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The number of prescriptions for new direct oral anticoagulants (DOACs) apixaban, edoxaban, rivaroxaban and dabigatran has increased exponentially in recent years, increasingly replacing the old gold standard, vitamin-K-antagonists. Due to their wide therapeutic range, therapeutic drug monitoring (TDM) is not required, although it has been proven that this could significantly reduce side effects. In order to develop a cost-efficient and simple method for the simultaneous detection of the DOACs and phenprocoumon, a new technology for sample preparation from capillary blood in the ambulant sector named VAMS® was integrated and an LC-MS detector with on-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone TM 1.0x50 mm column was used. The mobile phase consisted of methanol with water (3/97 v/v) and 0.1 % ammonia solution with a flow rate of 2.5 mL/min. For the chromatographic separation, a Phenomenex LTD Kinetex 2.6 µm C18 100 Å, 100x3.0 mm column with a flow rate of 0.3 mL/min in gradient mode was utilized. The mobile phase consisted of acetonitrile, water and formic acid (A: 10:90:0.1 v/v and B: 95:05:0.1 v/v). The method was fully validated in the therapeutic range of the substances according to current guidelines. The LLOQ ranged from 3.5 µg/L for rivaroxaban to 88 µg/L for phenprocoumon and the intra-day and inter-day precision was less than 13 % and 12 %, while the accuracy was within a range of 85.7-113 % and 88.7-106 %, respectively. Samples could be stored in the Mitra® devices for at least seven days at room temperature except of dabigatran. Because the Mitras® were used, exactly 10 µL of blood could be drawn and no significant haematocrit effect was observed. A reliable, simple and cost-effective extraction and analysis LC-MS method could be developed and validated. This method is therefore applicable in ambulatory care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In neonatal and pediatric intensive care units, Gram -positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram -positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram -positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS)., Methods: A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods., Results: The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%-114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin., Conclusions: A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

High-dose methotrexate is part of the polychemotherapy protocols for the treatment of Acute lymphoblastic leukaemia (ALL) with therapeutic drug monitoring (TDM) to adjust leucovorin rescue. An immunoassay is commonly used to analyse serum samples collected via venous blood sampling. However, immunoassays cannot distinguish between the parent drug and its metabolites. Besides, the blood volume required by venous blood sampling is high. Therefore, the aim of this project was to develop a fast, simple, reliable and cost-efficient micro sampling bioanalytical method using capillary blood to minimize the harm of children and to analyse both methotrexate and its metabolites. To achieve this aim, a LC-MS method with on-line solid phase extraction (SPE) for the simultaneous detection of methotrexate and its metabolites from capillary blood using volumetric-absorptive-microsampling (VAMS) technology was developed and fully validated. Besides, the method was also validated and modified for serum samples to compare the results with the immunoassay. A single-quadrupole MS detector was used for detection. Through the use of on-line SPE technology, a lower limit of quantitation of 0.03 µM for MTX and 7-OH-MTX and of 0.05 µM for DAMPA from a 10 μL capillary blood sample was achieved. The accuracy is between 90.0 and 104% and the precision between 4.7 and 12% for methotrexate and its metabolites, respectively. Because of the cross reactivity of the immunoassay a cross-validation was not successful. Besides, a correlation factor of 0.46 for MTX between plasma and whole-blood was found. A fast, simple, reliable and cost-efficient extraction and analysis LC-MS method could be developed and validated, which is applicable in ambulatory and clinical care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Georg Hempel reports equipment, drugs, or supplies was provided by Neoteryx, LLC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

For therapeutic drug monitoring (TDM) of axitinib, the new volumetric absorption microsampling technology (VAMS™) was applied to obtain capillary blood samples in an ambulatory setting and the results were compared to plasma samples as the gold standard. On-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone™ 1.0 × 500 mm column was used to reduce costs and working time. For the analytical separation, a Kinetex 2.6 µm C18 100 Å, 100 × 3.0 mm column with a flow rate of 0.3 mL/min in gradient mode was utilised. The mobile phase consisted of acetonitrile, water and formic acid (A: 05:95:0.1 v/v and B: 95:05:0.1 v/v). For the detection, a single-quadrupole MS detector was used. Through the use of on-line SPE technology, it is possible to reach a LLOQ of 0.5 µg/L from a 10 µL capillary blood sample. For lower concentrations, a MS/MS-detector coupled with the same chromatographic system was applied reaching a LLOQ of 0.04 µg/L. This newly developed method was validated with both detectors at different calibration ranges for plasma and capillary blood as matrix. The precision of the within- and between-runs was within a range of 0.6-7.8% and 1.8 - 14% CV, respectively, while the accuracy was within a range of 81.2-115% and 87.7-116%, respectively. A reliable, simple, less personnel-intensive and cost-efficient extraction and analysis LC-MS and LC-MS/MS method could be developed and validated, which is applicable in ambulatory and clinical care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Georg Hempel reports a relationship with AbbVie Corporation that includes: consulting or advisory. Charlotte Kloft reports a relationship with Charlotte Kloft PharMetrX industry consortium (AbbVie Deutschland GmbH & Co. KG, AstraZeneca Ltd., Boehringer Ingelheim Pharma GmbH & Co. KG, Grünenthal GmbH, F. Hoffmann-La Roche Ltd., Merck KGaA and Sanofi) that includes: funding grants. Oliver Scherf-Clavel reports a relationship with Horphag Research that includes: funding grants. Oliver Scherf-Clavel reports a relationship with Hector Stiftung II gGmbH that includes: funding grants., (Copyright © 2022 Elsevier B.V. All rights reserved.)

NaCrO 2 particles for high-rate sodium ion batteries were prepared on a multigram scale in segmented flow from chromium nitrate and sodium nitrate using a segregated flow water-in-oil emulsion drying process. Microfluidic processing is an environmentally friendly and rapid synthetic method, which can produce large-scale industrial implementation for the production of materials with superior properties. The reaction time for NaCrO 2 particles was reduced by almost one order of magnitude compared to a normal flask synthesis and by several orders of magntitude compared to a conventional solid-state reaction. In addition, it allows for an easy upscaling and was generalized for the synthesis of other layered oxides NaMO 2 (M = Cr, Fe, Co, Al). The automated water-in-oil emulsion approach circumvents the diffusion limits of solid-state reactions by allowing a rapid intermixing of the components at a molecular level in submicrometer-sized micelles. A combination of Raman and nuclear magnetic resonance spectroscopy ( 1 H, 23 Na), thermal analysis, X-ray diffraction and high resolution transmission electron microscopy provided insight into the formation mechanism of NaCrO 2 particles. The new synthesis method allows cathode materials of different types to be produced in a large scale, constant quality and in short reaction times in an automated manner.

Marine organisms combat bacterial colonization by biohalogenation of signaling compounds that interfere with bacterial communication. These reactions are catalyzed by haloperoxidase enzymes, whose activity can be emulated by nanoceria using milli- and micromolar concentrations of Br - and H 2 O 2 . We show that the haloperoxidase-like activity of nanoceria can greatly be enhanced by Ln substitution in Ce 1- x Ln x O 2- x /2 . Non-agglomerated nanosized Ce 1- x Ln x O 2- x /2 (Ln = Pr, Tb, particle size < 10 nm) was prepared mechanochemically from CeCl 3 and Na 2 CO 3 followed by short calcination. Lanthanide metals could be incorporated into the CeO 2 host without solubility limit, as shown for Tb. The distribution of the Ln 3+ defect sites in the CeO 2 host structure was analyzed by electron spin resonance spectroscopy. Ce 3+ and superoxide O 2 - species are present at surface sites. Their formation is promoted by increasing dopant concentration. Ce 1- x Ln x O 2- x /2 was prepared in copious amounts by ball-milling. This energy-saving and residue-free method can be upscaled to industrial scale. The surface defect chemistry of Ce 1- x Ln x O 2- x /2 was unravelled by vibrational spectroscopy. It is associated with the mechanochemical preparation and leads to enhanced catalytic activity. Although Ce 0.9 Pr 0.1 O 1.95 had a lower BET surface area than pure CeO 2 , its catalytic activity, calibrated by oxidative bromination of phenol red, was much higher because the ζ -potential increased from 15 mV (for CeO 2 ) to 30 mV (for Ce 0.9 Pr 0.1 O 1.95 ). This facilitates adsorption of Br - in aqueous conditions and explains the high catalytic activity of the Ln-substituted CeO 2 . Ce 1- x Ln x O 2- x /2 is an effective and "green" nanoparticle haloperoxidase mimic for antifouling applications, as no chemicals other than the ubiquitous Br - and H 2 O 2 (generated in daylight) are required, and only natural metabolites are released into the environment.

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

A general method to carry out the fluorination of metal oxides with poly(tetrafluoroethylene) (PTFE, Teflon) waste by spark plasma sintering (SPS) on a minute scale with Teflon is reported. The potential of this new approach is highlighted by the following results. i) The tantalum oxyfluorides Ta 3 O 7 F and TaO 2 F are obtained from plastic scrap without using toxic or caustic chemicals for fluorination. ii) Short reaction times (minutes rather than days) reduce the process time the energy costs by almost three orders of magnitude. iii) The oxyfluorides Ta 3 O 7 F and TaO 2 F are produced in gram amounts of nanoparticles. Their synthesis can be upscaled to the kg range with industrial sintering equipment. iv) SPS processing changes the catalytic properties: while conventionally prepared Ta 3 O 7 F and TaO 2 F show little catalytic activity, SPS-prepared Ta 3 O 7 F and TaO 2 F exhibit high activity for photocatalytic oxygen evolution, reaching photoconversion efficiencies up to 24.7% and applied bias to photoconversion values of 0.86%. This study shows that the materials properties are dictated by the processing which poses new challenges to understand and predict the underlying factors., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Cognitive reappraisal is an emotion regulation strategy that involves reinterpreting the meaning of an event or its outcome to change its emotional trajectory. In this study, we examined how cognitive reappraisal affects both emotional experience and memory outcomes. We also examined whether these outcomes are modulated by participants' self-reported success at generating reappraisals. To do this, we asked participants to use situation-focused reappraisals to decrease their emotional response to some negative images and to passively view other negative images while facial electromyography (EMG) was recorded. After each trial, participants rated the image's emotional valence and arousal. During reappraisal trials, participants also self-reported their success in generating a reappraisal. One week later, memory was assessed with a surprise free recall test followed by a recognition test. Compared with images that were passively viewed, participants ( N = 42) rated the successfully reappraised images as lower in arousal and less negative in valence. Meanwhile, there was an emotional cost associated with failures to generate reappraisals; participants rated these images as higher in arousal and more negative in valence. No similar effects emerged for the EMG ratings. In contrast to these emotional outcomes, a different pattern emerged for the memory outcomes. Instructions to reappraise led to enhanced recall and recognition and to greater memory confidence regardless of whether or not participants successfully generated the reappraisals. Taken together, these results suggest that trying, but failing, to generate a situation-focused cognitive reappraisal may be detrimental. In these situations, people feel worse but remember the situation well. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Modified nucleosides (mNS) in urine are shown to be encouraging markers in cancer, mostly in patients presenting with high tumor mass such is breast and lung cancer. To our knowledge, mNS have not been investigated in head and neck squamous cell carcinoma (HNSCC). HNSCC is characterized by early metastasis into locoregional lymph nodes and slow infiltrating growth, but even in the advanced stage exhibits only a relatively low cancer volume. Therefore, reliable distinction between HNSCC and healthy controls by urinary mNS might pose substantial analytical problems and even more as patients with HNSCC mostly have an increased exposure to tobacco smoke and excessive alcohol consumption which affect the renal mNS pattern., Materials and Methods: Urinary mNS in samples of 93 therapy-naive patients with HNSCC and 242 healthy controls were quantified by reversed-phase high-performance liquid chromatography. Considering that the circadian rhythm causes diuresis-induced variations in concentration, the mNS-to-creatinine ratio was chosen to compare patients and controls. For sensitivity and specificity in discriminating between patients and controls, the corresponding curve was plotted. Additionally, logistic regression was carried out and a multilayer perceptron neuronal network (NN) was created., Results: Fifteen mNS were detectable in cases and controls; concentrations of 11 were found to be significantly different. The sensitivity and specificity depend on the total volume of the lesion; HNSCC with volume <20 ml was reliably detected, but those with a volume of 20 ml or greater produced amounts of mNS which led to the most accurate detection of HNSCC based on HNSCC-specific mNS patterns., Conclusion: Analysis of urinary mNS allows for detection of small-volume HNSCC, with acceptable specificity and sensitivity if the tumor volume exceeds 20 ml., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Different organisms such as bacteria, molds and humans produce and release a relative unknown class of metabolites which are responsible for the individual olfactory pattern. These volatile organic metabolites (VOM) represent a kind of biosignature that reflects the sum of all multifactorial influences, including genetics, environmental factors, nutritional and disease status. As a result of pathological processes the individual body odor can be influenced by newly produced or altered compositions of the VOM. Until now, human VOM have been detected in various body media, such as on the skin, in the exhaled air as well as in body fluids such as saliva, mother's milk, sweat, blood and urine., Methods: In this retrospective case-control study urinary VOM of 53 therapy-naive patients with head and neck squamous cell carcinoma (HNSCC) and 82 healthy controls were semi-quantified by headspace solid-phase micro extraction (SPME) gas chromatography (GC) mass spectrometry (MS). At first, the procedure was optimized in respect to the extraction parameters. By using Student's t-test significant differences in the VOM pattern with the corresponding p-values were obtained. For multivariate metabolite pattern recognition the hierarchical cluster analysis by Ward was applied, followed by the supervised partial least squares-discriminant analysis (PLS-DA)., Results: In total 81 VOMs could identified in the urine samples of all study participants, of which 25 were significantly increased and of which were 10 significantly reduced in HNSCC-patients compared to the controls. In addition, the multivariate statistics confirmed that on the basis of the renal excreted pattern of the volatile metabolites a high discrimination can be carried out between patients with a tumor in the head and neck region and controls. The substance group of the saturated, unbranched aldehydes makes a substantial contribution in this context., Conclusions: The systematic pattern analysis of urinary VOMs appears to have potential clinical application as a diagnostic tool for cancer, especially HNSCC.

Although a group of people working together recalls more items than any one individual, they recall fewer unique items than the same number of people working apart whose responses are combined. This is known as collaborative inhibition, and it is a robust effect that occurs for both younger and older adults. However, almost all previous studies documenting collaborative inhibition have used stimuli that were neutral in emotional valence, low in arousal, and studied by all group members. In the current experiments, we tested the impact of picture-stimuli valence, picture-stimuli arousal, and information distribution in modulating the magnitude of collaborative inhibition. We included both younger and older adults because there are age differences in how people remember emotional pictures that could modulate any effects of emotion on collaborative inhibition. Results revealed that when information was shared (i.e., studied by all group members), there were robust collaborative inhibition effects for both neutral and emotional stimuli for both younger and older adults. However, when information was unshared (i.e., studied by only a single group member), these effects were attenuated. Together, these results provide mixed support for the retrieval strategy disruption account of collaborative inhibition. Supporting the retrieval strategy disruption account, unshared study information was less susceptible to collaborative inhibition than shared study information. Contradicting the retrieval strategy disruption account, emotional valence and arousal did not modulate the magnitude of collaborative inhibition despite the fact that participants clustered the emotional, but not neutral, information together in memory.

After reductions of fugitive and diffuse emissions by an industrial complex, a follow-up study was performed to determine the time variability of volatile organic compounds (VOCs) and the lifetime cancer risk (LCR). Passive samplers (3 M monitors) were placed outdoors (n = 179) and indoors (n = 75) in industrial, urban, and control areas for 4 weeks. Twenty-five compounds including n-alkanes, cycloalkanes, aromatics, chlorinated hydrocarbons, and terpenes were determined by GC/MS. The results show a significant decrease of all VOCs, especially in the industrial area and to a lesser extent in the urban area. The median outdoor concentration of benzene in the industrial area declined compared to the former study, around 85% and about 50% in the urban area, which in the past was strongly influenced by industrial emissions. Other carcinogenic compounds like styrene and tetrachloroethylene were reduced to approximately 60%. VOC concentrations in control areas remained nearly unchanged. According to the determined BTEX ratios and interspecies correlations, in contrast to the previous study, traffic was identified as the main emission source in the urban and control areas and showed an increased influence in the industrial area. The LCR, calculated for benzene, styrene, and tetrachloroethylene, shows a decrease of one order of magnitude in accordance to the decreased total VOC concentrations and is now acceptable according to values proposed by the World Health Organization.

Polyacrylamide hydrogel (PAAG) has been used as a tissue filler in facial corrective surgery and for breast augmentation in Kiev, Ukraine, for more than 10 years with reportedly very good results. These results, however, have not been published in peer-reviewed journals. A Danish/Swedish group of plastic surgeons with special interest in facial corrective surgery did a retrospective, systematic, pre-planned investigation of 104 patients treated at the center in Kiev. All data were entered into a pre-programmed database for data processing. The mean age of this population was 37.4 years and the mean time since the gel injection was 3.9 years. An average of 5.7 ml of PAAG was injected prior to the investigation. The gel was well tolerated and assessment of the outcome was judged to be very good by 78% and good by 22%, by both physicians and patients. It is concluded that PAAG is well tolerated and seems to be a promising product for facial corrective surgery. Currently, the product (Aquamid) is being studied in several prospective clinical trials, one of which is completed and in the process of preparation for publication.

Restrictions ordered by the U.S. Food and Drug Administration on the use of silicone gel-filled breast implants, as well as patient and surgeon dissatisfaction with the aesthetic results sometimes attained with saline solution-filled implants, have prompted new interest in developing alternative implant filler materials, including triglycerides. Soybean oil-filled breast implants are now in various stages of testing and use in the United States, Europe, and Canada. This article reports on experience with Trilucent breast implants (prefilled with soybean oil) by one plastic surgeon in Sweden. A total of 96 patients (191 implants) underwent primary augmentation or replacement augmentation mammaplasty between October 1995 and June 1997. Data have been analyzed for all 96 patients with a mean follow-up period of 15 months and for 67 patients (133 implants) with a mean follow-up of 18 months. The significant findings of the study include the absence of systemic reactions or unusual local complications, the low incidence (2.3%) of symptomatic capsular contracture (grades III and IV) among the 67 patients at the 18-month postoperative time point, and high patient satisfaction with the aesthetic results. The mammographic radiolucency of soybean oil-filled implants was also demonstrated. At the 18-month follow-up point, the only negative observations were the presence of skin wrinkling in 3% of the breasts and implant palpability in 46% of the breasts. These findings are in general agreement with preliminary data from the European clinical trials of Trilucent breast implants.