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1.
Curr Biol ; 29(22): 3928-3936.e3, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31679928

RESUMO

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.

2.
Obstet Gynecol ; 134(4): 667-676, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31503146

RESUMO

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.

3.
Cell Prolif ; 52(4): e12604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069891

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Reatores Biológicos , Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos
4.
J Tissue Eng Regen Med ; 13(7): 1203-1216, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31034735

RESUMO

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.

5.
Biotechnol Lett ; 40(11-12): 1567-1578, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30264297

RESUMO

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.

6.
Bioengineering (Basel) ; 5(1)2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29543727

RESUMO

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.

7.
Am J Obstet Gynecol ; 218(5): 521.e1-521.e12, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29523262

RESUMO

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.


Assuntos
Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Hipertensão/complicações , Idade Materna , Complicações na Gravidez/etiologia , Síndromes da Apneia do Sono/etiologia , Ronco/etiologia , Adolescente , Adulto , Feminino , Humanos , Hipertensão/fisiopatologia , Polissonografia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Prevalência , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Ronco/epidemiologia , Ronco/fisiopatologia , Adulto Jovem
8.
J Comp Neurol ; 526(7): 1209-1231, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29424420

RESUMO

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.

9.
Urology ; 114: 236-243, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29305940

RESUMO

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.

10.
Semin Cell Dev Biol ; 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29331210

RESUMO

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.

11.
Dev Biol ; 430(1): 90-104, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28807781

RESUMO

Chordates are characterised by contractile muscle on either side of the body that promotes movement by side-to-side undulation. In the lineage leading to modern jawed vertebrates (crown group gnathostomes), this system was refined: body muscle became segregated into distinct dorsal (epaxial) and ventral (hypaxial) components that are separately innervated by the medial and hypaxial motors column, respectively, via the dorsal and ventral ramus of the spinal nerves. This allows full three-dimensional mobility, which in turn was a key factor in their evolutionary success. How the new gnathostome system is established during embryogenesis and how it may have evolved in the ancestors of modern vertebrates is not known. Vertebrate Engrailed genes have a peculiar expression pattern as they temporarily demarcate a central domain of the developing musculature at the epaxial-hypaxial boundary. Moreover, they are the only genes known with this particular expression pattern. The aim of this study was to investigate whether Engrailed genes control epaxial-hypaxial muscle development and innervation. Investigating chick, mouse and zebrafish as major gnathostome model organisms, we found that the Engrailed expression domain was associated with the establishment of the epaxial-hypaxial boundary of muscle in all three species. Moreover, the outgrowing epaxial and hypaxial nerves orientated themselves with respect to this Engrailed domain. In the chicken, loss and gain of Engrailed function changed epaxial-hypaxial somite patterning. Importantly, in all animals studied, loss and gain of Engrailed function severely disrupted the pathfinding of the spinal motor axons, suggesting that Engrailed plays an evolutionarily conserved role in the separate innervation of vertebrate epaxial-hypaxial muscle.


Assuntos
Galinhas/metabolismo , Proteínas de Homeodomínio/metabolismo , Movimento , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Animais , Animais Recém-Nascidos , Axônios/metabolismo , Biomarcadores/metabolismo , Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Desenvolvimento Muscular/genética , Mioblastos/citologia , Mioblastos/metabolismo , Fenótipo , Somitos/metabolismo
12.
Am J Obstet Gynecol ; 217(5): 594.e1-594.e10, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28712949

RESUMO

BACKGROUND: Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. OBJECTIVE: We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. STUDY DESIGN: Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. RESULTS: Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. CONCLUSION: In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.


Assuntos
Peso ao Nascer , Fluxo Pulsátil , Artéria Uterina/diagnóstico por imagem , Resistência Vascular , Adolescente , Adulto , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Paridade , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Adulto Jovem
13.
J Matern Fetal Neonatal Med ; 30(9): 1066-1071, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27296015

RESUMO

OBJECTIVE: To assess the utility of cervical funnel volume as a predictor of cerclage failure. METHODS: We performed a retrospective cohort study of pregnant women with a McDonald cerclage and sonographic evidence of cervical funneling between 1/2008 and 2/2014. Funnel volume (FV) was calculated and used as a correction factor for cervical length (CL) or cerclage height (CH). Receiver operating characteristic (ROC) curves were used to compare the predictive value of CL, CL:FV, CH and CH:FV for cerclage failure at <28 or <34 weeks. CL:FV was further stratified to the <5th, <10th and >10th percentiles and analyzed for prediction of preterm delivery. RESULTS: Subjects with cerclage failure (n = 30) delivered at a mean gestational age of 29.8 +/- 5.3 weeks compared to 38.1+/- 1.39 weeks in those without failure (n = 27; p < 0.001). ROC curves demonstrated CL:FV was the best predictor of delivery <28 weeks (AUC 0.80), while CL was the best predictor of delivery <34 weeks (AUC 0.76). Stratification of CL:FV into <5th versus >10th percentile groups was predictive of early preterm delivery (25.1 weeks versus 34 weeks, p = 0.01). CONCLUSIONS: Volumetric assessment of cervical funneling may improve prediction of cerclage failure in the mid-trimester.


Assuntos
Cerclagem Cervical , Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Nascimento Prematuro/prevenção & controle , Adulto , Estudos de Casos e Controles , Colo do Útero/patologia , Feminino , Idade Gestacional , Humanos , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Falha de Tratamento , Adulto Jovem
14.
J Matern Fetal Neonatal Med ; 30(17): 2133-2137, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27744775

RESUMO

PURPOSE: The purpose of this study is to evaluate the incidence of maternal cell contamination (MCC) in the first few milliliters of amniotic fluid withdrawn during amniocentesis. METHODS: A prospective observational study was performed. The initial 2-3 ml of amniotic fluid withdrawn during amniocentesis was divided into direct analysis (uncultured) and cultured samples. A matching maternal buccal swab was obtained for MCC testing. MCC was determined by short-tandem repeat analysis. The primary outcome was measurement of clinically significant contamination (MCC >5%). Secondary outcomes included the determination of risk factors associated with MCC >5%. Outcomes were assessed by fisher's exact, independent t-test, binary logistic regression, and ANOVA. RESULTS: Direct analysis measured clinically significant contamination (MCC > 5%) in 26% of specimens, while any amount of MCC was present in 68% of specimens. Cultured specimens had MCC > 5% in 2%, and any amount of MCC in 24%. Only blood-tinged fluid was associated with an increased risk for MCC > 5%. Larger volumes of the discard sample were not associated with increased incidence of MCC greater than 5%. CONCLUSION: A significant amount of MCC is present with direct analysis of the initial few milliliters of amniotic fluid withdrawn and is not influenced by the volume of the discard sample. Our results suggest that the first few milliliters of amniotic fluid be removed and discarded when direct analysis is utilized for prenatal genetic testing.


Assuntos
Amniocentese/métodos , Líquido Amniótico/citologia , Contaminação por DNA , Amniocentese/normas , Líquido Amniótico/química , Células Cultivadas , Feminino , Humanos , Reação em Cadeia da Polimerase , Gravidez , Estudos Prospectivos , Fatores de Risco
15.
Gene ; 599: 78-86, 2017 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-27836664

RESUMO

Vesicle shuttling is critical for many cellular and organismal processes, including embryonic development. GDI proteins contribute to vesicle shuttling by regulating the activity of Rab GTPases, controlling their cycling between the inactive cytosol and active membrane bound states. While identifying genes controlled by A-form DNA sequences we discovered a previously unknown member of the GDI family, GDI3. The GDI3 gene is found only in amphibians and fish and is developmentally expressed in Xenopus from neurula stages onwards in the neural plate, and subsequently in both dorsal and anterior structures. Depletion or over-expression of the GDI3 protein in Xenopus embryos gives rise to very similar phenotypes, suggesting that strict control of GDI3 protein levels is required for correct embryonic development. Our analysis suggests the evolutionary origins of GDI3 and that it is functionally distinct from GDI1. Predicted structural analysis of GDI3 suggests that the key difference between GDI1 and GDI3 lies in their lipid binding pockets.


Assuntos
Inibidores de Dissociação do Nucleotídeo Guanina/metabolismo , Neurogênese/fisiologia , Proteínas de Xenopus/metabolismo , Xenopus/embriologia , Xenopus/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Sequência de Bases , Clonagem Molecular , DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Inibidores de Dissociação do Nucleotídeo Guanina/química , Inibidores de Dissociação do Nucleotídeo Guanina/genética , Modelos Moleculares , Neurogênese/genética , Filogenia , Xenopus/genética , Proteínas de Xenopus/química , Proteínas de Xenopus/genética , Proteínas rab de Ligação ao GTP/química , Proteínas rab de Ligação ao GTP/genética
16.
Obstet Gynecol ; 129(1): 31-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27926645

RESUMO

OBJECTIVE: To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models. RESULTS: Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM. CONCLUSION: There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.


Assuntos
Diabetes Gestacional/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Incidência , Polissonografia , Pré-Eclâmpsia/epidemiologia , Gravidez , Trimestres da Gravidez , Prevalência , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Estados Unidos/epidemiologia , Adulto Jovem
17.
Fetal Pediatr Pathol ; 35(2): 120-3, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26882246

RESUMO

BACKGROUND: The cause of primary immunodeficiency has expanded to nearly 200 distinct disorders. An improved understanding of these disorders has resulted in decreased morbidity and mortality with reciprocal improved life expectancy. Obstetricians should have knowledge of primary immunodeficiency, as more women with these disorders will reach reproductive age. CASE: 21-year-old G1P0 with purine nucleoside phosphorylase (PNP) deficiency delivered a viable infant vaginally at 37 weeks. Although the patient's diagnosis and pregnancy placed her at increased risk for infection, she remained asymptomatic and infection-free throughout pregnancy. CONCLUSION: The management of pregnancy complicated by PNP deficiency requires strict immune surveillance and regimented immunoglobulin replacement.


Assuntos
Complicações na Gravidez , Gravidez de Alto Risco , Purina-Núcleosídeo Fosforilase/deficiência , Erros Inatos do Metabolismo da Purina-Pirimidina , Feminino , Humanos , Gravidez , Adulto Jovem
18.
Cochrane Database Syst Rev ; (11): CD011445, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26544539

RESUMO

BACKGROUND: Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. OBJECTIVES: To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth < 48 hours after trial entry (one trial, 35 women; risk ratio (RR) 0.93, 95% confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR 1.06, 95% CI 0.31 to 3.58). Serious maternal adverse events and perinatal mortality were not reported by either of the two trials in this comparison. Maternal adverse events (overall) were not reported but one trial (42 women) reported that there were no maternal adverse events that required stopping or changing drug) in either group. One trial did report delay until delivery but this outcome was reported as a median with no mention of the standard deviation (median 19 days in ethanol group versus "less than 1" day in the glucose/water group). There were no differences in any secondary outcomes reported: preterm birth < 34 weeks or < 37 weeks; serious infant outcome; fetal alcohol syndrome/fetal alcohol spectrum disorder; or small-for-gestational age. Comparison 2: Ethanol versus other tocolytic (betamimetics) (nine trials, 1438 women) Compared to betamimetics (the only tocolytic used as a comparator in these studies), ethanol was associated with no clear difference in the rate of birth < 48 hours after trial entry (two trials, 130 women; average RR 1.12, 95% CI 0.53 to 2.37, Tau² = 0.19, I² = 59%), similar rates of perinatal mortality (six trials, 698 women; RR1.20, 95% CI 0.78 to 1.84), higher rates of neonatal mortality (eight trials, 1238 women; RR 1.43, 95% CI 1.02 to 2.02), higher rates of preterm birth < 34 weeks (two trials, 599 women; RR 1.56, 95% CI 1.11 to 2.19), higher rates of neonatal respiratory distress syndrome (three trials, 823 women; RR 1.76, 95% CI 1.33 to 2.33), and higher rates of low birthweight babies < 2500 g (five trials, 834 women; RR 1.30, 95% CI 1.09 to 1.54). These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics, which for all these comparisons were betamimetics. Serious maternal adverse events were not reported in any of the nine trial reports. However, ethanol had a trend towards a lower rate of maternal adverse events requiring stopping or changing the drug (three trials, 214 women; RR 0.25, 95% CI 0.06 to 0.97). There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events.Planned sensitivity analysis, excluding quasi-randomized trials did not substantially change the results of the primary outcome analyses with the exception of neonatal mortality which no longer showed a clear difference between the ethanol and other tocolytic groups (3 trials, 330 women; RR 1.49, 95% CI 0.82 to 2.72). AUTHORS' CONCLUSIONS: This review is based on evidence from twelve studies which were mostly low quality. There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo. There is some evidence that ethanol may be better tolerated than other tocolytics (in this case betamimetics), but this result is based on few studies and small sample size and therefore should be interpreted with caution. Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor.Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth in threatened preterm labour. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status.


Assuntos
Etanol/uso terapêutico , Trabalho de Parto Prematuro , Nascimento Prematuro/prevenção & controle , Tocolíticos/uso terapêutico , Feminino , Humanos , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Fetal Pediatr Pathol ; 34(6): 413-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26359803

RESUMO

Pseudomonoamniotic gestations are increasingly recognized through sonographic surveillance of monochorionic twins, though etiologic factors remain undefined. We present a case of spontaneous pseudomonoamniotic twins and propose umbilical cord insertion proximity as a sonographic marker. Systematic review of the literature was performed and additional cases with similar findings were noted. Approximately 75% of reported cases (28/37) were deemed spontaneous and several included short inter-cord distances. Shunting of blood away from the membranes in the region between the cord insertions may be responsible for membrane rupture. Further investigation is needed into short inter-cord distance as a marker for monochorionic twins at risk to become a pseudomonoamniotic gestation.


Assuntos
Âmnio/anormalidades , Córion , Doenças em Gêmeos , Cordão Umbilical/patologia , Adulto , Feminino , Humanos , Gravidez , Gravidez de Gêmeos , Gêmeos Monozigóticos
20.
Dev Dyn ; 244(10): 1202-14, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26228689

RESUMO

The early axon scaffold is the first axonal structure to appear in the rostral brain of vertebrates, paving the way for later, more complex connections. Several early axon scaffold components are conserved between all vertebrates; most notably two main ventral longitudinal tracts, the tract of the postoptic commissure and the medial longitudinal fascicle. While the overall structure is remarkably similar, differences both in the organization and the development of the early tracts are apparent. This review will bring together extensive data from the last 25 years in different vertebrates and for the first time, the timing and anatomy of these early tracts have been directly compared. Representatives of major vertebrate clades, including cat shark, Xenopus, chick, and mouse embryos, will be compared using immunohistochemistry staining based on previous results. There is still confusion over the nomenclature and homology of these tracts which this review will aim to address. The discussion here is relevant both for understanding the evolution of the early axon scaffold and for future studies into the molecular regulation of its formation.


Assuntos
Axônios , Evolução Biológica , Encéfalo/embriologia , Vertebrados/embriologia , Animais , Músculos da Mastigação/inervação
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