A new high-quality set of singly ((2) H) and doubly ((2) H and (18) O) stable isotope labeled reference waters for biomedical and other isotope-labeled research.

RATIONALE: Research using water with enriched levels of the rare stable isotopes of hydrogen and/or oxygen requires well-characterized enriched reference waters. The International Atomic Energy Agency (IAEA) did have such reference waters available, but these are now exhausted. New reference waters thus had to be produced in sufficient quantity, and higher characterization quality was desired. METHODS: The reference waters have been prepared gravimetrically from three parent waters: natural water, pure (2) H water and highly (18) O-enriched water. These parent waters have been thoroughly assessed for their full isotopic compositions. To ensure the integrity and correctness of the gravimetric procedure, validation measurements have been carried out on the isotopic composition of the produced reference waters by two of our laboratories. These measurements corroborate the values obtained on the basis of gravimetric data. RESULTS: Two new sets of three reference waters enriched in the stable isotopes have been produced and certified: one set of singly labeled waters, only enriched in (2) H, and another set of Doubly Labeled Waters, enriched in both (2) H and (18) O. They cover δ(2) H and δ(18) O values in the range of 800-16000 ‰ and 100-2000 ‰, respectively. The process has led to highly accurate isotopic values for these waters. CONCLUSIONS: These reference waters are now available (called IAEA-604 to IAEA-609). They will be valuable as reference materials for all fields using isotope labeling of water, most prominently, but not exclusively, biomedical research (body composition analyses, metabolic rate measurements). The two waters with the lowest enrichments will also be useful as anchor values for isotope measurements around the natural range.

Doubly Labelled Water analysis: preparation, memory correction, calibration and quality assurance for δ2H and δ18O measurements over four orders of magnitudes.

RATIONALE: The Doubly Labelled Water (DLW) method is an established way of determining the metabolic rate in humans and animals, with the advantage that the subjects need not be confined. The method, however, needs accurate determination of both the δ(2)H and the δ(18)O isotope values over a wide range of enrichments. METHODS: In this paper we describe a number of crucial steps in the process of isotope determination in body fluids. These steps include micro-distillation, correction of the measurements for sample-to-sample memory and calibration of the isotope scales over many orders of magnitudes. In contrast to several published protocols and guidelines, we also take highly enriched samples into account, as they are required for studying the metabolic rate of birds and small mammals. For our isotope scale calibration, we made a set of gravimetrically prepared, double labelled waters with known isotope values. Our quality assurance includes a scheme for easy calculation of the error propagation, leading to a reliable estimate of the analytical error in the metabolic rate. RESULTS: Our memory correction algorithm assumes the existence of three water "pools" that have different sizes and exchange rates with the injected samples. We show that the method can correct even huge memory signals, without the need for "true" values. CONCLUSIONS: With the presented building blocks, we show how to assure a reliable and accurate isotope analysis for the DLW method, both for human and for animal applications. Although our measurements have been performed using isotope ratio mass spectrometry, most of the procedures are also useful for laser spectrometry.

Comparison of different prognostic scores in estimating short- and long-term mortality in COVID-19 patients above 60 years old in a university hospital in Belgium.

BACKGROUND AND OBJECTIVES: Multiple scoring systems were used for risk stratification in COVID-19 patients. The objective was to determine among 6 scores which performed the best in predicting short-and long-term mortality in hospitalized COVID-19 patients ≥ 60 years. METHODS: An observational, retrospective cohort study conducted between 21/10/2020 and 20/01/2021. 6 scores were calculated (Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI), 4C Mortality Score (4CMS), NEWS score (NEWS), quick-SOFA score (qSOFA), and Quick COVID-19 Severity Index (qCSI)). We included unvaccinated hospitalized patients with COVID-19 ≥ 60 years old in Brugmann hospital, detected by PCR and/or suggestive CT thorax images. Old and nosocomial infections, and patients admitted immediately at the intensive care unit were excluded. RESULTS: 199 patients were included, mean age was 76.2 years (60-99). 47.2% were female. 56 patients (28%) died within 1 year after the first day of hospitalization. The 4CMS predicted the best intrahospital, 30 days and 6 months mortality, with area under the ROC curve (AUROC) 0.695 (0.58-0.81), 0.76 (0.65-0.86) and 0.72 (0.63-0.82) respectively. The CCI came right after with respectively AUROC of 0.69 (0.59-0.79), 0.74 (0.65-0.83) and 0.71 (0.64-0.8). To predict mortality at 12 months after hospitalization, the CCI had the highest AUROC with 0.77 (0.69-0.85), before the 4CMS with 0.69 (0.60-0.79). DISCUSSION: Among 6 scores, the 4CMS was the best to predict intrahospital, 30-day and 6-month mortality. To predict mortality at 12 months, CCI had the best performance before 4CMS. This reflects the importance of considering comorbidities for short- and long-term mortality after COVID 19. REGISTRATION: This study was approved by the ethical committee of Brugmann University Hospital (reference CE 2020/228).

[Influence of lithium on magnesium levels in the plasma, erythrocytes and brain of rats]. / Influence du lithium sur le taux de magnésium dans le plasma, l'érythrocyte et le cerveau chez le rat.

Intra peritoneal administration of LiCl to rat with a single dose or every day during a week shows that the correlation of brain Li with erythrocytes Li is better than the same correlation with plasmatic Li. With a single dose of Li the variation of the Li level doesn't give significant variations of Mg. With repetitive administrations of Li (near that which occurs in actual therapeutic treatment) we show (44 pairs of results with p less than 0.001) that the increase of Li in erythrocytes is correlated with a decrease of Mg in erythrocytes and an increase of this ion in plasma. The authors demonstrate that the nervous cells don't release Mg when Li get in the brain.

[Changes in cerebral calcium, sodium and potassium after single or repeated administration of lithium in the rat]. / Variations du calcium, sodium et potassium cérébral aprés administration unique ou répétée de lithium chez le rat.

A single administration (IP) of lithium chloride in the rat induces a decrease in erythrocyte calcium, proportional to the lithium level (p less than 0.01) and a diminution in cerebral calcium (p less than 0.001) which is accompanied by decrease in cerebral sodium and potassium levels (p less than 0.001). Repeated administration (IP + VO) has the same cerebral effects. The authors report that the reversible decrease in calcium, sodium and potassium, resulting from an increase in cerebral lithium levels, can be demonstrated on sampling at 1.30 and 3 hours (IP), or at 12 hours (VO). These results are relevant to the treatment of manic illnesses using calcium antagonists.

Reference values of total respiratory resistance and reactance between 4 and 26 Hz in children and adolescents aged 4-20 years.

In 403 healthy subjects, 4 to 20 years of age, we measured total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz. When possible, vital capacity and forced expiratory volume in one second were also determined. The Rrs and Xrs vs frequency data depend on age or height, on sex, and slightly on weight. During growth, Rrs and the frequency dependence of Rrs decrease while Xrs increases. Only part of these changes may be explained entirely by a size effect. The variations with growth of ventilation unevenness, of airway wall compliance and of the topographic distribution of airway resistances probably also play a role. The influence of the interactions between height and age, and height and weight on Rrs and Xrs differ between sexes. Adult values for Rrs and Xrs are attained at the age of 15 years in girls and 18 years in boys.