Prophage Diversity Across Salmonella and Verotoxin-Producing Escherichia coli in Agricultural Niches of British Columbia, Canada.

Prophages have long been regarded as an important contributor to the evolution of Salmonella and Verotoxin-producing E. coli (VTEC), members of the Enterobacteriaceae that cause millions of cases of foodborne illness in North America. In S. Typhimurium, prophages provide many of the genes required for invasion; similarly, in VTEC, the Verotoxin-encoding genes are located in cryptic prophages. The ability of prophages to quickly acquire and lose genes have driven their rapid evolution, leading to highly diversified populations of phages that can infect distantly-related bacterial hosts. To defend against foreign genetic materials (i.e., phages), bacteria have evolved Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) immunity, consisting of variable spacer regions that match short nucleic acid sequences of invaders previously encountered. The number of spacer regions varies widely amongst Enterobacteriaceae, and there is currently no clear consensus if the accumulation of spacers is linked to genomic prophage abundance. Given the immense prophage diversity and contribution to bacterial host phenotypes, we analyzed the prophage sequences within 118 strains of Salmonella and VTEC, 117 of which are of agricultural origin. Overall, 130 unique prophage sequences were identified and they were found to be remarkably diverse with <50% nucleotide similarity, particularly with the Gifsy-1 group which was identified in several Salmonella serovars and interestingly, a strain of VTEC. Additionally, we identified a novel plasmid-like phage that carried antibiotic resistance and bacteriocin resistance genes. The strains analyzed carried at least six distinct spacers which did not possess homology to prophages identified in the same genome. In fact, only a fraction of all identified spacers (14%) possessed significant homology to known prophages. Regression models did not discern a correlation between spacer and prophage abundance in our strains, although the relatively high number of spacers in our strains (an average of 27 in Salmonella and 19 in VTEC) suggest that high rates of infection may occur in agricultural niches and be a contributing driver in bacterial evolution. Cumulatively, these results shed insight into prophage diversity of Salmonella and VTEC, which will have further implications when informing development of phage therapies against these foodborne pathogens.

Efficacy of bimatoprost for the treatment of primary open-angle glaucoma: A protocol of systematic review and meta-analysis.

BACKGROUND: Bimatoprost has been reported to treat primary open-angle glaucoma (POAG) effectively. However, up-to-date, no systematic review has specifically addressed the efficacy and safety of bimatoprost for the treatment of POAG. Therefore, this study will propose to appraise the efficacy and safety of bimatoprost for the treatment of POAG. METHODS: We will perform a systematic search in MEDLINE, EMBASE, CINAHI, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception up to the March 1, 2020. We will include randomized controlled trials (RCTs) for evaluating the efficacy and safety of bimatoprost for the treatment of POAG. Primary outcome is the mean intraocular pressure (IOP) reduction from baseline to the endpoint, and change in best corrected visual acuity. Secondary outcomes are contrast sensitivity, rate of progression of glaucoma, quality of life, and incidence of adverse events. Study quality will be examined by Cochrane Collaboration tool, and strength of evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation tool. RESULTS: This proposed study will outline the current RCTs to assess the efficacy and safety of bimatoprost for the treatment of POAG. CONCLUSION: The findings of this study will confirm whether bimatoprost is beneficial to patients with POAG. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040118.

Utility of the Seattle Heart Failure Model for palliative care referral in advanced ambulatory heart failure.

BACKGROUND: Physicians face uncertainty when predicting death in heart failure (HF) leading to underutilisation of palliative care. To facilitate decision-making, we assessed the Seattle Heart Failure Model (SHFM) as a referral tool by evaluating its performance in predicting 1-year event-free survival from death, heart transplant (HTx), and ventricular assist device (VAD) implantation. METHODS: We retrospectively reviewed the charts of consecutive patients with advanced ambulatory HF with New York Heart Association Class III/IV HF and a left ventricular ejection fraction of ≤40% from 2000 to 2016. We evaluated SHFM's performance by using the Cox proportional hazards model, its discrimination using the c-statistic, its calibration by comparing the observed and predicted survival and its clinical utility by hypothetically assessing the proportion of patients adequately or inadequately referred to palliative care. RESULTS: We included 612 patients in our study. During the 1-year follow-up, there were 83 deaths, 4 HTx and 1 VAD. Although SHFM showed very good discrimination (c-statistic=0.71) and adequate calibration in medium to low-risk patients, it underestimated event-free survival by 12% in high-risk patients. SHFM's clinical utility was limited: 33% of eligible patients would have missed the opportunity for referral and only 27% of referred patients would have benefited. CONCLUSION: Use of SHFM could result in a high proportion of referrals while capturing the majority of patients who may benefit from palliative care. Though this may be a more encompassing and safer alternative than current referral practices, it could lead to many early referrals.

Effects of Shugan Jianpi Formula () on myeloid-derived suppression cells-mediated depression breast cancer mice.

OBJECTIVE: To observe the intervention effect of Shugan Jianpi Formula (, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. METHODS: The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine (GEM), and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell (MDSC) in the mouse spleen, T cell subsets, and the early apoptosis of CD8+ T cells. RESULTS: The SGJPF+GEM group had the highest inhibition rate and the longest survival time (P<0.01). The MDSC level and the apoptosis rate of CD8+ T cells was the highest in the SGJPF+GEM group (P<0.05). CONCLUSIONS: Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8+ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.

[The effect of curvatures on the accuracy of the electronic apex locator].

PURPOSE: To investigate the effect of canal curvatures on the accuracy of 3 electronic apex locators (EAL) in vitro. METHODS: Alginate and 123 canals were used to mimic the situation in vitro. Three kinds of electronic apex locators including Raypex5(®), Propex(®) and Rider(®) were applied to determine the length of the canals divided into 3 groups including straight (<5°), middle (>10°,<20°) and severe (>20 °) according to the root canal curvatures. Experimental measurements and the distances (IF value) between experimental and ideal actual measurements under the same measurement environment were recorded. Paired sample t test was applied to analyze the results by using SPSS11.5 software package. RESULTS: The results showed that with the allowance of ±0.5 mm, the accuracy ratios of straight canal, moderate and severe curvature canal were 84.6%, 81.6%, 87.5% for Raypex5(®) 76.9%,89.8%, 91.7% for Propex(®), and 92.3%, 89.8%, 87.5% for Rider(®), respectively. There was no significant difference in the accuracy between the EALs regarding three degrees of root canal curvatures. CONCLUSIONS: The curvatures of the root canals have no influence on the accuracy of the EALs, though the difference exists in the accuracy rate among the EALs.