Aseptic meningitis in Germany associated with echovirus type 13

BACKGROUND: Echoviruses are the commonest cause of aseptic meningitis. Echovirus type 13 which has not been isolated in Germany over a long period of time was the predominant enterovirus serotype associated with different local outbreaks of aseptic meningitis in Germany in 2000. METHODS: Virus isolation was performed from cerebrospinal fluid and stools. In order to study the genetic relationship of echovirus type 13 isolates, sequence analysis of a part of VP1 (~300 nt) was carried out. Isolates from different geographic regions were compared to each other as well as to elder viruses (prototype strain from 1953, four isolates from 1965–1986). RESULTS: Overall, 55 isolates of echovirus type 13 were obtained from different parts of Germany. It was shown that the new isolated strains have a very high degree of homology on the nucleotide level (> 98%)) but differ significantly from the old strains (76–85%). CONCLUSIONS: a) Rare enterovirus serotypes can cause serious illness. b) The molecular drift has also been shown for other enterovirus serotypes

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

<p>Abstract</p> <p>Background</p> <p>Immunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.</p> <p>Methods</p> <p>To estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for ≥ 6 months.</p> <p>Results</p> <p>Twenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for ≥ 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.</p> <p>Conclusion</p> <p>The results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.</p

Genotypic resistance testing in HIV by arrayed primer extension

The analysis of mutations that are associated with the occurrence of drug resistance is important for monitoring the antiretroviral therapy of patients infected with human immunodeficiency virus (HIV). Here, we describe the establishment and successful application of Arrayed Primer Extension (APEX) for genotypic resistance testing in HIV as a rapid and economical alternative to standard sequencing. The assay is based on an array of oligonucleotide primers that are immobilised via their 5′-ends. Upon hybridisation of template DNA, a primer extension reaction is performed in the presence of the four dideoxynucleotides, each labelled with a distinct fluorophore. The inserted label immediately indicates the sequence at the respective position. Any mutation changes the colour pattern. We designed a microarray for the analysis of 26 and 33 codons in the HIV protease and reverse transcriptase, respectively, which are of special interest with respect to drug resistance. The enormous genome variability of HIV represents a big challenge for genotypic resistance tests, which include a hybridisation step, both in terms of specificity and probe numbers. The use of degenerated oligonucleotides resulted in a significant reduction in the number of primers needed. For validation, DNA of 94 and 48 patients that exhibited resistance to inhibitors of HIV protease and reverse transcriptase, respectively, were analysed. The validation included HIV subtype B, prevalent in industrialised countries, as well as non-subtype B samples that are more common elsewhere

The Effect of Negative and Positive Emotionality on Associative Memory: An fMRI Study

In general, emotion is known to enhance memory processes. However, the effect of emotion on associative memory and the underling neural mechanisms remains largely unexplored. In this study, we explored brain activation during an associative memory task that involved the encoding and retrieval of word and face pairs. The word and face pairs consisted of either negative or positive words with neutral faces. Significant hippocampal activation was observed during both encoding and retrieval, regardless of whether the word was negative or positive. Negative and positive emotionality differentially affected the hemodynamic responses to encoding and retrieval in the amygdala, with increased responses during encoding negative word and face pairs. Furthermore, activation of the amygdala during encoding of negative word and neutral face pairs was inversely correlated with subsequent memory retrieval. These findings suggest that activation of the amygdala induced by negative emotion during encoding may disrupt associative memory performance

Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status

<p>Abstract</p> <p>Background</p> <p>Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status.</p> <p>Methods</p> <p>Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent <it>in situ </it>Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles.</p> <p>Results</p> <p>Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (<it>P </it>= 0.01) and 17p13-q21 (<it>P </it>< 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours.</p> <p>Conclusion</p> <p>NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.</p

Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status

<p>Abstract</p> <p>Background</p> <p>Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status.</p> <p>Methods</p> <p>Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent <it>in situ </it>Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles.</p> <p>Results</p> <p>Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (<it>P </it>= 0.01) and 17p13-q21 (<it>P </it>< 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours.</p> <p>Conclusion</p> <p>NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.</p

Utility of the Tourniquet Test and the White Blood Cell Count to Differentiate Dengue among Acute Febrile Illnesses in the Emergency Room

Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm3) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2–7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue

Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial

Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients.This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA(1c) (-0.10+/-0.65 % vs. 0.09+/-0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2+/-18.1 vs. 1.2+/-2.4 microg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes.ClinicalTrials.gov NCT00363233

Threshold Haemoglobin Levels and the Prognosis of Stable Coronary Disease: Two New Cohorts and a Systematic Review and Meta-Analysis

Background: Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated.Methods and findings: A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e. g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.Conclusions: There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality