Effect of pregnancy prolongation in early-onset pre-eclampsia on postpartum maternal cardiovascular, renal and metabolic function in primiparous women: an observational study.

OBJECTIVE: To evaluate the association between deferred delivery in early-onset pre-eclampsia and offspring outcome and maternal cardiovascular, renal and metabolic function in the postpartum period. DESIGN: Observational study. SETTING: Tertiary referral hospital. POPULATION: Nulliparous women diagnosed with pre-eclampsia before 34 weeks' gestation who participated in a routine postpartum cardiovascular risk assessment programme. Women with hypertension, diabetes mellitus or renal disease prior to pregnancy were excluded. METHODS: Regression analyses were performed to assess the association between pregnancy prolongation and outcome measures. MAIN OUTCOME MEASURES: Offspring outcome and prevalence of deviant maternal cardiovascular, renal and metabolic function. RESULTS: The study population included 564 women with a median pregnancy prolongation of 10 days (interquartile range [IQR] 4-18) who were assessed at on average 8 months (IQR 6-12) postpartum. Pregnancy prolongation after diagnosis resulted in a decrease in infant mortality (adjusted odd ratio [aOR] 0.907, 95% CI 0.852-0.965 per day prolongation). This improvement in offspring outcome was associated with an elevated risk of moderately increased albuminuria (aOR 1.025, 95% CI 1.006-1.045 per day prolongation), but not with aberrant cardiac geometry, cardiac systolic or diastolic dysfunction, persistent hypertension or metabolic syndrome. CONCLUSION: Pregnancy prolongation in early-onset pre-eclampsia is associated with improved offspring outcome and survival. These effects do not appear to be deleterious to short-term maternal cardiovascular and metabolic function but are associated with a modest increase in risk of residual albuminuria. TWEETABLE ABSTRACT: Pregnancy prolongation in pre-eclampsia has only a limited effect on postpartum maternal cardiovascular function

Fetal leg posture in uncomplicated breech and cephalic pregnancies

Background The objective of our study was to determine differences in prenatal leg posture development between breech and cephalic-born babies. Materials and methods Ten healthy fetuses in breech and ten healthy fetuses in cephalic presentation were observed by means of weekly ultrasounds from 33 weeks gestational age until birth to assess leg posture. Results The breech fetuses showed a clear preference for an extended leg position; they spent significantly more time with their knees in extension than the cephalic fetuses (p<0.001). The cephalic fetuses showed significantly more leg-crossing than the breech fetuses (p<0.01). For both findings, no significant change over time could be observed in either group. Conclusion These findings show that the intra-uterine position does influence the fetal postural and motor development. However, it seems unlikely that intra-uterine movement restriction can solely be held accountable for the observed differences in leg position between breech and cephalic fetuses. © 2008 The Author(s)

Identification of alleles of carotenoid pathway genes important for zeaxanthin accumulation in potato tubers

We have investigated the genetics and molecular biology of orange flesh colour in potato (Solanum tuberosum L.). To this end the natural diversity in three genes of the carotenoid pathway was assessed by SNP analyses. Association analysis was performed between SNP haplotypes and flesh colour phenotypes in diploid and tetraploid potato genotypes. We observed that among eleven beta-carotene hydroxylase 2 (Chy2) alleles only one dominant allele has a major effect, changing white into yellow flesh colour. In contrast, none of the lycopene epsilon cyclase (Lcye) alleles seemed to have a large effect on flesh colour. Analysis of zeaxanthin epoxidase (Zep) alleles showed that all (diploid) genotypes with orange tuber flesh were homozygous for one specific Zep allele. This Zep allele showed a reduced level of expression. The complete genomic sequence of the recessive Zep allele, including the promoter, was determined, and compared with the sequence of other Zep alleles. The most striking difference was the presence of a non-LTR retrotransposon sequence in intron 1 of the recessive Zep allele, which was absent in all other Zep alleles investigated. We hypothesise that the presence of this large sequence in intron 1 caused the lower expression level, resulting in reduced Zep activity and accumulation of zeaxanthin. Only genotypes combining presence of the dominant Chy2 allele with homozygosity for the recessive Zep allele produced orange-fleshed tubers that accumulated large amounts of zeaxanthin

QTL mapping in autotetraploids using SNP dosage information

Dense linkage maps derived by analysing SNP dosage in autotetraploids provide detailed information about the location of, and genetic model at, quantitative trait loci. Recent developments in sequencing and genotyping technologies enable researchers to generate high-density single nucleotide polymorphism (SNP) genotype data for mapping studies. For polyploid species, the SNP genotypes are informative about allele dosage, and Hackett et al. (PLoS ONE 8:e63939, 2013) presented theory about how dosage information can be used in linkage map construction and quantitative trait locus (QTL) mapping for an F1 population in an autotetraploid species. Here, QTL mapping using dosage information is explored for simulated phenotypic traits of moderate heritability and possibly non-additive effects. Different mapping strategies are compared, looking at additive and more complicated models, and model fitting as a single step or by iteratively re-weighted modelling. We recommend fitting an additive model without iterative re-weighting, and then exploring non-additive models for the genotype means estimated at the most likely position. We apply this strategy to re-analyse traits of high heritability from a potato population of 190 F1 individuals: flower colour, maturity, height and resistance to late blight (Phytophthora infestans (Mont.) de Bary) and potato cyst nematode (Globodera pallida), using a map of 3839 SNPs. The approximate confidence intervals for QTL locations have been improved by the detailed linkage map, and more information about the genetic model at each QTL has been revealed. For several of the reported QTLs, candidate SNPs can be identified, and used to propose candidate trait genes. We conclude that the high marker density is informative about the genetic model at loci of large effects, but that larger populations are needed to detect smaller QTLs

Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy

Background: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. Objective: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. Materials and methods: The study was a semiprospective analysis of a 12-year cohort of neonates born to mothers who had used cocaine during their pregnancy and who had follow-up according to a strict clinical protocol. Results: In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of the infants showed severe abnormalities. The abnormalities were not associated with the duration or maximum amount of cocaine use during pregnancy. Conclusion: None of the infants had severe abnormalities. Detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, we feel that routine cranial ultrasonography in this population is not warranted

Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study

BackgroundActivity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort.MethodsPatients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy.ResultsSeventeen patients completed the program with average participation duration of 21.3&nbsp;weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1&nbsp;N to 21.2&nbsp;N over 20&nbsp;weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline.ConclusionsA weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06–1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short disease-free survival

Repertoire of microRNAs in Epithelial Ovarian Cancer as Determined by Next Generation Sequencing of Small RNA cDNA Libraries

MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in cancer pathogenesis and have recently shown promise as blood-based biomarkers for cancer detection. Epithelial ovarian cancer is a deadly disease for which improved outcomes could be achieved by successful early detection and enhanced understanding of molecular pathogenesis that leads to improved therapies. A critical step toward these goals is to establish a comprehensive view of miRNAs expressed in epithelial ovarian cancer tissues as well as in normal ovarian surface epithelial cells.We used massively parallel pyrosequencing (i.e., "454 sequencing") to discover and characterize novel and known miRNAs expressed in primary cultures of normal human ovarian surface epithelium (HOSE) and in tissue from three of the most common histotypes of ovarian cancer. Deep sequencing of small RNA cDNA libraries derived from normal HOSE and ovarian cancer samples yielded a total of 738,710 high-quality sequence reads, generating comprehensive digital profiles of miRNA expression. Expression profiles for 498 previously annotated miRNAs were delineated and we discovered six novel miRNAs and 39 candidate miRNAs. A set of 124 miRNAs was differentially expressed in normal versus cancer samples and 38 miRNAs were differentially expressed across histologic subtypes of ovarian cancer. Taqman qRT-PCR performed on a subset of miRNAs confirmed results of the sequencing-based study.This report expands the body of miRNAs known to be expressed in epithelial ovarian cancer and provides a useful resource for future studies of the role of miRNAs in the pathogenesis and early detection of ovarian cancer

Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome

Background: Altered maternal inflammatory responses play a role in the development of preeclampsia and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. We examined whether allelic variants of the innate immune receptors toli-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain (NOD2), that impair the inflammatory response to endotexin are related to preeclampsia and HELLP syndrome. Methods and Finding: We determined five common mutations in TLR4 (D299G and T399I and NOD2 (R70W, G908R and L1007fs) in 340 primiparous women with a histo

Uncovering spatial topology represented by rat hippocampal population neuronal codes

Hippocampal population codes play an important role in representation of spatial environment and spatial navigation. Uncovering the internal representation of hippocampal population codes will help understand neural mechanisms of the hippocampus. For instance, uncovering the patterns represented by rat hippocampus (CA1) pyramidal cells during periods of either navigation or sleep has been an active research topic over the past decades. However, previous approaches to analyze or decode firing patterns of population neurons all assume the knowledge of the place fields, which are estimated from training data a priori. The question still remains unclear how can we extract information from population neuronal responses either without a priori knowledge or in the presence of finite sampling constraint. Finding the answer to this question would leverage our ability to examine the population neuronal codes under different experimental conditions. Using rat hippocampus as a model system, we attempt to uncover the hidden “spatial topology” represented by the hippocampal population codes. We develop a hidden Markov model (HMM) and a variational Bayesian (VB) inference algorithm to achieve this computational goal, and we apply the analysis to extensive simulation and experimental data. Our empirical results show promising direction for discovering structural patterns of ensemble spike activity during periods of active navigation. This study would also provide useful insights for future exploratory data analysis of population neuronal codes during periods of sleep.National Institutes of Health (U.S.) (NIH Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant MH061976