Influence of conception and delivery mode on stress response marker Oct4B1 and imprinted gene expression related to embryo development: A cohort study.

BACKGROUND: Recent scientific data support that the mode of conception and delivery may influence epigenetic regulation and therefore embryo development. Octamer-binding transcription factor 4-B1 (OCT4B1), a novel variant of OCT4 with yet unknown biological function, is suggested to have a potential role in mediating cellular stress response. Furthermore, Insulinlike Growth Factor 2 (IGF2), Mesoderm-specific Transcript (MEST) and paternally expressed gene 10 (PEG10) are genes known as imprinted and are regulated via means of epigenetic regulation. The influence of delivery mode and conception on epigenetic regulation is an active research field. OBJECTIVE: Our aim was to correlate the expression level of Oct4B1 and the expression and methylation level of IGF2, MEST, and PEG10 imprinted genes with the mode of delivery and conception in the umbilical cord blood of newborns. MATERIALS AND METHODS: Samples of umbilical cord blood from infants born after vaginal delivery, caesarean section (CS) with the infant in cephalic position and CS due to breech position were examined. Furthermore, the investigation included infants conceived through means of assisted reproductive technology. RESULTS: No statistically significant differences were found in mRNA expression levels between different modes of conception and delivery (p = 0.96). Oct4B1, IGF2, MEST, and PEG10 expression levels do not seem to be significantly affected by different modes of conception and delivery. CONCLUSION: These results indicate that the expression and methylation patterns of Oct4B1, IGF2, MEST and PEG10 in umbilical cord blood are not affected by the conception and delivery mode.

Infections of Deep Hand and Wrist Compartments.

The human hand is the most exposed part of the body to highest risk for injuries, loss of the skin integrity, and to the inoculation of bacteria, most commonly Staphylococcus aureus, Streptococcus ß-haemolytic, and gram-negative. In case of an infection, the mobile anatomical structures and the synovial membranes in close proximity to each other may spread the pus towards deep spaces and compartments. Mild early infections without an abscess formation may respond to antibiotics, but at more advanced stage, erythema, swelling, stiffness, and severe pain may ensue. Abscess formation will cause debilitating pain, fever, systemic symptoms, and even sepsis. Necrotizing infections may threaten not only the limb, but also patient's life. Therefore, an initially "trivial" hand injury should never be neglected, as it might turn into a deep space infection, which must be treated immediately with drainage, wound debridement, and i.v. antibiotics. Delay in diagnosis and inadequate initial management might rapidly lead to abscess formation, destruction of the gliding surfaces and the normal anatomy, and irreparable functional deterioration.

Linking Early Life Hypothalamic-Pituitary-Adrenal Axis Functioning, Brain Asymmetries, and Personality Traits in Dyslexia: An Informative Case Study.

Developmental dyslexia (DD) is a multi-system disorder, combining influences of susceptibility genes and environmental factors. The causative interaction between specific genetic factors, brain regions, and personality/mental disorders, as well as specific learning disabilities, has been thoroughly investigated with regard to the approach of developing a multifaceted diagnostic procedure with an intervention strategy potential. In an attempt to add new translational evidence to the interconnection of the above factors in the occurrence of DD, we performed a combinatorial analysis of brain asymmetries, personality traits, cognitive and learning skills, and expression profiles of selected genes in an adult, early diagnosed with DD, and in his son of typical development. We focused on the expression of genes, based on the assumption that the regulation of transcription may be affected by genetic and epigenetic factors. The results highlighted a potential chain link between neuroplasticity-related as well as stress-related genes, such as BDNF, Sox4, mineralocorticoid receptor (MR), and GILZ, leftward asymmetries in the amygdala and selective cerebellum lobules, and tendencies for personality disorders and dyslexia. This correlation may reflect the presence of a specific neuro-epigenetic component of DD, ensuing from the continuous, multifaceted difficulties in the acquisition of cognitive and learning skills, which in turn may act as a fostering mechanism for the onset of long-term disorders. This is in line with recent findings demonstrating a dysfunction in processes supported by rapid neural adaptation in children and adults with dyslexia. Accordingly, the co-evaluation of all the above parameters may indicate a stress-related dyslexia endophenotype that should be carefully considered for a more integrated diagnosis and effective intervention.

Unraveling the Serum Metabolomic Profile of Post-partum Depression.

Post-partum depression (PPD) is a severe psychiatric disorder affecting ∼15% of young mothers. Early life stressful conditions in periconceptual, fetal and early infant periods or exposure to maternal psychiatric disorders, have been linked to adverse childhood outcomes interfering with physiological, cognitive and emotional development. The molecular mechanisms of PPD are not yet fully understood. Unraveling the molecular underpinnings of PPD will allow timely detection and establishment of effective therapeutic approaches. To investigate the underlying molecular correlates of PPD in peripheral material, we compared the serum metabolomes of an in detail characterized group of mothers suffering from PPD and a control group of mothers, all from Heraklion, Crete in Greece. Serum samples were analyzed by a mass spectrometry platform for targeted metabolomics, based on selected reaction monitoring (SRM), which measures the levels of up to 300 metabolites. In the PPD group, we observed increased levels of glutathione-disulfide, adenylosuccinate, and ATP, which associate with oxidative stress, nucleotide biosynthesis and energy production pathways. We also followed up the metabolomic findings in a validation cohort of PPD mothers and controls. To the very best of our knowledge, this is the first metabolomic serum analysis in PPD. Our data show that molecular changes related to PPD are detectable in peripheral material, thus paving the way for additional studies in order to shed light on the molecular correlates of PPD.

Stressful Newborn Memories: Pre-Conceptual, In Utero, and Postnatal Events.

Early-life stressful experiences are critical for plasticity and development, shaping adult neuroendocrine response and future health. Stress response is mediated by the autonomous nervous system and the hypothalamic-pituitary-adrenal (HPA) axis while various environmental stimuli are encoded via epigenetic marks. The stress response system maintains homeostasis by regulating adaptation to the environmental changes. Pre-conceptual and in utero stressors form the fetal epigenetic profile together with the individual genetic profile, providing the background for individual stress response, vulnerability, or resilience. Postnatal and adult stressful experiences may act as the definitive switch. This review addresses the issue of how preconceptual in utero and postnatal events, together with individual differences, shape future stress responses. Putative markers of early-life adverse effects such as prematurity and low birth weight are emphasized, and the epigenetic, mitochondrial, and genomic architecture regulation of such events are discussed.

Partial monosomy 8p and trisomy 16q in two children with developmental delay detected by array comparative genomic hybridization.

Two cases of liveborn unrelated children with developmental delay and overlapping unbalanced translocations der(8)t(8;16)(p23.2;q23.3) and der (8)t(8;16)(p23.1;q23.1), leading to partial monosomy 8p and partial trisomy 16q, are reported in the present study. The first patient was a 10­year­old boy with mild developmental delay and minor congenital anomalies (borderline microcephaly, clinodactyly, hypertelorism, epicanthus, mild systolic murmur and kidney reflux). The second patient was a 3 year­old girl with developmental delay, gross motor milestone delay and dysmorphic features. Array­comparative genomic hybridization analysis revealed that partial chromosome 8p monosomy extended from 8p23.2 to 8pter (4.8 Mb) in Patient 1 and from 8p23.1 to 8pter (9.5 Mb) in Patient 2, and partial chromosome 16 trisomy extended from 16q23.3 to 16qter (5.6 Mb) in Patient 1 and from 16q23.1 to 16qter (11.7 Mb) in Patient 2. The mechanism of appearance of the rearrangement in association with the genes involved and the architecture of the region is discussed.

Mechanical stress affects methylation pattern of GNAS isoforms and osteogenic differentiation of hAT-MSCs.

Mechanical stress exerts a substantial role on skeletal-cell renewal systems, whereas accumulating evidence suggests that epigenetic mechanisms induce changes and differential gene expression. Although the underlying mechanisms remain to be fully elucidated, our study suggests that the influence of the long term mechanical stimulation elicits epigenetic modifications controlling osteogenic differentiation of human adipose tissue multipotential stromal cells (hAT-MSCs) and contributes to an accelerating in vitro osteogenesis. GNAS imprinting gene acts as a critical regulator of osteoblast differentiation and is implicated in human genetic disorders with pathological formation of ectopic-skeletal bone. Investigating a wide variety of stimuli, we showed that daily mechanical stretch on hAT-MSCs of 7th and 15th days' intervals induced a significant down-regulation in DNA methylation status of critical CpG sites of NESP and GNASXL isoforms, accompanied by up-regulation of the corresponding gene transcripts, and osteogenic differentiation earlier in culture. Importantly, methylation analysis of differentiating bone marrow-derived MSCs revealed similar methylation patterns. Bioinformatic analysis further showed that all CpG islands exhibiting significant methylation alterations encompassed transcriptional repressor CTCF binding sites. We hereby emphasize the need to investigate the epigenetic alterations on hAT-MSCs during environmental mechanical forces and to consider how the knowledge gained through these studies may foster new means of symptoms prevention and management of ectopic bone formation in the clinic.

A case of intractable epilepsy in a double cortex syndrome.

This article describes a very rare case of a double cortex syndrome in a man aged 32 years old who started from the age of 14 years having seizures and many other epileptic manifestations that continue to the present age, being always intractable to various therapeutic regimes. The neuroimaging revealed cortical ectopias in the cingulum, the visual cortex, in the middle part of the superior temporal gyrus, in the frontal pole as well as in the middle area of precentral gyrus. This article attempts to underline the behavioral disturbances, the learning difficulties, the psychological fluctuations, and the multitude of the seizures that have been released during the clinical course of the patient. The article attempts to correlate the clinical phenomena of the patient and the resistance to therapeutical interventions with the morphological changes as they have been visualized by the neuroimaging techniques, reviewing in addition relevant cases from the literature.

Serum levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) as a predictor of outcome in brucellosis.

OBJECTIVES AND METHODS: Brucellosis is characterized by chronicity and relapses despite efficacious treatment. Cytokines and especially the Th1/Th2 balance may be involved in the susceptibility or resistance to the Brucella species. In order to identify predictors of treatment outcome, we measured the pre and posttreatment levels of serum interleukin-2 (IL-2) and soluble IL-2 receptor alpha (sIL-2Ralpha) in 20 children with brucellosis. All children were treated for 6 weeks and three of them (15%) presented with a relapse at 2, 3 and 8 months after treatment had ended. RESULTS: Serum IL-2 levels, both pretreatment and posttreatment, did not significantly differ between patients and controls. By contrast, pretreatment sIL-2Ralpha levels were significantly higher in patients (P< or =0.0001) than in controls. sIL-2Ralpha levels significantly declined (P<0.001) after the 6-week antibiotic regimen in the 17 children who subsequently had a good outcome without relapses, but not in the three patients who relapsed. CONCLUSIONS: A decline in serum sIL-2Ralpha levels might be used as a marker of treatment efficacy in brucellosis.

Valproate-induced eosinophilia in children with epilepsy: role of interleukin-5.

Interleukin-5 contributes both in eosinophilopoiesis and neural development. Serum interleukin-5 levels were measured with enzyme-linked immunosorbent assay technique in 68 children with epilepsy receiving sodium valproate monotherapy and compared with the levels of 60 healthy controls and 14 children with epilepsy receiving carbamazepine. Eosinophilia was observed in 35.3% of children receiving valproate. Interleukin-5 in valproate users was significantly higher compared with children receiving carbamazepine and controls. Valproate users who exhibited eosinophilia had higher interleukin-5 levels compared with those without eosinophilia. However, the interleukin-5 level was also elevated, although to a lesser degree, in children without eosinophilia. The majority of valproate responders had high interleukin-5 levels. A positive correlation between interleukin-5 levels and the eosinophil count was also noted. We postulate that valproate contributes to the pathogenesis of eosinophilia, probably inducing interleukin-5 production. The finding that serum interleukin-5 was significantly elevated in valproate responders and even in valproate users without eosinophilia suggests that the increase in interleukin-5 might represent one of valproate's antiepileptic mechanisms.

Acute nephritis and respiratory tract infection caused by Mycoplasma pneumoniae: case report and review of the literature.

A 6-year-old boy presented with an acute infection caused by Mycoplasma pneumoniae associated with respiratory tract and kidney involvement. Renal manifestations included acute nephritis with decreased C3 fraction of serum complement, occurring concomitantly with the respiratory symptoms. The child had an excellent outcome, with rapid normalization of C3 and complete resolution of the acute nephritis.

Renal function and effect of aminoglycoside therapy during the first ten days of life.

The effect of aminoglycoside administration on kidney functional maturation was evaluated in groups of 30 preterm and 30 fullterm infants who were treated for 7 days because of suspected infection. One of three different aminoglycosides was administered to each subgroup of ten preterm and ten fullterm infants. Changes in tubular function in groups of ten preterm and ten fullterm infants who were not given antibiotics were also compared. The mean gestational age for preterm infants from 32.5 to 33.6 weeks and for fullterm infants between 39.2 and 39.5 weeks. The renal tubular function was assessed by examining the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium (FEMg) and uric acid (FEUA) as well as by the urinary excretion of calcium as the calcium/creatinine (UCa/UCr) ratio. Gentamicin affected the normal plasma creatinine (PCr) decline in both treated groups (fullterm and preterm). Disturbances in FENa and UCa/UCr were more pronounced in treated preterm than in fullterm infants especially after netilmicin and gentamicin administration. FEMg was significantly affected in preterm infants treated with gentamicin. The findings of this study indicate that the effect of aminoglycosides on tubular function is dependent upon kidney maturity and the type of the aminoglycoside used for therapy.

Transient lupus anticoagulant and prolonged activated partial thromboplastin time secondary to Epstein-Barr virus infection.

We describe the case of a previously well 19-month-old boy who presented with an acute Epstein-Barr virus infection and a prolonged activated partial thromboplastin time (APTT) associated with the presence of a transient lupus anticoagulant (LA). The boy had an excellent outcome, with gradual normalization of the APTT and disappearance of the LA.