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OBJECTIVE: Eating disorders (ED) have recently been studied from a network approach, conceptualising them as a complex system of interconnected variables, while highlighting the role of non-ED symptoms and personality dimensions. This study aims to explore the connections between personality and ED symptoms, identify central nodes, and compare the EDs network to a healthy control network. METHODS: We employed network analysis to examine the personality-ED symptom connections in 329 individuals with an ED diagnosis and 192 healthy controls. We estimated a regularised partial correlation network and the indices of centrality and bridge centrality to identify the most influential nodes for each group. Network differences between groups were also examined. RESULTS: Low Self-Directedness and high Harm avoidance emerged as central bridge nodes, displaying the strongest relationship with ED symptoms. Both networks differed in their global connectivity and structure, although no differences were found in bridge centrality and centrality indices. CONCLUSIONS: These findings shed light on the role of personality dimensions, such as Self-Directedness and Harm Avoidance in the maintenance of ED psychopathology, supporting the transdiagnostic conceptualisation of ED. This study advances a deeper understanding of the complex interplay between personality dimensions and ED symptoms, offering potential directions for clinical interventions.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Personalidad , Humanos , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Personalidad/fisiología , Adulto , Masculino , Adulto Joven , Adolescente , Estudios de Casos y ControlesRESUMEN
INTRODUCTION: The aim of this study was to use cluster analysis based on the trajectory of five cognitive-emotional processes (worry, rumination, metacognition, cognitive reappraisal and expressive suppression) over time to explore differences in clinical and performance variables in primary care patients with emotional symptoms. METHODS: We compared the effect of adding transdiagnostic cognitive-behavioural therapy (TD-CBT) to treatment as usual (TAU) according to cluster membership and sought to determine the variables that predicted cluster membership. 732 participants completed scales about cognitive-emotional processes, anxiety and depressive symptoms, functioning, and quality of life (QoL) at baseline, posttreatment, and at 12 months. Longitudinal cluster analysis and logistic regression analyses were carried out. RESULTS: A two-cluster solution was chosen as the best fit, named as "less" or "more" improvement in cognitive-emotional processes. Individuals who achieved more improvement in cognitive-emotional processes showed lower emotional symptoms and better QoL and functioning at all three time points. TAU+TD-CBT, income level, QoL and anxiety symptoms were significant predictors of cluster membership. CONCLUSIONS: These results underscore the value of adding TD-CBT to reduce maladaptive cognitive-emotional regulation strategies. These findings highlight the importance of the processes of change in therapy and demonstrate the relevance of the patient's cognitive-emotional profile in improving treatment outcomes.
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Cognición , Terapia Cognitivo-Conductual , Emociones , Calidad de Vida , Humanos , Masculino , Femenino , Terapia Cognitivo-Conductual/métodos , Análisis por Conglomerados , Adulto , Estudios Longitudinales , Persona de Mediana Edad , Cognición/fisiología , Ansiedad/terapia , Ansiedad/psicología , Depresión/terapia , Depresión/psicología , Resultado del TratamientoRESUMEN
BACKGROUND: To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer's disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI). METHODS: We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (Aß 1-42), and beta-amyloid 1-40 (Aß 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch's membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student's t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1. RESULTS: We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aß 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant. CONCLUSIONS: We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.
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Enfermedad de Alzheimer , Células Ganglionares de la Retina , Enfermedad de Alzheimer/patología , Biomarcadores , Lámina Basal de la Coroides/metabolismo , Humanos , Estudios Prospectivos , Retina , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: Patients with cancer are at increased risk of developing symptoms of depression and anxiety. However, data on the variables associated with these symptoms in the long term are scant. This study aims to evaluate rumination and thought suppression as explanatory variables of depressive and anxiety symptoms at one- and five-year follow-up in patients diagnosed with cancer. METHODS: A total of 131 patients with cancer were assessed at baseline (≤4 months of diagnosis), and at 1 and 5 years after diagnosis. A battery of self-reported measures was used to evaluate anxiety and depressive symptoms, rumination, thought suppression, social support, and self-efficacy. The associations among these variables were assessed with linear mixed-effects models. RESULTS: The models for depressive and anxiety symptoms explained 43.5% and 44.2% of the variance, respectively. Rumination was a significant explanatory variable of both depressive and anxiety symptoms over the five-year follow-up period, while thought suppression was only associated with anxiety symptoms. Female gender was associated with a higher risk of presenting anxiety symptoms but this same variable was also protective against depressive symptoms. CONCLUSIONS: The assessment and treatment of rumination and thought suppression in patients diagnosed with cancer is advisable, as these cognitive domains seem to be associated to symptoms of emotional disorders in the long term.
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Depresión , Neoplasias , Ansiedad/psicología , Cognición , Depresión/etiología , Femenino , Estudios de Seguimiento , HumanosRESUMEN
Cortical thickness has been widely studied in individuals with schizophrenia and, in particular, first-episode psychosis. Abnormalities have been described, although there is, to date, a lack of consensus regarding changes across time and correlations with clinical and functional outcomes of the illness. One hundred and twenty-three first-episode psychosis patients and 74 healthy volunteers were subjected to magnetic resonance imaging scans and clinical and functional assessments by different scales at four consecutive visits during a 10 year follow-up period. Linear mixed effects models were applied to our data to compute cortical thickness changes over time in (1) schizophrenia patients versus healthy controls and (2) in patients with good versus poor functional outcome. The associations between cortical thickness percentage changes and clinical and functional status at 10 years were also assessed. The patients presented a thinner cortex than the controls at baseline (b's = -0.06; q ≤ 0.00023) with non-significant coefficients for the interaction term (follow-up time x group) (b's = -0.001; q ≥ 0.681). Poor functioning patients presented statistically significant coefficients for the interaction term (follow-up time x functionality) (left: b = -0.005, q = 0.019; right: b = -0.005, q = 0.022). In contrast, no correlations were found between cortical thickness measurements and clinical variables at 10 years. Overall, there were widespread thickness anomalies in first-episode psychosis patients across cortical regions that remained stable across time. Progressive thickness changes were related to patient functional outcomes, with progressive and steeper cortical thinning in patients with worse functional outcomes and a stabilization in those with better outcomes.
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Grosor de la Corteza Cerebral , Esquizofrenia/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Escalas de Valoración Psiquiátrica , Esquizofrenia/patologíaRESUMEN
BACKGROUND: Reduced TCRζ chain surface has been reported in T cells from patients with different inflammatory conditions and cancer. However, the causes of this diminished expression in cancer remain elusive. METHODS: T cell-enriched populations of blood or tissue (tumoral and nontumoral) origin from 44 patients with gastric adenocarcinoma and 33 healthy subjects were obtained. Samples were subjected to cytofluorimetry, Western blot analysis, TCRζ cDNA sequencing experiments, measurement of TCRζ mRNA levels, and caspase-3 activity assays. RESULTS: Cytofluorimetry revealed a decreased TCRζ expression in T cells of patients, assessed either as percentage of cells expressing this chain (blood: control subjects 99.8 ± 0.1%, patients 98.8 ± 1.1%P < 0.001; tissue: control subjects 96.7 ± 0.9%, patients tumoral tissue 67.9 ± 27.0%, patients nontumoral tissue 82.8 ± 12.6%, P = 0.019) or mean fluorescence intensity (MFI) value (blood: control subjects 102.2 ± 26.0; patients 58.0 ± 12.3, P = 0.001; tissue: control subjects 99.4 ± 21.4; patients tumoral tissue 41.6 ± 21.4; patients nontumoral tissue 62.3 ± 16.6, P = 0.001). Other chains pertaining to the TCR-CD3 complex (CD3ε) showed no significant differences (MFI values). Subsequent TCRζ cDNA sequencing experiments or measurements of TCRζ mRNA levels disclosed no differences between patients and control subjects. Evaluation of caspase-3 activity showed higher levels in T cell extracts of patients, and this activity could be decreased by 70% with the use of the inhibitor Ac-DEVD-FMK, although CD3ζ expression levels did not recover. CONCLUSIONS: These results further place the defect responsible for the low TCRζ expression in cancer at the posttranscriptional level and suggests contrary to what has been proposed in other pathologies that elevated caspase-3 activity is not the causative agent.
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Caspasa 3/metabolismo , Regulación Neoplásica de la Expresión Génica , Procesamiento Postranscripcional del ARN , Receptores de Antígenos de Linfocitos T/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Humanos , Inmunofenotipificación , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptores de Antígenos de Linfocitos T/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
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Asma/inmunología , Microbioma Gastrointestinal/inmunología , Interacciones Microbiota-Huesped/inmunología , Obesidad/inmunología , Verrucomicrobia/inmunología , Adulto , Akkermansia , Animales , Asma/complicaciones , Asma/diagnóstico , Asma/microbiología , Modelos Animales de Enfermedad , Heces/microbiología , Femenino , Volumen Espiratorio Forzado , Voluntarios Sanos , Humanos , Masculino , Ratones , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/microbiología , Sistema Respiratorio/inmunología , Índice de Severidad de la Enfermedad , Verrucomicrobia/aislamiento & purificaciónRESUMEN
BACKGROUND: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. METHODS: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. RESULTS: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. CONCLUSION: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.
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Asma/prevención & control , Butiratos/análisis , Hipersensibilidad Inmediata/prevención & control , Propionatos/análisis , Animales , Asma/etiología , Cromatografía Líquida de Alta Presión , Dieta , Ácidos Grasos Volátiles/análisis , Heces/química , Femenino , Humanos , Hipersensibilidad Inmediata/etiología , Lactante , Masculino , RatonesRESUMEN
BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
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Colitis/inmunología , Colitis/prevención & control , Agricultores , Inflamación/inmunología , Inflamación/prevención & control , Ácidos Neuramínicos/inmunología , Enfermedades Respiratorias/inmunología , Enfermedades Respiratorias/prevención & control , Factores de Edad , Alérgenos/inmunología , Animales , Biomarcadores , Niño , Preescolar , Colitis/diagnóstico , Estudios Transversales , Modelos Animales de Enfermedad , Exposición a Riesgos Ambientales , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Lactante , Inflamación/diagnóstico , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones , Ratones Noqueados , Vigilancia de la Población , Enfermedades Respiratorias/diagnóstico , Índice de Severidad de la Enfermedad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.
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Infecciones por Bifidobacteriales/inmunología , Bifidobacterium longum/inmunología , Polisacáridos Bacterianos/inmunología , Células Th17/inmunología , Animales , Infecciones por Bifidobacteriales/microbiología , Bifidobacterium longum/genética , Citocinas/inmunología , Femenino , Humanos , Interleucina-17/inmunología , Ratones , Ratones Endogámicos BALB CRESUMEN
The Bifibobacterium longum subsp. longum 35624™ strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans. This paper presents (a) the genome sequence of the organism allowing the assignment to its correct subspeciation longum; (b) a comparative genome assessment with other B. longum strains and (c) the molecular structure of the 35624 exopolysaccharide (EPS624). Comparative genome analysis of the 35624 strain with other B. longum strains determined that the sub-speciation of the strain is longum and revealed the presence of a 35624-specific gene cluster, predicted to encode the biosynthetic machinery for EPS624. Following isolation and acid treatment of the EPS, its chemical structure was determined using gas and liquid chromatography for sugar constituent and linkage analysis, electrospray and matrix assisted laser desorption ionization mass spectrometry for sequencing and NMR. The EPS consists of a branched hexasaccharide repeating unit containing two galactose and two glucose moieties, galacturonic acid and the unusual sugar 6-deoxy-L-talose. These data demonstrate that the B. longum 35624 strain has specific genetic features, one of which leads to the generation of a characteristic exopolysaccharide.
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Cryoglobulinaemic vasculitis is characterised by immunoglobulin deposition at low temperatures. The most common manifestations are cutaneous involvement, arthralgias, Raynaud's phenomenon, peripheral neuropathy and renal disease. Myopathy is unusual and only a few cases have been reported. Here, we present a 31-year-old woman who developed progressive muscle weakness involving upper and lower extremities, dysphagia, paraesthesias and palpable purpura. Diagnostic studies revealed elevated creatine kinase, diffuse myopathic and sensorimotor axonal neuropathy on electromyography and nerve conduction studies, and inflammatory myopathy on muscle biospsy. Cryoglobulin levels were elevated on two occasions. She responded favourably to cyclophosphamide and high-dose corticosteroids. Cyclophosphamide was continued for 1 year followed by methotrexate. Prednisone was gradually tapered and discontinued 1 year later. She remained in clinical remission after 4 years of follow-up. This case suggests that cryoglobulinaemia should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.
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Crioglobulinemia/diagnóstico , Miositis/diagnóstico , Vasculitis/diagnóstico , Adulto , Crioglobulinemia/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Miositis/tratamiento farmacológico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Resultado del Tratamiento , Vasculitis/tratamiento farmacológicoRESUMEN
Uveitis is a clinical feature of the Blau syndrome, a disease linked to CARD15 (also referred to as NOD2) mutations. Three main mutations in this gene (R334W, R334Q and L469F) have been reported as Blau syndrome risk factors, a disease that manifests uveitis as one of its clinical features. However, little is known on the involvement of this gene in idiopathic uveitis. We thus sought to determine the frequency of these Blau-related CARD15 mutations in a cohort of Spanish patients with idiopathic uveitis. To this aim, 110 patients with idiopathic uveitis, followed at the Department of Ophtalmology of a tertiary hospital (Hospital Universitario Alcalá de Henares, Madrid. Spain) were enrolled. As a control population, 104 healthy subjects were used. DNA was extracted from blood samples and the Blau-related CARD15 mutations were analysed either by PCR-RFLP or direct DNA sequencing. None of the mutations studied was found in any of the individuals tested, whether diseased or healthy. It seems thus that Blau syndrome-related CARD15 mutations are not involved in idiopathic uveitis, a finding which allows us to suggest that the genetic aetiology of the idiopathic uveitis or the Blau-associated uveitis is different.