A Novel Bacteriophage with Broad Host Range against Clostridioides difficile Ribotype 078 Supports SlpA as the Likely Phage Receptor.

Bacteriophages represent a promising option for the treatment of Clostridioides difficile (formerly Clostridium difficile) infection (CDI), which at present relies on conventional antibiotic therapy. The specificity of bacteriophages should prevent dysbiosis of the colonic microbiota associated with antibiotic treatment of CDI. While numerous phages have been isolated, none have been characterized with broad host range activity toward PCR ribotype (RT) 078 strains, despite their relevance to medicine and agriculture. In this study, we isolated four novel C. difficile myoviruses: ΦCD08011, ΦCD418, ΦCD1801, and ΦCD2301. Their characterization revealed that each was comparable with other C. difficile phages described in the literature, with the exception of ΦCD1801, which exhibited broad host range activity toward RT 078, infecting 15/16 (93.8%) of the isolates tested. In order for wild-type phages to be exploited in the effective treatment of CDI, an optimal phage cocktail must be assembled that provides broad coverage against all C. difficile RTs. We conducted experiments to support previous findings suggesting that SlpA, a constituent of the C. difficile surface layer (S-layer) is the likely phage receptor. Through interpretation of phage-binding assays, our data suggested that ΦCD1801 could bind to an RT 012 strain only in the presence of a plasmid-borne S-layer cassette corresponding to the slpA allele found in RT 078. Armed with this information, efforts should be directed toward the isolation of phages with broad host range activity toward defined S-layer cassette types, which could form the basis of an effective phage cocktail for the treatment of CDI. IMPORTANCE Research into phage therapy has seen a resurgence in recent years owing to growing concerns regarding antimicrobial resistance. Phage research for potential therapy against Clostridioides difficile infection (CDI) is in its infancy, where an optimal "one size fits all" phage cocktail is yet to be derived. The pursuit thus far has aimed to find phages with the broadest possible host range. However, for C. difficile strains belonging to certain PCR ribotypes (RTs), in particular RT 078, phages with broad host range activity are yet to be discovered. In this study, we isolate four novel myoviruses, including ΦCD1801, which exerts the broadest host range activity toward RT 078 reported in the literature. Through the application of ΦCD1801 to phage-binding assays, we provide data to support the prior notion that SlpA represents the likely phage receptor on the bacterial cell surface. Our finding directs research attention toward the isolation of phages with activity toward strains possessing defined S-layer cassette types.

Beyond the molecular movie: Dynamics of bands and bonds during a photoinduced phase transition.

Ultrafast nonequilibrium dynamics offer a route to study the microscopic interactions that govern macroscopic behavior. In particular, photoinduced phase transitions (PIPTs) in solids provide a test case for how forces, and the resulting atomic motion along a reaction coordinate, originate from a nonequilibrium population of excited electronic states. Using femtosecond photoemission, we obtain access to the transient electronic structure during an ultrafast PIPT in a model system: indium nanowires on a silicon(111) surface. We uncover a detailed reaction pathway, allowing a direct comparison with the dynamics predicted by ab initio simulations. This further reveals the crucial role played by localized photoholes in shaping the potential energy landscape and enables a combined momentum- and real-space description of PIPTs, including the ultrafast formation of chemical bonds.

Effects of low to moderate levels of deoxynivalenol on feed and water intake, weight gain, and slaughtering traits of broiler chickens.

The aim of the study was to evaluate the effects of low to moderate oral exposure to the Fusarium toxin deoxynivalenol (DON; derived from culture material) on performance, water intake, and carcass parameters of broilers during early and late developmental phases. A total of 160 Ross 308 broilers were randomly allocated to four different feeding groups (n = 40/group) including 0 (control), 2.5, 5, and 10 mg DON/kg wheat-soybean meal-based feed. Three consecutive replicates of the experiment were performed. Half of the broilers were slaughtered in week 3 of the trial whereas the other half were slaughtered in week 5. Dry matter intake (DMI) and water intake (WI) were recorded on a daily basis and the body weight (BW) and BW gain (BWG) were determined weekly. The following carcass traits were recorded and calculated in absolute and relative data: dressed carcass weight, breast muscle weight, leg weight, and liver weight. Data showed that BW (P < 0.001), BWG (P = 0.005), and DMI (P < 0.001) were reduced by DON-feeding during the entire feeding period. The ratio of DMI to body weight gain (DMI/BWG) was not affected by the treatment. However, the ratio of water to DMI (WI/DMI) increased in DON-treated birds (P = 0.021). Contrast analysis showed that DON tendentially reduced slaughter weight (P = 0.082) and decreased leg yield (P = 0.037) in DON-fed chickens in week 5 of the experiment. Liver organ weight decreased in the 3-week-old DON-fed broilers compared to that in the control-fed birds (P = 0.037). In conclusion, the study suggests that DMI and BW were negatively affected under the experimental conditions at DON levels lower than the current guidance value in the European Union of 5 mg/kg feed. The study also indicates that broilers fed on low to moderate level DON-contaminated diets showed increased WI/DMI ratio which might have negative influence on wet litter syndrome.

Optically excited structural transition in atomic wires on surfaces at the quantum limit.

Transient control over the atomic potential-energy landscapes of solids could lead to new states of matter and to quantum control of nuclear motion on the timescale of lattice vibrations. Recently developed ultrafast time-resolved diffraction techniques combine ultrafast temporal manipulation with atomic-scale spatial resolution and femtosecond temporal resolution. These advances have enabled investigations of photo-induced structural changes in bulk solids that often occur on timescales as short as a few hundred femtoseconds. In contrast, experiments at surfaces and on single atomic layers such as graphene report timescales of structural changes that are orders of magnitude longer. This raises the question of whether the structural response of low-dimensional materials to femtosecond laser excitation is, in general, limited. Here we show that a photo-induced transition from the low- to high-symmetry state of a charge density wave in atomic indium (In) wires supported by a silicon (Si) surface takes place within 350 femtoseconds. The optical excitation breaks and creates In-In bonds, leading to the non-thermal excitation of soft phonon modes, and drives the structural transition in the limit of critically damped nuclear motion through coupling of these soft phonon modes to a manifold of surface and interface phonons that arise from the symmetry breaking at the silicon surface. This finding demonstrates that carefully tuned electronic excitations can create non-equilibrium potential energy surfaces that drive structural dynamics at interfaces in the quantum limit (that is, in a regime in which the nuclear motion is directed and deterministic). This technique could potentially be used to tune the dynamic response of a solid to optical excitation, and has widespread potential application, for example in ultrafast detectors.

A Three-Dimensional View on Soil Biogeochemistry: A Dataset for a Forested Headwater Catchment.

Current understanding of the variability in soil properties and their relationship to processes and spatial patterns in forested landscapes is limited due to the scarcity of datasets providing such information. Here we present a spatially highly resolved dataset () that provides detailed information on the three-dimensional variability of biogeochemical properties in the Wüstebach catchment (western Germany), a long-term environmental observation site of the TERENO (Terrestrial Environmental Observatories) project. High-resolution soil sampling was conducted, and physical and biogeochemical soil parameters were recorded per horizon. The dataset is helpful in the analysis of the spatial heterogeneity in biogeochemical properties within soil horizons and with depth through the soil profile. In addition, it shows links between hydrological and biogeochemical properties and processes within the system. Overall, the dataset provides a high-resolution view into (re)cycling, leaching, and storage of nutrients on the catchment scale in a forested headwater catchment.

Effect of past peat cultivation practices on present dynamics of dissolved organic carbon.

Peatlands are a major source of dissolved organic carbon (DOC) for aquatic ecosystems. Naturally high DOC concentrations in peatlands may be increased further by drainage. For agricultural purposes, peat has frequently been mixed with sand, but the effect of this measure on the release and cycling of DOC has rarely been investigated. This study examined the effects of (i) mixing peat with sand and (ii) water table depth (WTD) on DOC concentrations at three grassland sites on shallow organic soils. The soil solution was sampled bi-weekly for two years with suction plates at 15, 30 and 60cm depth. Selected samples were analysed for dissolved organic nitrogen (DON), δ13CDOM and δ15NDOM. Average DOC concentrations were surprisingly high, ranging from 161 to 192mgl-1. There was no significant impact of soil organic carbon (SOC) content or WTD on mean DOC concentrations. At all sites, DOC concentrations were highest at the boundary between the SOC-rich horizon and the mineral subsoil. In contrast to the mean concentrations, the temporal patterns of DOC concentrations, their drivers and the properties of dissolved organic matter (DOM) differed between peat-sand mixtures and peat. DOC concentrations responded to changes in environmental conditions, but only after a lag period of a few weeks. At the sites with a peat-sand mixture, temperature and therefore probably biological activity determined the DOC concentrations. At the peat site, the contribution of vegetation-derived DOM was higher. The highest concentrations occurred during long, cool periods of waterlogging, suggesting a stronger physicochemical-based DOC mobilisation. Overall, these results indicate that mixing peat with sand does not improve water quality and may result in DOC losses of around 200kg DOCha-1a-1.

Influence of structural defects and oxidation onto hole conductivity in P3HT.

The effect of structural imperfections as well as oxygen impurities on the quantum conductance of poly(3-hexylthiophene) is calculated from first-principles by solving the scattering problem for molecular structures obtained within density functional theory. It is shown that the conductivity of molecular crystals perpendicular to the polymer chains depends strongly on the stacking geometry and is roughly described within the Wentzel-Kramers-Brillouin approximation. Furthermore, it is found that local relaxation for twisted or bent polymer chains efficiently restores the conductance that drops substantially for sharp kinks with curvature radii smaller than 17 Å and rotations in excess of ∼60°. In contrast, isomer defects in the coupling along the chain direction are of minor importance for the intrachain transmission. Also, oxidation of the side chains as well as molecular sulfur barely changes the coherent transport properties, whereas oxidation of thiophene group carbon atoms drastically reduces the conductance.

Neurodevelopmental outcomes after hypothermia therapy in the era of Bayley-III.

OBJECTIVE: Bayley-III scales are currently used to evaluate outcomes of term infants following hypothermia therapy, while all before reported outcomes in this population have used Bayley-II. Our objectives were to determine the incidence of abnormal neurodevelopmental outcomes using Bayley III and the predictive value of Magnetic resonance imaging (MRI) in infants who received systemic hypothermia. STUDY DESIGN: We conducted a prospective cohort study of inborn infants who underwent hypothermia for moderate/severe neonatal encephalopathy from October 2005-November 2011. RESULT: Eighty newborns underwent hypothermia (incidence of 1/1000). Of the survivors, 89% had Bayley-III performed around 24 months of age. An abnormal outcome using Bayley-III <85 occurred in 50%, while Bayley III <70 occurred in 13%. MRI predicted Bayley III<85 with sensitivity of 73%, specificity of 84%, positive-predictive value of 84% and negative-predictive value of 74%. CONCLUSION: A Bayley-III 85 cutoff identifies a disability rate of 50%, and MRI was predictive of abnormal outcomes. Findings can be useful for counseling of families and planning of future studies using Bayley III.

A von Hamos x-ray spectrometer based on a segmented-type diffraction crystal for single-shot x-ray emission spectroscopy and time-resolved resonant inelastic x-ray scattering studies.

We report on the design and performance of a wavelength-dispersive type spectrometer based on the von Hamos geometry. The spectrometer is equipped with a segmented-type crystal for x-ray diffraction and provides an energy resolution in the order of 0.25 eV and 1 eV over an energy range of 8000 eV-9600 eV. The use of a segmented crystal results in a simple and straightforward crystal preparation that allows to preserve the spectrometer resolution and spectrometer efficiency. Application of the spectrometer for time-resolved resonant inelastic x-ray scattering and single-shot x-ray emission spectroscopy is demonstrated.

Histone deacetylase inhibitors and periodontal bone loss.

BACKGROUND AND OBJECTIVE: Bone loss caused by enhanced osteoclast activity is a significant feature of periodontitis. Histone deacetylase inhibitors (HDACi) can suppress osteoclast-mediated bone loss in vitro and in vivo. This study investigated whether HDACi can suppress bone loss in experimental periodontitis. MATERIAL AND METHODS: Experimental periodontitis was induced in mice by oral inoculation with Porphyromonas gingivalis bacteria. Mice were treated orally with olive oil alone, with olive oil and a novel compound - 1179.4b - which targets both Class I and Class II histone deacetylases (HDACs) or with olive oil and MS-275, which targets Class I HDACs. Micro-computed tomography scans of live mice, stereo imaging and histological analyses were used to detect changes in bone. RESULTS: In the absence of treatment there was a 13.2% increase in bone volume in controls compared with a 7.4% decrease in P. gingivalis-inoculated mice. 1179.4b significantly reduced bone loss, with a 3.4% increase in bone volume (p < 0.01). MS-275 did not have a significant effect on P. gingivalis-induced bone loss. Histological analysis revealed that 1179.4b reduced bone loss despite having no effect on inflammation. CONCLUSION: HDACi were found to effectively suppress bone loss in the mouse model of periodontitis. 1179.4b - the inhibitor of Class I and Class II HDACs - was more effective at suppressing bone loss than MS-275, which targets Class I HDACs only. These compounds may therefore have the potential to be used for the management of periodontitis.

Inhibitors of histone deacetylases in class I and class II suppress human osteoclasts in vitro.

Histone deacetylase inhibitors (HDACi) suppress cancer cell growth, inflammation, and bone resorption. The aim of this study was to determine the effect of inhibitors of different HDAC classes on human osteoclast activity in vitro. Human osteoclasts generated from blood mononuclear cells stimulated with receptor activator of nuclear factor kappa B (RANK) ligand were treated with a novel compound targeting classes I and II HDACs (1179.4b), MS-275 (targets class I HDACs), 2664.12 (targets class II HDACs), or suberoylanilide hydroxamic acid (SAHA; targets classes I and II HDACs). Osteoclast differentiation was assessed by expression of tartrate resistant acid phosphatase and resorption of dentine. Expression of mRNA encoding for osteoclast genes including RANK, calcitonin receptor (CTR), c-Fos, tumur necrosis factor (TNF) receptor associated factor (TRAF)6, nuclear factor of activated T cells (NFATc1), interferon-ß, TNF-like weak inducer of apoptosis (TWEAK), and osteoclast-associated receptor (OSCAR) were assessed. Expression of HDACs 1-10 during osteoclast development was also assessed. 1179.4b significantly reduced osteoclast activity (IC(50) < 0.16 nM). MS-275 (IC(50) 54.4 nM) and 2664.12 (IC(50) > 100 nM) were markedly less effective. A combination of MS-275 and 2664.12 inhibited osteoclast activity similar to 1179.4b (IC(50) 0.35 nM). SAHA was shown to suppress osteoclast activity (IC(50) 12 nM). 1179.4b significantly (P < 0.05) reduced NFATc1, CTR, and OSCAR expression during the later stages of osteoclast development. Class I HDAC 8 and Class II HDAC5 were both elevated (P < 0.05) during osteoclast development. Results suggest that inhibition of both classes I and II HDACs may be required to suppress human osteoclastic bone resorption in vitro.

Potent antimalarial activity of histone deacetylase inhibitor analogues.

The malaria parasite Plasmodium falciparum has at least five putative histone deacetylase (HDAC) enzymes, which have been proposed as new antimalarial drug targets and may play roles in regulating gene transcription, like the better-known and more intensively studied human HDACs (hHDACs). Fourteen new compounds derived from l-cysteine or 2-aminosuberic acid were designed to inhibit P. falciparum HDAC-1 (PfHDAC-1) based on homology modeling with human class I and class II HDAC enzymes. The compounds displayed highly potent antiproliferative activity against drug-resistant (Dd2) or drug sensitive (3D7) strains of P. falciparum in vitro (50% inhibitory concentration of 13 to 334 nM). Unlike known hHDAC inhibitors, some of these new compounds were significantly more toxic to P. falciparum parasites than to mammalian cells. The compounds inhibited P. falciparum growth in erythrocytes at both the early and late stages of the parasite's life cycle and caused altered histone acetylation patterns (hyperacetylation), which is a marker of HDAC inhibition in mammalian cells. These results support PfHDAC enzymes as being promising targets for new antimalarial drugs.

[Comparison of different review displays with respect to the detection of low-contrast details in digital radiographs]. / Vergleich unterschiedlicher Bildwiedergabegeräte bei der Erkennung von Niedrigkontrastdetails in digitalen Radiographien.

PURPOSE: Assessment of low-contrast details in digital radiographs on different review displays (RD). MATERIALS AND METHODS: 20" flat screen panels (RD1: standard color LCD-TFT, RD2: monochrome LCD-TFT for radiological reading, RD1*: RD1 with optional image inversion; 205 cd/m (2) luminance, respectively) were evaluated. At 30 lx ambient lighting, 10 radiologists gradually increased the contrast (constant steps) for both a homogeneous picture and a cutout of a thorax radiography of n = 480 simulated nodules until they became recognizable. RESULTS: In the case of bright nodules on an anthropomorphic background, the use of image inversion produced significantly better results. No other significant differences were detected. CONCLUSION: Provided that the working environment is not bright, the results suggest that low-cost RD can be used for the recognition of low-contrast details in radiographies of the chest. Further studies including more display models are necessary. Among different ambient lighting and luminance settings, these studies should include a closer analysis of the special features of digital systems such as brightness/contrast adaptation, picture enlargement (zoom shot), and image inversion.

New cysteine derivatives with antiproliferative activity on melanoma cells.

Here we describe the rational design, computer-aided virtual ligand docking and synthesis of 19 nonpeptidic compounds designed to inhibit histone deacetylases and kill melanoma cells. Compounds were derived from cysteine, fused at the S-terminus to 4-butanoyl hydroxamate, and at the N-terminus to 4-(dimethylamino)benzoic acid. The latter was extended by coupling to amines to form a small library of prospective anti-cancer compounds. Four compounds were cytotoxic at sub-micromolar concentrations against cells of a particularly aggressive human melanoma (MM96L), and nine compounds showed selectivities of >or=5:1 for killing human melanoma instead of normal human fibroblast cells. The most active compounds were shown to cause hyperacetylation of histones due to inhibition of histone deacetylases. Further refinement of these compounds may produce an anti-tumor drug suitable for treating melanoma.

[Digital teaching archive. Concept, implementation, and experiences in a university setting]. / Digitales Lehrarchiv Konzept, Implementation und Erfahrungen im universitären Umfeld.

Film-based teaching files require a substantial investment in human, logistic, and financial resources. The combination of computer and network technology facilitates the workflow integration of distributing radiologic teaching cases within an institution (intranet) or via the World Wide Web (Internet). A digital teaching file (DTF) should include the following basic functions: image import from different sources and of different formats, editing of imported images, uniform case classification, quality control (peer review), a controlled access of different user groups (in-house and external), and an efficient retrieval strategy. The portable network graphics image format (PNG) is especially suitable for DTFs because of several features: pixel support, 2D-interlacing, gamma correction, and lossless compression. The American College of Radiology (ACR) "Index for Radiological Diagnoses" is hierarchically organized and thus an ideal classification system for a DTF. Computer-based training (CBT) in radiology is described in numerous publications, from supplementing traditional learning methods to certified education via the Internet. Attractiveness of a CBT application can be increased by integration of graphical and interactive elements but makes workflow integration of daily case input more difficult. Our DTF was built with established Internet instruments and integrated into a heterogeneous PACS/RIS environment. It facilitates a quick transfer (DICOM_Send) of selected images at the time of interpretation to the DTF and access to the DTF application at any time anywhere within the university hospital intranet employing a standard web browser. A DTF is a small but important building block in an institutional strategy of knowledge management.

[Possibilities for workflow optimization in radiology departments beyond RIS and PACS]. / Möglichkeiten der Optimierung des Workflows in radiologischen Abteilungen jenseits von RIS und PACS.

Technological progress and the rising cost pressure on the healthcare system have led to a drastic change in the work environment of radiologists today. The pervasive demand for workflow optimization and increased efficiency of its activities raises the question of whether by employment of electronic systems, such as RIS and PACS, the potentials of digital technology are sufficiently used to fulfil this demand. This report describes the tasks and structures in radiology departments, which so far are only insufficiently supported by commercially available electronic systems but are nevertheless substantial. We developed and employed a web-based, integrated workplace system, which simplifies many daily tasks of departmental organization and administration apart from well-established tasks of documentation. Furthermore, we analyzed the effects exerted on departmental workflow by employment of this system for 3 years.

[PACS: storage and retrieval of digital radiological image data]. / PACS: Speicherung und Abruf digitaler radiologischer Bilddaten.

BACKGROUND: Efficient handling of both picture archiving and retrieval is a crucial factor when new PACS installations as well as technical upgrades are planned. MATERIALS AND METHODS: For a large PACS installation for 200 actual studies, the number, modality,and body region of available priors were evaluated. In addition, image access time of 100 CT studies from hard disk (RAID), magneto-optic disk (MOD), and tape archives (TAPE) were accessed. RESULTS: For current examinations priors existed in 61.1% with an averaged quantity of 7.7 studies. Thereof 56.3% were within 0-3 months, 84.9% within 12 months, 91.7% within 24 months, and 96.2% within 36 months. On average, access to images from the hard disk cache was more than 100 times faster then from MOD or TAPE. CONCLUSION: Since only PACS RAID provides online image access, at least current imaging of the past 12 months should be available from cache. An accurate prefetching mechanism facilitates effective use of the expensive online cache area. For that, however, close interaction of PACS, RIS, and KIS is an indispensable prerequisite.

[Recommendations for the selection of storage media for archiving digital radiological image data based on the comparison of retrieval times at different PACS archive levels]. / Empfehlungen zur Medienwahl für die Archivierung radiologischer Bilddaten auf der Basis einer Analyse der Zugriffszeiten auf verschiedene PACS-Archivebenen.

PURPOSE: Recommendations for archiving digital radiological image data based on the comparison of retrieval times for different PACS archive levels. MATERIALS AND METHODS: For a large PACS installation (Agfa Impax, Release 4.1), image retrieval times for radiological standard examinations (chest radiographs with 2, MRI with 250, CT with 100 and 1000 images; n = 120, each) from hard disk array, magneto-optical disk (MOD), and magnetic tape archives (TAPE) were examined in high and low network traffic load. RESULTS: Even large CT examinations (1000 images) were available from hard disk arrays within 4.0 +/- 0.8 s, smaller studies within 1.8 +/- 0.3 s. Radiographic image retrieval from MOD (30 +/- 4.7 s) was more then 50 % faster than from TAPE. For typical cross-sectional studies, the velocity gain amounted to 19 %. For both technologies, no significant difference was found for large CT examinations (651 +/- 144 s). For high and low network traffic load scenarios, image retrieval times from hard disk, MOD, and TAPE archives increased by 87 %, 7 %, and 22 %, respectively. CONCLUSION: Hard disk arrays are specifically suited as departmental intermediate storage media because they allow fast access to current and previous examinations within a short time. Performance properties enable both MOD and TAPE systems to serve as long-term archives. However, MOD archives are less flexible in the expansion of storage capacity and at present the medium costs per memory unit are about 2 - 3 times higher than for tape archives. The use of existing MOD-archives may be adequate as intermediate archives. For new PACS installations or system expansions, however, it is recommended to combine a sufficiently large local data memory (RAID) with data storage on tape archives outside the radiological unit that can be used by other departments as well. Future development of hard disk prices will show whether archiving for the whole data retention period may be handled by RAID systems. In any case, prefetching problems and waiting periods for demanded pre-studies would not occur any more.

IT services in a completely digitized radiological department: value and benefit of an in-house departmental IT group.

To analyze the benefit of a departmental IT group in comparison to support by hospital IT groups or system manufacturers in a completely digitized radiological department. The departmental IT group comprises a fulltime IT specialist, two student assistants and four clinical employees participating 1 day/week. For 18 months IT problems were quantified and specified according to urgency, responsibility and affected system by use of an intranet-based reporting system. For each IT service provider the performance and duration of problem solution was evaluated. In 18 months 3,234 IT problems emerged. 88.7% were solved by the departmental IT group. In 474 cases (14.7%) a solution within 2 h was required. The departmental IT group solved 35.8% within 30 min, system manufacturers needed 18 h 38 min in mean. The departmental IT group solved 90.2% of the problems within a time limit. System manufacturers met the limit in 60.1% with a mean duration of 7 days 21 h. In 6.7% of the cases, support by system manufacturers was indispensable. A considerable proportion of IT problems in completely digitized radiological departments can be solved by a departmental IT group, providing a fast and cost-efficient first-level IT support with effective prevention of major breaks in the workflow. In a small number of cases support by system manufacturers remains necessary.