Associations between TCA cycle plasma metabolites and fatigue in black females with systemic lupus erythematosus: An untargeted metabolomics pilot study.

OBJECTIVE: In this pilot study, we used untargeted metabolomics to identify biochemical mechanisms or biomarkers potentially underlying SLE-related fatigue. METHODS: Metabolon conducted untargeted metabolomic plasma profiling using ultrahigh performance liquid chromatography/tandem mass spectrometry on plasma samples of 23 Black females with systemic lupus erythematosus (SLE) and 21 no SLE controls. Fatigue phenotypes of general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation were measured with the reliable and valid Multidimensional Fatigue Inventory (MFI). RESULTS: A total of 290 metabolites were significantly different between the SLE and no SLE groups, encompassing metabolites related to glycolysis, TCA cycle activity, heme catabolism, branched chain amino acids, fatty acid metabolism, and steroids. Within the SLE group, controlling for age and co-morbidities, TCA cycle metabolites of alpha-ketoglutarate (AKG) and succinate were statistically significantly associated (p < .05) with physical and general fatigue. CONCLUSION: While pervasive perturbations in the entire TCA cycle have been implicated as a potential mechanism for fatigue, our results suggest individual metabolites of AKG and succinate may be potential biomarkers or targets of intervention for fatigue symptom management in SLE. Additionally, perturbations in heme metabolism in the SLE group provide additional insights into mechanisms that promote systemic inflammation.

Disparities by race/ethnicity in unplanned cesarean birth among healthy nulliparas: a secondary analysis of the nuMoM2b dataset.

BACKGROUND: Racial disparities exist in maternal morbidity and mortality, with most of these events occurring in healthy pregnant people. A known driver of these outcomes is unplanned cesarean birth. Less understood is to what extent maternal presenting race/ethnicity is associated with unplanned cesarean birth in healthy laboring people, and if there are differences by race/ethnicity in intrapartum decision-making prior to cesarean birth. METHODS: This secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) dataset involved nulliparas with no significant health complications at pregnancy onset who had a trial of labor at ≥ 37 weeks with a singleton, non-anomalous fetus in cephalic presentation (N = 5,095). Logistic regression models were used to examine associations between participant-identified presenting race/ethnicity and unplanned cesarean birth. Participant-identified presenting race/ethnicity was used to capture the influence of racism on participant's healthcare experiences. RESULTS: Unplanned cesarean birth occurred in 19.6% of labors. Rates were significantly higher among Black- (24.1%) and Hispanic- (24.7%) compared to white-presenting participants (17.4%). In adjusted models, white participants had 0.57 (97.5% CI [0.45-0.73], p < 0.001) lower odds of unplanned cesarean birth compared to Black-presenting participants, while Hispanic-presenting had similar odds as Black-presenting people. The primary indication for cesarean birth among Black- and Hispanic- compared to white-presenting people was non-reassuring fetal heart rate in the setting of spontaneous labor onset. CONCLUSIONS: Among healthy nulliparas with a trial of labor, white-presenting compared to Black or Hispanic-presenting race/ethnicity was associated with decreased odds of unplanned cesarean birth, even after adjustment for pertinent clinical factors. Future research and interventions should consider how healthcare providers' perception of maternal race/ethnicity may bias care decisions, leading to increased use of surgical birth in low-risk laboring people and racial disparities in birth outcomes.

Characterizing uterine responsiveness to oxytocin augmentation across four labor patterns in maternal obesity.

BACKGROUND: Optimizing care during labor protraction is a key strategy for reducing cesareans, especially among people with obesity. The pathophysiology of labor dystocia remains poorly understood, limiting precise interventions targeting the cause of protraction. METHODS: In this secondary analysis of nulliparas (n = 92) with obesity (BMI ≥ 30 kg/m2 ) and spontaneous labor onset, we classified labor into four phenotypes based on duration of protraction and birth route: (1) no protraction, (2) short protraction and vaginal birth, (3) extended protraction meeting criteria for labor arrest, but with eventual progression and vaginal birth, and (4) extended protraction meeting criteria for labor arrest and cesarean birth. Across these phenotypes, we compared MVU, oxytocin dose, and novel measures of uterine responsiveness to oxytocin augmentation (MVU to oxytocin dose ratios). RESULTS: In our sample, phenotype group 1 comprised 14.1% (n = 13); group 2 comprised 30.4% (n = 28); group 3 comprised 34.8% (n = 32); and group 4 comprised 20.7% (n = 19). Uterine responsiveness to oxytocin, but not MVU, decreased with each labor phenotype. Participants with cesarean birth had the lowest uterine responsiveness to oxytocin. CONCLUSION: Labor and birth outcomes were associated with measures of uterine responsiveness to oxytocin rather than MVU alone, and thus these may be more clinically appropriate measures for guiding clinical decision-making. Current criteria for labor arrest are likely too stringent for nulliparas with obesity, many of whom appear to progress to safe vaginal birth after longer labor durations. Differences in uterine responsiveness to oxytocin augmentation across the groups suggests underlying physiologic differences in the labor phenotypes, which should drive future research targeting pathophysiology.

Comparing Cesarean Birth Utilization Between US Hospitals: A Demonstration of the Robson Ten-Group Classification System for Use in Quality Improvement and Benchmarking.

BACKGROUND: The World Health Organization-endorsed Robson Ten-Group Classification System (TGCS) is a standard reporting mechanism for cesarean birth, yet this approach is not widely adopted in the United States. OBJECTIVE: To describe the application and utility of the TGCS to compare hospital-level cesarean births rates, for use in quality improvement and benchmarking. METHODS: We conducted a descriptive, secondary data analysis of the Consortium on Safe Labor dataset using data from 228 438 women's births, from 2002 to 2008, in 12 sites across the United States. We stratified births into 10 mutually exclusive groups and calculated within-group proportions of group size and cesarean birth rates for between-hospital comparisons of cesarean birth, trial of labor after cesarean (TOLAC), and labor induction utilization. RESULTS: There is variation in use of cesarean birth, labor induction, and TOLAC across the 12 sites. CONCLUSION: The TGCS provides a method for between-hospital comparisons, particularly for revealing usage patterns of labor induction, TOLAC, and cesarean birth. Adoption of the TGCS in the United States would provide organizations and quality improvement leaders with an effective benchmarking tool to assist in reducing the use of cesarean birth and increasing the support of TOLAC.

Adaptation of Metabolomics and Microbiomic Research Protocols During the COVID-19 Pandemic.

BACKGROUND: When the COVID-19 pandemic hit in 2020, researchers in the P30 Center for the Study of Symptom Science, Metabolomics, and Multiple Chronic Conditions at Emory University's Nell Hodgson Woodruff School of Nursing faced major challenges in recruitment and data collection because of limited access to the clinic and community facilities and the risk of COVID-19 exposure associated with in-person study contact. OBJECTIVES: The purpose of this article is to (a) describe how a cadre of pilot/supplement principal investigators adapted their studies to allow for safe and trustworthy data collection during the COVID-19 pandemic (March 2020 through date of publication) and (b) discuss steps that facilitated the technical aspects of remote data collection, especially involving biological specimens. RESULTS: Four pilot studies and two administrative supplements within the center-all at different stages of execution-adopted various alternative remote recruitment, enrollment, and data and specimen collection approaches to continue their research endeavors in a way that maximized the safety of both the research participants and the research teams. DISCUSSION: The article concludes with a discussion on the importance of a participant-centered approach when using remote methods, actions, or steps initiated to facilitate the technical aspects of remote data collection and reflections on the continued use of remote research strategies beyond the COVID-19 pandemic.

Induction of labor or expectant management? Birth outcomes for nulliparous individuals choosing midwifery care.

BACKGROUND: Induction of labor (IOL) has been studied as a strategy to reduce rates of cesarean birth (CB). Midwifery care models are also associated with lower CB rates, even considering that midwives perform fewer IOLs. In this study, we examined childbirth outcomes among individuals undergoing IOL in certified nurse-midwifery (CNM) care as compared to two categories of expectant management (EM). METHODS: Data were from two CNM practices in the United States (2007-2018). The sample was limited to term nulliparous, nondiabetic, singleton, vertex pregnancies. Individuals having an IOL in each week of gestation (37th, 38th, etc) were compared with those having EM. Two methods for defining EM were considered as each method when used alone limits interpretation. Inclusive EM included all births starting in the same week as IOL. The exclusive EM group was comprised of all births occurring in the next gestational age week relative to the IOL cases (ie, 39th week IOL versus all births occurring at 40 weeks or later). Adjusted regression models were used to examine differences in CB by IOL versus EM (inclusive or exclusive) at each week of gestation. RESULTS: Among 4057 CNM-attended pregnancies, the overall rate of IOL was 28.9% (95% CI 27.5%-30.3%) and CB was 19.4% (95% CI 18.1%-20.6%). Most IOLs involved obstetric indications. CB rates did not differ by IOL versus inclusive EM when performed between 37 and 40 weeks, though post hoc power calculations indicate these comparisons were low-powered. In multivarable models, IOL in the 40th week was associated with lower odds for CB versus exclusive EM definition (ie, births occurring at 41 0/7 weeks or later, OR (95% CI) = 0.57 (0.36-0.90)). This finding is explained by the large increase in CB rates after IOL during the 41st week (34.3%, up from 21.9% in the 40th week). Furthermore, the adjusted odds for CB in the 41st week were 55% higher relative to inclusive EM (all labors 41st week and later), OR (95% CI) = 1.55(1.11-2.15). Neonatal outcomes (aside from macrosomia) did not differ by IOL/EM at any gestational age. DISCUSSION: Outcomes for nulliparous individuals having IOL or EM in the context of a midwifery model of care include low overall use of CB and low frequency of IOL before 41 weeks. In this model, IOL in the 40th week may lower CB odds, especially in comparison to those who do not have spontaneous labor and later undergo an IOL in the 41st week.

Challenges in the Triage Care of Low-Risk Laboring Patients: A Comparison of 2 Models of Practice.

Triage and the timing of admission of low-risk pregnant women can affect the use of augmentation, epidural, and cesarean. The purpose of this analysis was to explore these outcomes in a community hospital by the type of provider staffing triage. This was a retrospective cohort study of low-risk nulliparous women with a term, vertex fetus laboring in a community hospital. Bivariate and multivariable statistics evaluated associations between triage provider type and labor and birth outcomes. Patients in this sample (N = 335) were predominantly White (89.5%), with private insurance (77.0%), and married (71.0%) with no significant differences in these characteristics by triage provider type. Patients admitted by midwives had lower odds of oxytocin augmentation (adjusted odds ratio [aOR] = 0.50, 95% confidence interval [CI] = 0.29-0.87), epidural (aOR = 0.29, 95% CI = 0.12-0.69), and cesarean birth (aOR = 0.308, 95% CI = 0.14-0.67), compared with those triaged by physicians after controlling for patient characteristics and triage timing. This study provides additional context to midwives as labor triage providers for healthy, low-risk pregnant individuals; however, challenges persisted with measurement. More research is needed on the specific components of care during labor that support low-risk patients to avoid medical interventions and poor outcomes.

Outcomes of trial of labor after cesarean birth by provider type in low-risk women.

BACKGROUND: One approach to decreasing the cesarean birth rate in the United States is to increase the availability of birth attendants, including certified nurse-midwives (CNMs), who offer trial of labor after cesarean (TOLAC). We examined associations between provider type and mode of birth for women attempting vaginal birth after cesarean (VBAC). METHODS: We performed a retrospective cohort study at a United States academic medical center using prospectively-collected data (2005-2012). We included healthy women with term singleton vertex pregnancies after one or two prior cesareans who were managed by obstetricians or CNMs. We assessed unplanned cesarean birth by provider type using univariate and logistic regression and examined labor interventions and predicted VBAC success. RESULTS: Overall VBAC success was 88% for 502 included patients. Unplanned cesarean rates were similar by provider type. Black race, no prior VBAC, recurring clinical indication for cesarean, labor augmentation/induction, and any Pitocin use were associated with increased unplanned cesarean. Higher parity and early-term gestational age at delivery were associated with decreased unplanned cesarean. Postpartum hemorrhage and composite maternal morbidity were increased with unplanned cesarean, but there was no difference in neonatal outcome by mode of delivery or provider type. Obstetricians had slightly higher composite adverse maternal outcomes. Nomogram-predicted VBAC success but not provider type was associated with unplanned cesarean. CONCLUSIONS: Unplanned cesarean was similar for patients attempting labor after cesarean managed by midwives or obstetricians. Increasing the number of CNMs who manage TOLAC may help decrease the high rate of cesareans.

The association between longer durations of the latent phase of labor and subsequent perinatal processes and outcomes among midwifery patients.

BACKGROUND/OBJECTIVE: To evaluate the association between the duration of the latent phase of labor and subsequent processes and outcomes. METHODS: Secondary analysis of prospectively collected data among 1,189 women with low-risk pregnancies and spontaneous labor. RESULTS: Longer latent phase duration was associated with labor dystocia (eg, nulliparous ≥ mean [compared with < mean] aOR 3.95 [2.70-5.79]; multiparous ≥ mean [compared with < mean] aOR 5.45 [3.43-8.65]), interventions to ameliorate dystocia, and epidurals to cope or rest (eg, oxytocin augmentation: nulliparous > 80th% [compared with < 80th%] aOR 6.39 [4.04-10.12]; multiparous ≥ 80th% [compared with < 80th%] aOR 6.35 [3.79-10.64]). Longer latent phase duration was also associated with longer active phase and second stage. There were no associations between latent phase duration and risk for cesarean delivery or postpartum hemorrhage in a practice setting with relatively low rates of primary cesarean. Newborns born to multiparous women with latent phase of labor durations at and beyond the 80th% were more frequently admitted to the NICU (≥80th% [compared with < 80th%] aOR 2.7 [1.22-5.84]); however, two-thirds of these NICU admissions were likely for observation only. CONCLUSIONS: Longer duration of the spontaneous latent phase of labor among women with low-risk pregnancies may signal longer total labor processes, leading to an increase in diagnosis of dystocia, interventions to manage dystocia, and epidural use. Apart from multiparous neonatal NICU admission, no other maternal or child morbidity outcomes were elevated with longer duration of the latent phase of labor.

Midwifery presence in United States medical centers and labor care and birth outcomes among low-risk nulliparous women: A Consortium on Safe Labor study.

BACKGROUND: The presence of midwives in a health system may affect perinatal outcomes but has been inadequately described in United States settings. Our objective was to compare labor processes and outcomes for low-risk nulliparous women birthing in United States medical centers with interprofessional care (midwives and physicians) versus noninterprofessional care (physicians only). METHODS: We conducted a retrospective cohort study using Consortium on Safe Labor data from low-risk nulliparous women who birthed in interprofessional (n = 7393) or noninterprofessional centers (n = 6982). Unadjusted, adjusted (age, race, health insurance type), propensity-adjusted, and propensity-matched logistic regression models were used to compare outcomes. RESULTS: There was concordance across logistic regression models, the most restrictive and conservative of which were propensity-matched models. With this approach, women at interprofessional medical centers, compared with women at noninterprofessional centers, were 74% less likely to undergo labor induction (risk ratio [RR] 0.26; 95% CI 0.24-0.29) and 75% less likely to have oxytocin augmentation (RR 0.25; 95% CI 0.22-0.29). The cesarean birth rate was 12% lower at interprofessional centers (RR 0.88; 95% CI 0.79-0.98). Adverse neonatal outcomes occurred in only 0.3% of births and were thus too rare to be modeled. CONCLUSIONS: The care processes and birth outcomes at interprofessional and noninterprofessional medical centers differed significantly. Nulliparous women receiving care at interprofessional centers were less likely to experience induction, oxytocin augmentation, and cesarean than women at noninterprofessional centers. Labor care and birth outcome differences between interprofessional and noninterprofessional centers may be the result of the presence of midwives and interprofessional collaboration, organizational culture, or both.

Influence of midwifery presence in United States centers on labor care and outcomes of low-risk parous women: A Consortium on Safe Labor study.

BACKGROUND: Sixty percent of United States births are to multiparous women. Hospital-level policies and culture may influence intrapartum care and birth outcomes for this large population, yet have been poorly explored using a large, diverse sample. We sought to use national United States data to analyze the association between midwifery presence in maternity care teams and the birth processes and outcomes of low-risk parous women. METHODS: We conducted a retrospective cohort study using Consortium on Safe Labor data from low-risk parous women in either interprofessional care (n = 12 125) or noninterprofessional care centers (n = 8996). Unadjusted, adjusted (age, race, health insurance type), propensity-adjusted, and propensity-matched logistic regression models were used to assess processes and outcomes. RESULTS: There was concordance in outcome differences across regression models. With propensity score matching, women at interprofessional centers, compared with women at noninterprofessional centers, were 85% less likely to have labor induced (risk ratio [RR] 0.15; 95% CI 0.14-0.17). The risk for primary cesarean birth among low-risk parous women was 36% lower at interprofessional centers (RR 0.64; 95% CI 00.52-0.79), whereas the likelihood of vaginal birth after cesarean for this population was 31% higher (RR 1.31; 95% CI 1.10-1.56). There were no significant differences in neonatal outcomes. CONCLUSIONS: Parous women have significantly higher rates of vaginal birth, including vaginal birth after cesarean, and lower likelihood of labor induction when cared for in centers with midwives. Our findings are consistent with smaller analyses of midwifery practice and support integrated, team-based models of perinatal care to improve maternal outcomes.

Association between provider type and cesarean birth in healthy nulliparous laboring women: A retrospective cohort study.

BACKGROUND: Term nulliparous women have the greatest variation across hospitals and providers in cesarean rates and therefore present an opportunity to improve quality through optimal care. We evaluated associations between provider type and mode of birth, including examination of intrapartum management in healthy, laboring nulliparous women. METHODS: Retrospective cohort study using prospectively collected perinatal data from a United States academic medical center (2005-2012). The sample included healthy nulliparous women with spontaneous labor onset and term, singleton, vertex fetus managed by either obstetricians or certified nurse-midwives. Univariate and multivariate logistic regression was used to compare labor interventions and mode of birth by provider type. RESULTS: A total of 1339 women received care by an obstetrician (n = 749) or nurse-midwife (n = 590). The cesarean rate was 13.4% (179/1339). Adjusting for maternal and pregnancy characteristics, care by obstetricians was associated with an increased risk of unplanned cesarean birth (adjusted odds ratio [aOR] 1.48 [95% confidence interval {CI} 1.04-2.12]) compared with care by midwives. Obstetricians more frequently used oxytocin augmentation (aOR 1.41 [95% CI 1.10-1.80]), neuraxial anesthesia (aOR 1.69 [95% CI 1.29-2.23]), and operative vaginal delivery with forceps or vacuum (aOR 2.79 [95% CI 1.75-4.44]). Adverse maternal or neonatal outcomes were not different by provider type across all modes of birth, but were more frequent in women with cesarean than vaginal births. DISCUSSION: In low-risk nulliparous laboring women, care by obstetricians compared with nurse-midwives was associated with increased risk of labor interventions and operative birth. Changes in labor management or increased use of nurse-midwives could decrease the rate of a first cesarean in low-risk laboring women.

Applying a physiologic partograph to Consortium on Safe Labor data to identify opportunities for safely decreasing cesarean births among nulliparous women.

BACKGROUND: The timing of hospital admission for women with spontaneous labor onset and the criteria used to assess active labor progress and diagnose labor dystocia may significantly influence women's risk for primary cesarean birth. Our aims were to assess associations of labor status at admission (i.e., preactive or active) and active labor progress (i.e., dystocic or physiologic) with oxytocin augmentation, cesarean birth, and adverse neonatal outcome rates. METHODS: A sample of low-risk, nulliparous women admitted to hospitals for spontaneous labor onset was extracted from the Consortium on Safe Labor (n = 27 077). Binomial logistic regression was used to assess associations between labor classifications and outcomes. RESULTS: At admission, 68.0% of women were in preactive labor and 32.0% were in active labor. Cesarean rates for these groups were 18.0% and 7.2%, respectively (adjusted odds ratio [AOR] 2.69; 95% CI 2.45-2.96). Oxytocin augmentation and adverse neonatal outcomes were more likely for women admitted in preactive labor. Among women admitted in active labor, 9.3% experienced labor dystocia and 90.7% progressed physiologically. Cesarean rates for these groups were 20.4% and 5.9%, respectively (AOR 3.02; 95% CI 2.45-3.73). Nearly half of the cesareans performed for dystocia among women admitted in active labor occurred when cervical dilation was physiologic. Oxytocin augmentation and adverse neonatal outcomes were more likely when active labor was dystocic. CONCLUSIONS: Adoption of evidence-based, standardized approaches for diagnosing active labor onset, assessing labor progress, and diagnosing dystocia may safely decrease oxytocin augmentation and cesarean birth rates in the United States.

Regulation of dendrite growth and maintenance by exocytosis.

Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop-exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments.

Parturition dysfunction in obesity: time to target the pathobiology.

Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents.

Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic blocks is necessary to rationally target them. Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. BH3 profiling identifies cells that require BCL-2 for survival and predicts sensitivity to the BCL-2 antagonist ABT-737. BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin.

A concept analysis of watchful waiting among providers caring for women in labour.

AIM: This paper is a report of an analysis of the concept of watchful waiting. BACKGROUND: Little is known about differences between the intrapartum care processes of midwives and physicians. In this time of growing rates of surgical birth outcomes, intrapartum care processes are a key area for research and improvement. Watchful waiting is a common care plan used by both midwives and physicians that involves the timing of interventions in labour. DESIGN: Rodgers' Evolutionary Model was used to conduct a concept analysis of the term watchful waiting. DATA SOURCES: Scientific literature authored by, and about, midwives and physicians, as located via an intrapartum-focused database search inclusive of years 1922-May 2012. Thirty English-language articles from nine different countries were located, representing the midwifery and physician scientific literature focusing on watchful waiting in labour and provider decision-making processes. REVIEW METHOD: Attributes, consequences, antecedents and affecting themes were identified through a thematic analysis of the identified articles. RESULTS: Data analysis reveals that many midwives and physicians define watchful waiting differently, based on their philosophies of care. CONCLUSION: The care of women in labour is complicated as a result of different understandings by some providers of common processes of intrapartum care.

Sparse codes for speech predict spectrotemporal receptive fields in the inferior colliculus.

We have developed a sparse mathematical representation of speech that minimizes the number of active model neurons needed to represent typical speech sounds. The model learns several well-known acoustic features of speech such as harmonic stacks, formants, onsets and terminations, but we also find more exotic structures in the spectrogram representation of sound such as localized checkerboard patterns and frequency-modulated excitatory subregions flanked by suppressive sidebands. Moreover, several of these novel features resemble neuronal receptive fields reported in the Inferior Colliculus (IC), as well as auditory thalamus and cortex, and our model neurons exhibit the same tradeoff in spectrotemporal resolution as has been observed in IC. To our knowledge, this is the first demonstration that receptive fields of neurons in the ascending mammalian auditory pathway beyond the auditory nerve can be predicted based on coding principles and the statistical properties of recorded sounds.

Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker.

Anti-apoptotic Bcl-2 family proteins are important oncology therapeutic targets. To date, BH3 mimetics that abrogate anti-apoptotic activity have largely been directed at Bcl-2 and/or Bcl-xL. One observed mechanism of resistance to these inhibitors is increased Mcl-1 levels in cells exposed to such therapeutics. For this reason, and because Mcl-1 is important in the onset of lymphoid, myeloid, and other cancers, it has become a target of great interest. However, small molecule inhibitors displaying potency and selectivity for Mcl-1 are lacking. Identifying such compounds has been challenging due to difficulties in translating the target selectivity observed at the biochemical level to the cellular level. Herein we report the results of an HTS strategy coupled with directed hit optimization. Compounds identified have selective Mcl-1 inhibitory activity with greater than 100-fold reduced affinity for Bcl-xL. The selectivity of these compounds at the cellular level was validated using BH3 profiling, a novel personalized diagnostic approach. This assay provides an important functional biomarker that allows for the characterization of cells based upon their dependencies on various anti-apoptotic Bcl-2 proteins. We demonstrate that cells dependent on Mcl-1 or Bcl-2/Bcl-xL for survival are commensurately responsive to compounds that genuinely target those proteins. The identification of compound 9 with uniquely validated and selective Mcl-1 inhibitory activity provides a valuable tool to those studying the intrinsic apoptosis pathway and highlights an important approach in the development of a first-in-class cancer therapeutic.

The Relationship Between Uterine Activity, Oxytocin Dosing, Labor Progress, and Mode of Birth in Nulliparas with Obesity: Minimal Usefulness of Montevideo Unit Measurement.

BACKGROUND: Maternal obesity and cesarean birth disproportionately affect Black parturients; thus, prevention of cesarean birth is a key modifiable factor to improve pregnancy outcomes and reduce disparities. The primary driver of unplanned cesarean birth among people with higher body mass index is prolonged labor duration. However, strategies to optimize outcomes in these situations have not been established. We aimed to evaluate the influence of oxytocin augmentation on uterine activity and labor progression in nulliparas with obesity. METHODS: This secondary analysis involved nulliparas with obesity (BMI ≥30 kg/m2) who had spontaneous labor onset followed by oxytocin augmentation and an intrauterine pressure catheter. Using Linear Mixed Models, we evaluated relationships between uterine activity measured in Montevideo units (MVU), oxytocin dose, and rate of cervical dilation normalized by labor duration. RESULTS: In this diverse sample (35.6% Caucasian, 16.11% African American, 40.2% Hispanic) of nulliparas with obesity (n = 87; BMI 35.54 ± 4.38 kg/m2), 31% ended labor with cesarean birth. Among those with vaginal birth, only 13% had MVU ≥200 prior to the final 2 hours of labor. MVUs were only minimally responsive to oxytocin dose and were not associated with labor progression nor birth route. CONCLUSION: MVU measurements may not be useful to diagnose labor arrest in nulliparas with obesity. Optimizing care for birthing people with obesity is essential for improving perinatal outcomes and for reducing racial health disparities.