Clinical characteristics of hypertensive encephalopathy in pediatric patients

PurposeThe aim of this study was to assess the clinical characteristics of hypertensive encephalopathy according to the underlying etiologies in children.MethodsWe retrospectively evaluated 33 pediatric patients who were diagnosed as having hypertensive encephalopathy in Chonbuk National University Children's Hospital. Among the patients, 18 were excluded because of incomplete data or because brain magnetic resonance imaging (MRI) was not performed. Finally, 17 patients were enrolled and divided into a renal-origin hypertension group and a non-renal-origin hypertension group according to the underlying cause. We compared the clinical features and brain MRI findings between the 2 groups.ResultsThe renal group included renal artery stenosis (4), acute poststreptococcal glomerulonephritis (2), lupus nephritis (2), and acute renal failure (1); the nonrenal group included essential hypertension (4), pheochromocytoma (2), thyrotoxicosis (1), and acute promyelocytic leukemia (1). The mean systolic blood pressure of the renal group (172.5±36.9 mmHg) was higher than that of the nonrenal group (137.1±11.1 mmHg, P<0.05). Seizure was the most common neurologic symptom, especially in the renal group (P<0.05). Posterior reversible encephalopathy syndrome (PRES), which is the most typical finding of hypertensive encephalopathy, was found predominantly in the renal group as compared with the nonrenal group (66.6% vs. 12.5%, P<0.05).ConclusionWe conclude that the patients with renal-origin hypertension had a more severe clinical course than those with non-renal-origin hypertension. Furthermore, the renal-origin group was highly associated with PRES on brain MRI

Genomic profile analysis of diffuse-type gastric cancers

Background: Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome. Results: We analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis. Conclusions: We report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors.open121

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Whole transcriptome analyses of six thoroughbred horses before and after exercise using RNA-Seq

Background: Thoroughbred horses are the most expensive domestic animals, and their running ability and knowledge about their muscle-related diseases are important in animal genetics. While the horse reference genome is available, there has been no large-scale functional annotation of the genome using expressed genes derived from transcriptomes. Results: We present a large-scale analysis of whole transcriptome data. We sequenced the whole mRNA from the blood and muscle tissues of six thoroughbred horses before and after exercise. By comparing current genome annotations, we identified 32,361 unigene clusters spanning 51.83 Mb that contained 11,933 (36.87%) annotated genes. More than 60% (20,428) of the unigene clusters did not match any current equine gene model. We also identified 189,973 single nucleotide variations (SNVs) from the sequences aligned against the horse reference genome. Most SNVs (171,558 SNVs; 90.31%) were novel when compared with over 1.1 million equine SNPs from two SNP databases. Using differential expression analysis, we further identified a number of exercise-regulated genes: 62 up-regulated and 80 down-regulated genes in the blood, and 878 up-regulated and 285 down-regulated genes in the muscle. Six of 28 previously-known exercise-related genes were over-expressed in the muscle after exercise. Among the differentially expressed genes, there were 91 transcription factor-encoding genes, which included 56 functionally unknown transcription factor candidates that are probably associated with an early regulatory exercise mechanism. In addition, we found interesting RNA expression patterns where different alternative splicing forms of the same gene showed reversed expressions before and after exercising. Conclusion: The first sequencing-based horse transcriptome data, extensive analyses results, deferentially expressed genes before and after exercise, and candidate genes that are related to the exercise are provided in this study.close151

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus

PurposeThis study investigated the prevalence of islet autoantibodies in children and adults with T1DM according to their age and the duration of disease.MethodsWe measured the levels of islet autoantibodies, including antiglutamic acid decarboxylase antibody (anti-GAD Ab), and combined these with anthropometric measurements and laboratory tests of 137 patients newly diagnosed with T1DM during the last 20 years. The subjects were subdivided into four groups according to their age at the onset of the disease. We then compared the prevalence of islet autoantibodies in the different age groups with the duration of disease.ResultsAmong the 137 patients, 68.9% tested positive for islet autoantibodies (71.4% within 1 year; 67.7% after 1 year of the disease onset). Within 1 year of the onset of the disease, 66.3% of the patients were positive for the anti-GAD Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was significantly higher in the prepubertal groups than in the postpubertal groups (80.0% vs. 58.3%). The rate of positive islet autoantibodies changed with the duration of disease, and it differed according to the type of autoantibody and the age of the patient.ConclusionThe rates of positive islet autoantibodies were significantly higher in younger than in older patients at the time of the diagnosis of the disease. The positive rates were significantly changed 1 year after the onset of the disease in the preschool and the children groups. So these findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in aldolescent group, carefully