Isolation of Issatchenkia occidentalis from the esophagus of a leukemic patient

Issatchenkia occidentalis was isolated from an esophageal biopsy of a young leukemic male patient who underwent bone marrow transplantation. At the time the specimen was collected, the patient was also suffering from esophageal herpetic lesions. The identification of the isolate was not possible by the use of the available commercial methods. Thus, its identification was done by PCR and DNA sequencing using panfungal primers.     

Management strategies: prophylaxis, empirical and preemptive treatment of established invasive candidiasis in the critically ill non-neutropenic patient

In critically ill non neutropenic patients there are four broad approaches for the management of antifungal treatment for invasive candidiasis: prophylaxis, empirical, preemptive therapy and treatment of established infections. All these approaches in relationship with risk strategies and microbiological indirect laboratory techniques for establishing invasive candidiasis will be discussed.     

Activation-induced deaminase: light and dark sides

Activation-induced deaminase (AID) is required for class switch recombination (CSR) and somatic hypermutation (SHM), which are responsible for secondary diversification of antibodies in germinal centers. AID initiates these processes by deamination of cytosines on the immunoglobulin (Ig) locus, a potentially mutagenic activity. AID expression is restricted to germinal-center B cells, but the mechanisms that regulate its target specificity are not completely understood. Here, we review the most recent findings on the regulation of AID targeting and discuss how AID activity on non-Ig genes is relevant to the generation of chromosome translocations and to lymphomagenesis.     

Efflux permease CgAcr3-1 of Corynebacterium glutamicum is an arsenite-specific antiporter

Resistance to arsenite (As(III)) by cells is generally accomplished by arsenite efflux permeases from Acr3 or ArsB unrelated families. We analyzed the function of three Acr3 proteins from Corynebacterium glutamicum, CgAcr3-1, CgAcr3-2, and CgAcr3-3. CgAcr3-1 conferred the highest level of As(III) resistance and accumulation in vivo. CgAcr3-1 was also the most active when everted membranes vesicles from Escherichia coli or C. glutamicum mutants were assayed for efflux with different energy sources. As(III) and antimonite (Sb(III)) resistance and accumulation studies using E. coli or C. glutamicum arsenite permease mutants clearly show that CgAcr3-1 is specific for As(III). In everted membrane vesicles expressing CgAcr3-1, dissipation of either the membrane potential or the pH gradient of the proton motive force did not prevent As(III) uptake, whereas dissipation of both components eliminated uptake. Further, a mutagenesis study of CgAcr3-1 suggested that a conserved cysteine and glutamate are involved in active transport. Therefore, we propose that CgAcr3-1 is an antiporter that catalyzes arsenite-proton exchange with residues Cys129 and Glu305 involved in efflux.     

Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients

Background

Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.

Methods and Findings

Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed.Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.

Conclusions

Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.

Trial Registration:

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00553930","term_id":"NCT00553930"}}NCT00553930     

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Background

In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates.

Methodology/Principal Findings

KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64).

Conclusions/Significance

This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.     

Immunocytochemical Evidence of the Localization of the Crumbs Homologue 3 Protein (CRB3) in the Developing and Mature Mouse Retina

CRB3 (Crumbs homologue 3), a member of the CRB protein family (homologous to the Drosophila Crumbs), is expressed in different epithelium-derived cell types in mammals, where it seems to be involved in regulating the establishment and stability of tight junctions and in ciliogenesis. This protein has been also detected in the retina, but little is known about its localization and function in this tissue. Our goal here was to perform an in-depth study of the presence of CRB3 protein in the mouse retina and to analyze its expression during photoreceptor ciliogenesis and the establishment of the plexiform retinal layers. Double immunofluorescence experiments for CRB3 and well-known markers for the different retinal cell types were performed to study the localization of the CRB3 protein. According to our results, CRB3 is present from postnatal day 0 (P0) until adulthood in the mouse retina. It is localized in the inner segments (IS) of photoreceptor cells, especially concentrated in the area where the connecting cilium is located, in their synaptic terminals in the outer plexiform layer (OPL), and in sub-populations of amacrine and bipolar cells in the inner plexiform layer (IPL).     

Advanced photobioreactor LED illumination system: Scale‐down approach to study microalgal growth kinetics

A newly designed and constructed LED illumination device for commercial cylindrical bioreactors is presented for application in microalgal cultivations and investigation of growth kinetics. An ideally illuminated volume is achieved by focusing the light toward the center of the reactor and thereby compensating the mutual shading of the cells. The relevant biomass concentration for homogeneous illumination depending on reactor radius was determined by light distribution measurements for Chlamydomonas to 0.2 g/L (equal 0.435 optical density at 750 nm). It is shown that cultivation experiments with the newly designed illumination device operated in batch mode can be successfully applied for determination of growth rates and photo conversion efficiencies. The exact knowledge of physiological reactions of specific strain(s) and the estimation of relevant parameters for scale‐up can be used for construction of economic pilot plant photobioreactors. The determination of light‐dependent kinetics of growth and product formation is the first necessary step to achieve this. A wide variety of different parameters can be examined like the effect of different illumination conditions (light intensity, frequency of day/night cycles, flashing light, light color…) and thereby for each single application specific, relevant, and interesting parameters will be examined.     

A two-dimension otolith growth inverse model

An inverse growth model was developed to describe fish otolith ontogenetic growth to find the most parsimonious growth field that drives the actual shape of an internal incremental structure to the actual external shape of the otolith. This approach is based in a pure physic model, and the single implicit assumption was that the otolith accretion occurred perpendicular to its external surface. The model could be used to define a general hypothesis situation, in the sense that it predicts the most plausible shape of the otolith at any time, assuming that no additional external forces have acted. Therefore, severe departures between the observed growth structure and the closest prediction to it could be used to identify anatomical constraints and physiological factors that modulate the pure physical expectations.