bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal clinical factors influencing HIV‐1 transmission
Authors: Tovo P‐A , Gabiano C. , Tulisso S.
Published: March 2012

The complex puzzle of maternal factors involved in mother‐to‐child human immunodeficiency virus type 1 (HIV‐1) transmission is being put together. The risk of perinatal infection increases with mother's disease progression, but it remains stable in women seroconverting to HIV‐1 during pregnancy and in consecutive pregnancies. Thus, transmission correlates with the HIV‐1 progression rather than the duration of infection in the mother. Nutritional alterations such as vitamin A deficiency may also have a significant impact, whereas geographic origin and mode of maternal infection are of no influence. Placenta membrane inflammation and concurrent sexually transmitted diseases are other significant covariates. The rate of transmission appears directly correlated with maternal age and inversely with length of gestation. A protective effect of caesarean section has been reported in some observational studies but, being controversial, these results need to be corroborated by randomized trials.
Identification of HIV infection in pregnancy: another era
Authors: Saba J.
Published: March 2012

In order to be successfully implemented, some interventions to prevent vertical transmission of human immunodeficiency virus (HIV) will require prior identification of HIV‐infected women. The testing and counselling of pregnant women should therefore be promoted. Promoting testing and counselling within prenatal clinics would be a good strategy; however, additional data on the social and economic implications of HIV testing are needed to demonstrate the relevance of such a strategy. Promotion of testing and counselling should be developed in collaboration with community‐based organizations, non‐governmental organizations and people living with HIV, in order to increase the involvement and understanding of the community at large.
The future of prenatal HIV testing*
Authors: Minkoff H. , Willoughby A.
Published: March 2012

The use of zidovudine for the prevention of mother‐to‐child transmission of human immunodeficiency virus, as well as continuing advances in our understanding of the determinants of that transmission, and of potential new avenues of intervention augur ever more efficient perinatal prevention strategies in the near future. In this paper the evolving role of prenatal testing in an era of ever more successful interventions will be discussed. At least four factors will be critical in determining what that role will be: clinical, legal, ethical and economic. Each of these are parochial, i.e. they will feature in eradication strategies in different ways in different geographical, economic and cultural settings. An understanding of these factors will help to suggest what course testing policy should take and to determine the role clinicians must play if any testing policy is to succeed in contributing to the end of pediatric HIV disease.
Reducing the risk of perinatal HIV‐1 transmission with zidovudine: results and implications of AIDS Clinical Trials Group protocol 076
Authors: Mofenson LM
Published: March 2012

This paper reviews the rationale for the AIDS Clinical Trials Group (ACTG) protocol 076 design, the study results and the implications of these results, including discussion of the US Public Health Service Task Force recommendations on the use of zidovudine to reduce perinatal transmission and for prenatal human immunodeficiency virus (HIV) counseling and testing.
Human immunodeficiency virus infection and mode of delivery
Authors: Peckham C. , Newell M‐L
Published: March 2012

Most children acquire human immunodeficiency virus (HIV) infection vertically from an infected mother. Indirect evidence suggests that a substantial proportion of infection is acquired around the time of delivery, which suggests that this would be an appropriate time to intervene. If intrapartum transmission of HIV occurs primarily through direct exposure of the infant to cell‐associated or free HIV in genital secretions or blood during passage through the birth canal, or by ascending infection, caesarean section performed prior to labour might reduce the risk of transmission. There is insufficient evidence to justify routine caesarean section deliveries for HIV‐infected women, and a randomized clinical trial of mode of delivery has started in Europe.
Overview of the potential role of vitamin A in mother‐to‐child transmission of HIV‐1
Authors: Semba RD
Published: March 2012

Vitamin A is an essential micronutrient for normal immune function. Vitamin A deficiency is common among human immunodeficiency virus (HIV)‐infected pregnant women and is associated with higher mother‐to‐child transmission of HIV‐1 and increased infant mortality. The biological mechanisms by which vitamin A deficiency could influence mother‐to‐child transmission of HIV‐1 include impairment of immune responses in both mother and infant, abnormal placental and vaginal pathology and increased HIV viral burden in breastmilk and blood. Clinical trials are currently in progress to determine whether daily micronutrient supplementation, including vitamin A, during pregnancy can reduce mother‐to‐child transmission of HIV‐1.
Breastfeeding and vertical transmission of HIV‐1
Authors: Kreiss J.
Published: March 2012

An estimated one‐third to one‐half of vertical transmission of human immunodeficiency virus type 1 (HIV‐1) worldwide is due to breastfeeding. The exact frequency of breast milk HIV‐1 transmission is unknown, but it has been estimated to be 14% in the setting of established maternal HIV‐1 infection and 29% in the setting of acute maternal infection. The timing of breast milk transmission during the course of lactation also remains unknown, but two studies have found an association between duration of breastfeeding and risk of infant infection. In one such study, prolonged breastfeeding for 15 months or longer was associated with a twofold increased transmission risk. Human immunodeficiency virus type 1 DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and vitamin A deficiency. The presence of breast milk HIV‐1 provirus is associated with increased transmission risk. Many current intervention strategies to prevent vertical transmission of HIV‐1 are aimed at in utero or perinatal transmission. In developing countries in which breastfeeding by HIV‐1 infected women is recommended practice, additional intervention strategies to reduce breast milk transmission warrant evaluation.
Gene regulation of cell adhesion molecules in neural morphogenesis
Authors: Edelman GM , Jones FS
Published: March 2012

A mounting body of evidence suggests that cell‐cell adhesion molecules (CAMs) play critical roles in morphogenetic patterning and in laying down the initial tissue scaffold of the nervous system. Perturbations of CAM binding can lead to altered tissue pattern and interruption of tissue interactions to altered patterns of CAM expression. The combined factors that regulate the expression of CAMs and that drive early neural development are, however, largely unknown. We have hypothesized that the coordinate expression of homeobox (Hox) and paired box (Pax) transcription factors in various axes of the body plan leads to differential expression of particular CAM genes. Following this hypothesis, we have characterized the promoters and other regulatory regions of a number of genes specifying CAMs and have identified cis‐regulatory elements that bind and respond to Hox and Pax proteins. Our recent experiments in vitro indicate, for example, that transcription factors encoded by Hox and Pax genes bind to specific DNA sequences in the N‐CAM promoter and activate expression of the N‐CAM gene. Experiments on transgenic mice carrying either the wild‐type N‐CAM promoter or a variant with mutations in the homeodomain binding sites (HBS) linked to a lac‐Z reporter gene indicate that interactions with these elements are important in establishing and maintaining N‐CAM expression in the spinal cord. We have also examined the regulatory sequences controlling expression of the gene for the neuron‐glia adhesion molecule (Ng‐CAM). Unlike N‐CAM, which is also expressed in many non‐neural sites, Ng‐CAM is restricted to cells of the nervous system. After identifying this promoter for the Ng‐CAM gene, we characterized a silencer region in the first intron of the gene that extinguishes the expression of Ng‐CAM in fibroblasts but not in neuronal cells. Thus, a default mechanism can account for the restriction of Ng‐CAM expression to the nervous system. The silencer region contains five neural‐restrictive silencer elements and a binding site for the Pax3 protein, which also appears to have silencing activity. All of these findings suggest that Hox and Pax transcription factors can have both activating and silencing functions in regulating CAM gene expression. The general significance of these accumulated observations is that they connect the place‐dependent expression of gene products capable of direct morphoregulation to the function of pattern‐forming genes.
Cortical dynamics
Authors: Gilbert CD
Published: March 2012

Our ability to interpret visual scenes involves assembling the components of objects into a unified percept and segregating them from background, storing information about earlier visual experiences and testing our interpretations of the visual world against incoming sensory input. The influences of context, experience and expectation are reflected in the response properties of cells at early stages in the visual pathway. The responses of cells in primary visual cortex depend not only on the attributes of features lying within the classical receptive field but also on the global characteristics of the contours and surfaces within which these features are embedded. The substrate for lateral interactions includes a plexus of long‐range horizontal connections within each cortical area that links columns of similar orientation specificity and cells with widely separated receptive fields. The horizontal connections also play a role in the plasticity of receptive field structure and of cortical functional architecture, induced over long time scales by retinal lesions and over short time scales by patterned visual stimulation. The long‐term changes are associated with synaptogenesis; and the short‐term changes with an increase in synaptic effectiveness. The dynamics of cortical function persist throughout adulthood and are general to all cortical areas, including primary sensory cortices.
Rise of neurogenetic determinism
Authors: Rose SPR
Published: March 2012

A critical review of the assumptions underlying the gene/environment dichotomy in explaining the origins of human behaviour, together with their biological and social consequences.
Nature and nurture in the development of postural control in human infants
Authors: Hadders‐Algra M. , Brogren E. , Forssberg H.
Published: March 2012

Nowadays, the controversy on “nature” and “nurture” in motor development focuses on the development of automatic motor patterns. The present paper discusses this issue within the framework of a recent study on the effect of maturation and training on the development of postural adjustments in sitting infants. This study revealed that already before the age of sitting without help, highly variable but direction‐specific muscle activation patterns are present. This suggests that postural adjustments develop via an innate repertoire of primary direction‐specific response patterns. The following developmental step consists of a decrease in muscle activation patterns, which results in selection of the most complete patterns of synergist activation. In accordance with Edelman's neuronal group selection theory, pattern selection turned out to be experience dependent, as it appeared to be guided by cues on head stabilization and enhanced by daily balance training.
Experience Producing Drive Theory: how genes drive experience and shape personality
Authors: Bouchard TJ
Published: March 2012

There is now a large body of evidence from twin and adoption studies linking genetic variation to phenotypic variation on virtually all human individual differences. Individuals unquestionably influence the nature of their experiences, e.g. high‐sensation seekers surround themselves with like‐minded peers and seek out quite different experiences than low‐sensation seekers. We propose a theory called Experience Producing Drive Theory—Revised, to account for the current findings in behavior genetics. This theory is based on the Darwinian view that complex organisms are active agents “designed” by natural selection to survive in the environments in which they evolved. The theory assumes that the behavior of complex organisms can best be understood in terms of motives, preferences and emotional responses that have evolved to drive specific behavioral patterns. We propose a number of ways in which this theory might be falsified.
Fetal and infant growth and impaired glucose tolerance in adulthood: the “thrifty phenotype” hypothesis revisited
Authors: Hales CN
Published: March 2012

The epidemiological links observed between fetal and infant growth and impaired glucose tolerance in adult life that led to the formulation of the “thrifty phenotype” hypothesis have been confirmed by others in widely differing populations. The proposed nutritional basis of these links has been tested in an animal model in which rat dams were fed an isocaloric low‐protein diet and the postwearing normally fed offspring were studied. Permanent changes in key hepatic enzymes of glycolysis and gluconeogenesis and reductions in both insulin and glucagon sensitivity of the liver have been observed. Glucose tolerance deteriorated more at age 15 months compared with controls but animals were not frankly diabetic. The longevity of offspring was affected positively when growth was retarded by postnatal protein restriction, but negatively when protein restriction during pregnancy was followed by cross‐fostering of pups to normally fed dams with consequent “catch‐up” growth. These effects were greatest in males. The thrifty phenotype hypothesis continues to provide a useful conceptual and experimental basis for the study of the aetiology of non‐insulin‐dependent diabetes.
The fetal origins of coronary heart disease
Authors: Barker DJP
Published: March 2012

Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological and structural parameters. Studies in humans have shown that men and women whose birthweights were at the lower end of the normal range, who were thin or short at birth or small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations.
Hypoxia‐ischaemia model in the 7‐day‐old rat: possibilities and shortcomings
Authors: Hagberg H. , Bona E. , Gilland E. , Puka‐Sundvall M.
Published: March 2012

The Levene model in 7‐day‐old rats is the most often used model of hypoxia—ischaemia (HI) in immature animals. The rat central nervous system is immature at birth and corresponds neurodevelopmentally to the term human infant during the second postnatal week. The Levene model of HI differs from clinical asphyxia with respect to the unilateral distribution of brain injury and lack of multi‐organ dysfunction. Furthermore, it does not allow cardiovascular monitoring or repeated blood sampling. On the other hand, the progressive nature of HI bears many similarities to birth asphyxia with regard to blood flow changes and cellular metabolic derangements. The model is well characterized, easy to carry out and the low cost allows inclusion of a sufficient number of animals for dose‐response evaluation of neuroprotective agents. In addition, it provides the unique opportunity of long‐term evaluation of neuropathological and functional outcome.
Vulnerable but invincible: high‐risk children from birth to adulthood
Authors: Werner EE
Published: March 2012

This report summarizes the major findings of a 40‐year longitudinal study of a multi‐racial cohort of children who had been exposed to poverty, perinatal stress, parental psychopathology and family discord. Individuals are members of the Kauai Longitudinal Study, which followed all children born in 1955 on a Hawaiian island from the prenatal period to middle age. Several clusters of protective factors were identified that enabled most of the high‐risk individuals to develop into competent, confident and caring adults. Implications of the findings for developmental theory were discussed and issues for future research identified.
Schizophrenia: developmental disturbance of brain and mind?
Authors: Stefan MD , Murray RM
Published: March 2012

Schizophrenia is the most severe of the mental illnesses and affects approximately 0.8% of the population in Western societies. Postmortem and neuroimaging studies show that patients with schizophrenia have slightly larger cerebral ventricles than normal and a decrease in cortical volume, most markedly in the left temporal lobe. These changes are present at diagnosis and appear to show little change over extended periods of follow‐up. Associated findings such as lack of normal cerebral asymmetry and cytoarchitectonic changes suggestive of impaired migration of cortical neurons implicate aberrant neurodevelopment. Schizophrenics also show an excess of pregnancy and birth complications, and an association with prenatal exposure to maternal influenza. These and reports of abnormal psychological development in pre‐schizophrenic children add further support to the theory that the disorder has neurodevelopmental origins.
New growth hormone assays: potential benefits
Authors: Strasburger CJ , Dattani MT
Published: March 2012

Three recently published new assays are described for the measurement of growth hormone (GH). Two of these – the eluted stain assay (ESTA) and the immunofunctional assay (IFA) – have been developed to measure the bioactivity of GH, rather than the immunoactivity as measured by conventional radioimmunoassays (RIAs). The third assay – the 22 kDa exclusion assay (22 k GHEA) – is designed to measure the concentrations of the different isoforms of GH present in the circulation. The ESTA is a variant of the Nb2 bioassay for lactogenic hormones, but has been adapted for specific GH measurement in serum samples. It has a lower detection limit than previous bioassays and permits the quantification of GH in large series of samples. The IFA uses a binding‐site‐specific antibody in combination with GH‐binding protein (GHBP) in order to quantify only those GH molecules that are able to dimerize the extracellular domain of the GH receptor (GHBP), which is a prerequisite for GH signal transduction in target cells. The IFA is as convenient to use as immunoassays and can be employed routinely for GH determinations. The clinical usefulness of the 22 k GHEA has not been established, but it should provide a means of augmenting our understanding of the regulation of GH and its various isoforms. Once the ESTA bioassay or the IFA become commercially and widely available, either could replace the RIA as the standard reference method for measuring GH, as both more closely reflect the biologically active proportion of GH in serum samples than that measured by RIA. □ Growth hormone assays, eluted stain assay, immunofunctional assay, bioassay, 22 kDa growth hormone exclusion assay, growth hormone isoforms
Secular changes in growth and maturation: an update
Authors: Hauspie RC , Vercauteren M. , Susanne C.
Published: March 2012

Secular changes in growth and maturation in recent decades have been reviewed for various populations. The secular increase in attained height during the growth period is continuing in most countries, but has slowed down. The increase in adult stature over the past decades has varied between 0.3 and 3.0 cm/decade. The secular trend in the tempo of growth (earlier menarche and peak height velocity, and shortening of the growth cycle) has come to a halt in some populations, but is continuing or has been reversed in others. The secular trend in attained height and in the tempo of growth is usually more pronounced in children from low socioeconomic backgrounds, in those with poorly educated parents or in those from rural areas. It is concluded that updates of growth standards are required in all populations. More marked secular changes appear to occur in the lower height centiles, which may have direct implications on the future definition of ‘short stature’ in a population. □Secular trend, adult stature, growth, menarche, tempo of growth
The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH‐releasing hormone receptor gene
Authors: Baumann G. , Maheshwari H.
Published: March 2012

We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone‐releasing hormone receptor (GHRH‐R) locus on chromosome 7. Amplification and sequencing of the GHRH‐R gene in affected subjects demonstrated an amber nonsense mutation (GAG → TAG; Glu50 → Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH‐R in its extracellular domain, which is likely to result in a severely disabled or non‐existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone‐releasing hormone (GHRH)–growth hormone—insulin‐like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH‐R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH‐R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD. □ Growth hormone deficiency, growth hormone‐releasing hormone receptor, nonsense mutation, dwarfism
Prader—Willi syndrome and the hypothalamus
Authors: Swaab DF
Published: March 2012

Dysfunction of various hypothalamic systems may be the basis of a number of symptoms in Prader—Willi syndrome. The often abnormal position of the baby in the uterus at the onset of labour, the high percentage of infants with asphyxia and the high proportion of children born prematurely or post‐maturely may all be related to abnormal fetal hypothalamic systems, as the fetal hypothalamus plays a crucial role in labour. Abnormal luteinizing hormone‐releasing hormone neurones are thought to be responsible for the decreased levels of sex hormones, resulting in non‐descended testes, undersized sex organs and insufficient growth during puberty. A lack of growth hormone‐releasing hormone may also contribute to the short stature of patients with Prader—Willi syndrome. In addition, the aberrant control of body temperature and daytime hypersomnolence may result from hypothalamic disturbances. The number of oxytocin neurones – the putative satiety neurones – in the hypothalamic paraventricular nucleus is markedly decreased in Prader—Willi syndrome. This is presumed to be the basis of the insatiable hunger and obesity of patients with the syndrome. □ Growth hormone, growth hormone‐releasing hormone, hypothalamus, insatiable hunger, obesity, oxytocin, perinatal problems, Prader—Willi syndrome
Effects of growth hormone treatment on growth and body composition in Prader—Willi syndrome: a preliminary report
Authors: Lindgren AC , Hagenäs L. , Müller J. , Blichfeldt S. , Rosenborg M. , Brismar T. , Ritzén EM ,   Swedish National Growth Hormone Advisory Group
Published: March 2012

A controlled, randomized study was conducted to assess the effect of growth hormone (GH) treatment on growth, body composition and behaviour in prepubertal children (3–12 years of age) with Prader—Willi syndrome. GH treatment was given to one group of 15 patients (group A) at a dose of 0.1 IU/kg/day for 2 years. The second group (group B; n = 12) was not treated for the first year and was then given GH at a dose of 0.2 IU/kg/day for the second year. All patients had low 24‐hour levels of GH and insulin‐like growth factor I before GH treatment. Height velocity SDS increased from −1.9 ± 2.0 to 6.0 ± 3.2 during the first year of GH treatment in group A, and from −1.4 ± 1.2 to 10.1 ± 3.9 in the second year of the study in group B. When GH treatment was stopped, height velocity declined dramatically. Height SDS followed a similar pattern. GH treatment reduced the percentage body fat and increased the muscle area of the thigh. Isometric muscle strength was also increased. In addition, GH treatment appeared to have psychological and behavioural benefits, which were reversed after cessation of treatment. It was concluded that GH treatment improves growth, body composition and behaviour in children with Prader—Willi syndrome. □ Prader—Willi syndrome, growth hormone treatment, growth, body composition, behaviour
One‐year results of growth hormone treatment of short stature in Prader—Willi syndrome
Authors: Hauffa BP
Published: March 2012

At least part of the short stature in Prader—Willi syndrome may be explained by a decreased growth hormone (GH) secretory capacity, which occurs in most patients. To study the effects of exogenous GH on growth and body composition, 17 prepubertal children with Prader—Willi syndrome, with a short projected final height, were randomized to a control group (n = 9) or a treatment group (n = 8). Children in the treatment group received GH (0.15 IU/kg/day s.c.) for 1 year. One patient in the treatment group developed pseudotumor cerebri, which resolved after discontinuation of GH; this patient was omitted from further analysis. After 1 year, height velocity in the GH‐treated group was significantly increased (+5.5 SD) compared with reference values for normal healthy children, whereas there was a decrease in the control group (–2.3 SD). The difference in height velocity between the treated and control groups was significant (p = 0.0012). Concentrations of both insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 increased significantly in the GH‐treated group (p < 0.008). A gain in height was noted for chronological age (+1.07 SD) after 1 year of GH treatment. Height gain (+1.02 SD) remained unchanged when analysed in relation to bone age. No differences between the groups were found for parameters of weight and body composition. In conclusion, although GH appears to have beneficial effects on height, long‐term studies are necessary before recommendations can be made concerning GH treatment in children with Prader—Willi syndrome. □ Body composition, growth, growth hormone treatment, height velocity, insulin‐like growth factor‐binding protein‐3, insulin‐like growth factor I, Prader—Willi syndrome, side‐effects
Hypothalamic targets for growth hormone secretagogues
Authors: Robinson ICAF
Published: March 2012

Various novel growth hormone (GH) secretagogues have been developed. GH secretagogues release GH directly from the pituitary via a pathway distinct from that involving GH‐releasing hormone (GHRH). However, they also act centrally to activate hypothalamic neurones, and require an intact GHRH system for potent in vivo activity. Both normal and transgenic growth‐retarded (Tgr) rats release GH in response to GH secretagogues, and their responses are sensitive to the pattern of secretagogue administration. GH secretagogues are not completely specific for GH release, but also activate the adrenocorticotrophin‐adrenal axis, implying that they have additional central actions. The recent cloning of an endogenous receptor for GH secretagogues now makes it possible to identify central targets for their action. An endogenous receptor implies the existence of an endogenous ligand, but its, site of production, relationship to the xenobiotic pharmacological agents and its underlying physiological relevance remain unclear. □ Growth hormone secretagogue, adrenocorticotrophin, growth hormone‐releasing hormone, transgenic rats, GH secretagogue receptor, growth hormone‐releasing peptide‐6
Age‐related growth hormone‐releasing activity of growth hormone secretagogues in humans
Authors: Arvat E. , Camanni F. , Ghigo E.
Published: March 2012

Growth hormone‐releasing peptides (GHRPs) are synthetic molecules with strong, dose‐related and reproducible growth hormone (GH)‐releasing activity in humans. GHRPs act at both the pituitary and the hypothalamic level, where specific receptors have been located. In adults, GHRPs release more GH than does GH‐releasing hormone (GHRH), whilst their co‐administration has a synergistic effect, indicating that they have, at least partially, different mechanisms of action. However, normal activity of GHRH‐secreting neurones is needed to achieve the full GH‐releasing effect of GHRPs. In contrast to GHRH, the GH‐releasing activity of GHRPs is not further increased by substances acting via inhibition of hypothalamic somatostatin, and is only blunted by substances that stimulate hypothalamic somatostatin release. Even free fatty acids and exogenous somatostatin, which act directly on somatotrophs, do no more than blunt the effect of GHRPs. Thus, the GH‐releasing activity of GHRPs is partially refractory to inhibitory influences. GHRPs act, at least in part, by antagonism of somatostatin activity, both at the pituitary and the hypothalamic level. The GH‐releasing effect of GHRPs is not dependent on gender, but undergoes age‐related variations. Gonadal steroids seem to influence the activity of GHRPs only in childhood. The reduced GH response to GHRPs in the elderly is probably due mainly to concomitant GHRH hypoactivity and somatostatinergic hyperactivity. A preserved GH‐releasing effect of GHRPs has been reported in acromegaly, anorexia nervosa, hyperthyroidism and in critically ill patients. GHRPs have also been found to increase GH release in children with idiopathic short stature, in GH deficiency and in obese patients, in whom there is a well‐known reduction of somatotroph function. The GH response to GHRPs is markedly reduced in hypothyroidism and Cushing's syndrome. □ Growth hormone, growth hormone‐releasing hormone, growth hormone‐releasing peptides, growth hormone secretagogues, ageing
Variation of bone age progression in healthy children
Authors: Benso L. , Vannelli S. , Pastorin L. , Benso A. , Milani S.
Published: March 2012

Bone age assessments were related to auxological variables in 407 Italian boys, between 7 and 12 years of age, in order to elucidate the factors that affect the rate of skeletal maturation and to examine the possibility of using measures of skeletal maturation to evaluate individual patients. Using the radius—ulna—short bones (RUS) method of assessment, bone age velocity was greater in the Italian boys than for the UK reference standards, although there was considerable interindividual dispersion around the mean. Bone age velocity and height velocity were poorly correlated, and there was little correlation between skeletal and pubertal maturation. There was a slight positive correlation between bone age velocity and height SDS and between bone age velocity and body mass index. Bone age estimations using RUS were greater than those obtained using the carpus. In conclusion, the marked interindividual deviation in measured bone ages makes it difficult to relate data on an individual basis to other measures of growth and maturation. □ Bone age, bone age velocity, skeletal maturation, height, height velocity, body mass index
Can we predict and prevent adult morbidity in males with childhood‐onset growth hormone deficiency?
Authors: Vandeweghe M.
Published: March 2012

In order to achieve an optimal quality of life and minimize morbidity in adulthood, the therapeutic management of patients with childhood‐onset growth hormone deficiency (GHD) should follow strict guidelines. Optimal final height should be obtained by the early diagnosis of GHD and subsequent adequate growth hormone (GH) dosing and duration of treatment. Moreover, particularly in males with associated gonadotrophin deficiency, the psychosexual maladjustment could be prevented by the earlier induction of puberty, completion of the male phenotype and testicular stimulation with gonadotropins or luteinizing hormone‐releasing hormone. Finally, a satisfactory peak bone mass could be attained by continuation of GH treatment for some years after cessation of linear growth. □ Childhood‐onset growth hormone deficiency, pubertal induction, quality of life, optimal peak bone mass
Morphometry of fetal growth
Authors: Hobbins J.
Published: March 2012

Intrauterine growth retardation (IUGR) complicates about 5% of all pregnancies and is responsible for substantial perinatal mortality and morbidity. With ultrasound, it is possible to assess fetal brain growth indirectly by measurement of the biparietal diameter, head circumference and transcerebellar diameter. As liver size is affected most profoundly by IUGR, measurement of the abdominal circumference of the fetus provides the earliest evidence of fetal growth restriction. Placental size, assessed with ultrasound, can also indicate the severity of the condition. Once a fetus is diagnosed as having IUGR, its well‐being can be monitored with standard heart‐rate testing and ultrasound assessment of fetal behaviour. Doppler analysis of the wave form of the fetal arterial and venous circulation hold the greatest promise for managing pregnancies complicated by IUGR. □ Intrauterine growth retardation, fetal growth, ultrasound measurements, brain growth, liver growth, placental size
Pathophysiology of intrauterine growth retardation: role of the placenta
Authors: Pardi G. , Marconi AM , Cetin I.
Published: March 2012

The placenta is essential for normal fetal development. Failure of the placenta can result in many fetal conditions, for example, intrauterine growth retardation (IUGR). Placentas from pregnancies complicated by IUGR show vascular damage, which may lead to the onset of pregnancy‐induced maternal hypertension. Accurate placental assessment may, therefore, indicate which fetuses are at risk of IUGR and so improve clinical evaluation and management of both the fetus and the mother. Placental development and function can be assessed by a number of methods, including measurement of placental weight at mid‐gestation (placental growth in the second trimester correlates strongly with placental weight at birth), assessment of fetal and placental circulation (an association between perinatal morbidity and abnormal blood velocity profiles has been established) and assessment of placental metabolism and nutritional transfer (a reduction in transfer of nutrients may be an early indicator of IUGR). □ Intrauterine growth retardation, placenta, placental growth, placental transport, placental metabolism
Hormonal status of short children born small for gestational age
Authors: Boguszewski M. , Bjarnason R. , Jansson C. , Rosberg S. , Albertsson‐Wikland K.
Published: March 2012

The present study was undertaken to evaluate the hormonal status in a subgroup of prepubertal children born small for gestational age (SGA) who lacked postnatal catch‐up growth. In this subgroup, a reduced rate of growth hormone (GH) secretion was found, compared with reference groups of healthy children born appropriate for gestational age, of either normal or short stature at the time of investigation. In addition, an abnormal pattern of GH secretion was observed in short children born SGA, which was most pronounced in the younger children, and involved an increased frequency of GH peaks of low amplitude, combined with increased baseline secretion. Levels of insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 were also reduced in short children bora SGA, compared with the reference groups. These findings may explain, in part, the lack of postnatal catch‐up growth in short children born SGA. □ Small for gestational age, growth hormone secretion, growth hormone‐binding protein, insulin‐like growth factor I, insulin‐like growth factor‐binding protein‐3
Growth hormone treatment of short children born small for gestational age
Authors: Czernichow P.
Published: March 2012

The administration of growth hormone (GH) for a short period to short children born small for gestational age increases growth velocity. Children receiving 2–3 times the replacement dose gained nearly 2.0 SDS in height over a 3‐year treatment period. This treatment is well tolerated, without significant side‐effects. Further studies of the growth rate following cessation of GH treatment will reveal whether the gain in height is maintained, and whether the final height prediction is improved. □ Growth hormone, intrauterine growth retardation, short stature, bone maturation, metabolism
Paternal Child Care and Relationship Quality: A Longitudinal Analysis of Reciprocal Associations
Authors: Schober Pia S.
Published: March 2012

This study explored reciprocal associations between paternal child‐care involvement and relationship quality by following British couples from the birth of a child until he or she reached school age. It extends the literature by distinguishing between paternal engagement in absolute terms and relative to the mother and by considering relationship quality reports of mothers and fathers and family breakdown. The analysis was based on the British Millennium Cohort Study, a representative survey of children born in 2000 and 2001 and their parents (N = 5,624 couples). The author applied ordinary least squares regression analysis with lagged dependent variables and event history modeling. Fathers' relative child‐care share was positively associated with mothers' relationship satisfaction, whereas fathers' absolute child‐care frequency was positively related to their own perceived relationship quality for most time periods. Fathers' relative and absolute child‐care contributions were positively associated with relationship stability over the preschool years. Greater perceived relationship quality of mothers, but not fathers, was associated with more frequent paternal engagement.
Farewell to Moms? Maternal Contact for Seven Countries in 1986 and 2001
Authors: Treas Judith , Gubernskaya Zoya
Published: March 2012

Challenging the popular narrative of the long‐run decline of the extended family, contemporary studies of intergenerational relations insist that the ties between adult children and their parents are increasing in importance. Although research documents a decline in multigenerational households, there is little empirical evidence on changes over time in other dimensions of intergenerational solidarity. Drawing on 1986 and 2001 data from the International Social Survey Programme, the authors analyzed trends in maternal contact in 7 Western countries: (a) Australia, (b) Austria, (c) Germany (West), (d) Great Britain, (e) Hungary, (f) Italy, and (g) the United States (N = 7,578). They found no evidence that adult children's contact with mothers became less frequent. In particular, contacts that do not require face‐to‐face interaction increased, consistent with the diffusion of cell phones and Internet use over the period. Although theorizing points to demographic developments as driving trends in intergenerational cohesion, changes in population composition played only a minor role.
Familism, Interparental Conflict, and Parenting in Mexican‐Origin Families: A Cultural–Contextual Framework
Authors: Taylor Zoe E. , Larsen‐Rife Dannelle , Conger Rand D. , Widaman Keith F.
Published: March 2012

The present investigation examined the relations between the cultural belief of familism and various aspects of family functioning and child adjustment, including interparental conflict, parenting, and children's attachment to school, in a sample of 549 two‐parent Mexican‐origin families. The results indicated that parents' familistic values were negatively associated with interparental conflict for both mothers and fathers. Parents' familistic values were also indirectly associated with parenting through the marital relationship. Interparental conflict was negatively associated with nurturant‐involved parenting for both parents, but particularly for fathers. Interparental conflict had an indirect negative effect on children's attachment to school via mothers' and fathers' nurturant‐involved parenting. Both paternal and maternal nurturant‐involved parenting behaviors were positively associated with children's attachment to school across two time points. Child gender differences are also discussed.
Life Course Changes of Children and Well‐being of Parents
Authors: Kalmijn Matthijs , De Graaf Paul M.
Published: March 2012

How do children's life course transitions affect the well‐being of their parents? Using a large panel survey among parents with longitudinal information on 2 randomly chosen children, the authors analyzed the effects of children's union formation, parenthood, and union dissolution on changes in depressive symptoms of parents. Negative effects were found for children's divorce, and positive effects were found for children's marriage and parenthood. Mothers suffered more from a child's divorce or separation than fathers. Effects depended in part on the parent's traditional family norms, pointing to a normative explanation of life course effects. Little evidence was found for explanations in terms of altruism or selfish motivations. In a more general sense, this article supports the notion of linked lives suggested by the life course perspective. This research provides stronger support for this notion than the few previous studies that have examined it.
Balance of human choline kinase isoforms is critical for cell cycle regulation
Authors: Gruber Jens , See Too Wei Cun , Wong Mun Teng , Lavie Arnon , McSorley Theresa , Konrad Manfred
Published: March 2012

The enzyme choline kinase (CK), which catalyzes the phosphorylation of choline to phosphorylcholine in the presence of ATP, has an essential role in the biosynthesis of phosphatidylcholine, the major constituent of all mammalian cell membranes. CK is encoded by two separate genes expressing the three isoforms CKα1, CKα2 and CKβ that are active as homodimeric or heterodimeric species. Metabolic changes observed in various cancer cell lines and tumors have been associated with differential and marked up‐regulation of the CKα genes, and specific inhibition of CKα activity has been proposed as a potential anti‐cancer strategy. As a result, less attention has been given to CKβ and its interaction with CKα. With the aim of profiling the intracellular roles of CKα and CKβ, we used RNA interference (RNAi) as a molecular approach to down‐regulate the expression of CK in HeLa cells. Individual and simultaneous RNAi‐based silencing of the CK α and β isoforms was achieved using different combinations of knockdown strategies. Efficient knockdown was confirmed by immunodetection using our isoform‐specific antibodies and by quantitative real‐time PCR. Our analyses of the phenotypic consequences of CK depletion showed the expected lethal effect of CKα knockdown. However, CKβ‐ and CKα + CKβ‐silenced cells had no aberrant phenotype. Therefore, our results support the hypothesis that the balance of the α and β isoforms is critical for cancer cell survival. The suppression of the cancer cell killing effect of CKα silencing by simultaneous knockdown of both isoforms implies that a more effective CK‐based anti‐cancer strategy can be achieved by reducing cross‐reactivity with CKβ.
Acute Effects of Ethanol on Glutamate Receptors
Authors: Möykkynen Tommi , Korpi Esa R.
Published: March 2012

Several studies have revealed that acute ethanol inhibits the function of glutamate receptors. Glutamate receptor‐mediated synaptic plasticity, such as N‐methyl‐d‐aspartate‐dependent long‐term potentiation, is also inhibited by ethanol. However, the inhibition seems to be restricted to certain brain areas such as the hippocampus, amygdala and striatum. Ethanol inhibition of glutamate receptors generally requires relatively high concentrations and may therefore explain consequences of severe ethanol intoxication such as impairment of motor performance and memory. Effects of ethanol on glutamate system of developing nervous system may have a role in causing foetal alcohol syndrome. Newly found regulatory proteins of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid AMPA receptors seem to affect ethanol inhibition thus opening new lines of research.
Deflationism (About Theories of Truth)
Authors: Armour‐Garb Bradley
Published: March 2012

In this article, I provide a general account of deflationism. After doing so, I turn to truth‐deflationism, where, after first describing some of the species, I highlight some challenges for those who wish to adopt it.
The triumph of regulatory politics: Benefit–cost analysis and political salience
Authors: Shapiro Stuart , Morrall III John F.
Published: March 2012

While benefit–cost analysis (BCA) is now a permanent part of the regulatory process in the United States, and many other countries around the world as well as the European Union have adopted it or are moving toward it, there have been few empirical attempts to assess either whether its use improves regulations or how BCA interacts with the political environment. We use a unique US database of the costs and benefits of 109 economically significant regulations issued between 2000 and 2009 to examine whether the amount of information provided in the BCA or political factors surrounding the regulation better correlate with the net benefits of the regulation. We find that there is little correlation between the information provided by the analysis and the net benefits. However, we find that regulations that receive few public comments and are not issued at the end of an administration, have the highest net benefits. These are the regulations that are the least politically salient. This interaction between the political environment and the economic performance of a regulation has been under‐examined and deserves further study.
Examination of ten thousand years of mitochondrial DNA diversity and population demographics in bowhead whales (Balaena mysticetus) of the Central Canadian Arctic
Authors: McLeod Brenna A. , Frasier Timothy R. , Dyke Arthur S. , Savelle James M. , White Bradley N.
Published: March 2012

Abstract

Mitochondrial DNA (mtDNA) sequences were analyzed from 106 bowhead whale (Balaena mysticetus) specimens dating 471 ± 44 14C b.p.–10,290 ± 150 14C b.p. to evaluate whether historical changes in distribution and connectivity were detectable in levels of diversity and population structuring in the Central Canadian Arctic. The species has maintained levels of mtDNA diversity over 10,000 yr comparable to other nonbottlenecked large whale species. When compared to data from the Holocene East Greenland/Spitsbergen and contemporary Bering‐Chuckchi‐Beaufort populations, differentiation was low (FST≤ 0.005, ΦST≤ 0.003) and no temporal or geographical genetic structuring was evident. A combination of analyses suggests that the population has expanded over the past 30,000 14C yr. This genetic signature of expansion could result from population growth, admixture of multiple gene pools, or a combination of both scenarios. Despite known climatic change that altered bowhead distribution and led to isolation of populations, there is no detectable population structuring or change in genetic diversity during the Holocene. This may be due to long generation time, occasional population connectivity and a historically large global population. These characteristics warrant caution when interpreting contemporary bowhead whale DNA data, as it is unlikely that any population will be in mutation‐drift equilibrium.