Sleep Quality, Emotion Regulation and Parenting Stress in Children with Congenital Heart Disease

The aim of this study is to evaluate parental perceptions of parent-infant bedtime interactions and quality of sleep, after hospital discharge, in a group of children diagnosed at birth with congenital heart disease (CHD), as compared with the perceptions of parents in a control group of children who were healthy at birth. More specifically, we evaluated the associations between parental stress, parental perceptions of infant emotion regulation, and infants’ bedtime and sleep routines in each of the two groups. Fifty Italian intact two-parent families (23 boys) of toddlers ageing from 11 to 36 months (M= 23.42, SD=7.10) were recruited. 20 families of CHD children group were recruited from the Department of Cardiology at the Bambino Gesù Children’s Hospital in Rome, Italy; 30 families of the healthy children group were recruited from two childcare units. Parents completed Emotion Regulation Checklist (Shields Cicchetti, 1997), Parent-Child Sleep Interaction Scale (PSIS; Alfano et al., 2013), Parent-Stress Index-Short Form (PSI-SF; Abidin, 1990) and ad-hoc semi-structured interview on child’s sleep quality. The independent-samples t-test evidenced that parents of healthy children reported significantly higher scores on children's emotion regulation compared with the CHD group Specifically CHD children and healthy children's emotion regulation reported both by mothers (respectively CHD children’s mothers: M= 26.11, SD= 2.9; healthy children’s mothers: M= 28.85, SD= 2.71; t(37) = 3.10, p= .004) and fathers (respectively CHD children’s fathers: M=25.76, SD= 2.79; healthy children’s fathers: M= 27.37, SD= 2.02; t(31)= 2.71, p= .010). Main correlational findings showed in the CHD children’s group that parenting stress total scores were positive related to difficult parent-infant bedtime interactions both for mothers (r=.58, p .01) and fathers (r= .70, p .01). Results show significant differences in emotion regulation between the two groups. The results of this research will show to the clinicians the aspects of parent-infant bedtime interactions to be addressed in parents of children with CHD

Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation

Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples. Methodology/Principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG. Conclusions/Significance: Our results show that even though partial methylation of the promoter region of SGK1 is present

Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate

Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation. Upstream of that pathway, inositols disrupt the ligand interaction between FGF and its receptor as well as with the EGF-transduction processes involving IGF-II receptor and AP-1 complexes. Additionally, Akt activation is severely impaired upon inositol addition. Downregulation of both Akt and ERK leads consequently to NF-kB inhibition and reduced expression of inflammatory markers (COX-2 and PGE2). Remarkably, inositol-induced downregulation of presenilin-1 interferes with the epithelial-mesenchymal transition and reduces Wnt-activation, β-catenin translocation, Notch-1, N-cadherin, and SNAI1 release. Inositols interfere also with the cytoskeleton by upregulating Focal Adhesion Kinase and E-cadherin and decreasing Fascin and Cofilin, two main components of pseudopodia, leading hence to invasiveness impairment. This effect is reinforced by the inositol-induced inhibition on metalloproteinases and ROCK1/2 release. Overall, these effects enable inositols to remodel the cytoskeleton architecture

Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

INTRODUCTION: Inositol and its derivatives comprise a huge field of biology. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates in its free form, with its isomers or its phosphate derivatives, to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response. AREAS COVERED: Bioavailability, safety, uptake and metabolism of inositol is discussed emphasizing the complexity of interconnected pathways leading to phosphoinositides, inositol phosphates and more complex molecules, like glycosyl-phosphatidylinositols. EXPERT OPINION: Besides being a structural element, myo-inositol exerts unexpected functions, mostly unknown. However, several reports indicate that inositol plays a key role during phenotypic transitions and developmental phases. Furthermore, dysfunctions in the regulation of inositol metabolism have been implicated in several chronic diseases. Clinical trials using inositol in pharmacological doses provide amazing results in the management of gynecological diseases, respiratory stress syndrome, Alzheimer's disease, metabolic syndrome, and cancer, for which conventional treatments are disappointing. However, despite the widespread studies carried out to identify inositol-based effects, no comprehensive understanding of inositol-based mechanisms has been achieved. An integrated metabolomics-genomic study to identify the cellular fate of therapeutically administered myo-inositol and its genomic/enzymatic targets is urgently warranted

Early transcriptional activation of the Hsp70.1 gene by osmotic stress in one-cell embryos of the mouse

In fertilized mouse eggs, de novo transcription of embryonic genes is first observed during the S phase of the one-cell stage. This transcription, however, is mostly limited to the male pronucleus and possibly uncoupled from translation, making the functional meaning obscure. We found that one-cell mouse embryos respond to the osmotic shock of in vitro isolation with migration of HSF1, the canonical stress activator of mammalian heat shock genes, to pronuclei and by transient transcription of the hsp70.1, but not hsp70.3 and hsp90, heat shock genes. Isolated growing dictyate oocytes also display a nuclear HSF1 localization, but, in contrast with embryos, they transcribe both hsp70.1 and hsp70.3 genes only after heat shock. Intranuclear injection of double-stranded oligodeoxyribonucleotides containing HSE, GAGA box or GC box consensus sequences, and antibodies raised to transcription factors HSF1, HSF2, Drosophila melanogaster GAGA factor, or Sp1 demonstrated that hsp70.1 transcription depends on HSF1 in both oocytes and embryos and that Sp1 is dispensable in oocytes and inhibitory in the embryos. Hsp70.1 thus represents the first endogenous gene so far identified to be physiologically activated and tightly regulated after fertilization in mammals

Preoperative evaluation of basal free triiodothyronine in patients undergoing coronary artery bypass grafting surgery. Does it help?

noBackground &amp; Objectives: The postoperative Low T3 syndrome has been considered as a possible source of reduced myocardial contractility, resulting in increased mortality after CABG. Effect of preoperative Low T3 has not been well studied in patients undergoing CABG surgery. Aim of our study is to evaluate effect of preoperative Low T3 syndrome in patients undergoing CABG surgery.Materials &amp; Methods: Six hundred and six patients undergoing CABG were included in this prospective study. The impact of the base-line FT3 concentration and of preoperative low T3 syndrome on the risk of postoperative low cardiac output and hospital death was analyzed.Results: Fifteen patients (2.3%) postoperatively and 159 (26.2%) developed major complications. At univariate analysis a reduced EF, the presence of peripheral vascular disease, the NYHA class, the surgical urgency, the aortic cross-clamp time, the CPB time and the FT3 concentration at admission were significantly associated with low CO and higher mortality. At multivariate analysis, the CPB time, an emergency procedure, a reduced LVEF, and the fT3 concentration were independently related to the development of low CO. However, in multivariate analysis low EF, and the fT3 concentration were the only predictors of hospital death.Conclusion: We conclude that preoperative low EF and low T3 syndrome independently causes low cardiac output and higher mortality in patients undergoing CABG. Therefore, all patients undergoing CABG should be evaluated for low T3 syndrome and patients with low T3 syndrome should be considered at increased risk. Appropriate preoperative T3 replacement therapy could decrease the postoperative complications in patients undergoing CABG.JCMS Nepal. 2015; 11(2):1-7</p

Does myo-inositol effect on PCOS follicles involve cytoskeleton regulation?

Inositol metabolism is severely impaired in follicles obtained from cystic ovaries, leading to deregulated insulin transduction and steroid synthesis. On the contrary, inositol administration to women suffering from polycystic ovary syndrome (PCOS) has been proven to efficiently counteract most of the clinical hallmarks displayed by PCOS patients, including insulin resistance, hyperandrogenism and oligo-amenorrhea. We have recently observed that myo-inositol induces significant changes in cytoske- letal architecture of breast cancer cells, by modulating different biochemical pathways, eventually mod- ulating the epithelial–mesenchymal transition. We hypothesize that inositol and its monophosphate derivatives, besides their effects on insulin transduction, may efficiently revert histological and functional features of cystic ovary by inducing cytoskeleton rearrangements. We propose an experimental model that could address not only whether inositol modulates cytoskeleton dynamics in both normal and cystic ovary cells, but also whether this effect may interfere with ovarian steroidogenesis. A more compelling understanding of the mechanisms of action of inositol (and its derivatives) would greatly improve its therapeutic utilization, by conferring to current treatments a well-grounded scientific rationale