Modeling brain dynamics in brain tumor patients using the virtual brain

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance

Associated factors of hope in cancer patients during treatment : a systematic literature review

Aim: To identify the associated factors of hope during treatment in cancer patients. Background: Hope is very important to cancer patients at all stages of the disease process. Hope is seen as an important coping mechanism. Most research about hope in cancer patients considered the end of life or in palliative care. Several and different factors are associated with hope. It is not yet sufficiently clear which factors are associated with hope during the treatment. Design: A systematic literature review of quantitative empirical studies on hope in cancer patients during treatment. Data Sources: Search in MEDLINE (PubMed interface), CINAHL (EBSCO interface), Psychinfo and Cochrane (January 2009-December 2018). Review Methods: Empirical quantitative studies were included regardless of the disease stage, written in English or Dutch, measuring hope from the perspective of cancer patients. Two authors independently screened all the studies and assessed their quality. Results: Thirty-three studies were included. Positive relationship has been established between hope and quality of life, social support, spiritual and existential well-being. Hope appears to be negatively associated with symptom burden, psychological distress and depression. There appears to be no relationship between hope and demographic and clinical variables. The relationship between anxiety and hope remains unclear. Conclusions: Hope primarily seems to be a process that takes place in a person's inner being rather than being determined from outside. Impact: Health professionals may want to focus on the meaning of hope for cancer patients in relation to the associated factors. A better understanding of the meaning of hope during treatment can be of great value in supporting cancer patients with regard to treatment decisions, psychosocial support, the experienced quality of life and symptom burden and any wishes they may have with regard to advanced care planning

Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group.

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option

Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection

E. coli folate synthesis and C. elegans ageing: Investigating the effect of sulfamethoxazole on bacterial lawn morphology and metabolism

The gut microbiota is essential for host nutrition and may influence ageing. The nematode worm C. elegans provides a useful simplified model for investigating bacterial-host interactions. E. coli is used as a food source for C. elegans. Previous research has shown a decrease in E. coli folate synthesis results in extension of C. elegans lifespan. Potential detrimental effects of bacteria when producing normal amounts of folate are unlikely to be mediated by bacterial growth rate or direct effects of folate on the nematode. Potential toxicity of metabolic chemicals produced by wild type E. coli could explain the shorter lifespan of C. elegans. This thesis aims to understand the interaction between E. coli and C. elegans by investigating components that may be affected by folate synthesis and influencing lifespan. Toxicity from bacterial formaldehyde synthesis was explored with a formaldehyde sensing lacZ reporter. A novel method was developed to quantify reporter output in a bacterial lawn. The lifespan of C. elegans maintained on E. coli constitutively expressing the formaldehyde detoxification enzymes FrmA/B was also investigated. Formaldehyde synthesis was not found to be a source of toxicity that accelerates C. elegans ageing. The effect of sulfamethoxazole on bacterial lawn growth, morphology and proliferation was examined and found to alter morphology, attenuate growth and impair proliferation compared to wild type and lifespan increasing mutant E. coli. A novel LC-MS/MS method was developed to analyse amino acids in agar. It revealed sulfamethoxazole alters bacterial amino acid metabolism associated with the serine-glycine pathway and growth. The absence of glycine in the media was also examined. It revealed changes to the exometabolome in both sulfamethoxazole treated and untreated conditions that may slow C. elegans ageing without altering bacterial growth. This work developed novel methods for exploring the bacterial lawn and metabolism, providing insight into the mechanism of how sulfamethoxazole disruption of bacterial folate synthesis may influence C. elegans ageing