McMaster University

About: McMaster University is a education organization based out in Hamilton, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 41361 authors who have published 101269 publications receiving 4251422 citations.

Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota

Abstract: Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.

Prognosis for gross motor function in cerebral palsy: creation of motor development curves.

Abstract: ContextLack of a valid classification of severity of cerebral palsy and the absence of longitudinal data on which to base an opinion have made it difficult to consider prognostic issues accurately.ObjectiveTo describe patterns of gross motor development of children with cerebral palsy by severity, using longitudinal observations, as a basis for prognostic counseling with parents and for planning clinical management.DesignLongitudinal cohort study of children with cerebral palsy, stratified by age and severity of motor function and observed serially for up to 4 years during the period from 1996 to 2001.SettingNineteen publicly funded regional children's ambulatory rehabilitation programs in Ontario.ParticipantsA total of 657 children aged 1 to 13 years at study onset, representing the full spectrum of clinical severity of motor impairment in children with cerebral palsy.Main Outcome MeasuresSeverity of cerebral palsy, classified with the 5-level Gross Motor Function Classification System; function, formally assessed with the Gross Motor Function Measure (GMFM).ResultsBased on a total of 2632 GMFM assessments, 5 distinct motor development curves were created; these describe important and significant differences in the rates and limits of gross motor development among children with cerebral palsy by severity. There is substantial within-stratum variation in gross motor development.ConclusionsEvidence-based prognostication about gross motor progress in children with cerebral palsy is now possible, providing parents and clinicians with a means to plan interventions and to judge progress over time. Further work is needed to describe motor function of adolescents with cerebral palsy.

Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes

Abstract: A b s t r ac t Background Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. Methods We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. Results Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P = 0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. Conclusions As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.)