Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope

Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScopeVR registry. For 208 Scedosporium spp. infections solid organ transplantation (n¼58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n¼28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n¼26, 46.4% versus n¼12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificans

A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization

Electron shuttle-mediated microbial Fe(III) reduction under alkaline conditions

Purpose: Extracellular Fe(III) reduction plays an important role in a variety of biogeochemical processes. Several mechanisms for microbial Fe(III) reduction in pH-neutral environments have been proposed, but pathways of microbial Fe(III) reduction within alkaline conditions have not been clearly identified. Alkaline soils are vastly distributed; thus, a better understanding of microbial Fe(III) reduction under alkaline conditions is of significance. The purpose of this study is to explore the dominant mechanism of bacterial iron reduction in alkaline environments. Materials and methods: We used antraquinone-2,6-disulfonate (AQDS) as a representative of quinone moities of humic substances and elemental sulfur and sulfate as sulfur species to investigate the potential role of humic substances and sulfur species in mediating microbial Fe(III) reduction in alkaline environments. We carried out thermodynamic calculations to predict the ability of bacteria to reduce Fe(III) (oxyhydr)oxides under alkaline conditions and the ability of AQDS and sulfur species to serve as electron acceptors for microbial anaerobic respiration in an assumed alkaline soil environments. A series of incubation experiments with two model dissimilatory metal reducing bacteria, Shewanella oneidensis MR-1 and Geobacter sulfurreducens PCA as well as mixed bacteria enriched from a soil were performed to confirm the contribution of AQDS and sulfur species to Fe(III) reduction under alkaline conditions. Results and discussion: Based on thermodynamic calculations, we predicted that, under alkaline conditions, the enzymatic reduction of Fe(III) (oxyhydr)oxides would be thermodynamically feasible but very weak. In our incubation experiments, the reduction of ferrihydrite by anaerobic cultures of Shewanella oneidensis MR-1, Geobacter sulfurreducens PCA or microbes enriched from a soil was significantly increased in the presence of S0 or AQDS. Notably, AQDS contributed more to promoting Fe(III) reduction as a soluble electron shuttle than S0 did under the alkaline conditions probably because of different mechanisms of microbial utilization of AQDS and S0. Conclusions: These results suggest that microbial reduction of Fe(III) (oxyhydr)oxides under alkaline conditions may proceed via a pathway mediated by electron shuttles such as AQDS and S0. Considering the high ability of electron shuttling and vast distribution of humic substances, we suggest that humic substance-mediated Fe(III) reduction may potentially be the dominant mechanism for Fe(III) reduction in alkaline environments

Changes in Clostridium (Clostridioides) difficile PCR-Ribotype Distribution and Antimicrobial Resistance in a German Tertiary Care Hospital Over the Last 10Years

Clostridium (Clostridioides) difficile ribotype 027 (RT027) was detected in Germany for the first time in 2007 during an outbreak in the region of Trier, Rhineland-Palatinate and is today the most prevalent ribotype (RT) in Europe. We aimed to determine the changes in RT distribution and corresponding antimicrobial resistance in clinical C. difficile isolates between two time points (2007 and 2017) in one tertiary care hospital in Germany. C. difficile isolates recovered in 2007 and in 2017 (80 isolates per year, respectively) from patients at a Tertiary Care University Hospital in North-Rhine Westphalia were analyzed. Isolates were characterized by ribotyping and susceptibility testing using gradient tests (metronidazole, vancomycin) and the disk diffusion method (moxifloxacin). Between 2007 and 2017, a clear switch from RT001 [18.75% (n=15) in 2007 versus 3.75% (n=3) in 2017 P=0.003] to RT027 [0% in 2007 versus 21.25% (n=17) in 2017] was evident. While minimal inhibitory concentrations (MICs) of vancomycin were stable, a significant metronidazole MIC creep was determined (MIC50=0.047 in 2007 versus MIC50=0.094 in 2017, P<0.0001 using the Man-Whitney test). We detected one metronidazole-resistant isolate (0.6%). Interestingly, in total we encountered more isolates resistant to moxifloxacin in 2007 (42 (52.25%) than in 2017 [(30 (37.5%), P=0.06)]). We could demonstrate that RT027 replaced RT001 in the last 10years in our hospital. Furthermore, our data show a metronidazole MIC creep in C. difficile isolates over the last 10years and an unexpected decrease of isolates resistant to moxifloxacin

Evaluation of the Use of Rectal Swabs for Laboratory Diagnosis of Clostridium difficile Infection

For the diagnosis of Clostridium difficile infection (CDI), microbiological testing is almost always accomplished through the analysis of stool specimens. We evaluated the performances of rectal swabs with liquid transport medium (FS) and nylon flocked dry swabs for the detection of C. difficile. Additionally, the impact on the diagnostic yield of storing swabs at -80 degrees C for up to 3 months was evaluated. Sixty clinical stool samples positive for C. difficile by PCR were used for simulating rectal swabbing. FS and dry swabs were dipped into the stool and tested by PCR directly after swabbing at 1 and 3 months after storage at -80 degrees C. Stool and the liquid medium of FS were additionally tested by a combination of glutamate dehydrogenase antigen (GDH) testing and toxin A/B enzyme immunoassay (EIA), as well as by toxigenic culture (TC). Using dry swabs, the PCR-based detection rate of C. difficile was equal to the rate using stool samples (30/3. [100%]), whereas the detection rate in FS was significantly lower (25/30 [83.2%]; P = 0.019). The sensitivities of FS for detecting C. difficile by PCR, TC, GDH testing, and toxin A/B EIA were 83.3%, 85.7%, 88%, and 68.9%, respectively. Storage of swabs at -80 degrees C had no impact on the detection rate. FS cannot replace stool samples in the two-step laboratory diagnosis of CDI, as the sensitivities were too low, probably due to diluting effects of the fecal sample in the liquid medium. For simple PCR-based detection of C. difficile, dry swabs proved to be a suitable alternative to the use of stool samples

Halogen-Bonding-Triggered Supramolecular Gel Formation

Supramolecular gels are topical soft materials involving the reversible formation of fibrous aggregates using non-covalent interactions. There is significant interest in controlling the properties of such materials by the formation of multicomponent systems, which exhibit non-additive properties emerging from interaction of the components. The use of hydrogen bonding to assemble supramolecular gels in organic solvents is well established. In contrast, the use of halogen bonding to trigger supramolecular gel formation in a two-component gel (‘co-gel’) is essentially unexplored, and forms the basis for this study. Here, we show that halogen bonding between a pyridyl substituent in a bis(pyridyl urea) and 1,4-diiodotetrafluorobenzene brings about gelation, even in polar media such as aqueous methanol and aqueous dimethylsulfoxide. This demonstrates that halogen bonding is sufficiently strong to interfere with competing gel-inhibitory interactions and create a ‘tipping point’ in gel assembly. Using this concept, we have prepared a halogen bond donor bis(urea) gelator that forms co-gels with halogen bond acceptors