRT-PCR, virus isolation and serological testing. The phylogenetic analysis of the partial HA1 gene sequence of the isolated virus indicated that it belongs to clade 1 of the Florida sub-lineage of the American lineage and is closely related to viruses isolated in the recent past. Study of the HA1 region (331 amino acids) of the virus identified in horses in racing facilities in Uruguay displayed the highest amino acid sequence identity with viruses detected in Argentina, Chile and the United Kingdom in 2018. The surveillance data reported illustrate the international spread of EIVs and support the recommendation of the World Organisation for Animal Health (OIE) Expert Surveillance Panel to include viruses of the Florida sub-lineage in vaccines.

La grippe équine est l'une des principales maladies respiratoires infectieuses affectant les équidés. En 2018, il a été confirmé que des foyers de maladie respiratoire enregistrés chez des chevaux au Chili et en Argentine étaient dus au virus de la grippe équine. Cette même année en Uruguay, pour la première fois dans ce pays, il a été établi par isolement viral et par des méthodes moléculaires que le virus de la grippe équine était l'agent causal d'une maladie respiratoire affectant cliniquement des centaines de chevaux pur-sang dans des centres d'entraînement et des hippodromes. La détection du virus s'est faite à partir d'écouvillons prélevés par voie naso-pharyngée en appliquant une technique d'amplification en chaîne par polymérase couplée à une transcription inverse en temps réel (rRT­PCR) à large spectre pour les virus influenza de type A. Une séquence nucléotidique partielle correspondant au gène de l'hémagglutinine 1 (HA1) (994 paires de bases) a fait l'objet d'une analyse phylogénétique au moyen du programme informatique MEGA X. Il a été procédé à la construction d'une matrice d'alignements de ces séquences d'acides aminés. D'autre part, des prélèvements de sérum issus de chevaux atteints ont été soumis à l'épreuve d'inhibition de l'hémagglutination et à une hémolyse radiale unique. Aussi bien la rRT­PCR que l'isolement viral et l'analyse sérologique ont confirmé le diagnostic de l'infection par le virus de la grippe équine. Il ressort de l'analyse phylogénétique du fragment de séquence du gène HA1 du virus isolé que ce dernier appartient au clade 1 de la sous-lignée Florida de la lignée américaine et qu'il est étroitement apparenté à des virus isolés au cours des dernières années. L'étude de la région HA1 (331 acides aminés) du virus détecté chez des chevaux de course en Uruguay a montré que les virus qui présentaient la plus grande similitude avec cette séquence d'acides aminés étaient ceux détectés en Argentine, au Chili et au Royaume-Uni en 2018. Les données de surveillance rapportées illustrent la propagation à l'échelle internationale des virus de la grippe équine et renforcent la recommandation émise par le Groupe d'experts de l'Organisation mondiale de la santé animale (OIE) chargé de la surveillance de la composition des vaccins contre la grippe équine d'inclure les virus de la sous-lignée Florida dans la composition de ces vaccins.

La gripe equina es una de las principales infecciones respiratorias que afectan al caballo. En 2018 se confirmó que el virus de la gripe equina era la causa de diversos brotes de afección respiratoria que habían afectado a caballos de Chile y Argentina. Ese mismo año, por primera vez en el Uruguay, se confirmó por aislamiento y análisis molecular que el virus de la gripe equina era la causa de una infección respiratoria que, acompañada de manifestaciones clínicas, afectó a cientos de caballos purasangre de hipódromos y centros de adiestramiento. El virus fue detectado en muestras de frotis nasales mediante una técnica de reacción en cadena de la polimerasa acoplada a transcripción inversa en tiempo real (rRT­PCR, por sus siglas en inglés) que reacciona ante todos los virus gripales de tipo A. Tras secuenciar parcialmente el gen de la hemaglutinina 1 (HA1 ) (994 pares de bases), se procedió a su análisis filogenético empleando el programa informático MEGA X. Además de crear una matriz de alineamiento de secuencias de aminoácidos, se sometieron muestras de suero a pruebas de inhibición de la hemaglutinación y hemólisis radial simple. Así, el diagnóstico que apuntaba al virus de la gripe equina fue confirmado por rRT­PCR, aislamiento vírico y análisis serológico. El análisis filogenético de la secuencia parcial del gen HA1 del virus aislado puso de manifiesto que pertenece al clado 1 del sublinaje Florida del linaje americano y guarda estrecho parentesco con otros virus aislados en fechas recientes. El estudio de la región HA1 (331 aminoácidos) del virus detectado en caballos de hipódromos uruguayos reveló que el mayor nivel de concordancia de su secuencia de aminoácidos se daba con virus detectados en Argentina, Chile y el Reino Unido en 2018. Los datos de vigilancia comunicados dan fe de la propagación internacional de los virus de la gripe equina y avalan la recomendación formulada por el Panel de expertos en vigilancia de la composición de las vacunas contra la gripe equina de la Organización Mundial de Sanidad Animal (OIE), que aboga por incluir virus del sublinaje Florida en las vacunas.

Pseudospin Symmetry and Microscopic Origin of Shape Coexistence in the

Lifetime measurements of excited states of the light N=52 isotones ^{88}Kr, ^{86}Se, and ^{84}Ge have been performed, using the recoil distance Doppler shift method and VAMOS and AGATA spectrometers for particle identification and gamma spectroscopy, respectively. The reduced electric quadrupole transition probabilities B(E2;2^{+}→0^{+}) and B(E2;4^{+}→2^{+}) were obtained for the first time for the hard-to-reach ^{84}Ge. While the B(E2;2^{+}→0^{+}) values of ^{88}Kr, ^{86}Se saturate the maximum quadrupole collectivity offered by the natural valence (3s, 2d, 1g_{7/2}, 1h_{11/2}) space of an inert ^{78}Ni core, the value obtained for ^{84}Ge largely exceeds it, suggesting that shape coexistence phenomena, previously reported at N≲49, extend beyond N=50. The onset of collectivity at Z=32 is understood as due to a pseudo-SU(3) organization of the proton single-particle sequence reflecting a clear manifestation of pseudospin symmetry. It is realized that the latter provides actually reliable guidance for understanding the observed proton and neutron single particle structure in the whole medium-mass region, from Ni to Sn, pointing towards the important role of the isovector-vector ρ field in shell-structure evolution.

Melatonin Treatment Enhances Aß Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis.

BACKGROUND: It has been postulated that inadequate clearance of the amyloid ß protein (Aß) plays an important role in the accumulation of Aß in sporadic late onset Alzheimer's disease (AD). While the blood brain barrier (BBB) has taken the center stage in processes involving Aß clearance, little information is available about the role of the lymphatic system. We previously reported that Aß is cleared through the lymphatic system. We now assessed lymphatic Aß clearance by treating a mouse model of AD amyloidosis with melatonin, an Aß aggregation inhibitor and immuno-regulatory neurohormone. OBJECTIVE: To confirm and expand our initial finding that Aß is cleared through the lymphatic system. Lymphatic clearance of metabolic and cellular "waste" products from the brain into the peripheral lymphatic system has been known for a long time. However, except for our prior report, there is no additional experimental data published about Aß being cleared into peripheral lymph nodes. METHODS: For these experiments, we used a transgenic mouse model (Tg2576) that over-expresses a mutant form of the Aß precursor protein (APP) in the brain. We examined levels of Aß in plasma and in lymph nodes of transgenic mice as surrogate markers of vascular and lymphatic clearance, respectively. Aß levels were also measured in the brain and in multiple tissues. RESULTS: Clearance of Aß peptides through the lymphatic system was confirmed in this study. Treatment with melatonin led to the following changes: 1-A statistically significant increase in soluble monomeric Aß40 and an increasing trend in Aß42 in cervical and axillary lymph nodes of treated mice. 2- Statistically significant decreases in oligomeric Aß40 and a decreasing trend Aß42 in the brain. CONCLUSION: The data expands on our prior report that the lymphatic system participates in Aß clearance from the brain. We propose that abnormalities in Aß clearance through the lymphatic system may contribute to the development of cerebral amyloidosis. Melatonin and related indole molecules (i.e., indole- 3-propionic acid) are known to inhibit Aß aggregation although they do not reverse aggregated Aß or amyloid fibrils. Therefore, these substances should be further explored in prevention trials for delaying the onset of cognitive impairment in high risk populations.

Construyendo la historia de la cirugía endovascular / Creating the history of endovascular surgery

Se relata la aparición de la cirugía mínimamente invasiva y dentro de ella la técnicas endovasculares, en relación con la evolución sociocultural de las relaciones médico-paciente desde la era del llamado paternalismo médico hasta que una vez aparecidos los derechos humanos y los derechos de los enfermos, estos pasan a tener autonomía sobre su salud y la técnicas diagnósticas y terapéuticas que reciben. Finalmente se relata brevemente la historia de las técnicas endovasculares y se propone formalmente el nombre de Cirugía Endovascular para englobarlas y se hacen unas consideraciones finales sobre la actual tecnolatría hacia el desarrollo tecnológico que conllevan (AU)

The appearance of minimally invasive surgery, and within it, the endovascular techniques, in relation to the sociocultural evolution of the doctor-patient relationship from the era of the so-called medical paternalism that, once the human rights and the rights of the patients came on the scene, patients gained freedom as regards their health, diagnosis and therapeutic techniques they receive. Finally, the history of endovascular techniques is briefly described, and the name Endovascular Surgery is formally proposed to include these. Finally, some thoughts are expressed on the current technolatry and the technological developments they entail (AU)

_{36}

Prompt γ-ray spectroscopy of the neutron-rich ^{96}Kr, produced in transfer- and fusion-induced fission reactions, has been performed using the combination of the Advanced Gamma Tracking Array and the VAMOS++ spectrometer. A second excited state, assigned to J^{π}=4^{+}, is observed for the first time, and a previously reported level energy of the first 2^{+} excited state is confirmed. The measured energy ratio R_{4/2}=E(4^{+})/E(2^{+})=2.12(1) indicates that this nucleus does not show a well-developed collectivity contrary to that seen in heavier N=60 isotones. This new measurement highlights an abrupt transition of the degree of collectivity as a function of the proton number at Z=36, of similar amplitude to that observed at N=60 at higher Z values. A possible reason for this abrupt transition could be related to the insufficient proton excitations in the g_{9/2}, d_{5/2}, and s_{1/2} orbitals to generate strong quadrupole correlations or to the coexistence of competing different shapes. An unexpected continuous decrease of R_{4/2} as a function of the neutron number up to N=60 is also evidenced. This measurement establishes the Kr isotopic chain as the low-Z boundary of the island of deformation for N=60 isotones. A comparison with available theoretical predictions using different beyond mean-field approaches shows that these models fail to reproduce the abrupt transitions at N=60 and Z=36.

[Treatment of attention deficit hyperactivity disorder in adults using virtual reality through a mindfulness programme]. / Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder, which presents a high comorbidity with anxiety and affective signs and symptoms. It has repercussions on the functioning of those suffering from it, who also have low therapy compliance and generate a significant cost both at a personal level and for society. Mindfulness is a psychological treatment that has proved to be effective for ADHD. Virtual reality is widely used as treatment in cases of phobias and other pathologies, with positive results. AIMS: To develop the first treatment for ADHD in adults based on virtual reality and mindfulness, while also resulting in increased treatment adherence and reduced costs. PATIENTS AND METHODS: We conducted a pilot study with 25 patients treated by means of virtual reality, in four 30-minute sessions, and 25 treated with psychostimulants. Measures will be taken pre-treatment, post-treatment and at 3 and 12 months post-treatment, to evaluate both ADHD and also depression, anxiety, functionality and quality of life. Data will be later analysed with the SPSS v. 20 statistical program. An ANOVA of independent groups will be performed to see the differences between treatments and also a test-retest to detect whether the changes will be maintained. RESULTS AND CONCLUSIONS: It is necessary to use treatments that are effective, reduce costs and increase therapy adherence. Treatment with virtual reality is an interesting alternative to the classical treatments, and is shorter and more attractive for patients.

TITLE: Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es un trastorno del neurodesarrollo altamente prevalente, presenta una elevada comorbilidad con sintomatologia afectiva y ansiosa, afecta a la funcionalidad de la persona que lo padece, tienen una baja adhesion terapeutica y genera unos costes sociales y personales elevados. El mindfulness es un tratamiento psicologico que ha demostrado ser eficaz para el TDAH. La realidad virtual es un tratamiento altamente utilizado en fobias y extendido a otras patologias con resultados positivos. Objetivo. Desarrollar el primer tratamiento con realidad virtual y mindfulness para el TDAH en la edad adulta, que suponga un aumento en la adhesion terapeutica y reduzca costes. Pacientes y metodos. Estudio piloto de 25 pacientes tratados con realidad virtual, mediante cuatro sesiones de 30 minutos, y 25 mediante psicoestimulantes. Se tomaran medidas de evaluacion pretratamiento, postratamiento y postratamiento a los 3 y 12 meses, tanto de TDAH como de depresion, ansiedad, funcionalidad y calidad de vida. Se analizaran posteriormente con el programa SPSS v. 20 y se realizara un ANOVA de grupos independientes para ver las diferencias entre tratamientos y un test-retest para detectar el mantenimiento de los cambios. Resultados y conclusiones. Es necesaria la utilizacion de tratamientos que sean efectivos, supongan una reduccion en los costes y un aumento en la adhesion terapeutica. El tratamiento con realidad virtual se plantea como una alternativa a los tratamientos clasicos, que sea mas breve y atractiva para los pacientes.

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population.

AIM: To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). METHODS: A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. RESULTS: In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P=0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963: D'=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963: D'=0.505, r2=0.0214, P=0.142. CONCLUSION: This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.