Second-trimester growth velocities in twin and singleton pregnancies.

OBJECTIVE: Previous small studies used individualized growth assessment (IGA) to characterize prenatal growth velocities of singletons and twins. We aimed to compare second-trimester growth velocities of individual anatomical parameters between monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins and singleton fetuses in a larger study. METHODS: This was a study of a novel cohort of 222 MCDA twins and previously published cohorts of 40 DCDA twins and 118 singletons with serial ultrasound data. Fetal biometric measurements of biparietal diameter, head circumference, abdominal circumference and femur diaphysis length from prenatal ultrasound examinations were used to calculate second-trimester growth velocities using direct calculation or linear regression analysis. Linear fit was assessed based on the coefficient of determination (R2 ). Mean growth velocities and variances were compared among the three groups. RESULTS: The majority of cases underwent three second-trimester ultrasound examinations with fetal biometry available. All fetuses had linear growth, with R2 > 99% for all parameters. Only 1-2% of all MCDA and DCDA anatomical parameters had abnormal growth velocity scores outside the 95% reference range for singletons. There were no significant differences in mean growth velocity for any parameter between MCDA twins and singletons. Femur diaphysis length growth velocity was significantly lower in DCDA twins than in both MCDA twins and singletons. There were no other significant differences among the groups. CONCLUSIONS: Expanding on prior work using IGA, we found that second-trimester growth velocity of the four major anatomical parameters overall was similar between twins and singletons and between MCDA and DCDA twins, supporting the use of singleton-derived growth standards for IGA in twins. Twin growth potential appears to be similar to that of singletons in the second trimester, suggesting that subsequent growth divergence may be due to third-trimester physiological or pathological changes in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ovarian hormone: lack of effect on reproductive structures of female Asian musk shrews.

Uterine and vaginal weights and histologies are not altered by ovariectomy or estrogen treatment in the Asian musk shrew (Suncus murinus). In addition, ovariectomized shrews mate. Thus, the role of ovarian hormones in the control of the reproductive status of this species does not conform to the accepted mammalian pattern.

Bent DNA functions as a replication enhancer in Saccharomyces cerevisiae.

Previous studies have demonstrated that bent DNA is a conserved property of Saccharomyces cerevisiae autonomously replicating sequences (ARSs). Here we showed that bending elements are contained within ARS subdomains identified by others as replication enhancers. To provide a direct test for the function of this unusual structure, we analyzed the ARS activity of plasmids that contained synthetic bent DNA substituted for the natural bending element in yeast ARS1. The results demonstrated that deletion of the natural bending locus impaired ARS activity which was restored to a near wild-type level with synthetic bent DNA. Since the only obvious common features of the natural and synthetic bending elements are the sequence patterns that give rise to DNA bending, the results suggest that the bent structure per se is crucial for ARS function.

Isolation and analysis of hepatoma nuclear proteins using monoclonal antibodies.

Monoclonal antibodies were prepared to nuclear nonhistone proteins from a 2-aminoacetyl fluorine-induced transplantable rat hepatocellular carcinoma. These antibodies recognized a total of six distinct antigens as revealed by molecular weight analysis. Studies of antigen specificity with respect to various tissues, tumors, cultured cells, and oncodevelopmental stages indicated that these nuclear species could be divided into two categories. Four antigens were classified as tumor related since they were significantly enriched in tumor tissue as compared to tissues of the normal adult rat. The remaining two antigens were detected only in tumors and transformed cells; one, only in certain hepatomas. Thus, these antigens were classified as tumor specific. As an initial step toward elucidating the function of these proteins, each antigen was isolated by immunoaffinity chromatography, radioiodinated in situ, and analyzed for the ability to bind DNA. Three antigens were positive for DNA binding, and one of these was selectively released from tumor nuclei with the transcriptionally active chromatin upon digestion with micrococcal nuclease. The implications of these results for the possible functional contribution of the six tumor antigens to transformation is discussed.

DNA distortion as a factor in nucleosome positioning.

In a previous report we constructed a synthetic DNA sequence that directed the deposition of histone octamers to a single site, and it was proposed that DNA distortion was involved in the positioning effect. In the present study we utilized the chemical probe potassium permanganate to identify sites of DNA distortion in the synthetic positioning sequence. A permanganate hypersite was identified 15 bp from the nucleosome pseudo-dyad at a site known to display DNA distortion in the mature nucleosome. The sequence of the site contained a TA step flanked by an oligo-pyrimidine tract. A series of substitutions were made in the region of the permanganate hypersite and the resulting constructs tested for affinity for histone octamers and translational positioning in in vitro studies. The results revealed that either a single base substitution at the TA step or in the adjacent homopolymeric tract dramatically affected affinity and positioning activity. The rotational orientation of the permanganate-sensitive sequence was shown to be important for functions, since altering the orientation of the site in a positioning fragment reduced positioning activity and octamer affinity, while altering the rotational orientation of the sequence in a non-positioning fragment had the opposite effects. A reconstituted 5 S rDNA positioning sequence from Lytechinus variegatus was also shown to display a permanganate hypersite 16 bp from its pseudo-dyad.

Flow kinetics of fibronectin secretion by livers of young preweanling rats.

Fibronectin is a high molecular weight adhesive glycoprotein present both on the cell surface (cellular fibronectin) and circulating free in the plasma (plasma fibronectin). To investigate the cellular origins of plasma fibronectin, monoclonal antibodies prepared against purified plasma fibronectin of the rat were used in both in vivo and in vitro pulse-chase experiments comparing livers of animals of different ages. For in vitro analyses, slices were pulsed with 3H-leucine and purified fractions of endoplasmic reticulum, Golgi apparatus and plasma membrane were prepared at various times post-chase and characterized morphologically. The total protein was solubilized with NP-40, and incorporation into fibronectin was determined from PAGE analysis of immunoprecipitates. Incorporation was greatest in 5-day-old animals, representing greater than 0.3% of the total radioactivity and was least in adults animals. Label appeared in fibronectin associated with the plasma membrane within 60 min. At earlier times, labeled fibronectin appeared first in the endoplasmic reticulum (30 min) and then in the Golgi apparatus (45 min). The findings demonstrate synthesis of fibronectin by rat liver and evidence for participation of liver endomembranes in its secretion.

Estrogen-induced uterine responses and growth: relationship to receptor estrogen binding by uterine nuclei.

The relationship between estrogen receptor(R) binding by uterine nuclei and uterotrophic responses was examined. Immature rats received a single injection of estradiol (E2) or estriol (E3) and the following parameters were measured: accumulation and retention of the estrogen receptor by the nuceus of uterine cells; incorporation of 14C-glucose into CO2 lipid, protein and RNA; RNA polymerase activity; water imbibition and increased dry weight. E2 and E3 were of equal potency with regard to the rapid accumulation of R by the nucleus but differed with respect to long term retention of R. The concentrations of nuclear RE2 and RE3 complexes were equivalent between 1 and 3 hr after estrogen injection; however, by 6 hr RE2 remained significantly elevated while RE3 levels had fallen to control values. E2 and E3 were also of equal potency with respect to the stimulation of enhanced glucose utilization, water imbibition, the incorporation of 14C-glucose into lipid, protein and RNA 3 hours following an injection of the hormone. Likewise the activity of RNA polymerase was equally stimulated by E2 and E3 3 hr after injection. Thus all early uterotropic responses (0-3 hrs) that were measured were equally stimulated by E2 and E3. However, E3 failed to stimulate true uterine growth (increase dry weight 24 hr after injection), whereas E2 produced a significant stimulation of true uterine growth. These data suggest that the RE complex is capable of stimulating early uterotrohic events regardless of which estrogen is present; however, in order to produce true uterine growth the RE complex must be retained in the nucleus for long periods of time. This proposal was tested by the administration of repetitive injections of E3. This treatment resulted in an increase in dry weight that was equivalent to the growth that was produced by repetitive injections of E2. These results demonstrate that E2 and E3 elicit early uterotrophic responses with equal facility following a single injection but that only E2 causes true uterine growth. The ability of E2 to stimulate true uterine growth appears to be related to the time of residence of the RE complex in the nucleus.

Role of the serum estrogen-binding protein in the control of tissue estradiol levels during postnatal development of the female rat.

The role of the serum estrogen-binding protein (EBP) in the control of tissue estradiol levels during postnatal development of the female rat was examined. The estradiol-binding capacity of serum from the 1-day-old rats far exceeded the physiological level of estradiol in serum. The binding capacity decreased exponentially during the first 5 weeks of life to reach the low adult level at about the time of vaginal opening on day 37. From these observations one would predict that EBP would bind estradiol in the serum of the neonate, thereby preventing tissue uptake of the hormone. As the levels of EBP decline with advancing age, there should be a corresponding shift in the distribution of estradiol from serum to tissues. We have taken in vivo and in vitro approaches to evaluate these proposals. Female rats of various ages (1 day to 1 yr old) were sacrificed 1 h after [3H]estradiol injection and the radioactivity in serum and tissues was determined. During the first 11 days of life, the concentration of [3H]estradiol in serum was greater than the concentration of this hormone in estrogen-sensitive (uterus) and insensitive (lung, cerebral cortex, and diaphragm) tissues. Tissue to serum ratios of [3H]estradiol increased progressively between 13-34 days and then plateaued at about the time of puberty (37 days of age) at levels which were 50- to 150-fold greater than those observed in the neonate. The increase in tissue to serum ratios of [3H]estradiol during postnatal development probably resulted from the decline in serum EBP, since injection of neonatal serum into 28-day-old rats reduced tissue to serum ratios of [3H]estradiol to levels which were similar to those observed in 16-day-old animals. To determine the effects of EBP on uterine uptake of estradiol in vitro, uteri from 21-day-old rats were incubated with [3H]estradiol and serum obtained from rats of various ages. As the concentration of serum EBP declined with advancing serum donor age, there was a corresponding increase in the uterine uptake of [3H]estradiol. These results suggest that the decline in EBP is responsible for the progressive increase in tissue to serum ratios of estradiol during the first 5 weeks of life. It is suggested that the increase in tissue to serum ratios of estradiol between days 13-37 postpartum is an important factor in the initiation of estrogenic events during postnatal sexual maturation in the female rat.

Compositional similarities between the human immunodeficiency virus and surface antigens of pathogens.

The genome of the human immunodeficiency virus (HIV) is rich in A but not U and deficient in C but not G. This asymmetric nucleotide bias is the major factor in determining the unusual composition of HIV proteins. In this report, we have identified the cellular genes in the GenBank database that are compositionally similar to HIV in order to further understand the significance of the nucleotide bias of the viral genome. A total of 101 genes in the bacterial and invertebrate subdivisions of the database were found to have a base composition that is similar to the composition of the HIV genome. The identified cellular sequences represent a discrete subset of the database since 81 of the 101 entries code for antigens from pathogens and nearly all of these organisms infect humans. The amino acid compositions of these surface antigens are also similar to the unusual composition of HIV proteins, which are deficient in proline and rich in lysine and other polar residues encoded by A-rich codons. The similarities between the HIV proteins and the immunodominant antigens from other pathogens may indicate a common pathogenic strategy for the promotion of immune dysregulation.

Major airway injury in closed chest trauma.

Major fracture of the intrathoracic airway following closed chest trauma is a potentially lethal injury which can be repaired successfully if the diagnosis is made early, Cough, dyspnea cyanosis, hemoptysis, mediastinal emphysema, or pneumothorax not responding to drainage via intercostal tube and a deterioration of the patient's clinical condition out of proportion to the apparent closed chest injury, should alert the clinician to the possiblity of this entity. This report describes the findings in a patient with a longitudinal disruption of the entire intrathoracic trachea and the findings in a second patient with complete transection of the right main bronchus. Each was repaired primarily, with eventual recovery, The principles of management of this difficult group of injuries are reviewed.

Surfing, self-medicating and safety: buying non-prescription and complementary medicines via the internet.

OBJECTIVE: To examine whether the sale of medicines via the internet supports their safe and appropriate use. DESIGN: e-Pharmacy websites were identified using key words and a metasearch engine and the quality of information published on these websites was surveyed using the DISCERN tool. A case scenario and internet pharmacy practice standards were also used to evaluate the quality of care delivered. SETTING AND PARTICIPANTS: Between July and September 2001 104 websites were surveyed and 27 sent either Sudafed (pseudoephedrine HCl), St John's wort products, or both to a residential address in Melbourne, Australia. MAIN OUTCOME MEASURES: Quality of health information (DISCERN ratings), information exchanged between e-pharmacy staff and consumers, and product and delivery costs. RESULTS: Of 104 e-pharmacies from at least 13 different countries, 63 websites provided some health information but overall the quality of the information was poor. Only three website operators provided adequate advice to consumers to avoid a potential drug interaction. The costs for a daily dose of pseudoephedrine HCl (240 mg) ranged from 0.81 Australian dollars to 3.04 Australian dollars, and delivery costs from 3.28 Australian dollars to 62.70 Australian dollars. CONCLUSION: Consumers who self-select medicines from websites have insufficient access to information and advice at the point of ordering and on delivery to make informed decisions about their safe and appropriate use.

Estimates of complications of medical care in the adult US population.

BACKGROUND: Total US population estimates of complications of medical care have relied on extrapolations of state-specific estimates. Generalizability is suspect because findings are limited by geographical location or time. We describe the relationship between the annual prevalence of complications of medical care (CM) and socio-demographic characteristics in the adult US population. METHODS: We used data from the National Health Interview Surveys, annual nationwide surveys of the resident, civilian, noninstitutionalized population of the United States. The main outcome of interest was self-reported conditions from CMs (ICD-9 996-999) and activity limitations that arise from such events. Univariate estimates and multivariably adjusted models accounting for selected socio-demographic characteristics and health status were derived. RESULTS: A total of 618,167 reports of conditions from 313,438 subjects 18 years and older from 1987 to 1994 were examined. In 1987, 830,386 adults reported complications of medical care, increasing by about 40% to 1,174,089 adults in 1994. Based on an extrapolation to the US adult population, rates increased by 25% from 558 to 678 per 100,000 during the same period. One-third reported onset a year prior to the interview; two-thirds visited a doctor six months prior; half experienced limitation in major activities; a quarter reported limitation in personal care activities. In the two weeks preceding the interview, complications of medical care caused an average of 1.72 days of restricted activity, 0.79 days spent in bed, and 0.58 days of work lost. Race modified the age-specific risk of these complications. CONCLUSIONS: Complications of medical care impose heavier morbidity than previously considered with some indication that socio-demographic variables modify the risk for injuries.

Improving question formulation for use in evidence appraisal in a tertiary care setting: a randomised controlled trial [ISRCTN66375463].

BACKGROUND: The specificity of clinical questions is gauged by explicit descriptions of four dimensions: subjects, interventions, comparators and outcomes of interest. This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the submitted question compared to using a standard form without instructions and examples. METHODS: A randomised controlled trial was conducted in an evidence-search and appraisal service. New participants were invited to reformulate clinical queries. The Control Group was given no instructions. The Intervention Group was given a brief explanation of proper formulation, written instructions, and diagrammatic examples. The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity. RESULTS: Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up. The remaining 17 Intervention Group and 22 Control Group participants were analysed. Baseline characteristics were comparable. Overall, 20% of initially submitted questions from both groups were properly specified (defined as an explicit statement describing all dimensions of specificity). On follow-up, 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up (p = 0.008) while the Control Group did not show any changes from baseline. Participants in the Intervention Group were also more likely to explicitly describe patients (p = 0.028), comparisons (p = 0.014), and outcomes (p = 0.008). CONCLUSIONS: This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries. The evaluation of the long-term impact of such changes is an area of continued research.

Preference for thinness in Singapore--a newly industrialised society.

BACKGROUND/AIMS: A cultural preference for thinness has been implicated in the development of eating disorders in Western, post-industrialised societies. In transitional societies like Singapore, a shift in expectations of ideal body size (toward thinness) may lead to an increase in eating disorders. This study investigated perceptions about body size and shape in over 200 youths living in Singapore, and the influences of adiposity, gender, Westernization and parents' education. METHODS: A self-administered questionnaire was used to gather social and cultural information from 137 males and 143 females, aged 17-22 years. It included questions relating to eating behaviour and body satisfaction from which a "preference for thinness score" was derived. Westernization was indicated by language spoken at home. Adiposity was measured by triceps skinfold and body mass index. Multiple linear regression analysis was used to assess the associations of adiposity, mother's education, father's education, and language spoken at home with the preference for thinness score. RESULTS: Dissatisfaction with body size and shape increased with tertile of adiposity among females, and thoughts about dieting and becoming thinner were present even among underweight girls. Unlike the females, the highest proportion of males satisfied with their body size and shape, was associated with the middle tertile of BMI. Speaking English at home, but not parents' education, was positively associated with body dissatisfaction after controlling for BMI. CONCLUSION: Chinese Singaporean female youths have a preference for thinness as an ideal body size. The epidemiology of eating disorders in Singapore and other newly industrialised societies warrants further investigation.