181 research outputs found

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    A Systems Level, Functional Genomics Analysis of Chronic Epilepsy

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    Neither the molecular basis of the pathologic tendency of neuronal circuits to generate spontaneous seizures (epileptogenicity) nor anti-epileptogenic mechanisms that maintain a seizure-free state are well understood. Here, we performed transcriptomic analysis in the intrahippocampal kainate model of temporal lobe epilepsy in rats using both Agilent and Codelink microarray platforms to characterize the epileptic processes. The experimental design allowed subtraction of the confounding effects of the lesion, identification of expression changes associated with epileptogenicity, and genes upregulated by seizures with potential homeostatic anti-epileptogenic effects. Using differential expression analysis, we identified several hundred expression changes in chronic epilepsy, including candidate genes associated with epileptogenicity such as Bdnf and Kcnj13. To analyze these data from a systems perspective, we applied weighted gene co-expression network analysis (WGCNA) to identify groups of co-expressed genes (modules) and their central (hub) genes. One such module contained genes upregulated in the epileptogenic region, including multiple epileptogenicity candidate genes, and was found to be involved the protection of glial cells against oxidative stress, implicating glial oxidative stress in epileptogenicity. Another distinct module corresponded to the effects of chronic seizures and represented changes in neuronal synaptic vesicle trafficking. We found that the network structure and connectivity of one hub gene, Sv2a, showed significant changes between normal and epileptogenic tissue, becoming more highly connected in epileptic brain. Since Sv2a is a target of the antiepileptic levetiracetam, this module may be important in controlling seizure activity. Bioinformatic analysis of this module also revealed a potential mechanism for the observed transcriptional changes via generation of longer alternatively polyadenlyated transcripts through the upregulation of the RNA binding protein HuD. In summary, combining conventional statistical methods and network analysis allowed us to interpret the differentially regulated genes from a systems perspective, yielding new insight into several biological pathways underlying homeostatic anti-epileptogenic effects and epileptogenicity

    High Healthcare Utilization at the Onset of Medically Unexplained Symptoms

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    Objective: Patients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans to understand the relationship of increasing physical symptom burden to healthcare utilization. Methods: Data was examined from a prospective study of OEF/OIF veterans assessed before and one year after deployment (n=335). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). Results: Increases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope = -0.26, F=4.07, p=0.04), specialist (slope = -.43, t=8.67, p=0.003), allied health therapy (e.g., physical therapy) (slope = -.41, t=5.71, p=0.02) and mental health (slope = -.32, F=4.04, p=0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. Conclusion: This is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset

    Relation of teacher qualification in the academic, professional an d pedagogical sphere with the preliminary concept of the course in accounting sciences

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    O objetivo do estudo é analisar a relação, com base na percepção do educador, da qualificação docente na esfera acadêmica, profissional e pedagógica com o Conceito Preliminar do Curso (CPC) em Ciências Contábeis na modalidade presencial. Aplicou-se questionário aos docentes obtendo 194 respondentes, sendo realizada análise descritiva, com a utilização de estatística descritiva e regressão linear múltipla. Cursos com maior CPC apresentam maior percentual de docentes com altas titulações, mas professores de CPC baixo apreciam mais a qualificação acadêmica. No âmbito profissional, a experiência de mercado é maior que dez anos em todos os CPCs. Na esfera pedagógica, o tempo de docência é maior nos CPCs altos e esses se associam ao índice de qualidade do ensino superior - Conceito ENADE. Assim, contribui-se na análise do quadro docente e de possíveis melhorias e investimentos em qualificação dos mesmos.El objetivo del estudio es analizar la relación, a partir de la percepción del educador, de la calificación docente en los ámbitos académico, profesional y pedagógico con el Concepto Preliminar del Curso (CPC) en Ciencias Contables en la modalidad presencial. Se aplicó un cuestionario a los profesores, obteniendo 194 encuestados, y se realizó un análisis descriptivo, utilizando estadística descriptiva y regresión lineal múltiple. Los cursos con un CPC más alto tienen un mayor porcentaje de profesores con títulos altos, pero los profesores con un CPC bajo aprecian más las calificaciones académicas. En el ámbito profesional, la experiencia en el mercado es de más de diez años en todos los CPC. En el ámbito pedagógico, el tiempo de docencia es mayor en los CPC altos y estos se asocian al índice de calidad de la educación superior - Concepto ENADE. Así, contribuye al análisis del profesorado y de las posibles mejoras e inversiones en su cualificación.The objective of the study is to analyze the relationship, based on the educator's perception, of the teaching qualification in the academic, professional and pedagogical spheres with the Preliminary Concept of the Course (CPC) in Accounting Sciences in the face-to-face modality. A questionnaire was applied to the professors, obtaining 194 respondents, and a descriptive analysis was performed, using descriptive statistics and multiple linear regressions. Courses with higher CPC have a higher percentage of professors with high degrees, but professors with low CPC are more appreciative of academic qualifications. In the professional sphere, the market experience is more than ten years in all CPCs. In the pedagogical sphere, teaching time is longer in high CPCs and these are associated with the higher education quality index - ENADE Concept. Thus, it contributes to the analysis of the teaching staff and possible improvements and investments in their qualification

    Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance

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    Aims: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. Results: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA—the response regulator—is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of COchallenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources

    High healthcare utilization near the onset of medically unexplained symptoms

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    Objective: Patients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) soldiers to understand the relationship of increasing physical symptom burden to healthcare utilization. Methods: Data was examined from a prospective study of OEF/OIF soldiers assessed before and one year after deployment (n = 336). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). Results: Increases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope = − 0.26, F = 4.07, p = 0.04), specialist (slope = − 0.43, F = 8.67, p = 0.003), allied health therapy (e.g., physical therapy) (slope = − 0.41, F = 5.71, p = 0.02) and mental health (slope = − 0.32, F = 4.04, p = 0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. Conclusion: This is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset

    The role of diet and other environmental factors in the causation of gastric cancer in Iran—A population based study

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    Despite a declining trend in the incidence of gastric cancer (GC), it is still a major global public health concern of the 21st century. The rates of GC reported from Ardabil Province, Iran, are among the highest in the world. To investigate risk factors for GC in Ardabil, we undertook a population-based case-control study. The study aimed to recruit all Ardabil residents newly diagnosed with GC in the time period of 2004–2005, and 2 controls per case. Participants were interviewed using a structured questionnaire. Ten milliliters of blood was collected for blood grouping and investigating the presence of IgG antibodies against Helicobacter pylori. During the study period, 217 people with GC and 394 controls were recruited. In multivariate analysis, diet and Helicobacter pylori infection (OR 5 2.41; 95% CI: 1.35–4.32) were found to be the factors that were most strongly related to GC. High intake of Allium vegetables (OR 5 0.35) and fruit, especially citrus fruit (OR 5 0.31) and consumption of fresh fish (OR 5 0.37) were significantly protective. On the other hand, consumption of red meat (OR 5 3.40) and dairy products (OR 5 2.28) were positively associated with the risk of GC. People who had a preference for higher salt intake (OR 5 3.10) and drinking strong and hot tea (OR 5 2.64 and 2.85, respectively) were at higher risk. In conclusion, Helicobacter pylori infection as measured by serum IgG as well as the consumption of red meat and dairy products increases the risk of GC in Ardabil, while the intake of fresh fruit and fresh fish decrease the risk

    A multi-layer network approach to MEG connectivity analysis

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    Recent years have shown the critical importance of inter-regional neural network connectivity in supporting healthy brain function. Such connectivity is measurable using neuroimaging techniques such as MEG, however the richness of the electrophysiological signal makes gaining a complete picture challenging. Specifically, connectivity can be calculated as statistical interdependencies between neural oscillations within a large range of different frequency bands. Further, connectivity can be computed between frequency bands. This pan-spectral network hierarchy likely helps to mediate simultaneous formation of multiple brain networks, which support ongoing task demand. However, to date it has been largely overlooked, with many electrophysiological functional connectivity studies treating individual frequency bands in isolation. Here, we combine oscillatory envelope based functional connectivity metrics with a multi-layer network framework in order to derive a more complete picture of connectivity within and between frequencies. We test this methodology using MEG data recorded during a visuomotor task, highlighting simultaneous and transient formation of motor networks in the beta band, visual networks in the gamma band and a beta to gamma interaction. Having tested our method, we use it to demonstrate differences in occipital alpha band connectivity in patients with schizophrenia compared to healthy controls. We further show that these connectivity differences are predictive of the severity of persistent symptoms of the disease, highlighting their clinical relevance. Our findings demonstrate the unique potential of MEG to characterise neural network formation and dissolution. Further, we add weight to the argument that dysconnectivity is a core feature of the neuropathology underlying schizophrenia
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