Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter

Brain Region-Specific Differences in Amyloid-β Plaque Composition in 5XFAD Mice

Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer’s disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical “full-length” Aβ species. Using immunohistochemistry, we analyzed the distribution of Aβ1-x, Aβx-42 and Aβ4-x species in amyloid deposits in the subiculum, hippocampus and cortex in 5XFAD mice during aging. Overall plaque load increased in all three brain regions, with the subiculum being the area with the strongest relative plaque coverage. In the subiculum, but not in the other brain regions, the Aβ1-x load peaked at an age of five months and decreased thereafter. In contrast, the density of plaques positive for N-terminally truncated Aβ4-x species increased continuously over time. We hypothesize that ongoing plaque remodeling takes place, leading to a conversion of deposited Aβ1-x peptides into Aβ4-x peptides in brain regions with a high Aβ plaque burden

J Gerontol A Biol Sci Med Sci

BACKGROUND: Visual impairment (VI) and determinants of poor cardiovascular health are very common in Sub-Saharan Africa. However, we do not know whether these determinants are associated with VI among older adults in this region. This study aimed at investigating the association between the determinants of poor cardiovascular health and near VI among older adults living in Congo. METHODS: Participants were Congolese adults aged 65 or older included in Epidemiology of Dementia in Central Africa-Follow-up population-based cohort. Near VI was defined as visual acuity less than 20/40 measured at 30 cm. Associations between determinants of poor cardiovascular health collected at baseline and near visual acuity measured at first follow-up were investigated using multivariable logistic regression models. RESULTS: Among the 549 participants included, 378 (68.8%; 95% confidence interval [CI]: 64.9%-72.7%]) had near VI. Of the determinants of poor cardiovascular health explored, we found that having high body mass index of at least 25 kg/m2 (odds ratio [OR] = 2.15; 95% CI: 1.25-3.68), diabetes (OR = 2.12; 95% CI: 1.06-4.25) and hypertension (OR = 1.65; 95% CI: 1.02-2.64) were independently associated with near VI. CONCLUSIONS: Several determinants of poor cardiovascular health were associated with near VI in this population. This study suggests that promoting good cardiovascular health could represent a target for VI prevention among older adults