Increased Inducible Nitric Oxide Synthase Expression in Organs Is Associated with a Higher Severity of H5N1 Influenza Virus Infection

BACKGROUND: The mechanisms of disease severity caused by H5N1 influenza virus infection remain somewhat unclear. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. However, enzymes of the nitric oxide synthase (NOS) family such as the inducible form of NOS (iNOS) generate NO, which serves as a potent anti-viral molecule to combat infection in combination with acute phase proteins and cytokines. Nevertheless, excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: There are dramatic differences in the severity of disease between chickens and ducks following H5N1 influenza infection. Chickens show a high level of mortality and associated pathology, whilst ducks show relatively minor symptoms. It is not clear how this varying pathogenicty comes about, although it has been suggested that an overactive inflammatory immune response to infection in the chicken, compared to the duck response, may be to blame for the disparity in observed pathology. In this study, we identify and investigate iNOS gene expression in ducks and chickens during H5N1 influenza infection. Infected chickens show a marked increase in iNOS expression in a wide range of organs. Contrastingly, infected duck tissues have lower levels of tissue related iNOS expression. CONCLUSIONS/SIGNIFICANCE: The differences in iNOS expression levels observed between chickens and ducks during H5N1 avian influenza infection may be important in the inflammatory response that contributes to the pathology. Understanding the regulation of iNOS expression and its role during H5N1 influenza infection may provide insights for the development of new therapeutic strategies in the treatment of avian influenza infection

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in Tanzania

Many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-Sahara African region. These include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. The current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-diagnosis and hence under-reporting. The study was designed as a cross-sectional survey. Semi-structured open-ended questionnaire was administered to medical practitioners to establish the knowledge of anthrax, rabies, brucellosis, trypanosomiasis, echinococcosis and bovine tuberculosis in selected health facilities within urban and rural settings in Tanzania between April and May 2005. Frequency data were analyzed using likelihood ratio chi-square in Minitab version 14 to compare practitioners' knowledge of transmission, clinical features and diagnosis of the zoonoses in the two settings. For each analysis, likelihood ratio chi-square p-value of less than 0.05 was considered to be significant. Fisher's exact test was used where expected results were less than five. Medical practitioners in rural health facilities had poor knowledge of transmission of sleeping sickness and clinical features of anthrax and rabies in humans compared to their urban counterparts. In both areas the practitioners had poor knowledge of how echinococcosis is transmitted to humans, clinical features of echinococcosis in humans, and diagnosis of bovine tuberculosis in humans. Knowledge of medical practitioners of zoonotic diseases could be a contributing factor to their under-diagnosis and under-reporting in Tanzania. Refresher courses on zoonotic diseases should be conducted particularly to practitioners in rural areas. More emphasis should be put on zoonotic diseases in teaching curricula of medical practitioners' training institutions in Tanzania to improve the diagnosis, reporting and control of zoonotic diseases. Veterinary and medical collaboration should be strengthened to enable more effective control of zoonotic diseases in Tanzania

Latent profile analysis in frontotemporal lobar degeneration and related disorders: clinical presentation and SPECT functional correlates

<p>Abstract</p> <p>Background</p> <p>Frontotemporal Lobar Degeneration (FTLD) thus recently renamed, refers to a spectrum of heterogeneous conditions. This same heterogeneity of presentation represents the major methodological limit for the correct evaluation of clinical designation and brain functional correlates. At present, no study has investigated clinical clusters due to specific cognitive and behavioural disturbances beyond current clinical criteria.</p> <p>The aim of this study was to identify clinical FTLD presentation, based on cognitive and behavioural profile, and to define their SPECT functional correlations.</p> <p>Methods</p> <p>Ninety-seven FTLD patients entered the study. A clinical evaluation and standardised assessment were preformed, as well as a brain SPECT perfusion imaging study. Latent Profile Analysis on clinical, neuropsychological, and behavioural data was performed. Voxel-basis analysis of SPECT data was computed.</p> <p>Results</p> <p>Three specific clusters were identified and named "pseudomanic behaviour" (LC1), "cognitive" (LC2), and "pseudodepressed behaviour" (LC3) endophenotypes. These endophenotypes showed a comparable hypoperfusion in left temporal lobe, but a specific pattern involving: medial and orbitobasal frontal cortex in LC1, subcortical brain region in LC2, and right dorsolateral frontal cortex and insula in LC3.</p> <p>Conclusion</p> <p>These findings provide evidence that specific functional-cluster symptom relationship can be delineated in FTLD patients by a standardised assessment. The understanding of the different functional correlates of clinical presentations will hopefully lead to the possibility of individuating diagnostic and treatment algorithms.</p

Training compliance control yields improvements in drawing as a function of beery scores

Many children have difficulty producing movements well enough to improve in sensori-motor learning. Previously, we developed a training method that supports active movement generation to allow improvement at a 3D tracing task requiring good compliance control. Here, we tested 7–8 year old children from several 2nd grade classrooms to determine whether 3D tracing performance could be predicted using the Beery VMI. We also examined whether 3D tracing training lead to improvements in drawing. Baseline testing included Beery, a drawing task on a tablet computer, and 3D tracing. We found that baseline performance in 3D tracing and drawing co-varied with the visual perception (VP) component of the Beery. Differences in 3D tracing between children scoring low versus high on the Beery VP replicated differences previously found between children with and without motor impairments, as did post-training performance that eliminated these differences. Drawing improved as a result of training in the 3D tracing task. The training method improved drawing and reduced differences predicted by Beery scores

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides

<p>Abstract</p> <p>Background</p> <p>The goal of the present study was to assess the effect of genetic variability at the APOA5/A4/C3/A1 cluster locus on the risk of metabolic syndrome.</p> <p>Methods</p> <p>The <it>APOA5 </it>Ser19Trp, <it>APOA5 </it>-12,238T>C, <it>APOA4 </it>Thr347Ser, <it>APOC3 </it>-482C>T and <it>APOC3 </it>3238C>G (<it>Sst</it>I) polymorphisms were analyzed in a representative population sample of 3138 men and women from France, including 932 individuals with metabolic syndrome and 2206 without metabolic syndrome, as defined by the NCEP criteria.</p> <p>Results</p> <p>Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03–1.66] (<it>p </it>= 0.03) for <it>APOA5 </it>Trp19 carriers, 0.81 [0.69–0.95] (<it>p </it>= 0.01) for <it>APOA5 </it>-12,238C carriers and 0.84 [0.70–0.99] (<it>p </it>= 0.04) for <it>APOA4 </it>Ser347 carriers. Adjustment for plasma triglycerides, (but not for waist girth, HDL, blood pressure or glycemia – the other components of metabolic syndrome) abolished these associations and suggests that triglyceride levels explain the association with metabolic syndrome. There was no association between the <it>APOC3 </it>-482C>T or <it>APOC3 </it>3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in <it>APOA5 </it>-12,238C and <it>APOA4 </it>Ser347 carriers merely reflected the fact that the <it>APOA5 </it>Trp19 allele was in negative linkage disequilibrium with the common alleles of <it>APOA5 </it>-12,238T>C and <it>APOA4 </it>Thr347Ser polymorphisms.</p> <p>Conclusion</p> <p>The <it>APOA5 </it>Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.</p

Keratin 8 expression in colon cancer associates with low faecal butyrate levels

<p>Abstract</p> <p>Background</p> <p>Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton <it>in vitro</it>. These and other data suggest a link between the role of diet and the implication of a central role for the keratin 8 (K8) as guardian of the colorectal epithelium.</p> <p>Methods</p> <p>In this cross-sectional study possible links between butyrate levels, field effects and keratin expression in cancer were addressed directly by analysing how levels of expression of the IF protein K8 in tumours, in adjacent fields and at a distant landmark site may be affected by the level of butyrate in the colon microenvironment. An immunohistochemical scoring protocol for K8 was developed and applied to samples, findings were further tested by immunoblotting.</p> <p>Results</p> <p>Levels of K8 in colorectal tumours are lower in subjects with higher levels of faecal butyrate. Immunoblotting supported this finding.Although there were no significant relationships with butyrate on the non-tumour tissues, there was a consistent trend in all measures of extent or intensity of staining towards a reduction in expression with elevated butyrate, consistent with the inverse association in tumours.</p> <p>Conclusions</p> <p>The data suggest that butyrate may associate with down-regulation of the expression of K8 in the cancerized colon. If further validated these findings may suggest the chemopreventive value of butyrate is limited to early stage carcinogenesis as low K8 expression is associated with a poor prognosis.</p

The development of endomycorrhizal root systems VIII. Effects of soil phosphorus and fungal colonization on the concentration of soluble carbohydrates in roots

Concentrations of phosphorus in shoot and soluble carbohydrates (fructose, glucose, sucrose and fructans) in root were measured in non-mycorrhizal and vesicular-arbuscular (VA) mycorrhizal (Glomus mosseae) leek plants (Allium porrum) raised at six concentrations of soil phosphate. In conditions when an increased concentration of soil phosphate reduced VA mycorrhizal infection, the concentrations of soluble carbohydrates in the root were at a maximum. Therefore the hypothesis that greater concentrations of soluble carbohydrates in roots favour VA mycorrhizal infection is discounted. There was a specific effect of VA mycorrhizas, in that infected roots contained a larger concentration of sucrose than did uninfected roots, in plants with similar phosphorus concentrations in dry matter of shoots. We conclude, first, that increased phosphorus supply from either phosphate addition to soil or VA mycorrhizal infection increases concentration of soluble carbohydrates in leek roots and, secondly, that the VA mycorrhizal root behaves as a particularly strong physiological sink when there is an excess concentration of sucrose in the host

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B

BACKGROUND: Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with cardiovascular diseases, but its role in persistent viral infection has not been well-defined. The present study was designed to investigate the association between RDW values and different disease states in hepatitis B virus (HBV)-infected patients. In addition, we analyzed whether RDW is associated with mortality in the HBV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-three patients, including 16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio and routine hematological testing. All patients were followed up for at least 4 months. A total of 10 clinical chemistry, hematology, and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. RDW values at admission in patients with CSHB (18.30±3.11%, P<0.001), CHB (16.37±2.43%, P<0.001) and AHB (14.38±1.72%, P<0.05) were significantly higher than those in healthy controls (13.03±1.33%). Increased RDW values were clinically associated with severe liver disease and increased 3-month mortality rate. Multivariate analysis demonstrated that RDW values and the model for end-stage liver disease score were independent predictors for mortality (both P<0.001). CONCLUSION: RDW values are significantly increased in patients with hepatitis B and associated with its severity. Moreover, RDW values are an independent predicting factor for the 3-month mortality rate in patients with hepatitis B