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  • buy EZ Cap Reagent GG Based on these considerations and the

    2018-10-23

    Based on these considerations and the presented microbiological and clinical observations, we decided to stop the PT trial at interim analysis. In summary, while phage therapy is still one very important alternative tool against antibiotic resistance, we need to understand in detail the in vivo interactions between phage and its host bacterium to judge the reliability and efficacy of such approaches. At the moment it is risky to conclude whether phage therapy is or is not a viable option against antibiotic-resistant bacterial pathogens.
    Competing Interests
    Author Contribution SAS is the PI of the clinical study responsible for study design, protocol writing, for defense of the protocol to institutional review boards, data collection tool development, data analysis, interpretation and manuscript writing; SS is the Co-PI of the clinical study responsible for defending the protocol at IRB, data collection tool development and data collection; GR did stool phage counting and streptococcal isolation; DM did library preparation, the sequencing and the assembly of the Strep genomes; PD did design the de novo genome assembly and data interpretation; FC did the phage susceptibility testing of fecal E. coli isolates; GB did the T4-like coliphages cocktail development, GMP production and release; SMC did the PCR detection of E. coli virulence buy EZ Cap Reagent GG in stool DNA; CN-B contributed to the bioinformatic analysis of the microbiota and the streptococcal genomes; TN did the statistical analysis; MA did the viable E. coli counts in fresh stools; SH collected the clinical data; FQ contributed to study design, data interpretation and supervised the etiology analysis in the clinical microbiology lab; KT did clinical microbiology data collection; MK did streptococcal genome data submission and annotation; MD did the qPCR analysis of elt and est genes; CL did the qPCR of total stool bacteria; YD searched the streptococcal genomes for virulence genes; SEA did the Dirichlet Multinomial Mixtures analysis; BB did acquisition, analysis and interpretation of microbiota data, and contributed to the writing of manuscript; HB designed with the PI the clinical protocol, coordinated and supervised the project and wrote the manuscript.
    Acknowledgments
    Introduction Gestational trophoblastic neoplasia (GTN) is a spectrum of pregnancy related malignancies including invasive molar disease, choriocarcinoma and the much rarer placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) (Hui et al., 2014). Prior to the development of cytotoxic chemotherapy these malignant conditions were invariably fatal. However, overall cure rates now exceed 98% due to the development of improved chemotherapeutic regimens and follow-up protocols (Seckl et al., 2010). A hallmark of GTN is the production of human chorionic gonadotropin (hCG). Serum hCG levels aid rapid diagnosis and accurate disease monitoring (Seckl et al., 2013). However, hCG secretion alone is not always diagnostic of GTN as some non-gestational malignancies also secrete hCG (Iles et al., 2010). Women with GTN fall into two groups; (i) those who following evacuation of a molar pregnancy are treated with a clinical diagnosis of GTN based on rising serum hCG levels and (ii) those who present with an hCG-secreting tumor. For the second group histopathological examination of tissue is important for determining the correct diagnosis and when the diagnosis remains unclear molecular genotyping can play an important role (Fisher et al., 2007). Most histological specimens of trophoblastic neoplasia are obtained via sampling of disease from the uterus. However GTN may be highly vascular and biopsy of tissue in the uterus or elsewhere may be deemed unsafe due to the risk of hemorrhage. Therefore some patients with metastatic disease, a raised serum hCG and characteristic history, such as a recent pregnancy, may be treated as a GTN without a histological diagnosis. This is because it is prudent to treat a highly curable disease, rather than risk morbidity and mortality via delay to achieve a histological diagnosis (Seckl et al., 2013). Patients who have GTN may therefore be left with uncertainty regarding their prognosis while patients with non-gestational tumors may be treated with inappropriate aggressive chemotherapy. For these women development of a blood based diagnostic test would be beneficial.