Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci

Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1–8?µg/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections.     

Adherence to Canada's Food Guide recommendations among Alberta's multi‐ethnic youths is a major concern: findings from the WHY ACT NOW project

Background

Dietary habits formed during youth may result in the development of obesity and chronic diseases in adulthood. We aimed to determine the frequency of the consumption of foods and beverages and the degree of adherence to Canada's Food Guide recommendations among multi‐ethnic youths.

Methods

Participants were recruited from 12 schools in the Edmonton, Alberta area by use of posters, school newsletters and advertisements. A 30‐item food frequency questionnaire was administered by a trained interviewer to assess dietary intake in a convenience sample of 557 (328 females and 229 males) youths aged 11–23 years; for the purpose of the present study, only the 14–18 years age group was considered in the analysis. Participants were divided by sex and self‐identified ethnicity into four groups [Indigenous, African & Middle Eastern (AME ), Asian, and European]. Statistical analysis of the data was undertaken using t ‐tests, Welch's analysis of variance and Games‐Howell tests. P  < 0.05 was considered statistically significant.

Results

Vegetables and Fruit recommendations were the least likely to be followed, with 90.7–96.8% of participants in all groups not consuming the recommended number of servings day^–1. The mean frequency of fruit consumption was lower among Indigenous youths compared to Asian youths (0.90 versus 1.37 times day^–1). A greater proportion of males than females (55.9% versus 44.3%) did not meet the minimum recommendations for Meat and Alternatives (P  = 0.016). The percentage of youths not adhering to recommendations for Milk and Alternatives was 81.7% for Indigenous, 73.3% for AME , 78.6% for Asian and 63.5% for European youths. Indigenous youths more frequently consumed potato chips and soft drinks compared to other ethnic youths. The most frequently consumed beverage was milk (1.25 times day^–1).

Conclusions

The majority of youths did not consume minimum daily recommended servings of Vegetables and Fruit, Milk and Alternatives, and/or Meat and Alternatives food groups. Evidence‐based dietary interventions and public health strategies are needed.

     

An in vitro evaluation of the responses of human osteoblast-like SaOs-2 cells to SLA titanium surfaces irradiated by erbium:yttrium–aluminum–garnet (Er:YAG) lasers

Erbium:yttrium–aluminum–garnet (Er:YAG) laser treatment is an effective option for the removal of bacterial plaques. Many studies have shown that Er:YAG lasers cannot re-establish the biocompatibility of titanium surfaces. The aim of this study was to evaluate the responses of the human osteoblast-like cell line, SaOs-2, to sand-blasted and acid-etched (SLA) titanium surface irradiation using different energy settings of an Er:YAG laser by examining cell viability and morphology. Forty SLA titanium disks were irradiated with an Er:YAG laser at a pulse energy of either 60 or 100 mJ with a pulse frequency of 10 Hz under water irrigation and placed in a 24-well plate. Human osteoblast-like SaOs-2 cells were seeded onto the disks in culture media. Cells were then kept in an incubator with 5 % carbon dioxide at 37 °C. Each experimental group was divided into two smaller groups to evaluate cell morphology by scanning electron microscope and cell viability using 3-4,5-dimethylthiazol 2,5-diphenyltetrazolium bromide test. In both the 60 and the 100 mJ experimental groups, spreading morphologies, with numerous cytoplasmic extensions, were observed prominently. Similarly, a majority of cells in the control group exhibited spreading morphologies with abundant cytoplasmic extensions. There were no significant differences among the laser and control groups. The highest cell viability rate was observed in the 100 mJ laser group. No significant differences were observed between the cell viability rates of the two experimental groups (p?=?1.00). In contrast, the control group was characterized by a significantly lower cell viability rate (p?<?0.001). Treatments with an Er:YAG laser at a pulse energy of either 60 or 100 mJ do not reduce the biocompatibility of SLA titanium surfaces. In fact, modifying SLA surfaces with Er:YAG lasers improved the biocompatibility of these surfaces.     

EDEN-dependent translational repression of maternal mRNAs is conserved between Xenopus and Drosophila.

Translational control is a key level in regulating gene expression in oocytes and eggs because many mRNAs are synthesized and stored during oogenesis for latter use at various stages of oocyte maturation and embryonic development. Understanding the molecular mechanisms that underlie this translational control is therefore crucial. Another important issue is the evolutionary conservation of these mechanisms--in other words the determination of their universal and specific aspects. We report here a comparative analysis of a translational repression mechanism that depends on the EDEN (embryo deadenylation element) element. This small cis-acting element, localized in the 3' untranslated region of c-mos and Eg mRNAs, was shown to be involved in a deadenylation process. We demonstrate here that in Xenopus embryos, mRNAs that contain an EDEN are translationally repressed. Next, transgenic flies were used to study the effect of the EDEN motif on translation in Drosophila oocytes. We show that this element also causes the translational repression of a reporter gene in Drosophila demonstrating that the EDEN-dependent translational repression is functionally conserved between Xenopus and Drosophila.