Project description:DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.
Project description:Study questionDo daughters of older mothers have lower fecundability?Summary answerIn this cohort study of North American pregnancy planners, there was virtually no association between maternal age ≥35 years and daughters' fecundability.What is known alreadyDespite suggestive evidence that daughters of older mothers may have lower fertility, only three retrospective studies have examined the association between maternal age and daughter's fecundability.Study design, size, durationProspective cohort study of 6689 pregnancy planners enrolled between March 2016 and January 2020.Participants/materials, setting, methodsPregnancy Study Online (PRESTO) is an ongoing pre-conception cohort study of pregnancy planners (age, 21-45 years) from the USA and Canada. We estimated fecundability ratios (FR) for maternal age at the participant's birth using multivariable proportional probabilities regression models.Main results and the role of chanceDaughters of mothers ≥30 years were less likely to have previous pregnancies (or pregnancy attempts) or risk factors for infertility, although they were more likely to report that their mother had experienced problems conceiving. The proportion of participants with prior unplanned pregnancies, a birth before age 21, ≥3 cycles of attempt at study entry or no follow-up was greater among daughters of mothers <25 years. Compared with maternal age 25-29 years, FRs (95% CI) for maternal age <20, 20-24, 30-34, and ≥35 were 0.72 (0.61, 0.84), 0.92 (0.85, 1.00), 1.08 (1.00, 1.17), and 1.00 (0.89, 1.12), respectively.Limitations, reasons for cautionAlthough the examined covariates did not meaningfully affect the associations, we had limited information on the participants' mother. Differences by maternal age in reproductive history, infertility risk factors and loss to follow-up suggest that selection bias may partly explain our results.Wider implications of the findingsOur finding that maternal age 35 years or older was not associated with daughter's fecundability is reassuring, considering the trend towards delayed childbirth. However, having been born to a young mother may be a marker of low fecundability among pregnancy planners.Study funding/competing interest(s)PRESTO was funded by NICHD Grants (R21-HD072326 and R01-HD086742) and has received in-kind donations from Swiss Precision Diagnostics, FertilityFriend.com, Kindara.com, and Sandstone Diagnostics. Dr Wise is a fibroid consultant for AbbVie, Inc.Trial registration numbern/a.
Project description:We examined the link between gestational biomarkers and breast cancer in 9169 daughters born into the Child Health and Development Studies from 1959 to 1967. We identified 137 breast cancer cases diagnosed by age 52 as of 2012. Markers of increased risk included higher placental volume and rapid 2nd trimester gestational weight gain. Protective markers were placental hemorrhage and fibrin deposition, indicators of resistance to placental trophoblast invasion. Paradoxically, higher ponderal index at birth was protective suggesting that fetal and placental pathways to breast cancer are multiple and distinct. Results link placental and fetal phenotypes to breast cancer, characterizing some as restrictive and others as permissive markers of tumor development. We found new biomarkers of breast cancer risk that can be mined to discover 'omic correlates in the pregnancy exposome using archived and contemporary pregnancy samples. This line of investigation may discover new pathways to risk and new opportunities for prevention.