Structure-Activity Relationship of Flavin Analogues That Target the Flavin Mononucleotide Riboswitch.

The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative, 5FDQD, that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties.

Dinosaur footprints and other ichnofauna from the cretaceous Kem Kem beds of Morocco.

We describe an extensive ichnofossil assemblage from the likely Cenomanian-age 'lower' and 'upper' units of the 'Kem Kem beds' in southeastern Morocco. In the lower unit, trace fossils include narrow vertical burrows in cross-bedded sandstones and borings in dinosaur bone, with the latter identified as the insect ichnotaxon Cubiculum ornatus. In the upper unit, several horizons preserve abundant footprints from theropod dinosaurs.

Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography.

Background: Among physicians who perform endoscopic retrograde cholangiopancreatography (ERCP), the relationship between procedure volume and outcome is unknown.

Objective: Quantify the ERCP volume-outcome relationship by measuring provider-specific failure rates, hospitalization rates, and other quality measures.

Research Design: Retrospective cohort.

Epidemiology of enteric disease in C-EnterNet's pilot site - Waterloo region, Ontario, 1990 to 2004.

Objective: The objective of the present study was to describe the epidemiology of reportable enteric illness in Ontario's Waterloo region, including comparing calculated incidence rates with published rates, and adjusting for under-reporting to determine the number of community cases, where published data were available.

Methods: Descriptive analyses were performed on reportable disease data for 13 enteric diseases collected in the Waterloo region from 1990 to 2004. Poisson and negative binomial regression analyses were used to investigate differences in incidence rates among age, sex, the 15 years of data and seasons.

Using GPS-enabled cell phones to track the travel patterns of adolescents.

Background: Few tools exist to directly measure the microsocial and physical environments of adolescents in circumstances where participatory observation is not practical or ethical. Yet measuring these environments is important as they are significantly associated with adolescent health-risk. For example, health-related behaviors such as cigarette smoking often occur in specific places where smoking may be relatively surreptitious.

Adolescent travel patterns: pilot data indicating distance from home varies by time of day and day of week.

We conducted a pilot study using new technology to track adolescent "place." Using Global Positioning System (GPS)-enabled cell phones, we recruited and tracked 15 female adolescents for a 1-week period. Distance away from home was greatest in the evenings on weekends or holidays.

Estimating the under-reporting rate for infectious gastrointestinal illness in Ontario.

Background: In Ontario, infectious gastrointestinal illness (IGI) reporting can be represented by a linear model of several sequential steps required for a case to be captured in the provincial reportable disease surveillance system. Since reportable enteric data are known to represent only a small fraction of the total IGI in the community, the objective of this study was to estimate the under-reporting rate for IGI in Ontario.

Methods: A distribution of plausible values for the under-reporting rate was estimated by specifying input distributions for the proportions reported at each step in the reporting chain, and multiplying these distributions together using simulation methods.

Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomas.

The Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) that occur in individuals immunosuppressed by solid organ transplant (SOT) or T cell-depleted stem cell transplantation (SCT) are unequivocally a result of T cell dysfunction. Reconstitution of "at-risk" patients with EBV-specific cytotoxic T lymphocyte (CTL) lines that have been reactivated and expanded in vitro, should prevent the development of post-transplant lymphoproliferative disease or treat pre-existing disease. We have provided over 125 infusions of donor-derived EBV-specific CTL to 60 recipients of T cell-depleted stem cells.

Growing Concerns and Recent Outbreaks Involving Non-O157:H7 Serotypes of Verotoxigenic Escherichia coli.

Verocytotoxin-producing E. coli (VTEC) of serotype O157:H7 have been shown to be important agents of foodborne disease in humans worldwide. While the majority of research effort has been targeted on this serotype it is becoming more evident that other serotypes of VTEC can also be associated with human disease.