Experimental colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972

Establishment of asymptomatic bacteriuria (ABU) with Escherichia coli 83972 is a viable prophylactic alternative to antibiotic therapy for the prevention of recurrent bacterial urinary tract infection in humans. Approximately 2 x 108 viable E. coli 83972 cells were introduced into the bladder of six healthy female dogs via a sterile urinary catheter. The presence of pyuria, depression, stranguria, pollakiuria and haematuria was documented for 6 weeks and urinalysis and aerobic bacterial cultures were performed every 24–72 h. Pyuria was present in all dogs on day 1 post-inoculation and 4/6 dogs (67%) had a positive urine culture on this day. Duration of colonization ranged from 0 to 10 days (median 4 days). Four dogs were re-inoculated on day 20. Duration of colonization following the second inoculation ranged from 1 to 3 days. No dog suffered pyrexia or appeared systemically unwell but all dogs initially exhibited mild pollakiuria and a small number displayed gross haematuria and/or stranguria. By day 3 of each trial all clinical signs had resolved. Persistent bacteriuria was not achieved in any dog but two dogs were colonized for 10 days following a single inoculation. Further research is required to determine whether establishment of ABU in dogs with recurrent urinary tract infection is a viable alternative to repeated doses of antimicrobial agents.

Uropathogenic Escherichia coli mediated urinary tract infection

Urinary tract infection (UTI) is among the most common infectious diseases of humans and is the most common nosocomial infection in the developed world. They cause significant morbidity and mortality, with approximately 150 million cases globally per year. It is estimated that 40-50% of women and 5% of men will develop a UTI in their lifetime, and UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenses each year in the USA. Uropathogenic E. coli (UPEC) is the primary cause of UTI. This review presents an overview of the primary virulence factors of UPEC, the major host responses to infection of the urinary tract, the emergence of specific multidrug resistant clones of UPEC, antibiotic treatment options for UPEC-mediated UTI and the current state of vaccine strategies as well as other novel anti-adhesive and prophylactic approaches to prevent UTI. New and emerging themes in UPEC research are also discussed in the context of future outlooks.

Occurrence of urinary tract tumors in miners highly exposed to dinitrotoluene

Between 1984 and 1997, six cases of urothelial cancer and 14 cases of renal cell cancer occurred in a group of 500 underground mining workers in the copper-mining industry of the former German Democratic Republic, with high exposures to explosives containing technical dinitrotoluene. Exposure durations ranged from 7 to 37 years, and latency periods ranged from 21 to 46 years. The incidences of both urothelial and renal cell tumors in this group were much higher than anticipated on the basis of the cancer registers of the German Democratic Republic by factors of 4.5 and 14.3, respectively. The cancer cases and a representative group of 183 formerly dinitrotoluene- exposed miners of this local industry were interviewed for their working history and grouped into four exposure categories. This categorization of the 14 renal cell tumor cases revealed no dose-dependency concerning explosives in any of the four exposure categories and was similar to that of the representative group of employees, whereas the urothelial tumor cases were predominantly confined to the high-exposure categories. Furthermore, all identified tumor patients were genotyped by polymerase chain reaction, using lymphocyte DNA, regarding their genetic status of the polymorphic xenobiotic metabolizing enzymes, including the N-acetyltransferase 2 and the glutathione-S-transferases M1 and T1. This genotyping revealed remarkable distributions only for the urothelial tumor cases, who were exclusively identified as 'slow acetylators.' This points to the possibility of human carcinogenicity of dinitrotoluene, with regard to the urothelium as the target tissue.

Molecular analysis of asymptomatic bacteriuria escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

Active fibers: Matching deformable tract templates to diffusion tensor images

Reliable quantitative analysis of white matter connectivity in the brain is an open problem in neuroimaging, with common solutions requiring tools for fiber tracking, tractography segmentation and estimation of intersubject correspondence. This paper proposes a novel, template matching approach to the problem. In the proposed method, a deformable fiber-bundle model is aligned directly with the subject tensor field, skipping the fiber tracking step. Furthermore, the use of a common template eliminates the need for tractography segmentation and defines intersubject shape correspondence. The method is validated using phantom DTI data and applications are presented, including automatic fiber-bundle reconstruction and tract-based morphometry. © 2009 Elsevier Inc. All rights reserved.

Heritability of white matter fiber tract shapes: A HARDI study of 198 twins

Genetic analysis of diffusion tensor images (DTI) shows great promise in revealing specific genetic variants that affect brain integrity and connectivity. Most genetic studies of DTI analyze voxel-based diffusivity indices in the image space (such as 3D maps of fractional anisotropy) and overlook tract geometry. Here we propose an automated workflow to cluster fibers using a white matter probabilistic atlas and perform genetic analysis on the shape characteristics of fiber tracts. We apply our approach to large study of 4-Tesla high angular resolution diffusion imaging (HARDI) data from 198 healthy, young adult twins (age: 20-30). Illustrative results show heritability for the shapes of several major tracts, as color-coded maps.

Labeling white matter tracts in hardi by fusing multiple tract atlases with applications to genetics

Accurate identification of white matter structures and segmentation of fibers into tracts is important in neuroimaging and has many potential applications. Even so, it is not trivial because whole brain tractography generates hundreds of thousands of streamlines that include many false positive fibers. We developed and tested an automatic tract labeling algorithm to segment anatomically meaningful tracts from diffusion weighted images. Our multi-atlas method incorporates information from multiple hand-labeled fiber tract atlases. In validations, we showed that the method outperformed the standard ROI-based labeling using a deformable, parcellated atlas. Finally, we show a high-throughput application of the method to genetic population studies. We use the sub-voxel diffusion information from fibers in the clustered tracts based on 105-gradient HARDI scans of 86 young normal twins. The whole workflow shows promise for larger population studies in the future.

Automatic population HARDI white matter tract clustering by label fusion of multiple tract atlases

Automatic labeling of white matter fibres in diffusion-weighted brain MRI is vital for comparing brain integrity and connectivity across populations, but is challenging. Whole brain tractography generates a vast set of fibres throughout the brain, but it is hard to cluster them into anatomically meaningful tracts, due to wide individual variations in the trajectory and shape of white matter pathways. We propose a novel automatic tract labeling algorithm that fuses information from tractography and multiple hand-labeled fibre tract atlases. As streamline tractography can generate a large number of false positive fibres, we developed a top-down approach to extract tracts consistent with known anatomy, based on a distance metric to multiple hand-labeled atlases. Clustering results from different atlases were fused, using a multi-stage fusion scheme. Our "label fusion" method reliably extracted the major tracts from 105-gradient HARDI scans of 100 young normal adults. © 2012 Springer-Verlag.

Infection and cellular defense dynamics in a novel 17beta-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (106–107 CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

Postprocedural effects of gastrointestinal endoscopy performed as a day case procedure in children : implications for patient and family education

A prospective design that included a survey tool, nursing care records, and telephone interview was used to determine postprocedural effects experienced by children and families following gastrointestinal endoscopy performed as a day procedure. One hundred twenty-one children attending a pediatric gastroenterology unit for endoscopy under general anesthesia participated in the study. Physical symptoms, day care/school attendance, behavioral issues, and economic factors in the 72 hours post procedure were identified. Over half the children (n = 69, 57%) experienced pain in the hospital post procedure. Pain was reported by 73 children (60%) at home on the day of the procedure, by 55 children (45%) on Day 1 post procedure, and by 37 children (31%) on Day 2 post procedure. The throat was the most common site of pain. Nausea or vomiting was experienced by 37 children (31%) at some time following their procedure but was not associated with procedure type, age, or fasting time. Over half the children (n = 53, 51%) who usually attended day care or school did not attend the day following their procedure. Twenty-four parents (40%) who would normally have worked on the day after the procedure did not attend employment. These findings have been used to improve the preprocedural information and discharge management of patients treated in a pediatric gastroenterology ambulatory setting. © The Society of Gastroenterology Nurses & Associates 2007. All Rights Reserved.

Perinatal nutrition and gastrointestinal disorders : Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

Metabolic programming during the perinatal period as a consequence of early nutrition is an emerging area of great interest. This concept is known as the "fetal origins of adult disease" theory (1). Numerous epidemiological studies published over the past 20 years or so have suggested that small body size at birth and during infancy and, more specifically, intrauterine growth retardation are associated later in life with lowered cognitive performance and increased rates of coronary heart disease and its major biological risk factors, ie, raised blood pressure, insulin resistance, coronary artery disease, and abnormalities in lipid metabolism. The molecular mechanisms that govern this phenomenon in humans, however, are unknown and need to be elucidated.

Therapeutic upper gastrointestinal endoscopy in children : An audit of 443 procedures and literature review

The safety, effectiveness and capabilities of therapeutic upper fibreoptic endoscopy in children undergoing therapeutic endoscopic procedures (n = 443) was studied. Therapy for gastrointestinal bleeding formed the major group (injection sclerotherapy for varices, n = 197 procedures; thermocoagulation for haemorrhagic gastritis, n = 1; and photocoaulation for Dieulafoy's disease, n = 1). Sclerotherapy was 97% effective in controlling acute bleeding and 84% effective in obliterating varices with no serious complications or deaths. Oesophageal dilatations for surgical, caustic, congenital and peptic strictures and achalasia (n = 193) were performed with no oesophageal perforations or deaths. Foreign bodies were retrieved (n = 34) with no failures or complications. Percutaneous endoscopic gastrostomy was performed (n = 11) with one failure, proceeding to an unsuccessful surgical gastrostomy. Miscellaneous procedures included endoscopic transpyloric tube placement (n = 5) and endoscopic diathermy of pyloric web (n = 1). Therapeutic fibreoptic endoscopy is therefore concluded to be safe and effective in children, replacing rigid oesophagoscopy and some traditional surgical approaches.

Urinary tract infection of mice to model human disease: Practicalities, implications and limitations

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Murine models of human UTI are vital experimental tools that have helped to elucidate UTI pathogenesis and advance knowledge of potential treatment and infection prevention strategies. Fundamentally, several variables are inherent in different murine models, and understanding the limitations of these variables provides an opportunity to understand how models may be best applied to research aimed at mimicking human disease. In this review, we discuss variables inherent in murine UTI model studies and how these affect model usage, data analysis and data interpretation. We examine recent studies that have elucidated UTI host–pathogen interactions from the perspective of gene expression, and review new studies of biofilm and UTI preventative approaches. We also consider potential standards for variables inherent in murine UTI models and discuss how these might expand the utility of models for mimicking human disease and uncovering new aspects of pathogenesis

Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection

Background CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14−/− mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14−/− mice. Exacerbation of infection in Cd14−/− mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.