Mental health status of individuals with sexual development disorders: A review.

Healthcare recommendations for people with disorders of sexual development (DSDs) include mental health attention and active participation of psychiatrists and psychologists in dedicated multidisciplinary teams. Therefore, it seems crucial for them to improve knowledge about specific difficulties and needs of these patients. The aim of this article is to report in a synthesizing manner the recent works evaluating the mental health and psychological status of individuals with DSDs. After research conducted using PubMed and ScienceDirect, 18 studies were inventoried and qualitatively analyzed in response to three main questions: Do individuals with DSDs suffer more frequently and/or more severely from psychological conditions or mental disorders? From what kind of disorder do they suffer? and What are the determinant factors involved in their development? This work highlights an increased risk of affective disorders in individuals with DSDs, particularly anxiety and depressive disorders and interpersonal difficulties. Studies identified some potentially determining factors implicated in their development, among which are the etiology of DSDs, the life stage, the age at the time of diagnosis, and the lack of conformity of sexual phenotype with sex assignment. Taken together, the etiology of DSDs, the lack of conformity of sexual phenotype with sex assignment, and the feeling of being different from peers seem to be interesting factors to study in the future. Multicentric and longitudinal studies using standardized evaluation and control groups should be the most robust way to improve knowledge about these preoccupations.

Synchrotron FTIR and Raman spectroscopy provide unique spectral fingerprints for Arabidopsis floral stem vascular tissues.

Cell walls are highly complex structures that are modified during plant growth and development. For example, the development of phloem and xylem vascular cells, which participate in the transport of sugars and water as well as providing support, can be influenced by cell-specific wall composition. Here, we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) and Raman spectroscopy to analyse the cell wall composition of floral stem vascular tissues of wild-type Arabidopsis and the double-mutant sweet11-1 sweet12-1, which has impaired sugar transport. The SR-FTIR spectra showed that in addition to modified xylem cell wall composition, phloem cell walls in the double-mutant line were characterized by modified hemicellulose composition. Combining Raman spectroscopy with a classification and regression tree (CART) method identified combinations of Raman shifts that could distinguish xylem vessels and fibers. In addition, the disruption of the SWEET11 and SWEET12 genes impacted on xylem wall composition in a cell-specific manner, with changes in hemicelluloses and cellulose observed at the xylem vessel interface. These results suggest that the facilitated transport of sugars by transporters that exist between vascular parenchyma cells and conducting cells is important in ensuring correct phloem and xylem cell wall composition.

When should foetal pH measurements be performed after a prolonged deceleration? An experimental study in a fetal sheep model.

OBJECTIVE: The aim of fetal heart rate monitoring during labour is to identify and prevent foetal distress, but its evaluation is not perfect. Fetal scalp blood sampling for pH measurement is one of the second-line methods of monitoring when fetal heart rate is classified as suspicious. This study aims to determine when pH testing should be performed after a prolonged deceleration. STUDY DESIGN: This was an experimental study in a fetal sheep model. A partial umbilical cord occlusion was performed for seven minutes followed by a recuperation period of 30 min. Hemodynamic parameters (heart rate, mean blood pressure and intra-amniotic pressure) and blood gases were recorded before occlusion (T0), during occlusion (T4), just after the end of occlusion (T7), and then 10, 20 and 30 min after occlusion (T17, T27 and T37 respectively). RESULTS: Ten experiments were carried out. During partial cord occlusion, the fetal pH decreased significantly to acidosis. After a prolonged deceleration with fetal acidosis, the pH recovered to a normal value, defined by a pH greater than or equal to 7.25, after 20 min of recuperation. CONCLUSION: After a prolonged deceleration, fetal pH normalizes between 20 and 30 min thereafter. Thus, if a foetal blood sample is indicated, this delay must be respected in order to avoid inducing an unnecessary intervention decision.

Exploring fetal response to acidosis in ewes: Choosing an adequate experimental model.

INTRODUCTION: Knowledge of fetal physiology during labor has been largely generated from animal models. Our team recently developed a new index to assess parasympathetic activity using different experimental protocols to obtain acidosis. The objective of the present study was to discuss the different protocols and to review other models proposed in the literature. MATERIAL AND METHODS: Pregnant ewes underwent a surgical procedure at the 123±2 days gestational age (term=145 days). Three experimental protocols were used: protocol A consisted of 25%, 50% and 75% umbilical cord occlusion (UCO) for 20min. Protocol B consisted of partial 75% UCO until reaching a pH<7.10. Protocol C consisted of brief, repetitive complete occlusion until severe acidosis occurred. Hemodynamic and blood gas parameters were compared to those of the stability period before UCO. RESULTS: Protocol A led to a progressive response depending on the degree of occlusion (decrease in fetal heart rate, arterial hypertension and pH). Protocol B led to severe acidosis, although the duration of UCO varied per animal. Protocol C also progressively led to acidosis. We observed high inter individual variability in the acidosis response. CONCLUSION: Pregnant ewes are a relevant model for exploring fetal response to acidosis. The frequency of UCO and partial or complete occlusion should be adapted to the expected effects. Knowledge of these protocols is important to respect ethical guidelines and to reduce the required number of animals. Moreover, it is important to consider the high individual variability of the acidosis response in the interpretation of the results.

Correlation of a new index reflecting the fluctuation of parasympathetic tone and fetal acidosis in an experimental study in a sheep model.

The autonomic nervous system plays a leading role in the control of fetal homeostasis. Fetal heart rate variability (HRV) analysis is a reflection of its activity. We developed a new index (the Fetal Stress Index, FSI) reflecting parasympathetic tone. The objective of this study was to evaluate this index as a predictor of fetal acid-base status. This was an experimental study on chronically instrumented fetal lambs (n = 11, surgery at 128 +/- 2 days gestational age, term = 145 days). The model was based on 75% occlusion of the umbilical cord for a maximum of 120 minutes or until an arterial pH ≤ 7.20 was reached. Hemodynamic, gasometric and FSI parameters were recorded throughout the experimentation. We studied the FSI during the 10 minutes prior to pH samplings and compared values for pH>7.20 and pH≤ 7.20. In order to analyze the FSI evolution during the 10 minutes periods, we analyzed the minimum, maximum and mean values of the FSI (respectively FSImin, FSImax and FSImean) over the periods. 11 experimentations were performed. During occlusion, the heart rate dropped with an increase in blood pressure (respectively 160(155-182) vs 106(101-120) bpm and 42(41-45) vs 58(55-62) mmHg after occlusion). The FSImin was 38.6 (35.2-43.3) in the group pH>7.20 and was higher in the group pH less than 7.20 (46.5 (43.3-52.0), p = 0.012). The correlation of FSImin was significant for arterial pH (coefficient of -0.671; p = 0.004) and for base excess (coefficient of -0.632; p = 0.009). The correlations were not significant for the other parameters. In conclusion, our new index seems well correlated with the fetal acid-base status. Other studies must be carried out in a situation close to the physiology of labor by sequential occlusion of the cord.

Review shows that implementing a nationwide protocol for congenital diaphragmatic hernia was a key factor in reducing mortality and morbidity.

The French Rare Disease Reference Center for congenital diaphragmatic hernia (CDH) was created in 2008, to implement a national protocol for foetuses and children with this serious condition. Neonatal mortality from CDH is 30-40%, mainly due to pulmonary hypoplasia and persistent pulmonary hypertension, and half of those who live have high respiratory, nutritional and digestive morbidity. CDH management requires long-term and specialised multidisciplinary care. It has been well established that a standardised management protocol improves the prognosis of children with CDH. CONCLUSION: Organising health care and implementing a nationwide French protocol were key factors for reducing mortality and morbidity from CDH.

A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model.

Analysis of heart rate variability (HRV) is a recognized tool in the assessment of autonomic nervous system (ANS) activity. Indeed, both time and spectral analysis techniques enable us to obtain indexes that are related to the way the ANS regulates the heart rate. However, these techniques are limited in terms of the lack of thresholds of the numerical indexes, which is primarily due to high inter-subject variability. We proposed a new fetal HRV analysis method related to the parasympathetic activity of the ANS. The aim of this study was to evaluate the performance of our method compared to commonly used HRV analysis, with regard to i) the ability to detect changes in ANS activity and ii) inter-subject variability. This study was performed in seven sheep fetuses. In order to evaluate the sensitivity and specificity of our index in evaluating parasympathetic activity, we directly administered 2.5 mg intravenous atropine, to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic activity. Our index, as well as time analysis (root mean square of the successive differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency (LF) spectral components obtained via fast Fourier transform), were measured before and after injection. Inter-subject variability was estimated by the coefficient of variance (%CV). In order to evaluate the ability of HRV parameters to detect fetal parasympathetic decrease, we also estimated the effect size for each HRV parameter before and after injections. As expected, our index, the HF spectral component, and the RMSSD were reduced after the atropine injection. Moreover, our index presented a higher effect size. The %CV was far lower for our index than for RMSSD, HF, and LF. Although LF decreased after propranolol administration, fetal stress index, RMSSD, and HF were not significantly different, confirming the fact that those indexes are specific to the parasympathetic nervous system. In conclusion, our method appeared to be effective in detecting parasympathetic inhibition. Moreover, inter-subject variability was much lower, and effect size higher, with our method compared to other HRV analysis methods.

Safety and tolerability of subcutaneous treprostinil in newborns with congenital diaphragmatic hernia and life-threatening pulmonary hypertension.

BACKGROUND: Prolonged pulmonary hypertension (PH) is highly predictive for pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of subcutaneous treprostinil in newborns with severe CDH and late life-threatening PH. METHODS: We recorded clinical and echocardiography data before and after starting subcutaneous treprostinil, on patients with severe CDH and late PH, refractory to inhaled nitric oxide and oral sildenafil. RESULTS: 14 patients were treated with treprostinil (gestational age: 39.1±2.0weeks; birth weight: 3200±600g). Prior to treatment, the pre- and post-ductal SpO2 difference (Δ SpO2) was 14±10%. Treprostinil was initiated at a median age of 12days [5-157]. After starting treprostinil, ΔSpO2 decreased to 3% at day 7 (p<0.05), and the mean blood flow velocities in the right pulmonary arteries increased by 110% (p<0.05). 2 of the 14 patients died. At the age of follow up (12months to 3years), the 12 surviving infants were all weaned from respiratory support and discharged home. CONCLUSION: The subcutaneous treprostinil improves pulmonary hemodynamics and outcomes in infants with CDH and life-threatening PH. We suggest that the treatment should be considered in infants with severe CDH and late PH. TYPE OF STUDY: Case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1-mutated patient's management.

Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non-steroidogenic tissues. NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non-sense NR5A1 mutation in a 46,XY-DSD with polysplenia female proband and her father, who had hypospadias and asplenia.

Carbetocin for prevention of postcesarean hemorrhage in women with severe preeclampsia: a before-after cohort comparison with oxytocin.

STUDY OBJECTIVE: The aim of the study was to compare the incidence of the use of additional uterotonics before and after the change of carbetocin to oxytocin for the prevention of postpartum hemorrhage after cesarean delivery in women with severe preeclampsia. DESIGN: This was an observational retrospective before-and-after study. SETTING: Operating room, postoperative recovery area. PATIENTS: Sixty women with severe preeclampsia undergoing cesarean delivery under spinal anesthesia; American Society of Anesthesiologists 3. INTERVENTIONS: Observational study. MEASUREMENTS: Blood pressure, heart rate, and biological data (hemoglobin, platelets, haptoglobin, prothrombin time index, activated partial thromboplastin time ratio, blood uric acid, aspartate aminotransferase, alanine aminotransferase, serum urea, serum creatinine, and albumin). MAIN RESULTS: The incidence of additional uterotonic administration in the carbetocin and oxytocin groups was 15% and 10%, respectively (P=.70). CONCLUSIONS: As carbetocin appears to be as effective and safe as oxytocin in preeclamptic women, its advantages make it a good uterotonic option in this particular setting.

Relationships between metals exposure and epidemiological parameters of two pathogens in urban pigeons.

Human activities often generate or increase concentration of chemical compounds including pesticides, hydrocarbons and metals that can potentially affect ecological interactions. We found that elevated levels of zinc in pigeon feathers were associated with both low prevalence of Chlamydiaceae (ornithosis disease) and low intensity of blood pathogens (Haemosporidian parasites). In contrast, high levels of lead in pigeon feathers were associated with high blood pathogens intensities. Our results suggest that metals linked to human activities in cities such as zinc and lead may play a significant role in the ecology of host-parasite interactions and could potentially affect the epidemiology of diseases in the urban environment.

[The long-term follow-up of patients with a congenital diaphragmatic hernia: review of the literature]. / Hernie de coupole diaphragmatique: devenir à long terme.

The increased survival rate reached in infants with congenital diaphragmatic hernia (CDH) has shown a concomitant increase in late morbidity. Many complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described. Long-term pulmonary morbidity in CDH consists of obstructive and restrictive lung function impairments due to altered lung structure and prolonged ventilatory support. Long-term consequences of pulmonary hypertension are unknown. Gastro-esophageal reflux disease (GERD) is also an important contributor to overall morbidity. Failure to thrive may be caused by GERD, insufficient intake due to oral aversion and increased caloric requirements due to pulmonary morbidity. Neurological outcome is determined by an increased risk of perinatal and neonatal hypoxemia in the first days of life of CDH patients. Many studies have addressed the substantial impact of the health problems described above, on the overall well-being of CDH patients, but only a few studies focus on the health-related quality of life. Considering the scattered data indicating substantial morbidity in long-term survivors of CDH, follow-up studies that systematically assess long-term sequelae are needed. Based on such studies, a more focused approach for routine multidisciplinary follow-up programs could be established. It is the goal of the French Collaborative Network to promote exchange of knowledge, future research and development of treatment protocols.

[Congenital diaphragmatic hernia: respiratory and vascular outcomes]. / Hernie de coupole diaphragmatique : devenir respiratoire et vasculaire pulmonaire.

Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly associated with a variable degree of pulmonary hypoplasia (PH) and persistent pulmonary hypertension (PPH). Despite remarkable advances in neonatal resuscitation and intensive care, and new postnatal treatment strategies, the rates of mortality and morbidity in the newborn with CDH remain high as the result of severe respiratory failure secondary to PH and PPH. Later, lung function assessments show obstructive and restrictive impairments due to altered lung structure and lung damage due to prolonged ventilatory support. The long-term consequences of pulmonary hypertension are unknown. Other problems include chronic pulmonary aspiration caused by gastro-oesophageal reflux and respiratory manifestations of allergy such as asthma or rhinitis. Finally, failure to thrive may be caused by increased caloric requirements due to pulmonary morbidity. Follow-up studies that systematically assess long-term sequelae are needed. Based on such studies, a more focused approach for routine multidisciplinary follow-up programs could be established. It is the goal of the French Collaborative Network to promote exchange of knowledge, future research and development of treatment protocols.

[Per and post-natal medical management of congenital diaphragmatic hernia]. / Prise en charge médicale per et post-natale de la hernie congénitale du diaphragme.

Congenital diaphragmatic hernia (CDH) is a 1 out of 3500 live-born malformation with persistent 30-40% mortality rate, related to severe pulmonary hypoplasia and hypertension. Better knowledge on the mechanisms inducing failure of adaptation at birth is a prerequisite for improving CDH prognosis. CDH is also associated with longterm morbidity, including prolonged respiratory failure, failure to growth, oral aversion, and scoliosis. Early prevention starting as soon as the first hours of life are required to reduced long term morbidity. The aims of the management are not only to reduce early mortality, related to persistent pulmonary hypertension, but also to prevent late morbidity.

[Pyeloplasty for pyelo-ureteric junction syndrome in children: lombo-assisted procedure versus lombotomy]. / Pyéloplastie pour syndrome de la jonction pyélo-urétérale chez l'enfant : voie lombo-assistée versus lombotomie.

Surgical treatment of pyelo-ureteric junction syndromes was classically at the child's, a pyeloplasty by posterior way or by lombotomy. For several years, assisted video techniques are proposed for this gesture. The purpose of our study was to compare the lombo-assisted pyeloplasty procedure with the lombotomy procedure, within the framework of this coverage. We made a retrospective study of procedures performed from January 2000 to December 2005, based on a file review of children operated for pyelo-ureteric junction syndrome. Children under the age of 2 years were excluded. Fifty-two children were divided in 2 groups: group 1: 24 children, 7 girls and 17 boys, average age of 86 months (extremes: 27-172) benefited from a lombo-assisted pyeloplasty. Group 2: 28 children, 12 girls and 16 boys, average age of 69 months (extremes: 24-129) benefited from a pyeloplasty by lombotomy. Operating times were significantly shorter in opened surgery than with the lombo-assisted procedure. There was no significant difference in terms of per- or post-operating complication, use of analgesic and hospitalization duration. On the other hand, the lombo-assisted procedure provided the same undisputable aesthetic benefit and the same muscular preservation than pure lomboscopy procedure. As a consequence, this procedure could be set up at no risk for the patient, even if it had lead to longer operating times. However, operating times stayed shorter than with the pure lomboscopy or the celioscopy procedures, compared to the literature.

[Management of severe respiratory failure in the newborn: indication of inhaled NO]. / Prise en charge de la détresse respiratoire sévère du nouveau-né: place du NO inhalé.

Severe respiratory failure results from large right to left shunting. In the newborn, both intrapulmonary and/or extrapulmonary shunting may cause severe respiratory failure. Right to left extrapulmonary shunting is associated with pulmonary hypertension (PPHN). Management depends on the main mechanism of the respiratory failure. Intrapulmonary shunting requires optimizing lung recrutment, whereas vascular recrutment is required to decrease extra-pulmonary shunting. Analysis of anamnesis, clinical examination, chest X-ray, and echocardiography allows distinguishing the mechanism of the respiratory failure. In case of PPHN, favorizing factors such as acidosis, stress, lung over distension, and polyglobuly should be treated. Inhaled NO is recommended in the treatment of PPHN after optimizing lung volume.

[Repair of hypospadias: the effect of urethral plate configuration on the outcome of Duplay-Snodgrass repair]. / Cure d'hypospadias. La forme de la plaque urétrale a-t-elle une influence sur le résultat de l'intervention de Duplay-Snodgrass?

OBJECTIVES: A number of factors potentially influence the outcome of hypospadias surgery. We evaluate the effect of catheter-size used during urethroplasty (a detail related to the depth of the urethral groove and width/elasticity of the urethral plate) on the complication rate following Duplay-Snodgrass repair. METHODS: The data of 113 patients undergoing primary hypospadias repair was retrospectively reviewed. Patients were divided into two groups based on the urethral plate width evaluated by the catheter-size used during urethral reconstruction, and the rate of complications was compared in the two groups. Other factors evaluated included age of patients and severity of the defect. RESULTS: Complications (urethro-cutaneous fistula and meatal stenosis) were more common in the narrow urethral plate 8F catheter group (three fistulae among 18 patients) compared to the wide urethral plate 10F catheter group (six fistulae and one meatal stenosis in 95 patients) (p=0.08). CONCLUSION: The width of the urethral plate during a modified Duplay urethroplasty has a significant impact on outcome. A smaller-sized catheter for neo-urethral reconstruction, implying a shallow urethral groove and a narrow or inelastic urethral plate, is associated with a higher rate of urethrocutaneous fistula and meatal stenosis.

Beta-naphthoflavone inhibits the induction of hepatic oestrogen-dependent proteins by 17alpha-ethynylestradiol in mosquitofish (Gambusia holbrooki).

The interactive effects of an aryl hydrocarbon receptor (AhR) agonist and of a xenoestrogen on biomarker responses were studied in the liver of male mosquitofish (Gambusia holbrooki). Hepatic 7-ethoxyresorufin O-deethylase (EROD) enzymatic activity was measured as a biomarker of exposure to the model AhR agonist beta-naphthoflavone (bNF). Hepatic proteins indicating the exposure of males to the synthetic oestrogen 17alpha-ethynylestradiol (EE2) were monitored by Western blot analysis using immunoserum prepared for this study. After a semi-static exposure only to waterborne EE2, Western blot analysis of liver homogenate revealed the induction of two protein bands (a double band at 205 kDa and a single band at 125 kDa). The interaction between bNF and EE2 was investigated by analysing, on the one hand, EROD activity and, on the other hand, immunoreactivity corresponding to the two oestrogen-dependent protein bands in the liver of fish exposed to different concentrations of bNF for 2 days, then to the same concentrations of bNF plus 0.1 microg l(-1) EE2 for 5 days. EE2 changed neither the basal activity of EROD nor its rate of induction with 1.0 and 4.0 microg l(-1) bNF. On the other hand, the induction of oestrogen-dependent proteins with 0.1 microg l(-1) EE2 was inhibited by exposure to 4.0 microg l(-1) bNF. These results together with literature data suggest that field monitoring of xenoestrogen contamination through the analysis of oestrogen-dependent protein in male fish as a biomarker should take into account the possible negative interference of AhR agonists.