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The nano-metric cutting process of single-crystal SiO 2 was studied using molecular dynamics simulation, where the effects of anisotropy on material removal and surface integrity were analyzed. The typical crystal directions on different crystal planes of SiO 2 were selected as cutting directions. The results show that the chip formation, temperature distribution in the machined area, cutting force, phase transformation and damage layer thickness vary according to the cutting direction. The crystal orientation of (110) [00−1] exhibits a large range of damage expansion while (110) [1−10] exhibits the smallest range. In addition, the radial distribution function results show that SiO 2 workpieces cut in different directions vary in crystal phase type and content to some degree, while a new phase is produced in the cutting direction of (111) [−101]. Therefore, the anisotropy of the selection of crystal planes and crystal directions is of great significance for the nano-metric cutting of SiO 2 to obtain quality machined surfaces of SiO 2 .

Vitamin D 3 , an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D 3 in oily drug products using supercritical fluid chromatography-mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D 3 and five non-esters including four that are isobaric to vitamin D 3 . Firstly, a screening study highlighted the Torus 1-AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make-up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid-liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC-MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non-ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC-MS as a valuable, versatile, and green tool for routine pharmaceutical QC., (© 2024 John Wiley & Sons Ltd.)

Correctly estimating the post-mortem interval (PMI) is essential in forensic practice. In recent decades, the measurement of vitreous humor analyte concentrations - especially of hypoxanthine and potassium - and their correlation with the PMI have returned good results. However, calculating the PMI from the data collected can be quite complex. The present paper describes a web resource ( http://modestya.usc.es:3838/Forensic/ ) that simplifies the procedure. The PMI is determined (with its 95% confidence interval) in a rapid, easy, and reliable manner based on the use of mathematical models, the biochemistry of the vitreous humor, and physical variables such as the ambient temperature, the rectal temperature, and bodyweight. The application is entirely free to use., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The K + and hypoxanthine (Hx) concentrations of the vitreous humour (VH) rise gradually after death, providing a means of estimating the post-mortem interval (PMI). The correlation between these analytes and the PMI is good since the vitreous chamber is partially isolated from autolytic events occurring elsewhere; the [K +] and [Hx] recorded is thus the result of changes within the eye. The present work provides a systematic review, following PRISMA recommendations, of 36 articles (3 reviews and 33 retrospective cohort studies) discussing the many procedures and regression models that have been developed for improving PMI estimates involving VH analytes. The results of a descriptive study are also provided, highlighting the causes and distribution of mortality as registered in medico-legal autopsies performed in 2019 in Galicia (northwestern Spain), and revealing the use of these PMI estimation methods in real forensic practice. Great heterogeneity was detected in the collection of VH samples, the treatments to which they were subjected before examination, and in their conservation and analysis. A lack of reproducibility in the analytical methods employed to estimate [K +] and [Hx] was noted, as well as an absence of external validation for most of the regression formulae used to determine the PMI from analyte values. The use of methods based on high-performance liquid chromatography, focal electrophoresis, or thermogravimetric/chemometric procedures might solve the problems encountered with traditional analytical techniques, offering reliable results more quickly and effectively (even when samples are contaminated). This study recommends using flexible multiple regression models that combine physical and chemical variables, and that population databases be constructed so that models can be properly validated., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC 50  = 15.0 nM and IC 50  = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t 1/2 of 6.84 min, an intrinsic clearance of 195.63 μL min -1 mg -1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depression., 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 © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Obtaining a reliable estimate of the post-mortem interval (PMI) has been a long-running challenge in forensic medicine. Several more or less successful techniques for making such estimates have been developed, but in recent years important advances have been made thanks to the detailed study of the relationship between the PMI and the analytes - in particular K + - of the vitreous humour (VH). The extraction and pre-treatment of VH samples has been standardized, the influence of certain environmental factors on analytical results has been quantified, and some of the circumstances under which techniques become unreliable have been identified. The present work examines how the conditions to which VH samples are subject in routine practice may alter the results of their analysis. Exposure to light and ambient temperature was found to alter the values returned in determinations of VH [K + ], [Na + ] and [Cl - ], while exposure to several freezing/thawing cycles (even with final heating) led to no significant modifications in determinations of VH [K + ] and [Na + ]. It is recommended that if analysis has to be delayed, VH should be frozen for storage in a refrigerator before bringing to room temperature for processing. It is also recommended that samples not be exposed to ambient light and temperature., (Copyright © 2021 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.)

The estimation of the time elapsed since death is of paramount importance in the field of forensic sciences and criminal investigation, owing, among other factors, to the possible legal repercussions. Over the past few years various formulae have been developed to calculate this interval using a combination of different statistical methods and the concentrations of substances found in the vitreous humor. Corrective factors, such as ambient temperature, cause of death or age, which can modify the concentration of these substances and therefore the estimation of the postmortem interval, have been incorporated into models. In this paper five simple and reliable models to estimate PMI based the on the analysis of potassium, hypoxanthine and urea in the vitreous humor are presented. Corrective factors, such as body weight, rectal temperature and ambient temperature, which can influence the estimation of this interval have been incorporated into the formulae. Finally, the R 2 and the mean squared error have been calculated for each model in order to select the best of the five. A free software program which calculates the PMI from the model and parameters used is available from the authors. It provides quick and reliable results as well as the error committed and R 2 for each case., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Evidence of pesticide transfer from grapes to wine, added to differences in the national regulations regarding the number and the maximum concentration of these species in wine, demands analytical procedures suitable for their routine control in this foodstuff. In this research, solid-phase extraction (SPE) and ultra-performance liquid chromatography (UPLC), with tandem mass spectrometry (MS/MS) detection, are combined to obtain a sensitive and rapid procedure to determine 50 pesticides in red and white wines. Efficiency and selectivity of sample preparation are correlated with the type of sorbent, the elution solvent, and the physicochemical properties of pesticides. SPE of 2-mL wine samples followed by direct injection of the extract in the UPLC-MS/MS system provides quantification limits (LOQs) below 1 ng mL -1 for 48 out of 50 compounds, linear responses up to 200 ng mL -1 , and acceptable accuracy, employing quantification against solvent-based standards, for 45 species. A total analysis time of 10 min, including compounds separation and re-equilibration of the UPLC column, was achieved. The developed methodology was applied to 25 wines (20 conventional and 5 ecological), produced in 7 different countries. Out of 27 pesticides quantified in these wines, 12 displayed occurrence frequencies above 24%; moreover, all wines, except one of the ecological ones, contained residues from at least one pesticide.

The Spanish scale to quantify or qualify bodily harm resulting from any unintentional traffic accident prior to 1 January 2016 is established by Royal Legislative Decree (RDL) 8/2004. This scale assigns points to the sequelae, which are converted into Euros using a table that is updated annually. The objective of this study is to develop a predictive model of sequelae points that will enable the estimation of compensation a short time after the accident. This will facilitate the calculation of the money reserve and rapid access to compensation for the injured party. To conduct this study, we developed a database with information from 999 individuals who had suffered car crash injuries which were evaluated according to the scale contained in RDL 8/2004 for medical experts. Predictive models based on logistic regression models were designed on this database. To choose the best model, we calculated Mallow's Cp. The use of hurdle models made it possible to predict the points received by an injured party within a relatively short period of time after the accident. Once these points are known, it is a simple matter to calculate the corresponding compensation. The prediction models developed provide an easy way to predict the compensation to be awarded to the injured party. These models use days of hospitalization, sex, age and the results of international scales based on the Abbreviated Injury Scale. These variables can be used soon after the occurrence of the crash.

Familial partial lipodystrophy are Mendelian disorders involving abnormal body fat distribution and insulin resistance. The current classification includes the Köbberling syndrome (type 1 familial partial lipodystrophy), characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas. Type 1 familial partial lipodystrophy appears to be heritable, but little is known about it, including putative contributing mutations. We aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy. This is a case-controlled study in which 98 women with type 1 familial partial lipodystrophy that lacked classical mutations known to cause familial partial lipodystrophy were compared with 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy (Dunnigan disease). Clinical course, body composition by dual-energy X-ray absorptiometry, HbA1c, lipid profile, insulin, leptin and family history were evaluated in all of the participants. Analyses of receiver-operating characteristic curve were performed for type 1 familial partial lipodystrophy diagnosis, comparing different truncal/limbs ratios. Among patients with type 1 familial partial lipodystrophy, 68 % developed recognizable lipodystrophy before adolescence, and most displayed an autosomal-dominant pattern (86 %). Women with type 1 familial partial lipodystrophy had less lower-limb adipose tissue than women without lipodystrophy, but significantly more than patients with Dunnigan disease. Moreover, metabolic disturbances occurred more frequently in the type 1 familial partial lipodystrophy group (81 %) than in the non-lipodystrophic group (30 %, p<0.05). The severity of metabolic disturbances was inversely proportional to the percentage of fat in the lower extremities and directly proportional to the amount of visceral adipose tissue. Metabolic profiles were worse in type 1 familial partial lipodystrophy than in Dunnigan disease. According to the receiver-operating characteristic curve analysis, the best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477 (sensitivity: 89 %; specificity: 84 %). Type 1 familial partial lipodystrophy was an early-onset, autosomal-dominant lipodystrophy, characterized by fat loss in the lower limbs and abnormal fat accumulation in the abdominal visceral region, associated to insulin resistance and metabolic disorders. A KöB index >3.477 is highly suggestive of this syndrome.

The use of scales to quantify or qualify bodily harm resulting from an unintentional car accident has been mandatory in Spain since 1995 and compensation for personal injuries resulting from a traffic accident is calculated according to a legal ruling established by Royal Decree 8/2004 (RDL). This present study assesses the reliability of the scale. Agreement between the evaluations for the same patient by 24 qualified observers following the Royal Decree 8/2004 was measured using the Kappa index. The variables assessed were the days of hospitalization, impeditive days, non impeditive days and the functional and aesthetic sequelae. The application of the Fleiss Kappa index obtained a result of 0.37, indicating a "fair agreement" according to the rating scale proposed by Landis and Koch. This study demonstrates the unreliability of the Spanish medical scale for the assessment of injury as described in the RDL 8/2004. The scale should adopt the measurement systems and clinical classifications of outcomes such as the ASIA, SCI scale or the Daniels scale of neurological injury and allow scientific discussion of the findings of the report. The resulting quantitative value should operate as a reliable indicator of a specific quality of the damage., (Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)