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Pedro Caldana Gordon,1,2 Josefa Cynara Xavier,2 Mario Rodrigues Louzã21Department of Psychiatry, Faculdade de Medicina, Universidade de São Paulo, Brazil; 2Schizophrenia Research Program, Institute of Psychiatry, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, BrazilBackground: In the last few decades, a large number of studies have produced compelling evidence that patients with schizophrenia are at increased risk for developing several medical conditions and diseases, including obesity, metabolic disturbances, and cardiovascular diseases. Several protocols have been designed with the aim of reducing such risk.Objective: To investigate current physical health status in a population of outpatients with schizophrenia.Methods: A cross-sectional study was conducted in our outpatient clinic, selecting subjects who met DSM-IV diagnosis criteria for schizophrenia. Data were collected regarding clinical characteristics, lifestyle, medication in use, and biometric and laboratory parameters.Results: A total of 261 patients were included. We found a high prevalence of elevated body mass index (BMI > 25) (70%), dyslipidemia (73.2%), and metabolic syndrome (28.7%). Patients' ages were associated with worsened lipid profiles, but other variables, such as disorder duration or type of antipsychotic in use, were not associated with any metabolic disturbance. Despite the increased prevalence of these conditions, only a small portion of the sample was under regular medical treatment.Conclusion: Outpatients with schizophrenia show signs of poor physical health conditions. These findings reinforce the need for an intensive and appropriate approach to assure that these patients receive adequate clinical referral and treatment.Keywords: psychosis, obesity, public health, antipsychotic drugs, cardiovascular disorders

Cephalopods play a major role in marine food webs as both predators and prey. Although most of the Hg in cephalopods is present in the muscle, most studies on its accumulation by predators are based on concentrations in beaks. Here, using upper and lower beaks and buccal masses of Moroteuthopsis longimana, we evaluated the relationship between Hg concentrations in different cephalopod tissues. Hg concentrations in muscle tissue (329.9 ± 166.4 ng.g -1 dw) were ≈100-fold higher than in different sections of the upper (3.5 ± 1.4 ng.g -1 dw) and lower (3.5 ± 1.0 ng.g -1 dw) beaks. A positive linear relationship was found between the Hg in the beak wing and in the muscle. Hg concentrations in the wing are therefore a useful proxy for the total Hg body burden, and their analysis provides a means of assessing the levels, transport and fate of Hg in marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Knowledge of how animals respond to weather and changes in their physical environment is increasingly important, given the higher frequency of extreme weather recorded in recent years and its forecasted increase globally. 1 , 2 Even species considered to be highly adapted to extremes of weather, as albatrosses are to strong winds, 3 , 4 , 5 may be disadvantaged by shifts in those extremes. Tracked albatrosses were shown recently to avoid storms and the strongest associated winds. 6 The drivers of this response are so far unknown, though we hypothesize that turbulent storm conditions restrict foraging success, possibly by reducing the detectability or accessibility of food, and albatrosses divert toward more profitable conditions where possible. We tested the impact of the physical environment-wind speed, rainfall, water clarity, and time of day-on feeding activity and success of two species of albatrosses with contrasting foraging strategies. We tracked 33 wandering and 48 black-browed albatrosses from Bird Island (South Georgia) with GPS and immersion loggers, and 19 and 7 individuals, respectively, with stomach-temperature loggers to record ingestions, providing an in-depth picture of foraging behavior. Reduced foraging profitability (probability of prey capture and overall mass) was associated with stormy conditions, specifically strong winds and heavy rain in surface-seizing wandering albatrosses, and the probability of prey capture was reduced in strong winds in black-browed albatrosses. We show that even highly wind-adapted species may frequently encounter conditions that make foraging difficult, giving context to storm avoidance in albatrosses. VIDEO ABSTRACT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Illicit drug toxicity (i.e., overdose) is the leading cause of death in British Columbia (BC) for people aged 10-59. Stimulants are increasingly detected among drug toxicity deaths. As stimulant use and detection in deaths rises, it is important to understand how people who die of stimulant toxicity differ from people who die of opioid toxicity., Methods: BC Coroners Service records were retrieved for all people who died of unintentional illicit drug toxicity (accidental or undetermined) between January 1, 2015, and December 31, 2019, whose coroner investigation had concluded and who had an opioid and/or stimulant detected in post-mortem toxicology and identified by the coroner as relevant to the death (N = 3788). BC Chronic Disease Registry definitions were used to identify people with chronic disease. Multinomial regression models were used to examine the relationship between chronic disease diagnoses and drug toxicity death type., Results: Of the 3788 deaths, 11.1% (N = 422) had stimulants but not opioids deemed relevant to the cause of death (stimulant group), 26.8% (N = 1014) had opioids but not stimulants deemed relevant (opioid group), and 62.1% (N = 2352) had both opioids and stimulants deemed relevant (opioid/stimulant group). People with ischemic heart disease (1.80 (1.14-2.85)) and people with heart failure (2.29 (1.25-4.20)) had approximately twice the odds of being in the stimulant group as compared to the opioid group., Conclusions: Findings suggest that people with heart disease who use illicit stimulants face an elevated risk of drug toxicity death. Future research should explore this association and should identify opportunities for targeted interventions to reduce drug toxicity deaths among people with medical comorbidities., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Data were assembled in the context of BC’s provincial overdose public health emergency under a Public Health Order. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Cephalopods play a central ecological role across all oceans and realms. However, under the current climate crisis, their physiology and behaviour are impacted, and we are beginning to comprehend the effects of environmental stressors at a molecular level. Here, we study the Hawaiian bobtail squid ( Euprymna scolopes ), known for its specific binary symbiosis with the bioluminescent bacterium Vibrio fischeri acquired post-hatching. We aim to understand the response (i.e., developmental and molecular) of E. scolopes after the embryogenetic exposure to different conditions: i) standard conditions (control), ii) increased CO 2 (ΔpH 0.4 units), iii) warming (+3°C), or iv) a combination of the two treatments. We observed a decrease in hatching success across all treatments relative to the control. Using transcriptomics, we identified a potential trade-off in favour of metabolism and energy production, at the expense of development under increased CO 2 . In contrast, elevated temperature shortened the developmental time and, at a molecular level, showed signs of alternative splicing and the potential for RNA editing. The data also suggest that the initiation of the symbiosis may be negatively affected by these environmental drivers of change in the biosphere, although coping mechanisms by the animal may occur., Competing Interests: 8Declaration of AI use We have not used AI-assisted technologies in creating this article. 10Conflict of interest declaration We declare no conflict of interest.

Summary: Catalytic reaction networks serve as fundamental models for understanding biochemical systems. CatReNet is a novel software designed to facilitate interactive analysis of such networks. It offers fast and exact algorithms for computing various types of self-sustaining autocatalytic subnetworks, including so-called CAFs (constructively autocatalytic food-generated networks), RAFs (reflexively autocatalytic food-generated networks), and pseudo-RAFs. It provides dynamic visualizations to aid exploration and understanding., Availability and Implementation: This open-source Java application runs on Linux, MacOS, and Windows. It is available at https://github.com/husonlab/catrenet under a GPL3 license., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Assessing the historical dynamics of key food web components is crucial to understand how climate change impacts the structure of Arctic marine ecosystems. Most retrospective stable isotopic studies to date assessed potential ecosystem shifts in the Arctic using vertebrate top predators and filter-feeding invertebrates as proxies. However, due to long life histories and specific ecologies, ecosystem shifts are not always detectable when using these taxa. Moreover, there are currently no retrospective stable isotopic studies on various other ecological and taxonomic groups of Arctic biota. To test whether climate-driven shifts in marine ecosystems are reflected in the ecology of short-living mesopredators, ontogenetic changes in stable isotope signatures in chitinous hard body structures were analysed in two abundant squids (Gonatus fabricii and Todarodes sagittatus) from the low latitude Arctic and adjacent waters, collected between 1844 and 2023., Results: We detected a temporal increase in diet and habitat-use generalism (= opportunistic choice rather than specialization), trophic position and niche width in G. fabricii from the low latitude Arctic waters. These shifts in trophic ecology matched with the Atlantification of the Arctic ecosystems, which includes increased generalization of food webs and higher primary production, and the influx of boreal species from the North Atlantic as a result of climate change. The Atlantification is especially marked since the late 1990s/early 2000s. The temporal patterns we found in G. fabricii's trophic ecology were largely unreported in previous Arctic retrospective isotopic ecology studies. Accordingly, T. sagittatus that occur nowadays in the high latitude North Atlantic have a more generalist diet than in the XIX th century., Conclusions: Our results suggest that abundant opportunistic mesopredators with short life cycles (such as squids) are good candidates for retrospective ecology studies in the marine ecosystems, and to identify ecosystem shifts driven by climate change. Enhanced generalization of Arctic food webs is reflected in increased diet generalism and niche width in squids, while increased abundance of boreal piscivorous fishes is reflected in squids' increased trophic position. These findings support opportunism and adaptability in squids, which renders them as potential winners of short-term shifts in Arctic ecosystems., (© 2024. The Author(s).)

Comprehensive spatial planning in international waters is key to achieving ocean sustainability.

The concept of an autocatalytic network of reactions that can form and persist, starting from just an available food source, has been formalized by the notion of a reflexively autocatalytic and food-generated (RAF) set. The theory and algorithmic results concerning RAFs have been applied to a range of settings, from metabolic questions arising at the origin of life, to ecological networks, and cognitive models in cultural evolution. In this article, we present new structural and algorithmic results concerning RAF sets, by studying more complex modes of catalysis that allow certain reactions to require multiple catalysts (or to not require catalysis at all), and discuss the differing ways catalysis has been viewed in the literature. We also focus on the structure and analysis of minimal RAFs and derive structural results and polynomial-time algorithms. We then apply these new methods to a large metabolic network to gain insights into possible biochemical scenarios near the origin of life.

Background: North America and the province of British Columbia (BC), Canada, is experiencing an unprecedented number of overdose deaths. In BC, overdose has become the leading cause of death for people between the ages of 10-59 years old. In January 2023, BC decriminalized personal possession of a number of illegal substances with one aim being to address overdose deaths through stigma reduction and promoting access to substance use services., Methods: We conducted a qualitative study to understand people who use drugs' (PWUD) perceptions of the new decriminalization policy, immediately prior to its' implementation (October-December 2022). To contextualize decriminalization within broader drug policy, we also asked PWUD what they perceived as the priority issues drug policy ought to address and the necessary solutions. Our final sample included 38 participants who used illegal drugs in the past month., Results: We identified four themes: 1) The illicit drug supply as the main driver of drug toxicity deaths 2) Concerns about the impact of decriminalization on drug toxicity deaths 3) Views towards decriminalization as a policy response in the context of the drug toxicity crisis 4) Regulation as a symbol of hope for reducing drug toxicity deaths., Conclusion: From our data it became clear that many anticipated that decriminalization would have minimal or no impact on the overdose crisis. Regulation was perceived as the necessary policy approach for effectively and candidly addressing the drivers of the ongoing overdose crisis. These findings are important as jurisdictions consider different approaches to moving away from prohibition-based drug policy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids., Methods: This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers., Results: We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using "down", heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again., Conclusions: Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS., (© 2024. The Author(s).)

Objective: to evaluate the association between risk classification and door-to-antibiotic time in patients with suspected sepsis., Method: retrospective cohort study, with a sample of 232 patients with suspected sepsis treated at the emergency department. They were divided into 2 groups: with and without risk classification. Once the door-to-antibiotic time was identified, one-way analysis of variance was performed with Bonferroni post hoc test or independent Student's t-test for continuous quantitative variables; Pearson correlation tests, point-biserial correlation or biserial correlation for association analyses; and bootstrap procedure when there was no normal distribution of variables. For data analysis, the Statistical Package for the Social Sciences software was used., Results: the door-to-antibiotic time did not differ between the group that received risk classification compared to the one that was not classified. Door-to-antibiotic time was significantly shorter in the group that received a high priority risk classification., Conclusion: there was no association between door-to-antibiotic time and whether or not the risk classification was performed, nor with hospitalization in infirmaries and intensive care units, or with the length of hospital stay. It was observed that the higher the priority, the shorter the door-to-antibiotic time.

Background: The increasing number of illicit drug toxicity deaths in British Columbia (BC) has led to calls for a regulated (pharmaceutical grade) supply of substances ("safe supply"). In order to inform safe supply recommendations, we aimed to identify why people currently smoke opioids and assess the preferred mode of consumption if people who use opioids were provided with opioid safe supply., Methods: The BC Harm Reduction Client Survey (HRCS) is an annual survey that gathers information about people who use drugs' (PWUD) substance use characteristic with the goal of contributing to evidence-based policy. This study utilized data from the 2021 HRCS. The outcome variable was "prefer smoking opioid safe supply" ('yes/no'). Explanatory variables included participants' demographics, drug use, and overdose characteristics. Bivariate and hierarchical multivariable logistic regressions were conducted to identify factors associated with the outcome., Results: Of 282 total participants who indicated a preference for a mode of consumption for opioid safe supply, 62.4% preferred a smokable option and 19.9% preferred to inject if provided with opioid safe supply. Variables significantly associated with the outcome (preferred smoking) included: being 19-29 years old (AOR=5.95, CI =1.93 - 18.31) compared to >50 years old, having witnessed an overdose in the last 6 months (AOR=2.26, CI=1.20 - 4.28), having smoked opioids in the last 3 days (AOR=6.35, CI=2.98 - 13.53) and having a preference to smoke stimulants safe supply (AOR=5.04, CI=2.53 - 10.07)., Conclusion: We found that over half of participants prefer smokable options when accessing opioid safe supply. Currently in BC, there are limited smokable opioid safe supply options as alternatives to the toxic street supply. To reduce overdose deaths, safe supply options should be expanded to accommodate PWUD that prefer smoking opioids., (© 2023. The Author(s).)

The Antarctic toothfish Dissostichus mawsoni is a Southern Ocean long-lived top predator which is regularly captured on an annual fishery operating in the region. By its biological and ecological characteristics, it is a potential bioindicator for the concentrations of trace and rare earth elements in the Antarctic. As these elements are mainly transferred through the diet and a deficiency or excess of these elements can lead to diverse health problems, it is important to measure their concentrations on the organisms. This study provides, for the first time, the concentration of 27 trace (major essential, minor essential and non-essential) and rare earth elements in the muscle of D. mawsoni captured in three areas of the Amundsen and Dumont D'Urville Seas (Antarctica). Major essential elements had the highest concentrations, with potassium (K) as the most concentrated, and rare earth elements the lowest. Significant differences between areas were found for most of the studied elements. No bioaccumulation nor biomagnification potential was found for the studied elements, with several elements decreasing concentrations towards larger individuals. Decreasing trends are related with the different habitats occupied by D. mawsoni through their life, suggesting that elements' concentrations in the water is determinant for the concentrations in this top predator, and/or there is a dilution effect as the fish grows. Our results also support that Se presents a detoxification potential for Hg in D. mawsoni, but only when Hg concentrations are higher to unhealthy levels. This study supports D. mawsoni as a potential bioindicator for the concentrations of the different trace and rare earth elements in the Southern Ocean, though only when comparing individuals of similar size/age, but also to evaluate annual changes on their concentrations. Furthermore, D. mawsoni can be a good source of major essential elements to humans with concentrations of major essential elements above some of other marine fish worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chalcones are present in a wide variety of plants, having in their structure two aromatic rings that are linked together by a chain composed of three carbon atoms with α, β-unsaturated to carbonyl system. Bacteria have several drug resistance mechanisms, among them the efflux pump; this mechanism, when active, is able to expel different compounds from inside bacterial cells. Several efflux pumps have already been identified for Staphylococcus aureus bacteria, including MepA and NorA. Many chalcones have been isolated and identified with various activities, such as antimicrobial. In view of this, this article aimed to evaluate the antibiotic modifying effect of chalcone (E)-1-(2-hydroxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one against S. aureus carrier of NorA and MepA efflux pump. Regarding the antibiotic, there was a synergism when associated with ciprofloxacin in SA-K2068 strain, showing this chalcone as an alternative to reverse the resistance to this medicine. The physicochemical properties calculated were fundamental in the description of the predicted pharmacokinetic properties. Despite the mutagenic risk caused by the metabolic activation of nitrochalcone, it is possible to notice a pharmacological principle in a longer half-life for the performance of biological activities. The compound has a good bioavailability, as it is highly absorbed in the intestine and easily transported by plasma proteins, in addition to not presenting neurotoxic, hepatotoxic, and cardiotoxic damage., (© 2022 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Cephalopods are important in Arctic marine ecosystems as predators and prey, but knowledge of their life cycles is poor. Consequently, they are under-represented in the Arctic ecosystems assessment models. One important parameter is the change in ecological role (habitat and diet) associated with individual ontogenies. Here, the life history of Gonatus fabricii, the most abundant Arctic cephalopod, is reconstructed by the analysis of individual ontogenetic trajectories of stable isotopes (δ13C and δ15N) in archival hard body structures. This approach allows the prediction of the exact mantle length (ML) and mass when the species changes its ecological role. Our results show that the life history of G. fabricii is divided into four stages, each having a distinct ecology: (1) epipelagic squid (ML < 20 mm), preying mostly on copepods; (2) epi- and occasionally mesopelagic squid (ML 20−50 mm), preying on larger crustaceans, fish, and cephalopods; (3) meso- and bathypelagic squid (ML > 50 mm), preying mainly on fish and cephalopods; and (4) non-feeding bathypelagic gelatinous females (ML > 200 mm). Existing Arctic ecosystem models do not reflect the different ecological roles of G. fabricii correctly, and the novel data provided here are a necessary baseline for Arctic ecosystem modelling and forecasting.

The use of cephalopod beaks in ecological and population dynamics studies has allowed major advances of our knowledge on the role of cephalopods in marine ecosystems in the last 60 years. Since the 1960's, with the pioneering research by Malcolm Clarke and colleagues, cephalopod beaks (also named jaws or mandibles) have been described to species level and their measurements have been shown to be related to cephalopod body size and mass, which permitted important information to be obtained on numerous biological and ecological aspects of cephalopods in marine ecosystems. In the last decade, a range of new techniques has been applied to cephalopod beaks, permitting new kinds of insight into cephalopod biology and ecology. The workshop on cephalopod beaks of the Cephalopod International Advisory Council Conference (Sesimbra, Portugal) in 2022 aimed to review the most recent scientific developments in this field and to identify future challenges, particularly in relation to taxonomy, age, growth, chemical composition (i.e., DNA, proteomics, stable isotopes, trace elements) and physical (i.e., structural) analyses. In terms of taxonomy, new techniques (e.g., 3D geometric morphometrics) for identifying cephalopods from their beaks are being developed with promising results, although the need for experts and reference collections of cephalopod beaks will continue. The use of beak microstructure for age and growth studies has been validated. Stable isotope analyses on beaks have proven to be an excellent technique to get valuable information on the ecology of cephalopods (namely habitat and trophic position). Trace element analyses is also possible using beaks, where concentrations are significantly lower than in other tissues (e.g., muscle, digestive gland, gills). Extracting DNA from beaks was only possible in one study so far. Protein analyses can also be made using cephalopod beaks. Future challenges in research using cephalopod beaks are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xavier, Golikov, Queirós, Perales-Raya, Rosas-Luis, Abreu, Bello, Bustamante, Capaz, Dimkovikj, González, Guímaro, Guerra-Marrero, Gomes-Pereira, Kubodera, Laptikhovsky, Lefkaditou, Lishchenko, Luna, Liu, Pierce, Pissarra, Reveillac, Romanov, Rosa, Roscian, Rose-Mann, Rouget, Sánchez, Sánchez-Márquez, Seixas, Souquet, Varela, Vidal and Cherel.)

A closer look at Wilhelm Ostwald's articles that originally proposed the concept of autocatalysis reveals that he accepted reactants, not just products, as potential autocatalysts. Therefore, that a process is catalyzed by some of its products, which is the common definition of autocatalysis, is only a proper subset of what Ostwald meant by "Autokatalyse." As a result, it is necessary to reconsider the definition of autocatalysis, which is especially important for origins-of-life research because autocatalysis provides an abiotic mechanism that yields reproduction-like dynamics. Here, we translate and briefly review the two key publications on autocatalysis by Ostwald to revive his understanding of autocatalysis, and we introduce the concepts of recessive and expansive autocatalysis. Then we discuss the twofold significance of such a revival: first, facilitating the search for candidate processes underlying the origins of life, and second, updating our view of autocatalysis in complex reaction networks and metabolism., (© 2022 Wiley Periodicals LLC.)

Introduction: Canada and the United States continue to experience increasing overdose deaths attributed to highly toxic illicit substances, driven by fentanyl and its analogues. Many bystanders report being hesitant to call 9-1-1 at an overdose due to fears around police presence and arrests. In Canada, a federal law was enacted in 2017, the Good Samaritan Drug Overdose Act (GSDOA), to provide protection from simple drug possession and related charges when 9-1-1 is called to an overdose. There is limited evidence, however, that the GSDOA has improved rates of intention to call 9-1-1 at overdose events. We therefore sought to examine intent to call 9-1-1 among persons who received GSDOA education and were at risk of witnessing an overdose., Methods: A cross-sectional survey was conducted with people at risk of witnessing an overdose recruited at 19 Take Home Naloxone (THN) program sites across British Columbia as well as online through Foundry from October 2020 to April 2021. Descriptive statistics were used to examine intention to call 9-1-1 at future overdoses. Multivariable logistic regression models were built in hierarchical fashion to examine factors associated with intention to call 9-1-1., Results: Overall, 89.6% (n = 404) of the eligible sample reported intention to call 9-1-1. In the multivariable model, factors positively associated with intention to call 9-1-1 included identifying as a cisgender woman (adjusted odds ratio [AOR]: 3.37; 95% CI: 1.19-9.50) and having previous GSDOA awareness ([AOR]: 4.16; 95% CI: 1.62-10.70). Having experienced a stimulant overdose in the past 6 months was negatively associated with intention to call 9-1-1 ([AOR]: 0.24; 95% CI: 0.09-0.65)., Conclusion: A small proportion of the respondents reported that, despite the enactment of GSDOA, they did not intend to call 9-1-1 and those who were aware of the act were more likely to report an intention to call at future overdose events. Increasing GSDOA awareness and/or additional interventions to support the aims of the GSDOA could address ongoing reluctance to seek emergency medical care by people who use drugs., (© 2022. The Author(s).)

Life and the genetic code are self-referential and so are autocatalytic networks made of simpler, small molecules. Several origins of life theories postulate autocatalytic chemical networks preceding the primordial genetic code, yet demonstration with biochemical systems is lacking. Here, small-molecule reflexively autocatalytic food-generated networks (RAFs) ranging in size from 3 to 619 reactions were found in all of 6683 prokaryotic metabolic networks searched. The average maximum RAF size is 275 reactions for a rich organic medium and 93 for a medium with a single organic cofactor, NAD. In the rich medium, all universally essential metabolites are produced with the exception of glycerol-1-p (archaeal lipid precursor), phenylalanine, histidine and arginine. The 300 most common reactions, present in at least 2732 RAFs, are mostly involved in amino acid biosynthesis and the metabolism of carbon, 2-oxocarboxylic acid and purines. ATP and NAD are central in generating network complexity, and because ATP is also one of the monomers of RNA, autocatalytic networks producing redox and energy currencies are a strong candidate niche of the origin of a primordial information-processing system. The wide distribution of small-molecule autocatalytic networks indicates that molecular reproduction may be much more prevalent in the Universe than hitherto predicted. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.

Under the climate change context, warming Southern Ocean waters may allow mercury (Hg) to become more bioavailable to the Antarctic marine food web (i.e., ice-stored Hg release and higher methylation rates by microorganisms), whose biomagnification processes are poorly documented. Biomagnification of Hg in the food web of the Antarctic Peninsula, one of the world's fastest-warming regions, was examined using carbon (δ 13 C) and nitrogen (δ 15 N) stable isotope ratios for estimating feeding habitat and trophic levels, respectively. The stable isotope signatures and total Hg (T-Hg) concentrations were measured in Antarctic krill Euphausia superba and several Antarctic predator species, including seabirds (gentoo penguins Pygoscelis papua, chinstrap penguins Pygoscelis antarcticus, brown skuas Stercorarius antarcticus, kelp gulls Larus dominicanus, southern giant petrels Macronectes giganteus) and marine mammals (southern elephant seals Mirounga leonina). Significant differences in δ 13 C values among species were noted with a great overlap between seabird species and M. leonina. As expected, significant differences in δ 15 N values among species were found due to interspecific variations in diet-related to their trophic position within the marine food web. The lowest Hg concentrations were registered in E. superba (0.007 ± 0.008 μg g -1 ) and the highest values in M. giganteus (12.090 ± 14.177 μg g -1 ). Additionally, a significant positive relationship was found between Hg concentrations and trophic levels (reflected by δ 15 N values), biomagnifying nearly 2 times its concentrations at each level. Our results support that trophic interaction is the major pathway for Hg biomagnification in Southern Ocean ecosystems and warn about an increase in the effects of Hg on long-lived (and high trophic level) Antarctic predators under climate change in the future., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Though all theories for the origin of life require a source of energy to promote primordial chemical reactions, the nature of energy that drove the emergence of metabolism at origins is still debated. We reasoned that evidence for the nature of energy at origins should be preserved in the biochemical reactions of life itself, whereby changes in free energy, Δ G , which determine whether a reaction can go forward or not, should help specify the source. By calculating values of Δ G across the conserved and universal core of 402 individual reactions that synthesize amino acids, nucleotides and cofactors from H 2 , CO 2 , NH 3 , H 2 S and phosphate in modern cells, we find that 95-97% of these reactions are exergonic (Δ G ≤ 0 kJ⋅mol -1 ) at pH 7-10 and 80-100°C under nonequilibrium conditions with H 2 replacing biochemical reductants. While 23% of the core's reactions involve ATP hydrolysis, 77% are ATP-independent, thermodynamically driven by Δ G of reactions involving carbon bonds. We identified 174 reactions that are exergonic by -20 to -300 kJ⋅mol -1 at pH 9 and 80°C and that fall into ten reaction types: six pterin dependent alkyl or acyl transfers, ten S-adenosylmethionine dependent alkyl transfers, four acyl phosphate hydrolyses, 14 thioester hydrolyses, 30 decarboxylations, 35 ring closure reactions, 31 aromatic ring formations, and 44 carbon reductions by reduced nicotinamide, flavins, ferredoxin, or formate. The 402 reactions of the biosynthetic core trace to the last universal common ancestor (LUCA), and reveal that synthesis of LUCA's chemical constituents required no external energy inputs such as electric discharge, UV-light or phosphide minerals. The biosynthetic reactions of LUCA uncover a natural thermodynamic tendency of metabolism to unfold from energy released by reactions of H 2 , CO 2 , NH 3 , H 2 S, and phosphate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wimmer, Xavier, Vieira, Pereira, Leidner, Sousa, Kleinermanns, Preiner and Martin.)

Bacterial resistance induced by efflux pumps is a frequent concern in clinical treatments involving multi-resistant bacteria. Staphylococcus aureus is a microorganism responsible for several types of infections and has several strains carrying efflux pumps, among them are the strain 1199B (NorA overexpresser), and the strain K2068 (MepA overexpresser). In this work, four chalcones derived from Croton anisodontus with modifications in the B ring in their structures were tested regarding their ability to inhibit NorA and MepA efflux pumps. The efflux pump inhibition mechanism was tested with the ethidium bromide substrate in the presence and absence of standard efflux pump inhibitors. The minimum inhibitory concentration values were also compared to those of strains that do not overexpress these efflux pumps. In order to gain some insights about the efflux pump mechanisms of these chalcones, two homology models were created (NorA and MepA) for a docking procedure. In addition, the ADME properties (absorption, distribution, metabolism and excretion) were also evaluated. The tested chalcones promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps. All four tested chalcones appear to bind to the binding sites of the efflux pump models in the same fashion as other chalcones with efflux pump inhibition capabilities. It was also verified that the chalcones 1-4 are well absorbed in the intestine, but with a decrease in their bioavailability, resulting in a low volume of distribution in the blood plasma, in addition to having a mild CNS activity. However, the chalcone 3 and 4 were not toxic due to metabolic activation. Whereas the chalcones 1 and 2 present a mutagenic risk, depending on the oral dose administered. The tested chalcones have not antibacterial activity; however, they are capable of inhibiting efflux pumps for the 1199B and K2068 strains. They promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps, as well as other associated mechanisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ocean circulation connects geographically distinct ecosystems across a wide range of spatial and temporal scales via exchanges of physical and biogeochemical properties. Remote oceanographic processes can be especially important for ecosystems in the Southern Ocean, where the Antarctic Circumpolar Current transports properties across ocean basins through both advection and mixing. Recent tracking studies have indicated the existence of two large-scale, open ocean habitats in the Southern Ocean used by grey petrels (Procellaria cinerea) from two populations (i.e., Kerguelen and Antipodes islands) during their nonbreeding season for extended periods during austral summer (i.e., October to February). In this work, we use a novel combination of large-scale oceanographic observations, surface drifter data, satellite-derived primary productivity, numerical adjoint sensitivity experiments, and output from a biogeochemical state estimate to examine local and remote influences on these grey petrel habitats. Our aim is to understand the oceanographic features that control these isolated foraging areas and to evaluate their ecological value as oligotrophic open ocean habitats. We estimate the minimum local primary productivity required to support these populations to be much <1% of the estimated local primary productivity. The region in the southeast Indian Ocean used by the birds from Kerguelen is connected by circulation to the productive Kerguelen shelf. In contrast, the region in the south-central Pacific Ocean used by seabirds from the Antipodes is relatively isolated suggesting it is more influenced by local factors or the cumulative effects of many seasonal cycles. This work exemplifies the potential use of predator distributions and oceanographic data to highlight areas of the open ocean that may be more dynamic and productive than previously thought. Our results highlight the need to consider advective connections between ecosystems in the Southern Ocean and to re-evaluate the ecological relevance of oligotrophic Southern Ocean regions from a conservation perspective., (© 2021 John Wiley & Sons Ltd.)

Microplastics (< 5 mm in size) are known to be widespread in the marine environment but are still poorly studied in Polar Regions, particularly in the Antarctic. As penguins have a wide distribution around Antarctica, three congeneric species: Adélie (Pygoscelis adeliae), chinstrap (Pygoscelis antarcticus) and gentoo penguins (Pygoscelis papua) were selected to evaluate the occurrence of microplastics across the Antarctic Peninsula and Scotia Sea. Scat samples (used as a proxy of ingestion), were collected from breeding colonies over seven seasons between 2006 and 2016. Antarctic krill (Euphausia superba), present in scat samples, contributed 85%, 66% and 54% of the diet in terms of frequency of occurrence to the diet of Adélie, gentoo and chinstrap penguins, respectively. Microplastics were found in 15%, 28% and 29% scats of Adélie, chinstrap and gentoo penguin respectively. A total of 92 particles were extracted from the scats (n = 317) and 32% (n = 29) were chemically identified via micro-Fourier Transform Infrared Spectroscopy (μ-FTIR). From all the particles extracted, 35% were identified as microplastics, particularly polyethylene (80%) and polyester (10%). It was not possible to ascertain the identification of the remaining 10% of samples. Other anthropogenic particles were identified in 55% of samples, identified as cellulose fibres. The results show a similar frequency of occurrence of particles across all colonies, suggesting there is no particular point source for microplastic pollution in the Scotia Sea. Additionally, no clear temporal variation in the number of microplastics in penguins was observed. Overall, this study reveals the presence of microplastics across Antarctica, in three penguin species and offers evidence of other anthropogenic particles in high numbers. Further research is needed to better understand the spatio-temporal dynamics, fate and effect of microplastics on these ecosystems, and improve plastic pollution policies in Antarctica., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Important findings from the second decade of the 21st century on the impact of environmental change on biological processes in the Antarctic were synthesised by 26 international experts. Ten key messages emerged that have stakeholder-relevance and/or a high impact for the scientific community. They address (i) altered biogeochemical cycles, (ii) ocean acidification, (iii) climate change hotspots, (iv) unexpected dynamism in seabed-dwelling populations, (v) spatial range shifts, (vi) adaptation and thermal resilience, (vii) sea ice related biological fluctuations, (viii) pollution, (ix) endangered terrestrial endemism and (x) the discovery of unknown habitats. Most Antarctic biotas are exposed to multiple stresses and considered vulnerable to environmental change due to narrow tolerance ranges, rapid change, projected circumpolar impacts, low potential for timely genetic adaptation, and migration barriers. Important ecosystem functions, such as primary production and energy transfer between trophic levels, have already changed, and biodiversity patterns have shifted. A confidence assessment of the degree of 'scientific understanding' revealed an intermediate level for most of the more detailed sub-messages, indicating that process-oriented research has been successful in the past decade. Additional efforts are necessary, however, to achieve the level of robustness in scientific knowledge that is required to inform protection measures of the unique Antarctic terrestrial and marine ecosystems, and their contributions to global biodiversity and ecosystem services., (© 2020 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

The last eukaryote common ancestor (LECA) possessed mitochondria and all key traits that make eukaryotic cells more complex than their prokaryotic ancestors, yet the timing of mitochondrial acquisition and the role of mitochondria in the origin of eukaryote complexity remain debated. Here, we report evidence from gene duplications in LECA indicating an early origin of mitochondria. Among 163,545 duplications in 24,571 gene trees spanning 150 sequenced eukaryotic genomes, we identify 713 gene duplication events that occurred in LECA. LECA's bacterial-derived genes include numerous mitochondrial functions and were duplicated significantly more often than archaeal-derived and eukaryote-specific genes. The surplus of bacterial-derived duplications in LECA most likely reflects the serial copying of genes from the mitochondrial endosymbiont to the archaeal host's chromosomes. Clustering, phylogenies and likelihood ratio tests for 22.4 million genes from 5,655 prokaryotic and 150 eukaryotic genomes reveal no evidence for lineage-specific gene acquisitions in eukaryotes, except from the plastid in the plant lineage. That finding, and the functions of bacterial genes duplicated in LECA, suggests that the bacterial genes in eukaryotes are acquisitions from the mitochondrion, followed by vertical gene evolution and differential loss across eukaryotic lineages, flanked by concomitant lateral gene transfer among prokaryotes. Overall, the data indicate that recurrent gene transfer via the copying of genes from a resident mitochondrial endosymbiont to archaeal host chromosomes preceded the onset of eukaryotic cellular complexity, favoring mitochondria-early over mitochondria-late hypotheses for eukaryote origin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Indicators of oxidative stress and metabolic capacity are key factors in understanding the fitness of wild populations. In the present study, these factors were evaluated in the pelagic Southern Ocean taxa Antarctic krill (Euphausia superba) and myctophid fish (Electrona antarctica, Gymnoscopelus braueri and G. nicholsi) to establish a baseline record for future studies. Mercury (Hg) concentrations were also analysed to evaluate its potential impacts on species biochemical performance. E. superba had higher metabolic activity than most of the myctophid species, which may explain the comparatively lower energy reserves found in the former. The activity of antioxidant enzymes showed, generally, a lower level in E. superba than in the myctophid species. The lack of any relationship between Hg concentrations and organisms' antioxidant and biotransformation defence mechanisms indicate that levels of Hg accumulated in the studied species were not high enough to affect their biochemical processes adversely., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biomagnification of mercury (Hg) in the Scotia Sea food web of the Southern Ocean was examined using the stable isotope ratios of nitrogen (δ 15 N) and carbon (δ 13 C) as proxies for trophic level and feeding habitat, respectively. Total Hg and stable isotopes were measured in samples of particulate organic matter (POM), zooplankton, squid, myctophid fish, notothenioid fish and seabird tissues collected in two years (austral summers 2007/08 and 2016/17). Overall, there was extensive overlap in δ 13 C values across taxonomic groups suggesting similarities in habitats, with the exception of the seabirds, which showed some differences, possibly due to the type of tissue analysed (feathers instead of muscle). δ 15 N showed increasing enrichment across groups in the order POM to zooplankton to squid to myctophid fish to notothenioid fish to seabirds. There were significant differences in δ 1 5 N and δ 1 3 C values among species within taxonomic groups, reflecting inter-specific variation in diet. Hg concentrations increased with trophic level, with the lowest values in POM (0.0005 ± 0.0002 μg g -1 dw) and highest values in seabirds (3.88 ± 2.41 μg g -1 in chicks of brown skuas Stercorarius antarcticus). Hg concentrations tended to be lower in 2016/17 than in 2007/08 for mid-trophic level species (squid and fish), but the opposite was found for top predators (i.e. seabirds), which had higher levels in the 2016/17 samples. This may reflect an interannual shift in the Scotia Sea marine food web, caused by the reduced availability of a key prey species, Antarctic krill Euphausia superba. In 2016/17, seabirds would have been forced to feed on higher trophic-level prey, such as myctophids, that have higher Hg burdens. These results suggest that changes in the food web are likely to affect the pathway of mercury to Southern Ocean top predators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bacteria are the most abundant cells on Earth. They are generally regarded as ancient, but due to striking diversity in their metabolic capacities and widespread lateral gene transfer, the physiology of the first bacteria is unknown. From 1089 reference genomes of bacterial anaerobes, we identified 146 protein families that trace to the last bacterial common ancestor, LBCA, and form the conserved predicted core of its metabolic network, which requires only nine genes to encompass all universal metabolites. Our results indicate that LBCA performed gluconeogenesis towards cell wall synthesis, and had numerous RNA modifications and multifunctional enzymes that permitted life with low gene content. In accordance with recent findings for LUCA and LACA, analyses of thousands of individual gene trees indicate that LBCA was rod-shaped and the first lineage to diverge from the ancestral bacterial stem was most similar to modern Clostridia, followed by other autotrophs that harbor the acetyl-CoA pathway.

The metabolism of cells contains evidence reflecting the process by which they arose. Here, we have identified the ancient core of autotrophic metabolism encompassing 404 reactions that comprise the reaction network from H 2 , CO 2 , and ammonia (NH 3 ) to amino acids, nucleic acid monomers, and the 19 cofactors required for their synthesis. Water is the most common reactant in the autotrophic core, indicating that the core arose in an aqueous environment. Seventy-seven core reactions involve the hydrolysis of high-energy phosphate bonds, furthermore suggesting the presence of a non-enzymatic and highly exergonic chemical reaction capable of continuously synthesizing activated phosphate bonds. CO 2 is the most common carbon-containing compound in the core. An abundance of NADH and NADPH-dependent redox reactions in the autotrophic core, the central role of CO 2 , and the circumstance that the core's main products are far more reduced than CO 2 indicate that the core arose in a highly reducing environment. The chemical reactions of the autotrophic core suggest that it arose from H 2 , inorganic carbon, and NH 3 in an aqueous environment marked by highly reducing and continuously far from equilibrium conditions. Such conditions are very similar to those found in serpentinizing hydrothermal systems.

Trophic niche and diet comparisons among closely sympatric marine species are important to understand complex food webs, particularly in regions most affected by climate change. Using stable isotope analyses, all ontogenetic stages of three sympatric species of Arctic cephalopods (genus Rossia) were studied to assess inter- and intraspecific competition with niche and diet overlap and partitioning in West Greenland and the Barents Sea. Seven traits related to resource and habitat utilization were identified in Rossia: no trait was shared by all three species. High boreal R. megaptera and Arctic endemic R. moelleri shared three traits with each other, while both R. megaptera and R. moelleri shared only two unique traits each with widespread boreal-Arctic R. palpebrosa. Thus all traits formed fully uncrossing pattern with each species having unique strategy of resource and habitat utilization. Predicted climate changes in the Arctic would have an impact on competition among Rossia with one potential 'winner' (R. megaptera in the Barents Sea) but no potential 'losers'.

Cephalopods represent an important pathway for mercury transfer through food webs. Due to the general difficulties in capturing oceanic squid, beaks found in the diet of top predators can be used to study their life-cycles and ecological role. Using upper beaks of the giant warty squid Moroteuthopsis longimana (major prey in the Southern Ocean), we describe a method to assess mercury concentrations along the life of cephalopods through the segmentary analysis of beak sections (i.e. tip of the rostrum and subsections along the hood). Distinct total mercury concentrations in the different subsections support that beaks can be used to study mercury levels in different periods of cephalopods' life-cycle. Mercury values in the anterior (1.3-7.9 μg kg -1 dw) and posterior (7.8-12.5 μg kg -1 dw) subsections of the hood reflect juvenile and adult stages, respectively. Furthermore, these results confirm that mercury bioaccumulates continuously throughout the individuals' life, with adults doubling their mercury concentrations to juveniles., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Metabolism across all known living systems combines two key features. First, all of the molecules that are required are either available in the environment or can be built up from available resources via other reactions within the system. Second, the reactions proceed in a fast and synchronized fashion via catalysts that are also produced within the system. Building on early work by Stuart Kauffman, a precise mathematical model for describing such self-sustaining autocatalytic systems (RAF theory) has been developed to explore the origins and organization of living systems within a general formal framework. In this paper, we develop this theory further by establishing new relationships between classes of RAFs and related classes of networks, and developing new algorithms to investigate and visualize RAF structures in detail. We illustrate our results by showing how it reveals further details into the structure of archaeal and bacterial metabolism near the origin of life, and provide techniques to study and visualize the core aspects of primitive biochemistry.

Long-term studies of pelagic nekton in the Southern Ocean and their responses to ongoing environmental change are rare. Using stable isotope ratios measured in squid beaks recovered from diet samples of wandering albatrosses Diomedea exulans, we assessed decadal variation (from 1976 to 2016) in the habitat (δ 13 C) and trophic level (δ 15 N) of five important Southern Ocean squid species in relation to indices of environmental conditions-Southern Oscillation Index (SOI) and Southern Annular Mode (SAM). Based on δ 13 C values, corrected for the Suess effect, habitat had changed over the last 50 years for Taonius sp. B (Voss), Gonatus antarcticus, Galiteuthis glacialis and Histioteuthis atlantica but not Moroteuthopsis longimana. By comparison, mean δ 15 N values were similar across decades for all five species, suggesting minimal changes in trophic levels. Both SAM and SOI have increased in strength and frequency over the study period but, of the five species, only in Taonius sp. B (Voss) did these indices correlate with, δ 13 C and δ 15 N values, indicating direct relationships between environmental conditions, habitat and trophic level. The five cephalopod species therefore changed their habitats with changing environmental conditions over the last 50 years but maintained similar trophic levels. Hence, cephalopods are likely to remain important prey for top predators in Southern Ocean food webs, despite ongoing climate change.