Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria

The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCM(con21)). 16S rRNA sequence analysis comparing LCM, LCM(con21) and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri(RR) strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut ecosystem. We provide evidence that this principle might be of general validity for invasion of bacteria in preformed gut ecosystems. This might be of relevance for human enteropathogen infections as well as therapeutic use of probiotic commensal bacteria.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Susceptibility-weighted imaging of the brain: Does gadolinium administration matter?

Susceptibility-weighted MR imaging (SWI) is usually obtained without administration of intravenous gadolinium (Gd). However, it is occasionally necessary to perform SWI after Gd is injected. The effects of Gd on SWI have not been systematically examined. The aim of this prospective study was to investigate whether performing SWI after Gd would influence the diagnostic image quality, parenchymal signal and vascular enhancement. An additional aim is to suggest potential future applications for Gd-enhanced SWI.

Combined use of pulsed arterial spin-labeling and susceptibility-weighted imaging in stroke at 3T

Background and Purpose: In acute stroke it is no longer sufficient to detect simply ischemia, but also to try to evaluate reperfusion/recanalization status and predict eventual hemorrhagic transformation. Arterial spin labeling (ASL) perfusion may have advantages over contrast-enhanced perfusion-weighted imaging (cePWI), and susceptibility weighted imaging (SWI) has an intrinsic sensitivity to paramagnetic effects in addition to its ability to detect small areas of bleeding and hemorrhage. We want to determine here if their combined use in acute stroke and stroke follow-up at 3T could bring new insight into the diagnosis and prognosis of stroke leading to eventual improved patient management. Methods: We prospectively examined 41 patients admitted for acute stroke (NIHSS >1). Early imaging was performed between 1 h and 2 weeks. The imaging protocol included ASL, cePWI, SWI, T2 and diffusion tensor imaging (DTI), in addition to standard stroke protocol. Results: We saw four kinds of imaging patterns based on ASL and SWI: patients with either hypoperfusion and hyperperfusion on ASL with or without changes on SWI. Hyperperfusion was observed on ASL in 12/41 cases, with hyperperfusion status that was not evident on conventional cePWI images. Signs of hemorrhage or blood-brain barrier breakdown were visible on SWI in 15/41 cases, not always resulting in poor outcome (2/15 were scored mRS = 0–6). Early SWI changes, together with hypoperfusion, were associated with the occurrence of hemorrhage. Hyperperfusion on ASL, even when associated with hemorrhage detected on SWI, resulted in good outcome. Hyperperfusion predicted a better outcome than hypoperfusion (p = 0.0148). Conclusions: ASL is able to detect acute-stage hyperperfusion corresponding to luxury perfusion previously reported by PET studies. The presence of hyperperfusion on ASL-type perfusion seems indicative of reperfusion/collateral flow that is protective of hemorrhagic transformation and a marker of favorable tissue outcome. The combination of hypoperfusion and changes on SWI seems on the other hand to predict hemorrhage and/or poor outcome.

Susceptibility-Weighted MR Imaging for Diagnosis of Capillary Telangiectasia of the Brain

BCT is a benign entity, whose appearance on conventional MR imaging makes its differentiation from neoplastic, inflammatory, or subacute ischemic disease challenging. SWI is sensitive to susceptibility effects from deoxyhemoglobin with excellent spatial resolution. Only scarce case reports have described the utility of SWI in cases of BCT. Our aim was to show the diagnostic value of SWI applied to a larger series of cases.

Susceptibility of Aethina tumida (Coleoptera: Nitidulidae) Larvae and Pupae to Entomopathogenic Nematodes

In this study, we evaluated the potential use of entomopathogenic nematodes as a control for the beetle Aethina tumida Murray (Coleoptera: Nitidulidae). In particular, we conducted 1) four screening bioassays to determine nematode (seven species, 10 total strains tested) and application level effects on A. tumida larvae and pupae, 2) a generational persistence bioassay to determine whether single inoculations with nematodes would control multiple generations of A. tumida larvae in treated soil, and 3) a field bioassay to determine whether the nematodes would remain efficacious in the field. In the screening bioassays, nematode efficacy varied significantly by tested nematode and the infective juvenile (IJ) level at which they were applied. Although nematode virulence was moderate in screening bioassays 1-3 (0 - 68% A. tumida mortality), A. tumida mortality approached higher levels in screening bioassay 4 (nearly 100% after 39 d) that suggest suitable applicability of some of the test nematodes as field controls for A. tumida. In the generational persistence bioassay, Steinernema Hobrave Cabanillas, Poinar & Raulston 7-12 strain and Heterorhabditis indica Poinar, Karunaka & David provided adequate A. tumida control for 19 wk after a single soil inoculation (76-94% mortality in A. tumida pupae). In the field bioassay, the same two nematode species also showed high virulence toward pupating A. tumida (88-100%) mortality. Our data suggest that nematode use may be an integral component of an integrated pest management scheme aimed at reducing A. tumida populations in bee colonies to tolerable levels.

An ONIOM Study of the Bergman Reaction: A Computationally Efficient and Accurate Method for Modeling the Enediyne Anticancer Antibiotics

The Bergman cyclization of large polycyclic enediyne systems that mimic the cores of the enediyne anticancer antibiotics was studied using the ONIOM hybrid method. Tests on small enediynes show that ONIOM can accurately match experimental data. The effect of the triggering reaction in the natural products is investigated, and we support the argument that it is strain effects that lower the cyclization barrier. The barrier for the triggered molecule is very low, leading to a reasonable half-life at biological temperatures. No evidence is found that would suggest a concerted cyclization/H-atom abstraction mechanism is necessary for DNA cleavage.

Semiempirical Study of the Bergman Reaction: Towards a Computationally Efficient and Accurate Method for Modeling Enediyne Anticancer Antibiotics

Over the past 7 years, the enediyne anticancer antibiotics have been widely studied due to their DNA cleaving ability. The focus of these antibiotics, represented by kedarcidin chromophore, neocarzinostatin chromophore, calicheamicin, esperamicin A, and dynemicin A, is on the enediyne moiety contained within each of these antibiotics. In its inactive form, the moiety is benign to its environment. Upon suitable activation, the system undergoes a Bergman cycloaromatization proceeding through a 1,4-dehydrobenzene diradical intermediate. It is this diradical intermediate that is thought to cleave double-stranded dna through hydrogen atom abstraction. Semiempirical, semiempiricalci, Hartree–Fock ab initio, and mp2 electron correlation methods have been used to investigate the inactive hex-3-ene-1,5-diyne reactant, the 1,4-dehydrobenzene diradical, and a transition state structure of the Bergman reaction. Geometries calculated with different basis sets and by semiempirical methods have been used for single-point calculations using electron correlation methods. These results are compared with the best experimental and theoretical results reported in the literature. Implications of these results for computational studies of the enediyne anticancer antibiotics are discussed.

Perioperative antibiotics to prevent infection after first-trimester abortion

There are two main strategies for the prevention of post-abortal upper genital tract infection: antibiotics given around the time of surgery for all women; and 'screen-and-treat', in which all women presenting for abortion are screened for genital infections and those with positive results are treated.

Peri-implantitis susceptibility as it relates to periodontal therapy and supportive care

To assess the long-term survival of implants inserted in periodontally susceptible patients and to investigate the influence of residual pockets on the incidence of peri-implantitis and implant loss.

Active surveillance of antibiotic resistance prevalence in urinary tract and skin infections in the outpatient setting

The aim of the study was to evaluate the need for active surveillance of antibiotic resistance in ambulatory infections. We measured the prevalence of antibiotic resistance in urinary tract infections (UTIs) (n = 1018) and skin infections (n = 213) diagnosed in outpatients between September 2008 and February 2009 in the Canton of Bern, Switzerland. Samples were stratified into 'solicited' (diagnostic work-up for study purpose only) and 'routine' (diagnostic work-up as part of standard care). Susceptibility patterns were compared for 463 Escherichia coli isolates from UTIs (231 solicited; 232 routine) and 87 Staphylococcus aureus isolates from skin infections (35 solicited; 52 routine). Overall, E. coli showed higher susceptibility to ampicillin, amoxicillin-clavulanic acid and norfloxacin in solicited than in routine samples. Among 15-45-year-old patients, susceptibility rates were comparable between solicited and routine samples for all antibiotics except for amoxicillin-clavulanic acid. However, among patients >45 years old, isolates from routine samples showed lower susceptibility to all β-lactams tested and quinolones than those from solicited samples. Extended-spectrum β-lactamase (ESBL)-producing E. coli isolates were rare (solicited, 0.4%; routine, 1.7%; p 0.4). Susceptibility patterns of S. aureus were comparable between solicited and routine samples. Therefore, in the outpatient setting, susceptibility rates for E. coli isolates differ by indication for urinary culture and age. Surveillance based on samples taken during standard care may underestimate susceptibility rates for uncomplicated infections, especially among the elderly. Reports of resistance data should include age stratification.