A clinical follow-up of 35 Brazilian patients with Prader-Willi Syndrome

OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.

Playing to Create New Ways of Playing: A Child with Prader-Willi Syndrome

This investigation evaluates the possibility of constructing new ways of playing for a child with Prader-Willi syndrome, by means of occupational therapy. It is a qualitative study which makes use of the case study methodology, whose starting point is the clinical intervention as data collect field. It also presents a short revision of the literature to subside discussions and reflections. It was observed that through the playing experience the occupational therapist led the child to know his own limitations and possibilities, by making him discover new ways of doing activities. Observing the therapist and learning with her, the patient experienced different situations throughout the therapeutic relationship, what enabled him to experiment them in his everyday life. Finally, this study aims at showing the clinical reasoning of an occupational therapist with a view to demonstrate Brazilian therapeutical conduct.

A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. (C) 2012 Wiley Periodicals, Inc.

1031-1034delTAAC (Leu125Stop): a novel familial UBE3A mutation causing Angelman syndrome in two siblings showing distinct phenotypes

Background More than 50 mutations in the UBE3A gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect. Case Presentation We here describe a novel UBE3A frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same UBE3A mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features. Conclusions We hypothesized that the mutation Leu125Stop causes both severe and milder phenotypes. Potential mechanisms include: i) maybe the proband has an additional problem (genetic or environmental) besides the UBE3A mutation; ii) since the two siblings have different fathers, the UBE3A mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the UBE3A mutation causes the severe phenotype; iii) this UBE3A mutation alone can cause either typical AS or the severe clinical picture seen in the proband.

Modulation of Maternal Immune System During Pregnancy in the Cow

There is a molecular crosstalk between the trophoblast and maternal immune cells of bovine endometrium. The uterine cells are able to secrete cytokine/chemokines to either induce a suppressive environment for establishment of the pregnancy or to recruit immune cells to the endometrium to fight infections. Despite morphological differences between women and cows, mechanisms for immune tolerance during pregnancy seem to be conserved. Mechanisms for uterine immunesuppression in the cow include: reduced expression of major histocompatability proteins by the trophoblast; recruitment of macrophages to the pregnant endometrium; and modulation of immune-related genes in response to the presence of the conceptus. Recently, an eGFP transgenic cloned embryo model developed by our group showed that there is modulation of foetal proteins expressed at the site of syncytium formation, suggesting that foetal cell can regulate not only by the secretion of specific factors such as interferon-tau, but also by regulating their own protein expression to avoid excessive maternal recognition by the local immune system. Furthermore, foetal DNA can be detected in the maternal circulation; this may reflect the occurrence of an invasion of trophoblast cells and/or their fragment beyond the uterine basement membrane in the cow. In fact, the newly description of exosome release by the trophoblast cell suggests that could be a new fashion of maternal-foetal communication at the placental barrier. Additionally, recent global transcriptome studies on bovine endometrium suggested that the immune system is aware, from an immunological point of view, of the presence of the foetus in the cow during early pregnancy.

The Regulation of Rasd1 Expression by Glucocorticoids and Prolactin Controls Peripartum Maternal Insulin Secretion

The transition from gestation to lactation is characterized by a robust adaptation of maternal pancreatic beta-cells. Consistent with the loss of beta-cell mass, glucose-induced insulin secretion is down-regulated in the islets of early lactating dams. Extensive experimental evidence has demonstrated that the surge of prolactin is responsible for the morphofunctional remodeling of the maternal endocrine pancreas during pregnancy, but the precise molecular mechanisms by which this phenotype is rapidly reversed after delivery are not completely understood. This study investigated whether glucocorticoid-regulated expression of Rasd1/Dexras, a small inhibitoryGprotein, is involved in this physiological plasticity. Immunofluorescent staining demonstrated that Rasd1 is localized within pancreatic beta-cells. Rasd1 expression in insulin-secreting cells was increased by dexamethasone and decreased by prolactin. In vivo data confirmed that Rasd1 expression is decreased in islets from pregnant rats and increased in islets from lactating mothers. Knockdown of Rasd1 abolished the inhibitory effects of dexamethasone on insulin secretion and the protein kinase A, protein kinase C, and ERK1/2 pathways. Chromatin immunoprecipitation experiments revealed that glucocorticoid receptor (GR) and signal transducer and activator of transcription 5b (STAT5b) cooperatively mediate glucocorticoid-induced Rasd1 expression in islets. Prolactin inhibited the stimulatory effect of GR/STAT5b complex on Rasd1 transcription. Overall, our data indicate that the stimulation of Rasd1 expression by glucocorticoid at the end of pregnancy reverses the increased insulin secretion that occurs during pregnancy. Prolactin negatively regulates this pathway by inhibiting GR/STAT5b transcriptional activity on the Rasd1 gene. (Endocrinology 153: 3668-3678, 2012)

Maternal Moderate Physical Training during Pregnancy Attenuates the Effects of a Low-Protein Diet on the Impaired Secretion of Insulin in Rats: Potential Role for Compensation of Insulin Resistance and Preventing Gestational Diabetes Mellitus

The effects of pregestational and gestational low-to-moderate physical training on insulin secretion in undernourished mothers were evaluated. Virgin female Wistar rats were divided into four groups as follows: control (C, n = 5); trained (T, n = 5); low-protein diet (LP, n = 5); trained with a low-protein diet (T + LP, n = 5). Trained rats ran on a treadmill over a period of 4 weeks before mate (5 days week(-1) and 60 min day(-1), at 65% of VO2max). At pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8% casein diet, and controls were provided with a 17% casein diet. At third day after delivery, mothers and pups were killed and islets were isolated by collagenase digestion of pancreas and incubated for a further 1 h with medium containing 5.6 or 16.7 mM glucose. T mothers showed increased insulin secretion by isolated islets incubated with 16.7 mM glucose, whereas LP group showed reduced secretion of insulin by isolated islets when compared with both C and LP + T groups. Physical training before and during pregnancy attenuated the effects of a low-protein diet on the secretion of insulin, suggesting a potential role for compensation of insulin resistance and preventing gestational diabetes mellitus.

Low Apgar scores at 5 minutes in a low risk population: maternal and obstetrical factors and postnatal outcome

Objective: To evaluate the association between Apgar scores of less than seven at five minutes (AS(5min) < 7) and antenatal factors and postnatal outcomes. Methods: A retrospective cohort and case-control study of 27,252 consecutive term newborns in a low risk obstetrical population between January 2003 and December 2010. Maternal and infant databases were reviewed from all cases with AS(5min) < 7 (n = 121; 0.4%) and 363 cases with AS(5min) >= 7 at 5 minutes who were randomly selected by a computer program. The main outcomes were neonatal death, newborn respiratory distress, need for orotracheal intubation and neonatal intensive care unit (NICU), and hypoxic-ischemic-encephalopathy. Results: After multiple regression analysis, repeated late decelerations on cardiotocography (OR: 2.4; 95% CI: 1.4-4.1) and prolonged second stage of labor (OR: 3.3; 95% CI: 1.3-8.3) were associated with AS(5min) < 7, as well as neonatal respiratory distress (OR: 3.0; 95% CI: 1.3-6.9), orotracheal intubation (OR: 2.5; 95% CI: 1.2-4.8), need for NICU (OR: 9.5; 95% CI: 6.7-16.8), and hypoxic-ischemic-encephalopathy (OR: 14.1; 95% CI: 3.6-54.7). No other antenatal factors were associated with AS(5min) < 7 (p > 0.05). Conclusion: Repeated late decelerations and prolonged second stage of labor in the low-risk population are predictors of AS(5min) < 7, a situation associated with increased risk of neonatal respiratory distress, need for mechanical ventilatory support and NICU, and hypoxic-ischemic-encephalopathy.

Maternal exposure to picrotoxin modifies the response of the GABA(A) receptor during sexual behavior of adult male rat offspring

This study investigated whether perinatal exposure to picrotoxin, a GABA(A) antagonist, modifies the effect of muscimol, a GABA(A) agonist, on the sexual behavior of adult male rats. Two hours after birth and then once daily during the next 9 days of lactation, dams received picrotoxin (0.75 mg/kg subcutaneously) or saline (1 ml/kg subcutaneously). The adult male offspring from the picrotoxin and saline groups received saline (1 ml/kg intraperitoneally) or muscimol (1 mg/kg intraperitoneally), and 15 min later, their sexual behavior was assessed. Muscimol treatment in the saline-exposed group increased the mount and intromission latencies. However, these effects were absent in the picrotoxin-exposed groups. The latencies to first ejaculation, postejaculatory mount, and intromission were decreased in both picrotoxin-exposed groups relative to the saline-exposed groups. The picrotoxin + muscimol-treated rats required more intromissions to ejaculate and the picrotoxin-exposed groups made more ejaculations than the saline-exposed groups. Thus, muscimol treatment did not increase the mount and intromission latencies following picrotoxin exposure, but increased the ejaculation frequency, which did not differ between the picrotoxin + muscimol and the picrotoxin + saline groups. These data indicate that perinatal picrotoxin treatment interfered with GABA(A) receptor development Behavioural Pharmacology 23:703-709 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Variations in Management of Mild Prenatal Hydronephrosis Among Maternal-Fetal Medicine Obstetricians, and Pediatric Urologists and Radiologists

Purpose: There are no current guidelines for diagnosing and managing mild prenatal hydronephrosis. Variations in physician approach make it difficult to analyze outcomes and establish optimal management. We determined the variability of diagnostic approach and management regarding prenatal hydronephrosis among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. Materials and Methods: Online surveys were sent to mailing lists for national societies for each specialty. Participants were surveyed regarding criteria for diagnosing mild prenatal hydronephrosis and recommendations for postnatal management, including use of antibiotic prophylaxis, followup scheduling and type of followup imaging. Results: A total of 308 maternal-fetal medicine obstetricians, 126 pediatric urologists and 112 pediatric radiologists responded. Pediatric urologists and radiologists were divided between Society for Fetal Urology criteria and use of anteroposterior pelvic diameter for diagnosis, while maternal-fetal medicine obstetricians preferred using the latter. For postnatal evaluation radiologists preferred using personal criteria, while urologists preferred using anteroposterior pelvic diameter or Society for Fetal Urology grading system. There was wide variation in the use of antibiotic prophylaxis among pediatric urologists. Regarding the use of voiding cystourethrography/radionuclide cystography in patients with prenatal hydronephrosis, neither urologists nor radiologists were consistent in their recommendations. Finally, there was no agreement on length of followup for mild prenatal hydronephrosis. Conclusions: We observed a lack of uniformity regarding grading criteria in diagnosing hydronephrosis prenatally and postnatally among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. There was also a lack of agreement on the management of mild intermittent prenatal hydronephrosis, resulting in these cases being managed inconsistently. A unified set of guidelines for diagnosis, evaluation and management of mild intermittent prenatal hydronephrosis would allow more effective evaluation of outcomes.

Maternal care in the Neotropical harvestman Liogonyleptoides tetracanthus (Opiliones: Gonyleptidae)

We describe post-ovipositional maternal care in Liogonyleptoides tetracanthus Mello-Leitao 1932 (Gonyleptinae) and experimentally evaluate the protective role of this behavior against egg predation under laboratory conditions. Females laid 138.8 eggs on average and remained close to the clutch during the entire day. Eggs hatched after 11-15 days and nymphs dispersed from maternal protection after one to two days. Most of the experimental clutches left unattended were entirely consumed by conspecifics in 2-3 days. There was no reduction in egg number in the clutches protected by females. Although biological data are scarce, there are cases of egg hiding, paternal and maternal care within the subfamily Gonyleptinae. This diversity of forms of parental care is unusual when compared to other gonyleptid subfamilies, and future systematic revisions of the polyphyletic Gonyleptinae should include parental care as a potential source of phylogenetic information.

Maternal Depression, Behavioral Profile and School Performance in School-Age Children

The aim of this study was to compare behavioral profile and school performance of school-age children living with a mother who presents clinical history of recurrent depression, diagnosed according to CID-10 criteria in order to verify the influences of such adversity. Thirty-eight mother-child dyads were evaluated using tests, interviews and questionnaires. Approximately two-thirds of the children presented behavioral and school performance difficulties with predominance of emotional and relationship problems, and impairment in the three areas of school performance which were assessed (writing, arithmetic and reading). Such difficulties may be associated with the negative impact of maternal depression. One-third of the children did not present difficulties, which suggests the use of protective mechanisms. The study highlights the importance of considering differences in children's profiles for the planning of mental health practices.

Maternal factors regulating preterm infants' responses to pain and stress while in maternal kangaroo care

The relationship between maternal factors and the response of preterm infants to pain and stress experienced during heel puncture while in maternal kangaroo care was investigated. This descriptive study included 42 mothers and their preterm infants cared for in a neonatal unit. Data were collected in the baseline, procedure, and recovery phases. We measured the neonates' facial actions, sleep and wake states, crying, salivary cortisol levels, and heart rate, in addition to the mothers' behavior, salivary cortisol levels, and mental condition. The influence of the maternal explanatory variables on the neonatal response variables were verified through bivariate analysis, ANOVA, and multiple regression. The mothers' behavior and depression and/or anxiety did not affect the neonates' responses to pain and stress, though the mothers' levels of salivary cortisol before the procedure explained the variance in the neonates' levels of salivary cortisol after the procedure (p=0.036). Additionally, the mothers' baseline levels of salivary cortisol along with the neonates' age explained the variance in the neonates' heart rate (p=0.001). The ability of mothers to regulate their own stress contributed to the infants' responses to pain and stress.

Maternal obesity in high-risk pregnancies and postpartum infectious complications

Objective: To analyze the association between maternal obesity and postnatal infectious complications in high-risk pregnancies. Methods: Prospective study from August 2009 through August 2010 with the following inclusion criteria: women up to the 5th postpartum day; age L 18 years; high-risk pregnancy; singleton pregnancy with live fetus at labor onset; delivery at the institution; maternal weight measured on day of delivery. The nutritional status in late pregnancy was assessed by the body mass index (BMI), with the application of the Atalah et al. curve. Patients were graded as underweight, adequate weight, overweight, or obese. Postpartum complications investigated during the hospital stay and 30 days post-discharge were: surgical wound infection and/or secretion, urinary infection, postpartum infection, fever, hospitalization, antibiotic use, and composite morbidity (at least one of the complications mentioned). Results: 374 puerperal women were included, graded according to the final BMI as: underweight (n = 54, 14.4%); adequate weight (n = 126, 33.7%); overweight (n = 105, 28.1%); and obese (n = 89, 23.8%). Maternal obesity was shown to have a significant association with the following postpartum complications: surgical wound infection (16.7%, p = 0.042), urinary infection (9.0%, p = 0.004), antibiotic use (12.3%, p < 0.001), and composite morbidity (25.6%, p = 0.016). By applying the logistic regression model, obesity in late pregnancy was found to be an independent variable regardless of the composite morbidity predicted (OR: 2.09; 95% CI: 1.15-3.80, p = 0.015). Conclusion: Maternal obesity during late pregnancy in high-risk patients is independently associated with postpartum infectious complications, which demonstrates the need for a closer follow-up of maternal weight gain in these pregnancies.

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring

Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. (C) 2012 Elsevier Inc. All rights reserved.