Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Epigenetic regulation of learning and memory by Drosophila EHMT/G9a

The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the "writers" of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5' and 3' ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.     

Inflammatory and Immunological parameters in adults with Down syndrome

Background  

The increase in life expectancy within the general population has resulted in an increasing number of elderly adults, including patients with Down syndrome (DS), with a current life expectancy of about 50 years. We evaluate the parameters of humoral and cellular immune response, the quantitative expression of the regulator of calcineurin1 gene (RCAN1) and the production of cytokines. The study group consisted of adults DS (n = 24) and a control group with intellectual disability without Down syndrome (ID) (n = 21) and living in a similar environmental background. It was evaluated serology, immunophenotyping, the quantitative gene expression of RCAN1 and the production of cytokines.     

The reaction center is the sensitive target of the mercury(II) ion in intact cells of photosynthetic bacteria

The sensitivity of intact cells of purple photosynthetic bacterium Rhodobacter sphaeroides wild type to low level (<100 μM) of mercury (Hg2?) contamination was evaluated by absorption and fluorescence spectroscopies of the bacteriochlorophyll-protein complexes. All assays related to the function of the reaction center (RC) protein (induction of the bacteriochlorophyll fluorescence, delayed fluorescence and light-induced oxidation and reduction of the bacteriochlorophyll dimer and energization of the photosynthetic membrane) showed prompt and later effects of the mercury ions. The damage expressed by decrease of the magnitude and changes of rates of the electron transfer kinetics followed complex (spatial and temporal) pattern according to the different Hg2? sensitivities of the electron transport (donor/acceptor) sites including the reduced bound and free cytochrome c? and the primary reduced quinone. In contrast to the RC, the light harvesting system and the bc? complex demonstrated much higher resistance against the mercury pollution. The 850 and 875 nm components of the peripheral and core complexes were particularly insensitive to the mercury(II) ions. The concentration of the photoactive RCs and the connectivity of the photosynthetic units decreased upon mercury treatment. The degree of inhibition of the photosynthetic apparatus was always higher when the cells were kept in the light than in the dark indicating the importance of metabolism in active transport of the mercury ions from outside to the intracytoplasmic membrane. Any of the tests applied in this study can be used for detection of changes in photosynthetic bacteria at the early stages of the action of toxicants.     

Acoustic evidence of airway opening during recruitment in excised dog lungs.

The aim of this study was to test the hypothesis that the mechanism of recruitment and the lower knee of the pressure-volume curve in the normal lung are primarily determined by airway reopenings via avalanches rather than simple alveolar recruitments. In isolated dog lung lobes, the pressure-volume loops were measured, and crackle sounds were recorded intrabronchially during both the first inflation from the collapsed state to total lobe capacity and a second inflation without prior degassing. The inflation flow contained transients that were accompanied by a series of crackles. Discrete volume increments were estimated from the flow transients, and the energy levels of the corresponding crackles were calculated from the sound recordings. Crackles were concentrated in the early phase of inflation, with the cumulative energy exceeding 90% of its final value by the lower knee of the pressure-volume curve. The values of volume increments were correlated with crackle energy during the flow transient for both the first and the second inflations (r(2) = 0.29-0.73 and 0.68-0.82, respectively). Because the distribution of volume increments followed a power law, the correlation between crackle energy and discrete volume increments suggests that an avalanche-like airway opening process governs the recruitment of collapsed normal lungs.     

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small alpha-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow alpha migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.     

Effects of atorvastatin on the HDL subpopulation profile of coronary heart disease patients

We investigated the effects of atorvastatin on the lipid and the apoA-I-containing HDL subpopulation profiles in 86 patients with established coronary heart disease (CHD). The entire drug treatment period lasted 12 weeks (4-week periods of 20 then 40, then 80 mg/day). Each dose of atorvastatin treatment resulted in significant reductions in plasma total-C, LDL-C, and triglyceride (TG), and non-significant increases in HDL-C levels compared with placebo treatment. ApoA-I levels did not change significantly during any of the treatment periods. Despite the modest increase of HDL-C (6%, 7%, 5%) and no change in apoA-I levels, the distribution of the apoA-I-containing HDL subpopulations changed significantly during each treatment period. There were significant increases in the concentrations of the large LpA-I alpha-1 (24%, 39%, 26%) and pre alpha-1 (51%, 61%, 63%) subpopulations at the expense of the small lipoprotein LpA-I:A-II alpha-3 subpopulations which decreased on all doses, and the decreases were significant on the 40 and 80 mg/day doses (6%, 5%). Atorvastatin influences the lipid-related risk for CHD in two ways: first, it significantly decreases LDL-C and TG levels while increasing HDL-C, and second, it significantly shifts the HDL subpopulation profile of CHD patients toward that observed in subjects without CHD.