Enurésie nocturne : quel traitement efficace non pharmacologique recommander ?

L'énurésie nocturne est une affection commune qui touche jusqu'à 20% des enfants de 5 ans. Cette prévalence diminue ensuite rapidement pour atteindre 7% à l'âge de 7 ans et pas plus de 2% à l'âge adulte. Quoique bénigne, elle est souvent source de stigmatisation sociale et peut affecter à la fois l'estime de soi et les relations avec les pairs. Les interventions de type comportemental (ICS) sont fréquentes et constituent souvent le premier choix des parents et de l'enfant. Une controverse persiste toutefois quant à leur efficacité. Le but de la mise à jour de cette revue est d'évaluer l'efficacité d'interventions comportementales simples (ICS : restriction hydrique, lever, réveil, récompenses, exercices de rétention), entre elles et par rapport à d'autres traitements

A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome.

BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin β2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype-phenotype correlations have been reported, often with great clinical variability. We hereby report a novel homozygous nonsense mutation in the LAMB2 gene, associated with a severe phenotype presentation. CASE DIAGNOSIS: We describe a term male infant born from consanguineous parents. The mother previously lost three children in the neonatal period, secondary to undefined renal disease, had two spontaneous abortions, and gave birth to one healthy daughter. The index case presented at birth with bilateral microcoria, severe hypotonia, respiratory distress, and congenital nephrotic syndrome associated with anuria and severe renal failure requiring peritoneal dialysis. The patients' clinical follow-up was unfavorable, and the newborn died at 7 days of life, after withdrawal of life support. Genetic analysis revealed a homozygous nonsense mutation at position c.2890C>T causing a premature stop codon (p.R964*) in LAMB2 gene. CONCLUSION: We here describe a novel nonsense homozygous mutation in LAMB2 gene causing a severe neonatal presentation of Pierson syndrome. This new mutation expands the genotype-phenotype spectrum of this rare disease and confirms that truncating mutations might be associated with severe clinical features

Management of cryptorchidism in children: guidelines

QUESTION: To develop clinical guidelines for the management of cryptorchidism in pre-pubertal boys, from early diagnosis through therapy to long-term follow-up and prognosis. METHOD: Systematic review of articles from the medical literature, referenced since 1966, using validated search strategies through the following databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, EMBASE, DARE, ACP Journal Club, National Guidelines Clearinghouse, Guidelines International Network. Relevant articles published after 1988 were taken as the basis for the statements. Each statement was graded on the basis of the study design and on its methodological quality (GRADE approach). A multidisciplinary panel of local experts discussed and evaluated each statement on the strength of this evidence. RESULTS: 28 statements based on the best available evidence were drafted. The experts agreed with all but two statements, which were rated uncertain. CONCLUSIONS: Cryptorchidism is best diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months, without a routine biopsy. If no testis is palpable, or if other signs of hypovirilisation such as hypospadias are present, the chromosomal sex and hormonal status must be assessed. Laparoscopy is the best way of diagnosing and managing intra-abdominal testes

Serum NGAL, BNP, PTH, and albumin do not improve glomerular filtration rate estimating formulas in children.

Glomerular filtration rate (GFR) is difficult to measure, and estimating formulas are notorious for lacking precision. This study aims to assess if the inclusion of additional biomarkers improves the performance of eGFR formulas. A hundred and sixteen children with renal diseases were enrolled. Data for age, weight, height, inulin clearance (iGFR), serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) were collected. These variables were added to the revised and combined (serum creatinine and cystatin C) Schwartz formulas, and the quadratic and combined quadratic formulas. We calculated the adjusted r-square (r <sup>2</sup> ) in relation to iGFR and tested the improvement in variance explained by means of the likelihood ratio test. The combined Schwartz and the combined quadratic formulas yielded best results with an r <sup>2</sup> of 0.676 and 0.730, respectively. The addition of BNP and PTH to the combined Schwartz and quadratic formulas improved the variance slightly. NGAL and albumin failed to improve the prediction of GFR further. These study results also confirm that the addition of cystatin C improves the performance of estimating GFR formulas, in particular the Schwartz formula.Conclusion: The addition of serum NGAL, BNP, PTH, and albumin to the combined Schwartz and quadratic formulas for estimating GFR did not improve GFR prediction in our population. What is Known: • Estimating glomerular filtration rate (GFR) formulas include serum creatinine and/or cystatin C but lack precision when compared to measured GFR. • The serum concentrations of some biological parameters such as neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) vary with the level of renal function. What is New: • The addition of BNP and PTH to the combined quadratic formula improved its performance only slightly. NGAL and albumin failed to improve the prediction of GFR further

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Transient Arterial Hypertension Induced by Gonadotropin-Releasing Hormone Agonist Treatment for Central Precocious Puberty.

Background: Gonadotropin-releasing hormone agonists (GnRHa) are a safe and effective treatment for precocious puberty. Triptorelin is one of the long lasting GnRHa, which reversibly suppresses the pituitary-gonadal axis. Triptorelin-induced hypertension (HTN) has rarely been reported in the literature. Clinical Case/Methods: We report a 10-year-old girl with central precocious puberty who, during treatment with triptorelin, developed an asymptomatic stage II HTN. Initial workup showed no renal, thyroid, or electrolytes abnormalities. The renal ultrasound showed no parenchymal disease and no increased renal resistance index suggestive of a renal artery stenosis. Echocardiography and ocular fundoscopy were normal. HTN (stage II) was confirmed with ambulatory blood pressure monitoring (ABPM). After extensive literature review, we found 3 other cases of HTN secondary to GnRHa, improving with endocrine treatment cessation. Therefore, antihypertensive treatment was not started immediately in our patient. Indeed, after completion of her treatment with triptorelin, we observed a complete normalization of her blood pressure (confirmed with ABPM) without any medication. Conclusion: Concomitantly to GnRHa treatment, our patient developed HTN, which completely subsided after stopping triptorelin. The complete normalization of her blood pressure, together with a negative workup for HTN strongly speaks for a causal effect of her endocrine treatment. In this setting, estrogen depletion might play a role, although this remains debated

Maternal exposure to high-fat diet induces long-term mitochondrial alterations in the offspring heart.

Heart disease is a leading cause of death worldwide, with its prevalence exacerbated by inadequate nutritional intake. Particularly concerning is the elevated risk induced by imbalanced nutrition during development, which can impact lifelong heart health. Recent research has underscored mitochondrial dysregulation as a pivotal mechanism driving the enduring consequences of nutritional excess. Building upon previous findings wherein a maternal high-fat diet (HFD) led to cardiac hypertrophy and fibrosis, our current study aimed to evaluate the impact of such a challenge on myocardial mitochondrial function. Female rats were fed a chow diet or HFD during gestation and lactation. The hearts of male offspring were analyzed at adulthood. Mitochondrial DNA abundance was evaluated by quantitative polymerase chain reaction. Proteins involved in mitochondrial biogenesis, fusion, fission, damage to the electron transport chain, metabolism, cell death, proliferation, and inflammation were measured by western blot. Mitochondrial clearance was evaluated by the measurement of mitophagy markers on isolated mitochondria. Lipids were visualized by histologic approaches. We detected decreased cardiac mitochondrial fission factor and mitochondrial adenosine triphosphate synthase beta subunit and increased Parkin, pro-tumor necrosis factor alpha, and pro-interleukin 1 beta protein levels associated with decreased microtubule-associated protein 1A/1B light chain 3B levels in cardiac mitochondrial fraction, with a tendency for increased Oil Red O staining in the adult hearts of male offspring exposed to HFD. Maternal exposure to HFD enhanced mitochondrial damage and impaired fission and clearance in offspring hearts at adulthood. These alterations were associated with altered expression of proteins involved in the mitochondrial electron transport chain coupled with a propensity for increased fatty acid accumulation and elevated proinflammatory markers

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research