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Introduction: Precocious puberty is defined as the appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Central precocious puberty (CPP) is a rare condition that is diagnosed when premature activation of the hypothalamic-pituitary-gonadal axis is detected, in association with precocious breast development or testicular growth. Idiopathic CPP is historically considered to be the most common form, but in recent years defects in a small but growing number of genes regulating the timing of puberty have been identified in an increasing proportion of cases of CPP. Delta-like non-canonical Notch ligand 1 (DLK1) is understood to be one of the key genes involved in the etiology of CPP, although its mechanistic role is not yet fully understood. Case Presentation: We identified a novel de novo variant of DLK1 (c.835C>T; p.Gln279*) in an 8-year-old girl of Bangladeshi origin. She presented with an advanced Tanner staging of B4P4A2, significantly advanced bone age (BA, 13 years), a near-adult proportioned uterus, with a history of menarche at the age of 7.4 years. Diagnosis was confirmed by raised basal luteinizing hormone concentration. She was found to have truncal obesity associated with abnormal fasting insulin levels and mildly elevated cholesterol levels. These findings are consistent with previous literature describing an association between patients with DLK1 deficiency and an impaired metabolic profile. The patient was treated for 2 years with GnRH agonists with ongoing biochemical follow-up into adolescence. Conclusion: This case illustrates the susceptibility to metabolic derangement for patients with mutations in DLK1 and the need for ongoing monitoring after puberty. Our summary of previously identified DLK1 variants and their metabolic consequences demonstrates the frequency of obesity, lipid abnormalities, and insulin dysregulation in this patient cohort in childhood and beyond. This knowledge can guide future clinical practice for patients with CPP patients due to DLK1 deficiency. [ABSTRACT FROM AUTHOR]

Insulin-like peptide 3 (INSL3) is a biomarker for Leydig cells in the testes of vertebrates, and it is principally involved in spermatogenesis through specific binding with the RXFP2 receptor. This study reports the insl3 gene transcript and the Insl3 prepropeptide expression in both non-reproductive and reproductive tissues of Danio rerio. An immunohistochemistry analysis shows that the hormone is present at a low level in the Leydig cells and germ cells at all stages of Danio rerio testis differentiation. Considering that the insl3 gene is transcribed in Leydig cells, our results highlight an autocrine and paracrine function of this hormone in the Danio rerio testis, adding new information on the Insl3 mode of action in reproduction. We also show that Insl3 and Rxfp2 belonging to Danio rerio and other vertebrate species share most of the amino acid residues involved in the ligand–receptor interaction and activation, suggesting a conserved mechanism of action during vertebrate evolution. [ABSTRACT FROM AUTHOR]

The msh/Msx family is a subclass of homeobox-containing genes suggested to perform a conserved function in the patterning of the early embryo. We had already isolated a member of this gene family (Ci-msxb) in Ciona intestinalis, which has a very complex expression pattern during embryogenesis. To identify the regulatory elements controlling its tissue-specific expression, we have characterized the gene structure and the regulatory upstream region. By electroporation experiments, we demonstrated that a 3.8-kb region located upstream of the gene contains all the regulatory elements able to reproduce its spatial expression pattern. Analyzing progressively truncated fragments of this region, three discrete and separate regions driving LacZ reporter gene expression in the ventral epidermis, primordial pharynx and neural territories have been identified. We further investigated the element(s) necessary for Ci-msxb activation in the nervous system during embryonic development by in vivo and in vitro experiments. Both electroporation and gel-shift assays of overlapping wild type and mutated oligonucleotides demonstrated that a unique sequence of 30 bp is involved in Ci-msxb neural activation from neurula to larva stage. This sequence contains consensus binding sites for various ubiquitous transcription factors such as TCF11 whose possible implication in formation of the regulatory complexes is discussed. Keywords: Promoter; Cis-element; Pharynx; Nervous system; LacZ reporter gene; Homeobox

Background. Anti-reflux surgery is an effective treatment for gastroesophageal reflux disease (GERD). Nevertheless, surgery is still indicated with great caution in relation to the risk of complications, and in particular to postoperative dysphagia (PD). Objective. To compare the clinical outcomes, with particular focus on the incidence and severity of PD, of laparoscopic Nissen–Rossetti fundoplication (NRF) and floppy Nissen fundoplication (FNF) with complete fundus mobilization, in the surgical treatment of GERD. Methods. Ninety patients with GERD were enrolled. Forty-four patients (21[47.7%] men, 23[52.2%] women; mean age 42.4 ± 14.3 years) underwent NRF (Group A), and 46 patients (23[50%] men, 23[50%] women; mean age 43.3 ± 15.4 years) received laparoscopic FNF with complete fundus mobilization (Group B). Clinical assessment was performed using a structured questionnaire and SF-36 quality of life (QoL) score. PD was assessed using a validated classification, and an overall outcome was also determined by asking the patient to score it. Results. At 24-month follow-up, 38 (88.3%) patients in Group A vs 39 (86.6%) in Group B reported to be completely satisfied with reflux relief and free of protonic pump inhibitors (PPIs), while 3 (6.9%) in Group A vs 2(4.4%) in Group B reported occasional PPI intake and 2(4.6%) in Group A vs 4(8.8%) in Group B needed regular PPI use. Persistent PD was observed in 8(18.6%) patients in Group A and in 2(4.4%) in Group B (P =.03). No significant differences were found in the QoL score and in the overall outcome perceived by the patients. Conclusion. FNF, with complete fundus mobilization, appears to be associated with a lower rate of postoperative persistent dysphagia. [ABSTRACT FROM AUTHOR]

Background: After initial enthusiasm in the use of a dedicated curved stapler (CCS-30 Contour Transtar) to perform stapled transanal rectal resection (STARR) for obstructed defecation syndrome (ODS), difficulties have emerged in this surgical technique.Objective: First, to compare surgeons' perception of difficulties of STARR performed with only Transtar versus STARR performed with the combined use of linear staplers and Transtar to cure ODS associated with large internal prolapse and rectocele; second, to compare the postoperative incidence of the urge to defecate between the 2 STARR procedures.Design and Setting: An Italian multicenter randomized trial involving 25 centers of colorectal surgery.Patients: Patients with obstructed defecation syndrome and rectocele or rectal intussusception, treated between January and December 2012.Interventions: Participants were randomly assigned to undergo STARR with a curved alone stapler (CAS group) or with the combined use of linear and curved staplers (LCS group).Main Outcome Measures: Primary end-points were the evaluation of surgeons' perception of difficulties score and the incidence of the "urge to defecate" at 3-month follow up. Secondary end-points included duration of hospital stay, rates of early and late complications, incidence of "urge to defecate" at 6 and 12 months, success of the procedures at 12 months of follow-up.Results: Of 771 patients evaluated, 270 patients (35%) satisfied the criteria. Follow-up data were available for 254 patients: 128 patients (114 women) in the CAS group (mean age, 52.1; range, 39-70 years) and 126 (116 women) in LCS group (mean age, 50.7 years; range, 41-75 years). The mean surgeons' perception score, was 15.36 (SD, 3.93) in the CAS group and 12.26 (SD, 4.22) in the LCS group (P < .0001; 2-sample t test). At 3-month follow-up, urge to defecate was observed in 18 (14.6%) CAS group patients and in 13 (10.7%) LCS group patients (P = .34; Fisher's exact test). These values drastically decrease at 6 months until no urge to defecate in all patients at 12 months was observed. At 12-month follow-up, a successful outcome was achieved in 100 (78.1%) CAS group patients and in 105 (83.3%) LCS group patients (P = .34; Fisher's exact test). No significant differences between groups were observed in the hospital stay and rates of early or late complications occurring after STARR.Conclusions: STARR with Transtar associated with prior decomposition of prolapse, using linear staplers, seems to be less difficult than that without decomposition. Both procedures appear to be safe and effective in the treatment of obstructed defecation syndrome resulting in similar success rates and complications. [ABSTRACT FROM AUTHOR]