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Mizukami T, Fujisawa M, Kanai Y, et al: Effects of trichostatin a, a histone deacetylase inhibitor, on mouse gonadal development in vitro. Merchant-Larios H: Germ and somatic cell interactions throughout gonadal morphogenesis. Bardoni B, Zabaria E, Guioli S, et al: A dosage delicate locus at chromosome Xp21 is involved in male to female intercourse reversal. Grimmond S, Van Hataren N, Siggers P, et al: Sexually dimorphic expression of protease nexin-1 and vanin-1 within the creating mouse gonad previous to overt differentiation suggests a task in mammalian sexual development. Hacker A, Capel B, Goodfellow P, Lovell-Badge R: Expression of Sry, the mouse sex-determining region gene. Buehr M, Gu S, McLaren A: Mesonephric contribution to testis differentiation within the fetal mouse. Swain A, Zanaria E, Hacker A, et al: Mouse Dax1 expression is consistent with a task in sex willpower in addition to in adrenal and hypothalamus perform. Kim Y, Bingham N, Sekido R, et al: Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation throughout male intercourse dedication. Hiramatsu R, Matoba S, Danai-Azuma M, et al: A crucial time window of Sry motion in gonadal sex dedication in mice. Sock E, Schmidt K, Hermanns-Borgmeyer I, et al: Idiopathic weight discount in mice deficient in the high-mobility-group transcription factor Sox8. Tannour-Louet M: Identification of de novo copy number variants related to human problems of sexual improvement. Bowles J, Bullejos M, Koopman P: A subtractive gene expression display suggests a job for vanin-1 in testis improvement in mice. Kumar S, Chatzi C, Brade T, et al: Sex-specific timing of meiotic initiation is regulated by Cyp26b1 unbiased of retinoic acid signalling. Baron D, Batista F, Chaffaux S, et al: Foxl2 gene and the event of the ovary: a story about goat, mouse, fish and lady. MacKenzie J, Chitayat D, McLorie G, et al: Penoscrotal transposition: a case report and evaluate. Haraguchi R, Suzuki K, Murakami R, et al: Molecular evaluation of exterior genitalia formation: the position of fibroblast growth factor (Fgf) genes during genital tubercle formation. Haraguchi R, Mo R, Hui C, et al: Unique capabilities of Sonic hedgehog signaling throughout external genitalia development. Human gonads of both sexes are intimately linked to the mesonephros all through early differentiation. Mesonephric cells, as well as cells from the ovarian surface epithelium, migrate concurrently with the primordial germ cells to populate and kind the future gonadal tissue at the ventrocranial aspect of the mesonephros. In the human, as in many other mammalian species, these events begin throughout fetal life, at a time when germ cells and somatic cells have populated the ovarian anlage. Meiosis and follicle formation are interrelated processes, the first being the prerequisite for the second, which secures survival of the oocyte. The primordial follicles thus fashioned will represent the ovarian reserve, providing a gradual variety of growing follicles, some of which is ready to develop to antral and potentially ovulatory phases in grownup life and their quantity thus determines the female reproductive lifespan. Once the theca cells have fashioned across the growing follicles, they provide the androgen substrate for conversion to estrogen by the granulosa cells, whereas differentiation of steroid-producing cells within the stroma could additionally be unrelated to the foregoing two events. In mammals the gonads come up from thickenings of the coelomic epithelium and are initially bipotential, having the capability to develop as a testis or an ovary. The proliferating germ cells (now termed oogonia) with intermingled somatic cells (precursors of the granulosa cell population) turn into separated from areas of somatic cells by a basement membrane. This prevents cell intermingling, although the basement membrane�enclosed regions are open on the periphery of the ovary. Within these germ cell cords, the germ cells divide with incomplete cytokinesis (forming what are sometimes referred to as germ cell nests), subsequently entering meiosis before nest breakdown and primordial follicle formation. The first indications that the detached gonad is becoming a testis are the formation of the testicular cords enclosing the germ cells15 and the rounding up of the organ.

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Fever results from an elevation of the temperature setpoint by inflammatory cytokines, such as interleukin-1, that elevate prostaglandin E ranges in the hypothalamus; regular physiologic mechanisms then maintain physique temperature at this elevated setpoint. Heat loss happens by way of the placenta, fetal skin, amniotic fluid, and uterine wall. After delivery, the neonate has tremendous warmth losses via the skin that require functioning thermoregulatory mechanisms to stop hypothermia. Premature and low-birthweight infants are sometimes unable to maintain applicable body temperature and behave like poikilotherms rather than homeotherms. How the hypothalamus matures to the environmental conditions after delivery is still unknown. Although the hypothalamus is necessary for integrating and expressing emotion, different areas of the brain, together with the cortex, limbic system, and thalamus, work together with the hypothalamus to bring in regards to the various types of responses. The sympatheticadrenal-medullary system causes the well-known stress-induced launch of epinephrine. Sympathetic-adrenal-medullary activation, which is dependent on characteristics of each the situation and the person, happens in response to challenges, with a sooner onset than activation of the hypothalamic-pituitary-adrenal axis. Stress induction of the hypothalamic-pituitary-adrenal axis is energetic in newborns, al though it may be transiently blunted in extraordinarily preterm infants. Once the noxious stimulus has been eliminated, in healthy neonates cortisol levels shortly return to basal ranges. Hypothalamic endocrine exercise could be divided into two distinct classes as established by the anatomy of the hypothalamopituitary unit. Because the posterior pituitary gland, or neurohypophysis, is composed of axonal projections from the hypothalamus, the hormones released into the circulation by the posterior pituitary are literally made in cell bodies of the hypothalamus. In distinction, the anterior pituitary gland, or adenohypophysis, is a definite gland. The hypothalamus secretes various releasing and inhibiting elements that regulate anterior pituitary hormone synthesis and launch. These elements are made in hypothalamic neurons and are carried down axons to the median eminence. They then reach the anterior pituitary by the particular hypothalamohypophysial portal circulation, whereas the anterior pituitary hormones attain their goal organs by the peripheral circulation. Hypothalamic hormones stimulate or inhibit anterior pituitary release of a hormone, and the circulating levels of the pituitary hormone feed back to regulate hypothalamic hormone launch. For instance, increases in circulating prolactin concentrations stimulate hypothalamic secretion of dopamine (prolactin-inhibiting factor) into the hypothalamohypophysial portal circulation to prevent extreme prolactin launch by the pituitary; high prolactin levels additionally inhibit hypothalamic launch of vasoactive intestinal polypeptide, a hormone that stimulates prolactin launch. Within a third-order feedback pathway, a number of kinds of feedback loops exist: lengthy, short, and ultrashort feedback. Long-loop suggestions happens when hormones from peripheral endocrine goal cells or substances from tissue metabolism influence the production of hypothalamic hormones. Short-loop suggestions is second-order suggestions inside a third-order feedback system. When hypothalamic hormone launch impacts its own synthesis, ultrashort feedback has occurred. The mechanism of this ultrashort suggestions is either via neurotransmission between two cells in the hypothalamus or via pituitary tanycyte launch of the hormone into cerebrospinal fluid, which might regulate hypothalamic activity because the hypothalamus is located on the base of the third ventricle. Two neurosecretory techniques produce hypothalamic hormones (summarized in Table 142-4): magnocellular and parvocellular. Stimulatory suggestions is depicted as a stable arrow, and inhibitory feedback is depicted as a dashed arrow. Ultrashort feedback is coloured in pink, brief suggestions in blue, and long feedback in black. In distinction, the parvocellular secretory cells are small neurons, principally in the region of the tuber cinereum beneath the third ventricle, that produce the hypophysiotropic hormones. Because the hormonal techniques of the anterior pituitary are reviewed in detail in Chapters one hundred forty four to 146 and 148, we concentrate on the magnocellular system.

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Recent analysis reviewed by Baron and colleagues193 has revealed some fascinating insights and delivered to mild the existence of another gene involved in ovarian development in mammals, together with people. The polled mutation in goats is an approximately 12-kb deletion from a cis-regulating region, on band q43 on goat chromosome 1, that controls the expression of three contiguous genes. The genetics of the polled trait itself illuminates another intriguing characteristic of sexual growth: the independence from hormonal influence of a characteristic of secondary sexual maturity. However, latest work has shown that conditional knockout of Dmrt1 in adult Sertoli cells induces them to transdifferentiate into granulosa cells. Conditional ablation of this gene leads to ectopic activation of Sox9 and transdifferentiation of granulosa and theca cell lineages into Sertoli-like and Leydig-like cell lineages. Collectively, therefore, these findings point out that a lot stays to be uncovered, and that the gene networks concerned within the preliminary fate selection between testis and ovary could additionally be to some degree distinct from these required to keep gonadal id in adult life. Indifferent (bipotential) exterior structures are initially current in males and females. The testis produces androgens, which masculinize the labioscrotal folds to type a scrotum and the genital tubercle to type the penis. Internally, the mesonephric (wolffian) and paramesonephric (m�llerian) ducts will turn into male or feminine structures, respectively. Testicular androgen promotes development of the wolffian ducts into epididymides, vasa deferentia, and seminal vesicles, and absence of androgens results in degeneration of the wolffian ducts. Information on genes controlling feminine secondary sexual growth can be obtained from research on sufferers with pseudohermaphroditism. Thus in male pseudohermaphroditism a genetic male, having a testis, has female or ambiguous exterior and/or internal genitalia. Instead, they keep the basic female configuration, and the sex of the person is diagnosed as feminine at birth. In feminine pseudohermaphroditism, individuals have ambiguous or male-type exterior genitalia with female gonads and karyotype. Perloff and colleagues200 and others201-204 have described a distinct type of female pseudohermaphroditism related to malformations of the internal genital, urinary, and gastrointestinal tracts. The position of growth components within the differentiation of the genital tubercle has been explored in mice. Fgf8 and Fgf10 are implicated in external sexual differentiation; knockout of Fgf10 leads to marked sexual ambiguity. Cultured genital tubercle explants treated with antibody to Shh additionally confirmed no external genitalia at 12. Recently it has been shown that Fgf8 additionally has a job upstream of Shh212 and downstream of androgens. In Wnt7a-knockout mice, males fail to bear regression of the m�llerian duct, and females present irregular oviduct/ uterine improvement. Multiple Hox genes, together with the Hoxa and Hoxd teams, are concerned in sexual differentiation. For instance, compound double homozygous deficiency of Hoxa13 and Hoxd13 resulted in a whole absence of exterior genitalia. Furthermore, the Jost precept envisioned active induction of the testis solely; the ovary developed by default within the absence of testisdetermining elements. Furthermore, the Jost precept envisioned that all improvement of sexual dimorphism apart from that of the gonads was as a end result of hormones and unbiased of genetic sex. The sex dedication pathway, like most developmental pathways, has a strong tendency to maintain its operate. Redundancy in pathways may be part of the mechanism by which the homeostatic continuation of sexual development happens. One can surmise that numerous genes in the pathway could be up-regulated or down-regulated to compensate for deficiencies in different members of the pathway. Further understanding of the sex willpower pathway will come from research of altered gene expression in poor states and the placement and identification of modifier genes that alter the pathway. Jeays-Ward K, Dandonneau M, Swain A: Wnt4 is required for correct male as properly as feminine sexual growth. Cortez D, Marin R, Toledo-Flores D, et al: Origin and useful evolution of Y chromosomes across animals.

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Prenatal screening allows for diagnostic testing and subsequent pregnancy options, together with termination of the pregnancy, preparation for the birth of a child with persistent or deadly sickness or using superior reproductive technology to avoid carrying a fetus with the disease in question. The validity of a screening take a look at is described by its sensitivity, specificity, and optimistic and adverse predictive values. Likelihood ratios enable the calculation of posttest odds primarily based on pretest odds and take a look at outcomes. To set cutoffs for tests with steady outcomes, a receiver operator attribute curve can be utilized. Pursuing multiple checks in sequence raises specificity whereas sacrificing sensitivity; conversely testing in parallel improves sensitivity at the expense of specificity. An efficient screening check should have wonderful specificity and sensitivity, must be acceptable to the population, must display for a prevalent and clinically necessary illness, should supply potential for diagnostic testing and intervention within the pure course of the illness and have to be price effective. Harms of screening include psychological distress and falsepositive results as well as harms resulting from subsequent diagnostic testing. Prenatal screening must be differentiated from prenatal diagnosis, during which a definitive prognosis is made. Prenatal prognosis first grew to become available in the 1960s with the introduction of amniocentesis for Down syndrome. At that point, the only display screen was maternal age; sufferers with advanced maternal age were offered amniocentesis as a diagnostic check. Prenatal screening contains both maternal (and sometimes paternal) and fetal screening. In the course of routine prenatal care, mothers are screened for a selection of situations corresponding to sexually transmitted ailments and gestational diabetes that can affect each the mom and fetus. Patients may be screened for carrying genetic ailments such as cystic fibrosis, haemoglobin S trait and Tay Sachs illness. Based on these results, additional testing similar to invasive fetal testing or paternal genetic testing may be beneficial. Finally, fetal screening focuses on screening the fetus for conditions corresponding to aneuploidy or congenital defects, and this may be accomplished both through maternal blood testing or fetal ultrasound. The outcomes of prenatal screening and subsequent diagnostic testing could additionally be used to decide to terminate a pregnancy, to prepare for the delivery of a child with chronic or fatal sickness or to use superior reproductive technology to keep away from carrying a fetus with the illness in query in a subsequent pregnancy. The objective of this chapter is to discover the basic principles underlying all of those screening exams. Persons with positive or suspicious findings should be referred to their physicians for analysis and essential remedy. Sensitivity is the power of a test to accurately establish those that have a disease. In this case, the sensitivity is 70/(70 + 30) = 70%, and the specificity is 800/(800 + 100) = 88. Predictive Values the ideas of sensitivity and specificity are properties of the take a look at itself. For instance, the sensitivity and specificity for detecting Down syndrome are greater than 99%, but in a 25-year-old lady (in whom the prevalence of Down syndrome is zero. Thus the fixed name for validation of latest exams in low-risk populations is improper because the sensitivity and specificity will clearly be the same regardless of the population examined. In our case, assume a pretest chance of Down syndrome of 10%, which was the prevalence of the syndrome in our fictitious inhabitants. We can covert the posttest odds again into a likelihood using the formula (probability = odds/[1 + odds]), which in our case is (P =. The placement of these reduce factors will tremendously influence the take a look at performance, particularly the sensitivity and specificity of the check. A classic example of minimize points in prenatal care is testing for gestational diabetes. Various research have tried to decide the optimal minimize level to differentiate between those who display screen optimistic and require a confirmatory diagnostic glucose tolerance check versus those who display adverse. To do that, the sensitivity for a number of reduce points is plotted on the y-axis of a graph as a operate of 1 � specificity on the x-axis. First, as described beforehand, the y-axis is the sensitivity, and the x-axis is 1 � specificity. The perfect diagnostic test maximises sensitivity and specificity and is represented by the upper left corner, the place the sensitivity and specificity are both 100%.

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Presently, this is solely possible using invasive diagnostic procedures corresponding to chorionic villus sampling or amniocentesis. Despite a number of makes an attempt over the past 20 years to retrieve and isolate fetal cells from the maternal circulation or cervix, this has not confirmed clinically viable. This screening technique has been quickly launched into medical care and is presently beneficial by main societies worldwide to be used in pregnancies at high threat for common whole-chromosome aneuploidies (trisomies 21, 18 and 13). This has the potential to be a true diagnostic take a look at utilizing improved molecular applied sciences similar to chromosomal microarray and sequencing. Their prevalence is estimated at 1 fetal to 104 to 108 maternal mononuclear cells. By far the largest problem with utilizing these rare and fragile cells for noninvasive testing stays their isolation from contaminating maternal cells without damage. Further separation during which the cells are stained with antibodies attached to ferrous beads identified to be fetal cell particular. Trophoblasts had been the first fetal cell sort to be detected in the maternal circulation24 but current challenges to their use for noninvasive prenatal prognosis. Despite these difficulties, modern studies proceed to present their potential worth. Of the cells higher than 15 M in measurement chosen by filtering, half had been confirmed as fetal. Concordance to fetal sex of 100 percent was potential if three or more fetal cells could be present in a sample. The average number of cells recovered per patient was 746 � fifty nine throughout the gestational ages. There was minimal maternal cell contamination, and 95% to one hundred pc of the cells isolated expressed confirmatory fetal-specific parameters. Nonetheless, to date, technical challenges have prevented this technology from growing right into a clinical tool. Although some teams are still exploring this approach, none has persistently demonstrated success. Fetal nucleated purple blood cells have been detected within the maternal circulation and have a relative quick half-life, making them particular to the current being pregnant. Stringent isolation standards are required to isolate and establish the fetal cells that are current at a focus of 1 in one hundred and five to 107 maternal nucleated cells. After initial staining with cell-specific markers, enrichment of fetal cells most frequently uses immunomagnetic or flow cytometric cell separation strategies, either alone or in combination. Other approaches attempted include separation by centrifugation utilizing a Ficoll gradient, filtration on a chip, lateral displacement and magnetophoresis, lectin-binding, dielectrophoresis, micromanipulation, laser microdissection and stress catapulting. Isolation of fetal nucleated cells for prenatal prognosis continues to be a expensive, labour-intensive and timeconsuming process and can remain so until dependable automated approaches turn into extra readily available. One example is the life science biotechnology company RareCyte, which has developed an progressive method utilizing sequential density fractionation to recover intact fetal cells. After discovery and characterisation, cells of interest are individually retrieved for extra downstream analysis. Mandel and Metais were the primary to report the presence of extracellular nucleic acids in the circulation in 1948. The ff remains comparatively stable between 10 and 21 weeks of gestation but then increases toward term. There is a significant unfavorable correlation between fetal fraction and maternal weight59 from a imply of about 12% for a maternal weight of 60 kg to 6% for a weight of a hundred and twenty kg. On the opposite hand, different research have shown fetal fraction to be lower with circumstances of trisomy 18 and monosomy X, probably related to a smaller placental measurement. The median fetal fraction per fetus in twin pregnancies is decrease than for singleton gestations. One million to 43 billion reads of 40 to 500 base pairs (bp) each may be obtained per run. Bioinformation analysis assigns sequences to their genomic origins, and the number of sequences per genomic task is counted. The variety of fragment reads from every specific chromosome are then quantified and compared with values from a traditional reference chromosome. A relative extra or deficiency in the variety of counts on the chromosome of interest compared with a reference chromosome will determine the danger for aneuploidy (trisomy or monosomy) for that particular chromosome.

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Independent of the origin, there are three phases of shock, and every phase is characterised by unique pathophysiologic changes. In the compensated phase, vital organ perform is maintained by intrinsic neurohormonal compensatory mechanisms leading to distribution of organ blood flow primarily to the heart, mind, and adrenal glands and away from different, "nonvital" organs. Several hormones and native components affecting myocardial function, organ blood move distribution, capillary integrity, systemic and pulmonary vascular resistance, and mobile metabolism are launched during this section. However, blood strain remains inside normal limits because the will increase in myocardial contractility and coronary heart rate preserve cardiac output near the traditional range. This statement may be particularly relevant for the nonacidotic extremely low-birth-weight preterm neonate with immature myocardium and compensated shock through the first postnatal day. If remedy is delayed or the situation is susceptible to speedy deterioration, such as in fulminant sepsis, myocarditis, or asphyxia with multiorgan failure, neonatal shock will enter the ultimate and irreversible part, in which mobile injury resulting in complete organ failure dominates the clinical picture, and death invariably happens. For instance, ammonium excretion and hence era of bicarbonate, in addition to sodium excretion, enhance through the recovery interval from hypocapnic-hypoxia within the fetal sheep. In addition to the results of hypoxemia on the renal compensatory mechanisms to preserve fetal acid-base stability, other adjustments in renal operate are induced by hypoxemia. Fractional excretion of sodium is increased by a lower in proximal tubule sodium reabsorption. Under normal conditions, the redox coupling reactions generate water on account of full O2 reduction with solely minimal (1%) univalent O2 reduction to the superoxide anion (O�2-). Under normal physiologic conditions, hypoxanthine is oxidized to urate by xanthine dehydrogenase and xanthine oxidase, with the latter producing O�2- and H2O2 as byproducts. Reactive O2 species trigger mobile damage by way of their opposed results on completely different cellular structures that lead to polysaccharide depolymerization, lipid peroxidation,fifty four alterations in the main construction of amino acids,fifty five and nucleic acid oxidation. The resultant hyperpolarization of the cell membrane decreases vascular tone by decreasing intracellular calcium by way of inhibition of voltage-gated calcium channels. Because expression of the cardiovascular adrenergic receptors and some components of their second-messenger systems is inducible by glucocorticoids,ninety five steroid administration presents a powerful scientific device to reverse the effects of adrenergic receptor down-regulation. However, enchancment in cardiovascular function occurs within 1 to 2 hours following hydrocortisone administration to neonates. Glucocorticoids inhibit catechol-O-methyltransferase, the rate-limiting enzyme in catecholamine metabolism, and reduce the reuptake of norepinephrine by sympathetic nerve endings, resulting in increases in the plasma concentration of catecholamines. Although eicosanoids have been implicated within the pathogenesis of organ failure and shock, their exact role remains to be elucidated. Rats deficient in important fatty acid, and thus unable to produce significant amounts of eicosanoids, are much less susceptible to endotoxic shock and have significantly improved survival charges in contrast with wildtype rats. Eicosanoids, such as the predominantly vasodilator prostacyclin and prostaglandin E2, and the vasoconstrictor thromboxane A2, play an essential position in the regulation of vascular tone. Some eicosanoids (thromboxane A2) induce platelet and neutrophil aggregation and thus have significant proinflammatory effects; whereas others, corresponding to prostaglandin E2, additionally exert an antiinflammatory action by down-regulating cytokine release by macrophages and lymphocytes. Indeed, there are both animal and human data supporting the position of prostaglandins as both proinflammatory and antiinflammatory brokers. An intact microcirculation, in turn, is dependent upon organ perfusion stress maintained by the interplay amongst cardiac output, preload, and afterload. Cardiac output is the product of stroke quantity and coronary heart fee and is decided by the amount of blood returning to the guts (preload), the power of myocardial contractility, and the resistance towards which the guts should pump (afterload). When myocardial perform is undamaged, cardiac output relies upon solely on preload and afterload, according to the relationships described by the Starling curve. Normal ranges for left and right ventricular output for preterm and time period neonates have been reported between 150 and 300 mL/kg/minute. Thus, decreases in preload (hypovolemia, cardiac arrhythmia), in addition to prematurity and hypoxic or infectious insults, all decrease contractility and lead to decreases in cardiac output. Depending on which circulation (systemic or pulmonary) is more severely affected, high afterload can impair the perform of either ventricle. However, through the following lower in blood return to the initially unaffected ventricle, discount in the output of one of many ventricles will affect the perform of the opposite ventricle. On the other hand, in the extraordinarily low-birth-weight neonate, regular postnatal closure of those fetal channels incessantly fails, and as the right-sided pressures fall, pulmonary edema might quickly develop, further compromising the hemodynamic standing of these critically unwell patients. In more mature preterm and term neonates, blood strain and organ blood flow appear to have a better correlation. Recent research have offered some insights into the attainable lower blood stress limit of the cerebral blood move autoregulatory curve. In extraordinarily low-birth-weight infants during the transitional interval (first 2 postnatal days), cerebral blood circulate was maintained if imply blood stress was larger than 29 mm Hg.

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Morphological classification of nuchal pores and skin in human fetuses with trisomy 21, 18, and thirteen at 12�18 weeks and in a trisomy 16 mouse. First-trimester trisomy screening: nuchal translucency measurement coaching and high quality assurance to appropriate and unify technique. Pregnancy-associated plasma protein a within the prediction of early pregnancy failure. Predictive value of hormone measurements in maternal and fetal complications of pregnancy. Trisomy 21 is related to variable defects in cytotrophoblast differentiation alongside the invasive pathway. First trimester screening for Down syndrome utilizing nuchal translucency, maternal serum pregnancy-associated plasma protein A, free- human chorionic gonadotrophin, placental progress issue and -fetoprotein. Likelihood ratio for trisomy 21 in fetuses with absent nasal bone on the 11-14-week scan. One-stop clinic for evaluation of danger for trisomy 21 at 11-14 weeks: a potential examine of 15 030 pregnancies. Absence of fetal nasal bone and aneuploidies at first-trimester nuchal translucency screening in unselected pregnancies. Frontomaxillary facial angle in screening for trisomy 21 at eleven + zero to thirteen + 6 weeks. The fetal frontomaxillary facial angle in regular and trisomy 21 ultrasounds at 11-13+6 weeks of gestation: findings among the ethnic Chinese compared with caucasian. An increase in cost-effectiveness of first trimester maternal screening programmes for fetal chromosome anomalies is obtained by contingent testing. Karyotype and end result of fetuses recognized with cystic hygroma in the first trimester in relation to nuchal translucency thickness. Accuracy of ultrasonography at 11-14 weeks of gestation for detection of fetal structural anomalies: a systematic evaluation. Combining fetal nuchal fold thickness with second trimester biochemistry to display screen for trisomy 21. New Down syndrome screening algorithm, ultrasonographic biometry and a number of serum markers combined with maternal age. Model predicted efficiency of second trimester Down syndrome screening with ultrasound prenasal thickness. Absent or shortened nasal bone size and the detection of Down syndrome in second-trimester fetuses. Prefrontal house ratio: comparability between trisomy 21 and euploid fetuses in the second trimester. The prefrontal area ratio in second and third trimester screening for trisomy 21. Secondtrimester prenatal screening markers for Down syndrome in ladies with insulin-dependent diabetes mellitus. Strict glycemic control within the diabetic pregnancy-implications for second-trimester screening for Down syndrome. Correction for insulin-dependent diabetes in maternal serum -fetoprotein testing has outlived its usefulness. First trimester maternal serum free -human chorionic gonadotropin and pregnancy-associated plasma protein a in pregnancies difficult by diabetes mellitus. Impact of type 1 diabetes and glycemic management on fetal aneuploidy biochemical markers. First trimester pregnancy-associated plasma protein-A in pregnancies difficult by subsequent gestational diabetes. A re-evaluation of the influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy. Biochemical screening for down syndrome in pregnancies following renal transplantation. Down syndrome risk calculation for a twin fetus taking account of the nuchal translucency in the co-twin.

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