MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner

Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related brain actions. We showed that MDMA dramatically reduced mitochondrial trafficking in hippocampal neurons in a Tau-dependent manner, in which glycogen synthase kinase 3β activity was implicated. Furthermore, we found that these trafficking abnormalities were rescued by over-expression of Mitofusin2 and dynamin-related protein 1, but not of Miro1. Given the relevance of mitochondrial targeting for neuronal function and neurotransmission, our data underscore a novel mechanism of action of MDMA that may contribute to our understanding of how this drug of abuse alters neuronal functioning. © 2014 Springer-Verlag.BFU2008-3980 (“Ministerio de Ciencia e Innovacion” (MICINN), Spain) and a grant from the “Plan Nacional de Drogas” to ES, and by the “Fundação para a Ciência e Tecnologia (FCT),” Portugal (Project PTDC/SAU-FCF/102958/2008), under the framework of the “Programa Operacional Temático Factores de Competitividade (COMPTE) do Quadro Comunitário de Apoio III” and “Fundo Comunitário Europeu (FEDE

Dependencia funcional, deterioro cognitivo y características de la marcha en adultos mayores con enfermedades crónicas

Objetivo: Identificar el nivel y relación de dependencia funcional (DF), deterioro cognitivo (DC) y características de la marcha en adultos mayores (AM) con enfermedades crónicas, habitantes del área metropolitana de Saltillo, Coahuila. Método: Diseño descriptivo correlacional. Muestra constituida por 105 AM de 60 años o más, usuarios de los Centros de Atención e Integración Familiar (CAIF). El tamaño de la muestra se determinó a través del paquete estadístico nQuery Advisor 7.0 considerando análisis de correlación bivariada, nivel de significancia de 0.5 y potencia del 95%. El muestreo fue por conveniencia. La recolección de datos se realizó a través de una cédula de datos socio-demográficas conjuntamente con cuatro instrumentos: para DF 1. Actividades Básicas de la Vida Diaria (AVD) y 2. Actividades Instrumentales de la Vida Diaria (AIVD); para DC 3. Mini Mental State Examination MMS-E; para las características de la marcha, 4. Sistema para Análisis de Marcha GaitRite ©, alphas de 0.730, 0.765, 0.720 y 0.811, respectivamente. Resultados. La edad promedio de los AM participantes es de 75 años (X = 75 ± 6) y escolaridad de 5 años (X = 5 ± 3). La mayor parte son mujeres (81.9%); que viven sin pareja (74.3%) y reportan alguna enfermedad crónico-degenerativa (65%) como Diabetes, 32.4%; Hipertensión, 61% y Enfermedades Articulares, 42%. La prevalencia de: dependencia severa en ABVD 5.7% y AIVD 21.9 %; DC 24 %; Los AM con mayor edad y menor escolaridad, reportan mayor grado de DC (r= .251; p<.05; r= -.259; p<.05, respectivamente) y dependencia para realizar ABVD (r=.297; p<.05) y AIVD (r=.351; p<.05); Por lo menos, el 30% de AM presentabó dificultades para mantener el equilibrio. Además, el 60% presentó dificultades para sentarse porque tienen problemas al medir la distancia entre su propio cuerpo y la silla, caen en la silla o se apoye en él con movimientos inseguros. 29% presentaba dificultades para elevar su pie derecho completamente. Discusión y Conclusiones. Los resultados de este estudio confirman lo que la literatura reporta acerca de la prevalencia y asociación de DF, DC y presencia de enfermedades crónicas características del AM como Diabetes e Hipertensión. Es necesario profundizar en el análisis de este estudio incorporando mediciones acerca del tiempo de diagnóstico de la enfermedad crónica, co-morbilidad, síntomas de depresión y diferencias de género, entre otros aspectos. También los factores asociados a la problemática de la marcha. Para el profesional de Enfermería, la continuidad de este fenómeno de estudio, fortalecerá el cuerpo de conocimientos disciplinares y la atención a las complejas necesidades de cuidado a la salud que demanda este segmento de la población. Palabras Clave: Adulto Mayor, Dependencia Funcional, Deterioro Cognitivo, Marcha

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMAassociated disruption of Ca2+ homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increasedmitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.Ministerio de Ciencia e Innovacion (MICINN), Spain (BFU2008-3980); Plan Nacional de Drogas, Spain; Fundação para a Ciência e a Tecnologia (Portugal) (FCT)

Factores psicosociales asociados al bajo rendimiento académico de los estudiantes del grado noveno (9º) de la institución educativa técnica ciudad de Ibagué comuna 13 de Ibagué – Tolima, 2012-2013.

Formato de recolección de datosEste proyecto de investigación se centró en el estudio de los factores psicosociales asociados al bajo rendimiento académico de los estudiantes del grado noveno (9º) de la Institución Educativa Técnica Ciudad de Ibagué. Se realizó una revisión de las investigaciones más recientes a nivel internacional y nacional frente al tema de los factores que incidían en el bajo rendimiento académico de los estudiantes; por ello se decidió abordar cuatro categorías que fueron: Motivacional, Familia, Docente y Pares. Estas categorías fueron soportadas bajo teóricos frente al tema de investigación. Se llevaron a cabo encuentros programados durante la investigación con la población objeto de estudio, teniendo en cuenta una muestra de 90 participantes, comprendida entre 50 estudiantes con bajo rendimiento académico, 25 docentes y 15 padres de familia. Se utilizó el enfoque cualitativo, abordado bajo el tipo de investigación crítico social, con una metodología investigación acción (IA), aplicando técnicas como la observación y la encuesta. Se emplearon instrumentos como el diario de campo, la entrevista abierta y semiestructura y estrategias como la observación, murales, juego de roles, metaplan, sociodrama. Basado en el análisis de los resultados arrojados en esta investigación se determinó que la familia es el factor predominante asociado al bajo rendimiento académico de los estudiantes, debido a la falta de apoyo y acompañamiento en las diferentes actividades relacionadas con el desempeño académico. Se sugiere implementar una propuesta de intervención a la población objeto de estudio con el fin de mejorar la calidad de vida del ser humano.This research project focused on the study of psychosocial factors associated with poor academic performance of students in the ninth grade (9th) Technical Educational Institution Ibague City. A review of recent research at international and national level on the issue of the factors that influenced underachievement of students, so she decided to address four categories were: Motivational, Family, Teachers and Peers. These categories were supported under theoretical research on the issue. Were conducted during the investigation scheduled meetings with the population under study, considering a sample of 90 participants, including 50 students with poor academic performance, 25 teachers and 15 parents. Qualitative approach was used, under the type addressed critical social research with action research methodology (IA), using techniques such as observation and survey. Instruments were used as the diary, open and semistructured interview and strategies such as observation, murals, role play, metaplan, skit. Based on the analysis of the results obtained in this investigation it was determined that the family is the predominant factor associated with poor academic performance of students, due to lack of support and assistance in various activities related to their academic performance. It is suggested to implement an intervention proposal to study population in order to improve the quality of human life

Quantification of inaccurate diagnosis of COPD in primary care medicine: an analysis of the COACH clinical audit

[Background] Inaccurate diagnosis in COPD is a current problem with relevant consequences in terms of inefficient health care, which has not been thoroughly studied in primary care medicine. The aim of the present study was to evaluate the degree of inaccurate diagnosis in Primary Care in Spain and study the determinants associated with it.[Methods] The Community Assessment of COPD Health Care (COACH) study is a national, observational, randomized, non-interventional, national clinical audit aimed at evaluating clinical practice for patients with COPD in primary care medicine in Spain. For the present analysis, a correct diagnosis was evaluated based on previous exposure and airway obstruction with and without the presence of symptoms. The association of patient-level and center-level variables with inaccurate diagnosis was studied using multivariate multilevel binomial logistic regression models.[Results] During the study 4,307 cases from 63 centers were audited. The rate of inaccurate diagnosis was 82.4% (inter-regional range from 76.8% to 90.2%). Patient-related interventions associated with inaccurate diagnosis were related to active smoking, lung function evaluation, and specific therapeutic interventions. Center-level variables related to the availability of certain complementary tests and different aspects of the resources available were also associated with an inaccurate diagnosis.[Conclusions] The prevalence data for the inaccurate diagnosis of COPD in primary care medicine in Spain establishes a point of reference in the clinical management of COPD. The descriptors of the variables associated with this inaccurate diagnosis can be used to identify cases and centers in which inaccurate diagnosis is occurring considerably, thus allowing for improvement.Peer reviewe

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series

[Background] Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published.[Objective] To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series.[Methods] We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series.[Results] Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid.[Conclusions] This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.Peer reviewe

Corporate reputation in the spanish context: An interaction between reporting to stakeholders and industry.

ABSTRACT: The authors describe the intensity and orientation of the corporate social responsibility (CSR) reporting in four Spanish industries and explore the relationship that exists between both concepts and an independent measurement of reputation for CSR (CSRR). The results demonstrate that the CSR reporting is especially relevant and useful in the finance industry. Finance companies report significantly more CSR information than most industries in Spain, and this reporting is more closely linked to their CSRR than the CSR reporting of basic, consumer goods and services industries. Borra

Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity

<p>Abstract</p> <p>Background</p> <p>Recently, proteins and peptides have become an added value to foodstuffs due to new knowledge about its structural analyses as related to antioxidant and anticancer activity. Our goal was to evaluate if protein fractions from cacao seeds show antitumor activity on lymphoma murine L5178Y model. The antioxidant activity of these fractions was also evaluated with the aim of finding a correlation with the antitumor activity.</p> <p>Methods</p> <p>Differential extraction of proteins from unfermented and semi-fermented-dry cacao seeds was performed and characterized by SDS-PAGE and FPLC size-exclusion chromatography. Antitumor activity was evaluated against murine lymphoma L5178Y in BALB/c mice (6 × 10⁴cells i.p.), with a treatment oral dose of 25 mg/kg/day of each protein fraction, over a period of 15 days. Antioxidant activity was evaluated by the ABTS⁺and ORAC-FL assays.</p> <p>Results</p> <p>Albumin, globulin and glutelin fractions from both cacao seed type were obtained by differential solubility extraction. Glutelins were the predominant fraction. In the albumin fraction, polypeptides of 42.3 and 8.5 kDa were found in native conditions, presumably in the form of two peptide chains of 21.5 kDa each one. The globulin fraction presented polypeptides of 86 and 57 kDa in unfermented cacao seed that produced the specific-cacao aroma precursors, and after fermentation the polypeptides were of 45 and 39 kDa. The glutelin fraction presented proteins >200 kDa and globulins components <100 KDa in lesser proportion. Regarding the semifermented-dry cacao seed, it was observed that the albumin fraction showed antitumoral activity, since it caused significant decreases (p < 0.05) in the ascetic fluid volume and packed cell volume, inhibiting cell growth in 59.98 ± 13.6% at 60% of the population; while the greatest antioxidant capacity due to free radical scavenging capacity was showed by the albumin and glutelin fraction in both methods assayed.</p> <p>Conclusion</p> <p>This study is the first report on the biological activity of semifermented-dry cacao protein fractions with their identification, supporting the traditional use of the plant. The albumin fraction showed antitumor and free radical scavenging capacity, however both activities were not correlated. The protein fractions could be considered as source of potential antitumor peptides.</p