Trace metal accumulation through the environment and wildlife at two derelict lead mines in Wales.

Trace metal pollution is globally widespread, largely resulting from human activities. Due to the persistence and high toxicity of trace metals, these pollutants can have serious effects across ecosystems. However, few studies have directly assessed the presence and impact of trace metal pollution across ecosystems, specifically across multiple environmental sources and animal taxa. This study was designed to assess the environmental health impacts of trace metal pollution by assessing its extent and possible transfer into wildlife in the areas surrounding two abandoned metalliferous mine complexes in Wales in the UK. Water, sediment, and soil at the mine sites and in areas downstream had notably elevated concentrations of Pb, Zn, and, to a lesser extent, Cd and Cu, when compared to nearby control sites. These high trace metal concentrations were mirrored in the body burdens of aquatic invertebrates collected in the contaminated streams both at, and downstream of, the mines. Wood mice collected in contaminated areas appeared to be able to regulate their Zn and Cu tissue concentrations, but, when compared to wood mice from a nearby control site, they had significantly elevated concentrations of Cd and, particularly, Pb, detected in their kidney, liver, and bone samples. The Pb concentrations found in these tissues correlated strongly with local soil concentrations (kidney: ρ = 0.690; liver: ρ = 0.668, bone: ρ = 0.649), and were potentially indicative of Pb toxicity in between 10 % and 82 % of the rodents sampled at the mine sites and in areas downstream. The high trace metal concentrations found in the environment and in common prey species (invertebrates and rodents) indicates that trace metal pollution can have far-reaching, ecosystem-wide health impacts long after the polluting activity has ceased, and far beyond the originating site of the pollution.

Cannabielsoin (CBE), a CBD Oxidation Product, Is a Biased CB1 Agonist.

Cannabielsoin (CBE) is primarily recognized as an oxidation byproduct of cannabidiol (CBD) and a minor mammalian metabolite of CBD. The pharmacological interactions between CBE and cannabinoid receptors remain largely unexplored, particularly with respect to cannabinoid receptor type 1 (CB1). The present study aimed to elucidate the interaction dynamics of CBE in relation to CB1 by employing cyclic adenosine monophosphate (cAMP) and ß-arrestin assays to assess its role as an agonist, antagonist, and positive allosteric modulator (PAM). To our knowledge, this is the first publication to investigate CBE's receptor activity in vitro. Our findings reveal that S-CBE acts as an agonist to CB1 with EC50 = 1.23 µg/mL (3.7 µM) in the cAMP assay. No agonist activity was observed in the ß-arrestin assay in concentrations up to 12 µM, suggesting a noteworthy affinity towards G-protein activation and the cAMP signaling pathway. Furthermore, in silico molecular docking simulations were conducted to provide a structural basis for the interaction between CBE and CB1, offering insights into the molecular determinants of its receptor affinity and functional selectivity.

CBD Versus CBDP: Comparing In Vitro Receptor-Binding Activities.

Phytocannabinoids with seven-carbon alkyl chains (phorols) have gained a lot of attention, as they are commonly believed to be more potent versions of typical cannabinoids with shorter alkyl chains. At the time of this article, cannabidiphorol (CBDP) and tetrahydrocannabiphorol (THCP) can both be purchased in the North American market, even though their biological activities are nearly unknown. To investigate their relative potency, we conducted in vitro receptor-binding experiments with CBDP (cannabinoid CB1/CB2 receptor antagonism, serotonin 5HT-1A agonism, dopamine D2S (short form) agonism, and mu-opioid negative allosteric modulation) and compared the observed activity with that of CBD. To our knowledge, this is the first publication to investigate CBDP's receptor activity in vitro. A similar activity profile was observed for both CBD and CBDP, with the only notable difference at the CB2 receptor. Contrary to common expectations, CBD was found to be a slightly more potent CB2 antagonist than CBDP (p < 0.05). At the highest tested concentration, CBD demonstrated antagonist activity with a 33% maximum response of SR144528 (selective CB2 antagonist/inverse agonist). CBDP at the same concentration produced a weaker antagonist activity. A radioligand binding assay revealed that among cannabinoid and serotonin receptors, CB2 is likely the main biological target of CBDP. However, both CBD and CBDP were found to be significantly less potent than SR144528. The interaction of CBDP with the mu-opioid receptor (MOR) produced unexpected results. Although the cannabidiol family is considered to be a set of negative allosteric modulators (NAMs) of opioid receptors, we observed a significant increase in met-enkephalin-induced mu-opioid internalization when cells were incubated with 3 µM of CBDP and 1 µM met-enkephalin, a type of activity expected from positive allosteric modulators (PAMs). To provide a structural explanation for the observed PAM effect, we conducted molecular docking simulations. These simulations revealed the co-binding potential of CBDP (or CBD) and met-enkephalin to the MOR.

Society of Radiologists in Ultrasound Consensus on Routine Pelvic US for Endometriosis.

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images. Given a substantial body of literature describing techniques to depict endometriosis at US, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to make recommendations aimed at improving the screening process for endometriosis. The panel was composed of experts in the imaging and management of endometriosis, including radiologists, sonographers, gynecologists, reproductive endocrinologists, and minimally invasive gynecologic surgeons. A comprehensive literature review combined with a modified Delphi technique achieved a consensus. This statement defines the targeted screening population, describes techniques for augmenting pelvic US, establishes direct and indirect observations for endometriosis at US, creates an observational grading and reporting system, and makes recommendations for additional imaging and patient management. The panel recommends transvaginal US of the posterior compartment, observation of the relative positioning of the uterus and ovaries, and the uterine sliding sign maneuver to improve the detection of endometriosis. These additional techniques can be performed in 5 minutes or less and could ultimately decrease the delay of an endometriosis diagnosis in at-risk patients.

Robot-assisted Laparoscopic Excision of Abdominal Wall Endometrioma Utilizing Intraoperative Ultrasound and Transabdominal Needle Placement.

OBJECTIVE: In patients with endometriosis, extra pelvic endometriosis is estimated to have an incidence of 11% and a rare subset of extra pelvic lesions include abdominal wall endometriosis with an incidence of 0.03% to 3.5% [1,2]. Evaluation for and surgical management of abdominal wall endometriosis are an essential skill set for the advanced gynecologic surgeon. In this video, we demonstrate a surgical technique for robot-assisted laparoscopic excision of abdominal wall endometriosis with intraoperative ultrasound-guided needle placement. DESIGN: Description and demonstration of surgical technique. SETTING: A patient with previous history of 2 cesarean sections and right lower quadrant cyclic abdominal wall pain; a tertiary care, academic center. INTERVENTIONS: Intraoperative ultrasound-guided needle placement to map location and boundaries of the lesion followed by minimally invasive resection of the lesion with the intermittent advancement and withdrawal of needles to confirm clear margins. CONCLUSION: Minimally invasive resection of abdominal wall endometriosis using intraoperative ultrasound-guided needle placement is an effective technique to guide surgical dissection and allow for clear surgical margins and successful treatment of this rare condition.

Micronutrients and socio-demographic factors were major predictors of anaemia among the Ethiopian population.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel-Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

Relationships between soil and badger elemental concentrations across a heterogeneously contaminated landscape.

Understanding the links between environmental and wildlife elemental concentrations is key to help assess ecosystem functions and the potential effects of legacy pollutants. In this study, livers from 448 European badgers (Meles meles) collected across the English Midlands were used to investigate the relationship between elemental concentrations in topsoils and wildlife. Mean soil sample concentrations within 2 km of each badger, determined using data from the British Geological Survey's 'Geochemical Baseline Survey of the Environment', were compared to badger liver elemental concentrations, focusing primarily on Ag, As, Cd, Cr, Cu, K, Mn, Pb, Se, Zn. Generally, the badgers appeared to have elemental concentrations comparable with those published for other related animals, though Cu concentrations tended to be lower than expected. While there was no relationship between soil and badger liver concentrations for most biologically essential elements, biologically non-essential elements, specifically Pb, Cd, As, and Ag, were positively correlated between soil and badger livers. Lead and Cd, the elements with the strongest relationships between soils and badger livers, were primarily elevated in badgers collected in Derbyshire, a county with a millennia-long history of Pb mining and significant Pb and Cd soil pollution. Cadmium concentrations in badgers were also, on average, almost nine times higher than the local soil concentrations, likely due to Cd biomagnification in earthworms, a dietary staple of badgers. While badgers are good models for studying associations between soil and wildlife elemental concentrations, due to their diet, burrowing behaviours, and site fidelity, all flora and fauna local to human-modified environments could be exposed to and impacted by legacy pollutants.

Soil and plant contamination by potentially toxic and emerging elements and the associated human health risk in some Egyptian environments.

The aim of this work was to assess the origins, mobility, bioavailability and potential health risks of V, Cr, Co, As, Se, Mo, Cd, Sn and Sb, which are not sufficiently studied in the terrestrial environment of Egypt. This has been carried out by employing a combination of chemical fractionation, plants uptake, mathematical modeling and risk assessment approaches on a wide range of soils and plants sampled from industrial, urban and agricultural locations across Egypt. The contents of As, Cd, Sn and Sb were elevated in the soils of some urban and industrial locations within Cairo, although their soil geo-accumulation (Igeo) indices remained ≤ 2, indicating only moderate contamination. Selenium showed moderate to heavy contamination levels (Igeo up to 4.7) in all sampling locations, and Sb was highly elevated (Igeo = 7.1; extreme contamination) in one industrial location. Therefore, Se was the most important contributor to the pollution load followed by Sb and Cd. Both principle component analysis (of total content) and geochemical fractionation (by sequential extraction) suggested that V, Cr and Co are mostly of geogenic origin, while Se and Sb contents appear to be highly influenced by anthropogenic inputs. The most mobile and bioavailable element was Cd with a large non-residual fraction in all soils (76% of total Cd). The bio-concentration factors of Cd in leafy and fruiting plants were 50 times larger than other elements (except Mo) indicating preferential systematic plant uptake of Cd. Risk assessment models showed an overall low noncarcinogenic and carcinogenic risks to the population of Egypt due to the studied elements with only a few anomalies.

Thyroid Nodule Margin Assessment Using ACR TI-RADS: Adding Points for Macrolobulation Impairs Performance.

OBJECTIVE: We evaluated the performance of ACR TI-RADS when points for lobulated margins are applied only when the margins meet a quantified measure of margin microlobulation and not applied when nodules only demonstrate macrolobulation. METHODS: We retrospectively reviewed ultrasound and pathology records (May 01, 2018 to July 31, 2020) to find all thyroid nodules at one institution characterized as having lobulated margins using the ACR TI-RADS lexicon and subsequently undergoing fine needle aspiration (FNA). Nodule margins were evaluated to note the presence or absence of microlobulation, quantitatively defined as a protrusion with a base <2.5 mm in length. The impact to detection of malignant nodules and avoidance of benign FNA when margin points for lobulation were added only when microlobulated was analyzed. RESULTS: 58 of 516 thyroid nodules undergoing US-guided FNA were classified as lobulated, comprising the study population. 21 (36.2%) had microlobulated margins, with 12 of the 21 (57.1%) being malignant. Comparatively, of the 37 nodules showing only macrolobulated margins without microlobulation, only 2 (5.4%) were malignant (P < .0001). For 53 nodules ≥10 mm, 15 (28.3%) benign nodules would not have met size criteria for FNA had points for margins not been applied when only showing macrolobulation, whereas all 10 malignant nodules would still have been sampled. CONCLUSION: Adding two points to the ACR TI-RADS score for lobulated thyroid nodules should only apply when microlobulations are present.

Bioaccessibility of iron in pearl millet flour contaminated with different soil types.

A controlled in-vitro experiment was conducted to determine the bioaccessibility of extrinsic soil iron in pearl millet contaminated with typical Malawian soils. Pearl millet was contaminated with soils at ratios typically encountered in real life. Iron concentrations of soil-contaminated flour increased such that soil-derived iron contributed 56, 83 and 91% of the total iron when the proportions of soil were 0.1, 0.5 and 1% (soil: grain w/w), respectively. When soils were digested alone, the concentration of bioaccessible iron differed depending on the type of soil. However, the concentration of bioaccessible iron in soil-contaminated flours did not exceed that of uncontaminated flour and there was no effect of soil type. This suggests that knowledge of the proportion of extrinsic soil iron in soil-contaminated grains would be useful for iron bioavailability estimations. Vanadium is a reliable indicator of the presence of extrinsic soil iron in grains and has potential applications in this regard.

Agronomic biofortification increases grain zinc concentration of maize grown under contrasting soil types in Malawi.

Zinc (Zn) deficiency remains a public health problem in Malawi, especially among poor and marginalized rural populations, linked with low dietary intake of Zn due to consumption of staple foods that are low in Zn content. The concentration of Zn in staple cereal grain can be increased through application of Zn-enriched fertilizers, a process called agronomic biofortification or agro-fortification. Field experiments were conducted at three Agricultural Research Station sites to assess the potential of agronomic biofortification to improve Zn concentration in maize grain in Malawi as described in registered report published previously. The hypotheses of the study were (i) that application of Zn-enriched fertilizers would increase in the concentration of Zn in maize grain to benefit dietary requirements of Zn and (ii) that Zn concentration in maize grain and the effectiveness of agronomic biofortification would be different between soil types. At each site two different subsites were used, each corresponding to one of two agriculturally important soil types of Malawi, Lixisols and Vertisols. Within each subsite, three Zn fertilizer rates (1, 30, and 90 kg ha-1) were applied to experimental plots, using standard soil application methods, in a randomized complete block design. The experiment had 10 replicates at each of the three sites as informed by a power analysis from a pilot study, published in the registered report for this experiment, designed to detect a 10% increase in grain Zn concentration at 90 kg ha-1, relative to the concentration at 1 kg ha-1. At harvest, maize grain yield and Zn concentration in grain were measured, and Zn uptake by maize grain and Zn harvest index were calculated. At 30 kg ha-1, Zn fertilizer increased maize grain yields by 11% compared with nationally recommended application rate of 1 kg ha-1. Grain Zn concentration increased by 15% and uptake by 23% at the application rate of 30 kg ha-1 relative to the national recommendation rate. The effects of Zn fertilizer application rate on the response variables were not dependent on soil type. The current study demonstrates the importance of increasing the national recommendation rate of Zn fertilizer to improve maize yield and increase the Zn nutritional value of the staple crop.

Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs.

Cannabidiol (CBD) containing dog food and treats are widely commercially available, mirroring the growing popularity of CBD as a supplement for humans. Despite this, experimental evidence of the safety and efficacy of long-term oral exposure in dogs is lacking. The purpose of this study was to address the gap in knowledge around the longer-term suitability and tolerance of a broad-spectrum CBD (THC-free) distillate in clinically healthy dogs. The study was a randomized, placebo-controlled, and blinded study where one group of twenty dogs received daily CBD capsules at a dose of 4 mg/kg of body weight (BW) for a period of 6 months. The control group of twenty dogs received placebo capsules. A comprehensive suite of physiological health measures was performed throughout the study at baseline, and after 2, 4, 10, 18, and 26 weeks of exposure, followed by 4 weeks of washout. CBD concentrations were measured at the same cadence in plasma, feces and urine. Health measures included biochemistry, hematology, urinalysis, in addition to fortnightly veterinary examinations, twice daily well-being observations, and a daily quality-of-life survey. Biochemistry and hematology showed no clinically significant alterations apart from a transient elevation in alkaline phosphatase (ALP) in just over half of the dogs receiving CBD. This elevation was observed in the absence of concurrent elevations of other liver parameters, and without any adverse effects on health and wellbeing. Furthermore, bone alkaline phosphatase (BALP) was simultaneously elevated with a significant, strong (r > 0.9) positive correlation between the two measures, suggesting that the elevation of total ALP was at least partly due to the bone-derived isoform. This study provides evidence that a once-daily oral dose of 4 mg CBD/kg BW is well tolerated in clinically healthy dogs for a duration of 6-months.

Non-Vascular Considerations When Interpreting Extremity Arterial and Venous Examinations.

Peripheral arterial and venous examinations are performed regularly in vascular labs and interpreted by physicians of different specialities. Many vascular examinations have nonvascular pathology that is either inadvertently imaged by the sonographer or imaged with intent as it relates to patient's symptoms. It is prudent for every reader of vascular studies to be acquainted with the sonographic appearance of these non-vascular lesions to enable appropriate and optimal interpretation that has a direct bearing on patient's clinical care. Our review includes a discussion of the nonvascular pathologies like lymph nodes, soft tissue edema, soft tissue fluid collections, musculotendinous injuries, soft tissue masses, and joint and bursal pathologies that may be encountered during interpretation of vascular exams. The pictorial essay includes a discussion of their sonographic appearances and pitfalls in interpretation. Multiple illustrative examples and sonographic images of the non-vascular pathologies found during interpretation of vascular studies have been utilized to highlight their appearances.

Human health implications from consuming eggs produced near a derelict metalliferous mine: a case study.

Lead pollution from metalliferous mines can have major environmental and health effects long after the mines have closed. Animals living near derelict mine sites can inadvertently ingest lead-contaminated soils, causing them to accumulate lead and potentially experience significant adverse health effects. Human food products, such as eggs, produced near metalliferous mines may also be contaminated with lead. The focus of this case study was to determine whether free-range chickens living near a derelict lead mine had high lead body burdens, whether they were producing eggs with elevated lead concentrations, and whether these eggs could be hazardous to human health. Soil samples and chicken egg, feather, blood, and bone samples were collected from a small farm near an abandoned metalliferous mine. The soil in and around the chicken pens contained lead concentrations that were elevated above established soil lead baseline concentrations. The lead concentrations in the chicken feather, blood, and bone samples were consistent with lead toxicity and indicated long-term, continuous exposure. Finally, the lead concentrations in the eggs were significantly greater than those found in commercial eggs. Based on previously established lead benchmark dose levels, humans, and in particular, children, could experience adverse health impacts if they routinely consumed these eggs. Environmental lead contamination continues to pose a major health risk for humans, and further research, understanding, and awareness are required to safeguard the public from the risks of consuming food produced near derelict mines.

Assessing the Lability and Environmental Mobility of Organically Bound Copper by Stable Isotope Dilution.

The environmental mobility of Cu and therefore its potential toxicity are closely linked to its attachment to natural organic matter (NOM). Geochemical models assume full lability of metals bound to NOM, especially under strong oxidizing conditions, which often leads to an overestimation of the lability of soil metals. Stable isotope dilution (SID) has been successfully applied to estimate the labile (isotopically exchangeable) pool of soil metals. However, its application to study the lability of NOM-Cu required development of a robust separation and detection approach so that free Cu ions can be discriminated from (the also soluble) NOM-Cu. We developed a SID protocol (with enriched 65Cu) to quantify the labile pool of NOM-Cu using size exclusion chromatography coupled to a UV detector (for the identification of different NOM molecular weights) and ICP-MS (for 65Cu/63Cu ratio measurement). The Cu isotopic-exchange technique was first characterized and verified using standard NOM (SR-NOM) before applying the developed technique to an "organic-rich" podzol soil extract. The developed protocol indicated that, in contrast to the common knowledge, significant proportions of SR-NOM-Cu (25%) and soil organic-Cu (55%) were not labile, i.e., permanently locked into inaccessible organic structures. These findings need to be considered in defining Cu interactions with the reactive pool of NOM using geochemical models and risk evaluation protocols in which complexed Cu has always been implicitly assumed to be fully labile and exchangeable with free Cu ions.

Geochemistry of selenium, barium, and iodine in representative soils of the Brazilian Amazon rainforest.

The Amazon rainforest is a heterogeneous ecosystem and its soils exhibit geographically variable concentrations of trace elements. In this region, anthropic activities - e.g., agriculture and mining - are numerous and varied, and even natural areas are at risk of contamination by trace elements, either of geogenic or anthropogenic origin. A reliable dataset of benchmark values for selenium (Se), barium (Ba), and iodine (I) concentrations in soils is needed for use as a reference in research and public policies in the region. In this study, 9 selected sites in the Brazilian Amazon rainforest within areas represented by Oxisols and Ultisols were assessed for relevant soil physicochemical characteristics, along with the concentrations of total Se (SeTot), total Ba (BaTot), and sequentially-extracted soluble Se (SeSol) and adsorbed Se (SeAd) in 3 different soil layers (0-20, 20-40, and 40-60 cm). In addition, organically bound-Se (SeOrg) and total I (ITot) concentrations in the surface layer (0-20 cm) were measured. Soil Se concentrations (SeTot) were considered safe and are likely a result of contributions of sedimentary deposits from the Andes. Available Se (SeSol + SeAd) accounted for 4.5% of SeTot, on average, while SeOrg in the topsoil accounted for more than 50% of SeTot. Barium in the western Amazon (state of Acre) and central Amazon (Anori, state of Amazonas) exceeded national prevention levels (PVs). Furthermore, the average ITot in the studied topsoils (5.4 mg kg-1) surpassed the worldwide mean. Notwithstanding, the close relationship found between the total content of the elements (Se, Ba, and I) and soil texture (clay, silt, and sand) suggests their geogenic source. Finally, our data regarding SeTot, BaTot, and ITot can be used to derive regional quality reference values for Amazon soils and also for updating prevention (PV) and investigation (IV) values established for selected elements by the Brazilian legislation.