A comparative study of ballpoint ink ageing parameters using GC/MS.

For more than a decade scientists tried to develop methods capable of dating ink by monitoring the loss of phenoxyethanol (PE) over time. While many methods were proposed in the literature, few were really used to solve practical cases and they still raise much concern within the scientific community. In fact, due to the complexity of ink drying processes it is particularly difficult to find a reliable ageing parameter to reproducibly follow ink ageing. Moreover, systematic experiments are required in order to evaluate how different factors actually influence the results over time. Therefore, this work aimed at evaluating the capacity of four different ageing parameters to reliably follow ink ageing over time: (1) the quantity of solvent PE in an ink line, (2) the relative peak area (RPA) normalising the PE results using stable volatile compounds present in the ink formulation, (3) the solvent loss ratio (R%) calculated from PE results obtained by the analyses of naturally and artificially aged samples, (4) a modified solvent loss ratio version (R%*) calculated from RPA results. After the determination of the limits of reliable measurements of the analytical method, the repeatability of the different ageing parameters was evaluated over time, as well as the influence of ink composition, writing pressure and storage conditions on the results. Surprisingly, our results showed that R% was not the most reliable parameter, as it showed the highest standard deviation. Discussion of the results in an ink dating perspective suggests that other proposed parameters, such as RPA values, may be more adequate to follow ink ageing over time.

A comparative study of ballpoint ink ageing parameters using GC/MS

For more than a decade scientists tried to develop methods capable of dating ink by monitoring the loss of phenoxyethanol (PE) over time. While many methods were proposed in the literature, few were really used to solve practical cases and they still raise much concern within the scientific community. In fact, due to the complexity of ink drying processes it is particularly difficult to find a reliable ageing parameter to reproducibly follow ink ageing. Moreover, systematic experiments are required in order to evaluate how different factors actually influence the results over time. Therefore, this work aimed at evaluating the capacity of four different ageing parameters to reliably follow ink ageing over time: (1) the quantity of solvent PE in an ink line, (2) the relative peak area (RPA) normalising the PE results using stable volatile compounds present in the ink formulation, (3) the solvent loss ratio (R%) calculated from PE results obtained by the analyses of naturally and artificially aged samples, (4) a modified solvent loss ratio version (R%*) calculated from RPA results. After the determination of the limits of reliable measurements of the analytical method, the repeatability of the different ageing parameters was evaluated over time, as well as the influence of ink composition, writing pressure and storage conditions on the results. Surprisingly, our results showed that R% was not the most reliable parameter, as it showed the highest standard deviation. Discussion of the results in an ink dating perspective suggests that other proposed parameters, such as RPA values, may be more adequate to follow ink ageing over time.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

(MA)LDI MS Imaging at High Specificity and Sensitivity

(Matrix-assisted) laser desorption/ionization ((MA)LDI) mass spectrometry imaging (MSI) has been driven by remarkable technological developments in the last couple of years. Although molecular information of a wide range of molecules including peptides, lipids, metabolites, and xenobiotics can be mapped, (MA)LDI MSI only leads to the detection of the most abundant soluble molecules in the cells and, consequently, does not provide access to the least expressed species, which can be very informative in the scope of disease research. Within a short period of time, numerous protocols and concepts have been developed and introduced in order to increase MSI sensitivity, including in situ tissue chemistry and solvent-free matrix depositions. In this chapter, we will discuss some of the latest developments in the field of high-sensitivity MSI using solvent-free matrix depositions and will detail protocols of two methods with their capability of enriching molecular MSI signal as demonstrated within our laboratory.

Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control analysis, which can be proposed in the future as a complement to the 'urinary module' for improving steroid abuse detection capabilities.

L'utilisation des anticoagulants oraux directs chez les patients âgés : les limites de la médecine fondée sur les preuves [The use of the new direct oral anticoagulants among older subjects: The limits of the evidence-based medicine?].

The growing use of direct oral anticoagulants, in particular among older subjects, raises questions about the limits of the evidence-based medicine. The phase III studies that have validated the efficacy and the safety profile of these molecules (dabigatran, rivaroxaban, apixaban, edoxaban) in their both indications, the venous thromboembolic disease and the non-valvular atrial fibrillation raise concerns in four major fields: the financial support of pharmaceutical companies, the links of interest for many authors with the industry, the study design (exclusively non-inferiority studies), and the poor representativeness of the older subjects included. All these points are discussed, using data of sub-groups studies, post-marketing studies and recent meta-analysis. The lack of data for the very old subjects, with frailty or comorbidities, remains the main concern from these phase III studies.

Vers une prescription médicamenteuse appropriée chez les patients âgés à l'aide de STOPP/START.v2

STOPP/START est un outil d'optimisation de la prescription médicamenteuse chez les patients âgés. Mis à jour en 2015, cet article en présente une adaptation pratique pour la médecine générale, en français (www.louvainmedical.be, page d'accueil, rubrique didactique: accès libre), ainsi que les critères les plus fréquemment rencontrés chez des patients âgés fragiles.

Evolution de l'autonomie fonctionnelle et des capacités d'auto-soins des patients âgés hospitalisés en médecine gériatrique : mieux comprendre pour mieux agir en soins infirmiers

De part le vieillissement démographique, la proportion de personnes âgées augmente et, certaines d'entre-elles nécessiteront des soins en milieu hospitalier. Chez l'aîné, l'expérience d'une maladie et d'une hospitalisation augmente le risque de perte d'autonomie dans les activités de la vie quotidienne (AVQ) et peut compromettre le retour à domicile, diminuer la qualité de vie et mobiliser des ressources du système socio-sanitaire. En Suisse, une étude a établi l'ampleur du problème de la dépendance dans les AVQ à domicile. Cependant, peu de connaissances récentes sont disponibles sur la perte d'autonomie à l'hôpital et aucune sur les trajectoires dans les AVQ. But : Le but de cette étude est d'actualiser et compléter les savoirs sur la perte d'autonomie et les trajectoires dans les AVQ des personnes âgées hospitalisées dans un hôpital tertiaire de Suisse romande. Cadre théorique : La présente étude se base sur la théorie du déficit en auto-soin de Dorothea Orem. Méthode : Cette étude descriptive corrélationnelle est une analyse secondaire des données recueillies dans l'unité pilote du projet Soins Aigus aux Séniors entre août 2011 et janvier 2012. Le déficit en auto-soin dans les AVQ a été mesuré avec l'Index de Katz, les habiletés de base avec le MiniCog, le MiniGDS et le CAM et, les facteurs prédisposant étaient l'âge, le genre, l'entourage et l'aide à domicile ainsi que l'état de santé. L'échantillon de 209 patients présentait un âge moyen de 85.4 ans (SD 7.2) et une proportion de 72.7% de femmes. Résultats : Les principaux résultats montrent que la majorité des patients ont une perte d'autonomie dans les AVQ avant l'admission à l'hôpital (56.2%) et que près d'un patient sur six (14.5%) continue d'expérimenter un déficit en auto-soin durant l'hospitalisation. Les facteurs prédisposant à une trajectoire de déficit en auto-soin entre le domicile et la sortie de l'hôpital identifiés ont été : l'état confusionnel aigu (OR=6.00, IC 95% 1.83 - 19.63), la dépendance en auto-soin à domicile (OR=1.44, IC 95% 1.02 - 2.02) et, une trajectoire de déficit en auto-soin entre le domicile et l'entrée à l'hôpital (OR=14.82, IC 95% 4.83 - 45.46). Conclusion : Cette étude met en évidence que les personnes âgées hospitalisées expérimentent des déficits dans les AVQ et qu'un des facteurs favorisants est la présence d'un état confusionnel aigu. D'autres recherches sont nécessaires pour renforcer et compléter ces résultats.