Ceanothanes Derivatives as Peripheric Anionic Site and Catalytic Active Site Inhibitors of Acetylcholinesterase: Insights for Future Drug Design.

Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and particularly in the formation of amyloid plaques; therefore, the inhibition of AChE has become one of the most promising strategies for the treatment of AD, particularly concerning AChE inhibitors that interact with the peripheral anionic site (PAS). Ceanothic acid isolated from the Chilean Rhamnaceae plants is an inhibitor of AChE through its interaction with PAS. In this study, six ceanothic acid derivatives were prepared, and all showed inhibitory activity against AChE. The structural modifications were performed starting from ceanothic acid by application of simple synthetic routes: esterification, reduction, and oxidation. AChE activity was determined by the Ellmann method for all compounds. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compounds would be produced by interaction with the PAS of AChE. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the ceanothane derivatives were performed using the Swiss ADME tool.

Stability of Bioactive Compounds and Antioxidant Activity in Rosehip Juice (Rosa spp.).

Rosehip fruits, characterized by their high concentrations of bioactive compounds and antioxidant activity (AA), have been traditionally used to make jams, infusions, and juices. Thus, the objective of this research was to evaluate the stability of rosehip juice by determining the concentrations of bioactive compounds and total phenols and the AA using chromatographic and spectroscopic methods. The stability of the juice was evaluated with three treatments and different storage conditions, namely, unpasteurized-refrigerated, pasteurized-room temperature, and pasteurized-refrigerated, and measurements were taken for eight months. Individual and total phenolic compounds, evaluated by chromatographic methods, reported differences until the end of this study. The total phenolic compounds by Folin-Ciocalteu method presented an average decrease of 57% in the three treatments in relation to the initial conditions. On the other hand, the ascorbic acid content decreased considerably, disappearing at week six. Furthermore, for the unpasteurized-refrigerated and pasteurized-refrigerated samples, a correlation was found between flavonols, total phenols, ascorbic acid, and antioxidant activity determined by the TEAC method. For the pasteurized-room temperature samples, correlations were found between the levels of several flavonols, hydroxycinnamic acid, total phenols, and ascorbic acid and the antioxidant activity determined by the CUPRAC method. The stability of the compounds was mainly correlated with the storage conditions of the juice and not with pasteurization. The highest stability was observed for the unpasteurized-refrigerated and pasteurized-refrigerated samples. Although the concentrations of the compounds evaluated decreased during this study, significant levels of AA persisted, providing beneficial characteristics for consumer health.

Synthesis and Isolation of Phenol- and Thiol-Derived Epicatechin Adducts Prepared from Avocado Peel Procyanidins Using Centrifugal Partition Chromatography and the Evaluation of Their Antimicrobial and Antioxidant Activity.

Polyphenols from agro-food waste represent a valuable source of bioactive molecules that can be recovered to be used for their functional properties. Another option is to use them as starting material to generate molecules with new and better properties through semi-synthesis. A proanthocyanidin-rich (PACs) extract from avocado peels was used to prepare several semi-synthetic derivatives of epicatechin by acid cleavage in the presence of phenol and thiol nucleophiles. The adducts formed by this reaction were successfully purified using one-step centrifugal partition chromatography (CPC) and identified by chromatographic and spectroscopic methods. The nine derivatives showed a concentration-dependent free radical scavenging activity in the DPPH assay. All compounds were also tested against a panel of pathogenic bacterial strains formed by Listeria monocytogenes (ATCC 7644 and 19115), Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 11775 and 25922), and Salmonella enterica (ATCC 13076). In addition, adducts were tested against two no-pathogenic strains, Limosilactobacillus fermentum UCO-979C and Lacticaseibacillus rhamnosus UCO-25A. Overall, thiol-derived adducts displayed antimicrobial properties and, in some specific cases, inhibited biofilm formation, particularly in Listeria monocytogenes (ATCC 7644). Interestingly, phenolic adducts were inactive against all the strains and could not inhibit its biofilm formation. Moreover, depending on the structure, in specific cases, biofilm formation was strongly promoted. These findings contribute to demonstrating that CPC is a powerful tool to isolate new semi-synthetic molecules using avocado peels as starting material for PACc extraction. These compounds represent new lead molecules with antioxidant and antimicrobial activity.

Stability of Phenolic Compounds, Antioxidant Activity and Color Parameters in Colored-Flesh Potato Chips.

Potato (Solanum tuberosum) chips are the most consumed snacks worldwide today. Colored potato chips prepared from potato cultivars with red and purple flesh are a novel alternative to traditional potato chips because of their higher phenolic compound content, such as anthocyanins and hydroxycinnamic acid derivatives (HCADs), which might make these chips healthier compared with traditional chips. There is little information on the stability of these compounds. In this study, the nutritional value of these chips was evaluated by determining phenolic profiles, antioxidant activity and color parameters with liquid chromatography diode array and mass spectrometry detection (HPLC-DAD-ESI-MS/MS) and spectrophotometric methods during storage for four months. Five anthocyanins and three HCADs were detected, with the latter compounds being the most abundant, with concentrations on average between the first (97.82 mg kg-1) and the last (31.44 mg kg-1) week of storage. Similar trends were observed in antioxidant activity and stability, with the CUPRAC method showing the highest response among all the methods employed. The color indices were stable throughout the storage time. Based on these results, colored-flesh potato chips are an optimal alternative for consumption because of their high retention of phenolic compounds and antioxidant activity during storage, providing potential benefits to human health.

Follow-up of gallbladder polyps in a high-risk population of gallbladder cancer: a cohort study and multivariate survival competing risk analysis.

BACKGROUND: The risk of neoplasia in gallbladder polyps seems to be low, but the evidence from populations at high-risk of gallbladder cancer is limited. We aimed to estimate the risk and to identify the factors associated with neoplastic polyps in a high-risk Hispanic population. METHODS: A retrospective cohort was recruited between January 2010 and December 2019 at a Chilean university center. Multivariate survival analyses were conducted. Fine-Gray models were fitted to account for competing risks. Covariate adjustment was conducted using propensity scores. The main outcome was the development of gallbladder adenomas or adenocarcinoma. RESULTS: Overall, 748 patients were included, 59.6% underwent cholecystectomy. The median follow-up of patients not subjected to cholecystectomy was 54.7 months (12-128.6 months). Seventeen patients (2.27%) developed the outcome. After adjustment by age, sex, intralesional blood flow, lithiasis and gallbladder wall thickening, only polyp size (≥10 mm, adjusted-HR: 15.01, 95%CI: 5.4-48.2) and number of polyps (≥3 polyps, adjusted-HR: 0.11, 95%CI: 0.01-0.55) were associated with neoplasia. CONCLUSION: In a Hispanic population at high-risk for gallbladder cancer, gallbladder polyps seem to have a low risk of neoplasia. Polyp size was the main risk factor, while having multiple polyps was associated with an underlying benign condition.

Noticeable Quantities of Functional Compounds and Antioxidant Activities Remain after Cooking of Colored Fleshed Potatoes Native from Southern Chile.

The effect of cooking on the concentrations of phenolic compounds and antioxidant activities in 33 colored-fleshed potatoes genotypes was evaluated. The phenolic profiles, concentrations, and antioxidant activity were evaluated with a liquid chromatography diode array detector coupled to a mass spectrometer with an electrospray ionization interface (HPLC-DAD-ESI-MS/MS). Eleven anthocyanins were detected; in the case of red-fleshed genotypes, these were mainly acyl-glycosides derivatives of pelargonidin, whereas, in purple-fleshed genotypes, acyl-glycosides derivatives of petunidin were the most important. In the case of the purple-fleshed genotypes, the most important compound was petunidin-3-coumaroylrutinoside-5-glucoside. Concentrations of total anthocyanins varied between 1.21 g kg-1 in fresh and 1.05 g kg-1 in cooked potato and the decreases due to cooking ranged between 3% and 59%. The genotypes that showed the highest levels of total phenols also presented the highest levels of antioxidant activity. These results are of relevance because they suggest anthocyanins are important contributors to the antioxidant activity of these potato genotypes, which is significant even after the drastic process of cooking.

In vitro micropropagation and alkaloids analysis by GC-MS of Chilean Amaryllidaceae plants: Rhodophiala pratensis.

INTRODUCTION: Plants from Amaryllidaceae family are of interest since they produce a particular type of alkaloid useful for the treatment of neurodegenerative diseases of the central nervous system, such as Galanthamine. Given the low content of these secondary metabolites in the plant, it is necessary to study mechanisms to increase the productivity of them. OBJECTIVE: To obtain fast qualitative and quantitative analysis of the alkaloids and extend the understanding of biosynthesis and metabolism in these kinds of plants. Furthermore, establish a reliable, simple and fast analytical method for the in vitro callus culture of vegetative organs for Rhodophiala pratensis species. METHODS: The alkaloids composition of the callus culture of R. pratensis were analysed by gas chromatography coupled with mass spectrometry (GC-MS). RESULTS: A methodology for the qualitative and quantitative analysis of the alkaloids present in fresh callus culture of this wild plant species was established. The analysis showed alternation in the alkaloids type ratio and number of compounds between wild bulbs, in vitro bulbs and callus. It was possible to identify 24 alkaloids from a pool of 60 signals whose fragmentation pattern corresponds to the alkaloids of Amaryllidaceae plants. Together with the aforementioned, the amount and type of alkaloid present in the plant material obtained by in vitro culture of R. pratensis was determined in the same way. The results show the high biosynthetic potential of in vitro grown bulbs and callus tissue that are able to produce significant amounts of pharmacologically relevant alkaloids from R. pratensis in various proportions that depend on the culture conditions such as supplementation with growth substances. The in vitro grown bulbs produce an alkaloidal extract that contain a 52.6% w/w of alkaloids. CONCLUSION: This study allowed the alkaloid content in callus culture of R. pratensis to be found by means of GC-MS. These results allowed a relationship between the type of growth regulator and the type of alkaloids found to be established. Finally, we can say that the results achieved to state that the production of alkaloids using different combinations of growth regulators could be directed during in vitro micropropagation from provided plant material.

A Crossover Comparison of Standard and Telerobotic Approaches to Prenatal Sonography.

OBJECTIVES: To determine the feasibility of a telerobotic approach to remotely perform prenatal sonographic examinations. METHODS: Thirty participants were prospectively recruited. Participants underwent a limited examination (assessing biometry, placental location, and amniotic fluid; n = 20) or a detailed examination (biometry, placental location, amniotic fluid, and fetal anatomic survey; n = 10) performed with a conventional ultrasound system. This examination was followed by an equivalent examination performed with a telerobotic ultrasound system, which enabled sonographers to remotely control all ultrasound settings and fine movements of the ultrasound transducer from a distance. Telerobotic images were read independently from conventional images. RESULTS: The mean gestational age ± SD of the 30 participants was 22.9 ± 5.3 weeks. Paired-sample t tests showed no statistically significant difference between conventional and telerobotic measurements of fetal head circumference, biparietal diameter, or single deepest vertical pocket of amniotic fluid; however, a small but statistically significant difference was observed in measurements of abdominal circumference and femur length (P < .05). Intraclass correlations showed excellent agreement (>0.90) between telerobotic and conventional measurements of all 4 biometric parameters. Of 21 fetal structures included in the anatomic survey, 80% of the structures attempted across all patients were sufficiently visualized by the telerobotic system (range, 57%-100% per patient). Ninety-seven percent of patients strongly or somewhat agreed that they would be willing to have another telerobotic examination in the future. CONCLUSIONS: A telerobotic approach is feasible for remotely performing prenatal sonographic examinations. Telerobotic sonography (robotic telesonography) may allow for the development of satellite ultrasound clinics in rural, remote, or low-volume communities, thereby increasing access to prenatal imaging in underserved communities.

Evaluation of microextraction by packed sorbent, liquid-liquid microextraction and derivatization pretreatment of diet-derived phenolic acids in plasma by gas chromatography with triple quadrupole mass spectrometry.

Miniaturized sample pretreatments for the analysis of phenolic metabolites in plasma, involving protein precipitation, enzymatic deconjugation, extraction procedures, and different derivatization reactions were systematically evaluated. The analyses were conducted by gas chromatography with mass spectrometry for the evaluation of 40 diet-derived phenolic compounds. Enzyme purification was necessary for the phenolic deconjugation before extraction. Trimethylsilanization reagent and two different tetrabutylammonium salts for derivatization reactions were compared. The optimum reaction conditions were 50 µL of trimethylsilanization reagent at 90°C for 30 min, while tetrabutylammonium salts were associated with loss of sensitivity due to rapid activation of the inert gas chromatograph liner. Phenolic acids extractions from plasma were optimized. Optimal microextraction by packed sorbent performance was achieved using an octadecylsilyl packed bed and better recoveries for less polar compounds, such as methoxylated derivatives, were observed. Despite the low recovery for many analytes, repeatability using an automated extraction procedure in the gas chromatograph inlet was 2.5%. Instead, using liquid-liquid microextraction, better recoveries (80-110%) for all analytes were observed at the expense of repeatability (3.8-18.4%). The phenolic compounds in gerbil plasma samples, collected before and 4 h after the administration of a calafate extract, were analyzed with the optimized methodology.

Initial Experience Using a Telerobotic Ultrasound System for Adult Abdominal Sonography.

PURPOSE: The study sought to assess the feasibility of performing adult abdominal examinations using a telerobotic ultrasound system in which radiologists or sonographers can control fine movements of a transducer and all ultrasound settings from a remote location. METHODS: Eighteen patients prospectively underwent a conventional sonography examination (using EPIQ 5 [Philips] or LOGIQ E9 [GE Healthcare]) followed by a telerobotic sonography examination (using the MELODY System [AdEchoTech] and SonixTablet [BK Ultrasound]) according to a standardized abdominal imaging protocol. For telerobotic examinations, patients were scanned remotely by a sonographer 2.75 km away. Conventional examinations were read independently from telerobotic examinations. Image quality and acceptability to patients and sonographers was assessed. RESULTS: Ninety-two percent of organs visualized on conventional examinations were sufficiently visualized on telerobotic examinations. Five pathological findings were identified on both telerobotic and conventional examinations, 3 findings were identified using only conventional sonography, and 2 findings were identified using only telerobotic sonography. A paired sample t test showed no significant difference between the 2 modalities in measurements of the liver, spleen, and diameter of the proximal aorta; however, telerobotic assessments overestimated distal aorta and common bile duct diameters and underestimated kidney lengths (P values < .05). All patients responded that they would be willing to have another telerobotic examination. CONCLUSIONS: A telerobotic ultrasound system is feasible for performing abdominal ultrasound examinations at a distant location with minimal training and setup requirements and a moderate learning curve. Telerobotic sonography (robotic telesonography) may open up the possibility of remote ultrasound clinics for communities that lack skilled sonographers and radiologists, thereby improving access to care.

Single and composite influence of growth-related candidate gene polymorphisms on additive genetic variation of birth weight in Charolais beef cattle.

The objective of the present experiment work was to evaluate the effect of the inclusion of genomic information on the additive genetic variance of birth weight (BW) of Charolais cattle in Mexico. Variance components and heritability were estimated using four linear models. The first model was the base model (BM) from which single and composite effects of selected single-nucleotide polymorphism (SNP) markers were evaluated (BM1, BM2, and a composite BM3). Genetic markers were included in a regression model and analyzed by stepwise regression against adjusted BW from a panel of growth-related traits candidate gene markers. After two regression rounds, two SNPs (R (2) > 0.02) were chosen to include into the animal models as fixed effects. Growth hormone receptor gene GHR 4.2 and GHR 6.1 SNPs were selected from a panel of 39 SNPs. GHR 4.2 had a negligible effect on BW, whilst GHR6.1, interestingly, explained ∼9 % of genetic variance (p = 0.0877) with an αG>A = 0.509. The inclusion of markers in M2 and M3 reduced 19 and 15 % of the additive genetic variance, respectively. Both adjusted significantly better the linear model (LRT = p < 0.01). Results obtained suggest that the previous selection of markers in a candidate gene approach and subsequent inclusion of selected SNPs into animal model might provide a better fit, avoiding the overestimation of genetic variance components and breeding values for BW.

A Simple Validated Method for the Estimation of Pepsin Activity in Microtiter Array for the INFOGEST Protocol.

The INFOGEST protocol has been widely used as a static in-vitro simulation of gastrointestinal food digestion for bioaccessibility assessments on bioactive compounds. The standardization of the activity of several enzymes, such as pepsin, via UV-spectrophotometry of digested hemoglobin at 280 nm is a key step in the protocol. Standardization is a crucial stage since it is necessary to determine the quantity of enzyme to be added to the sample for digestion. However, this method is yet to be analytically validated; it requires quartz cuvettes and large volumes of samples and is time-consuming. Thus, we reviewed and adapted a well-known colorimetric method in microplates array by using the Folin-Ciocalteu reagent, and this study is the first to report for miniaturization of this method, the advantages of which include its automation, ease of use, the low volume of samples required, the minimal use of reagents, and speed. This method was compared to the traditional UV method, and the comparison results show no statistical difference between the inter day means for each group (p > 0.05). The proposed method was validated, showing high reproducibility (8% as inter-day CV) and statistically comparable results with the traditional UV spectrophotometric method.

Berberis microphylla G. Forst Intake Reduces the Cardiovascular Disease Plasmatic Markers Associated with a High-Fat Diet in a Mice Model.

Polyphenols are bioactive substances that participate in the prevention of chronic illnesses. High content has been described in Berberis microphylla G. Forst (calafate), a wild berry extensively distributed in Chilean-Argentine Patagonia. We evaluated its beneficial effect through the study of mouse plasma metabolome changes after chronic consumption of this fruit. Characterized calafate extract was administered in water, for four months, to a group of mice fed with a high-fat diet and compared with a control diet. Metabolome changes were studied using UHPLC-DAD-QTOF-based untargeted metabolomics. The study was complemented by the analysis of protein biomarkers determined using Luminex technology, and quantification of OH radicals by electron paramagnetic resonance spectroscopy. Thirteen features were identified with a maximum annotation level-A, revealing an increase in succinic acid, activation of tricarboxylic acid and reduction of carnitine accumulation. Changes in plasma biomarkers were related to inflammation and cardiovascular disease, with changes in thrombomodulin (-24%), adiponectin (+68%), sE-selectin (-34%), sICAM-1 (-24%) and proMMP-9 (-31%) levels. The production of OH radicals in plasma was reduced after calafate intake (-17%), especially for the group fed with a high-fat diet. These changes could be associated with protection against atherosclerosis due to calafate consumption, which is discussed from a holistic and integrative point of view.

The Impact of 2-Ketones Released from Solid Lipid Nanoparticles on Growth Modulation and Antioxidant System of Lactuca sativa.

2-Ketones are signal molecules reported as plant growth stimulators, but their applications in vegetables have yet to be achieved. Solid lipid nanoparticles (SLNs) emerge as a relevant nanocarrier to develop formulations for the controlled release of 2-ketones. In this sense, seedlings of Lactuca sativa exposed to 125, 375, and 500 µL L-1 of encapsulated 2-nonanone and 2-tridecanone into SLNs were evaluated under controlled conditions. SLNs evidenced a spherical shape with a size of 230 nm. A controlled release of encapsulated doses of 2-nonanone and 2-tridecanone was observed, where a greater release was observed as the encapsulated dose of the compound increased. Root development was strongly stimulated mainly by 2-tridecanone and leaf area (25-32%) by 2-nonanone. Chlorophyll content increased by 15.8% with exposure to 500 µL L-1 of 2-nonanone, and carotenoid concentration was maintained with 2-nonanone. Antioxidant capacity decreased (13-62.7%) in L. sativa treated with 2-ketones, but the total phenol concentration strongly increased in seedlings exposed to some doses of 2-ketones. 2-Tridecanone strongly modulates the enzymatic activities associated with the scavenging of H2O2 at intra- and extracellular levels. In conclusion, 2-ketones released from SLNs modulated the growth and the antioxidant system of L. sativa, depending on the dose released.

The Roles of Protocols and Protocolization in Improving Outcome From Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization. METHODS: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances. RESULTS: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033). CONCLUSION: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability.

Testing the Impact of Protocolized Care of Patients With Severe Traumatic Brain Injury Without Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol.

BACKGROUND: Most patients with severe traumatic brain injury (sTBI) in low- or-middle-income countries and surprisingly many in high-income countries are managed without intracranial pressure (ICP) monitoring. The impact of the first published protocol (Imaging and Clinical Examination [ICE] protocol) is untested against nonprotocol management. OBJECTIVE: To determine whether patients treated in intensive care units (ICUs) using the ICE protocol have lower mortality and better neurobehavioral functioning than those treated in ICUs using no protocol. METHODS: This study involved nineteen mostly public South American hospitals. This is a prospective cohort study, enrolling patients older than 13 years with sTBI presenting within 24 h of injury (January 2014-July 2015) with 6-mo postinjury follow-up. Five hospitals treated all sTBI cases using the ICE protocol; 14 used no protocol. Primary outcome was prespecified composite of mortality, orientation, functional outcome, and neuropsychological measures. RESULTS: A total of 414 patients (89% male, mean age 34.8 years) enrolled; 81% had 6 months of follow-up. All participants included in composite outcome analysis: average percentile (SD) = 46.8 (24.0) nonprotocol, 56.9 (24.5) protocol. Generalized estimating equation (GEE) used to account for center effects (confounder-adjusted difference [95% CI] = 12.2 [4.6, 19.8], P = .002). Kaplan-Meier 6-month mortality (95% CI) = 36% (30%, 43%) nonprotocol, 25% (19%, 31%) protocol (GEE and confounder-adjusted hazard ratio [95% CI] = .69 [.43, 1.10], P = .118). Six-month Extended Glasgow Outcome Scale for 332 participants: average Extended Glasgow Outcome Scale score (SD) = 3.6 (2.6) nonprotocol, 4.7 (2.8) protocol (GEE and confounder-adjusted and lost to follow-up-adjusted difference [95% CI] = 1.36 [.55, 2.17], P = .001). CONCLUSION: ICUs managing patients with sTBI using the ICE protocol had better functional outcome than those not using a protocol. ICUs treating patients with sTBI without ICP monitoring should consider protocolization. The ICE protocol, tested here and previously, is 1 option.

B-value variations in the Central Chile seismic gap assessed by a Bayesian transdimensional approach.

The b-value can be used to characterize the seismic activity for a given earthquake catalog and provide information on the stress level accumulated at active faults. Here we develop an algorithm to objectively estimate variations of b-value along one arbitrary dimension. To this end, we employ a Bayesian transdimensional approach where the seismic domains will be self-defined according to information in the seismic catalog. This makes it unnecessary to prescribe the location and extent of domains, as it is commonly done. We first show the algorithm's robustness by performing regressions from synthetic catalogs, recovering the target models with great accuracy. We also apply the algorithm to a microseismicity catalog for the Central Chile region. This segment is considered a seismic gap where the last major earthquake with shallow slip was in 1730. Our results illuminate the downdip limit of the seismogenic zone and the transition to intraslab seismicity. In the along-strike direction, low b-value coincides with the extent of locked asperities, suggesting a high-stress loading at the Central Chile seismic gap. Our results indicate the reliability of the Bayesian transdimensional method for capturing robust b-value variations, allowing us to characterize the mechanical behavior on the plate interface of subduction zones.

Drugs of abuse in tap water from eight European countries: Determination by use of supramolecular solvents and tentative evaluation of risks to human health.

Recent research findings have confirmed the presence of illicit drugs in tap water from some European Union (UE) member states. Contaminants in tap water come directly from drinking water sources such as rivers or lakes owing to inefficient removal at wastewater treatment and water purification plants. This work was aimed at setting a starting point for assessing the health risks of exposure to twelve drugs of abuse through consumption of tap water in the European population. For this purpose, a method using supramolecular solvents (SUPRAS) was developed to extract drugs in the opioid, amphetamine, cocaine and cannabinoid groups from tap water for their determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 119 tap water samples were collected from eight EU countries for analysis. Seven drugs were found at concentrations from 0.3 to 340 ng/L in 72 of the samples (60.5%). The mean exposure to the drugs through consumption of tap water was calculated to be 0.0064-3.531 ng/kg·day for adults and 0.0247-6.7580 ng/kg·day for children, whereas that resulting from dermal contact was estimated to be 4-7 orders of magnitude lower. Exposure values were compared with the minimum required performance levels (MRPL) for the drugs in urine set by the World Anti-Doping Agency (WADA). Based on the results, a need clearly exists for further research into the adverse effects on health of inadvertent, sustained exposure to low doses of drugs of abuse.

Metabolic profile and antioxidant capacity of five Berberis leaves species: A comprehensive study to determine their potential as natural food or ingredient.

A comprehensive study of bioactive compounds was carried out in the leaves of the main Berberis species growing in Chile (Berberis microphylla, Berberis darwinii, Berberis empetrifolia, Berberis trigona, and the introduced Berberis vulgaris). We identified 117 compounds, by a detailed analysis of each molecule, including phenolic acids, alkaloids, flavonols, and other compounds, using high-performance liquid chromatography and high-resolution mass spectrometry. Quantitative analysis of main compound was also included for all species. Hydroxycinnamic acid derivatives were the main compounds in all the studied leaves, with the highest concentration in Berberis microphylla. Quercetin derivatives were the most relevant flavonols in all species, except in Berberis vulgaris, in which isorhamnetin-3-rutinoside was the most concentrated. The fatty acid profile, determined by gas chromatography mass spectrometry revealed the presence of linoleic and linolenic acids in all species studied. Berberis vulgaris showed higher levels of these fatty acids. The antioxidant capacity, explored by three in vitro methods, showed high values for all studied Berberis species. The obtained levels are higher than those of other prominent foods. The findings will inform novel approaches for the valorization of these leaves as natural food or ingredient.

Isolation of Three Lycorine Type Alkaloids from Rhodolirium speciosum (Herb.) Ravenna Using pH-Zone-Refinement Centrifugal Partition Chromatography and Their Acetylcholinesterase Inhibitory Activities.

Preparative separation of three lycorine type alkaloids from Rhodolirum speciosum (Amaryllidaceae) was successfully carried out using pH-zone-refinement centrifugal partition chromatography (CPC) using the solvent system methyl-tert-butyl ether/acetonitrile/water (4:1:5, v/v/v) in descending mode. Using this system, Alkaloid 1 (165.7 mg, 88.2%, purity), 2 (60.1 mg, 97.7% purity) and 3 (12.3 mg, 84.4% purity) were obtained in one step. For structure elucidation, the pure alkaloids were subjected to spectroscopy analysis using nuclear magnetic resonance experiments (1H-NMR, 13C-NMR) and gas chromatography coupled with mass spectrometry (GC-MS). Alkaloids 1, 2, and 3 were identified as 1-O-acetyl-5,6-dehydrolycorine, 1-O-acetyl-lycorine, and 1,2-O-diacetyl-5,6-dehydrolycorine, respectively. The acetylcholinesterase inhibitory activity of these alkaloids was IC50 151.1 µg/mL, IC50 203.5 µg/mL, IC50 470.0 µg/mL, and IC50 17.1 µg/mL, respectively.