Volumetric absorptive microsampling at home as an alternative tool for the monitoring of HbA1c in diabetes patients

Background: Microsampling techniques have several advantages over traditional blood collection. Dried blood spot (DBS) sampling and blood collection with heparinized capillaries are the standard techniques. Volumetric absorptive microsampling (VAMS) is a novel technique that collects a fixed volume of blood by applying an absorbent tip to a blood drop. In the present study we explored the feasibility of HbA(1c) monitoring with VAMS sampling at home and analysis in the laboratory. Methods: Diabetic patients were enrolled in this study during consultation with the endocrinologist. A venous (adults) or capillary (children) sample was taken for immediate HbA(1c) analysis. DBS (n=1)and dried VAMS (n=2) were collected at home and sent to the laboratory. For 25 pediatric patients one VAMS was collected during consultation for immediate analysis (without drying), referred to as "wet VAMS". HbA(1c) analyses were performed on a Tosoh HLC-723 G8 high-performance liquid chromatography (HPLC) analyzer. Results: The median time between sampling at home and analysis was 3 days. Results of HbA(1c) in dried VAMS showed a poor agreement with venous/capillary blood collected in hospital (concordance correlation coefficient CCC=0.72). Similar observations were found with standard DBS. An excellent agreement was obtained between HbA(1c) results on wet VAMS (CCC=0.996) and standard blood samples. Patients experienced VAMS and DBS as easy and convenient to use. Conclusions: Utilizing equipment standard available in the clinical laboratory, the use of home-sampled dried VAMS and DBS is not a reliable tool for the monitoring of HbA(1c). However, perfect agreement between HbA(1c) measured on wet VAMS and capillary microsamples was obtained

Deepening inside the pictorial layers of Etruscan sarcophagus of Hasti Afunei: An innovative micro-sampling technique for Raman/SERS analyses

The Hasti Afunei sarcophagus is a large Etruscan urn, made up of two chalky alabaster monoliths. Dated from the last quarter of the third century BC, it was found in 1826 in the small town of Chiusi (Tuscany- Il Colle place) by a landowner, Pietro Bonci Casuccini, who made it part of his private collection. The noble owner’s collection was sold in 1865 to the Royal Museum of Palermo (today under the name of Antonino Salinas Regional Archaeological Museum), where it is still displayed. The sarcophagus is characterized by a complex iconography that is meticulously illustrated through an excellent sculptural technique, despite having subjected to anthropic degradation and numerous restorative actions during the last century. During the restoration campaign carried out between 2016 and 2017, a targeted diagnostic campaign was carried out to identify the constituent materials of the artefact, the pigments employed and the executive technique, in order to get an overall picture of conservation status and conservative criticalities. In particular, this last intervention has allowed the use of the innovative micro-sampling technique, patented by the Cultural Heritage research group of Sapienza, in order to identify the employee of lake pigments through SERS analyses. Together with this analysis, Raman and NMR technique have completed the information requested by restorers, for what concerns the wax employed as protective layers, and allowed to rebuild the conservation history of the sarcophagus. In fact, together with the identification of red ocher and yellow ocher, carbon black, Egyptian blue and madder lake, pigments compatible with the historical period of the work, modern pigments (probably green Paris, chrome orange, barium yellow, blue phtalocyanine) have been recognized, attributable with not documented intervention during the eighteenth and twentieth centuries. © 2019 by the authors

Ca isotopic analysis of laser-cut microsamples of (bio)apatite without chemical purification

We report methodological innovations and an initial application to retrieve Ca isotopic (δ44/40Ca) compositions of (bio)apatite at high spatial resolution. We utilize laser-microsampling via laser-cut polygons followed by extraction of μg-sized bioapatite fragments; and apply a 1010 Ω resistor for 40Ca and parafilm-dam loading to minimize in-run Ca isotope fractionation for TIMS analysis. We obtain identical internally-normalized TIMS Ca isotopic ratios for natural calcite, apatite and bone meal SRM1486 without chemical separation, suggesting no need of chemical purification of these materials for such analysis. Our 42Ca–48Ca double spike (DS) corrected δ44/40Ca values of standard solutions HPSnew, Fisher07 and bone meal SRM1486 are 0.70 ± 0.18‰, 1.03 ± 0.20‰, and − 1.03 ± 0.19‰ (2SD), relative to SRM915a, all well in line with published data. Solutions prepared from both laser-cut and non-laser cut Durango apatite have similar δ44/40Ca values (0.70 ± 0.17‰, 2SD), suggesting no resolvable Ca isotope fractionation effect induced from laser-cutting.A δ44/40Ca profile of a third molar from a modern human female, laser-sampled in the growth direction of the enamel apatite, reveals a 0.5‰ increase from age ~ 11 to ~ 11.5, followed by a 0.7‰ drop at age ~ 12 and a final return to enriched Ca-isotope compositions until age ~ 14. We surmise that the initial increase is related to her known phase-out of dairy products, whereas the drop may coincide with hormonal changes at the onset of her menstruation. The latter hints at a relationship between physiological change and δ44/40Ca variation, and raises the need for proper evaluation of physiological effects on Ca isotopes before reliable environmental signals can be extracted from the large Ca-isotope variability previously observed in skeletal tissues.We also investigated the potential for Ca isotopic analysis using an IsoProbe MC-ICPMS in both solution and laser ablation (LA) modes. While the use of a collision cell almost completely removes 40Ar+ interference on 40Ca+, partially-resolved hydrocarbon interferences result in only ~ 30% useable peak flats, that potentially cause problems with peak jumping needed for analysis of 46Ca and 48Ca. Furthermore, it is difficult to correct for Ti isobaric interferences so that analysis without chemical separation is challenging. In-situ Ca isotope analysis of natural calcite (SRM915b), aragonite and apatite by LA-MC-ICPMS shows substantial matrix sensitivity, and therefore requires close matrix matching

A dried blood spot assay for paclitaxel and its metabolites

After being used for decades in clinical screening, dried blood spots (DBS) have recently received considerable attention for their application in pharmacokinetic and toxicokinetic studies in rodents. The goal of this study was to develop and apply a DBS-based assay for a pharmacokinetic study of paclitaxel (PTX) and its metabolites in SCID/Beige mice. A fast and sensitive UHPLC-MS/MS method has been developed for the simultaneous determination of PTX, its three metabolites (6 alpha-hydroxy-paclitaxel, 3'-p-hydroxypacli taxel, and 6a,3'-p-dihydroxy-paclitaxel) and its stereoisomer 7-epi-p aclitaxel. The 10 mu L DBS sample was extracted with methanol for 20 min at 37 degrees C. After dilution of the extracts with water in a ratio of 1:1, the analytes were separated on a reversed-phase 2.1 mm I.D. column using gradient elution. The total run time was 2.5 min. The analytes were detected by use of multiple reaction monitoring mass spectrometry. The extraction recoveries of the compounds were all greater than 60%, resulting in a quantification limit of 1 ng/ml. The calibration curves ranged from 1 to 1000 ng/ml. The intra-day and inter-day imprecision (%CV) across three validation runs over four quality control levels were less than or equal to 14.6%. The accuracy was within +/-11.9% in terms of relative error. The described method is advantageous in terms of its ease-of-use and speed compared to other published PTX assays. The method's usefulness was demonstrated by applying it to a preclinical pharmacokinetic investigation of PTX and its metabolites in SCID/Beige mice with an intraperitoneal administration of 50 mg/kg Abraxane (R)

Dried blood spots in toxicology : from the cradle to the grave?

About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e. g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology

Estratigrafía de Sr y evolución sedimentaria de los depósitos marinos del Mioceno temprano en el antepaís del norte de la Cuenca Austral (o Magallanes), Argentina

Early Miocene shallow marine deposits in the region of Lago Posadas-Meseta Belgrano (Argentina) represent part of the “Patagoniense” transgression, an Atlantic marine incursion that flooded large part of Patagonia, including the Austral (foreland) Basin (southern Patagonia). These deposits, referred as El Chacay (Argentina) or Guadal (Chile) formations, and the transition to the overlying Santa Cruz Formation were divided into six facies: subtidal sandbars, shallow marine sandy deposits, muddy shelf deposits, estuarine complex deposits, fluvial channels and fluvial floodplains. These are arranged in a general transgressive-regressive cycle, subdivided into two stratigraphic sequences, separated by a major erosional surface. 87Sr/86Sr ages from shell carbonate in eight oysters yielded an age range of 20.3 to 18.1 Ma for these “Patagoniense” deposits. Correlation with other dated “Patagoniense” sections in southern Patagonia, like those at Lago Argentino or Comodoro Rivadavia, indicates that they belong to a single transgression that flooded several Patagonian basins approximately at the same time. Eustasy, flexural subsidence created by tectonic loading in the adjacent fold-and-thrust belt, and basin floor paleo-topography controlled the duration of the depositional event and the sedimentation style of these shallow marine deposits.Los depósitos marino-someros del Mioceno temprano de la región del Lago Posadas-Meseta Belgano representan parte de la transgresión “Patagoniense”, una incursión marina atlántica que invadió gran parte de la Patagonia, incluyendo la Cuenca de antepaís Austral (Patagonia austral). Estos depósitos, referidos como formaciones El Chacay (Argentina) y Guadal (Chile), y su transición a la suprayacente Formación Santa Cruz, fueron divididos en seis facies: barras submareales, depósitos arenosos marino-someros, depósitos fangosos de plataforma, complejo estuarino, canales fluviales y planicie de inundación. Estas facies muestran un arreglo general transgresivo-regresivo, el que puede ser subdividido en dos secuencias estratigráficas separadas por una superficie erosiva. Resultados de ocho edades 87Sr/86Sr de carbonato tomado de valvas de ostras dieron un rango entre 20,3 Ma y 18,1 Ma para estos depósitos Patagonienses. La correlación con sucesiones equivalentes de edad conocida en la Patagonia Austral, como las del Lago Argentino o Comodoro Rivadavia, indican que estas pertenecen a una misma transgresión que inundó gran parte de la Patagonia aproximadamente al mismo tiempo. La eustacia, la subsidencia flexural creada por carga tectónica en la faja corrida y plegada adyacente, y la paleotopografía del fondo de la cuenca, controlaron la duración del evento depositacional y el estilo de sedimentación estos depósitos marino-someros.Fil: Cuitiño, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Ventura Santos, Roberto. Universidade de Brasília; BrasilFil: Alonso Muruaga, Pablo Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Scasso, Roberto Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentin

MULTI-INSTRUMENTAL IDENTIFICATION OF ORPIMENT IN ARCHAEOLOGICAL MORTUARY CONTEXTS

Indexación: Web of Science; Scielo.This paper reports on an unknown yellowish mineral compound found in an archaeological context from Chorrillos cemetery (Calama, Chile) dating to the Early Formative period (800 - 200 B.C.). We used optic microscopy, SEM, EDX, 1H-RMN, 13C-RMN, and infrared (IR) and Raman spectroscopy to tease out the chemical and molecular composition of the sample. The microscopic images show amorphous yellowish granulates with heterogeneous chemical surfaces. 1H-RMN and 13C-RMN negative results show that the sample is free of organic matter. The SEM and EDX indicate the presence of arsenic and sulfur in the sample. The IR and Raman analyses suggest the presence of orpiment which is a toxic yellow arsenic sulfide mineral.http://ref.scielo.org/mfcms

Sr Isotope Zoning in Plagioclase from Parinacota Volcano (Northern Chile): Quantifying Magma Mixing and Crustal Contamination

We present analyses of Sr isotope zoning by microdrilling and thermal ionization mass spectrometry in plagioclase crystals from Parinacota volcano (Central Volcanic Zone, northern Chile), which were analysed for major and minor element zoning in a previous study. Although the isotopic range of the bulk-rock samples is small at this volcano (0·7067-0·7070, except for one flow of mafic andesite at 0·7061), significant variations are seen (0·70649-0·70700) within and between plagioclase crystals. A general negative correlation is observed between Sr isotope composition and Sr concentration in the liquid in equilibrium with each plagioclase zone, as calculated from chemical zoning data and partition coefficients. Additional scatter is superimposed on this general trend, indicating a decoupling between isotopic and chemical variations for Sr. In one dacite sample a detailed isotopic profile shows increasing contamination during crystal growth, except for an abrupt decrease correlated with a dissolution surface and interpreted as a recharge event. We apply energy-constrained recharge, assimilation and fractional crystallization modelling to the melt evolution recorded in the chemical and isotopic zoning in this crystal. Results suggest 20% assimilation of the local wall-rock gneiss, at high initial temperatures. The isotopic data confirm the involvement of two contrasting mafic magmas, which are sampled at flank cinder cone vents. One (Lower Ajata) has a low Sr content with high 87Sr/86Sr, the other (Upper Ajata) has a high Sr content with lower 87Sr/86Sr. In some samples from Parinacota, the isotopic composition of plagioclase crystal rims or groundmass crystals is significantly higher than that of the high 87Sr/86Sr mafic magma. In others, where chemical zoning profiles suggest that recharge was from the low 87Sr/86Sr magma, the 87Sr/86Sr of the groundmass and crystal rims is higher than expected. This indicates either additional parent magmas to the two previously identified, or further crustal assimilation, either at lower crustal depths, before crystallization of plagioclase, or just after the last recharge. Our results illustrate the complexity of magma-crust interaction beneath Parinacota, which is likely to be representative of many other Central Andean volcanoes formed on thick crust. Such complex interactions can be revealed by combined study of chemical and isotopic zoning in plagioclase (in a textural petrographic context), despite a small whole-rock isotopic range. The distinct contamination patterns of various samples suggest an important role for the geometry, location and evolution of the magma plumbing system and, in general, variations of the thermal and compositional structure of the crust underneath the volcan

Does volumetric absorptive microsampling eliminate the hematocrit bias for caffeine and paraxanthine in dried blood samples? : a comparative study

Volumetric absorptive microsampling (VAMS) is a novel sampling technique that allows the straightforward collection of an accurate volume of blood (approximately 10 mu L) from a drop or pool of blood by dipping an absorbent polymeric tip into it. The resulting blood microsample is dried and analyzed as a whole. The aim of this study was to evaluate the potential of VAMS to overcome the hematocrit bias, an important issue in the analysis of dried blood microsamples. An LC-MS/MS method for analysis of the model compounds caffeine and paraxanthine in VAMS samples was fully validated and fulfilled all pre-established criteria. In conjunction with previously validated procedures for dried blood spots (DBS) and blood, this allowed us to set up a meticulous comparative study in which both compounds were determined in over 80 corresponding VAMS, DBS and liquid whole blood samples. These originated from authentic human patient samples, covering a wide hematocrit range (0.21-0.50). By calculating the differences with reference whole blood concentrations, we found that analyte concentrations in VAMS samples were not affected by a bias that changed over the evaluated hematocrit range, in contrast to DBS results. However, VAMS concentrations tend to overestimate whole blood concentrations, as a consistent positive bias was observed. A different behavior of VAMS samples prepared from incurred and spiked blood, combined with a somewhat reduced recovery of caffeine and paraxanthine from VAMS tips at high hematocrit values, an effect that was not observed for DBS using a very similar extraction procedure, was found to be at the basis of the observed VAMS-whole blood deviations. Based on this study, being the first in which the validity and robustness of VAMS is evaluated by analyzing incurred human samples, it can be concluded that VAMS effectively assists in eliminating the effect of hematocrit