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    Initial teacher training and planning in the multigrade classroom

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    El presente articulo reflexiona sobre la importancia y necesidad de aprender a planificar para el aula multigrado desde la formación inicial de maestros. La formación inicial de los docentes no contempla, o lo hace escasamente, la escuela rural y el aula multigrado. En consecuencia, los futuros maestros no conocen el proceso de enseñanza-aprendizaje en el aula rural, ni por supuesto la importancia y necesidad de la planificación multigrado para poder dar una respuesta adecuada a la diversidad y heterogeneidad características de este aula, y como instrumento clave para diseñar e implementar innovaciones educativas que faciliten la mejora de la calidad de la educación en los territorios rurales y visibilizen la escuela rural en el marco de las propias políticas y prácticas educativas

    Inversion of accommodation zones in salt-bearing extensional systems: insights from analog modeling

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    This work uses sandbox analog models to analyze the formation and subsequent inversion of a decoupled extensional system comprised of two segmented half-grabens separated by a diffuse accommodation zone with thick early syn-rift salt. The segmented half-grabens strike perpendicular to the direction of extension and subsequent shortening. Rifting first created a basement topography that was infilled by model salt, followed by a second phase of extension and sedimentation, followed afterwards by inversion. During the second phase of extension, syn-rift syncline minibasins developed above the basement extensional system and extended beyond the confines of the fault blocks. Sedimentary downbuilding and extension initiated the migration of model salt to the basement highs, forming salt anticlines, reactive diapirs, and salt walls perpendicular to the direction of extension, except for along the intervening accommodation zone where a slightly oblique salt anticline developed. Inversion resulted in decoupled cover and basement thrust systems. Thrusts in the cover system nucleated along squeezed salt structures and along primary welds. New primary welds developed where the cover sequence touched down on basement thrust tips due to uplift, salt extrusion, and syn-contractional downbuilding caused by the loading of syn-contractional sedimentation. Model geometries reveal the control imposed by the basement configuration and distribution of salt in the development of a thrust front from the inversion of a salt-bearing extensional system. In 3D, the interaction of salt migrating from adjacent syn-rift basins can modify the expected salt structure geometry, which may in turn influence the location and style of thrust in the cover sequence upon inversion. Results are compared to the Northern Lusitanian Basin, offshore Portugal, and the Isábena area of the South-Central Pyrenees, Spain

    Biological mechanisms underlying psychosocial stress response: The consequences of prenatal maternal distress and childhood maltreatment on the endocrine and immune systems

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    [eng] During critical periods of development, psychosocial stress experiences may alter key neural networks of the human brain, with long-lasting effects on behavior and mental health. However, the specific biological mechanisms through which early life stress impacts on present and future mental health are still not well understood. Hypothalamic-pituitary-adrenal (HPA) axis is the principal sensor and regulator of stress response. Its modulation begins early in development through fetus-placental dialogue and continues during postnatal life, from childhood to adolescence, being especially sensitive to early life’s adversities. Thus, HPA axis programming during prepostnatal developmental periods is proposed as a plausible mechanism of early sensitization that undermine future HPA axis functioning and associated mental disorders. Moreover, it should not be forgotten that the HPA axis dialogues with the immune system, exhibiting a bidirectional interaction. In this framework, the present dissertation aimed to disentangle the impact of psychosocial stress exposure during early sensitive periods of pre-postnatal brain development on HPA axis and immunity system. Cortisol (the HPA axis ultimate effector) and secretory immunoglobulin A (s-IgA) (an immunoglobulin of the mucosal surfaces) were selected in this thesis, respectively, as putative biomarkers of the endocrine and immune response to early psychosocial stress exposure in early life. The study of two mother/infant dyad cohorts, the Intramural_Maternal_Epi_project cohort and the COGESCOV-19 cohort, enable us to explore the respectively effects of the maternal distress and SARS-CoV-2 infection during pregnancy on the newborn’s early stress reactivity. In Intramural_Maternal_Epi_project, we observed that the presence of depressive symptoms flattened the maternal cortisol circadian pattern, especially during the second trimester of pregnancy. Furthermore, elevated maternal cortisol levels in mid-late pregnancy were associated with poor birth outcomes, including prematurity and low weight percentile at birth. These results underscore the importance of early detection of depressive symptoms, which are often manifested as a subclinical condition during pregnancy. Another hypothesis we tested with this cohort was based on the premise that maternal distress during pregnancy could influence DNA methylation patterns in placenta. Specifically, we studied the DNA methylation of FKBP5, NR3C1 and HSD11B2 genes in two different placental layers: maternal decidua and chorionic villi. We observed that while maternal cortisol levels in early pregnancy were associated with an increase in DNA methylation of CpG islands of NR3C1 gene and a decrease in DNA methylation of CpG islands of FKBP5 gene in the chorionic villi, at the level of the maternal decidua it was the increase in DNA methylation (at specific CpG sites of FKBP5 gene) that was strongly associated with the lower gestational age of the newborn at birth. Thus, stress during the pregnancy, and its associated cortisol levels could influence placental epigenetic signatures differently depending on the time of exposure, the placental layer, and the gene of study. Complementarily, we could explore the putative consequences of maternal exposure to SARS-CoV-2 during pregnancy in the neurodevelopmental outcomes of offspring, thanks to the COGESCOV-19 cohort. In this regard, we observed that infants born to mothers exposed to SARS-CoV-2 (serologically positive) showed poorer responses in items related to regulation and motor system domains (NBAS-Brazelton scale) at seven weeks old. This effect was especially evident in infants whose mothers were infected in the third trimester. Considering the magnitude of COVID-19 pandemic, children born to mothers infected during pregnancy, particularly in late pregnancy, should undergo additional longitudinal screening for neurodevelopmental milestones. On the other hand, in this thesis, we had the opportunity to explore the effect of the most severe psychosocial stress condition for a child, such as exposure to maltreatment during their early years of life. Our research was made possible thanks to Epi_young_stress cohort, which consists of a representative number of children and adolescents from the general population (aged between 7 and 17 years). This cohort has been recruited through the collaboration of various child and adolescent psychiatry units nationwide and includes both children with a current psychiatric diagnosis and a control group. For all subjects, the history of childhood maltreatment was thoroughly examined, and the Trier Social Stress Test for children (TSST-C) was also administered to assess the reactivity of the HPA axis to acute stress in this population. Regarding the functioning of the HPA axis in this young population, although children with maltreatment showed higher basal cortisol levels compared to those not exposed to maltreatment, when subjected to the acute stressor (TSST-C), they exhibited a flattened cortisol response but higher perceived anxiety. Noticeably, we also observed a dose-response relationship between the frequency and severity of the maltreatment and cortisol dysregulation. Furthermore, and in relation with putative immunity biomarkers in front psychosocial stress, we described that the acute exposure to the stress test was able to stimulate the secretion of s-IgA in young subjects after puberty. Additionally, concerning immune markers in response to acute stress, we found that exposure to the acute stressor (TSST-C) was able to stimulate the secretion of s-IgA in young subjects, but only after puberty. However, although s-IgA reactivity to acute stress was not observed in prepubescent children, when the presence of maltreatment was observed, these children had developed this immune response capability, suggesting that complex trauma could anticipates the immune maturation. Finally, considering our previous result that salivary s-IgA quickly rises after acute stress exposure, we wanted to know if salivary s-IgA could be a new promising biomarker of psychosocial stress reactivity in young population. A systematic review of the available scientific literature revealed that s-IgA can be considered a reliable biomarker of acute stress in under 18 population. However, further research is needed to specifically determine how psychosocial stress impacts on s-IgA circadian rhythm and basal levels. Together, the results of this thesis support the notion that psychosocial stress during prenatal and child-juvenile periods could alter endocrine and immune systems regulation, modifying early behavioral dimensions and the reactivity to stress, which might increase the risk of future mental health problems.[spa] Durante los periodos más precoces y sensibles del desarrollo del sistema nervioso central (SNC), la exposición al estrés psicosocial puede alterar los sistemas biológicos para el futuro funcionamiento adaptativo del sujeto. El cortisol (último efector del eje Hipotalámico Hipofisario Adrenal (HHA)) y la inmunoglobulina A secretora (s-IgA) se seleccionaron en esta tesis, respectivamente, como posibles biomarcadores de respuesta al estrés psicosocial en las primeras etapas de la vida. Se pudo estudiar el papel del distrés materno durante el embarazo, y su posible asociación con en el comportamiento y la reactividad ante el estrés del recién nacido, gracias a dos cohortes de diadas madre/niño seguidas durante el embarazo y hasta las primeras semanas postnatales: la cohorte del Intramural_Maternal_Epi_project y la cohorte COGESTCOV-19. En primer lugar, pudimos constatar que el patrón diurno de cortisol estaba desregulado en mujeres con síntomas de depresión, especialmente durante en el segundo trimestre del embarazo. Así mismo se observó que altos niveles de cortisol en esta etapa del embarazo se asociaban con prematuridad y bajo peso al nacer. Por otra parte, se pudo comprobar que los niveles altos de cortisol materno al principio del embarazo podrían asociarse con un perfil de metilación del ADN específico en genes placentarios implicados en la regulación del cortisol, incrementando el riesgo de un parto adelantado. Finalmente, se estudiaron las consecuencias de la infección materna por SARS-COV-2 durante el embarazo en las respuestas motoras y de regulación ante los estímulos del test de Brazelton en los niños a las 7 semanas de vida, constatando un mayor efecto si la infección afectaba al último trimestre de embarazo. Por otro lado, el estudio de una cohorte de niños/as y adolescentes con y sin patología mental (cohorte del proyecto Epi_young_stress) nos permitió analizar el papel del maltrato infantil en la posible sensibilización temprana del eje HHA y del sistema inmunitario de los sujetos expuestos. Para testar esta posible sensibilización, en este estudio se indujo estrés psicosocial agudo a todos los sujetos de la cohorte, mediante un protocolo de laboratorio cuasi experimental: el test de estrés psicosocial Trier para niños (TSST-C). Los niños/as y adolescentes expuestos a maltrato mostraron mayores niveles de cortisol basales y una hiporreactividad del eje HHA al TSST-C, a pesar de mostrar una mayor percepción de ansiedad ante estrés psicosocial agudo comparados con los niños no expuestos a maltrato. También se observó una relación dosis-efecto entre la exposición y severidad del maltrato y la desregulación del eje HHA. Además, el estrés psicosocial estimuló la secreción de s-IgA, pero sólo después de la pubertad. Sin embargo, los niños/as expuestos a maltrato infantil mostraron secreción de la s-IgA ante estrés psicosocial de forma similar a los adolescentes, sugiriendo una anticipación de la maduración del sistema inmune en los niños maltratados. El uso de la s-IgA como posible biomarcador de estrés agudo y crónico en etapas tempranas de la vida fue estudiado y discutido mediante una revisión sistemática. En conjunto, los resultados de esta tesis sostienen que la exposición al estrés psicosocial durante los periodos tempranos del desarrollo del SNC (prenatal, infancia y adolescencia) podrían alterar la respuesta al estrés de los sistemas endocrino e inmune, modificando algunos rasgos de la conducta temprana en el recién nacido y aumentando el riesgo de futuros problemas de salud mental

    Can Oncologists Prompt Patient Prognostic Awareness to Enhance Decision-Making? Data From the NEOetic Study

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    Introduction: Anti-neoplastic therapy improves the prognosis for advanced cancer, albeit it is not curative. An ethical dilemma that often arises during patients’ first appointment with the oncologist is to give them only the prognostic information they can tolerate, even at the cost of compromising preference-based decision-making, versus giving them full information to force prompt prognostic awareness, at the risk of causing psychological harm. Methods: We recruited 550 participants with advanced cancer. After the appointment, patients and clinicians completed several questionnaires about preferences, expectations, prognostic awareness, hope, psychological symptoms, and other treatment-related aspects. The aim was to characterize the prevalence, explanatory factors, and consequences of inaccurate prognostic awareness and interest in therapy. Results: Inaccurate prognostic awareness affected 74%, conditioned by the administration of vague information without alluding to death (odds ratio [OR] 2.54; 95% CI, 1.47-4.37, adjusted P = .006). A full 68% agreed to low-efficacy therapies. Ethical and psychological factors oriented firstline decision-making, in a trade-off in which some lose quality of life and mood, for others to gain autonomy. Imprecise prognostic awareness was associated with greater interest in low-efficacy treatments (OR 2.27; 95% CI, 1.31-3.84; adjusted P = .017), whereas realistic understanding increased anxiety (OR 1.63; 95% CI, 1.01-2.65; adjusted P = 0.038), depression (OR 1.96; 95% CI, 1.23-3.11; adjusted P = .020), and diminished quality of life (OR 0.47; 95% CI, 0.29-0.75; adjusted P = .011). Conclusion: In the age of immunotherapy and targeted therapies, many appear not to understand that antineoplastic therapy is not curative. Within the mix of inputs that comprise inaccurate prognostic awareness, many psychosocial factors are as relevant as the physicians’ disclosure of information. Thus, the desire for better decision-making can actually harm the patient

    The influence of oxytocin and prolactin during a first-episode of psychosis: the implication of sex differences, clinical features and cognitive performance

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    Background: Approximately 3% of the population suffers a first episode of psychosis (FEP), and a high percentage of these patients subsequently relapse. Because the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment, and outcome of such events and to define new therapeutic targets. Here we analyzed the plasma oxytocin and prolactin levels during an FEP, assessing their correlation with clinical and cognitive features. Methods: The oxytocin and prolactin in plasma was measured in 120 FEP patients and 106 healthy controls, all of whom were subjected to a clinical and neuropsychological assessment. Most patients were under antipsychotics. Statistical analyses aimed to identify factors associated with the FEP and to search for associations between the variables. This study is preliminary and exploratory because the P-values were not corrected for multiple comparisons. Results: FEP patients had less oxytocin, more prolactin, and a poor premorbid IQ, and they performed worse in sustained attention. Male patients with higher prolactin levels experienced more severe psychotic symptoms and required higher doses of antipsychotics. Low oxytocin was associated with poor sustained attention in women, whereas low oxytocin and high prolactin in men correlated with better performance in sustained attention. Conclusion: Low oxytocin, high prolactin, and poor premorbid IQ and sustained attention are factors associated with an FEP, representing potential therapeutic targets in these patients. These biological factors and cognitive domains might play an important role during a FEP, which could help us to develop new strategies that improve the outcomes of this disorder and that should perhaps be gender specific

    Country-level gender inequality is associated with structural differences in the brains of women and men

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    Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality

    Composició macromolecular de la llet materna, influència de factors materns, gestacionals i neonatals i impacte en el creixement del nounat prematur

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    [cat] El fracàs del creixement postnatal és un dels problemes més freqüents dels nadons prematurs. S'estima que al voltant del 50% del creixement depèn del suport nutricional que reben. El contingut de macronutrients de la llet humana és característic però variable. Aquesta variabilitat depèn del temps de lactància i de factors tant materns com neonatals, i pot tenir un paper determinant en el creixement i la salut dels nadons prematurs. La nostra hipòtesi és que certs factors materns i neonatals s'associen a canvis en la composició de macronutrients de la llet materna després d'un part prematur, i aquests canvis poden afectar el creixement i la salut del nounat. Els objectius del nostre estudi són: descriure la concentració de macronutrients i energia de la llet materna dels nadons molt prematurs durant les primeres vuit setmanes de vida i analitzar si el temps, certes característiques maternes, gestacionals i neonatals s'associaven a canvis en el seu estudi composició; descriure la ingesta enteral proteica i energètica de la nostra cohort, avaluant si s'adhereix a les recomanacions oficials i si hi ha associacions amb el creixement. Per això, vam dissenyar un estudi prospectiu de cohorts entre el gener del 2018 i el gener del 2020. Es van reclutar de forma consecutiva mares i els seus nadons molt prematurs d'edat gestacional igual o inferior a 32 setmanes i es van determinar les concentracions de macronutrients de la llet materna a la setmana 1, 2, 4 i 8 mitjançant l'analitzador de llet materna MIRIS. Avaluem 625 mostres (de 117 mares i 130 nadons molt prematurs). Les concentracions mitjana van ser: proteïna 1,3 ± 0,3 g/dl, carbohidrats 7,3 ± 0,6 g/dl, greix 3,7 ± 1,0 g/dl i energia 296,0 ± 41,0 kJ /dl (70,7 ± 9,8 kcal/dl). La variabilitat intra/interindividu era elevada. L'edat gestacional va correlacionar negativament amb la proteïna (rho: -0.307, p<0.001) i l'energia (r: -0.193, p=0.003). L'edat materna avançada, l'edat gestacional i la restricció del creixement intrauterí es van associar de manera independent amb el contingut de proteïna de la llet durant els primers 28 dies (R2 ajustat: 0,113, p=0,002). El creixement de la cohort va ser d'acord amb allò descrit en la literatura. Els pacients afectes de retard del creixement intrauterí van presentar un comportament diferent de la resta de la cohort. Després d'ajustar pels factors de confusió que poden influir en el creixement o en l'alimentació per via enteral, aquesta darrera només s'associava de manera independent amb menys rellevància amb l'evolució del pes al 28 dies i amb més força amb evolució del perímetre cranial a les 36 setmanes postmenstrual. Tot i les diferències composicionals descrites en aquesta tesi, no sembla que puguem elaborar unes directrius predictores de contingut macronutricional de la llet materna més enllà dels canvis temporals. El nostre estudi recolza la necessitat d'anàlisi de la composició de la llet humana a la pràctica clínica, que podria focalitzar-se en els nadons prematurs amb un creixement postnatal deficient o en mares amb factors associats a la producció de llet amb menor densitat nutricional. Segons els nostres resultats, el creixement està afectat tant per factors nutricionals com per factors no nutricionals com l'edat gestacional, el diagnòstic previ de retard de creixement intrauterí i les malalties relacionades amb la prematuritat. Pel que fa als factors nutricionals, l'aportació energètica sembla adequada en la majoria de casos, però sembla necessari millorar l'aportació proteica, que seria la que tindria més relació amb l'evolució somatomètrica, fet que dependria en gran mesura d'optimitzar les estratègies de fortificació.[spa] El fracaso del crecimiento postnatal es uno de los problemas más frecuentes de los recién nacidos prematuros. Se estima que alrededor del 50% de su crecimiento depende del soporte nutricional que reciben. El contenido de macronutrientes de la leche humana es característico pero variable. Esta variabilidad depende del tiempo de lactancia y de factores tanto maternos como neonatales, y puede desempeñar un papel determinante en el crecimiento y la salud de los recién nacidos prematuros. Nuestra hipótesis es que ciertos factores maternos y neonatales se asocian a cambios en la composición de macronutrientes de la leche materna después de un parto prematuro, y estos cambios pueden afectar al crecimiento y la salud del recién nacido. Los objetivos de nuestro estudio son: describir la concentración de macronutrientes y energía de la leche materna de los recién nacidos muy prematuros durante las primeras ocho semanas de vida y analizar si el tiempo, ciertas características maternas, gestacionales y neonatales se asociaban a cambios en su composición; describir la ingesta enteral proteica y energética de nuestra cohorte, evaluando si se adhiere a las recomendaciones oficiales y si existen asociaciones con el crecimiento. Para ello, diseñamos un estudio prospectivo de cohortes entre enero de 2018 y enero de 2020. Se reclutaron de forma consecutiva madres y sus recién nacidos muy prematuros de edad gestacional igual o inferior a 32 semanas y se determinaron las concentraciones de macronutrientes de la leche materna en la semana 1, 2, 4 y 8 mediante el analizador de leche materna MIRIS. Evaluamos 625 muestras (de 117 madres y 130 recién nacidos muy prematuros). Las concentraciones promedio fueron: proteína 1,3 ± 0,3 g/dl, carbohidratos 7,3 ± 0,6 g/dl, grasa 3,7 ± 1,0 g/dl y energía 296,0 ± 41,0 kJ/dl (70,7 ± 9,8 kcal/dl). La variabilidad intra/interindividuo era elevada. La edad gestacional correlacionó negativamente con la proteína (rho: -0.307, p<0.001) y la energía (r: -0.193, p=0.003). La edad materna avanzada, la edad gestacional y la restricción del crecimiento intrauterino se asociaron de forma independiente con el contenido de proteína de la leche durante los primeros 28 días (R2 ajustado: 0,113, p=0,002). El crecimiento de la cohorte fue acorde con lo descrito en la literatura. Los pacientes afectos de retraso del crecimiento intrauterino presentaron un comportamiento diferente al resto de la cohorte. Después de ajustar por los factores de confusión que pueden influir en el crecimiento o en la alimentación por vía enteral, esta última sólo se asociaba de forma independiente con menor relevancia con la evolución del peso al 28 días y con mayor fuerza con evolución del perímetro craneal a las 36 semanas de edad postmenstrual. Pese a las diferencias composicionales descritas en esta tesis, no parece que podamos elaborar unas directrices predictoras de contenido macronutricional de la leche materna más allá de los cambios temporales. Nuestro estudio apoya la necesidad de análisis de la composición de la leche humana en la práctica clínica, que podría focalizarse en los recién nacidos prematuros con un crecimiento postnatal deficiente o en madres con factores asociados a la producción de leche con menor densidad nutricional. Según nuestros resultados, el crecimiento se ve afectado tanto por factores nutricionales como por factores no nutricionales como la edad gestacional, el diagnóstico previo de retraso de crecimiento intrauterino y las enfermedades relacionadas con la prematuridad. Respecto a los factores nutricionales, el aporte energético parece adecuado en la mayoría de casos, pero parece necesario mejorar el aporte proteico, que seria el que mayor relacion tendria con la evolución somatometrica, hecho que dependería en gran medida de optimizar las estrategias de fortificación

    Probing the non-thermal physics of stellar bow shocks using radio observations<br />

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    Context. Massive runaway stars produce bow shocks in the interstellar medium. Recent observations revealed radio emission from a few of these objects, but the origin of this radiation remains poorly understood. Aims. We aim to interpret this radio emission and assess under which conditions it could be either thermal (free–free) or non-thermal (synchrotron), and how to use the observational data to infer physical properties of the bow shocks. Methods. We used an extended non-thermal emission model for stellar bow shocks for which we incorporated a consistent calculation of the thermal emission from the forward shock. We fitted this model to the available radio data (spectral and intensity maps), including largely unexplored data at low frequencies. In addition, we used a simplified one-zone model to estimate the gamma-ray emission from particles escaping the bow shocks. Results. We can only explain the radio data from the best sampled systems (BD+43°3654 and BD+60°2522) assuming a hard electron energy distribution below ∼1 GeV, a high efficiency of conversion of (shocked) wind kinetic power into relativistic electrons (∼1 − 5%), and a relatively high magnetic-to-thermal pressure ratio of ηB ∼ 0.2. In the other systems, the interpretation of the observed flux density is more ambiguous, although a non-thermal scenario is also favoured. We also show how complementary observations at other frequencies can allow us to place stronger constraints in the model. We also estimated the gamma-ray fluxes from the HII regions around the bow shocks of BD+43°3654 and BD+60°2522, and obtained luminosities at GeV energies of ∼1033 erg s−1 and 1032 erg s−1, respectively, under reasonable assumptions. Conclusions. Stellar bow shocks can potentially be very efficient particle accelerators. This work provides multi-wavelength predictions of their emission and demonstrates the key role of low-frequency radio observations in unveiling particle acceleration processes. The prospects of detections with next-generation observatories such as SKA and ngVLA are very promising. Finally, BD+43°3654 may be detected in GeV in the near future, while bow shocks in general may turn out to be non-negligible sources of (at least leptonic) low-energy cosmic rays

    Converging circuits between pain and depression: the ventral tegmental area as a therapeutic hub

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    Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the individuals suffering from it, while depression worsens the prognosis of chronic pain patients and may diminish the effectiveness of pain treatments. There is a high comorbidity rate between both pathologies, which might share overlapping mechanisms. This review explores the evidence pinpointing a role for the ventral tegmental area (VTA) as a hub where both pain and emotional processing might converge. In addition, the feasibility of using the VTA as a possible therapeutic target is discussed. The role of the VTA, and the dopaminergic system in general, is highly studied in mood disorders, especially in deficits in reward-processing and motivation. Conversely, the VTA is less regarded where it concerns the study of central mechanisms of pain and its mood-associated consequences. Here, we first outline the brain circuits involving central processing of pain and mood disorders, focusing on the often-understudied role of the dopaminergic system and the VTA. Next, we highlight the state-of-the-art findings supporting the emergence of the VTA as a link where both pathways converge. Thus, we envision a promising part for the VTA as a putative target for innovative therapeutic approaches to treat chronic pain and its effects on mood. Finally, we emphasize the urge to develop and use animal models where both pain and depression-like symptoms are considered in conjunction

    Exploring optimal graphene slit-pore width for the physical separation of water-methanol mixture

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    Efficient and sustainable techniques for separating water- alcohol mixtures are in high demand in the industry. Recent research has revealed that nanotechnology could be the optimal solution. In this study, we investigate how the width of a nano-confining graphene slit-pore affects the filtration and purification of water-methanol mixtures. Using Molecular Dynamics simulations of a coarse-grained model for mixtures containing up to 25 percent methanol, we found that specific pore sizes segregate the two components, with water being preferred in the center and methanol accumulating near the hydrophobic walls. Altering the pore width also affects non-monotonically the diffusivity of each component, with water diffusing faster than methanol. Hence, optimal pore size, leveraging segregation and diffusion differences, can enable the successful extraction of both components. However, the system requires external forces and work to maintain mechanical stability at specific pore widths. Our research indicates that Å pore size maximizes physical separation, ensuring that the energy cost of a filtering graphene membrane is minimized

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