Development of a sample preparation procedure for Sr isotope analysis of Portland cements.

The 87Sr/86Sr isotope ratio can, in principle, be used for provenancing of cement. However, while commercial cements consist of multiple components, no detailed investigation into their individual 87Sr/86Sr isotope ratios or their influence on the integral 87Sr/86Sr isotope ratio of the resulting cement was conducted previously. Therefore, the present study aimed at determining and comparing the conventional 87Sr/86Sr isotope ratios of a diverse set of Portland cements and their corresponding Portland clinkers, the major component of these cements. Two approaches to remove the additives from the cements, i.e. to measure the conventional 87Sr/86Sr isotopic fingerprint of the clinker only, were tested, namely, treatment with a potassium hydroxide/sucrose solution and sieving on a 11-µm sieve. Dissolution in concentrated hydrochloric acid/nitric acid and in diluted nitric acid was employed to determine the 87Sr/86Sr isotope ratios of the cements and the individual clinkers. The aim was to find the most appropriate sample preparation procedure for cement provenancing, and the selection was realised by comparing the 87Sr/86Sr isotope ratios of differently treated cements with those of the corresponding clinkers. None of the methods to separate the clinkers from the cements proved to be satisfactory. However, it was found that the 87Sr/86Sr isotope ratios of clinker and cement generally corresponded, meaning that the latter can be used as a proxy for the clinker 87Sr/86Sr isotope ratio. Finally, the concentrated hydrochloric acid/nitric acid dissolution method was found to be the most suitable sample preparation method for the cements; it is thus recommended for 87Sr/86Sr isotope analyses for cement provenancing.

Clindamycin-rifampin combination therapy for staphylococcal periprosthetic joint infections: a retrospective observational study.

BACKGROUND: Staphylococcal species account for more than 50% of periprosthetic joint infections (PJI) and antimicrobial therapy with rifampin-based combination regimens has been shown effective. The present study evaluates the safety and efficacy of clindamycin in combination with rifampin for the management of staphylococcal PJI. METHODS: In this retrospective cohort study, patients were included who received clindamycin-rifampin combination therapy to treat a periprosthetic hip or knee infection by Staphylococcus aureus or coagulase-negative staphylococci. Patients were treated according to a standardized treatment algorithm and followed for a median of 54 months. Of the 36 patients with periprosthetic staphylococcal infections, 31 had an infection of the hip, and five had an infection of the knee. Eighteen patients underwent debridement and retention of the implant (DAIR) for an early infection, the other 18 patients underwent revision of loose components in presumed aseptic loosening with unexpected positive cultures. RESULTS: In this study, we report a success rate of 86%, with five recurrent/persistent PJI in 36 treated patients. Cure rate was 78% (14/18) in the DAIR patients and 94% (17/18) in the revision group. Five patients (14%) discontinued clindamycin-rifampin due to side effects. Of the 31 patients completing the clindamycin-rifampin regimen 29 patients (94%) were cured. CONCLUSION: Combined therapy with clindamycin and rifampin is a safe, well tolerated and effective regimen for the treatment of staphylococcal periprosthetic infection.

Human TLR10 is an anti-inflammatory pattern-recognition receptor.

Toll-like receptor (TLR)10 is the only pattern-recognition receptor without known ligand specificity and biological function. We demonstrate that TLR10 is a modulatory receptor with mainly inhibitory effects. Blocking TLR10 by antagonistic antibodies enhanced proinflammatory cytokine production, including IL-1ß, specifically after exposure to TLR2 ligands. Blocking TLR10 after stimulation of peripheral blood mononuclear cells with pam3CSK4 (Pam3Cys) led to production of 2,065 ± 106 pg/mL IL-1ß (mean ± SEM) in comparison with 1,043 ± 51 pg/mL IL-1ß after addition of nonspecific IgG antibodies. Several mechanisms mediate the modulatory effects of TLR10: on the one hand, cotransfection in human cell lines showed that TLR10 acts as an inhibitory receptor when forming heterodimers with TLR2; on the other hand, cross-linking experiments showed specific induction of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra, 16 ± 1.7 ng/mL, mean ± SEM). After cross-linking anti-TLR10 antibody, no production of IL-1ß and other proinflammatory cytokines could be found. Furthermore, individuals bearing TLR10 polymorphisms displayed an increased capacity to produce IL-1ß, TNF-α, and IL-6 upon ligation of TLR2, in a gene-dose-dependent manner. The modulatory effects of TLR10 are complex, involving at least several mechanisms: there is competition for ligands or for the formation of heterodimer receptors with TLR2, as well as PI3K/Akt-mediated induction of the anti-inflammatory cytokine IL-1Ra. Finally, transgenic mice expressing human TLR10 produced fewer cytokines when challenged with a TLR2 agonist. In conclusion, to our knowledge we demonstrate for the first time that TLR10 is a modulatory pattern-recognition receptor with mainly inhibitory properties.

Autophagy modulates Borrelia burgdorferi-induced production of interleukin-1ß (IL-1ß).

Borrelia burgdorferi sensu lato is the causative agent of Lyme disease. Recent studies have shown that recognition of the spirochete is mediated by TLR2 and NOD2. The latter receptor has been associated with the induction of the intracellular degradation process called autophagy. The present study demonstrated for the first time the induction of autophagy by exposure to B. burgdorferi and that autophagy modulates the B. burgdorferi-dependent cytokine production. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increased IL-1ß and IL-6 production in response to the exposure of the spirochete, whereas TNFα production was unchanged. Autophagy induction against B. burgdorferi was dependent on reactive oxygen species (ROS) because cells from patients with chronic granulomatous disease, which are defective in ROS production, also produced elevated IL-1ß. Further, the enhanced production of the proinflammatory cytokines was because of the elevated mRNA expression in the absence of autophagy. Our results thus demonstrate the induction of autophagy, which, in turn, modulates cytokine production by B. burgdorferi for the first time.

Carbon isotope discrimination during branch photosynthesis of Fagus sylvatica: a Bayesian modelling approach.

Field measurements of photosynthetic carbon isotope discrimination ((13)Δ) of Fagus sylvatica, conducted with branch bags and laser spectrometry, revealed a high variability of (13)Δ, both on diurnal and day-to-day timescales. We tested the prediction capability of three versions of a commonly used model for (13)Δ [called here comprehensive ((13)(Δcomp)), simplified ((13) Δsimple) and revised ((13)(Δrevised)) versions]. A Bayesian approach was used to calibrate major model parameters. Constrained estimates were found for the fractionation during CO(2) fixation in (13)(Δcomp), but not in (13)(Δsimple), and partially for the mesophyll conductance for CO(2)(gi). No constrained estimates were found for fractionations during mitochondrial and photorespiration, and for a diurnally variable apparent fractionation between current assimilates and mitochondrial respiration, specific to (13)(Δrevised). A quantification of parameter estimation uncertainties and interdependencies further helped explore model structure and behaviour. We found that (13)(Δcomp) usually outperformed (13)(Δsimple) because of the explicit consideration of gi and the photorespiratory fractionation in (13)(Δcomp) that enabled a better description of the large observed diurnal variation (≈9‰) of (13)Δ. Flux-weighted daily means of (13)Δ were also better predicted with (13)(Δcomp) than with (13)(Δsimple).

Soil H2¹8O labelling reveals the effect of drought on C¹8OO fluxes to the atmosphere.

Above- and belowground processes in plants are tightly coupled via carbon and water fluxes through the soil-plant-atmosphere system. The oxygen isotopic composition of atmospheric CO2 and water vapour (H2Ov) provides a valuable tool for investigating the transport and cycling of carbon and water within this system. However, detailed studies on the coupling between ecosystem components and environmental drivers are sparse. Therefore, we conducted a H2 (18)O-labelling experiment to investigate the effect of drought on the speed of the link between below- and aboveground processes and its subsequent effect on C(18)OO released by leaves and soils. A custom-made chamber system, separating shoot from soil compartments, allowed separate measurements of shoot- and soil-related processes under controlled conditions. Gas exchange of oxygen stable isotopes in CO2 and H2Ov served as the main tool of investigation and was monitored in real time on Fagus sylvatica saplings using laser spectroscopy. H2(18)O-labelling showed that drought caused a slower transport of water molecules from soil to shoot, which was indicated by its direct derivation from independently measured concentrations and (18)O/(16)O ratios of CO2 and H2Ov, respectively. Furthermore, drought reduced the (18)O equilibrium between H2O and CO2 at the shoot level, resulting in less-enriched C(18)OO fluxes from leaf to atmosphere compared with control plants. Compared with the shoot, (18)O equilibrium was not instantaneous in the soil and no drought effect was apparent.

Carbon isotope discrimination during branch photosynthesis of Fagus sylvatica: field measurements using laser spectrometry.

On-line measurements of photosynthetic carbon isotope discrimination ((13)Δ) under field conditions are sparse. Hence, experimental verification of the natural variability of instantaneous (13)Δ is scarce, although (13)Δ is, explicitly and implicitly, used from leaf to global scales for inferring photosynthetic characteristics. This work presents the first on-line field measurements of (13)Δ of Fagus sylvatica branches, at hourly resolution, using three open branch bags and a laser spectrometer for CO2 isotopologue measurements (QCLAS-ISO). Data from two August/September field campaigns, in 2009 and 2010, in a temperate forest in Switzerland are shown. Diurnal variability of (13)Δ was substantial, with mean diurnal amplitudes of ~9‰ and maximum diurnal amplitudes of ~20‰. The highest (13)Δ were generally observed during early morning and late afternoon, and the lowest (13)Δ during midday. An assessment of propagated standard deviations of (13)Δ demonstrated that the observed diurnal variation of (13)Δ was not a measurement artefact. Day-to-day variations of (13)Δ were summarized with flux-weighted daily means of (13)Δ, which ranged from 15‰ to 23‰ in 2009 and from 18‰ to 29‰ in 2010, thus displaying a considerable range of 8-11‰. Generally, (13)Δ showed the expected negative relationship with intrinsic water use efficiency. Diurnal and day-to-day variability of (13)Δ was, however, always better predicted by that of net CO2 assimilation, especially in 2010 when soil moisture was high and vapour pressure deficit was low. Stomatal control of leaf gas exchange, and consequently (13)Δ, could only be identified under drier conditions in 2009.

Predominant association of Raoultella bacteremia with diseases of the biliary tract.

A case series of 14 patients with Raoultella bacteremia was compared with 28 Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-three percent of Raoultella bacteremia cases were associated with biliary tract disease, compared to 32% and 22% of patients with K. oxytoca and K. pneumoniae bacteremia, respectively.

Interpretable conservation laws as sparse invariants.

Discovering conservation laws for a given dynamical system is important but challenging. In a theorist setup (differential equations and basis functions are both known), we propose the sparse invariant detector (SID), an algorithm that autodiscovers conservation laws from differential equations. Its algorithmic simplicity allows robustness and interpretability of the discovered conserved quantities. We show that SID is able to rediscover known and even discover new conservation laws in a variety of systems. For two examples in fluid mechanics and atmospheric chemistry, SID discovers 14 and 3 conserved quantities, respectively, where only 12 and 2 were previously known to domain experts.

Nanostructure and Optical Property Tailoring of Zinc Tin Nitride Thin Films through Phenomenological Decoupling: A Pathway to Enhanced Control.

This work addresses the need for precise control of thin film sputtering processes to enable thin film material tailoring on the example of zinc tin nitride (ZTN) thin films deposited via microwave plasma-assisted high power reactive magnetron sputtering (MAR-HiPIMS). The applied in situ diagnostic techniques (Langmuir probe and energy-resolved time-of-flight mass spectrometry) supported monitoring changes in the deposition environment with respect to microwave (MW) power. During MAR-HiPIMS, the presence of nitride ions in the gas phase (ZnN+, ZnN2+, SnN+, SnN2+) was detected. This indicates that the MW plasma facilitated their production, as opposed to pure R-HiPIMS. Additionally, MW plasma caused post-ionisation of sputtered atoms and reduced the overall energy-per-charge range of incoming charged species. By varying the MW power and substrate biasing, films with comparable chemical compositions (approximately Zn0.92Sn1.08N2) but different structures, ranging from polycrystalline to preferentially textured, were successfully produced. The application of density functional theory (DFT) further enabled the relationship between the lattice parameters and the optical properties of ZTN to be explored, where the material's optical anisotropy nature was determined. It was found that despite considerable differences in crystallinity, the changes induced in the lattice parameters were subangstrom, causing only minor changes in the final optical properties of ZTN.

Ampicillin susceptibility testing of Haemophilus influenzae in the routine clinical laboratory by the EUCAST methodology compared to broth microdilution and the presence of ftsI gene mutations.

OBJECTIVES: To investigate the prevalence of ampicillin resistance in Haemophilus influenzae and the diagnostic accuracy of the EUCAST recommended disc diffusion method to detect the increasingly prevalent ampicillin resistance due to the presence of PBP3 alterations based on mutations in the ftsI gene. METHODS: During a 6-month period all consecutive non-duplicate H. influenzae isolates were prospectively collected and stored. MICs of ampicillin were determined by broth microdilution (BMD). PCR was performed to detect mutations in the ftsI gene. Results of routine disc diffusion susceptibility testing, including the penicillin screening test in accordance with the current EUCAST methodology, as well as additional Etest results, were compared to the BMD as the reference method. RESULTS: In 102 isolates, the prevalence of ampicillin resistance was 28% (29/102) by BMD. There was a good correlation between MICs of ampicillin and the presence of a ß-lactamase and/or an ftsI gene mutation. The prevalence of ampicillin resistance was overestimated using the EUCAST method (33% (34/102)) and underestimated when an additional Etest was used (24% (24/102)) (not significant). The sensitivity and specificity of the EUCAST methodology for the detection of ampicillin resistance were 97% ((28/29); 95% CI, 82-100%) and 92% ((67/73); 95% CI, 83-97%), respectively. CONCLUSIONS: The prevalence of ampicillin resistance was 28%, as determined by BMD. Although the overall diagnostic accuracy of the EUCAST ampicillin disc diffusion was high, misclassification of ampicillin susceptibility may still occur.

Correction: 29Si{27Al}, 27Al{29Si} and 27Al{1H} double-resonance NMR spectroscopy study of cementitious sodium aluminosilicate gels (geopolymers) and gel-zeolite composites.

[This corrects the article DOI: 10.1039/C8RA09246J.].

Overview of ICARUS-A Curated, Open Access, Online Repository for Atmospheric Simulation Chamber Data.

Atmospheric simulation chambers continue to be indispensable tools for research in the atmospheric sciences. Insights from chamber studies are integrated into atmospheric chemical transport models, which are used for science-informed policy decisions. However, a centralized data management and access infrastructure for their scientific products had not been available in the United States and many parts of the world. ICARUS (Integrated Chamber Atmospheric data Repository for Unified Science) is an open access, searchable, web-based infrastructure for storing, sharing, discovering, and utilizing atmospheric chamber data [https://icarus.ucdavis.edu]. ICARUS has two parts: a data intake portal and a search and discovery portal. Data in ICARUS are curated, uniform, interactive, indexed on popular search engines, mirrored by other repositories, version-tracked, vocabulary-controlled, and citable. ICARUS hosts both legacy data and new data in compliance with open access data mandates. Targeted data discovery is available based on key experimental parameters, including organic reactants and mixtures that are managed using the PubChem chemical database, oxidant information, nitrogen oxide (NOx) content, alkylperoxy radical (RO2) fate, seed particle information, environmental conditions, and reaction categories. A discipline-specific repository such as ICARUS with high amounts of metadata works to support the evaluation and revision of atmospheric model mechanisms, intercomparison of data and models, and the development of new model frameworks that can have more predictive power in the current and future atmosphere. The open accessibility and interactive nature of ICARUS data may also be useful for teaching, data mining, and training machine learning models.

Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism.

Borrelia burgdorferi spirochetes cause Lyme disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN-γ and IL-17 have been suggested to play an important role in the host defense against Borrelia, and in the immunopathology of Lyme disease. The caspase-1-dependent cytokine IL-1ß has been linked to the generation of IL-17-producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-γ production. In this study, we show by using knockout mice the role of inflammasome-activated caspase-1 in the regulation of cytokine responses by B. burgdorferi. Caspase-1-deficient cells showed significantly less IFN-γ and IL-17 production after Borrelia stimulation. A lack of IL-1ß was responsible for the defective IL-17 production, whereas IL-18 was crucial for the IFN-γ production. Caspase-1-dependent IL-33 played no role in the Borrelia-induced production of IL-1ß, IFN-γ or IL-17. In conclusion, we describe for the first time the role of the inflammasome-dependent caspase-1 activation of cytokines in the regulation of IL-17 production induced by Borrelia spp. As IL-17 has been implicated in the pathogenesis of chronic Lyme disease, these data suggest that caspase-1 targeting may represent a new immunomodulatory strategy for the treatment of complications of late stage Lyme disease.

Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease.

Interleukin-23 (IL-23) is known to play a crucial role in the development and maintenance of T helper 17 cells. It has been previously demonstrated that IL-17 is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi bacteria. However, the precise role of the IL-23 receptor (IL-23R) for the B. burgdorferi-induced IL-17 responses or human Lyme disease has not yet been elucidated. IL-23R single nucleotide polymorphism (SNP) rs11209026 was genotyped using the TaqMan assay. Functional studies were performed using peripheral blood mononuclear cells, and cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Dose-dependent production of IL-23 and IL-17 by B. burgdorferi could be observed. Interestingly, when IL-23 bioactivity was inhibited by a specific antibody against IL-23p19, IL-17 production was significantly downregulated. In contrast, production of gamma interferon (IFN-γ) was not affected after the blockade of IL-23 activity. Moreover, individuals bearing a single nucleotide polymorphism in the IL-23R gene (Arg381Gln) produced significantly less IL-17 after B. burgdorferi stimulation compared with that of the individuals bearing the wild type. Despite lower IL-17 production, the IL-23R gene polymorphism did not influence the development of chronic Lyme disease in a cohort of patients with Lyme disease. This study demonstrates that IL-23R signaling is needed for B. burgdorferi-induced IL-17 production in vitro and that an IL-23R gene SNP leads to impaired IL-17 production. However, the IL-23R gene polymorphism is not crucial for the pathogenesis of chronic Lyme.

Clinical impact of preincubation of blood cultures at 37°C.

The effect of immediate incubation of blood cultures at 37°C on the turnaround time and the impact of Gram stain results on antimicrobial management were investigated. During a 6-month period, blood cultures collected at the emergency department outside laboratory operating hours were preincubated at 37°C until transportation to the laboratory. Upon the arrival of blood cultures at the laboratory, Gram stains and subcultures were made from all bottles prior to further incubation in the automated system (Bactec 9240). Data from 1 year earlier, when all blood cultures were stored at room temperature, were used for comparison. In the study period, 79 episodes of bacteremia were detected for 75 patients, compared to 70 episodes for 67 patients in the control period. Preincubation of blood cultures at 37°C resulted in a 15-h reduction in the median time to reporting of Gram stain results, from 34 to 19 h (P, <0.001). With preincubation, 3 episodes (4%) of bacteremia were not detected by the Bactec 9240 system. Based on the reporting of the Gram stain results, appropriate antimicrobial therapy was initiated for 12% of all patients with positive blood cultures, while for 24% the therapy was streamlined. Thus, immediate incubation of blood cultures reduced the time to reporting of Gram stain results. However, not all episodes of bacteremia were detected by the Bactec 9240 system after preincubation at 37°C. Blood culture results contributed importantly to appropriate antimicrobial management.

The diel imprint of leaf metabolism on the δ13 C signal of soil respiration under control and drought conditions.

Recent (13) CO(2) canopy pulse chase labeling studies revealed that photosynthesis influences the carbon isotopic composition of soil respired CO(2) (δ(13) C(SR)) even on a diel timescale. However, the driving mechanisms underlying these short-term responses remain unclear, in particular under drought conditions. The gas exchange of CO(2) isotopes of canopy and soil was monitored in drought/nondrought-stressed beech (Fagus sylvatica) saplings after (13) CO(2) canopy pulse labeling. A combined canopy/soil chamber system with gas-tight separated soil and canopy compartments was coupled to a laser spectrometer measuring mixing ratios and isotopic composition of CO(2) in air at high temporal resolution. The measured δ(13) C(SR) signal was then explained and substantiated by a mechanistic carbon allocation model. Leaf metabolism had a strong imprint on diel cycles in control plants, as a result of an alternating substrate supply switching between sugar and transient starch. By contrast, diel cycles in drought-stressed plants were determined by the relative contributions of autotrophic and heterotrophic respiration throughout the day. Drought reduced the speed of the link between photosynthesis and soil respiration by a factor of c. 2.5, depending on the photosynthetic rate. Drought slows the coupling between photosynthesis and soil respiration and alters the underlying mechanism causing diel variations of δ(13) C(SR).

Performance and clinical significance of direct antimicrobial susceptibility testing on urine from hospitalized patients.

BACKGROUND: Urinary tract infections (UTIs) are common infections in the community and the hospital. With increasing antimicrobial resistance, specifically in the Gram-negative uropathogens, reliable, rapid antimicrobial susceptibility data would be useful to guide antimicrobial treatment. Direct antimicrobial susceptibility testing (DST) of urine with microscopic evidence of Gram-negative bacterial infection and its clinical significance was investigated in this study. METHODS: DST was performed by Kirby-Bauer disk diffusion method using undiluted urine as a non-standardized inoculum. Urine specimens with Gram-negative bacteria on microscopy were included. DST results from growth of Gram-negative bacteria were compared to routine antimicrobial susceptibility testing by Phoenix automated system (AST). Errors were scored as 'very major error' if susceptible by DST but resistant by AST and as 'major error' if resistant by DST but susceptible by AST. All other discrepancies were defined as 'minor error'. Discrepancies were resolved by determination of minimum inhibitory concentrations (MICs) using Etests. After discrepancy analysis, errors were scored as above using the Etest as the reference method. For analysis, specimens were divided into 3 categories: category A: 1 isolate found by DST as well as by routine culture; category B: 1 isolate detected by DST, but more than 1 isolate found on routine culture; category C: more than 1 isolate found by both DST and routine culture. The clinical significance of DST was determined prospectively by investigating the potential impact of DST on antimicrobial therapy. RESULTS: One hundred and sixteen urine specimens were included. For DST and AST there was agreement in 96% of 1152 comparisons in category A (n = 100), 88% of 41 comparisons in category B (n = 4), and 88% of 110 comparisons in category C (n = 12). The 64 discrepancies included 18 very major errors, 7 major errors, and 39 minor errors. Eight very major errors and 11 minor errors were not investigated because the isolates were not available. After Etest MIC determination for the 45 remaining discrepancies, DST showed 1 very major error, 1 major error, and 8 minor errors in category A, none in category B, and 5 major errors and 4 minor errors in category C. Antimicrobial therapy for UTI was prescribed for 53 patients. For 4 patients (8%) therapy was adjusted based on DST because of antimicrobial resistance and for 12 patients (23%) antimicrobial treatment could have been streamlined. CONCLUSIONS: DST on urine is reliable in monobacterial Gram-negative infections. With increasing antimicrobial resistance, DST can make an important contribution to patient management and reduce the use of broad-spectrum antimicrobials.

Ecological effects of selective decontamination on resistant gram-negative bacterial colonization.

RATIONALE: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) eradicate gram-negative bacteria (GNB) from the intestinal and respiratory tract in intensive care unit (ICU) patients, but their effect on antibiotic resistance remains controversial. OBJECTIVES: We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD, or standard care was used during consecutive periods of 6 months (de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, et al. N Engl J Med 2009;360:20-31). METHODS: Point prevalence surveys of rectal and respiratory samples were performed once monthly in all ICU patients (receiving or not receiving SOD/SDD). Effects of SDD on rectal, and of SDD/SOD on respiratory tract, carriage of GNB were determined by comparing results from consecutive point prevalence surveys during intervention (6 mo for SDD and 12 mo for SDD/SOD) with consecutive point prevalence data in the pre- and postintervention periods. MEASUREMENTS AND MAIN RESULTS: During SDD, average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin, or ciprofloxacin were 5, 7, and 7%, and increased to 15, 13, and 13% postintervention (P < 0.05). During SDD/SOD resistance levels in the respiratory tract were not more than 6% for all three antibiotics but increased gradually (for ceftazidime; P < 0.05 for trend) during intervention and to levels of 10% or more for all three antibiotics postintervention (P < 0.05). CONCLUSIONS: SOD and SDD have marked effects on the bacterial ecology in an ICU, with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD.

Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction.

Toll-like receptor 2 (TLR2) plays an important role in the recognition of Borrelia bacteria, the causative agent of Lyme disease, but the existence and importance of additional receptors in this process has been hypothesized. In the present study, we confirmed the role played by TLR2 in the recognition of Borrelia bacteria but also demonstrated a crucial role for the intracellular peptidoglycan receptor NOD2 for sensing the spirochete. Cells from individuals who were homozygous for the loss-of-function mutation 3020insC in the NOD2 gene were defective with respect to cytokine release after stimulation with Borrelia species, and this was confirmed in peritoneal macrophages from mice lacking RICK, the adaptor molecule used by NOD2. In contrast, NOD1 played no major role in the recognition of Borrelia spirochetes. This raises the intriguing possibility that recognition of Borrelia spirochetes is exerted by TLR2 in combination with NOD2 and that both receptors are necessary for an effective induction of cytokines by Borrelia species. The interplay between TLR2 and NOD2 might not only be necessary for the induction of a proper immune response but may also contribute to inflammatory-induced pathology.