New therapies are needed that target breast cancer metastases. In previous studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is effective against breast cancer metastases. In the study presented here, we have further enhanced the efficacy of Mage-b vaccination through the improved delivery of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping fragments of Mage-b as well as the complete protein-encoding region of Mage-b have been expressed as a fusion protein with a truncated non-cytolytic form of listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains were preventively tested for their efficacy against breast cancer metastases in a syngeneic mouse tumour model 4T1. The LM-LLO-Mageb/2nd, expressing position 311 -660 of the cDNA of Mage-b, was the most effective vaccine strain against metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage-b/2nd dramatically reduced the number of metastases by 96% compared with the saline group and by 88% compared with the vector control group (LM-LLO), and this correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed on 4T1 primary tumours, which may be the result of a complete absence of Mage-b-specific immune responses in the draining lymph nodes. Vaccination with LM-LLO-Mage-b/2nd could be an excellent follow-up after removal of the primary tumour, to eliminate metastases and residual tumour cells.

IntroductionResearch on the association between periodontitis and oral human papilloma virus (HPV) infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults.MethodsData from the 2014–2016 San Juan Overweight Adults Longitudinal Study (n = 740) was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0–8.4, p < 0.05) in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection.ConclusionsSevere periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammation's role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies.

Marijuana use was associated with periodontitis, but not with oral HPV infection. Further evaluation of the role of marijuana use in oral HPV infection and periodontitis may inform novel preventive public health strategies, as marijuana users could be at increased risk of oral cancer.

BackgroundOncogenic HPV infection is associated to anogenital cancer. We estimate the prevalence and correlates of anogenital HPV infection among a population-based sample of women aged 16–64 years living in the metropolitan area of Puerto Rico.Methods564 women completed face-to-face and computer assisted interviews and self-collected anal and cervical specimens. HPV DNA testing used MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for sample amplification. Positive specimens were typed by dot-blot hybridization.ResultsWeighted prevalence of cervical, anal, and cervical/anal co-infection was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%), correspondingly. Having ≥3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5–3.5) and last year anal intercourse (OR: 1.6; 95% CI: 1.1–2.5) increased the odds of anogenital HPV infection. Cervical infection was independently associated to anal infection (OR: 3.0; 95% CI: 2.0–4.6).ConclusionsSimilar to others, our results confirm the burden of anogenital HPV infection in women and its relationship with sexual behavior. As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease.

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Problem solving is an essential skill for students to be successful in life and careers. Students need to use efficient strategies to solve problems effectively. In this basic interpretive qualitative study, we aimed to (a) explore children’s problem-solving strategies in a game-based tool (i.e., puzzles), and (b) investigate the troubleshooting strategies they employed while solving the puzzles. We recorded students’ puzzle-solving efforts, and using an observation analysis approach, noted important moments, patterns in puzzle-solving, troubleshooting methods, and other noteworthy events. Our analysis showed that while solving computer-based puzzles, students demonstrated the use of three approaches: varying-one-thing-at-a-time (VOTAT), building all-at-once or change-all (CA), and a mixed approach. CA was the approach used most often, followed by VOTAT, and then the mixed approach. Of the two troubleshooting approaches, starting the sequence over was the preferred method. Others opted to search for the faulty tile in the sequence. We discuss how these findings can inform practice and provide some insights as to the usefulness of the game-based tool, Lightbot.

Background This study aims to understand the age‐related changes in vortex formation time (VFT) index in children, and thus, describe the ranges of VFT in different pediatric age groups with the ultimate goal of assessment of diastolic function. Methods and results Transthoracic echocardiograms in healthy (n = 84) subjects from birth to 20 years were analyzed to compute VFT and diastolic performance. LV apical and short‐axis views were used. Three separate measurements were performed, and the mean was used to derive VFT and other indices. Statistical comparisons were made amongst the groups, stratified by age. Results Vortex formation times in neonates (median 1.79, interquartile range 1.31–1.92) and infants (1.38, 1.07–1.72) were found to be significantly lower (P < .05) than the older age groups (1–5 years 2.47, 1.87–2.94, 5–10 years 2.18, 1.89–2.53, 10–20 years 2.34, 1.84–2.96). The changes in VFT correlate to the changes in diastolic function in children. Conclusion Our results show that unlike adults, VFT changes along with the growth‐related myocardial adaptations in children, and its range may be used to evaluate diastolic function. The present study is the first to test the significance of the trans‐mitral VFT in children by comparing different age groups of healthy subjects.

BackgroundTo understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area.MethodsAs part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16–64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR.Results32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 − 29%, HPV11 − 18%, HPV16 − 23%, and HPV18 − 17%; seroprevalence was high in the youngest age-group (16–19: 26–37%). HPV seropositivity was associated with having ≥ 3 lifetime sexual partners (OR=2.5, 95% CI=1.7–3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2–2.6).ConclusionsThe high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16.