Cultivation of \u3cem\u3eTropheryma whipplei\u3c/em\u3e from Cerebrospinal Fluid

Whipple disease (WD) is a systemic disorder caused by the bacterium Tropheryma whipplei. Since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. It was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. Here we report the isolation of 2 new strains of T. whipplei from cerebrospinal fluid (CSF) of 2 patients with intestinal WD but no neurological signs or symptoms. One culture-positive specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei–specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleicacid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy

Closed-Loop Multitarget Optimization for Discovery of New Emulsion Polymerization Recipes

Self-optimization of chemical reactions enables faster optimization of reaction conditions or discovery of molecules with required target properties. The technology of self-optimization has been expanded to discovery of new process recipes for manufacture of complex functional products. A new machine-learning algorithm, specifically designed for multiobjective target optimization with an explicit aim to minimize the number of “expensive” experiments, guides the discovery process. This “black-box” approach assumes no a priori knowledge of chemical system and hence particularly suited to rapid development of processes to manufacture specialist low-volume, high-value products. The approach was demonstrated in discovery of process recipes for a semibatch emulsion copolymerization, targeting a specific particle size and full conversion.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (EC FP7) Grant Agreement no. [NMP2-SL-2012-280827] and EPSRC project “Closed Loop Optimization for Sustainable Chemical Manufacture” [EP/L003309/1]

Cultivation of Tropheryma whipplei from cerebrospinal fluid

Whipple disease (WD) is a systemic disorder caused by the bacterium Tropheryma whipplei. Since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. It was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. Here we report the isolation of 2 new strains of T. whipplei from cerebrospinal fluid (CSF) of 2 patients with intestinal WD but no neurological signs or symptoms. One culture-positive specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei–specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleicacid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy

Rhinosporidium seeberi: a human pathogen from a novel group of aquatic protistan parasites.

Rhinosporidium seeberi, a microorganism that can infect the mucosal surfaces of humans and animals, has been classified as a fungus on the basis of morphologic and histochemical characteristics. Using consensus polymerase chain reaction (PCR), we amplified a portion of the R. seeberi 18S rRNA gene directly from infected tissue. Analysis of the aligned sequence and inference of phylogenetic relationships showed that R. seeberi is a protist from a novel clade of parasites that infect fish and amphibians. Fluorescence in situ hybridization and R. seeberi- specific PCR showed that this unique 18S rRNA sequence is also present in other tissues infected with R. seeberi. Our data support the R. seeberi phylogeny recently suggested by another group. R. seeberi is not a classic fungus, but rather the first known human pathogen from the DRIPs clade, a novel clade of aquatic protistan parasites (Ichthyosporea)

Comparative Nephrotoxicity of Cisplatin and Nedaplatin: Mechanisms and Histopathological Characteristics

The antineoplastic platinum complexes cisplatin and its analogues are widely used in the chemotherapy of a variety of human malignancies, and are especially active against several types of cancers. Nedaplatin is a second-generation platinum complex with reduced nephrotoxicity. However, their use commonly causes nephrotoxicity due to a lack of tumor tissue selectivity. Several recent studies have provided significant insights into the molecular and histopathological events associated with nedaplatin nephrotoxicity. In this review, we summarize findings concerning the renal histopathology and molecular pathogenesis induced by antineoplastic platinum complexes, with a particular focus on the comparative nephrotoxicity of cisplatin and nedaplatin in rats

Setting Research Priorities To Reduce Global Mortality from Childhood Diarrhoea by 2015

Olivier Fontaine and colleagues applied a priority-setting methodology to identify research priorities aimed at reducing global diarrhea mortality by 2015

Electrical properties of a-antimony selenide

This paper reports conduction mechanism in a-\sbse over a wide range of temperature (238K to 338K) and frequency (5Hz to 100kHz). The d.c. conductivity measured as a function of temperature shows semiconducting behaviour with activation energy $\Delta$E= 0.42 eV. Thermally induced changes in the electrical and dielectric properties of a-\sbse have been examined. The a.c. conductivity in the material has been explained using modified CBH model. The band conduction and single polaron hopping is dominant above room temperature. However, in the lower temperature range the bipolaron hopping dominates.Comment: 9 pages (RevTeX, LaTeX2e), 9 psfigures, also at http://pu.chd.nic.in/ftp/pub/san16 e-mail: gautam%[email protected]

Relationships among common illness symptoms and the protective effect of breastfeeding in early childhood in MAL-ED: An eight-country cohort study

Children in low-income countries experience multiple illness symptoms in early childhood. Breastfeeding is protective against diarrhea and respiratory infections, and these illnesses are thought to be risk factors of one another, but these relationships have not been explored simultaneously. In the eight-site MAL-ED study, 1,731 infants were enrolled near birth and followed for 2 years. We collected symptoms and diet information through twice-weekly household visits. Poisson regression was used to determine if recent illness history was associated with incidence of diarrhea or acute lower respiratory infections (ALRI), accounting for exclusive breastfeeding. Recent diarrhea was associated with higher risk of incident diarrhea after the first 6 months of life (relative risk [RR] 1.10, 95% confidence interval [CI] 1.04, 1.16) and with higher risk of incident ALRI in the 3- to 5-month period (RR 1.23, 95% CI 1.03, 1.47). Fever was a consistent risk factor for both diarrhea and ALRI. Exclusive breastfeeding 0-6 months was protective against diarrhea (0-2 months: RR 0.39, 95% CI 0.32, 0.49; 3-5 months: RR 0.83, 95% CI 0.75, 0.93) and ALRI (3-5 months: RR 0.81, 95% CI 0.68, 0.98). Children with recent illness who were exclusively breastfed were half as likely as those not exclusively breastfed to experience diarrhea in the first 3 months of life. Recent illness was associated with greater risk of new illness, causing illnesses to cluster within children, indicating that specific illness-prevention programs may have benefits for preventing other childhood illnesses. The results also underscore the importance of exclusive breastfeeding in the first 6 months of life for disease prevention

Non-destructive characterisation of iron gall ink drawings: not such a galling problem

Iron gall inks are of extraordinary historical significance considering their widespread use for over a millennium. Due to their corrosiveness, which is a consequence of their acidity and content of transition metals, iron gall inks accelerate the degradation of the writing or drawing support, which in this study is rag paper. Characterisation of acidity (pH) and degree of polymerisation (DP) of cellulose in paper is thus of high interest as it enables the estimation of material stability and assessment of risks associated with its handling. Based on a well-characterised set of samples with iron gall ink from the 18th and 19th centuries, we developed a near infrared spectroscopic method with partial least squares calibration for non-destructive determination of pH and DP of both inked areas and paper. Using this method, 27 18th and 19th century iron gall ink drawings from the British Museum collection were analysed and in all cases, inked areas turned out to be more acidic and degraded than the surrounding paper. Based on the obtained DP data, we were able to estimate the time needed for the inked areas to degrade to the point when they become at risk of damage due to handling. Using the average uncertainty of the calculated lifetime, we propose a quantitative stability classification method which could contribute to the curatorial and conservation decision-making process

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

<p>Abstract</p> <p>Background</p> <p>There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders.</p> <p>Results</p> <p>At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (S_A/S_Aand S_A/L_G) as compared to those with high expression(L_A/L_A), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.</p> <p>Conclusion</p> <p>This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.</p