Purpose To determine whether HPV DNA can be detected in the plasma of patients with HPV(+) oropharyngeal carcinoma (OP) and to monitor its temporal change during radiotherapy (RT). Methods and Materials We used PCR to detect HPV DNA in the culture media of HPV(+) SCC90, VU147T and the plasma of SCC90 and HeLa tumor bearing mice, non-tumor controls and those bearing HPV(-) tumors. We used real time quantitative PCR (qPCR) to quantify plasma HPV DNA in 40 HPV(+) OP, 24 HPV(-) head and neck cancer (HNC) patients and 10 non-cancer volunteers. Tumor HPV status was confirmed by p16INK4a staining and HPV16/18 PCR or HPV ISH. 14 patients had serial plasma samples for HPV DNA quantification during RT. Results HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in controls. It was detected in 65% of pretreatment plasma samples from HPV(+) OP patients using E6/7 qPCR. None of the HPV(-) HNC or non-cancer controls had detectable HPV DNA. Pretreatment plasma HPV DNA copy number correlated significantly with nodal metabolic tumor volume (assessed on FDG-PET). Serial measurements in 14 patients showed rapid decline in HPV DNA that became undetectable at RT completion. In 3 patients, HPV DNA rose to discernable level at the time of metastasis. Conclusions Xenograft studies indicated that plasma HPV DNA is released from HPV(+) tumors. Circulating HPV DNA is detectable in most HPV(+) OP patients. Plasma HPV DNA may be a valuable tool for identifying relapse.

Purpose To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment. Experimental Design Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit+/CD90+ SMG stem cells and BrdUrd+ salispheres. Results More than 99% of CD34+ huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit+ mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd+ salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non–stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit+/CD90+ SMG population and BrdUrd+ sphere formation compared with control. Conclusion This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy.

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Background Most residents and faculty in obstetrics and gynecology (Ob/Gyn) are women. However, only a third of Ob/Gyn academic leadership positions are held by women in the United States. Methods This is an IRB-approved cross-sectional study of leadership aspirations among Ob/Gyn residents in the U.S. as related to gender and mentorship using an electronic survey distributed nationwide in 2017. The primary outcome was resident interest in academic leadership. Mediator variables included demographics and training environment characteristics. Descriptive statistics and comparative analyses were performed using SPSS. Results We received 202 completed surveys, for a representative cross-section of 4% of all Ob/Gyn residents in the U.S. The majority (86%) of respondents were women ( n = 174), reflecting the same gender distribution of all Ob/Gyn residents in training. Sixty-seven percent of all respondents reported an interest in pursuing academic leadership ( n = 133). Women reported leadership aspirations less often than men (64% vs 86%, p < 0.05) and reported lower mean Likert scores (3.73 vs 4.14, p < 0.05) regarding interest in leadership. A marginal difference between mean Likert scores was observed between women and men when controlled for other demographics (coefficient − 0.344, SE 0.186; p = 0.066). No difference in leadership aspirations was noted between women and men when controlled for mentorship, presence of female program director, and presence of three or more female leaders in a program. Conclusions Gender disparity in goal-setting toward leadership is identified as early as residency training in Ob/Gyn. This imbalance in leadership aspirations can be addressed with targeted mentorship. Electronic supplementary material The online version of this article (10.1186/s12909-019-1757-x) contains supplementary material, which is available to authorized users.

This prospective cohort study assesses the prevalence of celiac disease in the infertile population undergoing IVF. Patients are followed and IVF outcomes are compared in patients who show serologic evidence of disease and those who do not.MATERIALS AND METHODS: Women ages 18-45 years participating in IVF at a single infertility center are being recruited for participation. Patients have serum tissue transglutaminase (tTG) and endomysial (EMA) immunoglobulin A testing to screen for celiac disease. Patients also complete a 10 question ''yes or no'' survey to assess their medical history, prior testing, dietary habits, and pertinent symptoms. These questions include assessment of classic GI symptoms in addition to extra-intestinal symptoms such as menstrual irregularities and history of pregnancy loss. IVF outcomes are being recorded prospectively.RESULTS: 730 patients have undergone serum screening with a mean age of 36.2 AE 4.5 years. Their median antimullerian hormone level is 1.95 ng/mL, mean day 3 FSH is 8.03 AE 3.08 IU/L and median antral follicle count is 13 (1-70) follicles demonstrating typical IVF patients. Of those patients who have completed their questionnaire, 583/665 (88%) reported at least one symptom and 415 (63%) reported at least two symptoms concerning for celiac disease. Despite this, only 10 patients (1.3%) were positive for both tTG and EMA immunoglobulin A which demonstrates positive screening for celiac disease, and only 6 patients were positive for one of the two immunoglobulins. Furthermore, in this analysis fertilization rates (92.0% v. 85.1%) and blastulation rates (50.7% v. 49.5%) were equivalent between those who were seropositive and seronegative. Even when seropositive patients achieved pregnancy (n¼8) there was only 1 loss. In a separate analysis, patients who reported being gluten-free regardless of serologic evidence of celiac disease (n¼42) had equivalent blastulation rates (p¼0.2627) and sustained implantation rates (p¼0.5866) to those patients who reported ingesting gluten. This indicates that a gluten-free diet does not impact outcomes.CONCLUSIONS: This is the first large prospective cohort study investigating the prevalence of seropositive celiac disease in infertile patients. In this analysis, the prevalence of celiac disease is consistent with that of the general population (0.7-1.4%) and therefore infertility alone is not an indication for screening. Of note, even when patients were seropositive, IVF outcomes were equivalent. Additionally, when patients implemented a gluten-free diet, there was no therapeutic advantage, and this intervention should not be implemented to solely impact IVF outcomes.SUPPORT: The Foundation for Embryonic Competence.