RESUMEN
A vexing problem in mitochondrial medicine is our limited capacity to evaluate the extent of brain disease in vivo. This limitation has hindered our understanding of the mechanisms that underlie the imaging phenotype in the brain of patients with mitochondrial diseases and our capacity to identify new biomarkers and therapeutic targets. Using comprehensive imaging, we analyzed the metabolic network that drives the brain structural and metabolic features of a mouse model of pyruvate dehydrogenase deficiency (PDHD). As the disease progressed in this animal, in vivo brain glucose uptake and glycolysis increased. Propionate served as a major anaplerotic substrate, predominantly metabolized by glial cells. A combination of propionate and a ketogenic diet extended lifespan, improved neuropathology, and ameliorated motor deficits in these animals. Together, intermediary metabolism is quite distinct in the PDHD brain-it plays a key role in the imaging phenotype, and it may uncover new treatments for this condition.
Asunto(s)
Encéfalo , Glucosa , Propionatos , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa , Animales , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Glucosa/metabolismo , Propionatos/metabolismo , Ratones , Dieta Cetogénica , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Masculino , GlucólisisRESUMEN
Cells configure their metabolism in a synchronized and timely manner to meet their energy demands throughout development and adulthood. Transitions of developmental stages are coupled to metabolic shifts, such that glycolysis is highly active during cell proliferation, whereas oxidative phosphorylation prevails in postmitotic states. In the cerebellum, metabolic transitions are remarkable given its protracted developmental timelines. Such distinctive feature, along with its high neuronal density and metabolic demands, make the cerebellum highly vulnerable to metabolic insults. Despite the expansion of metabolomic approaches to uncover biological mechanisms, little is known about the role of metabolism on cerebellar development and maintenance. To illuminate the intricate connections between metabolism, physiology, and cerebellar disorders, we examined here the impact of metabolism on cerebellar growth, maturation, and adulthood through the lens of inborn errors of metabolism.
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Cerebelo , Cerebelo/crecimiento & desarrollo , Cerebelo/metabolismo , Animales , HumanosRESUMEN
Resumen El objetivo de este estudio era el objetivo de la presente investigación comparativa es identificar los síntomas específicos de depresión en hombres y determinar si existe un sesgo diagnóstico en los criterios incluidos en el sistema DSM y CIE. Para ello se estudia una muestra clínica conformada por 156 hombres y 174 mujeres entre los 18 y los 65 años, con diagnóstico previo de depresión, y un grupo control compuesto por 149 hombres y 151 mujeres sin depresión. Para evaluar depresión se usó Cuestionario de Depresión en Hombres (CDH) y la Entrevista MINI (Mini International Neuropsychiatric Interview). Para los análisis psicométricos se empleó el Modelo de Rasch desde la Teoría de Respuesta al Ítem y análisis comparativos multivariados. Se concluye que los hombres se deprimen de forma significativamente diferente de las mujeres y que parte de los síntomas identificados no son considerados en los sistemas nosológicos vigentes.
Abstract The aim of this study was to identify if there are symptoms of depression in men who are not described in diagnostic manuals available. This clinical sample comprised 156 men and 174 women between 18 and 65 years prior to diagnosis of depression, and 149 men and 151 women without depression used as controls is studied. To evaluate Depression Questionnaire Depression in Men (CDH) and Interview MINI (Mini International Neuropsychiatric Interview) was used. For psychometric analyzes the Rasch model was used from the Item Response Theory and multivariate comparative analysis. We conclude that men are depressed significantly different from women and that some of the symptoms identified are not considered in the current nosological systems.
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Depresión/diagnóstico , Salud del Hombre/estadística & datos numéricos , Masculinidad/historiaRESUMEN
El objetivo del presente estudio fue evaluar la prevalencia de depresión, detectar el riesgo suicida e identificar los factores sociodemográficos y personales asociados a este trastorno. La muestra no aleatorizada estuvo conformada por 1525 hombres colombianos con edades entre 18 y 83 años procedentes de 22 departamentos y de distintos niveles educativos. Para evaluar la depresión se usó el Cuestionario de Depresión para Hombres (Álvarez y Londoño, 2012); para evaluar la comorbilidad con ansiedad se usó la Escala de Ansiedad HADS (Zigmond y Snaith, 1983) y el IMAFE (Lara, 1991); y para recolectar información acerca de los factores personales y sociodemográficos se usó una ficha de registro. Se analizaron los datos para calcular la prevalencia de corte, el riesgo suicida, la comorbilidad a través del uso del paquete estadístico SPSS. Se concluye que la prevalencia real reportada y el riesgo suicida en la población estudiada son más altos que los detectados usando un instrumento no sensible al género.
This epidemiologic study aimed to evaluate the prevalence of depression, the suicide risk and the demographic and personal factors associated with depression severity in men. The non-randomized sample of participants was formed by 1525 Colombian men aged 18 to 83 years old, from 22 departments and different educational levels. The instruments used to evaluate the above factors were the Men's Depression Questionnaire (Alvarez and Londoño, 2012), the Anxiety Scale HADS (Zigmond y Snaith, 1983) and the IMAFE (Lara 1991), and in order to collect data about personal and socio-demographic factors, a registration card was used. Data were analyzed to calculate the prevalence, suicide risk and comorbidity with anxiety through the use of SPSS. It was concluded that the prevalence of depression and suicide risk in the population object of study is higher than the one identified in previous studies when a non- gender sensitive questionnaire was used.
O objetivo deste estudo foi avaliar a prevalência de depressão, detectar o risco suicida e identificar os fatores sociodemográficos e pessoais associados com esse transtorno. A amostra não aleatorizada foi conformada por 1525 homens colombianos com idade entre 18 e 83 anos, procedentes de 22 estados e de diferentes níveis de escolaridade. Para avaliar a depressão, foi utilizado o Teste de Depressão para Homens (Álvarez e Londoño, 2012); para avaliar a comorbilidade com ansiedade, usou-se a Escala Hospitalar de Ansiedade e Depressão (Hads - Zigmond e Snaith, 1983) e o Inventário de Masculinidade e Feminilidade (Imafe - Lara, 1991); para coletar informação sobre os fatores pessoais e sociodemográficos, empregou-se um formulário de registro. Analisaram-se os dados para calcular a prevalência de corte, o risco suicida, a comorbilidade por meio do uso do SPSS. Conclui-se que a prevalência real relatada e o risco de suicídio na população estudada são mais altos do que os detectados usando um instrumento não sensível ao gênero.
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Humanos , Masculino , Adulto , Salud Mental , Conducta de Reducción del RiesgoRESUMEN
Only four cases of triplane distal radius fracture have been described in the literature. We report the first that has been treated with open reduction and internal fixation. A 15-year-old boy sustained a triplane fracture of the distal radius. After an unsuccessful attempt at closed reduction, open reduction and internal fixation were performed. Six months after injury, the patient is asymptomatic, but radiographs show a partial growth arrest. The goal of treatment is to achieve anatomic reduction of the articular surface. In this case interposed periosteum prevented anatomic reduction, requiring open reduction and internal fixation. Because of the patient's advanced age the partial physeal arrest should advance to complete arrest before length impairment or occurrence of angular deformity.
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Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Adolescente , Fijación Interna de Fracturas , Humanos , Masculino , Radiografía , Radio (Anatomía)/diagnóstico por imagenRESUMEN
INTRODUCTION: Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-ß1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. METHODS: Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-ß1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. RESULTS: Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. CONCLUSION: Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair.
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Tejido Adiposo/citología , Diferenciación Celular/fisiología , Condrocitos/citología , Condrogénesis/fisiología , Células Madre Mesenquimatosas/citología , Adenoviridae , Tejido Adiposo/metabolismo , Animales , Western Blotting , Supervivencia Celular , Células Cultivadas , Condrocitos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Técnicas de Transferencia de Gen , Humanos , Inmunohistoquímica , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción SOX9/metabolismo , Ovinos , Transducción Genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
This paper introduces the validation of the Spanish adaptation of the White Bear Suppression Inventory (WBSI) by Wegner and Zanakos (1994). A sample of 833 people from the general population completed the WBSI along with other questionnaires. The exploratory factor analysis and the confirmatory factor analysis supported a two-factor solution accounting for 51.8% of the cumulative variance. This structure is comprised of the two following factors: unwanted intrusive thoughts (alpha = .87, r = .70) and actions of distraction and suppression of thoughts (alpha = .80, r = .60). Both internal consistency reliability (alpha = .89) and test-retest reliability (r = .71) showed adequate homogeneity, sound consistency, and stability over time. The results are discussed bearing in mind both isolated factors and the possible relationships of the suppression factor with automatic negative thoughts and insomnia.
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Comparación Transcultural , Inventario de Personalidad/estadística & datos numéricos , Represión Psicológica , Pensamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención , Mecanismos de Defensa , Femenino , Humanos , Intención , Masculino , Persona de Mediana Edad , Psicometría/estadística & datos numéricos , Valores de Referencia , Reproducibilidad de los Resultados , España , Traducción , Adulto JovenRESUMEN
A new and completely automated method for the determination of ten relevant polycyclic aromatic hydrocarbons (PAHs) in olive oil is proposed using an extraction by the headspace (HS) technique. Quantification and confirmation steps are carried out by gas chromatography-mass spectrometry (GC-MS) combining simultaneously selected-ion monitoring (SIM) and tandem mass spectrometry (MS/MS). This combination offers on one hand an increased sensitivity and on the other hand, selective and reliable qualitative information. Sample pretreatment or clean-up are not necessary because the olive oil sample is put directly into an HS vial, automatically processed by HS and introduced into the GC-MS instrument for analysis. Because of its high selectivity and sensitivity, a triple-quadrupole (QqQ) detector coupled with the gas chromatograph allows us to limit handling. Each sample is completely processed in approximately 63 min (45 min for HS isolation and 18 min for GC-MS determination), a reduced time compared with previously published methods. The chemical and instrumental variables were preliminarily optimized using uncontaminated olive oil samples spiked with 25 microg kg(-1) of each target compound. The final method was validated to ensure the quality of the results. The precision was satisfactory, with relative standard deviation (RSD) values in the range 3-9%. Recovery rates ranged from 96 to 99%. Limits of detection (LOD) were calculated as 0.02-0.06 microg kg(-1) and the limits of quantification (LOQ) were obtained as 0.07-0.26 microg kg(-1). It must be mentioned that the LOD and LOQ are much lower than the maximum levels established by the European Union (EU) in oils and fats intended for direct human consumption or for use as an ingredient in foods, which are set at 2 microg kg(-1). All the figures of merit are completely in accordance with the latest EU legislation. This fact makes it possible to consider the proposed method as a useful tool for the control of PAHs in olive oils.
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Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Aceites de Plantas/química , Hidrocarburos Policíclicos Aromáticos/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Aceite de Oliva , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A new analytical strategy for the screening and confirmation/quantification of multiclass pesticide residues in vegetables has been established and validated. No complicated sample preparation was needed, but only a simple and rapid extraction using ethyl acetate and sodium sulfate, which required no cleanup. The approach is based on the use of the triple quadrupole (QqQ) mass spectrometry (MS) as detection system in gas chromatography (GC). In a first step, a GC-QqQ-MS screening method, which monitors only one MS/MS transition by compound, allows the identification of approximately 130 pesticides in 11.6 min. In this way, the differentiation between negative and potentially nonnegative samples is carried out. In the second step, the nonnegative samples are reanalyzed by the GC-QqQ-MS confirmation/quantification method, which monitors two or three MS/MS transitions by compound. Confirmation of pesticides was based on the comparison of intensity ratios for the main ions in samples with those obtained on the same day from the standard in a matrix containing the pesticides at a preestablished concentration level. Quantification of the identified and confirmed pesticides was based on the addition standard method, which avoids matrix effect. The proposed analytical strategy allowed a reliable identification and confirmation of the target pesticides at trace levels, reducing analysis time and increasing sample throughput in routine analytical laboratories.
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Contaminación de Alimentos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Residuos de Plaguicidas/análisis , Verduras/químicaRESUMEN
A simple method for multi-residue analysis of pesticides by low-pressure gas chromatography-tandem mass spectrometry (LP-GC-MS-MS) has been validated in compost samples. The pesticide residues were extracted from the lyophilised samples with organic solvent by stirring. No sample clean-up was required prior to the analysis. The method was applied to determine the fate of two organochlorine pesticides (lindane and endosulfan) and two organophosphates (malathion and chlorpyrifos-methyl) during the composting process in the reactor of a pilot plant. Malathion, chlorpyrifos-methyl and lindane residues almost fully disappeared after 8 days of maturation in the reactor, while endosulfan residues were only partially degraded. Alongside this, a study of natural disappearance of the pesticides was carried out in the laboratory and a characteristic time profile was traced for each pesticide class.
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Cromatografía de Gases y Espectrometría de Masas/métodos , Plaguicidas/química , Suelo/análisis , Biodegradación Ambiental , Humedad , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
A selective and reliable extraction procedure was developed and validated to determine multiclass pesticide residues in lyophilized agricultural plants by low-pressure gas chromatography coupled with tandem mass spectrometry. The method is based on a rapid and simple extraction of the lyophilized sample with dichloromethane. The results were compared with those obtained by using fresh and naturally dried samples. Slightly better recoveries and precision values were obtained for the lyophilized samples. The application of the proposed methodology was tested by analyzing French bean plants from an agricultural area of Almería (Spain). The availability of this methodology, which is capable of detecting a high number of analytes in a single analysis, has priority in analyses for a large number of pesticides used on individual commodities.