Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis

Background Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neuro-specific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analysed for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and multiple inflammatory markers. Results were compared with 2 control groups; patients with 1) a fatty filum (abnormal filum terminale of the spinal cord), and 2) pulmonary tuberculosis (pTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results Data were collected from 44 TBM cases (median age 3.3 [0.3–13.1] years), 11 fatty filum (median age 2.8 [0.8–8] years) and 9 pTB controls (median age 3.7 [1.3–11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated IL-12p40, IP-10 and MCP-1 concentrations, whereas infarcts were associated with elevated TNF-α, MIP-1α, IL-6 and IL-8. Conclusion CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM

Use of Photography in Geography Teaching

This dissertation is concerned on visual literacy and the usage of photograph. The theoretical part shows different views on photographs. Photograph is described by psychologists, sociologists, journalists and as a picture material and research task. The practical part is based on classification of visual literacy. At first the author judges the literacy on a model example and afterwards he does research based on his own questionary. The questionary is devided into four packs of questions. The first pack introduces the research to the respondents and states their gender, age and education. The other three packs are filled with questions tied with certain photographs. The individual questions are mostly devided into two parts, the first part seeks for a concrete answer and the second part asks the respondents to explain the way they found their answers. The study has the nature of a pilot project that verifies the dependance of visual literacy, or more precisely validity of answers, according to education, age, gender and field of study. Based on the respondents' answers their ways of perception, reading, interpretation and further work with information contained in the photographs are investigated. The addenda contain some examples of exercises that can be used to practice the work with photographs. Powered..

Additional file 2: Figure S1. of Epigenetic assimilation in the aging human brain

Examples of data distribution for DNA modification and transcriptome data in older (>75 years) and younger (>75 years) individuals. Violin plots showing representative densities of DNA modification (beta values) and probe signal intensities in transcriptome data for older and younger individuals for a given probe. One-tailed F-test was used to identify cases where older individuals had lower variance than the young (i.e., F-test p < 0.05). a An example of a DNA modification probe where the older individuals had significantly lower variance than the younger individuals. b An example of a DNA modification probe where older individuals did not show significantly smaller variance compared with the younger individuals. c An example of a transcript with smaller variance in older compared with younger individuals. d An example of a transcript with non-significant difference of variance. (PDF 410 kb

Additional file 4: Figure S2. of Epigenetic assimilation in the aging human brain

Permuted null distribution of mean ICC in AD twin samples. ICC densities of the permuted null from all samples compared with the mean ICC in the indicated subset sample of interest (red dashed line). a EAO cortex versus cerebellum using the top 5 % of differentially modified loci (permuted p = 0.014). b EAO cortex versus cerebellum using the bottom 5 % of differentially modified loci (permuted p = 0.51). c EAO cortex versus cerebellum using the nominally significant (p < 0.05) DNA modification loci (permuted p < 10-6). d AD affected versus unaffected co-twin buccal samples using the top 5 % of differentially modified loci (permuted p = 1.4 × 10-3). e AD affected versus unaffected co-twin buccal samples using the bottom 5 % of differentially modified loci (permuted p = 0.43). f AD affected versus unaffected co-twin buccal samples using the nominally significant (p < 0.05) DNA modification loci from the cortex (permuted p = 0.07). (PDF 441 kb

Additional file 1: Table S1. of Epigenetic assimilation in the aging human brain

Sample information. (PDF 40 kb

Additional file 7: Figure S4. of Epigenetic assimilation in the aging human brain

Permuted null distribution of mean domain length. The histogram represents the densities of the permuted null distribution from all samples and the red dashed line is the mean domain length in the indicated subset sample of interest (i.e., older individuals (>75 years), EAO cortex, or AD buccal cells). a Mean DNA modification domain length of older individual in the cerebral cortex (permuted p = 0.01). b Mean DNA modification domain length of older individual in the cerebellum (permuted p = 0.13). c Mean domain length of older individual transcriptome in the cerebral cortex (permuted p = 0.01). d Mean domain length of older individual transcriptome in the cerebellum (permuted p = 0.51). e Mean domain length of the EAO cerebral cortex (permuted p = 0.015). f Mean domain length of the AD-affected twin buccal samples (permuted p = 0.04). (PDF 131 kb

Additional file 5: Figure S3. of Epigenetic assimilation in the aging human brain

ICC of DNA modification for the 82 disease-specific differentially modified loci (p < 0.05). The Z-scores are normalized ICC coefficients, where positive Z-scores represent ICC coefficients that are higher than the mean, while negative Z-scores show the opposite. Cumulative Z-scores for normalized ICC coefficients represent the following: 0 % includes none, 50 % includes half, and 100 % includes all Z-scores. a Approximately 90 % of Z-scores are positive in the comparison of the EAO AD cortex samples versus cerebellum (CB) but only ~25 % of Z-scores are positive in the LAO versus cerebellum, indicating a more advanced state of dedifferentiation for EAO AD cortices. LAO versus EAO show an even distribution. b Buccal cell analysis showed that ~75 % AD twins, but only ~50 % of their healthy co-twins, had higher than average similarity as measured by Z-scores of ICC. (PDF 123 kb

Additional file 3: Table S2. of Epigenetic assimilation in the aging human brain

List of significant loci (p < 0.05) in the cerebral cortex of twins different for AD age of onset. (PDF 73 kb