31 research outputs found

    Проблемы специализированной помощи обожженным в России и пути их решения

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    На основании изучения динамики ожогового травматизма в России, тяжести травм и летальности среди больных с ожогами отмечено увеличение тяжести термической травмы, частоты раннего ожогового сепсиса и летальности среди взрослого населения, определены организационные и научные пути решения проблемы, повышения эффективности работы ожоговых центров.Basing on the study of the dynamics of burns in Russia, severity of the injury and death rate in the patients with burns the authors emphasize the increase in severity of thermal injury, incidence of early burn sepsis and death rate in adults. Organizational and scientific ways to solve the problem as well as to increase the efficacy of work of burn centers are defined

    Fusion transcripts and their genomic breakpoints in polyadenylated and ribosomal RNA-minus RNA sequencing data

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    BACKGROUND: Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints. RESULTS: We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an entire reference genome into account as search space. This includes exons but also introns, intergenic regions, and sequences that do not meet splice junction motifs. Using 1,275 RNA-seq samples, we investigated to what extent genomic breakpoints can be extracted from RNA-seq data and their implications regarding poly(A)-enriched and ribosomal RNA–minus RNA-seq data. Comparison with whole-genome sequencing data revealed that most genomic breakpoints are not, or minimally, transcribed while, in contrast, the genomic breakpoints of all 32 TMPRSS2-ERG–positive tumours were present at RNA level. We also revealed tumours in which the ERG breakpoint was located before ERG, which co-existed with additional deletions and messenger RNA that incorporated intergenic cryptic exons. In breast cancer we identified rearrangement hot spots near CCND1 and in glioma near CDK4 and MDM2 and could directly associate this with increased expression. Furthermore, in all datasets we find fusions to intergenic regions, often spanning multiple cryptic exons that potentially encode neo-antigens. Thus, fusion transcripts other than classical gene-to-gene fusions are prominently present and can be identified using RNA-seq. CONCLUSION: By using the full potential of non–poly(A)-enriched RNA-seq data, sophisticated analysis can reliably identify expressed genomic breakpoints and their transcriptional effects

    Development and body mass inversely affect children’s brain activation in dorsolateral prefrontal cortex during food choice

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    Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.</p

    Consensus molecular subtype classification of colorectal adenomas

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    Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC

    Neural processing of healthy foods in normal-weight and overweight children and adults

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    Childhood obesity is a growing problem almost everywhere in the world. The chance for an overweight child to become an overweight adult is much larger than for a normal-weight child, which emphasizes the importance of prevention. Weight gain, and thus overweight and obesity, is largely caused by overconsumption, which in turn is driven by food choices. These decisions on what, when, and how much to eat are made in the brain, which integrates a multitude of neural and hormonal signals arising in response to the body’s internal state and the environment. Understanding how the brain responds to food and how eating decisions are made in the brain, is crucial for elucidating the neural processes underlying maladaptive eating behaviors. This knowledge may provide novel approaches for the prevention of childhood obesity and for healthy eating interventions. In this thesis, how the brain responds to food is measured by functional Magnetic Resonance Imaging (fMRI). fMRI is a non-invasive neuroimaging technique which enables measuring which parts of the brain become more active when a certain task is performed. Food-related brain activation in children is expected to differ from that in adults because their brain is still developing. This applies in particular to the prefrontal cortex, which is among the last brain regions to mature and which is involved in the control of behavior and the inhibition of impulsive responses. The aim was to examine the neural responses to healthy and unhealthy food viewing and food choice in normal- and overweight children and adults. The conclusion of this thesis was that children had weaker brain responses related to cognitive control than adults when viewing unhealthy foods and when making food choices. Children who are overweight had even weaker responses in this area. This pattern of brain activation was accompanied by more unhealthy choices in children. Taken together, children in general and overweight children in particular may be more vulnerable to unhealthy foods in their environment and less able to resist unhealthy choice options. The results presented in this thesis make a strong case for decreasing the marketing of unhealthy foods directed at children and adapting the food environment to promote healthier choices

    Food Decision-Making : Effects of Weight Status and Age

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    Food decisions determine energy intake. Since overconsumption is the main driver of obesity, the effects of weight status on food decision-making are of increasing interest. An additional factor of interest is age, given the rise in childhood obesity, weight gain with aging, and the increased chance of type 2 diabetes in the elderly. The effects of weight status and age on food preference, food cue sensitivity, and self-control are discussed, as these are important components of food decision-making. Furthermore, the neural correlates of food anticipation and choice and how these are affected by weight status and age are discussed. Behavioral studies show that in particular, poor self-control may have an adverse effect on food choice in children and adults with overweight and obesity. Neuroimaging studies show that overweight and obese individuals have altered neural responses to food in brain areas related to reward, self-control, and interoception. Longitudinal studies across the lifespan will be invaluable to unravel the causal factors driving (changes in) food choice, overconsumption, and weight gain

    Blood-brain barrier (BBB): an overview of the research of the blood-brain barrier using microfluidic devices

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    The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential. This chapter highlights the anatomy and physiology of the BBB and gives an overview of the current available in vitro models to study the BBB in detail. Proof-of-concept work of BBB-on-Chips are described. Additionally, examples are given to optimize the present devices by engineering the microenvironment to better mimic the in vivo situation. This combination of biomedical science and micro-engineering will generate exciting new results in the field of neurovascular biology

    Daily distracted consumption patterns and their relationship with BMI

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    The rapidly increasing prevalence of overweight and obesity has heightened the need for a better understanding of obesity-related eating patterns and dietary behaviours. Recent work suggests that distracted eating is causally related to increased immediate and later food, pushing the need for a better understanding of the prevalence of distracted consumption and how this relates to body weight. To extract insights in the relationship between demographics, daily consumption settings, and BMI, we performed secondary data analyses on data from 1011 individuals representative of the Dutch population (adults, 507F, BMI 17–50 kg/m2). The most commonly reported distractions were talking to others (32.7%) and watching television (21.7%). Only 18.4% of respondents reported no distractions during meals. To examine how different distractions related to BMI, we performed OLS regression which showed, among other things, that watching tv while eating lunch (η2 = 0.37) and working during dinner were associated with a higher BMI (η2 = 1.63). To examine the robustness of these findings, machine learning techniques were used. A random forest analysis (RMSE = 4.09) showed that next to age and education level, distraction during lunch and snack was amongst the largest predictors of BMI. Multiple linear regression with lasso penalty (RMSE = 4.13) showed that specifically watching tv while eating lunch or snacks was associated with a higher BMI. In conclusion, our analyses confirmed the assumption that people are regularly distracted during their daily meals, with distinct distractors relating to BMI. These findings provide a starting point for evidence-based recommendations on which consumption settings are associated with healthier eating patterns and body weight.</p

    Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults

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    Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is involved in self-control. We aimed to examine the neural correlates of food choice in children, and how considering healthiness affects neural activity and choice behavior. 24 children and 28 adults performed a food choice task while being scanned with fMRI and provided health and taste ratings of the foods afterwards. During the choice task participants considered either the healthiness or tastiness of the food or chose naturally. Health rating was a positive predictor of choice in adults, but a negative predictor in children. Children had weaker dlPFC activation than adults during yes vs. no independent of health or taste condition. Both children and adults made healthier choices when considering healthiness. Taste rating modulated mPFC activation in both children and adults. When considering the healthiness, health rating positively modulated mPFC activation in adults, but negatively in children. Considering the healthiness increased connectivity between dlPFC and mPFC in adults, but not in children. In conclusion, considering healthiness can promote healthier choices in both children and adults, but is accompanied by an opposing pattern of brain activation in the mPFC. Since the absolute number of healthy choices remained lower in children, this suggests that children may not yet be geared to modify their choices away from their natural tendency to choose unhealthy tasty foods. Thus, this study suggests that it may be promising to develop interventions that increase children's preference for healthy food, for example by increasing the habitual consumption of healthy foods from a young age

    Standardized food images : A photographing protocol and image database

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    The regulation of food intake has gained much research interest because of the current obesity epidemic. For research purposes, food images are a good and convenient alternative for real food because many dietary decisions are made based on the sight of foods. Food pictures are assumed to elicit anticipatory responses similar to real foods because of learned associations between visual food characteristics and post-ingestive consequences. In contemporary food science, a wide variety of images are used which introduces between-study variability and hampers comparison and meta-analysis of results. Therefore, we created an easy-to-use photographing protocol which enables researchers to generate high resolution food images appropriate for their study objective and population. In addition, we provide a high quality standardized picture set which was characterized in seven European countries. With the use of this photographing protocol a large number of food images were created. Of these images, 80 were selected based on their recognizability in Scotland, Greece and The Netherlands. We collected image characteristics such as liking, perceived calories and/or perceived healthiness ratings from 449 adults and 191 children. The majority of the foods were recognized and liked at all sites. The differences in liking ratings, perceived calories and perceived healthiness between sites were minimal. Furthermore, perceived caloric content and healthiness ratings correlated strongly (r ≥ 0.8) with actual caloric content in both adults and children. The photographing protocol as well as the images and the data are freely available for research use on http://nutritionalneuroscience.eu/. By providing the research community with standardized images and the tools to create their own, comparability between studies will be improved and a head-start is made for a world-wide standardized food image database
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