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Diffraction data and quasicrystallography provide average quasiperiodic structures for real quasicrystals. In the present paper it is reported a detailed analysis of one of these quasiperiodic structures, with the emphasis on complementarity of Mackay- and Bergman-like polyhedra as well as on chemical order aspects. [Copyright &y& Elsevier]

Study Question: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls?, Summary Answer: This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP., What Is Known Already: Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool., Study Design, Size, Duration: This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed., Participants/materials, Setting, Methods: This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA., Main Results and the Role of Chance: The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort., Limitations, Reasons for Caution: This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity., Wider Implications of the Findings: The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity., Study Funding/competing Interest(s): No specific funding was used. All authors declared no conflict of interest., Trial Registration Number: In-house #23-5214 registered study., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disorder involving isolated aldosterone deficiency without any compromise of other adrenal hormones. This condition manifests mainly in the neonatal period and in infants as a salt wasting syndrome with vomiting and failure to thrive. Due to its potentially life-threatening effects, ASD requires a careful and early diagnosis based on appropriate hormonal investigations in order to initiate adequate management: rehydration as well as salt and fludrocortisone supplementation. Genetic analysis of the CYP11B2 gene will confirm ASD in most cases. We report the case of a newborn with a typical clinical presentation associated with some uncommon phenotypic features (hyperhidrosis, liver injury). Furthermore, our patient carries a new CYP11B2 splicing variant to be added to the approximately 60 pathogenic or likely pathogenic variants already reported., Competing Interests: Declaration of Competing Interest No support has been received from any source, and there are no potential conflicts of interest to disclose in this case report., (Copyright © 2023. Published by Elsevier Masson SAS.)

Oxetanes are strained heterocycles with unique properties that have triggered significant advances in medicinal chemistry. However, their synthesis still presents significant challenges that limit the use of this class of compounds in practical applications. In this Letter, we present a methodology that introduces a new synthetic disconnection to access oxetanes from native alcohol substrates. The generality of the approach is demonstrated by the application in late-stage functionalization chemistry, which is further exploited to develop a single-step synthesis of a known bioactive synthetic steroid derivative that previously required at least four synthetic steps from available precursors.

Objectives: Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave's disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay., Methods: All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC)., Results: We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval., Conclusions: The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

To gain more insight on the pathogenesis of somatotroph pituitary adenomas, recent studies have focused on a subgroup of patients with acromegaly displaying a paradoxical growth hormone (GH) response during oral glucose tolerance test (OGTT). The paradoxical rise of GH after oral glucose intake occurs in about one-third of acromegaly patients and has been pathogenetically linked, by analogy to glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome, to the ectopic expression of GIP receptor (GIPR) in somatotroph adenoma cells. GIPR-expressing adenomas are negative for activating GNAS gene mutations and display distinct cytogenetic and DNA methylation profiles, highlighting their unique molecular pathogenesis. Acromegaly patients with a paradoxical GH response pattern seem to display higher insulin-like growth factor-1 (IGF-1) concentrations and harbour smaller adenomas that are more often of the densely granulated phenotype. They seem also to show a better response to somatostatin receptor ligands. In addition, persistent paradoxical GH response after surgery may be a biological marker of the residual disease postoperatively. Targeted therapy to antagonize GIP receptor on GIPR-expressing somatotroph adenomas could be a new treatment approach for acromegaly patients with a paradoxical pattern of GH response to OGTT.

Despite recent advances, a general method for the synthesis of α-carbonyl-α'-(hetero)aryl sulfoxonium ylides is needed to benefit more greatly from the potential safety advantages offered by these compounds over the parent diazo compounds. Herein, we report the palladium-catalyzed cross-coupling of aryl bromides and triflates with α-carbonyl sulfoxonium ylides. We also report the use of this method for the modification of an active pharmaceutical ingredient and for the synthesis of a key precursor of antagonists of the neurokinin-1 receptor. In addition, the mechanism of the reaction was inferred from several observations. Thus, the oxidative addition complex [(XPhos)PhPdBr] and its dimer were observed by  31 P{ 1 H} NMR, and these complexes were shown to be catalytically and kinetically competent. Moreover, a complex resulting from the transmetalation of [(XPhos)ArPdBr] (Ar = p -CF 3 -C 6 H 4 ) with a model sulfoxonium ylide was observed by mass spectrometry. Finally, the partial rate law suggests that the transmetalation and the subsequent deprotonation are rate-determining in the catalytic cycle.

The lack of general access to bis-substituted sulfoxonium ylides is addressed by developing a palladium-catalyzed C-H cross-coupling of α-ester sulfoxonium ylides with (hetero)aryl iodides, bromides, and triflates. Three different catalysts have been evaluated. This method is amenable to the late-stage functionalization of active pharmaceutical ingredients.

The functionalization of carbon-hydrogen bonds in non-nucleophilic substrates using α-carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross-coupling reactions of sulfoxonium ylides with C(sp 2 )-H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C-H activation, migratory insertion of the ylide into the carbon-metal bond, and protodemetalation, the last step being turnover-limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium-catalyzed dehydrative cyclization., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a role in adipocyte differentiation and insulin sensitization. We identified and characterized a new C/T substitution at position -689 (-689C>T) in the P2 promoter of PPARgamma in a putative GATA binding site. By electrophoretic mobility shift assay, both GATA2 and GATA3 proteins could bind weakly to the wild-type P2 -689 GATA binding site but not to the mutated site. Neither GATA2 nor GATA3 was able to regulate significantly the P2 promoter activity in a reporter-luciferase assay, whatever the allele at position -689 was, suggesting that the -689 putative GATA site was probably not a functional target for GATAs. However, the presence of the -689T allele rendered the P2 promoter less active at the basal state. We genotyped a population of 1155 men and women for the -689C>T polymorphism and looked for possible associations with anthropometric and lipid variables. The carriers of the -689T allele had elevated body weight and LDL-cholesterol concentrations compared with the homozygous for the common allele. Haplotype analyses including the -681C>G (P3 promoter), -689C>T (P2 promoter), and Pro12Ala (exon B) polymorphisms were performed. Carriers of the G-T-Ala haplotype (corresponding to the P3 -681C>G, P2 -689C>T and Pro12Ala polymorphisms in this order) had elevated LDL-cholesterol concentrations and body weight compared with C-C-Pro individuals. In conclusion, we identified a new polymorphism in the P2 promoter of PPARgamma. The P3 -681C>G, P2 -689C>T, and Pro12Ala polymorphisms and related haplotypes were associated with higher body weight and plasma LDL-cholesterol concentrations.

Background: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft., Study Design and Methods: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated. The statistical incidence of prefreeze and postthaw parameters as well as patient characteristics and conditioning regimens on hematologic recovery were analyzed., Results: By multivariate analysis, prefreeze and postthaw CD34+ cells were the only two variables significantly and independently correlated to hematologic recovery. Low prefreeze and postthaw CD34+ cell numbers associated to a low CD34+ yield characterize PBPC grafts from patients who have the slowest hematologic recovery. The postthaw PBPC CD34+ cell number can be estimated before conditioning regimen by thawing a small aliquot of the graft., Conclusion: In association to prefreeze CD34+ cell number and to CD34+ yield, postthaw CD34+ cell number may be useful in monitoring cell loss during processing and identifying patients at risk of slow PBPC engraftment.

The latest generation of cell separators such as Trima (Gambro), Amicus (Baxter) and AS-TEC 204 (Fresenius), allow the collection of leucocyte-reduced platelet concentrates without secondary filtration. Fresenius has recently developed the COMTEC cell separator whose performance has been evaluated by several teams in France. This new cell separator is an improved version of the Fresenius AS-TEC 204 cell separator, designed to allow more efficient platelet collections. This study reports on the experience of six French teams (from Bordeaux, Clermont-Ferrand, Creteil, Dijon, Lille and Nancy) who obtained 696 leucocyte-reduced plateletpheresis concentrates in the course of collection using the new Fresenius COMTEC cell separator. All healthy volunteer donors fulfilled French selection criteria for platelet apheresis. Donors were eligible if they had suitable venous accesses, if their bodyweight was *50 kg and if their pre-apheresis platelet count was >150 x 10(9) l(-1). Between 4606 and 5229 ml of blood were processed. The mean volume of the platelet concentrates was between 439 and 493 ml (mean 460 +/- 63 ml). The platelet yield was of the order of 5.18 +/- 1.02 x 10(11) with only one platelet concentrate below the norm of 2 x 10(11) platelets (0.91 x 10(11)). No plausible explanation for this was found. The residual leucocyte levels conform to current norms. The platelet concentrates contained less than 1 x 10(6) leucocytes per concentrate (mean 0.233 +/- 0.150 x 10(6) leucocytes) in more than 97% of the components produced with >95% statistical confidence. The efficacy of the cell separator (52.44 +/- 7.35%) is comparable to that of other separators. The Fresenius COMTEC cell separator makes it possible to obtain leucocyte-reduced platelet concentrates which comply with current standards both in terms of platelet content and residual leucocyte level.

Background and Objectives: Posttransfusion hepatitis still occurs at an incidence of about 1 in 118,000 for HBV and 1 in 220,000 for HCV. This collaborative study aimed to determine the prevalence of a novel flavivirus, GBV-C/HGV, even though its role in transfusion-associated hepatitis is uncertain., Materials and Methods: GBV-C/HGV RNA was detected by PCR using either the Boehringer detection kit or by primers previously described. HGV antibodies were detected by a serological assay from Boehringer., Results: The observed GBV-C/HGV RNA frequency was 3.4%. HGV antibodies occurred in 9.5% of donors., Conclusion: In our study, 12. 9% of the donors had been in contact with the GBV-C/HGV virus.

The development of bone marrow transplantation in mismatched or matched unrelated donor situations, the recent use of peripheral blood stem cells for allogeneic transplants, the standardization and respect of good methodology practices highlight the need to evaluate new safe methods of T cell depletion (TCD). We have performed 79 in vitro TCD using five techniques: rabbit complement cytotoxicity, CD2-CD7 immunomagnetic depletion, CD5-CD8 panning system, CD34 positive purging and counterflow centrifugation elutriation (CCE). We analyzed these different approaches with regard to the degree of T and B depletion, recovery of progenitors and NK cells. In our hands, the 5 systems evaluated showed a TCD of between 1.3 and 3 log. The CCE, immunomagnetic, complement and panning methods all give similar a TCD of around 2 log. In contrast, we obtained a TCD of approximately 3 log with CD34 positive purging. The progenitor yield was around 50% regardless of the technique used. However, the degree of B and NK cell depletion was dependent on the method: specific TCD resulted in low BCD (under 0.5 log), whereas CCE or CD34 positive purging gave a BCD of greater than 1 log. Moreover, CD34 positive selection resulted in a virtually complete elimination of NK cells. CCE was the only technique allowing isolation of the small lymphocyte population which can be useful for adoptive therapy. To obtain TCD over three logarithms, double purging techniques are necessary. Because specific roles of T cells subsets in engraftment, graft versus host disease, Epstein Barr virus associated B cell lymphoproliferative disorders and disease relapse have not yet been completely elucidated, new techniques such as CD34 positive purging and double purging methods (positive and negative purging) need to be clinically evaluated, especially with respect to peripheral blood stem cells.

Background: A recent hepatitis C virus (HCV) outbreak has been suspected of being caused by an infusion of intravenous immune globulin., Study Design and Methods: Three laboratories were mandated by the French regulatory agency to prospectively screen on a national scale those persons having received suspected batches: 233 exposed patients were recalled and tested for HCV antibody and for HCV RNA., Results: Nineteen patients (8.1%) were found positive for HCV RNA; 7 of these 19 were positive for the HCV antibody., Conclusion: The link between HCV infection and intravenous immune globulin was reinforced by the overrepresentation of the 2b genotype (58%), which contrasts with the low prevalence of this genotype in France (1%).

Correlations between different peripheral blood parameters and harvesting yields of stem cells were analysed in 230 leukaphereses performed on 61 patients. According to multivariate analysis, the number of circulating CD34 positive cells was found to provide the best preleukapheresis parameter for predicting the quality of peripheral blood progenitor cell harvest. A high correlation coefficient and small 95% confidence and prediction intervals would indicate the assay of CD34 positive cells in peripheral blood to be a unique tool essential for monitoring the collection of circulating haematopoietic progenitors.

To screen and identify irregular antibodies, whatever the technique used, fresh erythrocytes (RBCs) are needed to set up the panel. Solid-phase tests using dried blood cells are available, but the technique is based on the adherence of sensitized RBCs, which have a short life span. We have checked antigen survival on membranes with a saline test and an antiglobulin test for two methods to preserve the antigen substrate: freeze-drying of RBCs and preparation of RBC membranes. The different antigens of the ABO, Rhesus, Kell, P, Lewis, MNSs, Lutheran, Duffy, Kidd and Li systems are well recognized on the membranes after isolation and on freeze-dried cells. Demonstration of antigen survival leads us to consider using membranes or freeze-dried cells in new immunological tests.

Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration-dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo.