Nicotinamide, an acetylcholinesterase uncompetitive inhibitor, protects the blood‒brain barrier and improves cognitive function in rats fed a hypercaloric diet.

Oxidative stress and inflammation induced by abundant consumption of high-energy foods and caloric overload are implicated in the dysfunction of the blood‒brain barrier (BBB), cognitive impairment, and overactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes hydrolyse acetylcholine, affecting anti-inflammatory cholinergic signalling. Our aim was to evaluate whether nicotinamide (NAM) attenuates the impairment of the BBB and cognitive function, improving cholinergic signalling. Forty male rats were distributed into five groups: one group was fed a standard diet, and the remaining groups were fed a high-fat diet and a beverage with 40% sucrose (HFS; high-fat sucrose). In three of the HFS groups, the carbohydrate was replaced by drinking water containing different concentrations of NAM for 5 h every morning for 12 weeks. The biochemical profile, levels of stress and inflammation markers, cholinesterase activities, BBB permeability, and cognitive capacity were evaluated. The results showed that the HFS diet disturbed the metabolism of carbohydrates and lipids, causing insulin resistance. Simultaneously, AChE and BChE activities, levels of proinflammatory cytokines, oxidation of proteins and lipoperoxidation increased along with decreased antioxidant capacity in serum. In the hippocampus, increased activity of cholinesterases, protein carbonylation and lipoperoxidation were associated with decreased antioxidant capacity. Systemic and hippocampal changes were reflected in increased BBB permeability and cognitive impairment. In contrast, NAM attenuated the above changes by reducing oxidative stress and inflammation through decreasing cholinesterase activities, especially by uncompetitive inhibition. NAM may be a potential systemic and neuroprotective agent to mitigate cognitive damage due to hypercaloric diets.

Analysis of spurious peaks at series resonance in solidly mounted resonators by combined BVD-Mason modelling.

Solidly Mounted Resonators (SMRs) for high frequency RF filters and sensing applications often display spurious resonances that distort their frequency response. In this work, we try to identify the origin of spurious resonances accompanying the main series resonances in AlN-based SMRs with the help of modified Butterworth Van Dyke (BVD) and Mason's models. By manufacturing SMRs of different sizes and shapes and studying the influence of the position of the electrical probing spot, we have demonstrated both theoretically and experimentally that devices with larger areas are more likely to display these additional peaks. Our updated models accurately simulate the frequency response of the SMRs, revealing that spurious peaks are mostly related to the resistance of the electrodes. Our study clarifies the origin of the spurious resonances and offers solutions for both, the optimal design and measurement method of SMRs.

Oxidative stress in the ovaries of mice chronically exposed to a low lead concentration: A generational approach.

Lead (Pb) is a heavy metal that alters the oxidation-reduction balance, affecting reproductive health and transfer during pregnancy and lactation. However, the multigenerational impact of exposure to low concentrations of Pb on mammalian ovaries has not been assessed. This study evaluated general parameters, histology, redox state (RS), protein carbonylation (PC), lipid peroxidation (LP), and hormone concentrations in the ovaries of mice (CD1® ICR) of three successive generations with both unigenerational (E1) and multigenerational (E2) exposure to 0.2 ppm lead acetate through the drinking water and a control group. Body weight, food consumption, the number of born pups, and their weight after weaning were not significantly affected by Pb exposure in E1 and E2. However, the ovaries of three successive generations of the E1 group, in which only the F0 was exposed, showed alterations in the ovarian histoarchitecture, increase in follicular atresia, decrease in the number of available follicles, and a significant RS and PC elevation that were surprisingly similar to those observed in the E2 group. LP increased in the second generation of E1 and E2, while hormone concentration was not altered. This is the first demonstration that exposure to low concentration of Pb induces multigenerational histological alterations and oxidative stress in mouse ovaries, that the termination of this exposure does not ensure the safety of later generations and that the lack of modifications in general parameters may facilitate the silent development of pathologies that affect ovarian health.

Impulsividad en el trastorno por déficit de atención e hiperactividad en niños después de una intervención de 8 semanas con dieta mediterránea y/o ácidos grasos omega-3: ensayo clínico aleatorizado / Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: A randomised clinical trial

Introducción: La Escala de Impulsividad de Barratt (BIS) es un instrumento de autoinforme diseñado para evaluar la construcción de personalidad y comportamiento de la impulsividad. La impulsividad se ha asociado con varios trastornos psiquiátricos, como el trastorno por déficit de atención e hiperactividad (TDAH). Este estudio evalúa el progreso de la conducta de impulsividad en niños con TDAH después de una intervención dietética de 8 semanas con dieta mediterránea y/o suplemento de ácidos grasos omega-3, mediante el uso de la BIS-11 adaptada para niños (BIS-11c). Métodos: Este estudio transversal incluyó a 60 niños españoles con TDAH de la provincia de Madrid, España. Los participantes se dividieron en 4 grupos, un grupo de control (G1) y 3 grupos de intervención (dieta mediterránea [G2], suplemento de omega-3 [G3] y dieta mediterránea + suplemento de omega-3 [G4]). Se diseñó una dieta mediterránea personalizada para los grupos 2 y 4. Se administró BIS-11c para determinar los niveles de impulsividad y se usó el KIDMED para evaluar la adherencia a la dieta mediterránea. Resultados: El grupo suplemento mostró una caída bastante significativa (p = 0,049) en la puntuación total de Barratt después del seguimiento. La puntuación cognitiva total disminuyó ligeramente en los grupos de dieta y suplemento. Solo el grupo control tuvo una disminución notable con respecto a la puntuación total de la impulsividad motora. Las puntuaciones totales de «falta de planificación» fueron menores en todos los grupos tras la intervención. Las asociaciones entre las puntuaciones iniciales y finales del BIS-11c y los tratamientos presentaron una correlación positiva (r > 0,9). [...](AU)

Introduction: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). Methods: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group (G1) and 3 intervention groups (Mediterranean diet [G2]; omega-3 supplementation [G3]; and Mediterranean diet plus omega-3 supplementation [G4]). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. Results: The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). Conclusion: An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population. (AU)

Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: a randomised clinical trial.

INTRODUCTION: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group and 3 intervention groups (Mediterranean diet; omega-3 supplementation; and Mediterranean diet plus omega-3 supplementation). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS: The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). CONCLUSION: An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.

The role of dopamine receptors in lymphocytes and their changes in schizophrenia.

Dopamine and its 5 receptors, which are grouped into two families (D1-like and D2-like), modulate functions at a systemic level in both the central nervous system and periphery. The central nervous system and the immune system are the main adaptive systems, which participate in a continuous and functional crosstalk to guarantee homeostasis. On binding to its 5 dopamine receptors, dopamine acts as a co-regulator of the immune system, contributing to the interaction of the central nervous system and inflammatory events and as a source of communication between the different immune cells. Dopaminergic perturbations in the central nervous system are observed in several neurological and psychiatric disorders. Schizophrenia is one of the most common mental disorders with a poorly understood pathoaetiology that includes genetic and environmental components that promote alterations in the dopaminergic system. Interestingly, abnormalities in dopamine receptors expression in lymphocytes of schizophrenia patients have been reported, often significantly correlating with the severity of the psychotic illness. Here, we review the current literature regarding the dopaminergic system in human lymphocytes and its alterations in schizophrenia.

Characterization of Anthocyanins From Intraspecific Crosses of Monastrell With Other Premium Varieties.

One way in which the wine sector is reacting to the challenge of climate change is to develop plant material that is adapted to the new conditions. Such a strategy will allow the continuation of quality viticulture in traditional winemaking areas that will otherwise be abandoned. The objective of this study was to characterize the anthocyanin composition and content of selected intraspecific hybrids of Monastrell with two other varieties (Syrah and Cabernet Sauvignon). The experiment was carried out over three successive seasons, and the polyphenolic quality of the grapes and wines was assessed along with the adaptation of the hybrids to the high temperatures which will inevitably affect our area (south-eastern Spain). The results showed that, compared with grapes of the Monastrell variety and the wines made from them, most of the hybrids (MS10, MS34, and MC111) had a higher total anthocyanin concentration and overall content of acylated anthocyanins, depending on the year studied.

Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis.

The development of effective combined anti-retroviral therapy (cART) led to a significant reduction in the death rate associated with human immunodeficiency virus type 1 (HIV-1) infection. However, recent studies indicate that considerably more than 50% of all HIV-1 infected patients develop HIV-1-associated neurocognitive disorder (HAND). Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS), and so, are also likely to contribute to the neurotoxicity observed in HAND. The activation of microglia induces the release of pro-inflammatory markers and altered secretion of cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS) which activate signalling pathways that initiate neuroinflammation. In turn, ROS and inflammation also play critical roles in HAND. However, more efforts are required to understand the physiology of microglia and the processes involved in their activation in order to better understand the how HIV-1-infected microglia are involved in the development of HAND. In this review, we summarize the current state of knowledge about the involvement of oxidative stress mechanisms and role of HIV-induced ROS in the development of HAND. We also examine the academic literature regarding crucial HIV-1 pathogenicity factors implicated in neurotoxicity and inflammation in order to identify molecular pathways that could serve as potential therapeutic targets for treatment of this disease. KEY MESSAGES Neuroinflammation and excitotoxicity mechanisms are crucial in the pathogenesis of HAND. CNS infiltration by HIV-1 and immune cells through the blood brain barrier is a key process involved in the pathogenicity of HAND. Factors including calcium dysregulation and autophagy are the main challenges involved in HAND.

Braquiterapia adaptativa guiada por resonancia magnética para el cáncer cervical localmente avanzado: experiencia del Hospital Carlos Van Buren / MRI-guided adaptive brachytherapy for locally advanced cervical cancer: experience at Carlos Van Buren Hospital

Introducción y objetivos: El tratamiento estándar para pacientes con cáncer cervical localmente avanzado (CCLA) se basa en radioterapia externa y quimioterapia concomitante seguida de braquiterapia adaptativa guiada por imágenes (BTAGI). El objetivo de este estudio fue describir los resultados del protocolo de BTAGI de resonancia magnética del Servicio de Oncología del Hospital Carlos Van Buren. Métodos: En pacientes con CCLA tratadas con Radioquimioterapia concomitante seguida de BTAGI de resonancia magnética se evaluó la reducción tumoral, parámetros dosimétricos y la toxicidad aguda. Resultados: Se evaluó la reducción tumoral entre el diagnóstico y el momento de la braquiterapia en 34 pacientes. Todas las pacientes completaron el tratamiento de radioterapia externa. Veinticuatro pacientes recibieron 3 sesiones de braquiterapia. Dosis equivalentes totales > 80 Gy se logro en todos los pacientes. Doce pacientes presentaron reducción del volumen tumoral mayor al 70%. La mediana de las dosis equivalentes totales prescritas al D2cc de vejiga fue 73.9 Gy, al recto 65.6 Gy y al intestino fue de 69.1 Gy. Una paciente presento toxicidad gastrointestinal grado ≥ 3. No hubo diferencias estadísticamente significativas al comparar pacientes que recibieron dosis equivalentes totales desde los 85 Gy con las que recibieron menor dosis respecto a toxicidad gastrointestinal (p=0.33) y genitourinaria (p=0.97). Conclusión: La braquiterapia adaptativa guiada por resonancia magnética se puede realizar en el sistema público de salud y cumplir con las recomendaciones internacionales requeridas para el tratamiento estándar del CCLA.

Introduction and purpose: External beam radiation therapy with concomitant chemotherapy followed by adaptive image-guided brachytherapy (IGABT) is the standard of care for patients with locally advanced cervical cancer (LACC). The purpose of this study was to describe the local outcomes of the magnetic resonance IGABT protocol at the radiation oncology department of the Carlos Van Buren Hospital. Methods: Tumor reduction, dosimetric parameters and acute toxicity were evaluated in patients with LACC treated with concomitant radiochemotherapy followed by magnetic resonance IGABT. Results: Tumor reduction between diagnosis and brachytherapy was evaluated in 34 patients. All patients completed external radiation therapy treatment. Twenty-four patients received 3 sessions of brachytherapy. All patients received a total equivalent dose > 80 Gy. Twelve patients showed a tumor volume reduction greater than 70%. The median total equivalent dose prescribed to the bladder D2cc was 73.9 Gy, the rectum 65.6 Gy, and the intestine 69.1 Gy. One patient presented grade ≥ 3 gastrointestinal toxicity. No statistically significant differences were found when comparing patients who received total equivalent doses larger than 85 Gy with those who received lower doses regarding gastrointestinal (p = 0.33) and genitourinary (p = 0.97) toxicity. Conclusion: MRI-guided adaptive brachytherapy can be performed in the public health system and achieve the international recommendations required as standard of care treatment of LACC.

Nicotinamide reduces inflammation and oxidative stress via the cholinergic system in fructose-induced metabolic syndrome in rats.

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.

Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: A randomised clinical trial. / Impulsividad en el trastorno por déficit de atención e hiperactividad en niños después de una intervención de 8 semanas con dieta mediterránea y/o ácidos grasos omega-3: ensayo clínico aleatorizado.

INTRODUCTION: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group (G1) and 3 intervention groups (Mediterranean diet [G2]; omega-3 supplementation [G3]; and Mediterranean diet plus omega-3 supplementation [G4]). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS: The supplementation group showed a fairly significant decrease in the total BIS-11c (P=.049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r>0.9). CONCLUSION: An intake of 550mg EPA fatty acid and 225mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.

Non-Invasive Forehead Segmentation in Thermographic Imaging.

The temperature of the forehead is known to be highly correlated with the internal body temperature. This area is widely used in thermal comfort systems, lie-detection systems, etc. However, there is a lack of tools to achieve the segmentation of the forehead using thermographic images and non-intrusive methods. In fact, this is usually segmented manually. This work proposes a simple and novel method to segment the forehead region and to extract the average temperature from this area solving this lack of non-user interaction tools. Our method is invariant to the position of the face, and other different morphologies even with the presence of external objects. The results provide an accuracy of 90% compared to the manual segmentation using the coefficient of Jaccard as a metric of similitude. Moreover, due to the simplicity of the proposed method, it can work with real-time constraints at 83 frames per second in embedded systems with low computational resources. Finally, a new dataset of thermal face images is presented, which includes some features which are difficult to find in other sets, such as glasses, beards, moustaches, breathing masks, and different neck rotations and flexions.

Low loss optical waveguides fabricated in LiTaO3 by swift heavy ion irradiation.

Optical waveguides are fabricated by irradiation of LiTaO3 with a variety of swift heavy ions that provide increasing levels of both nuclear and electronic damage rates, including C, F and Si ions, in the energy range of 15-40 MeV. A systematic study of the role of the ion fluence has been carried out in the broad range of 1e13-2e15 at/cm2. The kinetics of damage is initially of nuclear origin for the lowest fluences and stopping powers and, then, is enhanced by the electronic excitation (for F and Si ions) in synergy with the nuclear damage. Applying suitable annealing treatments, optical propagation losses values as low as 0.1 dB have been achieved. The damage rates found in LiTaO3 have been compared with those known for the reference LiNbO3 and discussed in the context of the thermal spike model.

Amortiguación de los saltos verticales según el propósito del movimiento deportivo posterior / Cushioning of Vertical Jumps According to the Purpose of Posterior Sport Movement

El principal objetivo ha sido detectar las diferencias biomecánicas de tres modelos de aterrizaje: a) aterrizaje discreto (AD), con misión de amortiguar un salto vertical, b) aterrizaje preparatorio al salto vertical (APS) y c) aterrizaje que precedía a una carrera (APC). Han participado 29 deportistas donde el salto constituye una habilidad básica. Se ha utilizado una plataforma de fuerza sincronizada a una cámara de vídeo que registraba el plano sagital de los saltos. Los resultados indican que los APS y APC amortiguan más los picos de fuerza de reacción vertical que los AD. El modelo cinemático utilizado para los APS fue similar al AD, aunque la mayor actividad neural y refleja propia del ciclo estiramiento-acortamiento para realizar el posterior salto vertical haría más eficiente la absorción de impactos. La estrategia utilizada para los APC muestra un incremento del riesgo de lesión como consecuencia del desplazamiento hacia delante de la tibia

The main objective of this study was to identify biomechanical differences among three landing styles: a) discrete landing (DL) from a drop jump; b) preparatory landing preceding jumping (LPJ), and c) landing preceding running (LPR). The sample was composed of 29 athletes who perform jumps routinely. Sagittal plane jump parameters were recorded using a camera synchronized with a force plate. Peak reaction forces were attenuated more efficiently in PL and LR, as compared to DL. The kinematic model used for PL was similar to that for DL. Yet, neural and reflex activity during muscle flexion-extension during DL makes impact absorption more efficient. LR is associated with an increased risk for injury as a result of the forward displacement of the tibia

G protein ßγ subunits play a critical role in the actions of amphetamine.

Abnormal levels of dopamine (DA) are thought to contribute to several neurological and psychiatric disorders including drug addiction. Extracellular DA levels are regulated primarily via reuptake by the DA transporter (DAT). Amphetamine, a potent psychostimulant, increases extracellular DA by inducing efflux through DAT. Recently, we discovered that G protein ßγ subunits (Gßγ) interact with DAT, and that in vitro activation of Gßγ promotes DAT-mediated efflux. Here, we investigated the role of Gßγ in the actions of amphetamine in DA neurons in culture, ex vivo nucleus accumbens (NAc), and freely moving rats. Activation of Gßγ with the peptide myr-Ser-Ile-Arg-Lys-Ala-Leu-Asn-Ile-Leu-Gly-Tyr-Pro-Asp-Tyr-Asp (mSIRK) in the NAc potentiated amphetamine-induced hyperlocomotion, but not cocaine-induced hyperlocomotion, and systemic or intra-accumbal administration of the Gßγ inhibitor gallein attenuated amphetamine-induced, but not cocaine-induced hyperlocomotion. Infusion into the NAc of a TAT-fused peptide that targets the Gßγ-binding site on DAT (TAT-DATct1) also attenuated amphetamine-induced but not cocaine-induced hyperlocomotion. In DA neurons in culture, inhibition of Gßγ with gallein or blockade of the Gßγ-DAT interaction with the TAT-DATct1 peptide decreased amphetamine-induced DA efflux. Furthermore, activation of Gßγ with mSIRK potentiated and inhibition of Gßγ with gallein reduced amphetamine-induced increases of extracellular DA in the NAc in vitro and in freely moving rats. Finally, systemic or intra-accumbal inhibition of Gßγ with gallein blocked the development of amphetamine-induced, but not cocaine-induced place preference. Collectively, these results suggest that interaction between Gßγ and DAT plays a critical role in the actions of amphetamine and presents a novel target for modulating the actions of amphetamine in vivo.

Influence of methyl jasmonate and benzothiadiazole on the composition of grape skin cell walls and wines.

Phenolic compounds are very important in crop plants, particularly in grapes. The different strategies to increase their levels include the use of elicitors such as methyl jasmonate (MeJ) and benzothiadiazole (BTH). In an attempt to improve the quality of wines, our aim was to evaluate the effect of preharvest application of these elicitors on the composition and structure of the skin cell walls of Monastrell, Merlot and Cabernet Sauvignon grapes, and to ascertain any relationship with the extractability of phenolic compounds during winemaking. The results indicated that the exogenous application of MeJ and BTH during veraison caused significant changes in several components of the skin cell walls, such as phenolic compounds, proteins and structural sugars. However these changes manifested themselves in different proportions in each variety and year, pointing to the varietal and meteorological dependence of the response to the application of these elicitors. The treatments delayed the maturation process in all varieties when rainfall was low. This observation, together with the observed increase in proteins and phenols in the skin cell wall of Monastrell and Cabernet Sauvignon, could contribute to the strength necessary to maintain the integrity of berries and to increasing resistance to fungal pathogens as the phenolic compounds evolve, thus improving the phenolic profile. However, the structural integrity of Merlot variety tended to decrease in the same conditions.

[Anatomical reconstruction of the acromioclavicular joint using autologous semitendinosus graft: modified surgical technique]. / Reconstrucción anatómica de la articulación acromioclavicular mediante injerto autólogo de semitendinoso: técnica quirúrgica modificada.

INTRODUCTION: Dislocation of the acromioclavicular joint is a common injury, which is observed mainly in young adults; indications for surgical management and the most appropriate technique remain controversial. MATERIAL AND METHODS: We present a surgical technique, whose objective is the anatomical reconstruction of the coracoclavicular ligaments with autologous semitendinous graft, without tunnels in the collarbone and without fixing devices. RESULTS: This technique is reliable for stabilizing the joint in the short term and we consider that it could neutralize the anteroposterior translation of the distal collarbone. DISCUSSION: Studies are required to report on functional and radiological results, with the use of this surgical technique so that we can then point out that it has advantages over other therapeutic options existing today.

INTRODUCCIÓN: La luxación de la articulación acromioclavicular es una lesión común que se observa principalmente en adultos jóvenes. Las indicaciones para el manejo quirúrgico y la técnica más adecuada siguen siendo controvertidas. MATERIAL Y MÉTODOS: La técnica quirúrgica presentada se basa en una reconstrucción anatómica de los ligamentos coracoclaviculares mediante un injerto autólogo del tendón del semitendinoso, sin túneles en la clavícula y sin ningún dispositivo de fijación, ya que se utilizan sólo suturas. RESULTADOS: Se logró la reconstrucción anatómica y biológica de los ligamentos coracoclaviculares, la cual utilizó un autoinjerto tendinoso sin ningún dispositivo de fijación adicional, lo que minimiza el riesgo de complicaciones relacionadas con el uso de tornillos o implantes metálicos. DISCUSIÓN: Este procedimiento es un método eficaz y confiable para estabilizar la articulación. Se requieren estudios que informen los resultados funcionales y radiológicos con el empleo de esta técnica quirúrgica para entonces poder asegurar que tiene ventajas sobre otras opciones terapéuticas existentes en la actualidad.

The neurobiological hypothesis of neurotrophins in the pathophysiology of schizophrenia: A meta-analysis.

BACKGROUND: Schizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological interactions known to contribute to the disease pathology. One potential contributor is the family of neurotrophins which are proteins involved in multiple functional processes in the nervous system, with crucial roles in neurodevelopment, synaptogenesis and neuroplasticity. With these roles in mind, abnormal neurotrophin profiles have been hypothesized to contribute to the pathology of schizophrenia. METHODS: We performed a systematic review and a meta-analysis to scrutinize the neurobiological hypothesis of neurotrophins in schizophrenia, examining the correlation between peripheral levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4/5) associated with schizophrenia. RESULTS: Fifty-two studies were reviewed and twenty-two studies were included in this meta-analysis. Using a random effects model, we confirmed that decreased levels of neurotrophins (BDNF, NGF and NT-4/5) were associated with schizophrenia (Hedges's g = -0.846; SE = 0.058; 95% confidence interval: -0.960 to -0.733; Z-value = -14.632; p-value = 0.000). Subgroup analysis indicated that neurotrophin levels are significantly decreased in both medicated and drug-näive patients. Meta-regression of continuous variables such as mean age, duration of illness and PANSS total score did not show significant effects (p > 0.05) in relation to neurotrophins levels. DISCUSSION: We confirm that decreased peripheral neurotrophin levels are significantly associated with schizophrenia, thereby confirming the neurobiological hypothesis of neurotrophins in schizophrenia. Low levels of neurotrophins in peripheral blood of patients with schizophrenia may explain, in part, the pathophysiology of schizophrenia.

ErbB4 signaling in dopaminergic axonal projections increases extracellular dopamine levels and regulates spatial/working memory behaviors.

Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function. Here we report that ErbB4 in midbrain DAergic axonal projections regulates extracellular DA levels and relevant behaviors. Mice lacking ErbB4 in tyrosine hydroxylase-positive (TH+) neurons, but not in PV+ GABAergic interneurons, exhibit different regional imbalances of basal DA levels and fail to increase DA in response to local NRG1 infusion into the dorsal hippocampus, medial prefrontal cortex and dorsal striatum measured by reverse microdialysis. Using Lund Human Mesencephalic (LUHMES) cells, we show that NRG/ErbB signaling increases extracellular DA levels, at least in part, by reducing DA transporter (DAT)-dependent uptake. Interestingly, TH-Cre;ErbB4f/f mice manifest deficits in learning, spatial and working memory-related behaviors, but not in numerous other behaviors altered in PV-Cre;ErbB4f/f mice. Importantly, microinjection of a Cre-inducible ErbB4 virus (AAV-ErbB4.DIO) into the mesencephalon of TH-Cre;ErbB4f/f mice, which selectively restores ErbB4 expression in DAergic neurons, rescues DA dysfunction and ameliorates behavioral deficits. Our results indicate that direct NRG/ErbB4 signaling in DAergic axonal projections modulates DA homeostasis, and that NRG/ErbB4 signaling in both GABAergic interneurons and DA neurons contribute to the modulation of behaviors relevant to psychiatric disorders.