N-glycomic Profile in Combat Related Post- Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra- performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N- glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N- glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms

A Set of Reliable Samples for the Study of Biomarkers for the Early Diagnosis of Parkinson's Disease

BackgroundParkinson's disease (PD) is a progressive neurodegenerative disorder, diagnosed according to the clinical criteria that occur in already advanced stages of PD. The definition of biomarkers for the early diagnosis of PD represents a challenge that might improve treatment and avoid complications in this disease. Therefore, we propose a set of reliable samples for the identification of altered metabolites to find potential prognostic biomarkers for early PD. MethodsThis case-control study included plasma samples of 12 patients with PD and 21 control subjects, from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)-Navarra cohort, part of the EPIC-Spain study. All the case samples were provided by healthy volunteers who were followed-up for 15.9 (+/- 4.1) years and developed PD disease later on, after the sample collection. Liquid chromatography coupled to tandem mass spectrometry was used for the analysis of samples. ResultsOut of 40 that were selected and studied due to their involvement in established cases of PD, seven significantly different metabolites between PD cases and healthy control subjects were obtained in this study (benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol, and quinolinic acid). These metabolites are related to mitochondrial dysfunction, the oxidative stress, and the mechanisms of energy production. ConclusionWe propose the samples from the EPIC study as reliable and invaluable samples for the search of early biomarkers of PD. Likewise, this study might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.he EPIC study received financial support from the International Agency for Research on Cancer (AEP/93/06), the European Commission (SO-97-200302-05F02 and SP23-CT-2005-006438), the Health Research Fund (FIS) of the Spanish Ministry of Health, the Red Temática de Investigación Cooperativa de Centros de Cáncer (RTICCC C03/10 and RD06/0020), the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), the participating Regional Governments of Andalusia, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO). This study was furthermore supported by the Ministry of Health of the Basque Government, Exp 20161109

Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentration and BDNF/TrkB Gene Polymorphisms in Croatian Adults with Asthma

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B (TrkB) receptor might contribute to normal lung functioning and immune responses ; however, their role in asthma remains unclear. Plasma BDNF concentrations, as well as BDNF and NTRK2 (TrkB gene) polymorphisms, were investigated in 120 asthma patients and 120 healthy individuals using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. The genotype and allele frequencies of BDNF Val66Met (rs6265) and NTRK2 rs1439050 polymorphisms did not differ between healthy individuals and asthma patients, nor between patients grouped according to severity or different asthma phenotypes. Although plasma BDNF concentrations were higher among healthy subjects carrying the BDNF Val66Met GG genotype compared to the A allele carriers, such differences were not detected in asthma patients, suggesting the influences of other factors. Plasma BDNF concentration was not affected by NTRK2 rs1439050 polymorphism. Asthma patients had higher plasma BDNF concentrations than control subjects ; however, no differences were found between patients subdivided according to asthma severity, or Type-2, allergic, and eosinophilic asthma. Higher plasma BDNF levels were observed in asthma patients with aspirin sensitivity and aspirin-exacerbated respiratory disease. These results suggest that plasma BDNF may serve as a potential peripheral biomarker for asthma, particularly asthma with aspirin sensitivity

Lipid peroxidation in obesity: Can bariatric surgery help?

Obesity and chronic oxidative stress, often being associated with each other in a vicious circle, are important factors of chronic diseases. Although it was usually considered to accompany aging and wealth, global trends show the increase in obesity among children even in Third World countries. Being manifested by an imbalance between energy consumption and food intake, obesity is characterized by an excessive or abnormal fat accumulation, impaired redox homeostasis and metabolic changes often associated with the self- catalyzed lipid peroxidation generating 4- hydroxynonenal, pluripotent bioactive peroxidation product of polyunsaturated fatty acids. Conservative methods targeting obesity produced only modest and transient results in the treatment of morbid obesity. Therefore, in recent years, surgery, primarily bariatric, became an attractive treatment for morbid obesity. Since adipose tissue is well known as a stress organ with pronounced endocrine functions, surgery results in redox balance and metabolic improvement of the entire organism. The source of bioactive lipids and lipid- soluble antioxidants, and the complex pathophysiology of lipid peroxidation should thus be considered from the aspects of personalized and integrative biomedicine to treat obesity in an appropriate way

Short overview on metabolomic approach and redox changes in psychiatric disorders

Schizophrenia, depression and posttraumatic stress disorder (PTSD) are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment. Metabolomics is a discipline that combines different strategies with the aim to extract, detect, identify and quantify all metabolites that are present in a biological sample and might provide mechanistic insights into the etiology of various psychiatric disorders. Therefore, oxidative stress research combined with metabolomics might offer a novel approach in dissecting psychiatric disorders, since these data-driven but not necessarily hypothesis-driven methods might identify new targets, molecules and pathways responsible for development of schizophrenia, depression or PTSD. Findings from the oxidative research in psychiatry together with metabolomics data might facilitate development of specific and validated prognostic, therapeutic and clinical biomarkers. These methods might reveal bio- signatures of individual patients, leading to individualized treatment approach. In reviewing findings related to oxidative stress and metabolomics in selected psychiatric disorders, we have highlighted how these novel approaches might make a unique contribution to deeper understanding of psychopathological alterations underlying schizophrenia, depression and PTSD

Genetic and Epigenetic Association of Hepatocyte Nuclear Factor-1α with Glycosylation in Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a complex trauma-related disorder, the etiology and underlying molecular mechanisms of which are still unclear and probably involve different (epi)genetic and environmental factors. Protein N- glycosylation is a common post-translational modification that has been associated with several pathophysiological states, including inflammation and PTSD. Hepatocyte nuclear factor-1α (HNF1A) is a transcriptional regulator of many genes involved in the inflammatory processes, and it has been identified as master regulator of plasma protein glycosylation. The aim of this study was to determine the association between N-glycan levels in plasma and immunoglobulin G, methylation at four CpG positions in the HNF1A gene, HNF1A antisense RNA 1 (HNF1A-AS1), rs7953249 and HNF1A rs735396 polymorphisms in a total of 555 PTSD and control subjects. We found significant association of rs7953249 and rs735396 polymorphisms, as well as HNF1A gene methylation at the CpG3 site, with highly branched, galactosylated and sialyated plasma N-glycans, mostly in patients with PTSD. HNF1A-AS1 rs7953249 polymorphism was also associated with PTSD ; however, none of the polymorphisms were associated with HNF1A gene methylation. These results indicate a possible regulatory role of the investigated HNF1A polymorphisms with respect to the abundance of complex plasma N-glycans previously associated with proinflammatory response, which could contribute to the clinical manifestation of PTSD and its comorbiditie

Unidad de Currícum y Evaluación : objetivos fundamentales y contenidos mínimos obligatorios de la Educación Básica y Media de Adultos

Contiene el Decreto Supremo de Educación 239 del Ministerio de Educación del Gobierno de Chile, publicado el 15 de noviembre de 2004, por el que se establecen los objetivos fundamentales y objetivos mínimos obligatorios para la enseñanza de adultos en sus tres subdivisiones: Enseñanza Básica, Enseñanza Media Humanístico-Científica y Enseñanza Media Técnico-Profesional. También se incluyen los planes de estudio para cada uno de los niveles de cada etapa, donde se recoge la fundamentación, principios básicos, objetivos fundamentales y contenidos mínimos de todas las materias de cada nivel. Los objetivos fundamentales y contenidos mínimos obligatorios de la Educación de Adultos fueron enriquecidos y precisados por los resultados del proceso de Consulta Nacional, que tuvo lugar en el año 2003 y en el que participaron cuatro mil ciento treinta directivos y docentes de este nivel de enseñanza.Ministerio Educación. RIEJACH