The association of first trimester uterine arteries Doppler velocimetry with different clinical phenotypes of hypertensive disorders of pregnancy: a longitudinal study

Introduction: Current classification of hypertensive disorders of pregnancy (HDP) is mostly based on temporal classification differentiating HDP according to early and late onset of the disease. However, epidemiological and clinical data suggest that there are two different clinical phenotypes of HDP that coexist at any gestational age: HDP associated to intrauterine growth restriction (HDP-IUGR) and HDP associated to appropriate for gestational age fetal growth (HDP-AGAf). The aim of the study was to evaluate the association of first trimester uterine arteries (UtA) by Doppler velocimetry, and maternal risk factors with HDP according to two different classifications: one based on gestational age at delivery (early- and late-HDP), and one based on longitudinal ultrasound evaluation of fetal growth (HDP-IUGR and HDP-AGAf), independently of the gestational age.

Methods: Maternal characteristics and mean pulsatility index (PI) of UtA were collected at 11–13 gestational weeks. A longitudinal ultrasound follow-up of fetal growth in each trimester and clinical outcome were obtained in 4290 singleton pregnancies.

Results: UtA-PI was significantly higher in women who developed HDP-IUGR (n?=?22) and the odds ratio (OR) to develop HDP-IUGR from 25 to 39 weeks was 8.6 (p?n?=?112) was significantly associated with a higher BMI, multiparity, and maternal age, but not with UtA-PI (OR 1.3; p?=?.2). In women with an abnormal UtA-PI, the odds of developing early (n?=?15) and late-HDP (n?=?119) were 3.0 (p?=?.03) and 1.7 (p?=?.002), respectively. The AUCs for HDP-IUGR and early-HDP were 0.84 and 0.71, respectively.

Discussion: UtA Doppler velocimetry in the first trimester was strongly associated with HDP-IUGR all along gestation, as a proxy of placental insufficiency, and showed no association with HDP-AGAf. Our findings suggest an efficacy of first trimester UtA Doppler velocimetry to identify HDP-IUGR independently of the gestational age, and a limited value for HDP not associated with intrauterine growth restriction (IUGR).     

Age-associated DNA methylation in pediatric populations

DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis, monozygotic twins show indistinguishable childhood methylation, suggesting that DNAm is highly coordinated throughout early development. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from a cross-sectional study of 398 boys, aged 3-17 yr, and find significant age-associated changes in DNAm at 2078 loci. These findings correspond well with pyrosequencing data and replicate in a second pediatric population (N = 78). Moreover, we report a deficit of age-related loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. Meta-analysis (N = 1158) with two adult populations reveals that despite a significant overlap of age-associated loci, most methylation changes do not follow a lifelong linear pattern due to a threefold to fourfold higher rate of change in children compared with adults; consequently, the vast majority of changes are more accurately modeled as a function of logarithmic age. We therefore conclude that age-related DNAm changes in peripheral blood occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies should be matched closely for age.     

Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits

Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome-wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive-Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self-report questionnaires completed by the TwinsUK population-based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed-up signals from various strata using a two-stage replication strategy in two independent cohorts of European ancestry. We meta-analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive-Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED-related phenotypes, we detected association of eight genetic variants with P?相似文献   

Quorum-quenching endophytic bacteria inhibit disease caused by Pseudomonas syringae pv. syringae in Citrus cultivars

Two strains of 64 endophytic bacteria, Bacillus cereus Si-Ps1 and Pseudomonas azotoformans La-Pot3-3, isolated from Citrus sinensis and C. sinensis var. Thomson's leaves, respectively, reduced N-acyl homoserine-based quorum sensing in bioindicator strain Pseudomonas syringae pv. syringae (Pss) B728a and the biofilm production and swarming motility of field isolate Pss 3289. A homolog of aiiA gene encoding an AHL-lactonase was found in B. cereus (Si-Ps1), suggesting that this isolate can degrade the quorum-sensing signal molecules of Pss 3289. The crude extract of endophytic bacterium, B. cereus (Si-Ps1), inhibited Pss 3289 biofilm formation after 48 and 96 h by 55% and 58%, respectively. Similar reductions in biofilm formation were conferred by crude extracts of P. azotoformans (La-Pot3-3). Correspondingly, the number of planktonic cells in cultures treated with these extracts was higher than in control cultures, indicating a direct effect on biofilm formation and not on cell growth. In greenhouse assays, the virulence of Pss 3289 to different citrus cultivars was decreased when coinoculated with these endophytic bacteria.     

A novel frame shift mutation in the PQBP1 gene identified in a Tunisian family with X-linked mental retardation

Mental retardation (MR) is the most frequent cause of serious handicap in children and young adults. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Linkage studies followed by mutational analysis of known X-chromosomal genes related to mental retardation (MRX genes) localized within defined genetic intervals represent a rational strategy to identify a genetic cause of the disorder. Here, we report a Tunisian family including 3 males with severe to mild mental retardation, short stature, lean body and microcephaly; we mapped the disease to a unique interval encompassing Xp21.1-Xq21.33 (with a maximum LOD score of 0.90). Subsequent mutation analysis of genes located in this interval allowed us to identify a truncating mutation in the PQBP1 gene. This mutation is an insertion of an adenosine residue in exon 5 (c.631insA). This frameshift insertion causes premature stop codon at amino acid position 226. The observed mutation was found in all males with MR in this family. Together with previously reported observations, our data further confirm that PQBP1 gene should be tested for males showing mental retardation, short stature, lean body and microcephaly.     

Persecutory Entrapment and Flights in and out of Situations: A Question of Survival

This paper considers the occurrence of entrapment, invasion and phobic functioning ‘in’ and ‘out’(side) the consulting room as well as states of mind connected with safety and survival. Patient and therapist set sail on a troubled analytic journey beset by dangerous, terrifying mother imagoes, a mafia gang and a watchful life-saving ally. It is an epic journey into the unknown that involves inter alia thrills, braving the elements and the antagonistic forces of Thanatos and Eros. ‘No one dies and no one is hurt’, but emotional storms are created in media res. The patient then takes many flights. Firstly, into the place of her worst ‘nightmare’ and secondly, into action and inaction. In reality, a truly secure space and object cannot be found – only a feeling of captivity and disintegration remains. The use and function of potent and evocative objects may be significant for the patient in terms of safeguarding against re-experiencing primitive disasters, while achieving (a retroactive) control and mastery over the original trauma and helplessness. The author navigates a wide range of psychoanalytic theory, finding correspondence between classical and contemporary psychoanalytic traditions.     

Inflammatory pathways in children with insufficient or disordered sleep

Sleep is not only an essential physiological function, but also serves important roles in promoting growth, maturation, and overall health of children and adolescents. There is increasing interest regarding the impact of sleep and its disorders on the regulation of inflammatory processes and end-organ morbidities, particularly in the context of metabolic and cardiovascular diseases (CVD) and their complications. Obstructive sleep apnea syndrome (OSAS) is an increasingly common health problem in children, and in the last decade, the emergence of increasing obesity rates has further led to remarkable increases in the prevalence of OSAS, along with more prominent neurocognitive, behavioral, cardiovascular and metabolic morbidities. Although the underlying mechanisms leading to OSAS-induced morbidities are likely multi-factorial, and remain to be fully elucidated, activation of inflammatory pathways by OSAS has emerged as an important pathophysiological component of the end-organ injury associated with this disorder. To this effect, it would appear that OSAS could be viewed as a chronic, low-grade inflammatory disorder. Furthermore, the concurrent presence of obesity and OSAS poses a theoretically increased risk of OSAS-related complications. In this review, we will critically review the current state of research regarding the impact of insufficient and disrupted sleep and OSAS on the immune processes and inflammatory pathways that underlie childhood OSAS as a distinctive systemic inflammatory condition in children, and will explore potential interactions between OSAS and obesity.