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Objective: To investigate whether women using intravaginal progesterone suppositories for preterm birth prevention during pregnancy will have lower rates of group B streptococcus (GBS) colonisation at term, compared with women receiving intramuscular 17-alpha-hydroxyprogesterone caproate., Design: This was a retrospective observational cohort study of women who were prescribed a progestogen during their pregnancy for preterm birth prevention, and who delivered at term., Setting: A tertiary referral hospital in central Ohio., Population: Patients who were prescribed a progestogen during their pregnancy for preterm birth prevention between 2004 and 2017 were included in the study. Patients who delivered at <37 weeks of pregnancy, switched progestogen type during the pregnancy, or had a pessary or cerclage placed were excluded., Methods: Baseline characteristics were compared using Mann-Whitney U-test or Chi-square test as appropriate. The association between type of progestogen and GBS colonisation was assessed using bivariate and multivariable analyses., Main Outcome Measures: The primary outcome was GBS colonisation., Results: In all, 565 patients were included in the study, of whom 173 received intravaginal progesterone, and 392 17-alpha-hydroxyprogesterone caproate. Patients receiving intravaginal progesterone were less likely to be colonised with GBS (19.7 versus 28.1%). After adjustments for potential confounders were made in a multivariable logistic regression analysis, receiving intravaginal progesterone suppositories (adjusted odds ratio [OR] 0.61, 95% CI 0.39-0.95) was associated with reduced GBS colonisation., Conclusions: Intravaginal progesterone is associated with a decreased prevalence of rectovaginal GBS colonisation at term., Tweetable Abstract: Vaginal progesterone is associated with a lower incidence of rectovaginal GBS colonisation, compared with 17α-hydroxyprogesterone caproate., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Purpose The current study used a case review diagnostic assessment task to examine the diagnostic decisions speech-language pathologists (SLPs) working in the United States made after reviewing child language cases. Method Fourteen SLPs were given 5 case studies that presented either congruent or incongruent results between standardized testing and informal measures. After reviewing the assessment data, SLPs were asked to make a diagnostic decision. Results Unanimous consensus regarding diagnostic decisions was found when the assessment data were congruent. When the data were incongruent, unanimous consensus was not achieved. Standardized testing seemed to guide the diagnostic decision. This pattern of reliance on standardized testing was evident even when 80% of SLPs reviewed informal language data. In 97% of cases, a standardized test was used to guide clinical decision making. Conclusion Three patterns of clinical decision making in child language assessment emerged: (a) use of both standardized testing and informal measures, (b) a reported concern tool as a 1st step in the process, and (c) standardized testing as the most influential data for guiding diagnostic decisions. Although this study provides initial evidence regarding the process of diagnostic decision making, future studies should examine decision making in real time to further validate the implicit rules used during decision making. Supplemental Material https://doi.org/10.23641/asha.7991174.

Objective: We sought to identify fetal heart rate (FHR) characteristics that are associated with neonatal encephalopathy (NE)., Design: Retrospective case-control study., Setting: A single medical centre in Shanghai, China, 2006-2015., Sample: Women delivering a singleton, non-anomalous infant at ≥36 weeks' gestation diagnosed with NE (cases, n = 109) were compared with a group of women with unaffected infants (controls, n = 233)., Methods: Two physicians blinded to the outcome independently reviewed FHR tracings during the last 30 minutes of tracing prior to delivery. FHR characteristics were compared in the two groups and multivariable logistic regression was used to adjust for confounding., Main Outcome Measures: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for the presence of specific FHR categories and characteristics., Results: Category II FHR tracings were observed in 89% of women prior to delivery and were not independently associated with NE. Notably, a category III FHR was observed in 17.4% of women in the NE group compared with 0.9% of women in the control group (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late decelerations and prolonged decelerations were independently associated with NE, whereas accelerations were protective. Similar findings were found when the cases were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women with category II tracings., Conclusions: Category III tracings, while infrequent, are not uncommon prior to delivery among fetuses who develop NE. In contrast, most FHR tracings are category II prior to delivery; however, individual FHR characteristics within this category are associated with NE., Funding: This research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong University., Tweetable Abstract: Category III tracings are not uncommon prior to delivery among fetuses who develop neonatal encephalopathy., (© 2018 Royal College of Obstetricians and Gynaecologists.)

The hypothesis of this study was that the leukocyte populations and expression levels of genes related to immune response, growth factors and apoptosis would be altered at the fetal-maternal interface in somatic cell nuclear transfer (SCNT)-generated sheep pregnancies. Placental and endometrial samples from sheep pregnancies established by SCNT and natural breeding (control) were collected at 45 days and at term. Expression of genes related to growth factors, apoptosis and immune response was examined using quantitative reverse transcription polymerase chain reaction. Endometrial leukocyte populations and major histocompatibility class I (MHC-I) protein expression were examined by immunohistochemistry. At term we observed altered expression of genes related to apoptosis, growth factors and immune response in placental and endometrial tissue of SCNT pregnancies. In Day-45 pregnancies there was less-pronounced abnormal expression and only genes related to apoptosis and growth factors were abnormal in the placenta. Endometrial gene expression profiles were similar to age-matched controls. Placental MHC-I protein expression was similar in SCNT and controls at 45 days but increased in the SCNT at term. The altered gene expression at the fetal-maternal interface likely contributes to the placental dysfunction and overgrowth observed in sheep SCNT pregnancies.

Purpose: This study used a structured open interview approach to elicit information from school-based speech-language pathologists (SLPs) regarding their assessment practices for children with suspected language impairment., Method: Phone interviews were conducted with 39 school-based SLPs who were employed across the United States. The interviews explored assessment topics related to assessment tool selection and rationale and the integration of assessment data to determine treatment eligibility., Results: The results of this study suggest that SLPs use both standardized testing and informal testing for their diagnostic procedures. Standardized testing appears to be the tool that drives diagnostic decisions regarding eligibility and severity. Informal measures, such as parent/teacher interviews and language sampling, were used by school-based SLPs to gather information regarding naturalistic language use; however, they seem less important in the diagnostic decision-making process. Also, SLPs reported completing language sample transcription and analysis in real time while interacting with a child., Conclusions: School-based SLPs appear to rely on the results from standardized testing when determining treatment eligibility for children with language impairment. The reliance on standardized testing appears to be driven by institutional policies. We discuss the potential impact of federal/state/district guidelines on diagnostic decisions and consider the research-to-practice gap.

Purpose: This feasibility study examines the convergent and divergent validity of the Grammaticality and Utterance Length Instrument (GLi), a tool designed to assess the grammaticality and average utterance length of a child's prerecorded story retell., Method: Three raters used the GLi to rate audio-recorded story retells from 100 English-speaking preschool children. To examine convergent validity, the results of the GLi were correlated with 2 language sample measures, mean length of utterance in words and percentage of grammatical utterances, and with the results of the Structured Photographic Expressive Language Test-Third Edition (Dawson, Stout, & Eyer, 2003). To examine divergent validity, the results of the GLi were correlated with the results of the Kaufman Brief Intelligence Test-Second Edition (Kaufman & Kaufman, 2004). Comparisons between task completion time for the GLi and Systematic Analysis of Language Transcripts (SALT; Miller & Iglesias, 2010) transcription and analysis were also conducted. Last, preliminary discriminant analysis was used to examine the diagnostic potential of the GLi., Results: The results of this study provide evidence of convergent and divergent validity for the GLi. The task completion time for the GLi was considerably shorter than the SALT transcription and analysis. Preliminary analysis of diagnostic accuracy suggests that the GLi has the potential to be a good tool to identify children with language impairment., Discussion: The GLi has good convergent and divergent validity and is a reliable instrument to assess utterance length and grammaticality of prerecorded language samples. However, SALT transcription and analysis provide a more detailed and comprehensive analysis of the language skills of a child.

Introduction: We performed RNA sequencing with the primary goal of discovering key placental villous trophoblast (VT) and decidua basalis (DB) transcripts differentially expressed in intra-amniotic infection (IAI)-induced preterm birth (PTB)., Methods: RNA was extracted from 15 paired VT and DB specimens delivered of women with: 1) spontaneous PTB in the setting of amniocentesis-proven IAI and histological chorioamnionitis (n = 5); 2) spontaneous idiopathic PTB (iPTB, n = 5); and 3) physiologic term pregnancy (n = 5). RNA sequencing was performed using the Illumina HiSeq 2500 platform, and a spectrum of computational tools was used for gene prioritization and pathway analyses., Results: In the VT specimens, 128 unique long transcripts and 7 mature microRNAs differed significantly between pregnancies complicated by IAI relative to iPTB (FDR<0.1). The up-regulated transcripts included many characteristic of myeloblast-derived cells, and bioinformatic analyses revealed enrichment for multiple pathways associated with acute inflammation. In an expanded cohort including additional IAI and iPTB specimens, the expression of three proteins (cathepsin S, lysozyme, and hexokinase 3) and two microRNAs (miR-133a and miR-223) was validated using immunohistochemistry and quantitative PCR, respectively. In the DB specimens, only 11 long transcripts and no microRNAs differed significantly between IAI cases and iPTB controls (FDR<0.1). Comparison of the VT and DB specimens in each clinical scenario revealed signatures distinguishing these placental regions., Discussion: IAI is associated with a transcriptional signature consistent with acute inflammation in the villous trophoblast. The present findings illuminate novel signaling pathways involved in IAI, and suggest putative therapeutic targets and potential biomarkers associated with this condition., (Copyright © 2016. Published by Elsevier Ltd.)

Background: High Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6., Methods: We assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin., Results: AF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments., Conclusions: Our research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Late obstetric emergencies are time critical presentations in the emergency department. Evaluation to ensure the safety of mother and child includes rapid assessment of fetal viability, fetal heart rate (FHR), fetal lie, and estimated gestational age (EGA). Point-of-care (POC) obstetric ultrasound (OBUS) offers the advantage of being able to provide all these measurements. We studied the impact of POC OBUS training on emergency physician (EP) confidence, knowledge, and OBUS skill performance on a live model., Methods: This is a prospective observational study evaluating an educational intervention we designed, called the BE-SAFE curriculum (BEdside Sonography for the Assessment of the Fetus in Emergencies). Subjects were a convenience sample of EP attendings (N=17) and residents (N=14). Prior to the educational intervention, participants completed a self-assessment survey on their confidence regarding OBUS, and took a pre-test to assess their baseline knowledge of OBUS. They then completed a 3-hour training session consisting of didactic and hands-on education in OBUS. After training, each subject's time and accuracy of performance of FHR, EGA, and fetal lie was recorded. Post-intervention knowledge tests and confidence surveys were administered. Results were compared with non-parametric t-tests., Results: Pre- and post-test knowledge assessment scores for previously untrained EPs improved from 65.7% [SD=20.8] to 90% [SD=8.2] (p<0.0007). Self-confidence on a scale of 1-6 improved significantly for identification of FHR, fetal lie, and EGA. After training, the average times for completion of OBUS critical skills were as follows: cardiac activity (9s), FHR (68.6s), fetal lie (28.1s), and EGA (158.1 sec). EGA estimates averaged 28w0d (25w0d-30w6d) for the model's true gestational age of 27w0d., Conclusion: After a focused POC OBUS training intervention, the BE-SAFE educational intervention, EPs can accurately and rapidly use ultrasound to determine FHR, fetal lie, and estimate gestational age in mid-late pregnancy.

Markedly elevated maternal serum alpha-fetoprotein (MSAFP) levels were found in a 26 year old healthy, nulliparous Polish woman during pregnancy. No fetal abnormalities were identified on targeted ultrasound and amniocentesis revealed normal amniotic fluid alpha-fetoprotein (AFP) values. Maternal ultrasound screening for liver and ovarian germ cell malignancies were also negative. The mother delivered a live, healthy female at term and a repeat maternal serum AFP postpartum remained markedly elevated, suggestive of hereditary persistence of alpha-fetoprotein.

Circulating tumor cells (CTCs) are those cells that have separated from a macroscopic tumor and spread through the blood and lymph systems to seed secondary tumors(1,2,3). CTCs are indicators of metastatic disease and their detection in blood samples may be used to diagnose cancer and monitor a patient's response to therapy. Since CTCs are rare, comprising about one tumor cell among billions of normal blood cells in advanced cancer patients, their detection and enumeration is a difficult task. We exploit the presence of pigment in most melanoma cells to generate photoacoustic, or laser induced ultrasonic waves in a custom flow cytometer for detection of circulating melanoma cells (CMCs)(4,5). This process entails separating a whole blood sample using centrifugation and obtaining the white blood cell layer. If present in whole blood, CMCs will separate with the white blood cells due to similar density. These cells are resuspended in phosphate buffered saline (PBS) and introduced into the flowmeter. Rather than a continuous flow of the blood cell suspension, we induced two phase flow in order to capture these cells for further study. In two phase flow, two immiscible liquids in a microfluidic system meet at a junction and form alternating slugs of liquid(6,7). PBS suspended white blood cells and air form microliter slugs that are sequentially irradiated with laser light. The addition of a surfactant to the liquid phase allows uniform slug formation and the user can create different sized slugs by altering the flow rates of the two phases. Slugs of air and slugs of PBS with white blood cells contain no light absorbers and hence, do not produce photoacoustic waves. However, slugs of white blood cells that contain even single CMCs absorb laser light and produce high frequency acoustic waves. These slugs that generate photoacoustic waves are sequestered and collected for cytochemical staining for verification of CMCs.

We examined central venous catheter (CVC) sepsis in newborn surgical patients, as this group appeared to have a higher incidence of this complication. During a 3-year period 79 patients on the surgical service required a tunneled, cuffed, Broviac CVC. Nineteen patients (24% or 9.9 episodes per 1000 catheter days) had proven sepsis and 8 (10% or 1.9/1000 catheter days) had suspected sepsis. An intestinal stoma was definitely related to CVC sepsis ( p<0.001). Other risk factors included lower gestational age, more operations, and younger age at first stoma. Temperature, white blood cell (WBC) count, and platelet count did not correlate with CVC sepsis. We found no better indicator of CVC sepsis than the presentation of an ill child. Certainly temperature, WBC, and platelet count are not reliable indicators. Surgeons have little control over the factors that were found to be related to CVC sepsis. It would appear reasonable from these results to maintain a high index of suspicion in the high-risk groups, to use peripherally inserted central catheters (PIC lines) as the first line of long-term vascular access, and to bring CVCs out of a nonabdominal site, perhaps the scalp, in patients with stomas.

Background/purpose: The authors compared 3 quantitative methods for assisting clinicians in the differential diagnosis of abdominal pain in children, where the most common important endpoint is whether the patient has appendicitis. Pretest probability in different age and sex groups were determined to perform Bayesian analysis, binary logistic regression was used to determine which variables were statistically significantly likely to contribute to a diagnosis, and recursive partitioning was used to build decision trees with quantitative endpoints., Methods: The records of all children (1,208) seen at a large urban emergency department (ED) with a chief complaint of abdominal pain were immediately reviewed retrospectively (24 to 72 hours after the encounter). Attempts were made to contact all the patients' families to determine an accurate final diagnosis. A total of 1,008 (83%) families were contacted. Data were analyzed by calculation of the posttest probability, recursive partitioning, and binary logistic regression., Results: In all groups the most common diagnosis was abdominal pain (ICD-9 Code 789). After this, however, the order of the most common final diagnoses for abdominal pain varied significantly. The entire group had a pretest probability of appendicitis of 0.06. This varied with age and sex from 0.02 in boys 2 to 5 years old to 0.16 in boys older than 12 years. In boys age 5 to 12, recursive partitioning and binary logistic regression agreed on guarding and anorexia as important variables. Guarding and tenderness were important in girls age 5 to 12. In boys age greater than 12, both agreed on guarding and anorexia. Using sensitivities and specificities from the literature, computed tomography improved the posttest probability for the group from.06 to.33; ultrasound improved it from.06 to.48; and barium enema improved it from.06 to.58., Conclusions: Knowing the pretest probabilities in a specific population allows the physician to evaluate the likely diagnoses first. Other quantitative methods can help judge how much importance a certain criterion should have in the decision making and how much a particular test is likely to influence the probability of a correct diagnosis. It now should be possible to make these sophisticated quantitative methods readily available to clinicians via the computer., (Copyright 2001 by W.B. Saunders Company.)

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

The interaction between recombinant Strongylocentrotus purpuratus sperm bindin and a recombinant fragment of the putative egg bindin receptor of the same species was measured in vitro. In solution these molecules interact with simple bimolecular kinetics, displaying an equilibrium dissociation constant of about 0.1 microM. Thus, as implied by many observations in vivo and in vitro, bindin and the putative egg receptor display a specific affinity for one another.

We have analyzed the binding of Sp1, a ubiquitously expressed transactivator, to the promoter region of the gamma genes. Low-affinity Sp1 sites were found at -50 and -200. A high-affinity site was detected at -140, over the CACCC sequence. To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, were cotransfected with an Sp1 expression plasmid and gamma globin promoter-CAT constructs. In these assays, the gamma promoter was significantly stronger in the presence than in the absence of Sp1. Thus, the three Sp1 sites in the gamma promoter allow binding as well as transactivation of the promoter. The majority of this transactivation was due to the strong binding site at -140 because introduction of a point mutation at -144 (CACCC----AACCC) reduced Sp1-dependent promoter strength by 57%. Analysis of the -200 region suggested that in the wild-type promoter, Sp1 binding at this site contributes little to promoter strength. However, a point mutation (-198 T----C) associated with hereditary persistence of fetal hemoglobin (HPFH) dramatically increased the affinity of this site for Sp1 and significantly increased Sp1 dependent promoter strength in SL-2 cells. Three other point mutations associated with HPFH did not significantly affect the interaction of Sp1 with the -200 region.

We have introduced into the mouse germ line the 40-kilobase (kb) Kpn I fragment containing the beta-globin gene cluster from an individual with a non-deletion form of hereditary persistence of fetal hemoglobin (HPFH) believed to be due to a point mutation at position -202 of the G gamma-globin gene. The G gamma-globin gene, as well as the beta-globin gene, was expressed in adult erythroid tissues of the resulting transgenic mice. The level of expression of the G gamma-globin gene was about 20% of that of the beta-globin gene. Others have previously shown that cloned individual normal human beta- and gamma-globin genes containing a limited amount of 5'- and 3'-flanking DNA are expressed in a manner similar to that of their corresponding murine homologs during development in transgenic mice. In contrast, we have observed that the pattern of expression of the normal (non-mutated) A gamma- and beta-globin genes in the 40-kb insert was different from that of their corresponding murine homologs. The beta-globin gene remained inactive at the fetal stage, whereas the normal A gamma-globin gene was expressed beyond the embryonic (yolk sac) stage into the fetal stage of development and then became inactive in adult erythroid cells. The pattern of expression of the human globin transgenes during mouse development resembles that observed during human development. These results suggest that the gross organization of the human beta-like globin gene cluster is important for stage-specific expression of each human globin gene during development.