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We challenge all eye health stakeholders to use this definition to help achieve eye health for everyone, everywhere. As we prepared the recent I Lancet Global Health i Commission on Global Eye Health,1 we recognised that establishing a clear definition of eye health could help galvanise the eye health community towards its ambitious aims in the coming decade. Current definitions fall short of describing all the aspects of eye health that are needed to achieve good quality, people-centred eye care that enables everyone to achieve their full potential. [Extracted from the article]

The emergence of new synthetic cannabinoid receptor agonists (SCRAs) onto the illicit drugs market continues to cause harm, and the overall availability of physicochemical and pharmacokinetic data for new psychoactive substances is lacking. The lipophilicity of 23 SCRAs and the plasma protein binding (PPB) of 11 SCRAs was determined. Lipophilicity was determined using a validated chromatographic hydrophobicity index (CHI) log D method; tested SCRAs showed moderate to high lipophilicity, with experimental log D 7.4 ranging from 2.48 (AB-FUBINACA) to 4.95 (4F-ABUTINACA). These results were also compared to in silico predictions generated using seven commercially available software packages and online tools (Canvas; ChemDraw; Gastroplus; MoKa; PreADMET; SwissADME; and XlogP). Licenced, dedicated software packages provided more accurate lipophilicity predictions than those which were free or had prediction as a secondary function; however, the latter still provided competitive estimates in most cases. PPB of tested SCRAs, as determined by equilibrium dialysis, was in the upper range of the lipophilicity scale, ranging from 90.8% (ADB-BUTINACA) to 99.9% (BZO-HEXOXIZID). The high PPB of these drugs may contribute to reduced rate of clearance and extended durations of pharmacological effects compared to lesser-bound SCRAs. The presented data improve understanding of the behaviour of these drugs in the body. Ultimately, similar data and predictions may be used in the prediction of the structure and properties of drugs yet to emerge on the illicit market., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Objective: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects., Study Design: Experimental study; randomized, crossover design., Animals: Six healthy adult horses., Methods: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored., Results: T max (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while C max (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted., Conclusion: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and T max than IV CRI administration but would be highly bioavailable., Clinical Significance: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted., (© 2024 The Author(s). Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Drug use within prisons is increasingly complex and unpredictable. Benzodiazepines are currently one of the most common drugs detected in individuals leaving Scottish prisons; however, understanding illicit benzodiazepine use within prisons and assessing the potential harm to individuals is challenging due to the lack of available analytical data on the substances circulating. Increasingly, materials, such as paper and clothing, infused with novel benzodiazepines have been identified as a smuggling route into Scottish prisons. Methods were developed for the qualitative and quantitative analysis of benzodiazepines using gas chromatography-mass spectrometry (GC-MS) and applied to 495 seized samples from 11 Scottish prisons, including papers, cards, blotters, powders, tablets, and clothing. Evolution in the benzodiazepines being detected was demonstrated, with etizolam being the most prevalent throughout 2020/2021 following which flubromazepam and bromazolam detections increased. Additionally, significant changes in the smuggling methods and drug formats detected occurred over time following policy changes within prisons. These data represent the first reported widescale etizolam quantitation data and demonstrate high levels of variability across all sample types, most notably within tablets (0.34-2.33 mg per tablet). Additionally, concentration mapping of a whole seized card sample revealed the total concentration of drug present (312.5 mg) and demonstrated variability across the surface of the card (1.16-1.87 mg/cm 2 ). These data highlight the challenges of consistent dosing for individuals and the high risks of unintentional overdose. Increased understanding of the challenge of such drug smuggling and benzodiazepine use will aid in the development of strategies to reduce supply and mitigate harm., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or tert -leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D 7.4 ranged from 2.81 (AB-FUBINACA) to 4.95 (MDMB-4en-PINACA) and all SCRAs tested were highly protein bound, ranging from 88.9 ± 0.49% (( R )-4F-MDMB-BINACA) to 99.5 ± 0.08% (( S )-MDMB-FUBINACA). Most tested SCRAs were cleared rapidly in vitro in pooled human liver microsomes (pHLM) and pooled cryopreserved human hepatocytes (pHHeps). Intrinsic clearance (CL int ) ranged from 13.7 ± 4.06 (( R )-AB-FUBINACA) to 2944 ± 95.9 mL min -1 kg -1 (( S )-AMB-FUBINACA) in pHLM, and from 110 ± 34.5 (( S )-AB-FUBINACA) to 3216 ± 607 mL min -1 kg -1 (( S )-AMB-FUBINACA) in pHHeps. Predicted Human in vivo hepatic clearance (CL H ) ranged from 0.34 ± 0.09 (( S )-AB-FUBINACA) to 17.79 ± 0.20 mL min -1 kg -1 (( S )-5F-AMB-PINACA) in pHLM and 1.39 ± 0.27 (( S )-MDMB-FUBINACA) to 18.25 ± 0.12 mL min -1 kg -1 (( S )-5F-AMB-PINACA) in pHHeps. Valinate and tert -leucinate indole and indazole-3-carboxamide SCRAs are often rapidly metabolised in vitro but are highly protein bound in vivo and therefore predicted in vivo CL H is much slower than CL int . This is likely to give rise to longer detection windows of these substances and their metabolites in urine, possibly as a result of accumulation of parent drug in lipid-rich tissues, with redistribution into the circulatory system and subsequent metabolism.

As the global threat of plastic pollution has grown in scale and urgency, so have efforts to find sustainable and efficient solutions. Research conducted over the past few years has identified gut environments within insect larvae, including Tenebrio molitor (yellow mealworms), as microenvironments uniquely suited to rapid plastic biodegradation. However, there is currently limited understanding of how the insect host and its gut microbiome collaborate to create an environment conducive to plastic biodegradation. In this work, we provide evidence that T. molitor secretes one or more emulsifying factor(s) (30-100 kDa) that mediate plastic bioavailability. We also demonstrate that the insect gut microbiome secretes factor(s) (<30 kDa) that enhance respiration on polystyrene (PS). We apply these insights to culture PS-fed gut microbiome enrichments, with elevated rates of respiration and degradation compared to the unenriched gut microbiome. Within the enrichment, we identified eight unique gut microorganisms associated with PS biodegradation including Citrobacter freundii , Serratia marcescens , and Klebsiella aerogenes . Our results demonstrate that both the mealworm itself and its gut microbiome contribute to accelerated plastic biodegradation. This work provides new insights into insect-mediated mechanisms of plastic degradation and potential strategies for cultivation of plastic-degrading microorganisms in future investigations and scale-up.

Larvae of Zophobas atratus (synonym as Z. morio, or Z. rugipes Kirsch, Coleoptera: Tenebrionidae) are capable of eating foams of expanded polystyrene (EPS) and low-density polyethylene (LDPE), similar to larvae of Tenebrio molitor. We evaluated biodegradation of EPS and LDPE in the larvae from Guangzhou, China (strain G) and Marion, Illinois, U.S. (strain M) at 25 °C. Within 33 days, strain G larvae ingested respective LDPE and PS foams as their sole diet with respective consumption rates of 58.7 ± 1.8 mg and 61.5 ± 1.6 mg 100 larvae -1 d -1 . Meanwhile, strain M required co-diet (bran or cabbage) with respective consumption rates of 57.1 ± 2.5 mg and 30.3 ± 7.7 mg 100 larvae -1 d -1 . Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, and thermal gravimetric analyses indicated oxidation and biodegradation of LDPE and EPS in the two strains. Gel permeation chromatography analysis revealed that strain G performed broad depolymerization of EPS, i.e., both weight-average molecular weight (M w ) and number-average molecular weight (M n ) of residual polymers decreased, while strain M performed limited extent depolymerization, i.e., M w and M n increased. However, both strains performed limited extent depolymerization of LDPE. After feeding antibiotic gentamicin, gut microbes were suppressed, and M w and M n of residual LDPE and EPS in frass were basically unchanged, implying a dependence on gut microbes for depolymerization/biodegradation. Our discoveries indicate that gut microbe-dependent LDPE and EPS biodegradation is present within Z. atratus in Tenebrionidae, but that the limited extent depolymerization pattern resulted in undigested polymers with high molecular weights in egested frass., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier Ltd.)

As awareness of the ubiquity and magnitude of plastic pollution has increased, so has interest in the long term fate of plastics. To date, however, the fate of potentially toxic plastic additives has received comparatively little attention. In this study, we investigated the fate of the flame retardant hexabromocyclododecane (HBCD) in polystyrene (PS)-degrading mealworms and in mealworm-fed shrimp. Most of the commercial HBCD consumed by the mealworms was egested in frass within 24 h (1-log removal) with nearly a 3-log removal after 48 h. In mealworms fed PS containing high HBCD levels, only 0.27 ± 0.10%, of the ingested HBCD remained in the mealworm body tissue. This value did not increase over the course of the experiment, indicating little or no bioaccumulation. Additionally, no evidence of higher trophic level bioaccumulation or toxicity was observed when L. vannamei (Pacific whiteleg shrimp) were fed mealworm biomass grown with PS containing HBCD. Differences in shrimp survival were attributable to the fraction of mealworm biomass incorporated into the diet, not HBCD. We conclude that the environmental effects of PS ingestion need further evaluation as the generation of smaller, more contaminated particles is possible, and may contribute to toxicity at nanoscale.

Accumulation of plastic pollution in aquatic ecosystems is the predictable result of high demand for plastic functionalities, optimized production with economies of scale, and recalcitrance. Strategies are needed for end-of-life conversion of recalcitrant plastics into useful feedstocks and for transition to materials that are biodegradable, non-bioaccumulative, and non-toxic. Promising alternatives are the polyhydroxyalkanoates (PHAs), a vast family of polymers amenable to decentralized production from renewable feedstocks. Establishment of a global-scale PHA-based industry will require identification of PHAs with tailored properties for use as 'drop-in' replacements for existing plastics; use of low-cost renewable/waste-derived feedstocks; high productivity cultures that may be genetically modified microorganisms or non-axenic mixed cultures maintained by selection pressures that favor high PHA-producing strains; and low-cost extraction/purification schemes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Academics researchers and "citizen scientists" from 22 countries confirmed that yellow mealworms, the larvae of Tenebrio molitor Linnaeus, can survive by eating polystyrene (PS) foam. More detailed assessments of this capability for mealworms were carried out by12 sources: five from the USA, six from China, and one from Northern Ireland. All of these mealworms digested PS foam. PS mass decreased and depolymerization was observed, with appearance of lower molecular weight residuals and functional groups indicative of oxidative transformations in extracts from the frass (insect excrement). An addition of gentamycin (30 mg g -1 ), a bactericidal antibiotic, inhibited depolymerization, implicating the gut microbiome in the biodegradation process. Microbial community analyses demonstrated significant taxonomic shifts for mealworms fed diets of PS plus bran and PS alone. The results indicate that mealworms from diverse locations eat and metabolize PS and support the hypothesis that this capacity is independent of the geographic origin of the mealworms, and is likely ubiquitous to members of this species., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recent studies have demonstrated the ability for polystyrene (PS) degradation within the gut of mealworms ( Tenebrio molitor). To determine whether plastics may be broadly susceptible to biodegradation within mealworms, we evaluated the fate of polyethylene (PE) and mixtures (PE + PS). We find that PE biodegrades at comparable rates to PS. Mass balances indicate conversion of up 49.0 ± 1.4% of the ingested PE into a putative gas fraction (CO 2 ). The molecular weights ( M n ) of egested polymer residues decreased by 40.1 ± 8.5% in PE-fed mealworms and by 12.8 ± 3.1% in PS-fed mealworms. NMR and FTIR analyses revealed chemical modifications consistent with degradation and partial oxidation of the polymer. Mixtures likewise degraded. Our results are consistent with a nonspecific degradation mechanism. Analysis of the gut microbiome by next-generation sequencing revealed two OTUs ( Citrobacter sp. and Kosakonia sp.) strongly associated with both PE and PS as well as OTUs unique to each plastic. Our results suggest that adaptability of the mealworm gut microbiome enables degradation of chemically dissimilar plastics.

Commercial production of polystyrene (PS) -a persistent plastic that is not biodegradable at appreciable rates in most environments-has led to its accumulation as a major contaminant of land, rivers, lakes, and oceans. Recently, however, an environment was identified in which PS is susceptible to rapid biodegradation: the larval gut of Tenebrio molitor Linnaeus (yellow mealworms). In this study, we evaluate PS degradation capabilities of a previously untested strain of T. molitor and assess its survival and PS biodegradation rates for a range of conditions (two simulated food wastes, three temperatures, seven PS waste types). For larvae fed PS alone, the %PS removed in the short (12-15 h) residence time of the mealworm gut gradually increased for 2-3 weeks then stabilized at values up to 65%. Thirty two-day survival rates were >85% versus 54% for unfed larvae. For mealworms fed ∼10% w/w PS and ∼90% bran, an agricultural byproduct, rates of PS degradation at 25 °C nearly doubled compared to mealworms fed PS alone. Polymer residues in the frass showed evidence of partial depolymerization and oxidation. All of the tested PS wastes degraded, with the less dense foams degrading most rapidly. Mealworms fed bran and PS completed all life cycle stages (larvae, pupae, beetles, egg), and the second generation had favorable PS degradation, opening the door for selective breeding., (Copyright © 2017 Elsevier Ltd. All rights reserved.)