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The concept of the organic serves as a keyword capturing emerging practices and epistemologies through which Africans navigate increasingly toxic lifeworlds. Noting a growing preoccupation with this term, the authors unpack its meaning based on their ethnographic fieldwork concerning two East African idioms: kienyeji and kiasili. What it means to be(come) organic is tied to older notions such as life flow, tradition, and the natural. Tracing how this concept engages with central themes in Africanist debates, the authors demonstrate that an Africanist theorizing about it foregrounds critical claims about the vitality of bodies and the viability of environments.
Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability.
Methods
We evaluated spontaneous reports of terms such as “alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse” in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA.
Results
We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for “drug abuse.” In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method.
Conclusion
The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.
The sustainable management of herbicides is critical to modern agriculture and the environment. This article examines the evolution and environmental implications of herbicide use in Saskatchewan, Canada, agriculture. It quantifies changes in herbicide use and their environmental impacts by analyzing farm-level herbicide use data from 1991 to 1994 and from 2016 to 2019 through the environmental impact quotient. Results confirm significant reductions in both environmental and toxicological impacts of herbicides used, underlining the pivotal shift from tillage-based weed control to herbicide-resistant cropping systems. The environmental impact of the top five herbicides (glufosinate, glyphosate, clethodim, imazamox, and 2,4-D) used from 2016 to 2019 is 65% lower than that for those herbicides (MCPA, 2,4-D, bromoxynil, diclofop-methyl, and trifluralin) used from 1991 to 1994, with a 45% reduction in the active ingredient applied per acre. Despite increased herbicide use due to more crop acres being seeded, the findings highlight a marked improvement in the sustainability of herbicide use, affirming the importance of technological advancements in agriculture. This research contributes valuable insights into long-term trends in herbicide use, offering a practical framework for informed decisions aligning with sustainable agricultural practices as well as reduced biodiversity impacts.
Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.
Over the past several decades, clay minerals have been applied in various bio-fields such as drug and drug additives, animal medicine and feed additives, cosmetics, biosensors, etc. Among various research areas, however, the medical application of clay minerals is an emerging field not only in academia but also in industry. In particular, cationic and anionic clays have long been considered as drug delivery vehicles for developing advanced drug delivery systems (DDSs), which is the most important of the various research fields including new drugs and medicines, in vitro and in vivo diagnostics, implants, biocompatible materials, etc., in nanomedicine. These applications are obviously related to global issues such as improvements in welfare and quality of life with life expectancy increasing. Many scientists, therefore, in various disciplines, such as clay mineralogy, material chemistry, molecular biology, pharmacology, and medical science, have been endeavoring to find solutions to such global issues. One of the strategic approaches is probably to explore new drugs possessing intrinsic therapeutic effects or to develop advanced materials with theranostic functions. With this is mind, discussions of examples of cationic and anionic clays with bio- and medical applications based on nanomedicine are relevant. In this tutorial review, nanomedicine based on clay minerals are described in terms of synthetic strategies of clay nanohybrids, in vitro and in vivo toxicity, biocompatibility, oral and injectable medications, diagnostics, theranosis, etc.
Mexican devil [Ageratina adenophora (Spreng.) R.M. King & H. Rob.], a globally invasive weed with destructive effects on forests, has spread to numerous countries. To elucidate the inhibition of tree growth by A. adenophora, a study was conducted using the fungi (Lactarius deliciosus, Ceriporia lacerata, and Fomitopsis palustris) involved in the recycling of carbon and nutrients in forests. The focus was on investigating soil nitrogen and phosphorus availability in response to aqueous extracts from uncomposted and aerobically composted A. adenophora (EUA and ECA, respectively). The samples of composted A. adenophora from different sites exhibited a significant reduction in the concentration of allelochemicals 4,7-dimethyl-1-(propan-2-ylidene)-1,4,4a,8a-tetrahydronaphthalene-2,6(1H, 7H)-dione and 6-hydroxy-5-isopropyl-3,8-dimethyl-4a,5,6,7,8,8a-hexahydronaphthalen-2(1H)-one. This reduction more than 94% when compared with the concentration of these allelochemicals in CA. The EUA solutions at 5 and 10 mg L−1 (oven-dried plant biomass base) minimized L. deliciosus and C. lacerata growth, and significantly decreased F. palustris growth on the soil surface and within the soil. However, soil with ECA had no effect or promoting effect on the fungal growth. Compared with CK (only fungal inoculation in tested soil), the EUA solution reduced soil nitrogen and phosphorus, while ECA had the opposite effect; soil pH was increased by 0.01 to 0.08 under EUA treatment, while it decreased by 0.5 to 0.41under ECA treatment. Nitrogen and phosphorus availability were positively correlated with protease and phosphatase activity (r = 0.723 to 0.944), while available phosphorus was inversely correlated with pH in tested soils (r = -(0.809 to 0.978)). As such, the EUA solution decreased soil nitrogen and phosphorus supplies by inhibiting the liberation of proteases, phosphatases, and protons, which may lead to poor growth or even mortality of three fungal species. The in situ aerobically composted A. adenophora residues left behind may directly supply fungal species with nutrients and indirectly increase soil nutrient availability via the promotion of nitrogen and phosphorus mobilization.
The purpose of the human sperm survival assay (HSSA) is to test disposables, media and reagents for potential sources of cytotoxicity in a human assisted reproductive technology (ART) laboratories before their use in in vitro fertilization (IVF)/andrology procedures. The contact bioassay is a cornerstone of a successful and safe ART laboratory, and in many countries, the use of a contact bioassay is required by law. When using a bioassay in the laboratory, it must be useful rather than just fulfilling a legal requirement. This means that the assay should be able to detect very subtle levels of toxicity consistently without any false-negative or false-positive results. Several alternative contact bioassays have been described that may fulfil these requirements, but they are not all equally affordable, accessible and practical to execute. The use of human sperm in a contact bioassay is inexpensive and convenient, as well as invaluable for consistent quality assurance in ART laboratories. If used appropriately, the HSSA is sensitive, repeatable, readily available and each sample acts as its own control.
Ensuring proper quality control (QC) in the laboratory is critical to the success of any in vitro fertilization (IVF) programme, as the environment of the laboratory can alter the quality of the embryos produced. The ultimate role of the embryology laboratory is to maintain the inherent viability of the gametes and embryos in an environment outside the female reproductive tract. There is a need for objective, sensitive and reproducible methods and assays for testing materials for embryo toxicity as well as growth promoting and inhibiting factors. The manufacturers test commercially available IVF media and plastic ware and provide the results of their testing with the shipment of supplies. It may be advisable to test media and supplies upon arrival to confirm that nothing occurred during shipping. The suitability of various reagents and materials for use in human IVF can be tested using a range of bioassays. While the most used bioassays for QC in IVF laboratories are the human sperm survival assay and the mouse embryo bioassay (MEA), the one-cell MEA has been consistently shown to be the most sensitive.
Edited by
Dennis S. Chi, Memorial Sloan-Kettering Cancer Center, New York,Nisha Lakhi, Richmond University Medical Center, Staten Island,Nicoletta Colombo, University of Milan-Bicocca
Intraperitoneal (IP) chemotherapy, the delivery of unheated chemotherapy into the peritoneal cavity through a catheter connected to an implanted port, was once a strongly recommended, though controversial, treatment for women with advanced ovarian cancer after optimal cytoreductive surgery. Historically, direct drug delivery to the IP cavity and improved pharmacokinetics yielded improved progression-free and overall survival outcomes. However, the improved disease control and survival came at the cost of significantly increased toxicity, worse quality of life, and added expense. The most recent randomized clinical trial of IP therapy identified a less toxic regimen but failed to demonstrate any survival benefit. The negative results of this study, taken in the setting of more recent advances in biologic therapies, illustrate that in the modern therapeutic landscape for ovarian cancer there is no role for IP chemotherapy. IP therapy is too toxic, too expensive, and historical IP therapy survival outcomes are no longer relevant.
Edited by
Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine,David Castle, University of Tasmania, Australia,Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
New synthetic cannabinoid agonists have been synthesized during the last decades and promoted for their psychoactive effects, mimicking those of delta-9-tetrahydrocannabinol. These newest cannabimimetic drugs show binding affinities for the cannabinoid CB1 and/or the CB2 receptors. They are manufactured by spraying the synthetic cannabinoid onto relatively inert vegetable material or by solubilizing them in ’e-liquids’ for electronic cigarettes. They are lipid soluble and non-polar and volatilize easily when smoked. However, these drugs have been associated with psychiatric and medical complications. The most typical adverse effects of synthetic cannabinoid agonists included agitation, confusion, anxiety, psychosis, nausea, and vomiting, but drowsiness, tachycardia, and hypertension are also reported frequently. Atypical effects can also manifest, including shock, seizures, fever, rhabdomyolysis, myocardial infarction, stroke, acute kidney injury, and multiple organ failure. The cardiovascular and neuropsychiatric effects, which in some cases can be severe and long-lasting, are among the most common reasons for emergency medical treatment. Due to limited knowledge about their pharmacology and toxicity, managing acute intoxications is challenging and treatment strategies are mostly limited to symptomatic and supportive care.
New product development processes need to be compliant to regulatory requirements, and this chapter highlights the salient processes and quality systems to put into place to achieve success. Project management is made simple with specific tools provided here. Customer feedback is channeled into specific product characteristics, and the right tools are shown in this chapter. The biopharma industry has statistics showing less than 10% of starting compounds succeed in reaching market approval, and this chapter explains what causes these failures. The key issues that have repeatedly caused failure during device and diagnostic product development are also pointed out. Ethical decisions have to be made during product development as shown in this chapter. Outsourcing is a real option due to the availability of many contract research and manufacturing organizations, and judicious use of this option is discussed in this chapter. Key milestones that reduce risk and show transition from early stage to preclinical prototype stages are reviewed here. Does the popular concept of minimum viable product in software development apply in biomedicine prototyping? Other similar questions that help the reader understand pitfalls and best practices are answered here.
Lithium has a narrow therapeutic window. Frequent monitoring of both serum levels and clinical signs of toxicity is warranted because toxicity may be present even when concentrations are within the therapeutic range. Persistent neurological signs and symptoms of lithium intoxication gained clinical attention in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT).
Objectives
To review the long-term neurological sequelae of lithium intoxication (SILENT) to highlight their clinical presentation, assessment, management and preventive measures.
Methods
Non-systematic review of literature through search on PubMed/MEDLINE for publications up to 2021, following the terms syndrome of irreversible lithium-effectuated neurotoxicity.
Results
Neurological manifestations of lithium poisoning may persist, even after effective removal of the drug – SILENT. The most frequent sequelae are cerebellum and brain stem dysfunction, extrapyramidal symptoms and dementia. They may last for weeks, months or years. Infection, dehydration, deteriorating renal function or the addition of other drugs may precipitate acute toxicity. Irreversible damage is difficult to treat. Some cases show spontaneous recovery that may be total, but in others, sequelae persist. Helpful measures include the avoidance of acute intoxications with lithium, long-term and continuous dose adjustment and serum level monitoring, stricter exclusion criteria for starting lithium, and aggressive treatment of acute neurotoxicity. Once the long-term neurologic sequelae have set in, the patient should be managed according to the impediment (physical rehabilitation, speech, cognitive training).
Conclusions
It is important to raise the awareness of SILENT so that clinicians are able to avoid it. There should be a low threshold for suspecting the existence of toxicity.
Five compounds 2-(2-hydroxybenzylidene)-N-(prop-2-en-1-yl)hydrazinecarbothioamide (H2L), bis[μ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]hydrazinylidene}methyl)phenolato-S,N,O:O]diaquadicopper(II) nitrate (1), bis[μ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]hydrazinylidene}methyl)phenolato-S,N,O:O]diimidazoldicopper(II) nitrate (2), bis[μ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]-hydrazinylidene}methyl)phenolato-S,N,O:O]bis-(3,5-dibromopyridine)dicopper(II) nitrate (3), bis[μ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]-hydrazinylidene}methyl)phenolato-S,N,O:O]bis(4-methylpyridine)dicopper(II) nitrate hexahydrate (4) were synthesized. The antiproliferative properties of these compounds toward cancer cell lines RD, HeLa, and normal cell line MDCK have been investigated. The tested complexes surpass Doxorubicin (DOXO) in the efficiency of anticancer activity as their IC50 values toward cancer cells are lower than the corresponding values of DOXO and the selectivity indexes exceed the corresponding SI value of DOXO. The tested compounds demonstrated a high antioxidant effect against ABTS•+ radical cations as well as low toxicity on Daphnia magna.
The optimal treatment of adult craniopharyngioma (CP) remains controversial. Although benign, these tumors tend to recur locally. The choice between gross total resection (GTR) versus subtotal resection (STR) with adjuvant or delayed radiotherapy (RT) is debated. The objective of this study is to review our experience with adult CPs over a 20-year period and identify an optimal management strategy.
Methods:
From 1999 to 2020, we reviewed all patients diagnosed with CP at our institution. We collected data regarding tumor characteristics, treatments, and toxicity. Disease progression was defined as growth on imaging. Descriptive statistics were used to assess patient characteristics. The Kaplan Meier method was used to assess progression-free survival (PFS) and corresponding 95% confidence intervals (CI) from the time since treatment initiation.
Results:
Twenty-four patients with a median age of 50 were included in this study. The median follow-up was 85 months. Seven patients had initial GTR, 10 STR, and 7 STR + RT. The overall 5-year PFS was 56% (95% CI: 38–83%): 100% in the STR + RT group, 69% in the GTR group, and 18% in the STR group (p = 0.01). Of the 17 patients initially treated with surgery alone, 3 with GTR and 6 with STR required salvage RT at a median of 46 months, with no further progression after salvage RT.
Conclusions:
Our study underscores the importance of RT for local control and suggests that STR + RT should be considered a viable option in the management of these tumors as it may be associated with improved PFS compared to surgery alone.
Lithium is a gold standard maintenance treatment in bipolar affective disorder. It has a narrow therapeutic range, and at higher serum lithium levels there is a risk of adverse effects and toxicity. There are three patterns of lithium intoxication: acute, acute-on-chronic and chronic. We describe risk factors for lithium intoxication, mechanisms of toxicity and clinical symptoms seen in lithium intoxication. We describe both the acute and chronic effects of lithium toxicity. Lithium intoxication may be life-threatening and associated with longer-term sequelae. The management of lithium intoxication involves determining the type of intoxication. We discuss treatment strategies aimed at reducing absorption and increasing elimination of lithium. We discuss clinical indications for extracorporeal methods such as dialysis, which are used to limit the time and degree of exposure of the central nervous system to toxic lithium concentrations. Haemodialysis is the most rapid method of eliminating lithium from the body, but careful monitoring is required. Preventive strategies to mitigate the risk for lithium intoxication are discussed.
Primary non-Hodgkin’s lymphoma (NHL) of the orbit is rare. Orbital NHLs show good response to both radiotherapy (RT) and chemotherapy, and hence, the emphasis should be to ensure maximum cure rate with minimum morbidity. In this study, we present the clinical profile and treatment outcomes of patients with NHL who had initial presentation in the orbit.
Materials and methods:
In this retrospective analysis, case records of patients with a diagnosis of NHL of the orbit were analysed from January 2005 to January 2015. Patients were worked up and staged according to the Ann Arbor system. Patients with large tumours were initially given chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin and prednisolone) three weekly for 4–6 cycles. Patients with residual disease were given RT 20–30 Gy at 2 Gy per fraction. RT when given as a primary treatment consisted of 36–45 Gy at 1·8–2 Gy per fraction on either Cobalt 60 machine or linear accelerator.
Results:
A total of 52 patients with diagnosis of orbital NHL were included in this study. Median age at presentation was 57 years (range 13–71). Left, right and bilateral orbit was involved in 21 (40%), 28(54%) and 3(6%) patients, respectively. Low- and high-grade pathology was seen in 39(75%) and 13(25%) patients, respectively. On immunohistochemistry, 23(44%) tumors were CD 20 positive. After staging, 33 (63%) patients had stage I disease. Median tumour size was 4·0 × 3·2 × 1·5 cm (1·7 × 1·7 × 1·4 cm to 5·8 × 4·0 × 4·7 cm). Primary RT was given to 7(13%) patients. Upfront chemotherapy was given in 45(86·5%) patients, out of which 24 had stage I disease. RT consolidation was done in 26 (50%) patients for residual disease after chemotherapy. Median follow-up was 88 months (range 29–183 months). Relapse occurred in 6(9·6%) patients; 2 local; 2 local + distant and in 2 distant alone. These patients were successfully salvaged with systemic chemotherapy and local RT. One patient died due to neutropenia. Overall survival in this series was 96%.
Conclusions:
Excellent local control was achieved with initial chemotherapy followed by RT for primary orbital NHL with minimal toxicity. We recommend a dose of 36–40 Gy for definitive RT and 30 Gy for lymphoma following chemotherapy using 2 Gy/fraction for Indian patients who present with bulky tumours. RT should be incorporated in treatment of orbital NHL whenever possible as it is safe, effective and is associated with minimal complications.
The nanoencapsulation of biocomposites with anthelmintic action has been proposed as an alternative for improving their efficiency. Thus, the current study aimed to evaluate the efficacy of carvacryl acetate nanoencapsulated with biopolymers (nCVA) in the control of sheep gastrointestinal nematodes. CVA was nanoencapsulated with chitosan/chichá gum and characterized in terms of its efficacy of encapsulation (EE), yield and zeta potential. The acute toxicity of nCVA was evaluated in mice. For the fecal egg count reduction test, 40 animals were divided into four groups (n = 10) and orally administered the following treatments: G1, 250 mg kg−1 CVA; G2, 250 mg kg−1 nCVA; G3, chitosan/chichá gum (negative control) and G4, 2.5 mg kg−1 monepantel (positive control). Feces were collected on days 0 and 16 posttreatment to determine the eggs per gram of feces (epg). The EE and yield of nCVA were 72.8 and 57.5%, respectively. The nanoparticles showed a size of 764.5 ± 302.5 nm, and the zeta potential at pH 3.2 was +22.0 mV. nCVA presented a 50% lethal dose (LD50) of 2609 mg kg−1. By 16 days posttreatment, CVA, nCVA and monepantel reduced the epg by 52.9.7, 71.5 and 98.7%, respectively, and the epg of sheep treated with nCVA differed from that of the negative control (P > 0.05) but did not differ from that of sheep treated with CVA. In conclusion, the nanoencapsulation of CVA reduced its toxicity, and nCVA showed anthelmintic activity.
Petroleum hydrocarbons (PH) toxicity and bioaccumulation in aquatic organisms have been investigated for almost 50 years. Continuous oil spillages necessitate a further understanding of the toxicological effects of PH on brachyuran crabs. Crabs can be exposed to PH through various routes such as the water column, sediment and diet. Numerous investigations have been dedicated to evaluating PH toxicity on different life stages of crab species, but the majority of them have focused on the blue crab Callinectes sapidus as it represents an edible and favourable seafood commodity for human consumption. The objective of the review is to critically assess studies related to PH toxicity on different life stages of 41 crab species representing 13 families across the world. Several physiological, biochemical and genetic endpoints of marine crabs were evaluated in addition to the sublethal effects of PH on crab metabolism, behaviour, moulting, growth and survival. A concise summary of PH deleterious effects on different taxonomic species of marine crabs is discussed and provides evidence that crabs can be used as indicator organisms of biomarker significance for marine pollution. Overall, larval stages appeared to be the most sensitive to the deleterious effects of PH compared with juveniles and adults. However, adult stages have received more research attention than other life stages, followed by larval stages, and juvenile stages are the least investigated stages with respect to PH toxicity. Finally, hepatopancreas and gills were the organs where greatest accumulation of PH was recorded.
The aim of this study was to test the appearance of negative dominance in coronavirus disease (COVID-19) vaccine-related information and activity online. We hypothesized that if negative dominance appeared, it would be a reflection of peaks in adverse events related to the vaccine, that negative content would attract more engagement on social media than other vaccine-related posts, and posts referencing adverse events related to COVID-19 vaccination would have a higher average toxicity score.
Methods:
We collected data using Google Trends for search behavior, CrowdTangle for social media data, and Media Cloud for media stories, and compared them against the dates of key adverse events related to COVID-19. We used Communalytic to analyze the toxicity of social media posts by platform and topic.
Results:
While our first hypothesis was partially supported, with peaks in search behavior for image and YouTube videos driven by adverse events, we did not find negative dominance in other types of searches or patterns of attention by news media or on social media.
Conclusion:
We did not find evidence in our data to prove the negative dominance of adverse events related to COVID-19 vaccination on social media. Future studies should corroborate these findings and, if consistent, focus on explaining why this may be the case.
Humans may live in the Anthropocene, but this does not affect all in the same way. How would the Anthropocene look if, instead of searching its traces in the geosphere, researchers would look for them in the organosphere, in the ecologies of humans in their entanglements with the environment? Looking at this embodied stratigraphy of power and toxicity, more than the Anthropocene, we will discover the Wasteocene. The imposition of wasting relationships on subaltern human and more-than-human communities implies the construction of toxic ecologies made of contaminating substances and narratives. While official accounts have systematically erased any trace of those wasting relationships, another kind of narrative has been written in flesh, blood, and cells. Traveling between Naples (Italy) and Agbogbloshie (Ghana), science fiction and epidemic outbreaks, this Element will take the readers into the bowels of the Wasteocene, but it will also indicate the commoning practices which are dismantling it.