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.

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.

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.

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.

Comparison of PAC and MOAH for understanding the carcinogenic and developmental toxicity potential of mineral oils.

The carcinogenicity and developmental toxicity of unrefined mineral oil is related to its 3-7 ring polycyclic aromatic compounds (PAC) content. Therefore, refining operations focus on the targeted removal PAC from mineral oil that may contain aromatics of low toxicological concern. There are thus, two types of aromatic substances in mineral oil: hazardous and non-hazardous. The first type consists of 3-7 ring PAC which may be naked (unsubstituted) or lowly alkylated. The second type or non-hazardous consists of 1-7 ring aromatics with high degree of alkylation or lack of bay or fjord regions. Although these are toxicologically different, they may both elute in the same fraction when using chromatography. To understand how these two aromatic types are related we have assessed the entire mineral oil refinement process by measuring total mineral oil aromatic hydrocarbons (MOAH) content by chromatography next to regulatory hazard tests which focus on 3-7 ring PAC. MOAH content is positively correlated to its molecular weight resulting in aromatic content bias for high viscosity substances. Hazard to 3-7 ring PAC is best controlled by the validated IP346 or modified Ames test. We explain the concept of high vs low alkylation by shortly reviewing new data on alkylated PAC.

Analysis of polycyclic aromatic hydrocarbons (PAHs) in surface sediments and edible aquatic species in an oil-contaminated mangrove ecosystem in Bodo, Niger Delta, Nigeria: Bioaccumulation and human health risk assessment.

This work investigated the occurrence and risks associated with polycyclic aromatic hydrocarbons (PAHs) in tissues from five commonly consumed aquatic species (swimming crabs, estuarine shrimp, tiger prawns, periwinkles, and tilapia) and sediment across six sites in the area around Bodo town, in the Niger Delta region of Nigeria. We aimed to establish a relationship between PAH concentrations in sediment and biota, and to derive biota-sediment accumulation factors (BSAFs). Risks to human health associated with consumption of impacted food sources were assessed based on measured biotic concentrations of PAHs. The average concentration of PAHs and the number of PAHs measured above the limit of quantification varied greatly between different biota, with the lowest average concentrations observed in tilapia, followed by tiger prawns, crabs, estuarine shrimp, and the highest concentrations were observed in periwinkles. Similar to biotic concentrations, BSAFs were found to vary greatly across species, sites, and PAHs, though BSAFs for all organisms except periwinkles were below a value of 1. In periwinkles, BSAFs exceeded a value of 1 for phenanthrene (BSAF = 1.7), pyrene (1.5) and benzo[k]fluoranthene (1.7). Risks to human health associated with consumption of these species were assessed using the BaP toxic-equivalent approach for cancer risks and the toxic unit approach which jointly considered carcinogenic but also non-cancer hazards. The BaP toxic-equivalent approach showed that the excess lifetime cancer risk resulting from daily consumption of 0.2 kg of seafood ranged between 1.3 × 10-6 for tiger prawn and tilapia to 4.1 × 10-6 for periwinkles, which is below the excess lifetime cancer risk of 10-4 used by Dutch and Nigerian authorities for sediment intervention values. This finding is supported by the results obtained from the toxic unit approach which indicates that the ratios of the estimated dose and the maximal permissible risk level for summed PAHs never exceeded 1.

GTL synthetic paraffin oil shows low liver and tissue retention compared to mineral oil.

Oral exposure to mineral oil may result in a narrow fraction of mineral oil saturated hydrocarbon (MOSH) being retained in tissues. Excess of MOSH hepatic retention may lead to the formation of lipogranuloma caused by predominantly multiring cycloalkanes (naphthenics) in a critical range of C25-C35. Although hepatic lipogranuloma is of low pathological concern, MOSH tissue deposition could be minimized by using an oil of similar quality but devoid of naphthenic structures to decrease hepatic retention. Synthetic Gas to liquid (GTL) oils offer an alternative to petroleum derived mineral oils, because they do not contain naphthenic structures. To demonstrate this point, SD rats were fed either GTL oil (99% iso-alkanes) or naphthenic mineral oil (84% cycloalkanes) at 200 mg/kg bw/day for 90 or 134 days with a recovery group. Liver, fat and mesenteric lymph nodes were analyzed for alkane sub-type levels using Online-HPLC-GC-FID and GCxGC-TOF-MS. Results indicate that at equal external dose, GTL hydrocarbons result in lower tissue levels and more rapid excretion than MOSH. GTL retained hepatic fractions were also qualitatively different than MOSH constituents. Because chemical composition differences, GTL oil show low absorption and tissue retention potential and thus an advantageous alternative to conventional mineral oil.

A 12-Week Randomized Double-Blind Placebo-Controlled Clinical Trial, Evaluating the Effect of Supplementation with a Spinach Extract on Skeletal Muscle Fitness in Adults Older Than 50 Years of Age.

The aim of a 12-week randomized double-blind placebo-controlled study was to assess the effect of daily supplementation with a natural extract of Spinacia oleracea L. (4 × 500 mg capsules/day; total 2 g per day) combined with a moderate-intensity training program (1 h session/3 times a week) on skeletal muscle fitness in adults over 50 years of age. Muscle strength assessed by isokinetic and isometric dynamometry improved significantly in the experimental (n = 23) and the placebo (n = 22) groups, but the magnitude of improvement was higher in the experimental group, with between-group differences in almost all variables, including isokinetic at 60° s-1 in knee extension, peak torque (p < 0.007); total work per repetition maximum (p < 0.009); isokinetic at 180°s-1 in knee extension, peak torque (p < 0.002); total work (p < 0.007); total work per repetition maximum (p < 0.005); average power (p < 0.027); isometric in knee extension, peak torque (p < 0.005); and average peak torque (p < 0.002). Similar findings were observed for muscle quality. Changes in quality of life (SF-36) were not found, except for improvements in the role physical (p < 0.023) and role emotional (p < 0.001) domains, likely as a result of the physical training sessions. A nutritional survey did not revealed changes in dietary habits. No adverse events were recorded. In subjects over 50 years of age, moderate-intensity strength training combined with daily supplementation for 12 weeks with a natural extract of Spinacia oleracea L. improved muscle-related variables and muscle quality. Maintaining muscle health is a key component of healthy aging.

Minimum reporting standards based on a comprehensive review of the zebrafish embryo teratogenicity assay.

Reproductive toxicity chemical safety assessment involves extensive use of vertebrate animals for regulatory testing purposes. Although alternative methods such as the zebrafish embryo teratogenicity assay (identified in the present manuscript by the acronym ZETA) are promising for replacing tests with mammals, challenges to regulatory application involve lack of standardization and incomplete validation. To identify key protocol aspects and ultimately support improving this situation, a comprehensive review of the literature on the level of harmonization/standardization and validation status of the ZETA has been conducted. The gaps and needed advances of the available ZETA protocols were evaluated and discussed with respect to its applicability as an alternative approach for teratogenicity assessment. Based on the review outcomes, a set of minimum reporting standards for the experimental protocol is proposed. Together with other initiatives towards implementation of alternative approaches at the screening and regulatory levels, the application of minimum reporting requirements is anticipated to support future method standardization and validation, as well as identifying potential improvement aspects. Present findings are expected to ultimately support advancing the ongoing validation initiatives towards the regulatory acceptance of the ZETA.

Relevance of animal studies in the toxicological assessment of oil and wax hydrocarbons. Solving the puzzle for a new outlook in risk assessment.

Paraffin waxes and white mineral oils are distinct petroleum products separated from a common feedstock by crystallization, where only n-alkanes, iso- and cyclo-alkanes with a linear backbone of ∼ 20 carbon atoms long, selectively crystalize out from the oil to form the wax, which is solid at room temperature, whereas oils remain liquid. Up until the 90's, these differences were reflected in separated regulatory assessments. A paradigm shift occurred when Fischer 344 rats (F-344) developed liver epithelioid granuloma following exposure to low and medium viscosity oils or waxes. This lesion was used as common denominator between these products to be jointly assessed under the common term "mineral hydrocarbons - MHC", obviating compositional differences. This regulatory paradigm dominated for the next 30 years, exacerbated by the EFSA 2012 evaluation using the analytical term "MOSH" (mineral oil saturated hydrocarbons) which encompassed these products under single chromatography fraction. The reconstruction of historical developments, together with recent EFSA-sponsored studies of toxicity and accumulation and supporting literature, has allowed us to understand the etiology of the F-344 rat hepatic epithelioid granuloma, which is presented in an adverse outcome pathway (AOP). Considering chemical composition, it clearly demonstrates that the hepatic effects in F-344 rats caused by linear alkanes of waxes are irrelevant for humans. Waxes are thus not MOSH and should thus be evaluated on their own merit. The term MOSH should not include n-alkanes and be exclusively used to mineral oil fractions when considering their chemical makeup for a relevant human hazard assessment.

Acute Effects of Surgical and FFP2 Face Masks on Physiological Responses and Strength Performance in Persons with Sarcopenia.

Due to COVID-19, wearing a face mask to reduce virus transmission is currently mandatory in some countries when participants practice exercise in sports centers. Therefore, the aim of the present study was to analyze the effect of wearing a surgical or FFP2 mask during a resistance training session. Fourteen people with sarcopenia (age: 59.40 ± 5.46 years; weight: 68.78 ± 8.31 kg; height: 163.84 ± 9.08 cm) that participated in the study performed three training sessions in a randomized order: 4 sets of 10 repetitions of a half-squat at 60% of the one-repetition maximum and 90 s of rest between set and were either (a) without a mask (NM), (b) wearing a surgical face mask (SM), and (c) wearing a FFP2 face mask (FFP2). We found that wearing face masks had no effect on strength performance (session mean propulsive velocity (m/s): WM: 0.396 ± 0.042; SM: 0.387 ± 0.037; and FFP2: 0.391 ± 0.042 (p = 0.918)). Additionally, no impact of wearing a mask was found on heart rate, heart rate variability, blood lactate concentration (WM: 4.17 ± 1.89; SM: 4.49 ± 2.07; and FFP2: 5.28 ± 2.45 mmol/L (p = 0.447)), or rating of perceived exertion. Wearing a surgical or FFP2 face mask during a resistance training session resulted in similar strength performance and physiological responses than the same exercise without a mask in persons with sarcopenia.

Early management of critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with a severe acute respiratory condition requiring respiratory support and mechanical ventilation. Based on the pathophysiology and clinical course of the disease, a therapeutic approach can be adapted. Three phases have been identified, in which different strategies are recommended in a stepwise invasiveness approach. In the second or acute phase, patients are frequently admitted to the ICU for severe pneumonia and hypoxemia with evidence of a proinflammatory and hypercoagulable state. This stage is an opportunity to intervene early in the disease. Medical strategies and mechanical ventilation should be individualized to improve outcomes.

An investigation of the acute central nervous system effects of n-decane.

Acute central nervous system (CNS) depression is the most sensitive toxicological effect associated with aliphatic hydrocarbon exposure. No observed effect levels for the CNS effects of aliphatic constituents decrease with increasing carbon number to C10 (Lammers et al., 2011; McKee et al., 2011), whereas constituents with carbon numbers > C10 do not produce CNS effects at maximally attainable vapor concentrations (Nilsen et al., 1988). Accordingly, as n-decane appeared to be the "worst case" for acute CNS effects among aliphatic hydrocarbon solvent constituents, experimental studies were conducted to more precisely define the no effect level. Rats were exposed for 8 h to n-decane, either constantly at 3000 mg/m3 or at higher levels using a discontinuous exposure protocol to assess the influence of fluctuating exposures. Neurobehavioral testing methods including visual discrimination performance and motor activity were used to assess performance, and concentrations of n-decane in blood and brain were measured to obtain pharmacokinetic data. No statistically significant differences were observed in the neurobehavioral tests, establishing 3000 mg/m3 as the no effect level for CNS effects in rats. These data support the recommended guidance value of 1050 mg/m3 for C9-C15 aliphatic hydrocarbons for use in calculating occupational exposure levels for complex hydrocarbon solvents and provide empirical evidence that advice from the ACGIH® that within a working day there should be no more than 3 fluctuations, not longer than 15 min and not exceeding 3 times the Threshold Limit Value (TLV®), is reasonable for this group of substances.

The selective determination of potentially carcinogenic polycyclic aromatic compounds in lubricant base oils by the DMSO extraction method IP346 and its correlation to mouse skin painting carcinogenicity assays.

Mineral oils are produced by vacuum distillation of crude oil at temperatures from ∼300 °C to ∼600 °C. Subsequent refining processes to eliminate the carcinogenic potential of mineral oils (by extraction and/or hydrotreatment) are based on the principle of removing substances associated with carcinogenic activity; i.e. PAC (polycyclic aromatic compounds), which include PAH and N or S heterocycles. Traditionally, the carcinogenic potential of the refined product was tested in the mouse skin painting assay. This bioassay is considered the gold standard for petroleum derived products since it uses the most sensitive species and route of exposure, and because mice and humans develop the same type of skin tumors it is a relevant model to assess the carcinogenic potential of mineral oils. Mouse skin painting studies have also been important in distinguishing two types of aromatic compounds found in mineral oil. The first type includes the 3-7 ring PAC associated with potential carcinogenic effects found in the 340-535 °C boiling range, which are removed by refinement. The second type includes highly alkylated aromatic compounds (predominantly 1-2 rings) which are not bioactivated and non-carcinogenic, which are typical of a refined oil. Because mouse skin painting studies are time consuming, a DMSO based method was developed that is capable to distinguish these two types of aromatics. Although this industry method, known as the IP346, has been applied for more than 30 years, the background experimental data underlying its development has not yet been published. This paper presents and discusses the chemical and biological features of mineral oil PAC structures assessed by IP346, especially the crucial role of the DMSO extraction step which allows to discriminate between the two types of aromatics. The DMSO selectivity towards the toxicological relevant PAC is discussed by comparing the composition of the DMSO extract of a distillate aromatic extract and mineral oils of varying viscosities and refining conditions. PAC which have >3 rings (naked or partially alkylated) are preferentially encompassed by the DMSO extract, whereas those PAC which have relatively long alkyl side chains are not. Thus, according to the IP346, refined oils will have lower levels of DMSO extractable material compared to less refined oils. DMSO selectivity towards the potentially carcinogenic >3 ring PAC makes the IP346 method therefore highly correlated to the outcome of mouse skin painting studies, using a pass/fail dichotomy. The accuracy, including the false negative results of the IP346 in the prediction of mineral oil carcinogenicity is discussed. The DMSO based IP346 is thus a simple but clear reflection of refinement efficacy. It links manufacturing conditions to carcinogenic potential of an oil, supported by solid physical-chemical and toxicological associations. In Europe it is the only legally binding method to assess, classify and label lubricating base oils and inherently more reliable for hazard assessment than the determination of an arbitrary selection of PAH.

SPECIES: A platform for the exploration of ecological data.

The modeling of ecological data that include both abiotic and biotic factors is fundamental to our understanding of ecosystems. Repositories of biodiversity data, such as GBIF, iDigBio, Atlas of Living Australia, and SNIB (Mexico's National System of Biodiversity Information), contain a great deal of information that can lead to knowledge discovery about ecosystems. However, there is a lack of tools with which to efficiently extract such knowledge. In this paper, we present SPECIES, an open, web-based platform designed to extract implicit information contained in large scale sets of ecological data. SPECIES is based on a tested methodology, wherein the correlations of variables of arbitrary type and spatial resolution, both biotic and abiotic, discrete and continuous, may be explored from both niche and network perspectives. In distinction to other modeling systems, SPECIES is a full stack exploratory tool that integrates the three basic components: data (which is incrementally growing), a statistical modeling and analysis engine, and an interactive visualization front end. Combined, these components provide a powerful tool that may guide ecologists toward new insights. SPECIES is optimized to support fast hypothesis prototyping and testing, analyzing thousands of biotic and abiotic variables, and presenting descriptive results to the user at different levels of detail. SPECIES is an open-access platform available online (http://species.conabio.gob.mx), that is, powerful, flexible, and easy to use. It allows for the exploration and incorporation of ecological data and its subsequent integration into predictive models for both potential ecological niche and geographic distribution. It also provides an ecosystemic, network-based analysis that may guide the researcher in identifying relations between different biota, such as the relation between disease vectors and potential disease hosts.