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PubMed2003

The normative development of child and adolescent problem behavior.

The aim of this study was to identify normative developmental trajectories of parent-reported problems assessed with the Child Behavior Checklist (CBCL; T. M. Achenbach, 1991) in a representative sample of 2,076 children aged 4 to 18 years from the general population. The trajectories were determined by multilevel growth curve analyses on the CBCL syndromes in a Longitudinal multiple birth-cohort sample that was assessed 5 times with 2-year intervals. Most syndromes showed a linear increase or decrease with age or a curvilinear trajectory, except for thought problems. Trajectories for most syndromes differed for boys versus girls, except those for withdrawn, social problems, and thought problems. These normative developmental trajectories provide information against which developmental deviance in childhood and adolescence can be detected.

Adolescent↗
PubMed2003

Maternal atopy and the number of offspring: is there an association?

We investigated the association between maternal atopy and the number of offspring. In a population- and pregnancy-based survey (part of the European Studies on Infertility and Subfecundity), we obtained information on the number of offspring, adverse pregnancy outcomes, age at pregnancy, and waiting time to pregnancy. The German portion of these surveys also included information on physician-diagnosis of asthma, atopic eczema, or hay fever. The odds ratio (OR) adjusted for age showed that the number of children was reduced among women with atopy (OR = 0.75, 95% CI: 0.57-0.98 in the pregnancy-based sample; OR = 0.79, 95% CI: 0.63-0.99 in the population-based sample). We did not identify other signs of reduced reproductive ability in atopic women. The results provide support for two assumptions: (i) either a lower number of offspring in atopic mothers combined with an increased risk of atopy in offspring of atopic mothers may explain the protective effect of a higher number of siblings on atopy in offspring; or (ii) successive pregnancies may decrease the atopic response of the mother and thus the risk of developing atopy in subsequent offspring.

Adult↗
PubMed2002

Breast-feeding multiples.

Human breast milk is the best nutrition for human infants. Its advantages over the milk of other species, such as cows, include both a reduced risk for infections, allergies and chronic diseases, together with the full nutritional requirements for growth and development. Breast-feeding is as important for multiples as for singletons. Despite the advantages, multiples receive less breast-feeding than singletons. Common reasons for not breast-feeding multiples include the fear of not fulfilling the infants' needs and the difficulty of coping with the demands on the mother's time. In addition, many multiples are delivered prematurely and by Caesarean section. Maternal pain and discomfort together with anxiety over the infants' condition are not conducive to successful breast-feeding. During lactation, the mother needs to add calories to her daily diet. It has been recommended to add approximately 500-600 kcal/day for each infant. Thus, between eating, nursing and sleeping, life is very busy for the mother of multiples. However, there is evidence that, with appropriate nutrition, one mother can nourish more than one infant. Also, simultaneous breast-feeding can save much time. Combined efforts of parents, close family, friends and the medical team can help to make either full or partial breast-feeding of multiples possible. However, when breast-feeding is not possible, health care workers need to carefully avoid judgmental approaches that may induce feelings of guilt.

Breast Feeding↗
PubMed2006

Comparison of multiple vertebrate genomes reveals the birth and evolution of human exons.

Orthologous gene structures in eight vertebrate species were compared on a genomic scale to detect the birth and maturation of new internal exons during the course of evolution. We found that 40% of new human exons are alternatively spliced, and most of these are cassette exons (exons that are either included or skipped in their entirety) with low inclusion rates. This proportion decreases steadily as older and older exons are examined, even as splicing efficiency increases. Remarkably, the great majority of new cassette exons are composed of highly repeated sequences, especially Alu. Many new cassette exons are 5' untranslated exons; the proportion that code for protein increases steadily with age. New protein-coding exons evolve at a high rate, as evidenced by the initially high substitution rates (K(s) and K(a)), as well as the SNP density compared with older exons. This dynamic picture suggests that de novo recruitment rather than shuffling is the major route by which exons are added to genes, and that species-specific repeats could play a significant role in recent evolution.

Alternative Splicing↗
PubMed2004

Cystic renal neoplasia following conditional inactivation of apc in mouse renal tubular epithelium.

Alterations in Wnt/beta-catenin signaling have been linked to abnormal kidney development and tumorigenesis. To gain more insights into the effects of these alterations, we created mice carrying a conditional deletion of the Apc tumor suppressor gene specifically in the renal epithelium. As expected, the loss of Apc leads to increased levels of beta-catenin protein in renal epithelium. Most of these mice die shortly after birth, and multiple kidney cysts were found upon histological examination. Only rarely did these animals survive to adulthood. Analysis of these adults revealed severely cystic kidneys associated with the presence of renal adenomas. Our results confirm an important role for proper regulation of Wnt/beta-catenin signaling in renal development and provide evidence that dysregulation of the pathway can initiate tumorigenesis in the kidney.

Adenoma↗
PubMed1998

Perinatal factors influencing survival in extremely low-birthweight infants.

The majority of deaths in normally formed infants occur in extremely low birth weight infants (< 1000 g). Survival rates for these infants have improved greatly but still vary from centre to centre and accurate local outcome figures are important for counselling parents and upholding standards of care. In the Rotunda Hospital, Dublin, over the 6 year period from 1 January 1990 to 31 December 1995, there were 34 474 deliveries over 500 g birthweight. One hundred and twenty-six of these were normally formed infants between 500 g and 999 g. Our objective was to analyse the factors influencing survival in these extremely low birthweight (ELBW) infants. Overall survival in the group was 63%. The most significant factors influencing survival to 28 days were gestation and birthweight. Survival increased from 33% at 24 weeks to 100% at 28 weeks' gestation and from 29% at 500-599 g to 87% at 900-999 g birthweight. Having controlled for gestational age, none of the following variables had a significant effect on survival: year of birth; gender; multiple pregnancy; 1-minute Apgar score; maternal age; parity; use of antenatal steroids; a history of antepartum haemorrhage, pre-eclamptic toxaemia or prolonged rupture of membranes. A 5-min Apgar score > 5 increased the chance of survival by 3.97 (95% CI: 1.46- 10). Both mode of delivery and incidence of chorioamnionitis had an influence on survival which varied according to the gestational age. A larger cohort of survivors would illustrate the effect of these variables more clearly.

Journal Article↗
PubMed1994

Twin children in The Gambia: evidence for genetic regulation of physical characteristics in the presence of sub-optimal nutrition.

It has been demonstrated that physical growth characteristics are subject to genetic regulation. However, in developing countries, environmental factors such as food availability and frequent infections are associated with growth faltering which is particularly marked in infancy. We have conducted anthropometric measurements of a cohort of twin children aged less than 14 years living in a rural area of The Gambia to ascertain the extent to which genetic factors influence physical growth in the presence of a sub-optimal diet. Almost 25% of the children were more than 2SD below the median of the reference population in terms of their height-for-age Z score, indicating a marked level of undernutrition. Nevertheless, the within-pair variances were significantly less for monozygous than for dizygous twin pairs for the following variables: height, head circumference and body mass index (p < 0.01); weight (p < 0.02) and mid upper arm circumference (p < 0.1), indicating that there is a strong genetic influence on growth regulation despite the sub-optimal nutrition.

Adolescent↗
PubMed2003

Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death.

Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be caspase-dependent, apparently involving mitochondrial release of cytochrome c, a known pro-apoptogenic factor. We extend those studies and report that activation of caspases in MKs, either constitutively or after Fas ligation, yields platelets that are functionally responsive and evade immediate phagocytic clearance, and retain mitochondrial transmembrane potential until constitutive platelet death ensues. Furthermore, the exclusion from the platelet progeny of caspase-9 present in the progenitor accounts for failure of mitochondrial release of cytochrome c to activate caspase-3 during platelet death. Thus, progenitor cell death by apoptosis can result in birth of multiple functional anucleate daughter cells.

Amino Acid Chloromethyl Ketones↗
PubMed1971

The mouse intestinal microflora with emphasis on the strict anaerobes.

The various components of the intestinal microflora in the mouse become established according to a definite time sequence; the strict anaerobes are the last groups of bacteria to reach their maximum population levels, 14-16 days after birth. The multiplication of these strict anaerobes in the mouse intestine seems to depend upon the prior multiplication of other bacterial species, and coincides with the ingestion of food other than maternal milk. These two conditioning factors may correspond to the establishment of a suitably reduced Eh potential and to the provision of certain metabolites. Once established, the strict anaerobes constitute by far the largest percentage of the total intestinal microflora; most of them are associated in a viable form with the mucosa. In normal animals they persist at very high levels throughout the life span. However, their populations can be drastically reduced by dietary manipulation of the animal, by administration of vancomycin, or by certain disease processes of the intestine. The strict anaerobic bacteria seem to play an important, and perhaps essential role in the maintenance of the anatomic structures and physiological functions of the intestine. They also seem to hold in check several species of intestinal bacteria, in particular the coliform bacilli.

Age Factors↗
PubMed2003

Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development.

BACKGROUND: It is of fundamental importance for IVF clinics to determine the most viable embryos for transfer. The challenge for ART clinics is to transfer fewer embryos, thereby minimizing the risk of multiple-infant births, while still maintaining the greatest chance of pregnancy for their patients. In this study, an investigation was made to determine if developmental markers on the day of fertilization (day 1) can predict good subsequent blastocyst development. METHODS AND RESULTS: A total of 1550 individually cultured 2PN embryos from 191 patients undergoing IVF/ICSI treatment at the Yale University Center for Reproductive Medicine and Infertility from February to December 2001 was included. The results showed a significant positive relationship between early-cleaving 2-cell embryos and subsequent good quality > or =4-cell, > or =7-cell and blastocyst development (P < 0.05). PN symmetry (the relative size of the PN to each other), when checked at the time fertilization, is also a significant indictor of good quality > or =4-cell, > or =7-cell stage embryos and blastocysts. Combined, a developing embryo showing PN symmetry with early cleavage and subsequent good > or =4-cell and > or =7-cell cleavage, has a one in two chance of developing into a good-quality blastocyst. CONCLUSION: Early embryo assessment can be used as an indicator of subsequent good blastocyst development.

Adult↗
PubMed2004

Identification of a direct Dlx homeodomain target in the developing mouse forebrain and retina by optimization of chromatin immunoprecipitation.

Understanding homeobox gene specificity and function has been hampered by the lack of proven direct transcriptional targets during development. Dlx genes are expressed in the developing forebrain, retina, craniofacial structures and limbs. Dlx1/Dlx2 double knockout mice die at birth with multiple defects including abnormal forebrain development and decreased Dlx5 and Dlx6 expression. We have successfully applied chromatin immunoprecipitation (ChIP) to identify a direct transcriptional target of DLX homeoproteins from embryonic tissues in vivo. We optimized cross-linking conditions to enrich for protein-DNA complexes, then using specific high affinity DLX antibodies captured immunoenriched DLX genomic DNA transcriptional targets. DLX homeobox proteins bind differentially to the Dlx5/Dlx6 intergenic enhancer in newborn retina (DLX2) and embryonic striatum (DLX1, DLX2) in situ. Reporter gene assays demonstrated the functional significance of the binding of DLX proteins to this regulatory element, confirmed in vitro by electrophoretic mobility shift assays, using tissue extracts or recombinant DLX proteins. ChIP provides the best approach to identify direct Dlx homeoprotein targets from developing tissues in situ. The use of this technology will advance our understanding of Dlx gene function in the vertebrate in vivo and can be applied to examine targets of other homeobox genes and other classes of transcription factors.

Animals↗
PubMed1996

Decision making in the neonatal intensive care environment.

Consideration as to whether withdrawal of intensive care support might be a more appropriate line of action than to continue with full intensive care has become a part of the life and death decision making process undertaken in neonatal intensive care units. After outlining the moral objectives of delivery of health care, the arguments for taking quality of life and its various components into account during these deliberations are presented. The circumstances in which the appropriateness of continuing care should be considered are highlighted and the care options presented. The crucial importance of allowing time for parents to come to terms with the situation is emphasised as is the need for giving clear guidelines to junior staff over resuscitation issues. Finally, an environment for providing optimal family support during the process of withdrawal is suggested.

Abnormalities, Multiple↗