Association between Sleep Disordered Breathing and Neonatal Outcomes in Nulliparous Individuals.

OBJECTIVE: Our objective was to determine whether objectively measured sleep-disordered breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals. STUDY DESIGN: Secondary analysis of the nuMom2b sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early (6-15 weeks' gestation) and mid-pregnancy (22-31 weeks' gestation). SDB was defined as an apnea-hypopnea index ≥5 events/h at either time point. The primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age, seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into (1) early pregnancy SDB (6-15 weeks' gestation), (2) new onset mid-pregnancy SDB (22-31 weeks' gestation), and (3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CIs) representing the association. RESULTS: Among 2,106 participants, 3% (n = 75) had early pregnancy SDB and 5.7% (n = 119) developed new-onset mid-pregnancy SDB. The incidence of the primary outcome was higher in the offspring of individuals with early (29.3%) and new onset mid-pregnancy SDB (30.3%) compared with individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, and body mass index, new onset mid-pregnancy SDB conferred increased risk (RR = 1.43, 95% CI: 1.05, 1.94), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome. CONCLUSION: New onset, mid-pregnancy SDB is independently associated with neonatal morbidity. KEY POINTS: · Sleep disordered breathing (SDB) is a common condition impacting pregnancy with known maternal risks.. · Objectively defined SDB in pregnancy was associated with a composite of adverse neonatal outcomes.. · New onset SDB in mid pregnancy conferred statistically significant increased risk..

Cardiac competence of the paraxial head mesoderm fades concomitant with a shift towards the head skeletal muscle programme.

The vertebrate head mesoderm provides the heart, the great vessels, some smooth and most head skeletal muscle, in addition to parts of the skull. It has been speculated that the ability to generate cardiac and smooth muscle is the evolutionary ground-state of the tissue. However, whether indeed the entire head mesoderm has generic cardiac competence, how long this may last, and what happens as cardiac competence fades, is not clear. Bone morphogenetic proteins (Bmps) are known to promote cardiogenesis. Using 41 different marker genes in the chicken embryo, we show that the paraxial head mesoderm that normally does not engage in cardiogenesis has the ability to respond to Bmp for a long time. However, Bmp signals are interpreted differently at different time points. Up to early head fold stages, the paraxial head mesoderm is able to read Bmps as signal to engage in the cardiac programme; the ability to upregulate smooth muscle markers is retained slightly longer. Notably, as cardiac competence fades, Bmp promotes the head skeletal muscle programme instead. The switch from cardiac to skeletal muscle competence is Wnt-independent as Wnt caudalises the head mesoderm and also suppresses Msc-inducing Bmp provided by the prechordal plate, thus suppressing both the cardiac and the head skeletal muscle programmes. Our study for the first time suggests a specific transition state in the embryo when cardiac competence is replaced by skeletal muscle competence. It sets the stage to unravel the cardiac-skeletal muscle antagonism that is known to partially collapse in heart failure.

A review of synthetic and augmented training data for machine learning in ultrasonic non-destructive evaluation.

Ultrasonic Testing (UT) has seen increasing application of machine learning (ML) in recent years, promoting higher-level automation and decision-making in flaw detection and classification. Building a generalized training dataset to apply ML in non-destructive evaluation (NDE), and thus UT, is exceptionally difficult since data on pristine and representative flawed specimens are needed. Yet, in most UT test cases flawed specimen data is inherently rare making data coverage the leading problem when applying ML. Common data augmentation (DA) strategies offer limited solutions as they don't increase the dataset variance, which can lead to overfitting of the training data. The virtual defect method and the recent application of generative adversarial neural networks (GANs) in UT are sophisticated DA methods targeting to solve this problem. On the other hand, well-established research in modeling ultrasonic wave propagations allows for the generation of synthetic UT training data. In this context, we present a first thematic review to summarize the progress of the last decades on synthetic and augmented UT training data in NDE. Additionally, an overview of methods for synthetic UT data generation and augmentation is presented. Among numerical methods such as finite element, finite difference, and elastodynamic finite integration methods, semi-analytical methods such as general point source synthesis, superposition of Gaussian beams, and the pencil method as well as other UT modeling software are presented and discussed. Likewise, existing DA methods for one- and multidimensional UT data, feature space augmentation, and GANs for augmentation are presented and discussed. The paper closes with an in-detail discussion of the advantages and limitations of existing methods for both synthetic UT training data generation and DA of UT data to aid the decision-making of the reader for the application to specific test cases.

The Neuronal Circuit of the Dorsal Circadian Clock Neurons in Drosophila melanogaster.

Drosophila's dorsal clock neurons (DNs) consist of four clusters (DN1as, DN1ps, DN2s, and DN3s) that largely differ in size. While the DN1as and the DN2s encompass only two neurons, the DN1ps consist of ∼15 neurons, and the DN3s comprise ∼40 neurons per brain hemisphere. In comparison to the well-characterized lateral clock neurons (LNs), the neuroanatomy and function of the DNs are still not clear. Over the past decade, numerous studies have addressed their role in the fly's circadian system, leading to several sometimes divergent results. Nonetheless, these studies agreed that the DNs are important to fine-tune activity under light and temperature cycles and play essential roles in linking the output from the LNs to downstream neurons that control sleep and metabolism. Here, we used the Flybow system, specific split-GAL4 lines, trans-Tango, and the recently published fly connectome (called hemibrain) to describe the morphology of the DNs in greater detail, including their synaptic connections to other clock and non-clock neurons. We show that some DN groups are largely heterogenous. While certain DNs are strongly connected with the LNs, others are mainly output neurons that signal to circuits downstream of the clock. Among the latter are mushroom body neurons, central complex neurons, tubercle bulb neurons, neurosecretory cells in the pars intercerebralis, and other still unidentified partners. This heterogeneity of the DNs may explain some of the conflicting results previously found about their functionality. Most importantly, we identify two putative novel communication centers of the clock network: one fiber bundle in the superior lateral protocerebrum running toward the anterior optic tubercle and one fiber hub in the posterior lateral protocerebrum. Both are invaded by several DNs and LNs and might play an instrumental role in the clock network.

Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

Adjustment of Mechanical Properties of Medium Manganese Steel Produced by Laser Powder Bed Fusion with a Subsequent Heat Treatment.

Medium manganese steels can exhibit both high strength and ductility due to transformation-induced plasticity (TRIP), caused by metastable retained austenite, which in turn can be adjusted by intercritical annealing. This study addresses the laser additive processability and mechanical properties of the third-generation advanced high strength steels (AHSS) on the basis of medium manganese steel using Laser Powder Bed Fusion (LPBF). For the investigations, an alloy with a manganese concentration of 5 wt.% was gas atomized and processed by LPBF. Intercritical annealing was subsequently performed at different temperatures (630 and 770 °C) and three annealing times (3, 10 and 60 min) to adjust the stability of the retained austenite. Higher annealing temperatures lead to lower yield strength but an increase in tensile strength due to a stronger work-hardening. The maximum elongation at fracture was approximately in the middle of the examined temperature field. The microstructure and properties of the alloy were further investigated by scanning electron microscopy (SEM), hardness measurements, X-ray diffraction (XRD), electron backscatter diffraction (EBSD) and element mapping.

Anatomical Survey Versus Fetal Echocardiograms for Diagnosis of Cardiac Defects with a Single Umbilical Artery Cases: A Retrospective Cohort Study and Diagnostic Meta-analysis.

OBJECTIVE: To determine the utility of fetal echocardiography in diagnosing cardiac defects in fetuses with a single umbilical artery (SUA). METHODS: A retrospective cohort study of prenatally diagnosed SUA was conducted over a 10-year period at a single institution. Cardiac anatomy on detailed anatomical survey was compared with fetal echocardiogram for fetuses with prenatally diagnosed SUA. A diagnostic meta-analysis of studies comparing fetal anatomical survey to fetal echocardiogram in fetuses with SUA between 2010 to 2019 was also performed. RESULTS: Three hundred and twenty fetuses with SUA were identified, 113 of which had completed both ultrasound and echocardiography. There were 36 cases of cardiac defects on prenatal echocardiogram and all had abnormal anatomical ultrasounds. There were zero cases of abnormal cardiac exams (0%) when the cardiac views on anatomical survey were normal. The sensitivity, specificity, positive predictive value and negative predictive value of ultrasound were 100%, 77%, 73% and 100%, respectively. A summary ROC curve demonstrated a high predictive value of routine anatomic survey for cardiac defects (AUC: 0.99). CONCLUSION: Anatomic survey is highly predictive in the detection of cardiac defects in fetuses with SUA. Fetal echocardiogram is unnecessary in SUA when cardiac views are normal on ultrasound.

A Functional Clock Within the Main Morning and Evening Neurons of D. melanogaster Is Not Sufficient for Wild-Type Locomotor Activity Under Changing Day Length.

A major challenge for all organisms that live in temperate and subpolar regions is to adapt physiology and activity to different photoperiods. A long-standing model assumes that there are morning (M) and evening (E) oscillators with different photoreceptive properties that couple to dawn and dusk, respectively, and by this way adjust activity to the different photoperiods. In the fruit fly Drosophila melanogaster, M and E oscillators have been localized to specific circadian clock neurons in the brain. Here, we investigate under different photoperiods the activity pattern of flies expressing the clock protein PERIOD (PER) only in subsets of M and E oscillators. We found that all fly lines that expressed PER only in subsets of the clock neurons had difficulties to track the morning and evening in a wild-type manner. The lack of the E oscillators advanced M activity under short days, whereas the lack of the M oscillators delayed E activity under the same conditions. In addition, we found that flies expressing PER only in subsets of clock neurons showed higher activity levels at certain times of day or night, suggesting that M and E clock neurons might inhibit activity at specific moments throughout the 24 h. Altogether, we show that the proper interaction between all clock cells is important for adapting the flies' activity to different photoperiods and discuss our findings in the light of the current literature.

Life at High Latitudes Does Not Require Circadian Behavioral Rhythmicity under Constant Darkness.

Nearly all organisms evolved endogenous self-sustained timekeeping mechanisms to track and anticipate cyclic changes in the environment. Circadian clocks, with a periodicity of about 24 h, allow animals to adapt to day-night cycles. Biological clocks are highly adaptive, but strong behavioral rhythms might be a disadvantage for adaptation to weakly rhythmic environments such as polar areas [1, 2]. Several high-latitude species, including Drosophila species, were found to be highly arrhythmic under constant conditions [3-6]. Furthermore, Drosophila species from subarctic regions can extend evening activity until dusk under long days. These traits depend on the clock network neurochemistry, and we previously proposed that high-latitude Drosophila species evolved specific clock adaptations to colonize polar regions [5, 7, 8]. We broadened our analysis to 3 species of the Chymomyza genus, which diverged circa 5 million years before the Drosophila radiation [9] and colonized both low and high latitudes [10, 11]. C. costata, pararufithorax, and procnemis, independently of their latitude of origin, possess the clock neuronal network of low-latitude Drosophila species, and their locomotor activity does not track dusk under long photoperiods. Nevertheless, the high-latitude C. costata becomes arrhythmic under constant darkness (DD), whereas the two low-latitude species remain rhythmic. Different mechanisms are behind the arrhythmicity in DD of C. costata and the high-latitude Drosophila ezoana, suggesting that the ability to maintain behavioral rhythms has been lost more than once during drosophilids' evolution and that it might indeed be an evolutionary adaptation for life at high latitudes.

Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes.

OBJECTIVE: To examine the relationship between prospectively assessed maternal sleep position and subsequent adverse pregnancy outcomes. METHODS: This was a secondary analysis of a prospective observational multicenter cohort study of nulliparous women with singleton gestations who were enrolled between October 2010 and May 2014. Participants had three study visits that were not part of clinical care. They prospectively completed in-depth sleep questionnaires between 6 0/7 and 13 6/7 weeks of gestation and 22 0/7 and 29 6/7 weeks of gestation, the first and third study visits. A subset of women also underwent level 3 home sleep tests using the Embletta Gold device. The primary outcome was a composite of adverse pregnancy outcomes such as stillbirth, a small-for-gestational-age newborn, and gestational hypertensive disorders. RESULTS: A total of 8,706 (of 10,038) women had data from at least one sleep questionnaire and for pregnancy outcomes, and they comprised the population for this analysis. The primary outcome occurred in 1,903 pregnancies (22%). There was no association between reported non-left lateral or supine sleep during the last week of the first visit (adjusted odds ratio [aOR] 1.00 [95% CI 0.89-1.14]) or third visit (aOR 0.99 [95% CI 0.89-1.11] and the composite or any individual outcome, except for an apparent protective effect for stillbirth at the third visit (aOR 0.27 (95% CI 0.09-0.75). Women with objectively measured supine sleep position for at least 50% of the time were no more likely than those in the supine position 50% or less of the time to have the composite adverse outcome. CONCLUSIONS: Going to sleep in the supine or right lateral position, as self-reported before the development of pregnancy outcome and objectively assessed through 30 weeks of gestation, was not associated with an increased risk of stillbirth, a small-for-gestational-age newborn, or gestational hypertensive disorders.

Effect of inoculum density on human-induced pluripotent stem cell expansion in 3D bioreactors.

OBJECTIVE: For optimized expansion of human-induced pluripotent stem cells (hiPSCs) with regards to clinical applications, we investigated the influence of the inoculum density on the expansion procedure in 3D hollow-fibre bioreactors. MATERIALS AND METHODS: Analytical-scale bioreactors with a cell compartment volume of 3 mL or a large-scale bioreactor with a cell compartment volume of 17 mL were used and inoculated with either 10 × 106 or 50 × 106 hiPSCs. Cells were cultured in bioreactors over 15 days; daily measurements of biochemical parameters were performed. At the end of the experiment, the CellTiter-Blue® Assay was used for culture activity evaluation and cell quantification. Also, cell compartment sections were removed for gene expression and immunohistochemistry analysis. RESULTS: The results revealed significantly higher values for cell metabolism, cell activity and cell yields when using the higher inoculation number, but also a more distinct differentiation. As large inoculation numbers require cost and time-extensive pre-expansion, low inoculation numbers may be used preferably for long-term expansion of hiPSCs. Expansion of hiPSCs in the large-scale bioreactor led to a successful production of 5.4 × 109 hiPSCs, thereby achieving sufficient cell amounts for clinical applications. CONCLUSIONS: In conclusion, the results show a significant effect of the inoculum density on cell expansion, differentiation and production of hiPSCs, emphasizing the importance of the inoculum density for downstream applications of hiPSCs. Furthermore, the bioreactor technology was successfully applied for controlled and scalable production of hiPSCs for clinical use.

Online measurement of oxygen enables continuous noninvasive evaluation of human-induced pluripotent stem cell (hiPSC) culture in a perfused 3D hollow-fiber bioreactor.

For clinical and/or pharmaceutical use of human-induced pluripotent stem cells (hiPSCs), large cell quantities of high quality are demanded. Therefore, we combined the expansion of hiPSCs in closed, perfusion-based 3D bioreactors with noninvasive online monitoring of oxygen as culture control mechanism. Bioreactors with a cell compartment volume of 3 or 17 ml were inoculated with either 10 × 106 or 50 × 106 cells, and cells were expanded over 15 days with online oxygen and offline glucose and lactate measurements being performed. The CellTiter-Blue® Assay was performed at the end of the bioreactor experiments for indirect cell quantification. Model simulations enabled an estimation of cell numbers based on kinetic equations and experimental data during the 15-day bioreactor cultures. Calculated oxygen uptake rates (OUR), glucose consumption rates (GCR), and lactate production rates (LPR) revealed a highly significant correlation (p < 0.0001). Oxygen consumption, which was measured at the beginning and the end of the experiment, showed a strong culture growth in line with the OUR and GCR data. Furthermore, the yield coefficient of lactate from glucose and the OUR to GCR ratio revealed a shift from nonoxidative to oxidative metabolism. The presented results indicate that oxygen is equally as applicable as parameter for hiPSC expansion as glucose while providing an accurate real-time impression of hiPSC culture development. Additionally, oxygen measurements inform about the metabolic state of the cells. Thus, the use of oxygen online monitoring for culture control facilitates the translation of hiPSC use to the clinical setting.

To roll the eyes and snap a bite - function, development and evolution of craniofacial muscles.

Craniofacial muscles, muscles that move the eyes, control facial expression and allow food uptake and speech, have long been regarded as a variation on the general body muscle scheme. However, evidence has accumulated that the function of head muscles, their developmental anatomy and the underlying regulatory cascades are distinct. This article reviews the key aspects of craniofacial muscle and muscle stem cell formation and discusses how this differs from the trunk programme of myogenesis; we show novel RNAseq data to support this notion. We also trace the origin of head muscle in the chordate ancestors of vertebrates and discuss links with smooth-type muscle in the primitive chordate pharynx. We look out as to how the special properties of head muscle precursor and stem cells, in particular their competence to contribute to the heart, could be exploited in regenerative medicine.

Evaluation of the mass transfer rate using computer simulation in a three-dimensional interwoven hollow fiber-type bioartificial liver.

OBJECTIVES: To determine the most efficient design of a hollow fiber-based bioreactor device for a bioartificial liver support system through comparative bioengineering evaluations. RESULTS: We compared two types of hollow fiber-based bioreactors, the interwoven-type bioreactor (IWBAL) and the dialyzer-type bioreactor (DBAL), by evaluating the overall mass transfer coefficient (K) and the convective coefficient (X). The creatinine and albumin mass transfer coefficients and convective coefficients were calculated using our mathematical model based on the homoporous theory and the modified Powell method. Additionally, using our model, we simulated the mass transport efficiency in clinical-scale BALs. The results of this experiment demonstrate that the mass transfer coefficients for creatinine and albumin increased proportionally with velocity with the IWBAL, and were consistently greater than that found with the DBAL. These differences were further enhanced in the simulation of the large-scale model. CONCLUSIONS: Our findings indicate that the IWBAL with its unique 30° cross hollow fiber design can provide greater solute removal and more efficient metabolism when compared to the conventional DBAL design.

Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.

The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

Predictors of sleep-disordered breathing in pregnancy.

BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system.

Drosophila melanogaster is a long-standing model organism in the circadian clock research. A major advantage is the relative small number of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor-labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s-LNv ) and one ITP positive dorsolateral neuron (LNd ). These two clock neurons share the same spatial and functional properties. We found both neurons innervating the same brain areas with similar pre- and postsynaptic sites in the brain. Here the anatomical findings support their shared function as a main evening oscillator in the clock network like also found in previous studies. A second quite surprising finding addresses the large lateral ventral PDF-neurons (l-LNv s). We could show that the four hardly distinguishable l-LNv s consist of two subgroups with different innervation patterns. While three of the neurons reflect the well-known branching pattern reproduced by PDF immunohistochemistry, one neuron per brain hemisphere has a distinguished innervation profile and is restricted only to the proximal part of the medulla-surface. We named this neuron "extra" l-LNv (l-LNv x). We suggest the anatomical findings reflect different functional properties of the two l-LNv subgroups.

Complications and Outcomes of Pregnancy and Cesarean Delivery in Women With Neuropathic Bladder and Lower Urinary Tract Reconstruction.

OBJECTIVE: To determine the outcomes of pregnancy and cesarean delivery (CD) in women with neuropathic bladder (NB) and pediatric lower urinary tract reconstruction (LUTR) as these women often have normal fertility and may become pregnant. METHODS: We reviewed consecutive patients with NB due to spinal dysraphism who underwent LUTR, became pregnant, and had a CD at our institution from July 2001 to June 2016. We collected data on demographics, hydronephrosis, symptomatic urinary tract infection, continence, and catheterization during pregnancy. CD data included gestational age, abdominal or uterine incisions, and complications. RESULTS: We identified 18 pregnancies in 11 women. Fifteen live newborns were delivered via CD (53.3% term births). Thirteen of 15 patients (86.7%) developed new (10) or worsening (3) hydronephrosis. Six of 13 patients (46.2%) underwent nephrostomy tube placement. Eight of 15 patients (53.3%) developed difficulty catheterizing (66.7% via native urethra, 44.4% via catheterizable channel); 50.0% of patients required an indwelling catheter. Five of 15 patients (33.3%) developed urinary incontinence during pregnancy. Ten of 15 patients (66.7%) had a urinary tract infection (30.0% febrile). A urologist was present for all CDs: 5 were scheduled, 10 occurred emergently. Complications occurred in 40.0% (5 cystotomies, 1 bowel deserosalization, 1 vaginal laceration). All cystotomies occurred during emergent CD. Three patients (20.0%) developed urinary fistulae after emergent CD. CONCLUSIONS: Women with NB and LUTR have high rates of complications during pregnancy and CD, despite routine involvement of urologists. Women with prolonged labor, previous CD, or those with a history of noncompliance developed the worst complications. Based on our experience, a urologist should always be present and participate in the CD.