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BackgroundIn the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region.MethodsWe assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression.ResultsAfter adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category.ConclusionIn this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.

Background Little is known about how maternal obesity impacts breast milk (BM) composition and how BM composition may impact growth. We sought to determine the role of maternal body mass index (BMI) on BM inflammatory and oxidative stress markers and to delineate the role of these BM markers on infant growth. Methods This was a secondary analysis of 40 mother-infant dyads. We first assessed the association between maternal BMI and BM marker (omega-6:omega-3 polyunsaturated fatty acid ratio (n-6:n-3 PUFA), leptin, interleukin (IL)-8, IL-6, IL-1[beta] and malondialdehyde (MDA)) concentration at one (V1) and four (V4) months postpartum. We then examined the association between BM markers on infant growth trajectory from birth to seven months. Results Higher maternal BMI was associated with higher BM n-6:n-3 PUFA (V1 [beta] = 0.12, 95% CI 0.01, 0.2; V4 [beta] = 0.13, 95% CI 0.01, 0.3) and leptin (V1 [beta] = 107, 95% CI 29, 184; V4 [beta] = 254, 95% CI 105, 403) concentrations. Infants exposed to high BM n-6:n-3 PUFA had higher BMI z-scores over time (p = 0.01). Higher BM leptin was associated with lower infant percent fat mass at V4 ([beta] = -9, 95% CI -17, -0.6). Infants exposed to high BM IL-8, IL-6, or IL-1[beta] had higher weight z-scores over time (IL-8 p < 0.001; IL-6 p < 0.001; IL-1[beta] p = 0.02). There was no association between BM MDA and maternal BMI or infant growth. Conclusions Higher maternal BMI is associated with higher BM n-6:n-3 PUFA and leptin concentrations. In addition, higher BM n-6:n-3 PUFA and inflammatory cytokines were associated with accelerated weight gain in infancy., Author(s): Samantha Enstad [sup.1] , Sukhinder Cheema [sup.2] , Raymond Thomas [sup.3] , Raina N. Fichorova [sup.4] [sup.5] , Camilia R. Martin [sup.5] [sup.6] , Perrie O'Tierney-Ginn [sup.7] , Carol [...]

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3(+) and CD45(+) cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score, Escherichia coli, and Enterococcus and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45(+) and CD3(+) cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.

The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves -2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.

BackgroundTopical microbicides against the human immunodeficiency virus (HIV) 1 that are nonirritating to the female genital epithelium are urgently needed to slow the heterosexual spread of HIV infection. Products that are also effective contraceptives provide additional benefits. Cellulose sulfate (CS) is a noncytotoxic antifertility agent that exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV.MethodsWe performed a multicenter, Phase I, placebo-controlled, randomized study to evaluate the genital toxicity of CS. Two cohorts of healthy women used 3.5 ml of 6% CS gel or 3.5 ml of K-Y Jelly, vaginally, bid, for 14 days. The first cohort was sexually abstinent, and the second cohort was sexually active.ResultsCS was associated with only a slightly higher odds ratio (OR) of symptoms of minor urogenital irritation compared to the inactive lubricant K-Y Jelly (OR=2.02, 95% confidence interval=0.90-4.53). In addition, there were minor shifts in some genital flora, but there was no evidence of greater inflammation as evidenced by few colposcopic findings, decreased influx of polymorphonuclear cells and minimal changes in proinflammatory cytokines. Moreover, both products appeared acceptable to most women. Product leakage was identified as more of a problem in sexually abstinent women, but less so in women using the product for sexual intercourse, as would be the case in actual practice.ConclusionCS was safe for twice-daily use for 14 days. CS is appropriate for future studies in effectiveness trials.