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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Risk factors for low birthweight in north-east Brazil: the role of caesarean section.

Caesarean section (CS) delivery is associated with low birthweight (LBW) in south-east Brazil. A hospital-based study was conducted on singleton infants from mothers residing in São Luís, to assess if an association between CS and LBW was found in the northern part of the country, where the CS rate is lower than in the south-east. A standardised questionnaire was administered to a sample of 2541 mothers in 10 hospitals, representing 94% of all deliveries, from March 1997 to February 1998. In a logistic model, type of delivery was the independent variable, the other variables were treated as confounders, and interaction terms were added between type of delivery and all other factors. LBW was associated with low maternal height, maternal smoking, primiparity, previous LBW, public insurance, preterm birth and CS. The CS rate was 33.7%. The risk of CS was higher for primiparous and married mothers, those with high level of schooling and attended by the same physician during prenatal and delivery care, deliveries held in private hospitals, daylight hours or evenings, and for those mothers who had adequate prenatal care. Because it appears unlikely that only medical reasons are operative, it is a possibility that CS could cause LBW, reflecting abusive indications for elective CS.

Adult↗

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↗

Natural variation in the human sex ratio.

Analysis of the effect of multiple birth, birth order, age of parents and the sexes of preceding siblings on the secondary sex ratio was performed for 815 891 children, born in Denmark, 1980-1993. The proportion of males was analysed as a function of multiple birth, birth order, age of parents and the sexes of preceding siblings, using contingency tables, chi(2) tests and logistic regression analysis. The secondary sex ratio decreased with increased number of children per plural birth and with paternal age, whereas no independent effect was observed for maternal age, birth order, the sex of the preceding child, or the combination of sexes of previously born children in the family.

Adult↗

Live-birth rates and multiple-birth risk of assisted reproductive technology pregnancies conceived using thawed embryos, USA 1999-2000.

BACKGROUND: Increasing use of assisted reproductive technology treatments has been associated with the current rise in multiple births in the USA. Embryo cryopreservation and subsequent thawed embryo transfer may favourably impact the multiple-birth risk by relieving some pressure that patients and providers may feel to transfer several embryos in a single cycle. The study objective was to examine both live-birth rates and multiple-birth risk in thawed cycles. METHODS: The authors used a population-based sample of 21 555 assisted reproductive technology procedures performed in US clinics in 1999 and 2000 that used thawed embryos derived from the patient's oocytes. RESULTS: Both patient age and the number of embryos transferred were independent predictors of live birth. Even among women aged 20-29 years, the transfer of three embryos resulted in an increase in the live-birth rate compared with cycles in which one or two embryos were transferred. This increase in success was accompanied by an increased multiple-birth risk. In all age groups up to 40 years, the transfer of just two embryos resulted in a multiple-birth risk of 16-17%. The multiple-birth risk increased with the number of embryos transferred. CONCLUSIONS: Patient age and the number of embryos transferred significantly affect live-birth and multiple-birth rates among women who use thawed embryos.

Adult↗

A 39-year followup of the Genain quadruplets.

The Genains, a unique group of monozygotic female quadruplets, all developed a schizophrenic disorder by age 24. They have been studied since the 1950s, because of the rarity of this occurrence (estimated to be one in 1.5 billion) and because their illnesses varied in severity. The identical inheritance would tend to rule out genetic differences as the cause of the neuropsychological differences; however, we cannot disentangle the effects of early brain injury and harsh punitive treatment as factors accounting for the differences in the severity of their disorders. We conducted neuropsychological examinations of the Genains at age 66, compared their test profiles, and contrasted certain test scores at 66 with those at ages 27 and 51. Test results indicate generally stable (or even improved) performance over time and support the notion that cognitive decline is not a degenerative process in schizophrenia. The Genains remind us of the exquisite interaction among variables that must be understood before additional, satisfactory progress can be made in preventing the development and predicting the course of schizophrenia.

Adult↗

Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions.

According to National Vital Statistics Reports, premature infants (< 36 weeks gestation) account for approximately 7.4% of all births. During the 8 years from 1989 to 1997, multiple births steadily increased across all categories from twin to quintuplet and higher orders. During that same period low birth weight (< 2500 g) births increased almost 12%, and very low birth weight (< 1500 g) births increased approximately 20%.Attendant to these national trends in multiple and preterm births, overall gestation-specific survival rates have improved substantially. This improved outcome can be attributed in large measure to advances in neonatal care and technology. Despite the encouraging statistics on survival, infants born prematurely, at low or very low birth weights and/or with chronic conditions that predispose to lower respiratory tract illness, continue to incur serious risk of long term morbidity and the consumption of inpatient hospital services. In a recent 2-year study of US children, low and very low birth weights were found to be independent risk factors for bronchiolitis-associated mortality. In the past 14 years what defines bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) has shifted away from clinical, radiographic and pathologic findings in the preterm infant toward the pathophysiology of arrested lung development and the need for supportive care beyond 36 weeks corrected gestational age. The incidence of BPD/CLD ranges from 14 to 43%, with higher rates observed among infants of lower gestational age and birth weight. The health care team approach to the management of BPD directs its efforts toward minimizing pulmonary vascular resistance, alleviating airway obstruction and improving short term lung mechanics. Measures to prevent BPD/CLD attempt to forestall both acute and chronic lung function abnormalities. To that end researchers have investigated the early use of continuous positive airway pressure, vitamin supplementation and recombinant human copper/zinc superoxide dismutase. Despite significant gains in the survival of infants born at lower gestational ages, prematurity, low birth weight and/or underlying chronic pulmonary disease put the pediatric patient at risk for increased frequency and severity of respiratory syncytial virus lower respiratory tract illness and the potential for its long term sequelae.

Airway Obstruction↗

Reference birth-length range for multiple-birth neonates in Japan.

AIM: To clarify the birth length of twins according to gestational age. METHODS: We studied a total of 51,910 live-birth-live-birth pairs of twins, 4,561 triplet live births and 256 quadruplet live births, using data obtained from corresponding birth certificates. The birth length of twins was analyzed according to gestational age. RESULTS: Compared to singleton neonates, the median birth length of twins was approximately 0.5 cm smaller after the gestational age of 34 weeks, increasing to approximately 2.0 cm at 42 weeks of gestation. The median birth length according to gestational age was found to be the greatest in twins, lower in triplets and the lowest in quadruplets, in which the difference was <2.0 cm. CONCLUSION: The birth length of twins was smaller than that of singletons, but the difference was smaller than the difference in birthweight between twins and singletons.

Birth Order↗

Causes of late fetal death in New Zealand 1980-1999.

BACKGROUND: In recent years there has been an emerging interest in sudden unexplained intrauterine death. AIMS: To determine the major causes of late fetal death (LFD) in New Zealand during 1980-1999 and to document the proportion of deaths considered unexplained. In addition, to quantify the number of LFD undergoing post-mortem during this period. METHODS: Using the Office for National Statistics (UK) hierarchical classification system, all information available on death certificates was used to assign a single cause to LFD for the period 1980-1999. Trends were analysed using logistic regression and risk factor profiles established for each cause of death. Post-mortem rates and the characteristics of those failing to undergo post-mortem were analysed for the period 1989-1999. RESULTS: LFD rates declined from 60.1 per 10 000 in 1980-1981 to 30.5 in 1998-1999. The declines were not uniform across all causes, with intrapartum deaths declining 73%, congenital anomalies 70% and antepartum asphyxia 50%. In contrast, unspecified deaths increased 1%, and with the decline in other causes of death, also increased proportionally, from 10.8% of LFD in 1980-81 to 28.1% in 1998-1999. Post-mortem rates fell by 31% during 1989-1999, with Maori and Pacific babies and those in more deprived New Zealand Deprivation Index areas being significantly less likely to undergo post-mortem. CONCLUSIONS: While total LFD rates declined significantly during 1980-1999, rates of unspecified LFD remained static. Low post-mortem rates, however, suggest that many of these deaths may be uninvestigated rather than truly unexplained. Nevertheless, the persistence of a category of death which, to date, has failed to improve with advances in obstetric technology suggests that further measures are necessary if New Zealand's LFD rates are to continue to decline.

Adult↗

Breastfeeding twins and higher-order multiples.

The benefits of breastfeeding for pre-term and full-term infants are well documented. Breastfeeding facilitates maternal-infant attachment, provides optimal infant nutrition and immunologic protection, and minimizes economic impact. These benefits are multiplied with twins and higher-order multiples, who often are born at risk. Supporting a mother as she initiates and continues to breastfeed one infant requires specific knowledge and skills. Health professionals need additional knowledge and skills if they are to provide appropriate assessment, intervention, and support when a mother breastfeeds twins or higher-order multiples.

Breast Feeding↗