EMT: 2016.

The significant parallels between cell plasticity during embryonic development and carcinoma progression have helped us understand the importance of the epithelial-mesenchymal transition (EMT) in human disease. Our expanding knowledge of EMT has led to a clarification of the EMT program as a set of multiple and dynamic transitional states between the epithelial and mesenchymal phenotypes, as opposed to a process involving a single binary decision. EMT and its intermediate states have recently been identified as crucial drivers of organ fibrosis and tumor progression, although there is some need for caution when interpreting its contribution to metastatic colonization. Here, we discuss the current state-of-the-art and latest findings regarding the concept of cellular plasticity and heterogeneity in EMT. We raise some of the questions pending and identify the challenges faced in this fast-moving field.

Characteristics and Patterns of Cigarette Smoking and Vaping By Past-Year Smokers Who Reported Using Electronic Nicotine Delivery System to Help Quit Smoking in the Past Year: Findings From the 2018-2019 Tobacco Use Supplement to the Current Population Survey.

INTRODUCTION: Cigarette smoking has declined, while electronic nicotine delivery system (ENDS) use has increased in the United States. Understanding the role of ENDS in adult smoking quit attempts and cessation is important for estimating their population health impact. AIMS AND METHODS: We used data from 2018 to 2019 tobacco use supplement to the current population survey to examine demographic characteristics and ENDS use patterns among adult ENDS users who reported quitting smoking in the past year by trying to switch to ENDS ("switchers") and smokers who did or did not make a quit attempt in the past year. χ2 tests of proportions and t-tests were used to compare characteristics between groups. RESULTS: In 2018-2019, about three-quarters of switchers reported daily use of ENDS compared to only one-third of dual users with a recent quit attempt by trying to switch to ENDS. Compared to dual users who made a quit attempt by trying to switch to ENDS, switchers were more likely to use menthol/mint-flavored ENDS exclusively (5.6% vs. 13.1%; p = .004) but less likely to use tobacco-flavored ENDS exclusively (21.2% vs. 13.7%; p = .01). CONCLUSIONS: ENDS users who quit smoking in the past year and reported trying to quit by switching to ENDS were more likely to use menthol/mint flavors exclusively and use ENDS daily compared to dual users who made a quit attempt by trying to switch to ENDS. Longer-term prospective data may better clarify the role of ENDS in smoking quit attempts and cessation. IMPLICATIONS: This study provides information on patterns of ENDS use in former smokers and current smokers who tried to quit smoking by switching to ENDS in a national sample of U.S. adults. These results can inform policy actions concerning ENDS products.

Transitions to smokeless tobacco use among adult cigarette smokers in the Population Assessment of Tobacco and Health (PATH) Study, Waves 3-5 (2015-2019).

OBJECTIVE: Examine patterns of dual use of cigarettes and smokeless tobacco and complete switching over time among adult current cigarette smokers using data from the Population Assessment of Tobacco and Health Study Wave 3 (2015-2016), Wave 4 (2016-2018) and Wave 5 (2018-2019). METHODS: We examined four tobacco use states among 6834 exclusive smokers and 372 dual users at Wave 3 with two waves of follow-up data: exclusive cigarette use, exclusive smokeless tobacco use, dual use and use of neither product. RESULTS: Among exclusive smokers at Wave 3, only 1.6% (95% CI: 1.3% to 2.1%) transitioned to dual use at Wave 4, and 0.1% (95% CI: 0.07% to 0.2%) switched to exclusive smokeless tobacco use. Among exclusive smokers who switched to dual use, 53.1% (95% CI: 40.9% to 64.9%) returned to exclusive cigarette smoking, 34.3% (95% CI: 23.8% to 46.6%) maintained dual use and 12.6% (95% CI: 7.0% to 21.7%) did not smoke cigarettes after an additional wave of follow-up. Dual users at Wave 3 were likely to maintain their dual use status at Wave 4, 51.2% (95% CI: 46.1% to 56.3%) and Wave 5, 47.9% (95% CI: 40.1% to 55.8%). CONCLUSIONS: Very few cigarette smokers transition to smokeless tobacco use, and among those who do, dual use is more common than exclusive smokeless tobacco use. Further, the majority of exclusive cigarette smokers who transition to dual use at Wave 4 continue smoking cigarettes at Wave 5, either as dual users or as exclusive smokers.

Calcium modulation of doxorubicin cytotoxicity in yeast and human cells.

Doxorubicin is a widely used chemotherapeutic agent, but its utility is limited by cellular resistance and off-target effects. To understand the molecular mechanisms regulating chemotherapeutic responses to doxorubicin, we previously carried out a genomewide search of doxorubicin-resistance genes in Schizosaccharomyces pombe fission yeast and showed that these genes are organized into networks that counteract doxorubicin cytotoxicity. Here, we describe the identification of a subgroup of doxorubicin-resistance genes that, when disrupted, leads to reduced tolerance to exogenous calcium. Unexpectedly, we observed a suppressive effect of calcium on doxorubicin cytotoxicity, where concurrent calcium and doxorubicin treatment resulted in significantly higher cell survival compared with cells treated with doxorubicin alone. Conversely, inhibitors of voltage-gated calcium channels enhanced doxorubicin cytotoxicity in the mutants. Consistent with these observations in fission yeast, calcium also suppressed doxorubicin cytotoxicity in human breast cancer cells. Further epistasis analyses in yeast showed that this suppression of doxorubicin toxicity by calcium was synergistically dependent on Rav1 and Vph2, two regulators of vacuolar-ATPase assembly; this suggests potential modulation of the calcium-doxorubicin interaction by fluctuating proton concentrations within the cellular environment. Thus, the modulatory effects of drugs or diet on calcium concentrations should be considered in doxorubicin treatment regimes.

Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility.

Single nucleotide polymorphisms (SNPs) are important biomolecular markers in health and disease. Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. Here, we highlight associations between SNPs in several important enzymes involved in the one-carbon folate metabolic pathway and the elevated maternal risk of having a child with Down syndrome. Our survey highlights that the combination of SNPs may be a more reliable predictor of the Down syndrome phenotype than single SNPs alone. We also describe recent links between SNPs in p53 and its related pathway proteins and Down syndrome, as well as highlight several proteins that help to associate apoptosis and p53 signaling with the Down syndrome phenotype. In addition to a comprehensive review of the literature, we also demonstrate that several SNPs reside within the same regions as these Down syndrome-linked SNPs, and propose that these closely located nucleotide changes may provide new candidates for future exploration.

Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin.

Phosphotyrosine-binding domains, typified by the SH2 (Src homology 2) and PTB domains, are critical upstream components of signal transduction pathways. The E3 ubiquitin ligase Hakai targets tyrosine-phosphorylated E-cadherin via an uncharacterized domain. In this study, the crystal structure of Hakai (amino acids 106-206) revealed that it forms an atypical, zinc-coordinated homodimer by utilizing residues from the phosphotyrosine-binding domain of two Hakai monomers. Hakai dimerization allows the formation of a phosphotyrosine-binding pocket that recognizes specific phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. NMR and mutational analysis identified the Hakai residues required for target binding within the binding pocket, now named the HYB domain. ZNF645 also possesses a HYB domain but demonstrates different target specificities. The HYB domain is structurally different from other phosphotyrosine-binding domains and is a potential drug target due to its novel structural features.

Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.

The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orients the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.

Direct association of Sprouty-related protein with an EVH1 domain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate/kinase interactions.

The mammalian SPRED (Sprouty-related protein with an EVH1 domain) proteins include a family of three members, SPRED1-3. Currently, little is known about their biochemistry. The best described, SPRED1, has been shown to inhibit the Ras/ERK pathway downstream of Ras. All three SPREDs have a cysteine-rich domain (CRD) that has high homology to the CRD of the Sprouty family of proteins, several of which are also Ras/ERK inhibitors. In the belief that binding partners would clarify SPRED function, we assayed for their associated proteins. Here, we describe the direct and endogenous interaction of SPRED1 and SPRED2 with the novel kinase, DYRK1A. DYRK1A has become the subject of recent research focus as it plays a central role in Caenorhabditis elegans oocyte maturation and egg activation, and there is strong evidence that it could be involved in Down syndrome in humans. Both SPRED1 and SPRED2 inhibit the ability of DYRK1A to phosphorylate its substrates, Tau and STAT3. This inhibition occurs via an interaction of the CRD of the SPREDs with the kinase domain of DYRK1A. DYRK1A substrates must bind to the kinase to enable phosphorylation, and SPRED proteins compete for the same binding site to modify this process. Our accumulated evidence indicates that the SPRED proteins are likely physiological modifiers of DYRK1A.

Symptom resolution after hysterectomy and alternative treatments for chronic pelvic pain: does depression make a difference?

OBJECTIVE: The purpose of this study was to determine whether depression influences treatment outcomes and to identify predictors of symptom resolution among women with chronic pelvic pain (CPP). STUDY DESIGN: Analysis of 701 women with CPP in the Study of Pelvic Problems, Hysterectomy and Intervention Alternatives prospective cohort study, which included 153 women (22%) with depression. We conducted multivariable analyses to evaluate the influence of depression on pre-/posttreatment differences in symptoms and health-related quality of life and to identify other predictors of symptom improvement. RESULTS: CPP treatments included hysterectomy (9%), other surgical treatments (9%), hormonal medications (50%), narcotic analgesics (47%), physical therapy (12%), and nonprescription medications (93%). Depression predicted lower gains in health perception (P < .05) but not in symptom resolution, sexual functioning, or other aspects of health-related quality of life. Symptom resolution was predicted by hysterectomy (P < .001), entering menopause (P < .001), and pretreatment satisfaction with sex (P = .039). CONCLUSION: Depression does not influence substantially treatment-related gains in CPP symptom resolution and health-related quality of life. Coexisting depression should not delay treatment for CPP.

Success of uterus-preserving treatments for abnormal uterine bleeding, chronic pelvic pain, and symptomatic fibroids: age and bridges to menopause.

OBJECTIVE: The purpose of this study was to determine whether age at first uterus-preserving treatment (UPT) predicts symptom resolution among women with common pelvic problems. STUDY DESIGN: We conducted an analysis of 557 participants in the Study of Pelvic Problems, Hysterectomy and Intervention Alternatives cohort who reported having undergone a UPT. We performed multivariable regression modeling age at first UPT, hysterectomy, menopause, and other covariates to predict symptom resolution. RESULTS: Mean ± SD age at enrollment was 42.7 ± 4.7 years; mean follow-up time was 4.4 ± 2.7 years. Sixteen percent of the women underwent hysterectomy; 37% of the women entered menopause. Hysterectomy was a strong predictor of symptom resolution (P < .001). Compared with women who were younger (first UPT at age <40 years), older women reported greater symptom resolution, even after the data were controlled for hysterectomy use and menopausal status (P = .028). CONCLUSION: Women who are ≥40 years old when they undergo their first uterus-preserving treatment experience greater symptom resolution than younger women. Framing UPTs as hysterectomy alternatives may be accurate only for a subset of women who are >40 years old.

A randomized controlled trial of methylergonovine prophylaxis after dilation and evacuation abortion.

OBJECTIVE: To evaluate the efficacy of intramuscular methylergonovine maleate as prophylaxis against excessive bleeding when given after dilation and evacuation (D&E) at 20-24 weeks. STUDY DESIGN: We performed a randomized, double-blinded, placebo-controlled trial in patients without excessive bleeding requiring intervention after D&E completion. We administered study treatment within one minute of the end of the procedure. We primarily compared outcomes using a composite of indicators of excessive post-procedure blood loss (post-procedure measured blood loss exceeding 125 mL, uterine massage or compression for at least two minutes, administration of additional uterotonic medication, intrauterine balloon tamponade, uterine re-aspiration, blood transfusion, uterine artery embolization, hospital admission for bleeding, or major surgery). Secondary outcomes included individual indicator occurrences, satisfaction, and side effects. RESULTS: From March 3, 2015 to March 31, 2017, we randomized 284 participants (n = 140 methylergonovine, n = 144 placebo), five before we registered the trial with clinicaltrials.gov. Baseline characteristics were similar between groups. The composite outcome occurred in 78 (56%) methylergonovine and 75 (52%) placebo participants (p = 0.5). Methylergonovine recipients required more intrauterine balloon use (n = 20 [14%]) versus placebo (n = 10 [7%]), p = 0.04. We also observed a non-significant trend towards more uterotonic administration (n = 56 [40%] versus n = 43 [30%], p = 0.07) and hospital admissions for bleeding (n = 4 [3%] versus n = 0, p = 0.06) in the methylergonovine group compared to placebo. CONCLUSION: We observed no improvement in the composite outcome for excessive bleeding with prophylactic post-procedure methylergonovine. In addition, individual excessive bleeding outcomes occurred more frequently in the methylergonovine group, potentially indicating harm with its prophylactic use after D&E. IMPLICATIONS: When administered prophylactically immediately after dilation and evacuation abortion at 20-24 weeks, methylergonovine increases uterine bleeding. Given the lack of data for effectiveness as a prophylactic agent and our findings indicating harm, we do not recommend its use for post-operative prophylaxis.

Use of Comprehensive Participatory Planning and Evaluation in Rural Patient Engagement.

Comprehensive participatory planning and evaluation (CPPE), a model used in community engagement research, has not been applied to patient engagement in research. We describe our methodology and interim results using CPPE in a project focused on improving research engagement of rural and distant patients and stakeholders. Specifically, we describe our development of a causal map and the subsequent use of the map to guide patient and stakeholder-driven evaluation.

ENDS Flavor Preference by Menthol Cigarette Smoking Status among US Adults, 2018-2019.

E-cigarette flavor preference may differ among smokers using e-cigarettes, but little information is available on preferences by menthol cigarette status. Using nationally representative data for US adults from the 2018-2019 Tobacco Use Supplement to the Current Population Survey, we analyzed e-cigarette flavor preference by menthol cigarette status and e-cigarette device type for dual-cigarette and e-cigarette users and e-cigarette users who had recently quit smoking by trying to switch to e-cigarettes ("switchers"). Approximately half (52.2%) of dual users of menthol cigarettes and e-cigarettes reported using menthol/mint-flavored e-cigarettes as did 41.4% of "switchers" who had smoked menthol cigarettes; exclusive menthol/mint flavor use was 13.1% for dual users and 21.3% for "switchers." A similar proportion (45.1%) of dual users who smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes, but only 26.7% of "switchers" who had smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes. Approximately 60% of dual users and "switchers" used fruit/other flavors, regardless of menthol cigarette use. By device type, 63.9% of dual users of cartridge-based e-cigarettes and menthol cigarettes used menthol/mint-flavored e-cigarettes. Approximately 75% of dual users and 85% of "switchers" who used tank or mod systems used fruit/other flavors. Menthol cigarette smokers may be particularly likely to use menthol/mint e-cigarettes, and a majority of dual users and "switchers" used fruit/other flavors. These results can inform policy measures concerning flavored electronic nicotine delivery system products.

Predictors of abortion provision among practicing obstetrician-gynecologists: a national survey.

OBJECTIVE: The objective of the study was to identify the factors that predict whether physicians include pregnancy termination in their practices. STUDY DESIGN: We surveyed all 5055 obstetrician-gynecologists who became board certified between 1998 and 2001 about personal characteristics, career plans, intention to provide abortions before residency, residency training, and current abortion practice. RESULTS: Of 2149 respondents (43%), 22% had provided elective abortion in the past year. In multivariate analysis controlling for preresidency intentions, personal beliefs, and other variables, the following were independently associated with current abortion provision: completing a residency program with abortion training (odds ratio [OR], 1.6; confidence interval [CI], 1.1-2.3; P = .007) and performing a greater number of abortions during residency (>25 abortions: OR, 2.8; CI, 1.9-4.1; P < .001). Factors negatively associated with working in a practice (OR, 0.4; CI, 0.2-0.6; P < .001) or hospital (OR, 0.4; CI, 0.3-0.6; P < .001) that prohibits abortion. CONCLUSION: Regardless of intention to provide abortion before residency, abortion training availability was positively correlated with providing abortion in future practice.

Predictors of delay in each step leading to an abortion.

BACKGROUND: Approximately 1 out of 10 abortions in the United States occurs in the second trimester of pregnancy. This study uses survival analysis to identify the factors which delay each step of the process of obtaining an abortion. STUDY DESIGN: This is a secondary data analysis of a cross-sectional study investigating a sample of 398 women who presented for elective abortion at an urban hospital. Respondents completed a survey using an audio-assisted self-interviewing program and provided a timeline for their process of obtaining an abortion. RESULTS: In our analysis, we divided the abortion process into three steps ending in three distinct events (first pregnancy test, calling a clinic, getting an abortion). Factors associated with delay during the first step include obesity [hazard ratio (HR) 0.8, 95% CI 0.6-1.0], abuse of drugs or alcohol (HR 0.7, 95% CI 0.6-1.0), prior second-trimester abortion (HR 0.6, 95% CI 0.4-0.8) and being unsure of last menstrual period (HR 0.6, 95% CI 0.4-0.7) and emotional factors such as being in denial (HR 0.8, 95% CI 0.6-1.0) and fear of abortion (HR 0.7, 95% CI 0.5-1.0). CONCLUSION: This study identified key factors associated with delay in obtaining abortion care. Interventions which seek to address these factors, especially those factors associated with later pregnancy suspicion and testing, may reduce abortion delay and facilitate women obtaining their abortions when medical risk and overall cost are lower.

Effect of noncancerous pelvic problems on health-related quality of life and sexual functioning.

OBJECTIVE: To assess the effect of abnormal uterine bleeding and pelvic pain and pressure on health-related quality of life and sexual functioning and assess treatment satisfaction. METHODS: This is a cross-sectional study of 1,493 sociodemographically diverse women who were seeking care for noncancerous pelvic problems and who had not undergone hysterectomy. Participants were asked about symptoms, attitudes, health-related quality of life, sexual functioning, and treatment satisfaction. Preference for current health was measured using the time tradeoff metric, which asked respondents to estimate the number of years of life they would be willing to trade off to not have a uterine condition. Multivariable logistic regression was used to identify determinants of treatment satisfaction. RESULTS: Most (82.7%) participants reported a complete lack of or only partial symptom resolution, and 42.3% reported that their pelvic problems interfered with their ability to have and enjoy sex. Mean Short Form-12 Physical (43-49) and Mental (41-44) Component Summary scores were substantially lower than population norms for women aged 40-49 years. Mean current health time tradeoff scores ranged from 0.78 to 0.88. Satisfaction with Western medicines ranged from 31.3% (progestin intrauterine device) to 58.2% (opiates) and with uterine-preserving surgery from 20.0% (dilation and curettage) to 51.0% (myomectomy); 27.7 % of the women who used acupuncture were satisfied. Participants with lower educational attainment, greater symptom resolution, and less interference of pelvic problems with sex were more likely to be satisfied. CONCLUSION: Noncancerous pelvic problems are associated with serious decrements in health-related quality of life and sexual functioning and low rates of treatment satisfaction. LEVEL OF EVIDENCE: II.

Feasibility of Vaginal Hysterectomy for Female-to-Male Transgender Men.

OBJECTIVE: To describe the hysterectomy data among a cohort of transgender men and nontransgender (ie, cisgender) women with a particular goal to evaluate the feasibility of vaginal hysterectomy among transgender men. METHODS: This cohort study includes all hysterectomies performed for benign indications on transgender men and cisgender women at a single academic county hospital from 2000 to 2012. Hysterectomy cases and patient gender were identified by billing records and confirmed by review of medical records. Primary study outcome was the hysterectomy route among transgender men compared with cisgender women. We also examined risk factors and operative outcomes. Student two-sided t tests, χ analysis, and descriptive statistics are presented; sensitivity analyses using regression techniques were performed. RESULTS: Hysterectomies for benign gynecologic procedures were performed in 883 people: 33 on transgender men and 850 on cisgender women. Transgender men were younger, had fewer pregnancies and deliveries, and smaller uteri. The leading indication for hysterectomy differed significantly: pain (85%) was most common among transgender men (compared with 22% in cisgender women; P<.001), whereas leiomyomas (64%) was most common for cisgender women (compared with 21% in transgender men; P<.001). Vaginal hysterectomies were performed in 24% transgender men and 42% of cisgender women. Estimated blood loss was less among transgender men (P=.002), but when uterine size and route of hysterectomy were considered, the difference between gender groups was no longer significant. There was no difference in patients experiencing complications between the groups. CONCLUSION: Transgender men and cisgender women have different preoperative characteristics and surgical indications. Vaginal hysterectomies have been successfully completed among transgender men. Because vaginal hysterectomy is a viable procedure for this population, it should be considered in surgical planning for transgender men.

The EMT spectrum and therapeutic opportunities.

Carcinomas are phenotypically arrayed along an epithelial-mesenchymal transition (EMT) spectrum, a developmental program currently exploited to understand the acquisition of drug resistance through a re-routing of growth factor signaling. This review collates the current approaches employed in developing therapeutics against cancer-associated EMT, and provides an assessment of their respective strengths and drawbacks. We reflect on the close relationship between EMT and chemoresistance against current targeted therapeutics, with a special focus on the epigenetic mechanisms that link these processes. This prompts the hypothesis that carcinoma-associated EMT shares a common epigenetic pathway to cellular plasticity as somatic cell reprogramming during tissue repair and regeneration. Indeed, their striking resemblance suggests that EMT in carcinoma is a pathological adaptation of an intrinsic program of cellular plasticity that is crucial to tissue homeostasis. We thus propose a revised approach that targets the epigenetic mechanisms underlying pathogenic EMT to arrest cellular plasticity regardless of upstream cancer-driving mutations.

Coordinated fibroblast growth factor and heparan sulfate regulation of osteogenesis.

Growth and lineage-specific differentiation constitute crucial phases in the development of stem cells. Control over these processes is exerted by particular elements of the extracellular matrix, which ultimately trigger a cascade of signals that regulate uncommitted cells, by modulating their survival and cell cycle progression, to shape developmental processes. Uncontrolled, constitutive activation of fibroblast growth factor receptors (FGFR) results in bone abnormalities, underlining the stringent control over fibroblast growth factor (FGF) activity that must be maintained for normal osteogenesis to proceed. Mounting evidence suggests that FGF signalling, together with a large number of other growth and adhesive factors, is controlled by the extracellular glycosaminoglycan sugar, heparan sulfate (HS). In this review, we focus on FGF activity during osteogenesis, their receptors, and the use of HS as a therapeutic adjuvant for bone repair.

Risk factors associated with presenting for abortion in the second trimester.

OBJECTIVE: To determine factors associated with delay of induced abortion into the second trimester of pregnancy. METHODS: Using audio computer-assisted self-interviewing, 398 women from 5 to 23 weeks of gestation at an urban hospital described steps and reasons that could have led to a delayed abortion. Multivariable logistic regression identified independent contributors to delay. RESULTS: Half of the 70-day difference between the average gestational durations in first- and second-trimester abortions is due to later suspicion of pregnancy and administration of a pregnancy test. Delays in suspecting and testing for pregnancy cumulatively caused 58% of second-trimester patients to miss the opportunity to have a first-trimester abortion. Women presenting in the second trimester experienced more delaying factors (3.2 versus 2.0, P < .001), with logistical delays occurring more frequently for these women (63.3% versus 30.4%, P < .001). Factors associated with second-trimester abortion in logistic regression were prior second-trimester abortion, delay in obtaining state insurance, difficulty locating a provider, initial referral elsewhere, and uncertainty about last menstrual period. Factors associated with decreased likelihood of second-trimester abortion were presence of nausea or vomiting, prior abortion, and contraception use. CONCLUSION: Abortion delay results from myriad factors, many of them logistical, such as inappropriate or delayed referrals and delays in obtaining public insurance. Public health interventions could promote earlier recognition of pregnancy, more timely referrals, more easily obtainable public funding, and improved abortion access for indigent women. However, accessible second-trimester abortion services will remain necessary for the women who present late due to delayed recognition of and testing for pregnancy. LEVEL OF EVIDENCE: II-2.