Emergency Contraception: Access and Challenges at Times of Uncertainty.

BACKGROUND: The UN Commission on Life-Saving Commodities for Women and Children identified emergency contraceptive pills as 1 of the 13 essential underused, low-cost, and high-impact commodities that could save the lives of millions of women and children worldwide. In the US, 2 emergency contraceptive regimens are currently approved, and their most plausible mechanism of action involves delaying and/or inhibiting ovulation. AREAS OF UNCERTAINTY: Abortion and contraception are recognized as essential components of reproductive health care. In the US, in the wake of the Dobbs v. Jackson Women's Health Organization Supreme Court decision on June 24, 2022, 26 states began to or are expected to severely restrict abortion. It is anticipated that these restrictions will increase the demand for emergency contraception (EC). Several obstacles to EC access have been described, and these include cost, hurdles to over-the-counter purchase, low awareness, myths about their mechanisms of action, widespread misinformation, and barriers that special populations face in accessing them. The politicization of EC is a major factor limiting access. Improving sex education and health literacy, along with eHealth literacy, are important initiatives to improve EC uptake and access. DATA SOURCES: PubMed, The Guttmacher Institute, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization, The United Nations. THERAPEUTIC ADVANCES: A randomized noninferiority trial showed that the 52 mg levonorgestrel intrauterine device was noninferior to the copper intrauterine device when used as an EC method in the first 5 days after unprotected intercourse. This is a promising and highly effective emergency contraceptive option, particularly for overweight and obese patients, and a contraceptive option with a different bleeding profile than the copper intrauterine device. CONCLUSIONS: EC represents an important facet of medicine and public health. The 2 medical regimens currently approved in the US are very effective, have virtually no medical contraindications, and novel formulations are actively being investigated to make them more convenient and effective for all patient populations. Barriers to accessing EC, including the widespread presence of contraception deserts , threaten to broaden and accentuate the already existing inequities and disparities in society, at a time when they have reached the dimensions of a public health crisis.

The Zika virus: an opportunity to revisit reproductive health needs and disparities.

First isolated in 1947, the Zika virus was initially connected only to limited or sporadic human infections. In late 2015, the temporal clustering of a Zika outbreak and microcephaly in newborn babies from northeastern Brazil, and the identification of a causal link between the two, led to the characterization of the congenital Zika syndrome. In the wake of the epidemic, several countries from Latin America advised women to postpone pregnancies for periods ranging from six months to two years. These recommendations initiated critical conversations about the challenges of implementing them in societies with limited access to contraception, widespread socioeconomic inequalities, and high rates of unplanned and adolescent pregnancies. The messaging targeted exclusively women, despite a high prevalence of imbalances in the relationship power, and addressed all women as a group, failing to recognize that the decision to postpone pregnancies will impact different women in different ways, depending on their age at the time. Finally, in several countries affected by the Zika epidemic, due to restrictive reproductive policies, legally terminating a pregnancy is no longer an option even at the earliest time when brain malformations as part of the congenital Zika syndrome can be detected by ultrasonography. The virus continued to circulate after 2016 in several countries. Climate change models predict an expansion of the geographical area where local Zika transmission may occur, indicating that the interface between the virus, teratogenesis, and reproductive rights is a topic of considerable interest for medicine, social sciences, and public health for years to come.

Rapid Simulation of Unprocessed DEER Decay Data for Protein Fold Prediction.

Despite advances in sampling and scoring strategies, Monte Carlo modeling methods still struggle to accurately predict de novo the structures of large proteins, membrane proteins, or proteins of complex topologies. Previous approaches have addressed these shortcomings by leveraging sparse distance data gathered using site-directed spin labeling and electron paramagnetic resonance spectroscopy to improve protein structure prediction and refinement outcomes. However, existing computational implementations entail compromises between coarse-grained models of the spin label that lower the resolution and explicit models that lead to resource-intense simulations. These methods are further limited by their reliance on distance distributions, which are calculated from a primary refocused echo decay signal and contain uncertainties that may require manual refinement. Here, we addressed these challenges by developing RosettaDEER, a scoring method within the Rosetta software suite capable of simulating double electron-electron resonance spectroscopy decay traces and distance distributions between spin labels fast enough to fold proteins de novo. We demonstrate that the accuracy of resulting distance distributions match or exceed those generated by more computationally intensive methods. Moreover, decay traces generated from these distributions recapitulate intermolecular background coupling parameters even when the time window of data collection is truncated. As a result, RosettaDEER can discriminate between poorly folded and native-like models by using decay traces that cannot be accurately converted into distance distributions using regularized fitting approaches. Finally, using two challenging test cases, we demonstrate that RosettaDEER leverages these experimental data for protein fold prediction more effectively than previous methods. These benchmarking results confirm that RosettaDEER can effectively leverage sparse experimental data for a wide array of modeling applications built into the Rosetta software suite.

Randomized Controlled Trial of Home-Based Lifestyle Therapy on Postpartum Weight in Underserved Women with Overweight or Obesity.

OBJECTIVE: This study aimed to assess the efficacy of a home-based lifestyle intervention delivered through Parents as Teachers (PAT), a national home-visiting organization, designed to minimize excessive weight gain through 12 months post partum in socioeconomically disadvantaged (SED) African American women with overweight or obesity. METHODS: This randomized controlled trial was conducted at a single center as part of the Lifestyle Interventions for Expectant Moms (LIFE-Moms) consortium. Analysis was conducted with 185 SED African American women (BMI 25.0-45.0 kg/m2 at pregnancy onset) retained from an original sample of 267 randomized to standard PAT or PAT+Lifestyle, which embedded lifestyle therapy within standard PAT delivered prenatally and for 12 months post partum. RESULTS: Compared with standard PAT, the PAT+Lifestyle group gained less weight (2.5 kg vs. 5.7 kg; P = 0.01) and were more likely to return to their baseline weight (38.0% vs. 21.5%; P = 0.01) from baseline to 12 months post partum. There were no differences between groups in cardiometabolic outcomes, indices of glycemic control and insulin sensitivity, and plasma lipid profile. The estimated cost of PAT+Lifestyle was $81 more to deliver per family than standard PAT. CONCLUSIONS: PAT+Lifestyle decreases weight gain during pregnancy through 12 months post partum in SED African American women with overweight or obesity at the start of pregnancy with minimal additional cost.

Design of a randomized trial testing a multi-level weight-control intervention to reduce obesity and related health conditions in low-income workers.

Weight-control is a major public health focus for preventing multiple obesity-related health conditions. While clinic-based intensive lifestyle interventions are successful, low-socioeconomic-status (SES) populations, which have a higher burden of obesity, are difficult to reach; thus, the workplace offers a useful setting to target low-SES workers. The current paper presents the design of a study testing a workplace intervention aimed at low-SES employees. Partnering with a large healthcare system and affiliated university, this project will test an innovative multi-level intervention ("Working for You") adapted from existing group- and individual-level intervention models to promote healthy weight among low-wage workers. The individual-level component is an interactive obesity treatment approach (iOTA) program that involves assessment of behavior risks, collaborative goal-setting with a health coach, and interactive SMS text-messages for ongoing support and self-monitoring. This mHealth intervention is embedded in the group-level component, a workplace participatory program that involves worker teams engaged in the design and implementation of interventions to change their workplace environments. These nested interventions are being tested in a group-randomized trial among 22 work groups (~1000 total workers, ~300 workers with obesity). The primary outcome will be program effects on weight at 2-year follow-up, compared to control, and the secondary outcomes will be effects on diet and physical activity; iOTA adherence, process measures, and work environment/support will also be examined. This pragmatic clinical trial will test scalable interventions that can be translated to other work settings to reduce obesity and related health risks among low-SES workers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02934113.

Effect of a Home-Based Lifestyle Intervention on Breastfeeding Initiation Among Socioeconomically Disadvantaged African American Women with Overweight or Obesity.

BACKGROUND: Socioeconomically disadvantaged (SED) African American women with overweight or obesity are less likely to breastfeed. OBJECTIVE: To test whether a home-based lifestyle intervention impacts breastfeeding initiation rates in SED African American women with overweight or obesity. STUDY DESIGN: This was a secondary analysis of a randomized controlled trial from October 2012 to March 2016 at a university-based hospital within the LIFE-Moms consortium. SED African American women with overweight or obesity and singleton gestations were randomized by 16 weeks to Parents as Teachers (PAT)-a home-based parenting support and child development educational intervention-or PAT+, PAT with additional content on breastfeeding. Participants completed a breastfeeding survey. Outcomes included breastfeeding initiation and reasons for not initiating or not continuing breastfeeding. RESULTS: One hundred eighteen women were included: 59 in PAT+; 59 in PAT. Breastfeeding initiation rates were similar in each group (78.00% in PAT+; 74.58% in PAT). On a one to four scale, with four denoting "very important," women in PAT+ and PAT were equally likely to rate their beliefs that formula was better than breast milk or breastfeeding would be too inconvenient as the most important reasons to not initiate breastfeeding. On the same scale, women similarly rated their difficulty latching or concern for low milk supply as the most important reasons for breastfeeding cessation. CONCLUSION: SED African American women with overweight or obesity who received a home-based educational intervention had higher breastfeeding rates than is reported nationally for black women (59%). However, the intervention with more breastfeeding content did not further increase breastfeeding rates or impact reasons for breastfeeding cessation. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01768793.

Estimation of the receptor-state affinity constants of ligands in functional studies using wild type and constitutively active mutant receptors: Implications for estimation of agonist bias.

We describe a method for estimating the affinities of ligands for active and inactive states of a G protein-coupled receptor (GPCR). Our protocol involves measuring agonist-induced signaling responses of a wild type GPCR and a constitutively active mutant of it under control conditions and after partial receptor inactivation or reduced receptor expression. Our subsequent analysis is based on the assumption that the activating mutation increases receptor isomerization into the active state without affecting the affinities of ligands for receptor states. A means of confirming this assumption is provided. Global nonlinear regression analysis yields estimates of 1) the active (Kact) and inactive (Kinact) receptor-state affinity constants, 2) the isomerization constant of the unoccupied receptor (Kq-obs), and 3) the sensitivity constant of the signaling pathway (KE-obs). The latter two parameters define the output response of the receptor, and hence, their ratio (Kq-obs/KE) is a useful measure of system bias. If the cellular system is reasonably stable and the Kq-obs and KE-obs values of the signaling pathway are known, the Kact and Kinact values of additional agonists can be estimated in subsequent experiments on cells expressing the wild type receptor. We validated our method through computer simulation, an analytical proof, and analysis of previously published data. Our approach provides 1) a more meaningful analysis of structure-activity relationships, 2) a means of validating in silico docking experiments on active and inactive receptor structures and 3) an absolute, in contrast to relative, measure of agonist bias.

Behavioral economic predictors of overweight children's weight loss.

OBJECTIVE: Our goal was to determine whether behavioral economic constructs-including impulsivity (i.e., steep discounting of delayed food and monetary rewards), the relative reinforcing value of food (RRVfood), and environmental enrichment (i.e., the presence of alternatives to unhealthy foods in the home and neighborhood environments)-are significant pretreatment predictors of overweight children's weight loss within family-based treatment. METHOD: Overweight children (N = 241; ages 7-12 years; 63% female; 65% non-Hispanic White) enrolled in a 16-week family-based obesity treatment with at least one parent. At baseline, children completed a task to assess RRVfood and delay discounting measures of snack foods and money to assess impulsivity. Parents completed questionnaires to assess environmental enrichment. RESULTS: Children who found food highly reinforcing and steeply discounted future food rewards at baseline showed a blunted response to treatment compared with children without this combination of risk factors. High environmental enrichment was associated with treatment success only among children who did not find food highly reinforcing. Monetary discounting rate predicted weight loss, regardless of children's level of RRVfood. CONCLUSIONS: Investigation is warranted into novel approaches to obesity treatment that target underlying impulsivity and RRVfood. Enriching the environment with alternatives to unhealthy eating may facilitate weight loss, especially for children with low RRVfood.