Candidiasis caused by Candida kefyr in a neonate: Case report

<p>Abstract</p> <p>Background</p> <p>Systemic <it>Candidia </it>infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic <it>Candida </it>infection. We report a very rare case of candidiasis caused by <it>Candida kefyr </it>in a term neonate.</p> <p>Case Presentation</p> <p>Renal agenesis on the left side was diagnosed antenatally and anal atresia postnatally. Moreover, a vesico-ureteral-reflux (VUR) grade V was detected by cystography. The first surgical procedure, creating a protective colostoma, was uneventful. Afterwards our patient developed urosepsis caused by <it>Enterococcus faecalis </it>and was treated with piperacillin. The child improved initially, but deteriorated again. A further urine analysis revealed <it>Candida kefyr </it>in a significant number. As antibiotic resistance data about this non-<it>albicans Candida </it>species are limited, we started liposomal amphotericin B (AMB), but later changed to fluconazole after receiving the antibiogram. Candiduria persisted and abdominal imaging showed a <it>Candida </it>pyelonephritis. Since high grade reflux was prevalent we instilled AMB into the child's bladder as a therapeutic approach. While undergoing surgery (creating a neo-rectum) a recto-vesical fistula could be shown and subsequently was resected. The child recovered completely under systemic fluconazole therapy over 3 months.</p> <p>Conclusions</p> <p>Candidiasis is still of major concern in neonates with accompanying risk factors. As clinicians are confronted with an increasing number of non-<it>albicans Candida </it>species, knowledge about these pathogens and their sensitivities is of major importance.</p

Increased Asymmetric and Multi-Daughter Cell Division in Mechanically Confined Microenvironments

As the microenvironment of a cell changes, associated mechanical cues may lead to changes in biochemical signaling and inherently mechanical processes such as mitosis. Here we explore the effects of confined mechanical environments on cellular responses during mitosis. Previously, effects of mechanical confinement have been difficult to optically observe in three-dimensional and in vivo systems. To address this challenge, we present a novel microfluidic perfusion culture system that allows controllable variation in the level of confinement in a single axis allowing observation of cell growth and division at the single-cell level. The device is capable of creating precise confinement conditions in the vertical direction varying from high (3 µm) to low (7 µm) confinement while also varying the substrate stiffness (E = 130 kPa and 1 MPa). The Human cervical carcinoma (HeLa) model with a known 3N+ karyotype was used for this study. For this cell line, we observe that mechanically confined cell cycles resulted in stressed cell divisions: (i) delayed mitosis, (ii) multi- daughter mitosis events (from 3 up to 5 daughter cells), (iii) unevenly sized daughter cells, and (iv) induction of cell death. In the highest confined conditions, the frequency of divisions producing more than two progeny was increased an astounding 50-fold from unconfined environments, representing about one half of all successful mitotic events. Notably, the majority of daughter cells resulting from multipolar divisions were viable after cytokinesis and, perhaps suggesting another regulatory checkpoint in the cell cycle, were in some cases observed to re-fuse with neighboring cells post-cytokinesis. The higher instances of abnormal mitosis that we report in confined mechanically stiff spaces, may lead to increased rates of abnormal, viable, cells in the population. This work provides support to a hypothesis that environmental mechanical cues influences structural mechanisms of mitosis such as geometric orientation of the mitotic plane or planes

Evolution of Streptococcus pneumoniae and Its Close Commensal Relatives

Streptococcus pneumoniae is a member of the Mitis group of streptococci which, according to 16S rRNA-sequence based phylogenetic reconstruction, includes 12 species. While other species of this group are considered prototypes of commensal bacteria, S. pneumoniae is among the most frequent microbial killers worldwide. Population genetic analysis of 118 strains, supported by demonstration of a distinct cell wall carbohydrate structure and competence pheromone sequence signature, shows that S. pneumoniae is one of several hundred evolutionary lineages forming a cluster separate from Streptococcus oralis and Streptococcus infantis. The remaining lineages of this distinct cluster are commensals previously collectively referred to as Streptococcus mitis and each represent separate species by traditional taxonomic standard. Virulence genes including the operon for capsule polysaccharide synthesis and genes encoding IgA1 protease, pneumolysin, and autolysin were randomly distributed among S. mitis lineages. Estimates of the evolutionary age of the lineages, the identical location of remnants of virulence genes in the genomes of commensal strains, the pattern of genome reductions, and the proportion of unique genes and their origin support the model that the entire cluster of S. pneumoniae, S. pseudopneumoniae, and S. mitis lineages evolved from pneumococcus-like bacteria presumably pathogenic to the common immediate ancestor of hominoids. During their adaptation to a commensal life style, most of the lineages gradually lost the majority of genes determining virulence and became genetically distinct due to sexual isolation in their respective hosts

Holocene dynamics of the Southern Hemisphere westerly winds and possible links to CO2 outgassing

The Southern Hemisphere westerly winds (SHW) play an important role in regulating the capacity of the Southern Ocean carbon sink. They modulate upwelling of carbon-rich deep water and, with sea ice, determine the ocean surface area available for air–sea gas exchange. Some models indicate that the current strengthening and poleward shift of these winds will weaken the carbon sink. If correct, centennial- to millennial-scale reconstructions of the SHW intensity should be linked with past changes in atmospheric CO2, temperature and sea ice. Here we present a 12,300-year reconstruction of wind strength based on three independent proxies that track inputs of sea-salt aerosols and minerogenic particles accumulating in lake sediments on sub-Antarctic Macquarie Island. Between about 12.1 thousand years ago (ka) and 11.2 ka, and since about 7 ka, the wind intensities were above their long-term mean and corresponded with increasing atmospheric CO2. Conversely, from about 11.2 to 7.2 ka, the wind intensities were below their long-term mean and corresponded with decreasing atmospheric CO2. These observations are consistent with model inferences of enhanced SHW contributing to the long-term outgassing of CO2 from the Southern Ocean

The relation between endothelial dependent flow mediated dilation of the brachial artery and coronary collateral development – a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Endothelial dysfunction is thought to be a potential mechanism for the decreased presence of coronary collaterals. The aim of the study was to investigate the association between systemic endothelial function and the extent of coronary collaterals.</p> <p>Methods</p> <p>We investigated the association between endothelial function assessed via flow mediated dilation (FMD) of the brachial artery following reactive hyperemia and the extent of coronary collaterals graded from 0 to 3 according to Rentrop classification in a cohort of 171 consecutive patients who had high grade coronary stenosis or occlusion on their angiograms.</p> <p>Results</p> <p>Mean age was 61 years and 75% were males. Of the 171 patients 88 (51%) had well developed collaterals (grades of 2 or 3) whereas 83 (49%) had impaired collateral development (grades of 0 or 1). Patients with poor collaterals were significantly more likely to have diabetes (<it>p </it>= 0.001), but less likely to have used statins (<it>p </it>= 0.083). FMD measurements were not significantly different among good and poor collateral groups (11.5 ± 5.6 vs. 10.4 ± 6.2% respectively, <it>p </it>= 0.214). Nitroglycerin mediated dilation was also similar (13.4 ± 5.9 vs. 12.8 ± 6.5%, <it>p </it>= 0.521).</p> <p>Conclusion</p> <p>No significant association was found between the extent of angiographically visible coronary collaterals and systemic endothelial function assessed by FMD of the brachial artery.</p

Financial and monetary policy responses to oil price shocks: evidence from oil-importing and oil-exporting countries

In this study, we investigate the financial and monetary policy responses to oil price shocks using a Structural VAR framework. We distinguish between net oil-importing and net oil-exporting countries. Since the 80s, a significant number of empirical studies have been published investigating the effect of oil prices on macroeconomic and financial variables. Most of these studies though, do not make a distinction between oil-importing and oil-exporting economies. Overall, our results indicate that the level of inflation in both net oil-exporting and net oil-importing countries is significantly affected by oil price innovations. Furthermore, we find that the response of interest rates to an oil price shock depends heavily on the monetary policy regime of each country. Finally, stock markets operating in net oil-importing countries exhibit a negative response to increased oil prices. The reverse is true for the stock market of the net oil-exporting countries. We find evidence that the magnitude of stock market responses to oil price shocks is higher for the newly established and/or less liquid stock market

Working without a blindfold: the critical role of diagnostics in malaria control

Diagnostic testing for malaria has for many years been eschewed, lest it be an obstacle to the delivery of rapid, life-saving treatment. The approach of treating malaria without confirmatory testing has been reinforced by the availability of inexpensive treatment with few side effects, by the great difficulty of establishing quality-assured microscopy in rural and resource-poor settings, and by the preeminence of malaria as a cause of important fever in endemic regions. Within the last decade, all three of these factors have changed. More expensive artemisinin combination therapy (ACT) has been widely introduced, simple immunochromatographic tests for malaria have been developed that can be used as an alternative to microscopy by village health workers, and recognition of the health cost of mismanaging non-malarial fever is growing. In most of the world a small fraction of fever is due to malaria, and reflex treatment with ACT does not make medical or economic sense. Global malaria control efforts have been energized by the availability of new sources of funding, and by the rapid reduction in malaria prevalence in a number of settings where bed nets, indoor residual spraying with insecticides, and ACT have been systematically deployed. This momentum has been captured by a new call for malaria elimination. Without wide implementation of accurate and discriminating diagnostic testing, and reporting of results, most fever will be inappropriately managed, millions of doses of ACT will be wasted, and malaria control programmes will be blindfolded to the impact of their efforts

Distribution of Hyperpolarized Xenon in the Brain Following Sensory Stimulation: Preliminary MRI Findings

In hyperpolarized xenon magnetic resonance imaging (HP 129Xe MRI), the inhaled spin-1/2 isotope of xenon gas is used to generate the MR signal. Because hyperpolarized xenon is an MR signal source with properties very different from those generated from water-protons, HP 129Xe MRI may yield structural and functional information not detectable by conventional proton-based MRI methods. Here we demonstrate the differential distribution of HP 129Xe in the cerebral cortex of the rat following a pain stimulus evoked in the animal's forepaw. Areas of higher HP 129Xe signal corresponded to those areas previously demonstrated by conventional functional MRI (fMRI) methods as being activated by a forepaw pain stimulus. The percent increase in HP 129Xe signal over baseline was 13–28%, and was detectable with a single set of pre and post stimulus images. Recent innovations in the production of highly polarized 129Xe should make feasible the emergence of HP 129Xe MRI as a viable adjunct method to conventional MRI for the study of brain function and disease

Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP® Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner

A Variable Region within the Genome of Streptococcus pneumoniae Contributes to Strain-Strain Variation in Virulence

The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies