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The exploration of chemical space is a fundamental aspect of chemoinformatics, particularly when one explores a large compound data set to relate chemical structures with molecular properties. In this study, we extend our previous work on chemical space visualization at the pharmacophoric level. Instead of using conventional binary classification of affinity (active vs inactive), we introduce a refined approach that categorizes compounds into four distinct classes based on their activity levels: super active, very active, active, and inactive. This classification enriches the color scheme applied to pharmacophore space, where the color representation of a pharmacophore hypothesis is driven by the associated compounds. Using the BCR-ABL tyrosine kinase as a case study, we identified intriguing regions corresponding to pharmacophore activity discontinuities, providing valuable insights for structure-activity relationships analysis., (© 2024 Wiley-VCH GmbH.)

This paper presents a novel approach called Pharmacophore Activity Delta for extracting outstanding pharmacophores from a chemogenomic dataset, with a specific focus on a kinase target known as BCR-ABL. The method involves constructing a Hasse diagram, referred to as the pharmacophore network, by utilizing the subgraph partial order as an initial step, leading to the identification of pharmacophores for further evaluation. A pharmacophore is classified as a 'Pharmacophore Activity Delta' if its capability to effectively discriminate between active vs inactive molecules significantly deviates (by at least δ standard deviations) from the mean capability of its related pharmacophores. Among the 1479 molecules associated to BCR-ABL binding data, 130 Pharmacophore Activity Delta were identified. The pharmacophore network reveals distinct regions associated with active and inactive molecules. The study includes a discussion on representative key areas linked to different pharmacophores, emphasizing structure-activity relationships., (© 2023. The Author(s).)

This paper introduces a general method that can be used to create groups of pharmacophores to support their further in-depth analysis. A BCR-ABL molecular dataset was used to calculate graph edit distances between pharmacophores and led to their organization into a novel pharmacophore network. The application of a graph layout algorithm allowed us to discriminate between the pharmacophores associated with active compounds and those associated with inactive compounds. A clustering approach was used to refine the partitioning by grouping the pharmacophores based on their structures, activities, and binding modes. Analysis of a newly spatialized pharmacophore network provided us with critical insight into structure-activity relationships, most notably those that revealed distinctions between activity classes and chemical families. As shown, this method permits us to identify families of structurally homogeneous pharmacophores.

Objective: To evaluate prenatal ultrasound parameters as prognostic factors for complex and vanishing gastroschisis., Methods: Retrospective multicentre study of 200 gastroschisis over 13 years (2000-2013). Collection of prenatal ultrasound evaluation on maternal and fetal growth parameters, intra- and extra-abdominal bowel and stomach dilation, abdominal wall defect diameter and changes in bowel appearance. Correlation of these factors with the presence of mechanical intestinal complications at birth, named 'complex gastroschisis'., Results: Fifty-two patients (26%) had complex gastroschisis (CG), including ten vanishing gastroschisis. The presence of intra-abdominal bowel dilation at the second (T2) or third (T3) trimester ultrasound was predictive for CG, with odds ratios at 6.69 (95%CI 2.41-18.55) and 4.72 (95%CI 2.16-10.28), respectively, with a cut-off value at the last examination of >19 mm. A small abdominal wall defect diameter was also predictive for CG, with cut-off values of <9.2 mm at T2 and <12.5 mm at T3. Vanishing gastroschisis recorded earlier intra-abdominal bowel dilation diagnosis, associated with a small wall defect and no extra-abdominal dilation., Conclusion: Intra-abdominal bowel dilation and a small abdominal wall defect diameter accurately predict CG and could be a first sign of vanishing gastroschisis when they occur early. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Background: There is a wide difference of opinion between the medical-surgical community and advocacy group regarding Disorders of Sexual Development (DSD) secondary to congenital adrenal hyperplasia (CAH) being ranked in the intersex category. This rupture is even more evident when the issue of genitoplasty is brought up. For physicians it is obvious and unequivocal that a person with CAH and an XX karyotype has a female gender identity, whereas associations tend to rank persons with CAH in the intersex category and advocate holding-off on surgical management., Material/methods: A retrospective case study vs. control group, spanning over 40years, included 21 patients who were treated in 3 different centers. Each patient and their parents were contacted independently and interviewed regarding interpersonal relationships, psychological impact of genitoplasty, gender identity and opinion on optimal care management for this disorder. Three couples controls (parent-child) per CAH patients were used and matched according to age, sex assigned at birth and ethnic origin., Results: Sex assigned at birth seemed to concord with the gender identity perceived by the patients in 85.7% of cases. In fact, 89.7% of patients and 100% of parents felt that feminizing genitoplasty should be performed within the first year of life. There is however a significant difference compared to controls who felt that surgical management should occur later on in life. No difference was highlighted during childhood regarding parents-child relationships or social integration. However, during adolescence, the parents-child relationship tended to be significantly more painful for the CAH group. Integrating their parenting role was significantly harder for patients in the CAH-DSD group. In the population of CAH-DSD patients who had genitoplasty the level of sexual fulfillment was not lower to the one reported by the control group., Conclusion: Female sex assignment seems legitimate according to this study and the development of gender identity in these patients matches the sex assigned at birth. Resolving early on the adequacy of the genital anatomy with the sex assigned is promoted by patients as well as their parents. Proper psychomotor development and sexual satisfaction underline the absence of complications related to the surgical technique and the relevance of early surgical management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study is to analyze the effectiveness of an Alexis wound retractor (AWR) device for staged gastroschisis closures., Patients and Methods: AWR device was used to cover unreduced viscera of a gastroschisis when primary abdominal wall closure was not convenient. The eviscerated organs were covered with one of the two spring-loaded rings of the AWR inserted underneath the abdominal wall. Gradual reduction was guaranteed through careful traction on the external ring. We retrospectively analyzed the prenatal, post-natal and operative data of the first patients treated with AWR and report their post-operative outcomes., Results: The AWR device was used for staged closure in eight cases. Complete reduction and fascial closure were performed at a median of 3.5 ± 1.6 days. Ventilatory support was necessary for 4.0 ± 3 days and full parenteral feeds for 7.5 ± 6.1 days after fascial closure. Median full enteral feeding was observed at 18 ± 12.5 days after closure allowing discharge in a median period of 30.5 ± 15.6 days after closure., Conclusion: The AWR device is not only a safe and efficient silo for a progressive reduction of severe gastroschisis, but also an interesting tool for continuous stretching leading to an increase of the peritoneal cavity volume, enhancing the equalizing of the viscero-abdominal disproportion.

Introduction: Ureteral stent placement is a key urologic procedure used to manage ureteral obstructions. It is usually performed under general anesthesia (GA) with its inherent risks. The objective was to evaluate safety, feasibility and tolerance of ureteral stent placement under local anesthesia (LA) in women., Materials and Methods: From January 2010 to January 2013, we prospectively and consecutively reviewed all female patients who had an urgent retrograde ureteral stent placement under LA. Only primary stent placements were included in the study. Pain was assessed after surgery by Visual Analog Scale (VAS) and pain and comfort assessment during stent placement were reported. We compared outcomes and tolerance with patients under general anesthesia (GA) matched by age and operatives indications during the same period., Results: We included 36 patients (18 under LA and 18 under GA) with a mean age of 59.4 +/- 22.4 years. The mean operative time was 24.4 +/- 12.9 min and 18.8 +/- 6.5 min in LA group and GA group (p = 0.110), respectively. One patient needed GA due to a poor tolerance. The mean perioperative VAS scores under LA and GA were 5.89 +/-2.95 and 2.06 +/- 2.67 (p < 0.0001), respectively. There were no intraoperative complications in either group. The procedure was painful for 16 (88.8%) patients from the LA group and 9 (50%) patients would not accept to undergo this intervention under LA again., Conclusion: Ureteral stent placement under LA in women can be performed safely and effectively. However, this procedure is painful and should be proposed only to selected cases.