Maternal hybrid immunity and risk of infant COVID-19 hospitalizations: national case-control study in Israel.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy.

Fetal Inguinal Hernia: Case Report and Review of the Literature.

Fetal inguinal hernia (FIH) is a rare event and only few cases were published in the medical literature. In the present study, we aimed to characterize the sonographic features, clinical presentation, management, outcomes, and differential diagnoses of FIH. Accordingly, we reviewed all 17 cases of FIH published in the medical literature, including one new case evaluated by our group. All 17 cases (100%) were male, and FIH is presented as a scrotal mass with a mean diameter of 38 ± 9.5 mm. The right side was dominant (62%). Peristalsis was reported in 80% of the cases, and blood flow was reported in two-thirds. Most cases were diagnosed in the third trimester (88%) at a mean gestational age (GA) of 33.1 ± 5.2 weeks. 60% of the cases had isolated FIH, and 40% had another sonographic or genetic abnormality. Three cases (18%) were syndromic with multiple malformations: trisomy 18, skeletal anomalies due to Jarcho-Levin syndrome, and undefined multiple joint contractures. Two cases (12%) had copathologies in the gastrointestinal tract: one had an echogenic bowel due to homozygosity for cystic fibrosis, and the other had low anorectal malformation. Bowel loop dilatation was observed prenatally in both cases and in another one isolated case (18%). GA at delivery was 38 ± 1.8 weeks, and the median time between diagnosis and delivery was 3 weeks. All three cases of neonatal death occurred in syndromic fetuses. All patients with nonsyndromic inguinal hernias underwent definitive surgical repair at a median of 13 days postpartum. No signs of strangulation and only one case of edematous bowel without necrosis have been reported. In conclusion, FIH should be suspected in male fetuses when an intrascrotal mass with peristalsis is diagnosed during the third trimester. Close follow-up until term in the absence of signs of bowel obstruction is reasonable, and in isolated FIH, the prognosis is favorable.

Expert review: preeclampsia Type I and Type II.

Pregnancy involves an interplay between maternal and fetal factors affecting changes to maternal anatomy and physiology to support the developing fetus and ensure the well-being of both the mother and offspring. A century of research has provided evidence of the imperative role of the placenta in the development of preeclampsia. Recently, a growing body of evidence has supported the adaptations of the maternal cardiovascular system during normal pregnancy and its maladaptation in preeclampsia. Debate surrounds the roles of the placenta vs the maternal cardiovascular system in the pathophysiology of preeclampsia. We proposed an integrated model of the maternal cardiac-placental-fetal array and the development of preeclampsia, which reconciles the disease phenotypes and their proposed origins, whether placenta-dominant or maternal cardiovascular system-dominant. These phenotypes are sufficiently diverse to define 2 distinct types: preeclampsia Type I and Type II. Type I preeclampsia may present earlier, characterized by placental dysfunction or malperfusion, shallow trophoblast invasion, inadequate spiral artery conversion, profound syncytiotrophoblast stress, elevated soluble fms-like tyrosine kinase-1 levels, reduced placental growth factor levels, high peripheral vascular resistance, and low cardiac output. Type I is more often accompanied by fetal growth restriction, and low placental growth factor levels have a measurable impact on maternal cardiac remodeling and function. Type II preeclampsia typically occurs in the later stages of pregnancy and entails an evolving maternal cardiovascular intolerance to the demands of pregnancy, with a moderately dysfunctional placenta and inadequate blood supply. The soluble fms-like tyrosine kinase-1-placental growth factor ratio may be normal or slightly disturbed, peripheral vascular resistance is low, and cardiac output is high, but these adaptations still fail to meet demand. Emergent placental dysfunction, coupled with an increasing inability to meet demand, more often appears with fetal macrosomia, multiple pregnancies, or prolonged pregnancy. Support for the notion of 2 types of preeclampsia observable on the molecular level is provided by single-cell transcriptomic survey of gene expression patterns across different cell classes. This revealed widespread dysregulation of gene expression across all cell types, and significant imbalance in fms-like tyrosine kinase-1 (FLT1) and placental growth factor, particularly marked in the syncytium of early preeclampsia cases. Classification of preeclampsia into Type I and Type II can inform future research to develop targeted screening, prevention, and treatment approaches.

Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

Boosting maternal and neonatal anti-SARS-CoV-2 humoral immunity using a third mRNA vaccine dose.

BACKGROUND: To minimize COVID-19 pandemic burden and spread, 3-dose vaccination campaigns commenced worldwide. Since patients who are pregnant are at increased risk for severe disease, they were recently included in that policy, despite the lack of available evidence regarding the impact of a third boosting dose during pregnancy, underscoring the urgent need for relevant data. We aimed to characterize the effect of the third boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy. METHODS: We performed a prospective cohort study of anti-SARS-CoV-2 antibody titers (n = 213) upon delivery in maternal and cord blood of naive fully vaccinated parturients who received a third dose (n = 86) as compared with 2-dose recipients (n = 127). RESULTS: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery, when comparing pregnancies in which the mother received a third boosting dose with 2-dose recipients. The effect of the third boosting dose remained significant when controlling for the trimester of last exposure, suggesting additive immunity extends beyond that obtained after the second dose. Milder side effects were reported following the third dose, as compared with the second vaccine dose, among the fully vaccinated group. CONCLUSION: The third boosting dose of mRNA Pfizer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among patients who are pregnant. FUNDING: Israel Science Foundation KillCorona grant 3777/19; Research grant from the "Ofek" Program of the Hadassah Medical Center.

Partogram of Grandmultiparous Parturients: A Multicenter Cohort Study.

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2-5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs' and MPs' cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs' uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients.

Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses' vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83-96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26-99%), and 48% (95% CI 37-57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.

Norethisterone Reduces Vaginal Bleeding Caused by Progesterone-Only Birth Control Pills.

(1) Background: Progesterone-only pills (POP) are widely used contraceptives. About 40% of women taking these pills report vaginal bleeding/spotting; 25% find this a reason for cessation. To date, no effective remedy has been described. We aimed to examine the therapeutic approaches offered by health providers. (2) Methods: A prospective questionnaire-based study of women experiencing vaginal bleeding due to POP, comparing the effectiveness of prescribed therapies. Women were recruited through social networks, and subsequently divided into groups according to the treatment offered: (1) POP with norethisterone (n = 36); (2) double dose POP (n = 19); (3) single dose POP (continuing initial treatment, n = 57); and (4) different POP formula (n = 8). Women rated bleeding quantity and frequency at four intervals, at weeks 0, 2, 4, and 6. (3) Results: Women who added 5 mg norethisterone acetate reported a significant decrease in bleeding frequency compared to the other groups, observed after 2, 4, and 6 weeks (p-values 0.019, 0.002, and 0.002, respectively). Women also reported an overall decrease in combined bleeding quantity and frequency (p-values 0.028, 0.003, and 0.005, respectively). There was no difference in the rate of side effects among groups. (4) Conclusions: Adding 5 mg norethisterone acetate (Primolut-nor) to progesterone-only pills significantly reduces bleeding and spotting associated with POP contraception.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Formation and function of dauer ascarosides in the nematodes Caenorhabditis briggsae and Caenorhabditis elegans.

The biosynthetic pathways and functions of ascaroside signaling molecules in the nematode Caenorhabditis elegans have been studied to better understand complex, integrative developmental decision-making. Although it is known that ascarosides play multiple roles in the development and behavior of nematode species other than C. elegans, these parallel pheromone systems have not been well-studied. Here, we show that ascarosides in the nematode Caenorhabditis briggsae are biosynthesized in the same manner as C. elegans and act to induce the alternative developmental pathway that generates the stress-resistant dauer lifestage. We show that ascr#2 is the primary component of crude dauer pheromone in C. briggsae; in contrast, C. elegans dauer pheromone relies on a combination of ascr#2, ascr#3, and several other components. We further demonstrate that Cbr-daf-22, like its C. elegans ortholog Cel-daf-22, is necessary to produce short-chain ascarosides. Moreover, Cbr-daf-22 and Cel-daf-22 mutants produce an ascaroside-independent metabolite that acts antagonistically to crude dauer pheromone and inhibits dauer formation.

Prediction of neonatal subgaleal hemorrhage using first stage of labor data: A machine-learning based model.

BACKGROUND: Subgaleal hemorrhage (SGH) is a rare neonatal condition, mainly associated with instrumental delivery, mainly vacuum extractor (VE). The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for Subgaleal hemorrhage (SGH) following vacuum extraction (VE), based on maternal and fetal variables collected during the first stage of labor. MATERIALS AND METHODS: A retrospective cohort study on data from a university affiliated hospital, recorded between January 2013 and February 2017. Balanced random forest algorithm was used to develop a machine learning model to predict personalized risk of the neonate developing SGH, in the eventuality that vacuum extraction was used during delivery. RESULTS: During the study period, 35,552 term, singleton spontaneous or induced trials of labor deliveries were included in this study. Neonatal SGH following vacuum extraction (SGH-VE) occurred in 109 cases (0.3%). Two machine learning models were developed: a proof of concept model (model A), based on a cohort limited to the (n=2955) instances of vacuum extraction, and the clinical support model (model B), based on all spontaneous or induced trials of labor (n=35,552). The models stratified parturients into high- and low-risk groups for development of SGH-VE. Model A showed a 2-fold increase in the high-risk group of parturients compared to the low risk group (OR=2.76, CI 95% 1.85-4.11). In model B, a 4-fold increase in the odds of SGH was observed in the high-risk group of parturients compared to the low risk group (OR=4.2, CI 2.2-8.1), while identifying 90.8% (99/109) of the SGH cases. CONCLUSIONS: Our machine learning-based model stratified births to high or low risk for SGH, making it an applicable tool for personalized decision-making during labor regarding the application of VE. This model may contribute to improved neonatal outcomes.

A conserved behavioral role for a nematode interneuron neuropeptide receptor.

Neuropeptides are evolutionarily conserved modulators of many aspects of animal behavior and physiology, and expand the repertoire of processes that can be controlled by a limited number of neurons. Deciphering the neuropeptidergic codes that govern distinct processes requires systematic functional analyses of neuropeptides and their cognate receptors. Even in well-studied model organisms like Caenorhabditis elegans, however, such efforts have been precluded by a lack of mutant reagents. Here, we generated and screened 21 C. elegans neuropeptide G-protein coupled receptor mutants with no pre-existing reagents for the touch-evoked escape response, and implicated six receptors expressed in diverse neuron classes representing multiple circuit levels in this behavior. We further characterized the mutant with the most severe phenotype, frpr-14, which was defective in multiple behavioral paradigms. We leveraged this range of phenotypes to reveal that FRPR-14 modulation of different precommand interneuron classes, AVH and AIB, can drive distinct behavioral subsets, demonstrating cellular context-dependent roles for FRPR-14 signaling. We then show that Caenorhabditis briggsae CBR-FRPR-14 modulates an AVH-like interneuron pair to regulate the same behaviors as C. elegans but to a smaller extent. Our results also suggest that differences in touch-evoked escape circuit architecture between closely related species results from changes in neuropeptide receptor expression pattern, as opposed to ligand-receptor pairing. This study provides insights into the principles utilized by a compact, multiplexed nervous system to generate intraspecific behavioral complexity and interspecific variation.

An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascular-placental-fetal array.

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia.

The Relation between Head Circumference and Mid-Pelvic Circumference: A Simple Index for Cephalopelvic Disproportion Evaluation.

INTRODUCTION: Cephalopelvic disproportion (CPD) is one of the most common obstetric complications. Since CPD is the disproportion between the fetal head and maternal bony pelvis, evaluation of the head circumference (HC) relative to the maternal bony pelvis may be a useful adjunct to pre-labor CPD evaluation. The aim of the present study was a proof-of-concept evaluation of the ratio between HC and pelvic circumference (PC) as a predictor of CPD. METHODS: Of 11,822 deliveries, 104 cases that underwent an abdominopelvic CT for any medical indication and who underwent normal vaginal deliveries (NVDs) (n = 84) or cesarean deliveries (CD) due to CPD (n = 20) were included retrospectively. Maternal pelvis dimensions were reconstructed and neonatal HC, as a proxy for fetal HC, was measured. The correlation between cases of CPD and cephalopelvic circumference index (CPCI), which represents the ratio between the HC and PC in percentage (HC/PC × 100), was evaluated. RESULTS: The mid-pelvis CPCI (MP-CPCI) was larger in CD groups as compared to the NVD group: 103 ± 11 versus 97 ± 8%, respectively (p = 0.0003). In logistic regression analysis, the MP-CPCI was found to be independently associated with CD due to CPD: each 1% increase in MP-CPCI increased the likelihood of CD for CPD by 11% (adjusted odds ratio [aOR] 1.11, 95% CI, 1.03-1.19, p = 0.004). The aOR for CD due to CPD increased incrementally as the MP-CPCI increased, from 3.56 (95% CI, 1.01-12.6) at MP-CPCI of 100 to 5.6 (95% CI, 1.63-19.45) at 105, 21.44 (95% CI, 3.05-150.84) at 110, and 28.88 (95% CI, 2.3-362.27) at MP-CPCI of 115. CONCLUSIONS: The MP-CPCI, representing the relative dimensions of the fetal HC and maternal PC, is a simple tool that can potentially distinguish between parturients at lower and higher risk of CPD. Prospective randomized studies are required to evaluate the feasibility of prenatal pelvimetry and MP-CPCI to predict the risk of CPD during labor.

Transporting an Artificial Intelligence Model to Predict Emergency Cesarean Delivery: Overcoming Challenges Posed by Interfacility Variation.

Research using artificial intelligence (AI) in medicine is expected to significantly influence the practice of medicine and the delivery of health care in the near future. However, for successful deployment, the results must be transported across health care facilities. We present a cross-facilities application of an AI model that predicts the need for an emergency caesarean during birth. The transported model showed benefit; however, there can be challenges associated with interfacility variation in reporting practices.

Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival.

The recently discovered modular glucosides (MOGLs) form a large metabolite library derived from combinatorial assembly of moieties from amino acid, neurotransmitter, and lipid metabolism in the model organism C. elegans. Combining CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis, we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible for specific 2-O-acylation of diverse glucose scaffolds with a wide variety of building blocks, resulting in more than 150 different MOGLs. We further show that this biosynthetic role is conserved for the closest homologue of Cel-CEST-1.2 in the related nematode species C. briggsae, Cbr-CEST-2. Expression of Cel-cest-1.2 and MOGL biosynthesis are strongly induced by starvation conditions in C. elegans, one of the premier model systems for mechanisms connecting nutrition and physiology. Cel-cest-1.2-deletion results in early death of adult animals under starvation conditions, providing first insights into the biological functions of MOGLs.

Normal labor curve in twin gestation.

BACKGROUND: Failure to progress is one of the leading indications for cesarean delivery in trials of labor in twin gestations. However, assessment of labor progression in twin labors is managed according to singleton labor curves. OBJECTIVE: This study aimed to establish a partogram for twin deliveries that reflects normal and abnormal labor progression and customized labor curves for different subgroups of twin labors. STUDY DESIGN: This was a multicenter, retrospective cohort analysis of twin deliveries that were recorded in 3 tertiary medical centers between 2003 and 2017. Eligible parturients were those with twin gestations at ≥34 weeks' gestation with cephalic presentation of the presenting twin and ≥2 cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, major fetal anomalies, and fetal demise. The study group comprised twin gestations, whereas singleton gestations comprised the control group. Statistical analysis was performed using Python 3.7.3 and SPSS, version 27. Categorical variables were analyzed using chi-square tests. Student t test and Mann-Whitney U test were applied to analyze the differences in continuous variables, as appropriate. RESULTS: A total of 1375 twin deliveries and 142,659 singleton deliveries met the inclusion criteria. Duration of the active phase of labor was significantly longer in twin labors than in singleton labors in both nulliparous and multiparous parturients; the 95th percentile duration was 2 hours longer in nulliparous twin labors and >3.5 hours longer in multiparous twin labors than in singleton labors. The cervical dilation progression rate was significantly slower in twin deliveries than in singleton deliveries with a mean rate in twin deliveries of 1.89 cm/h (95th percentile, 0.51 cm/h) and a mean rate of 2.48 cm/h (95th percentile, 0.73 cm/h) in singleton deliveries (P<.001). In addition, epidural use further slowed labor progression in twin deliveries. The second stage of labor was also markedly longer in twin deliveries, both in nulliparous and multiparous women (95th percentile, 3.04 vs 2.83 hours, P=.002). CONCLUSION: Twin labors are characterized by a slower progression of the active phase and second stage of labor compared with singleton labors in nulliparous and multiparous parturients. Epidural analgesia further slows labor progression in twin labors. Implementation of these findings in clinical management might lower cesarean delivery rates among cases with protracted labor in twin gestations.

A Mutation of lips-6 in C. elegans.

The lips-6 gene encodes a putative lipase that plays a role in adult starvation response through a pathway that is parallel to the dauer pathway in larval Caenorhabditis elegans worms. We created a mutation of lips-6 to study its effects on lifespan and the ascaroside profile. We found that lips-6 had a wild-type lifespan and a wild-type ascaroside profile. These results suggest that the lips-6 gene plays a minimal role in C. elegans lifespan biology and does not affect the ascaroside profile until it is specifically activated by starvation in adult worms.