New flow relaxation mechanism explains scour fields at the end of submarine channels.

Particle-laden gravity flows, called turbidity currents, flow through river-like channels across the ocean floor. These submarine channels funnel sediment, nutrients, pollutants and organic carbon into ocean basins and can extend for over 1000's of kilometers. Upon reaching the end of these channels, flows lose their confinement, decelerate, and deposit their sediment load; this is what we read in textbooks. However, sea floor observations have shown the opposite: turbidity currents tend to erode the seafloor upon losing confinement. Here we use a state-of-the-art scaling method to produce the first experimental turbidity currents that erode upon leaving a channel. The experiments reveal a novel flow mechanism, here called flow relaxation, that explains this erosion. Flow relaxation is rapid flow deformation resulting from the loss of confinement, which enhances basal shearing of the turbidity current and leads to scouring. This flow mechanism plays a key role in the propagation of submarine channel systems.

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.

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.

[Managing late-effects after allogeneic stem cell transplantation in children: recommendations from the SFGM-TC]. / Prise en charge des séquelles après greffe de cellules souches hématopoïétiques chez l'enfant : recommandations de la SFGM-TC.

In this report, we address the issue of late-effects after allogeneic stem cell transplantation in children. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille.

Childhood-onset narcolepsy, obesity and puberty in four consecutive children: a close temporal link.

Narcolepsy is a rare but disabling condition that causes excessive daytime sleepiness. Interestingly, weight gain is frequent in patients with narcolepsy and it has sometimes been described very early in the course of the disease. Here, we report four consecutive obese children who were referred to our sleep laboratory for excessive daytime sleepiness and suspected sleep apnoea syndrome. They underwent nocturnal polysomnography associated with multiple sleep latency tests. Narcolepsy was diagnosed in all children with a close temporal link between the onset of narcolepsy, obesity and puberty. Scientifically, the relationship between sleep, weight, growth rate and puberty onset is striking and merits further investigation. From the clinical point of view, narcolepsy must be investigated in obese sleepy children along with obstructive sleep apnoea. Indeed, it can be controlled with appropriate treatment but the proper diagnosis relies not only upon nocturnal polysomnography but involves the systematic use of multiple sleep latency tests.

Undervirilization in XY newborns may hide a 5α-reductase deficiency: report of three new SRD5A2 gene mutations.

The observation of ambiguous genitalia in the newborn signals a medical, surgical and psychological emergency. The most crucial decision will be the choice of sex assignment. Rapid and precise diagnosis is thus essential. In XY newborns with normal/high plasma testosterone (T), partial androgen insensitivity syndrome (PAIS) is usually the first diagnosis evoked, which implies an androgen receptor (AR) defect. The diagnosis of steroid-5-alpha-reductase deficiency is rarely considered by the paediatrician. We report three new SRD5A2 gene mutations in four newborns from France, Morocco and Turkey. The newborns presented with ambiguous genitalia and normal plasma T values and the initial diagnosis\PAIS. In all four cases, normal sequences of the complete AR gene excluded this diagnosis and raised the hypothesis of 5α-reductase deficiency. The entire coding region (5 exons) of the SRD5A2 gene was assessed by PCR and direct sequencing analysis. For patient 1, we identified a new homozygous 2bp deletion in exon 1 (c.122_123delAG). Patient 2 had a known homozygous mutation, p.G115D, in exon 2. New compound heterozygous mutations in exon 4 (p.A215V) and exon 5 (p.X255Q) were found in patient 3. Patient 4 presented a new substitution in exon 1 (p.S14R) associated with a known polymorphism (p.V89L). Our data confirm our previous experience and clearly demonstrate that a 5-α reductase defect should be considered in all XY newborns with ambiguous genitalia and normal plasma T secretion, whatever their geographic area or ethnic group; moreover, this defect was not linked to specific phenotype. Early molecular diagnosis is indispensable for the crucial decision of the newborn's sex of rearing.

p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-hydroxylase deficiency.

CONTEXT: Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia with good genotype/phenotype relationships for common mutations. To determine the severity of rare mutations is essential for genetic counseling and better understanding of the structure-function of the cytochrome P450c21. OBJECTIVE: The p.H62L mutation was the most frequent of 60 new mutations detected in 2900 steroid 21-hydroxylase deficiency patients, either isolated or associated on the same allele with a mild mutation (p.P453S, p.P30L, or partial promoter). Because phenotypes seemed to differ between patients with isolated or associated p.H62L, a detailed phenotype description and functional studies were performed. RESULTS: Regarding phenotype, patients with isolated p.H62L had a nonclassical form, whereas patients with the association p.H62L + mild mutation had a simple virilizing form. Functional studies showed that p.H62L reduced the conversion of the two substrates, progesterone and 17-hydroxyprogesterone, in the same way as the mild p.P453S; the association p.H62L + p.P453S decreased enzymatic activity more strongly while conserving residual activity at a level intermediate between p.P453S and p.I172N. This suggested that p.H62L was a mild mutation, whereas a synergistic effect occurred when it was associated. Analysis of p.H62L in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects, the H62 being located in a domain implied in membrane anchoring. CONCLUSION: According to phenotype and functional studies, p.H62L is a mild mutation, responsible for a more severe phenotype when associated with another mild mutation. These data are important for patient management and genetic counseling.

Congenital disorder of glycosylation Ib (CDG-Ib) without gastrointestinal symptoms.

We report a 7-year-old girl with hyperinsulinaemic hypoglycaemia and hepatomegaly due to congenital disorder of glycosylation (CDG) Ib without gastrointestinal symptoms. Oral mannose therapy produced clinical and biochemical normalization after 2 years of treatment.

[Type Ib pseudohypoaldosteronism: clinical aspects and nosological problems. Apropos of 3 cases]. / Pseudo-hypoaldostéronisme de type Ib: particularités cliniques et problèmes nosologiques. A propos de trois cas.

BACKGROUND: Type Ib pseudohypoaldosteronism is a congenital disorder characterized in the newborn by salt loss caused by multiple end-organ resistance to aldosterone. An autosomal recessive mode of inheritance has been reported. Its particularity is the spontaneous improvement by 18 months to 2 years, due to an improved tubular response of the kidneys to mineralocorticoids, or earlier when given salt supplements once the diagnosis is made. OBSERVATIONS: We observed three children with this disease, which was revealed by day 8 to day 15 of life; one of these presented respiratory symptoms identical to those of cystic fibrosis, and another one an apparently chance association with a rod myopathy. CONCLUSION: Recent findings in the literature demonstrate the molecular aspects of pseudohypoaldosteronism and lead to an interesting comparison with cystic fibrosis by explaining their similar physiopathology through the activity of epithelial sodium channels.

PEG1 expression in maternal uniparental disomy 7.

PAG1/MEST is an imprinted gene mapping to human chromosome 7q32. In human embryos and placenta, PEG1 is expressed from the paternally derived allele only, while maternal and paternal alleles are transcribed in adult blood lymphocytes. We aimed at investigating the origin of the maternal PEG1 transcript by studying PEG1 mRNA in two maternal uniparental disomy 7 patients suffering from severe pre- and post-natal growth restriction. PEG1 expression has been characterised by RT-PCR from leukocytes RNA using several primer pairs. The distal coding region in PEG1 mRNA could be repeatedly amplified from mUPD patients blood cells, but no amplification could be performed from the first exon, suggesting that the first exon was not a component of the maternal PEG1 transcript. As six independent database sequences showed that exon 2 was exactly joined to a novel sequence unrelated to exon 1 but identical in the common region of the six sequences, we hypothesized that our observation of PEG1 expression in the two maternal uniparental disomy 7 patients could be explained by transcription of the maternal allele from an alternate maternal upstream promoter.