Dietary supplementation with a wild green oat extract (Avena sativa L.) to improve wellness and wellbeing during smoking reduction or cessation: a randomized double-blind controlled study.

Objective: Smoking reduction or cessation are critical public health goals, given the well-documented risks of tobacco use to health. Reducing smoking frequency and cessation entirely are challenging due to nicotine addiction and withdrawal symptoms, which can significantly affect mental wellness and overall wellbeing. Previous research has suggested that certain dietary supplements may support smoking cessation and reduction efforts by mitigating these adverse effects. The objective of this study was to assess the effect of supplementation with 900 mg/day of Neuravena®, a green oat extract (GOE) of Avena sativa L., in enhancing wellness and wellbeing during a smoking reduction or cessation experience. Methods: This was an 8-week randomized, double-blind, placebo-controlled study, ClinicalTrials Identifier: NCT04749017 (https://classic.clinicaltrials.gov/ct2/show/NCT04749017). Participants were assigned to one of the study groups, 72 participants were assigned to GOE and 73 to placebo. The subjects were followed for 8-weeks intervention period as well as an additional 4-week follow-up period. At subsequent visits, they underwent clinical assessments including assessments of quality of life, perceived stress, depression, nicotine dependence, anxiety, cognitive performance, and specific assessments of craving intensity. Results: GOE was associated with greater improvements in elements of the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire as compared with placebo. Similar results were obtained from the SF-36 questionnaire and a visual QoL analogue scale (VAS). Perceived stress levels showed greater decline from baseline among the GOE supplemented participants as compared to placebo. Sleep quality parameters improved with GOE supplementation and worsened in the placebo group. At the end of the intervention period, the percentage of successful reducers (defined as >20% reduction in daily cigarettes) was higher in the GOE group as compared to placebo (66.7% vs. 49.3%, p = 0.034). The improvements from baseline in QoL measures in the GOE group persisted at 4 weeks after termination of the intervention. Conclusion: GOE supplementation demonstrated greater improvements in quality of life measures, stress and sleep related parameters during a smoking reduction or cessation experience and the product was shown to be safe and well tolerated.

Dietary supplementation with plant extracts for amelioration of persistent myofascial discomfort in the cervical and back regions: a randomized double-blind controlled study.

Background: Back pain is a common health problem that affects both workers and older people, reducing their quality of life. The primary objective was to assess the effect of dietary supplementation with plant extracts of rosemary, ashwagandha, and sesame consumed for 12 weeks on the intensity of back pain. Methods: A single-center randomized double-blind study with three parallel arms depending on the product consumed. The duration of treatment was 12 weeks. The investigational product, Berelief®, contained a blend of three polyphenolic standardized extracts: rosemary (Rosmarinus officinalis L.), ashwagandha (Withania somnifera L.), and sesame (Sesamum indicum L.) seed. Two doses were tested: low dose (400 mg) and high dose (800 mg). There were 42 subjects in the placebo group, 39 in the low dose and 42 in the high dose groups. Study variables included back pain intensity [VAS score, Patient-Reported Outcomes Measurement Information System (PROMIS-29), and Cornell Musculoskeletal Discomfort Questionnaire; functionality Roland-Morris Disability (RMD) questionnaire]; quality of life (QoL) [36-item Short Form Survey (SF-36), the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Perceived Stress Scale (PSS)]; sleep quality [accelerometer and Pittsburgh Sleep Quality Index (PSQI)]. Results: The improvement in back pain recorded by the visual analogue scale (VAS) at the study visits after the beginning of treatment, as well as on a weekly basis recorded in the diary card was significantly higher in the intervention group than in the placebo group (p < 0.044 dose-low; p < 0.005 dose-high). Significant differences in pain intensity of the PROMIS-29 (p = 0.002) and upper back pain in the Cornell questionnaire (p = 0.011) in favour of the investigational product were found. Furthermore, benefits in improving health-related quality of life, mood and sleep quality were also detected. Conclusion: Dietary supplementation for 12 weeks of a blend of polyphenolic standardized extracts of rosemary, ashwagandha, and sesame was effective in reducing the intensity of pain in subjects with chronic myofascial cervical and back pain.

Metabolism of alcohol ethoxylates (AEs) in rat, hamster, and human hepatocytes and liver S9: a pilot study for metabolic stability, metabolic pathway, and metabolites identification in vitro and in silico.

Alcohol ethoxylates (AEs) are a well-known class of non-ionic surfactants widely used by the personal care market. The aim of this study was to evaluate and characterize the in vitro metabolism of AEs and identify metabolites. Five selected individual homologue AEs (C8EO4, C10EO5, C12EO4, C16EO8, and C18EO3) were incubated using human, rat, and hamster liver S9 fraction and cryopreserved hepatocytes. LC-MS was used to identify metabolites following the incubation of AEs by liver S9 and hepatocytes of all three species. All AEs were metabolized in these systems with a half-life ranging from 2 to 139 min. In general, incubation of AE with human liver S9 showed a shorter half-life compared to rat liver S9. While rat hepatocytes metabolized AEs faster than human hepatocytes. Both hydrophobic alkyl chain and hydrophilic EO head group groups of AEs were found to be target sites of metabolism. Metabolites were identified that show primary hydroxylation and dehydrogenation, followed by O-dealkylation (shortening of EO head groups) and glucuronidation. Additionally, the detection of whole EO groups indicates the cleavage of the ether bond between the alkyl chain and the EO groups as a minor metabolic pathway in the current testing system. Furthermore, no difference in metabolic patterns of each individual homologue AE investigated was observed, regardless of alkyl chain length or the number of EO groups. Moreover, there is an excellent agreement between the in vitro experimental data and the metabolite profile simulations using in silico approaches (OECD QSAR Toolbox). Altogether, these data indicate fast metabolism of all AEs with a qualitatively similar metabolic pathway with some quantitative differences observed in the metabolite profiles. These metabolic studies using different species can provide important reference values for further safety evaluation.

Dietary Supplementation with an Extract of Aloysia citrodora (Lemon verbena) Improves Sleep Quality in Healthy Subjects: A Randomized Double-Blind Controlled Study.

Seventy-one healthy subjects with sleep disturbances participated in a randomized, double-blind controlled trial in which dietary supplementation with an extract of Aloysia citrodora (lemon verbena) (n = 33) or placebo (n = 38) was administered for 90 days. There were between-group differences in favor of the experimental group in the visual analogue scale (VAS) for sleep quality (6.5 ± 1.6 vs. 5.5 ± 2.1, p = 0.021) as well as in the overall score (5.8 ± 2.4, p = 0.008) and scores for sleep latency (1.6 ± 1.0 vs. 1.9 ± 0.7, p = 0.027) and sleep efficiency (84.5 ± 12.8 vs. 79.8 ± 13.6, p = 0.023) in the Pittsburgh Sleep Quality Index (PSQI). Sleep-related variables (latency, efficiency, wakefulness after sleep onset, awakenings) assessed by actigraphy also showed better scores in the experimental group (p = 0.001). Plasma nocturnal melatonin levels also increased significantly in the experimental group (199.7 ± 135.3 vs. 174.7 ± 115.4 pg/mL, p = 0.048). Changes in anthropometric parameters and physical activity levels were not found. In summary, a dietary supplement of lemon verbena administered for 3 months was associated with a significant improvement in sleep quality as compared with placebo in a population of healthy subjects with sleep problems.

The Clade Replacement Theory: a framework to study age-dependent extinction.

There is no scientific consensus about whether and how species' evolutionary age, or the elapsed time since their origination, might affect their probability of going extinct. Different age-dependent extinction (ADE) patterns have been proposed in theoretical and empirical studies, while the existence of a consistent and universal pattern across the tree of life remains debated. If evolutionary age predicts species extinction probability, then the study of ADE should comprise the elapsed time and the ecological process acting on species from their origin to their extinction or to the present for extant species. Additionally, given that closely related species share traits associated with fitness, evolutionary proximity could generate similar ADE patterns. Considering the historical context and extinction selectivity based on evolutionary relatedness, we build on previous theoretical work to formalize the Clade Replacement Theory (CRT) as a framework that considers the ecological and evolutionary aspects of species age and extinction probability to produce testable predictions on ADE patterns. CRT's domain is the diversification dynamics of two or more clades competing for environmental space throughout time, and its propositions or derived hypotheses are as follows: (i) incumbency effects by an early arriving clade that limit the colonization and the diversification of a younger clade leading to a negative ADE scenario (younger species more prone to extinction than older ones) and (ii) an ecological shift triggered by an environmental change that imposes a new selective regime over the environmental space and leads to a positive ADE scenario (extinction probability increasing with age). From these propositions, we developed the prediction that the ADE scenario would be defined by whether an ecological shift happens or not. We discuss how the CRT could be tested with empirical data and provide examples where it could be applied. We hope this article will provide a common ground to unify results from different fields and foster new empirical tests of the mechanisms derived here while providing insights into CRT theoretical structuration.

Skin secretions of Leptodactylidae (Anura) and their potential applications.

The skin of anuran species is a protective barrier against predators and pathogens, showing also chemical defense by substances that represent a potential source for bioactive substances. This review describes the current chemical and biological knowledge from the skin secretions of Leptodactylidae species, one of the most diverse neotropical frog families. These skin secretions reveal a variety of substances such as amines (12), neuropeptides (16), and antimicrobial peptides (72). The amines include histamine and its methylated derivatives, tryptamine derivatives and quaternary amines. The peptides of Leptodactylidae species show molecular weight up to 3364 Da and ocellatins are the most reported. The peptides exhibit commonly glycine (G) or glycine-valine (GV) as C-terminal amino acids, and the most common N-terminal amino acids are glutamic acid (E), lysine (K), and valine (V). The substances from Leptodactylidae species have been evaluated against pathogenic microorganisms, particularly Escherichia coli and Staphylococcus aureus, and the most active peptides showed MIC of 1-15 µM. Furthermore, some compounds showed also pharmacological properties such as immunomodulation, treatment of degenerative diseases, anticancer, and antioxidant. Currently, only 9% of the species in this family have been properly studied, highlighting a large number of unstudied species such as an entire subfamily (Paratelmatobiinae). The ecological context, functions, and evolution of peptides and amines in this family are poorly understood and represent a large field for further exploration.

Evaluating the in vitro developmental toxicity potency of a series of petroleum substance extracts using new approach methodologies (NAMs).

The present study evaluates the in vitro developmental toxicity and the possible underlying mode of action of DMSO extracts of a series of highly complex petroleum substances in the mouse embryonic stem cell test (mEST), the zebrafish embryotoxicity test (ZET) and the aryl hydrocarbon receptor reporter gene assay (AhR CALUX assay). Results show that two out of sixteen samples tested, both being poorly refined products that may contain a substantial amount of 3- to 7-ring polycyclic aromatic compounds (PACs), induced sustained AhR activation in the AhR CALUX assay, and concentration-dependent developmental toxicity in both mEST and ZET. The other samples tested, representing highly refined petroleum substances and petroleum-derived waxes (containing typically a very low amount or no PACs at all), were negative in all assays applied, pointing to their inability to induce developmental toxicity in vitro. The refining processes applied during the production of highly refined petroleum products, such as solvent extraction and hydrotreatment which focus on the removal of undesired constituents, including 3- to 7-ring PACs, abolish the in vitro developmental toxicity. In conclusion, the obtained results support the hypothesis that 3- to 7-ring PACs are the primary inducers of the developmental toxicity induced by some (i.e., poorly refined) petroleum substances and that the observed effect is partially AhR-mediated.

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats.

Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides, and detergent alcohols. The potential toxicity of five HO (i.e., 1-Octene, Nonene, Decene, Hexadecene, and 1-Octadecene) with carbon ranging from C8 to C18 was examined in a combined repeated dose and reproduction/developmental toxicity screening study (OECD TG 422). These five HO were administered to Han Wistar rats by gavage at 0 (controls), 100, 300, and 1000 mg/kg bw/day. As a group of substances, adaptive changes in the liver (liver weight increase without pathological evidence), as well as increased kidney weight in male rats, were observed in HO with carbon numbers from C8 to C10. The overall systemic no observed adverse effect level (NOAEL) for all HO was determined at 1000 mg/kg bw/day. In the reproductive/developmental toxicity assessment, offspring viability, size, and weights were reduced in litters from females treated with Nonene at 1000 mg/kg bw/day. The overall no observed effects level (NOEL) for reproductive toxicity was considered to be 300 mg/kg bw/day for Nonene and 1000 mg/kg bw/day for the other four HO, respectively. These data significantly enrich the database on the toxicity of linear and branched HO, allowing comparison with similar data published on a range of linear and branched HO. Comparisons between structural class and study outcome provide further supportive data in order to validate the read-across hypothesis as part of an overall holistic testing strategy.

Pleistocene South American native ungulates (Notoungulata and Litopterna) of the historical Roth collections in Switzerland, from the Pampean Region of Argentina.

The fossil collections made by early explorers in South America have been fundamental to reveal the past diversity of extinct mammals and unravel their evolutionary history. One important early explorer in South America was the Swiss-Argentine palaeontologist Kaspar Jacob Roth, known as Santiago Roth (1850, Herisau, Switzerland-1924, Buenos Aires, Argentina), who made significant collections of fossil mammals that are housed in museums in Europe and Argentina. The important collections of Roth in Switzerland include iconic Pleistocene megafauna from the Pampean Region (Argentina). The palaeontological significance of the Pampean Region relies on its abundant record of fossil vertebrates that documents diversity dynamics and paleoenvironmental change in southern South America, serving as the basis for the South American biostratigraphical scale of the late Neogene and Quaternary. The South American native ungulates (SANUs) were hoofed placental mammals that radiated in South America. The clades Notoungulata and Litopterna include, among others, the last representatives of SANUs megafauna in the continent. We revise and describe for the first time the SANUs specimens from the Pampean Region of the Roth collections in Switzerland. The collections include two species of notoungulates (Toxodon cf. T. platensis and Mesotherium cristatum) and one litoptern species (Macrauchenia patachonica). The occurrences are restricted to the early and middle Pleistocene (pre-Lujanian Stages/Ages). Although the SANUs diversity in the Roth collections is low in comparison with other groups (e.g., xenarthrans), some of the specimens are very complete, including skulls and postcranial remains. The completeness of the Ma. patachonica material allows an update and reinterpretation of some of the details of the dentition and the postcranial skeleton of this iconic species. In addition to its historical importance, the SANU specimens from the Roth collections provide important information to study the paleobiology and evolution of South American megafauna and evaluate hypotheses about their extinction in the continent.

Las colecciones de fósiles realizadas por los primeros exploradores en América del Sur han sido fundamentales para revelar la diversidad pasada de los mamíferos sudamericanos y desentrañar su historia evolutiva. Un importante explorador en América del Sur fue el paleontólogo suizo-argentino Kaspar Jacob Roth, conocido como Santiago Roth (1850, Herisau, Suiza-1924, Buenos Aires, Argentina), quien realizó importantes colecciones de mamíferos fósiles que se encuentran en museos de Europa y Argentina. Las colecciones de Roth en Suiza incluyen la icónica megafauna del Pleistoceno de la Región Pampeana (Argentina). La importancia paleontológica de la Región Pampeana se basa en su abundante registro de vertebrados fósiles que documenta la diversidad y el cambio paleoambiental en el sur de Sudamérica, sirviendo como base para la escala bioestratigráfica sudamericana del Neógeno tardío y Cuaternario. Los ungulados nativos sudamericanos (SANUs, por sus siglas en inglés) eran mamíferos placentarios con pezuñas que radiaron en Sudamérica. Los clados Notoungulata y Litopterna incluyen, entre otros, los últimos representantes de la megafauna de SANUs en el continente. En este trabajo, revisamos y describimos por primera vez los SANUs de la Región Pampeana de las colecciónes de Roth en Suiza. Las colecciónes incluyen dos especies de notungulados (Toxodon cf. T. platensis y Mesotherium cristatum) y una especie de litopterna (Macrauchenia patachonica). Las ocurrencias están restringidas al Pleistoceno temprano y medio (Pisos/Edades anteriores al Lujanense). Aunque la diversidad de SANU en las colecciónes Roth es baja en comparación con otros grupos (por ejemplo, xenarthros), algunos de los especímenes son muy completos, e incluyen cráneos y restos poscraneales. Lo completo del material de Ma. patachonica permite una actualización y reinterpretación de algunos de los detalles de la dentición y el esqueleto poscraneal de esta icónica especie. Además de su importancia histórica, los SANUs de la colección Roth brindan información importante para estudiar la paleobiología y evolución de la megafauna sudamericana y evaluar hipótesis sobre su extinción en el continente.

Efficacy of Boswellia serrata Extract and/or an Omega-3-Based Product for Improving Pain and Function in People Older Than 40 Years with Persistent Knee Pain: A Randomized Double-Blind Controlled Clinical Trial.

A single-center, randomized, double-blind, controlled clinical trial with four arms was conducted in healthy subjects with persistent knee discomfort (pain intensity on 1-10 cm visual analog scale (VAS) > 3) aged 40 years and older treated with a dietary supplement for 8 weeks. The study groups were Boswellia serrata extract (n = 29), an omega-3-based product (AvailOm® 50 High EPA) (n = 31), Boswellia + AvailOm® (n = 30), and placebo (n = 30). The intake of Boswellia + AvailOm® improved the quality of life (QoL) (WOMAC index) and some variables of muscle strength. Statistically significant differences between the AvailOm® and the placebo groups in the decrease of pain intensity were found. Weekly VAS scores showed a significant decrease in pain perception when comparing the AvailOm® product to the placebo, with the lowest VAS scores at week 8. Consumption of Boswellia improved sleep latency. The time to perform the Up and Go test decreased after the intake of AvailOm®. There was an increase in the omega-3 fatty acids, with the greatest increase in the Boswellia + AvailOm® group. AvailOm® was safe and effective in reducing pain and improving the QoL and functionality of subjects over 40 years with persistent knee pain.

A Novel Active Device for Shoulder Rotation Based on Force Control.

This article describes a one-degree-of-freedom haptic device that can be applied to perform three different exercises for shoulder rehabilitation. The device is based on a force control architecture and an adaptive speed PI controller. It is a portable equipment that is easy to use for any patient, and was optimized for rehabilitating external rotation movements of the shoulder in patients in whom this was limited by muscle-skeletal injuries. The sample consisted of 12 shoulder rehabilitation sessions with different shoulder pathologies that limited their range of shoulder mobility. The mean and standard deviations of the external rotation of shoulder were 42.91 ± 4.53° for the pre-intervention measurements and 53.88 ± 4.26° for the post-intervention measurement. In addition, patients reported high levels of acceptance of the device. Scores on the SUS questionnaire ranged from 65 to 97.5, with an average score of 82.70 ± 9.21, indicating a high degree of acceptance. The preliminary results suggest that the use of this device and the incorporation of such equipment into rehabilitation services could be of great help for patients in their rehabilitation process and for physiotherapists in applying their therapies.

Impact of genetic structural variants in factor XI deficiency: identification, accurate characterization, and inferred mechanism by long-read sequencing.

BACKGROUND: Congenital factor XI (FXI) deficiency is a probably underestimated coagulopathy that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single-nucleotide variants and small insertion/deletions because they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVES: To identify and characterize the SVs affecting F11. METHODS: The study was performed in 93 unrelated subjects with FXI deficiency recruited in Spanish hospitals over a period of 25 years (1997-2022). F11 was analyzed by next-generation sequencing, multiplex ligand probe amplification, and long-read sequencing. RESULTS: Our study identified 30 different genetic variants. Interestingly, we found 3 SVs, all heterozygous: a complex duplication affecting exons 8 and 9, a tandem duplication of exon 14, and a large deletion affecting the whole gene. Nucleotide resolution obtained by long-read sequencing revealed Alu repetitive elements involved in all breakpoints. The large deletion was probably generated de novo in the paternal allele during gametogenesis, and despite affecting 30 additional genes, no syndromic features were described. CONCLUSION: SVs may account for a high proportion of F11 genetic defects implicated in the molecular pathology of congenital FXI deficiency. These SVs, likely caused by a nonallelic homologous recombination involving repetitive elements, are heterogeneous in both type and length and may be de novo. These data support the inclusion of methods to detect SVs in this disorder, with long-read-based methods being the most appropriate because they detect all SVs and achieve adequate nucleotide resolution.

Development of a specific real-time PCR assay for simultaneous detection and differentiation of Coxiella burnetii strains from environmental soil samples.

Coxiella burnetii, the causative agent of Q fever, is a small, coccoid, Gram-negative strict intracellular pathogen. One of the most common ways of acquiring Q fever is through inhalation of aerosols containing the bacteria. Because C. burnetii is highly infectious, spreads easily through the air, and is very resistant to environmental conditions, it is considered a biological threat. This paper presents the development and validation of a specific real-time polymerase chain reaction (real-time PCR or qPCR) assay for the detection of C. burnetii, based on the amplification of a fragment of the isocitrate dehydrogenase (icd) encoding gene. This real-time PCR is highly specific, reproducible, and sensitive, allowing the detection of as few as 5 genome equivalents (GEs) of C. burnetii per reaction. The method enables a rapid preliminary differentiation among strains, based on a point mutation at nucleotide 745 of the icd gene. The assay was successfully evaluated in environmental soil samples; a limit of detection of 3 × 104 colony forming units per 0.5 g of soil (∼3 GEs per reaction) was achieved. The newly developed real-time PCR offers a valuable tool for differential detection of C. burnetii strains in environmental soil samples.

Human impacts outpace natural processes in the Amazon.

Amazonian environments are being degraded by modern industrial and agricultural activities at a pace far above anything previously known, imperiling its vast biodiversity reserves and globally important ecosystem services. The most substantial threats come from regional deforestation, because of export market demands, and global climate change. The Amazon is currently perched to transition rapidly from a largely forested to a nonforested landscape. These changes are happening much too rapidly for Amazonian species, peoples, and ecosystems to respond adaptively. Policies to prevent the worst outcomes are known and must be enacted immediately. We now need political will and leadership to act on this information. To fail the Amazon is to fail the biosphere, and we fail to act at our peril.

The neural correlates of value representation: From single items to bundles.

One of the core questions in Neuro-economics is to determine where value is represented. To date, most studies have focused on simple options and identified the ventromedial prefrontal cortex (VMPFC) as the common value region. We report the findings of an fMRI study in which we asked participants to make pairwise comparisons involving options of varying complexity: single items (Control condition), bundles made of the same two single items (Scaling condition) and bundles made of two different single items (Bundling condition). We construct a measure of choice consistency to capture how coherent the choices of a participant are with one another. We also record brain activity while participants make these choices. We find that a common core of regions involving the left VMPFC, the left dorsolateral prefrontal cortex (DLPFC), regions associated with complex visual processing and the left cerebellum track value across all conditions. Also, regions in the DLPFC, the ventrolateral prefrontal cortex (VLPFC) and the cerebellum are differentially recruited across conditions. Last, variations in activity in VMPFC and DLPFC value-tracking regions are associated with variations in choice consistency. This suggests that value based decision-making recruits a core set of regions as well as specific regions based on task demands. Further, correlations between consistency and the magnitude of signal change with lateral portions of the PFC suggest the possibility that activity in these regions may play a causal role in decision quality.

Madagascar's extraordinary biodiversity: Evolution, distribution, and use.

Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique "living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.

Madagascar's extraordinary biodiversity: Threats and opportunities.

Madagascar's unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar's terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as the most prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar.

Modeling of the Influence of Operational Parameters on Tire Lateral Dynamics.

Tires play a critical role in vehicle safety. Proper modeling of tire-road interaction is essential for optimal performance of active safety systems. This work studies the influence of temperature, longitudinal vehicle speed, steering frequency, vertical load, and inflation pressure on lateral tire dynamics. To this end, a tire test bench that allows the accurate control of these parameters and the measurement of the variables of interest was used. The obtained results made it possible to propose a simple model that allowed the determination of relaxation length as a function of tire vertical load and vehicle linear speed, and the determination of a representative tread temperature. Additionally, a model has been proposed to determine the lateral friction coefficient from the aforementioned temperature. Finally, results also showed that some variables had little influence on the parameters that characterize lateral dynamics.

Assessment of the Intestinal Absorption of Higher Olefins by the Everted Gut Sac Model in Combination with In Silico New Approach Methodologies.

To reduce the number of animals and studies needed to fulfill the information requirements as required by Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (EC no. 1907/2006), a read-across approach was used to support approximately 30 higher olefins. This study aimed to assess the absorption potential of higher olefins through the gut wall as the experimentally determined bioavailability which would strengthen the read-across hypothesis and justification, reducing the need for toxicity studies on all of the higher olefins. The absorption potential of a series of higher olefins (carbon range from 6 to 28, with five configurations of the double bond) was determined in the in vitro everted rat small intestinal sac model and subsequently ranked. In addition, in silico approaches were applied to predict the reactivity, lipophilicity, and permeability of higher olefins. In the in vitro model, everted sacs were incubated in "fed-state simulated small intestinal fluid" saturated with individual higher olefins. The sac contents were then collected, extracted, and analyzed for olefin content using gas chromatography with a flame ionization detector. The C6 to C10 molecules were readily absorbed into the intestinal sacs. Marked inter-compound differences were observed, with the amount of absorption generally decreasing with the increase in carbon number. Higher olefins with ≥C14 carbons were either not absorbed or very poorly absorbed. In the reactivity simulation study, the reactivity is well described by the position of the double bond rather than the number of carbon atoms. In the lipophilicity and permeability analysis, both parameter descriptors depend mainly on the number of carbon atoms and less on the position of the double bond. In conclusion, these new approach methodologies provide supporting information on any trends or breakpoints in intestinal uptake and a hazard matrix based on carbon number and position of the double bond. This matrix will further assist in the selection of substances for inclusion in the mammalian toxicity testing programme.

Anti-Inflammatory and Antioxidant Capacity of a Fruit and Vegetable-Based Nutraceutical Measured by Urinary Oxylipin Concentration in a Healthy Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Oxylipins, lipid biomarkers of inflammation are considered the gold standard method to evaluate the inflammatory and antioxidant status. The aim of the present study was to investigate whether the administration of a polyphenolic extract shot in the form of a nutraceutical was able to reduce inflammation, measured in urine markers. Ninety-two participants (45 males, 47 females, age 34 ± 11 years, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, BMI 24.40 ± 3.43 kg/m2) completed the study after an intervention of two 16-week periods consuming extract or placebo separated by a 4-week washout period. The results showed significant differences in terms of reduction of different pro-inflammatory oxylipins (15-keto-PGF2α (from 0.90 ± 0.25 ng/mL to 0.74 ± 0.19 ng/mL p < 0.05), ent-PGF2α (from 1.59 ± 0.37 ng/mL to 1.44 ± 0.32 ng/mL p < 0.05), 2,3-dinor-15-F2t-Isop) (from 1.17 ± 0.35 ng/mL to 1.02 ± 0.27 ng/mL p < 0.05), in total oxylipins count (from 8.03 ± 1.86 ng/mL to 7.25 ± 1.23 ng/mL p < 0.05), and increase in PGE2 (from 1.02 ± 0.38 ng/mL to 1.26 ± 0.38 ng/mL p < 0.05) which has an anti-inflammatory character, after extract consumption compared to placebo. The available data seem to indicate that long-term consumption of a nutraceutical with high polyphenol content improves inflammation and oxidation parameters measured in urine, through UHPLC-QqQ-ESI-MS/MS.