Evaluation of Follow-up Colposcopy Procedures After Abnormal Cervical Screening Result Across a Statewide Study in Mississippi.

Purpose: Cervical screening is used to detect and treat precancers to prevent invasive cancers. However, successful prevention also requires adequate follow-up and treatment of individuals with abnormal screening results. The aim was to investigate demographics, clinical characteristics, and follow-up status for individuals needing colposcopy after an abnormal screening result. Methods: The STRIDES (Studying Risk to Improve DisparitiES) cohort comprises individuals undergoing cervical cancer screening and management at a Mississippi Health Department or University of Mississippi clinic. Follow-up status, demographics, and clinical data were assessed from electronic health records and, if necessary, patient navigation on individuals identified as needing a colposcopy after an abnormal screening. Results: Of the 1,458 individuals requiring colposcopy, 43.0% had the procedure within 4 months, 16.4% had a delayed procedure, and 39.5% had no documented follow-up, with significant predictors of follow-up identified as age and cytology diagnosis. Based on age, individuals 30 + were more likely to follow up with a colposcopy compared to individuals < 30 years (49% and 38.7%, respectively; p < .001). Individuals with cytology diagnoses of LSIL (52.9%), ASC-H (51.4%), and HSIL (62.3%) had higher percentages of adherence to follow-up colposcopy guidelines (p < .001). Conclusion: Despite high cervical cancer screening rates among Mississippians, a substantial portion did not have adequate next-step intervention. However, it is encouraging that highest risk individuals were more likely to have a colposcopy. Regardless, continuing to understand the underlying causes for incomplete follow-up is crucial for timely secondary targeted interventions to reduce cervical cancer burden, promote awareness, and improve health outcomes.

Adaptation and Validation of E-Probe Diagnostic Nucleic Acid Analysis for Detection of Escherichia coli O157:H7 in Metagenomic Data from Complex Food Matrices.

The Centers for Disease Control and Prevention recently emphasized the need for enhanced technologies to use in investigations of outbreaks of foodborne illnesses. To address this need, e-probe diagnostic nucleic acid analysis (EDNA) was adapted and validated as a tool for the rapid, effective identification and characterization of multiple pathogens in a food matrix. In EDNA, unassembled next generation sequencing data sets from food sample metagenomes are queried using pathogen-specific sequences known as electronic probes (e-probes). In this study, the query of mock sequence databases demonstrated the potential of EDNA for the detection of foodborne pathogens. The method was then validated using next generation sequencing data sets created by sequencing the metagenome of alfalfa sprouts inoculated with Escherichia coli O157:H7. Nonspecific hits in the negative control sample indicated the need for additional filtration of the e-probes to enhance specificity. There was no significant difference in the ability of an e-probe to detect the target pathogen based upon the length of the probe set oligonucleotides. The results from the queries of the sample database using E. coli e-probe sets were significantly different from those obtained using random decoy probe sets and exhibited 100% precision. The results support the use of EDNA as a rapid response methodology in foodborne outbreaks and investigations for establishing comprehensive microbial profiles of complex food samples.

Toxicological evaluation of two flavors with modifying properties: 3-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propylpropanamide and (S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one.

A toxicological evaluation of two structurally related flavors with modifying properties, 3-((4-amino-2,2-dioxido-1H- benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propylpropanamide (S6973; CAS 1093200-92-0) and (S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one (S617; CAS 1469426-64-9), was completed for the purpose of assessing their safety for use in food and beverage applications. Both compounds exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, were poorly absorbed and rapidly eliminated. Neither compound exhibited genotoxic concerns. S6973 and S617 were not found to be mutagenic or clastogenic, and did not induce micronuclei in vitro or in vivo. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-levels (NOAELs) were 20 mg/kg/day and 100 mg/kg/day (highest doses tested) for S6973 and S617, respectively, when administered as a food ad-mix for 90 consecutive days. Furthermore, S617 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

E-probe Diagnostic Nucleic acid Analysis (EDNA): a theoretical approach for handling of next generation sequencing data for diagnostics.

Plant biosecurity requires rapid identification of pathogenic organisms. While there are many pathogen-specific diagnostic assays, the ability to test for large numbers of pathogens simultaneously is lacking. Next generation sequencing (NGS) allows one to detect all organisms within a given sample, but has computational limitations during assembly and similarity searching of sequence data which extend the time needed to make a diagnostic decision. To minimize the amount of bioinformatic processing time needed, unique pathogen-specific sequences (termed e-probes) were designed to be used in searches of unassembled, non-quality checked, sequence data. E-probes have been designed and tested for several selected phytopathogens, including an RNA virus, a DNA virus, bacteria, fungi, and an oomycete, illustrating the ability to detect several diverse plant pathogens. E-probes of 80 or more nucleotides in length provided satisfactory levels of precision (75%). The number of e-probes designed for each pathogen varied with the genome size of the pathogen. To give confidence to diagnostic calls, a statistical method of determining the presence of a given pathogen was developed, in which target e-probe signals (detection signal) are compared to signals generated by a decoy set of e-probes (background signal). The E-probe Diagnostic Nucleic acid Analysis (EDNA) process provides the framework for a new sequence-based detection system that eliminates the need for assembly of NGS data.