Individual and cumulative risk factors in developmental language disorder: A case-control study.

Many mental disorders (MD) share common etiology, fuelling debates about the specificity of clinical categories and whether the presence of specific risk factors (RF) can distinguish among them. The study of developmental language disorder (DLD), more specifically, has been further hindered by a lack of consensus regarding its definition. These limitations increase the risk of under-detection and lifelong consequences for affected children. This paper aims (1) to document which individual RF allow differentiating DLD from other MD and (2) to compare the cumulative RF between children with DLD versus other MD. This case-control design study used medical records of a psychiatric sample of 795 preschoolers (mean age 4:11, 75% boys). A logistic regression measured the predictive value of potential RF on DLD. Later first sentences, maternal immigration and family history of language delay were identified as significant in explaining 30% of the variance for DLD diagnosis. An ANCOVA revealed that children with DLD were exposed to a significantly higher number of RF than were children with other MD. Public health policies informed with the knowledge of specific RF associated with DLD, and their cumulative impact, could improve early detection and reduce the cascade of negative consequences associated with DLD.

TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs.

Nowadays, numerous websites attempt to commercialize over the internet various products, regardless of the lack of approval by the EMA or the FDA either for human or veterinary use. These products are often produced after aborted drug development due to insufficient or deleterious biological effects, synthesized based on natural products, or only based on scientific literature. However, the administration of such products is dangerous, considering the lack of official control over the production of these substances and the absence of approval by health authorities. In this short communication, we provide an extensive analysis of three misbranded and adulterated products sold over the internet named TB500, TB1000, and SGF1000. We confirm that the content of TB500/TB1000 products is not systematically consistent with it's former descriptions, but also that SGF1000 is mainly composed of sheep extracellular matrix (ECM) and blood proteins, and the signal corresponding to the purported growth promoters is excessively diluted.

Development of a Standardized Microflow LC Gradient to Enable Sensitive and Long-Term Detection of Synthetic Anabolic-Androgenic Steroids for High-Throughput Doping Controls.

Synthetic androgenic anabolic steroids (AAS) are banned compounds and considered as major threats by both racing and sports international authorities. Hence, doping control laboratories are continually looking into analytical improvements to increase their detection capabilities, notably by means of emerging technologies. To enhance analytical performances for the detection of synthetic AAS such as stanozolol, specific chromatographic procedures have been developed using recent quaternary liquid chromatography technology originally designed for high-throughput standardized proteomics connected to mass spectrometry. Applying the newly designed elution procedures described in this paper to the analyses of stanozolol and its metabolites in complex matrixes revealed improved sensitivity compared to previously described high-throughput methods. Indeed, we report the consistent and reliable detection of 16ß-hydroxy-stanozolol down to 10 pg/mL in equine urine and being detectable up-to 3 months after a microdosing administration. Furthermore, a five months long elimination of stanozolol and its metabolites could be monitored on horse mane sections after a single dose administration. Our work highlights novel solutions to detect AAS with improved sensitivity. The application of such developments constitutes new landmarks for doping control laboratories and could be extended to other targeted compounds in residue analysis, toxicology, and metabolomics. Based on this work, the developed chromatographic method is now freely available within the Evosep Plus program.

Comprehensive characterization of the peroxisome proliferator activated receptor-δ agonist GW501516 for horse doping control analysis.

According to international sport institutions, the use of peroxisome proliferator activated receptor (PPAR)-δ agonists is forbidden at any time in athlete career due to their capabilities to increase physical and endurance performances. The (PPAR)-δ agonist GW501516 is prohibited for sale but is easily available on internet and can be used by cheaters. In the context of doping control, urine is the preferred matrix because of the non-invasive nature of sampling and providing broader exposure detection times to forbidden molecules but often not detected under its native form due to the organism's metabolism. Even if urinary metabolism of G501516 has been extensively studied in human subjects, knowledge on GW501516 metabolism in horses remains limited. To fight against doping practices in horses' races, GW501516 metabolism has to be studied in horse urine to identify and characterize the most relevant target metabolites to ensure an efficient doping control. In this article, in vitro and in vivo experiments have been conducted using horse S9 liver microsome fractions and horse oral administration route, respectively. These investigations determined that the detection of GW501516 must be performed in urine on its metabolites because the parent molecule was extremely metabolized. To maximize analytical method sensitivity, the extraction conditions have been optimized. In accordance with these results, a qualitative analytical method was validated to detect the abuse of GW501516 based on its most relevant metabolites in urine. This work enabled the Laboratoire des Courses Hippiques (LCH) to highlight two cases of illicit administration of this forbidden molecule in post-race samples.

MetIDfyR: An Open-Source R Package to Decipher Small-Molecule Drug Metabolism through High-Resolution Mass Spectrometry.

With recent advances in analytical chemistry, liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) has become an essential tool for metabolite discovery and detection. Even if most of the common drug transformations have already been extensively described, manual search of drug metabolites in LC-HRMS/MS datasets is still a common practice in toxicology laboratories, complicating metabolite discovery. Furthermore, the availability of free open-source software for metabolite discovery is still limited. In this article, we present MetIDfyR, an open-source and cross-platform R package for in silico drug phase I/II biotransformation prediction and mass-spectrometric data mining. MetIDfyR has proven its efficacy for advanced metabolite identification in semi-complex and complex mixtures in in vitro or in vivo drug studies and is freely available at github.com/agnesblch/MetIDfyR.

Screening and confirmatory analysis of recombinant human erythropoietin for racing camels' doping control.

Recombinant human erythropoietin (rHuEPO) belongs to the therapeutic class of erythropoiesis stimulating agents (ESAs) due to its implication in the creation pathway of red blood cells and thus enhancement of oxygenation. Because of this bioactivity, rHuEPO has been considered as a major doping agent in sports competitions for decades. Over the years, doping control laboratories designed several analytical strategies applied to human and animal samples to highlight any misuse. Even though multiple analytical approaches have been reported, none has yet been dedicated to racing camels. Here, we describe an analytical strategy to test camel plasma samples at screening using an ELISA assay and a targeted nano-liquid chromatography-high-resolution tandem mass spectrometry for confirmatory analysis. The method was validated and has been successfully applied to post-race samples, allowing the detection of a positive case of rHuEPO administration.