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Suprascapular nerve palsy has been frequently reported in athletes, particularly baseball pitchers, volleyball players, and weight lifters, but it is easily overlooked during the evaluation of shoulder pain. Entrapment of the suprascapular nerve is usually suspected only after atrophy is noted. The presence of painless weakness of the external rotator muscles should alert the clinician to the presence of nerve damage, which can be confirmed by electromyography. This case study demonstrates the usefulness of isokinetic testing and magnetic resonance imaging in identifying cystic lesions causing neuropathy among athletes who have failed conservative treatment for shoulder pain. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: A variety of health status questionnaires have been used in physical rehabilitation studies involving women with breast cancer, but the usefulness of these questionnaires as measures of physical, mental, and social well-being has not been firmly established in this population. This study was conducted to assess the convergent and discriminative properties of the RAND 36-Item Health Survey and the Functional Living Index-Cancer (FLIC). SUBJECTS: Both questionnaires were administered concurrently to 110 outpatients treated surgically for breast cancer at a National Cancer Institute-designated Comprehensive Cancer Center. METHODS: Bivariate correlations and a multi-trait-multi-method matrix were used to evaluate convergent validity between summary and subscale scores from both questionnaires. Discriminative validity was assessed by testing for expected differences between women who were treated for breast cancer with and without secondary lymphedema. RESULTS: Correlations between overall quality-of-life scores produced by both questionnaires were modest, indicating that the instruments focus on somewhat different aspects of health-related quality of life. Global quality-of-life and physical well-being scores were lower among women with lymphedema secondary to breast cancer. The FLIC demonstrated greater sensitivity to group differences in emotional well-being. DISCUSSION AND CONCLUSION: The results suggest that neither questionnaire can be replaced by the other in studies of women treated for breast cancer. Both questionnaires were able to distinguish physical functioning deficits in women with lymphedema secondary to breast cancer, but symptom- or treatment-specific measures may be required to assess more subtle difficulties related to the emotional aspects of health and functioning in this population. [ABSTRACT FROM AUTHOR]

This article describes the implementation and outcomes of an intervention to create a healthy workplace in an emergency department. The phases of the intervention are delineated in the process the staff called 'The Creating Our Future Program.' Tangible practice and process improvements are presented from 4 action planning teams for organized patient care, rapid patient disposition, diagnostics, and initiation of care. Outcomes included the elimination of RN vacancies and agency use, and improvements in patient and employee satisfaction, including interaction between staff and with physicians. Staff reported feeling empowered to continuously improve the emergency department. [ABSTRACT FROM AUTHOR]

This research examines the implications of an aging society on the demand for prehospital emergency medical services (EMS). Using a large comprehensive set of population-based EMS utilization data (N = 73874) and population data from the 1990 Census for the City of Dallas, Texas, rates of utilization for eight age groups were computed for total EMS incidents, incidents requiring transport services, and a sub-category of transport services for individuals requiring services for life-threatening conditions. The pattern of utilization associated with age was found to be tri-modal with rates rising geometrically with age for individuals aged 65 and over. Compared to the age group 45 to 64 years of age, rates of utilization for those aged 85 years and older were 3.4 times higher (P < 0.001) for total EMS incidents, 4.5 times higher (P < 0.001) for emergency transports and 5.2 times higher (P < 0.001) for incidents of a life-threatening nature. A broad categorization of all EMS incidents by reason for requiring services indicates that the observed age-associated increase in utilization is due primarily to medical conditions rather than incidents arising from trauma. Finally, gender and racial/ethnic differences in utilization are briefly considered. [ABSTRACT FROM AUTHOR]

Changes in land use, a warming climate and increased drought have amplified wildfire frequency and magnitude globally. Subsequent rainfall in wildfire-scarred watersheds washes ash into aquatic systems, increasing water pH and exposing organisms to environmental alkalinization. In this study, 15 or 20 °C-acclimated Chinook salmon (Oncorhynchus tshawytscha) yearlings were exposed to an environmentally-relevant ash concentration (0.25 % w/v), increasing water pH from ∼8.1 to ∼9.2. Salmon experienced significant disturbance to blood plasma pH (pH e ) and red blood cell intracellular pH (RBC pH i ) within 1 h, but recovered within 24 h. Impacts on plasma ion concentrations were relatively mild, and plasma glucose increased by 2- to 4-fold at both temperatures. Temperature-specific differences were observed: 20 °C salmon recovered their pH e more rapidly, perhaps facilitated by higher basal metabolism and anaerobic metabolic H + production. Additionally, 20 °C salmon experienced dramatically greater spikes in plasma total ammonia, [NH 3 ] and [NH 4 + ] after 1 h of exposure that decreased over time, whereas 15 °C salmon experienced a gradual nitrogenous waste accumulation. Despite pH e and RBC pH i recovery and non-lethal nitrogenous waste levels, we observed 20 % and 33 % mortality in 15 and 20 °C treatments within 12 h of exposure, respectively. The mortalities cannot be explained by high water pH alone, nor was it likely to be singularly attributable to a heavy metal or organic compound released from ash input. This demonstrates post-wildfire ash input can induce lethal yet previously unexplored physiological disturbances in fish, and further highlights the complex interaction with warmer temperatures typical of wildfire-scarred landscapes., Competing Interests: Declaration of competing interest No competing interests declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Industrial pollution is a major driver of ecosystem degradation, but it can also act as a driver of contemporary evolution. As a result of intense mining activity during the Industrial Revolution, several rivers across the southwest of England are polluted with high concentrations of metals. Despite the documented negative impacts of ongoing metal pollution, brown trout (Salmo trutta L.) survive and thrive in many of these metal-impacted rivers. We used population genomics, transcriptomics, and metal burdens to investigate the genomic and transcriptomic signatures of potential metal tolerance. RADseq analysis of six populations (originating from three metal-impacted and three control rivers) revealed strong genetic substructuring between impacted and control populations. We identified selection signatures at 122 loci, including genes related to metal homeostasis and oxidative stress. Trout sampled from metal-impacted rivers exhibited significantly higher tissue concentrations of cadmium, copper, nickel and zinc, which remained elevated after 11 days in metal-free water. After depuration, we used RNAseq to quantify gene expression differences between metal-impacted and control trout, identifying 2042 differentially expressed genes (DEGs) in the gill, and 311 DEGs in the liver. Transcriptomic signatures in the gill were enriched for genes involved in ion transport processes, metal homeostasis, oxidative stress, hypoxia, and response to xenobiotics. Our findings reveal shared genomic and transcriptomic pathways involved in detoxification, oxidative stress responses and ion regulation. Overall, our results demonstrate the diverse effects of metal pollution in shaping both neutral and adaptive genetic variation, whilst also highlighting the potential role of constitutive gene expression in promoting metal tolerance., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Objectives: This large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy., Methods: We queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVIs), herpesvirus, fungal infections and mortality using Cox regression., Results: A total of 2256 patients who received CAR T-cell therapy were included, 1867 (82.7%) were CD19-targeted and 400 (17.7%) were B-cell maturation antigen-targeted. After CAR T-cell infusion, RVIs were the most prevalent (23.3%) with a median onset of 160 days (interquartile range [IQR]: 52-348 days), whereas herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR, 18-252) and 73 days (IQR, 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukaemia (hazard ratio [HR], 1.61), prior haematopoietic cell transplant (HCT; HR, 1.29), cytokine release syndrome (HR, 1.41), hemophagocytic lymphohistiocytosis (HR, 1.96) and glucocorticoids (HR, 3.37). Prior HCT (HR, 2.00), hypogammaglobulinemia (HR, 1.51), immune effector cell-associated neurotoxicity syndrome (HR, 1.52) and hemophagocytic lymphohistiocytosis (HR, 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR, 1.59), cytokine release syndrome (HR, 1.58) and hypogammaglobulinemia (HR, 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR, 0.39 and 0.44, respectively)., Discussion: In a large cohort of CAR T-cell therapy recipients, RVIs were the most common but occurred later, whereas herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aim: To identify the physiological role of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC), in red blood cells (RBC) of the model teleost fish, rainbow trout., Methods: We used: (i) super-resolution microscopy to determine the subcellular location of sAC protein; (ii) live-cell imaging of RBC intracellular pH (pH i ) with specific sAC inhibition (KH7 or LRE1) to determine its role in cellular acid-base regulation; (iii) spectrophotometric measurements of haemoglobin-oxygen (Hb-O 2 ) binding in steady-state conditions; and (iv) during simulated arterial-venous transit, to determine the role of sAC in systemic O 2 transport., Results: Distinct pools of sAC protein were detected in the RBC cytoplasm, at the plasma membrane and within the nucleus. Inhibition of sAC decreased the setpoint for RBC pH i regulation by ~0.25 pH units compared to controls, and slowed the rates of RBC pH i recovery after an acid-base disturbance. RBC pH i recovery was entirely through the anion exchanger (AE) that was in part regulated by HCO 3 - -dependent sAC signaling. Inhibition of sAC decreased Hb-O 2 affinity during a respiratory acidosis compared to controls and reduced the cooperativity of O 2 binding. During in vitro simulations of arterial-venous transit, sAC inhibition decreased the amount of O 2 that is unloaded by ~11%., Conclusion: sAC represents a novel acid-base sensor in the RBCs of rainbow trout, where it participates in the modulation of RBC pH i and blood O 2 transport though the regulation of AE activity. If substantiated in other species, these findings may have broad implications for our understanding of cardiovascular physiology in vertebrates., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Background: Arabian killifish, Aphanius dispar, lives in marine coastal areas of the Middle East, as well as in streams that experience a wide range of salinities and temperatures. It has been used as a mosquito control agent and for studying the toxicities of environmental pollutants. A. dispar's eggshell (chorion) and embryos are highly transparent and are suitable for high resolution microscopic observations, offering excellent visibility of live tissues., Results: In this study, the staging of normal embryonic development of A. dispar was described and investigated at different temperatures. Embryonic development was then examined under different thermal environments from 26 to 34°C. Our data suggest that temperature has a significant effect on embryonic development, with accelerated development at higher temperatures., Conclusion: A. dispar exhibits broad thermal tolerance and extended independent feeding capabilities, making it a promising model organism for toxicology and pathogenesis studies conducted over an extended period of time (12 days post-fertilization)., (© 2024 The Author(s). Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: There are a variety of published standard methods and water chemistry recommendations for zebrafish ( Danio rerio ) husbandry, but empirical evidence for their justification is often lacking, as is information on some variables that have important biological effects on fish. Importantly, these different recommendations could contribute to variability in results and fish welfare between or within institutions., Methods: Here we document the current range of water chemistry used by various research institutions around the world and report initial findings on their effects on the development and growth of zebrafish. Over 40 institutes responded to a survey that revealed a large variation in water chemistry used for zebrafish husbandry including differences in the set-points and acceptable ranges for temperature, pH and conductivity. In subsequent experiments, zebrafish ( D. rerio , WIK) embryos/larvae exposed to a large range of salt concentrations (50μM to 10mM Na + or 30 - 2500 μS/cm) and CO 2 levels (400 - 8,000 μatm)., Results: Larvae exposed to the lowest salt concentration (5 μM Na + or < 30μS/cm) had a slower response to touch and their swim bladders were not inflated. Larvae exposed to 5-100 μM Na + were 5 % shorter in total body length than those exposed to higher salt concentrations (>100 μM Na + ). Zebrafish embryo/larvae exposed to intermediate pCO 2 values (~2000 μatm) were 1 to 3.5% longer than those exposed to either ambient (400 μatm) or higher (4000 μatm) pCO 2 , but pCO 2 did not affect developmental endpoints up to 4 dpf., Conclusions: Overall, we highlight the magnitude of variation in water chemistry used within zebrafish research and provide some empirical evidence to show that not all of these water conditions might be optimal for developing zebrafish and reproducibility of research, although further research is necessary to determine longer-term effects of water chemistry on older larvae, juveniles and adults., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Porteus CS et al.)

The mechanisms that determine the temperature tolerances of fish are poorly understood, creating barriers to disentangle how additional environmental challenges-such as CO 2 -induced aquatic acidification and fluctuating oxygen availability-may exacerbate vulnerability to a warming climate and extreme heat events. Here, we explored whether two acute exposures (~0.5 hours or ~72 hours) to increased CO 2 impact acute temperature tolerance limits in a freshwater fish, rainbow trout ( Oncorhynchus mykiss ). We separated the potential effects of acute high CO 2 exposure on critical thermal maximum (CT max ), caused via either respiratory acidosis (reduced internal pH) or O 2 supply capacity (aerobic scope), by exposing rainbow trout to ~1 kPa CO 2 (~1% or 10 000 μatm) in combination with normoxia or hyperoxia (~21 or 42 kPa O 2 , respectively). In normoxia, acute exposure to high CO 2 caused a large acidosis in trout (blood pH decreased by 0.43 units), while a combination of hyperoxia and ~1 kPa CO 2 increased the aerobic scope of trout by 28%. Despite large changes in blood pH and aerobic scope between treatments, we observed no impacts on the CT max of trout. Our results suggest that the mechanisms that determine the maximum temperature tolerance of trout are independent of blood acid-base balance or the capacity to deliver O 2 to tissues., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press and the Society for Experimental Biology.)

The physiological processes underlying the post-prandial rise in metabolic rate, most commonly known as the 'specific dynamic action' (SDA), remain debated and controversial. This Commentary examines the SDA response from two opposing hypotheses: (i) the classic interpretation, where the SDA represents the energy cost of digestion, versus (ii) the alternative view that much of the SDA represents the energy cost of growth. The traditional viewpoint implies that individuals with a reduced SDA should grow faster given the same caloric intake, but experimental evidence for this effect remains scarce and inconclusive. Alternatively, we suggest that the SDA reflects an organism's efficacy in allocating the ingested food to growth, emphasising the role of post-absorptive processes, particularly protein synthesis. Although both viewpoints recognise the trade-offs in energy allocation and the dynamic nature of energy distribution among physiological processes, we argue that equating the SDA with 'the energy cost of digestion' oversimplifies the complexities of energy use in relation to the SDA and growth. In many instances, a reduced SDA may reflect diminished nutrient absorption (e.g. due to lower digestive efficiency) rather than increased 'free' energy available for somatic growth. Considering these perspectives, we summarise evidence both for and against the opposing hypotheses with a focus on ectothermic vertebrates. We conclude by presenting a number of future directions for experiments that may clarify what the SDA is, and what it is not., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

This keynote lecture and corresponding presentation discuss the anatomy and pathophysiology surrounding spinal cord injury in aortic surgery. This article will discuss risk factors and mechanisms for spinal cord injury, including loss of direct and collateral spinal cord perfusion and ischemia-reperfusion injury. This review will examine these elements in both the laboratory and clinical setting, in addition to other neuroprotective strategies applied in clinical practice. Addressing spinal cord injury requires an integrated and considerate approach to simultaneously optimize spinal cord blood flow, promote collateralization and improve ischemic tolerance. Given the catastrophic clinical consequences for both the patient and their caregivers, continuing to investigate and examine spinal cord injury is of the utmost importance., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2023 Annals of Cardiothoracic Surgery. All rights reserved.)

Anthropogenic pressures are restructuring coral reefs globally. Sound predictions of the expected changes in key reef functions require adequate knowledge of their drivers. Here we investigate the determinants of a poorly-studied yet relevant biogeochemical function sustained by marine bony fishes: the excretion of intestinal carbonates. Compiling carbonate excretion rates and mineralogical composition from 382 individual coral reef fishes (85 species and 35 families), we identify the environmental factors and fish traits that predict them. We find that body mass and relative intestinal length (RIL) are the strongest predictors of carbonate excretion. Larger fishes and those with longer intestines excrete disproportionately less carbonate per unit mass than smaller fishes and those with shorter intestines. The mineralogical composition of excreted carbonates is highly conserved within families, but also controlled by RIL and temperature. These results fundamentally advance our understanding of the role of fishes in inorganic carbon cycling and how this contribution will change as community composition shifts under increasing anthropogenic pressures., (© 2023. The Author(s).)

Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest. All authors read and approved the final manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gaining meaningful blood samples from water-breathing fish is a significant challenge. Two main methods typically used are grab 'n' stab and surgical cannulation. Both methods have benefits, but also significant limitations under various scenarios. Here we present a method of blood sampling laboratory fish involving gradual induction of anaesthesia within their home tank, avoiding physical struggling associated with capture, followed by rapid transfer to a gill irrigation system to maintain artificial ventilation via adequate gill water flow and then followed by sampling the caudal vasculature. This method negates many blood chemistry disturbances associated with grab 'n' stab (i.e., low pH and oxygen, elevated lactate, CO 2 and stress hormones) and generates results that are directly comparable to cannulated fish under a wide range of experimentally-induced acid-base scenarios (acidosis and alkalosis). Crucially this method was successful in achieving accurate acid-base blood measurements from fish ten times smaller than are typically suitable for cannulation. This opens opportunities not previously possible for studies that relate to basic physiology, sustainable aquaculture, ecotoxicology, conservation, and climate change., (© 2023. The Author(s).)

Predatory fish in the wild consume whole prey including hard skeletal parts like shell and bone. Shell and bone are made up of the buffering minerals calcium carbonate (CaCO 3 ) and calcium phosphate (Ca 3 (PO 4 ) 2 ). These minerals resist changes in pH, meaning they could have physiological consequences for gastric acidity, digestion and metabolism in fish. Using isocaloric diets supplemented with either CaCO 3 , Ca 3 (PO 4 ) 2 or CaCl 2 as non-buffering control, we investigated the impacts of dietary buffering on the energetic cost of digestion (i.e. specific dynamic action or SDA), gastric pH, the postprandial blood alkalosis (the "alkaline tide") and growth in juvenile rainbow trout (Oncorhynchus mykiss). Increases in dietary buffering were significantly associated with increased stomach chyme pH, postprandial blood HCO 3 - , net base excretion, the total SDA and peak SDA but did not influence growth efficiency in a 21 day trial. This result shows that aspects of a meal that have no nutritional value can influence the physiological and energetic costs associated with digestion in fish, but that a reduction in the SDA will not always lead to improvements in growth efficiency. We discuss the broader implications of these findings for the gastrointestinal physiology of fishes, trade-offs in prey choice in the wild, anthropogenic warming and feed formulation in aquaculture., (© 2022. The Author(s).)

Extending the potential of precision dosing requires evaluating methodologies offering more flexibility and higher degree of personalization. Reinforcement learning (RL) holds promise in its ability to integrate multidimensional data in an adaptive process built toward efficient decision making centered on sustainable value creation. For general anesthesia in intensive care units, RL is applied and automatically adjusts dosing through monitoring of patient's consciousness. We further explore the problem of optimal control of anesthesia with propofol by combining RL with state-of-the-art tools used to inform dosing in drug development. In particular, we used pharmacokinetic-pharmacodynamic (PK-PD) modeling as a simulation engine to generate experience from dosing scenarios, which cannot be tested experimentally. Through simulations, we show that, when learning from retrospective trial data, more than 100 patients are needed to reach an accuracy within the range of what is achieved with a standard dosing solution. However, embedding a model of drug effect within the RL algorithm improves accuracy by reducing errors to target by 90% through learning to take dosing actions maximizing long-term benefit. Data residual variability impacts accuracy while the algorithm efficiently coped with up to 50% interindividual variability in the PK and 25% in the PD model's parameters. We illustrate how extending the state definition of the RL agent with meaningful variables is key to achieve high accuracy of optimal dosing policy. These results suggest that RL constitutes an attractive approach for precision dosing when rich data are available or when complemented with synthetic data from model-based tools used in model-informed drug development., (© 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Peripheral artery disease (PAD) commonly refers to atherosclerotic narrowing of noncoronary arteries, primarily those supplying the lower extremities. The risk factors for PAD include smoking, hyperlipidemia, hypertension, and diabetes mellitus. Patients with PAD are at a heightened risk of major adverse cardiovascular events (including myocardial infarction, stroke, and cardiovascular death) and major adverse limb events (including progressive symptoms or limb ischemia requiring peripheral revascularization, amputation, and acute limb ischemia), highlighting the need for guideline-directed therapies. Lifestyle modifications and medical therapies are utilized to improve function and outcomes in this patient population. Adherence to a healthy diet and smoking cessation are both associated with better outcomes in patients with PAD. Medical therapies targeting axes of risk, including lipid-modifying therapies, antithrombotic therapies, and targeted diabetes therapies, are available to reduce this risk in patients with PAD; however, significant residual risk remains. Unfortunately, despite guideline recommendations and efforts at education, even available medical therapies remain underutilized in patients with PAD. Continued development of novel therapies and efforts to improve the provision of care in patients with PAD are needed., (© 2022 The Author(s).)

Aerobic metabolism generates 15-20 times more energy (ATP) than anaerobic metabolism, which is crucial in maintaining energy budgets in animals, fueling metabolism, activity, growth and reproduction. For ectothermic water-breathers such as fishes, low dissolved oxygen may limit oxygen uptake and hence aerobic metabolism. Here, we assess, within a phylogenetic context, how abiotic and biotic drivers explain the variation in hypoxia tolerance observed in fishes. To do so, we assembled a database of hypoxia tolerance, measured as critical oxygen tensions (P crit ) for 195 fish species. Overall, we found that hypoxia tolerance has a clear phylogenetic signal and is further modulated by temperature, body mass, cell size, salinity and metabolic rate. Marine fishes were more susceptible to hypoxia than freshwater fishes. This pattern is consistent with greater fluctuations in oxygen and temperature in freshwater habitats. Fishes with higher oxygen requirements (e.g. a high metabolic rate relative to body mass) also were more susceptible to hypoxia. We also found evidence that hypoxia and warming can act synergistically, as hypoxia tolerance was generally lower in warmer waters. However, we found significant interactions between temperature and the body and cell size of a fish. Constraints in oxygen uptake related to cellular surface area to volume ratios and effects of viscosity on the thickness of the boundary layers enveloping the gills could explain these thermal dependencies. The lower hypoxia tolerance in warmer waters was particularly pronounced for fishes with larger bodies and larger cell sizes. Previous studies have found a wide diversity in the direction and strength of relationships between P crit and body mass. By including interactions with temperature, our study may help resolve these divergent findings, explaining the size dependency of hypoxia tolerance in fish., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Parkinson's disease (PD) is an ageing disorder caused by dopaminergic neuron depletion with age. Growing research in the field of metabolomics is expected to play a major role in PD diagnosis, prognosis and therapeutic development. In this study, we looked at how SNCA and GBA1 gene mutations, as well as metabolomic abnormalities of kynurenine and cholesterol metabolites, were linked to alpha-synuclein (α-syn) and clinical characteristics in three different PD age groups. In all three age groups, a metabolomics analysis revealed an increased amount of 27-hydroxycholesterol (27-OHC) and a lower level of kynurenic acid (KYNA). The effect of 27-OHC on SNCA and GBA1 modifications was shown to be significant (P < 0.05) only in the A53T variant of the SNCA gene in late-onset and early-onset PD groups, whereas GBA1 variants were not. Based on the findings, we observed that the increase in 27-OHC would have elevated α-syn expression, which triggered the changes in the SNCA gene but not in the GBA1 gene. Missense variations in the SNCA and GBA1 genes were investigated using the sequencing technique. SNCA mutation A53T has been linked to increased PD symptoms, but there is no phenotypic link between GBA1 and PD. As a result of the data, we hypothesise that cholesterol and kynurenine metabolites play an important role in PD, with the metabolite 27-OHC potentially serving as a PD biomarker. These findings will aid in the investigation of pathogenic causes as well as the development of therapeutic and preventative measures for PD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described., Methods: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial., Results: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks., Conclusion: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

Feeding and digestion are metabolically demanding causing a rise on metabolic rate called Specific Dynamic Action (SDA). Although SDA has been vastly reported in fish, its potential consequences on the oxidative-antioxidant balance has not been evaluated to date in fish, a model with a long alkaline tide associated with feeding as well. Using rainbow trout (Oncorhynchus mykiss) as a model species, the aims of the present study were to: (1) assess potential oxidative damages and changes in oxidative defences after feeding on a single meal, and (2) identify the timescale of such changes over a 96 h post-feeding period. Oxidative damage in proteins and lipids and the activities of four enzymatic antioxidant defences: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were measured in gill, stomach, intestine and liver. DNA damage was measured in red blood cells. Fish were sampled before and after 1.5, 6, 24, 48, 72 and 96 h of ingestion of a 3% body mass ration. Trends of post-prandial damage were present in all tissues, but only protein oxidation varied significatively during digestion in the stomach. The intestine and stomach presented the highest enzymatic activities, likely due to the high metabolic action that these tissues have during digestion, with peaks during post-feeding: at 24 h of SOD in stomach and at 48 h of CAT in intestine. Observed GPx peaks during post-feeding in gills are likely due to the exacerbated demands for ion fluxes and/or oxygen during feeding. The differential response of the antioxidant system observed in tissues of rainbow trout during digestion indicates a coordinated and tissue-specific antioxidant defence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2 and 1 kPa CO2 (2000-10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate for the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 min, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 h, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3- in blood, which increased from ∼4 to ∼22 mmol l-1. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3- and pH, probably because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Alzheimer's disease (AD) is one of the most common forms of dementia contributing to more than 70% of the cases. The factors accounting for the cause and progression of neurodegenerative diseases like AD are primarily genetic, in addition to life style and environmental factors. Early and accurate diagnoses of AD empower practitioners to take timely clinical decisions and preventive actions. This being the motivation, the work proposes a novel pattern matching and scoring method on genetic material towards devising an effective classifier. We propose a distinctive disease causing gene sequence pattern identification using suffix trees as a base detection model with an accuracy of 91.5% in linear time complexity. A scoring mechanism is implemented to assign scores to genes based on the severity of the disease causing and disease resistant Single Nucleotide Polymorphisms associated with the genes. These scores are then used as a remarkable feature in the gradient boosted decision tree classifier to enhance the classification of AD versus healthy control. The efficiency of the proposed gene powered EGBDT classifier is evaluated on ADNI benchmark data set with the prediction accuracy of 94.16% and is found to be efficient compared to the recent works in the literature.

Acute aortic syndromes represent a spectrum of life-threatening aortic pathologies. Prompt diagnosis and proper management of these syndromes are important in reducing overall mortality and morbidity, which remains high. Acute aortic dissections represent most of these aortic wall pathologies, but intramural haematomas and penetrating atherosclerotic ulcers have been increasingly diagnosed. Type A dissections require prompt surgical treatment, with endovascular options on the horizon. Type B dissections can be complicated or uncomplicated, and treatment is determined based on this designation. Complicated Type B dissections require prompt repair with thoracic endovascular aortic repair (TEVAR) becoming the preferred method. Uncomplicated Type B dissections require medical management, but early TEVAR in the subacute setting is becoming more prominent. Proper surveillance for an uncomplicated Type B dissection is crucial in detecting aortic degeneration and need for intervention. Intramural haematomas and penetrating atherosclerotic ulcers are managed similarly to aortic dissections, but more research is needed to determine the proper management algorithms. Multi-disciplinary aortic programmes have been shown to improve patient outcomes and are necessary in optimizing long-term follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: The community outreach program is one of the main activities of the University of Rwanda, and both staff and students get involved in this tremendous initiative to serve the community free of charge., Purpose: The main objectives of this community engagement activity were to raise awareness of medical imaging services and abdominal ultrasound screening., Methods: The project proposal was planned by the Medical Imaging Department, University of Rwanda College of Medicine and Health Sciences, Remera Campus. It took place at Kigali's main car park. Two ultrasound machines were used, and screening was done by students under supervision of registered sonographers. A cross-sectional design with random sampling was employed, and SPSS version 21 was used for data analysis. Statistical techniques were used to calculate inter-observer reliability by comparing patient complaints and sonographic diagnosis., Results: Herein we report the first medical imaging community outreach, on which 86 patients received ultrasound abdominal scans free of charge. Of these, 33 (38.5%) were male and 53 (61.5%) were female. Their ages varied from 20 to 76 years, with a mean age of 48. The screened organs included the liver, gall bladder, pancreas, spleen, kidneys, urinary bladder, prostate, uterus and ovaries, and abnormalities were identified in different organs. The results showed a high degree of reliability between what was presented by the patients and measurements found after diagnosis by the sonographer. The average measure of the intraclass correlation coefficient was 0.973, with 95% confidence intervals ranging from 0.959 to 0.983 (F (85,85) = 37.537, p < 0.001)., Conclusion: This experience was beneficial to the Medical Imaging Sciences Department staff and students, as well as to the Society of Medical Imaging and Radiation in Rwanda. The results showed that this outreach was also very positive for the community at large., (© 2020. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Coral reef fish perform numerous important functional roles on coral reefs. Of these, carbonate sediment production, as a by-product of parrotfish feeding, is especially important for contributing to reef framework construction and reef-associated landform development. However, only limited data exist on: (i) how production rates vary among reef habitats as a function of parrotfish assemblages, (ii) the relative importance of sediment produced from eroded, reworked, and endogenous sources, or (iii) the size fractions of sediment generated by different parrotfish species and size classes. These parameters influence not only overall reef-derived sediment supply, but also influence the transport potential and depositional fate of this sedimentary material. Here, we show that parrotfish sediment production varies significantly between reef-platform habitats on an atoll-margin Maldivian reef. Highest rates of production (over 0.8 kg m -2  year -1 ) were calculated in three of the eight platform habitats; a rubble-dominated zone, an Acropora spp. dominated zone, and a patch reef zone. Habitat spatial extent and differences in associated parrotfish assemblages strongly influenced the total quantities of sediment generated within each habitat. Nearly half of total parrotfish sediment production occurred in the rubble habitat, which comprised only 8% of the total platform area. Over 90% of this sedimentary material originated from eroded reef framework as opposed to being reworked existing or endogenously produced sediment, and comprised predominantly coral sands (predominantly 125-1000 µm in diameter). This is comparable to the dominant sand types and size fractions found on Maldivian reef islands. By contrast, nearly half of the sediment egested by parrotfish in the Acropora spp. dominated and patch reef habitats resulted from reworked existing sediments. These differences between habitats are a result of the different parrotfish assemblages supported. Endogenous carbonate production was found to be insignificant compared to the quantity of eroded and reworked material. Our findings have important implications for identifying key habitats and species which act as major sources of sediment for reef-island systems., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Conjugated molecular chains have the potential to act as "molecular wires" that can be employed in a variety of technologies, including catalysis, molecular electronics, and quantum information technologies. Their successful application relies on a detailed understanding of the factors governing the electronic energy landscape and the dynamics of electrons in such molecules. We can gain insights into the energetics and dynamics of charges in conjugated molecules using time-resolved infrared (TRIR) detection combined with pulse radiolysis. Nitrile ν (C[triple bond, length as m-dash]N) bands can act as IR probes for charges, based on IR frequency shifts, because of their exquisite sensitivity to the degree of electron delocalization and induced electric field. Here, we show that the IR intensity and linewidth can also provide unique and complementary information on the nature of charges. Quantifications of IR intensity and linewidth in a series of nitrile-functionalized oligophenylenes reveal that the C[triple bond, length as m-dash]N vibration is coupled to the nuclear and electronic structural changes, which become more prominent when an excess charge is present. We synthesized a new series of ladder-type oligophenylenes that possess planar aromatic structures, as revealed by X-ray crystallography. Using these, we demonstrate that C[triple bond, length as m-dash]N vibrations can report charge fluctuations associated with nuclear movements, namely those driven by motions of flexible dihedral angles. This happens only when a charge has room to fluctuate in space., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chemical pollution is one of the major threats to global freshwater biodiversity and will be exacerbated through changes in temperature and rainfall patterns, acid-base chemistry, and reduced freshwater availability due to climate change. In this review we show how physico-chemical features of natural fresh waters, including pH, temperature, oxygen, carbon dioxide, divalent cations, anions, carbonate alkalinity, salinity and dissolved organic matter, can affect the environmental risk to aquatic wildlife of pollutant chemicals. We evidence how these features of freshwater physico-chemistry directly and/or indirectly affect the solubility, speciation, bioavailability and uptake of chemicals [including via alterations in the trans-epithelial electric potential (TEP) across the gills or skin] as well as the internal physiology/biochemistry of the organisms, and hence ultimately toxicity. We also show how toxicity can vary with species and ontogeny. We use a new database of global freshwater chemistry (GLORICH) to demonstrate the huge variability (often >1000-fold) for these physico-chemical variables in natural fresh waters, and hence their importance to ecotoxicology. We emphasise that a better understanding of chemical toxicity and more accurate environmental risk assessment requires greater consideration of the natural water physico-chemistry in which the organisms we seek to protect live., (© 2021 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Arabinose is a major plant aldopentose in the form of arabinans complexed in cell wall polysaccharides or glycoproteins (AGP), but comparatively rare as a monosaccharide. l-arabinose is an important bacterial metabolite, accessed by pectolytic micro-organisms such as Pectobacterium atrosepticum via pectin and hemicellulose degrading enzymes. However, not all plant-associated microbes encode cell-wall-degrading enzymes, yet can metabolize l-arabinose, raising questions about their use of and access to the glycan in plants. Therefore, we examined l-arabinose metabolism in the food-borne pathogen Escherichia coli O157:H7 (isolate Sakai) during its colonization of plants. l-arabinose metabolism ( araBA ) and transport ( araF ) genes were activated at 18 °C in vitro by l-arabinose and expressed over prolonged periods in planta . Although deletion of araBAD did not impact the colonization ability of E. coli O157:H7 (Sakai) on spinach and lettuce plants (both associated with STEC outbreaks), araA was induced on exposure to spinach cell-wall polysaccharides. Furthermore, debranched and arabinan oligosaccharides induced ara metabolism gene expression in vitro , and stimulated modest proliferation, while immobilized pectin did not. Thus, E. coli O157:H7 (Sakai) can utilize pectin/AGP-derived l-arabinose as a metabolite. Furthermore, it differs fundamentally in ara gene organization, transport and regulation from the related pectinolytic species P. atrosepticum , reflective of distinct plant-associated lifestyles.

Parkinson's disease (PD) is a neurodegenerative disease with multifactorial aetiology that influences the quality of life. However, the association of possible factors with PD is need to be investigated in Indian population, hence we aimed to determine the association of lifestyle, environmental factors, biochemical parameters and genetic insights of MT-ND1 gene in PD patients. Using a standardised questionnaire, PD patients and control group of about 146 subjects were interviewed on demographic, lifestyle and environmental factors. The subjects includes n = 73 Parkinson's patients [juvenile (n = 4); early-onset (n = 8); late-onset (n = 61)] with equal number of age and sex matched controls, further we had obtained institutional ethical clearance and informed consent from study participants. Biomarker investigations and MT-ND1 alterations were investigated by appropriate molecular techniques. During the average follow-up years of 5.1, significant association was observed among smoking, alcohol, caffeinated drinks, surgery, pesticide exposure at p < 0.05 in varied PD age groups. Occupational exposure to agriculture and industry showed an increased risk among the late-onset group. The biomarkers uric acid (UA) and dopamine (DA) were significant at p < 0.05 in all the three PD age groups. The MT-ND1 alteration with A3843 G variant was significant at p < 0.05 for AG allele in all the three PD groups but the highest prevalence was observed in late-onset group. From our study, smoking, alcohol, caffeinated drinks, occupational influence of agriculture and industry and pesticide exposure had more association with PD occurrence. Hence, to the best of our knowledge, this is the first kind of study in Tamil Nadu population, India to validate the various factors with PD. Therefore we suggest that further research is mandatory to detect other possible associations among PD, using comprehensive larger sample size., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival., Method: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon, Spain and the United States, to assess the duration of IV therapy and appropriate time to step-down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down., Results: Candida albicans contributed to 45% of bloodstream infection versus 55% of infection caused by Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU, whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. Forty-five patients were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step-down was 5 days. Patients who had a stepdown had more favorable outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1-4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75)., Conclusion: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step-down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections., Competing Interests: Competing interests: Dr. Ray Hachem serves on the board of Worldwide Institute for Medical Education (WIME). Dr. Issam Raad gave a talk in 2020 in CME conference sponsored by Pfizer.

Soluble adenylyl cyclase (sAC) is a HC O 3   - -stimulated enzyme that produces the ubiquitous signalling molecule cAMP, and deemed an evolutionarily conserved acid-base sensor. However, its presence is not yet confirmed in bony fishes, the most abundant and diverse of vertebrates. Here, we identified sAC genes in various cartilaginous, ray-finned and lobe-finned fish species. Next, we focused on rainbow trout sAC (rtsAC) and identified 20 potential alternative spliced mRNAs coding for protein isoforms ranging in size from 28 to 186 kDa. Biochemical and kinetic analyses on purified recombinant rtsAC protein determined stimulation by HC O 3   - at physiologically relevant levels for fish internal fluids (EC 50 ∼ 7 mM). rtsAC activity was sensitive to KH7, LRE1, and DIDS (established inhibitors of sAC from other organisms), and insensitive to forskolin and 2,5-dideoxyadenosine (modulators of transmembrane adenylyl cyclases). Western blot and immunocytochemistry revealed high rtsAC expression in gill ion-transporting cells, hepatocytes, red blood cells, myocytes and cardiomyocytes. Analyses in the cell line RTgill-W1 suggested that some of the longer rtsAC isoforms may be preferentially localized in the nucleus, the Golgi apparatus and podosomes. These results indicate that sAC is poised to mediate multiple acid-base homeostatic responses in bony fishes, and provide cues about potential novel functions in mammals., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Competing Interests: Competing interests: None declared.

Context: Osteopathic manipulative treatment (OMT) and mindfulness-based interventions are both efficacious pain management strategies. Combining these two therapeutic approaches may offer added benefits to pain patients., Objectives: To determine whether engaging in a mindfulness-based intervention before an OMT session improved OMT session outcomes., Methods: Patients seeking OMT care from a single osteopathic physician at an integrative health clinic were recruited for this pilot randomized, controlled trial at an academic hospital. All patients scheduled for osteopathic structural evaluation and treatment with the provider from March 2019 to September 2019 were eligible and invited to participate during the reminder call before their visit. Participants were randomly assigned to listen to one of two audio recordings matched for length: (1) the history of osteopathic medicine, or (2) a guided mindfulness meditation practice. Patients completed surveys including numeric rating scales to measure mindfulness and embodied safety (a self-reported feeling that the patient's body was in a safe place) immediately before and after listening to the audio recording. A global pain rating report along with a sensation manikin (a digital human figure silhouette overlaid with a grid of 786 "sensation" pixels) capturing both pleasant and unpleasant sensation were collected before and after the OMT session. Session satisfaction was also assessed with a single survey item., Results: A total of 57 participants were enrolled in the study; however, 18 were unable to listen to the full audio recording and were excluded from further analysis. The final study sample consisted of 39 patients, with 19 (48.7%) randomized to the history audio recording and 20 (51.3%) randomized to the mindfulness recording. The mean age of patients was 57 years (standard deviation, 11.75 years); 25 (64.1%) were women and 14 (35.9%) were men. The most common primary pain location was the neck (16; 41.0%), followed by back (12; 30.8%) and joint (5; 12.8%). Twenty (51.3%) participants were cancer patients; 19 (48.8%) did not have a cancer diagnosis. Practicing mindfulness before OMT increased patients' sense of mindful connection to (p=0.036) and safety within (p=0.026) their bodies as well as their overall session satisfaction (p=0.037). Additionally, OMT paired with either study condition (mindfulness vs. history) decreased pain (p<0.001) and increased the ratio of pleasant to unpleasant sensations reported by patients (p<0.001). Finally, regardless of experimental condition (mindfulness vs. history), increased safety within the body predicted greater pain relief ( β =-0.33, p=0.035) and larger sensation ratio changes ( β =0.37, p=0.030) at the OMT session's end. Additionally, increased mindful connection to the body predicted less pain ( β =-0.41, p=0.005) at the session's end., Conclusions: This study demonstrated the feasibility of integrating a mindfulness-based intervention with OMT and results suggest that having patients listen to an audio-guided mindfulness practice while waiting for their OMT session may increase their mindful connection to and safety within their bodies as well as their session satisfaction. This study also provides empirical evidence that OMT may increase the distribution of pleasant sensations reported by pain patients while decreasing the distribution of unpleasant sensations reported., (© 2020 Adam W. Hanley et al., published by De Gruyter, Berlin/Boston.)

Global ocean pCO 2 is increasing as a result of anthropogenic CO 2 emissions, driving a decline in seawater pH. However, coastal waters already undergo fluctuations in pCO 2 /pH conditions over far shorter timescales, with values regularly exceeding those predicted for the open ocean by the year 2100. The speciation of copper, and therefore its potential toxicity, is affected by changing seawater pH, yet little is known concerning how present-day natural fluctuations in seawater pH affect copper toxicity to marine biota. Here, we test the hypothesis that a fluctuating seawater pCO 2 /pH regime will alter the responses of the mussel Mytilus edulis and the ragworm Alitta virens to sub-lethal copper, compared to a static seawater pCO 2 /pH scenario. Mussels and worms were exposed to 0.1 and 0.25 μM copper respectively, concentrations determined to produce comparable toxicity responses in these species, for two weeks under a fluctuating 12-hour pCO 2 /pH cycle (pH 8.14-7.53, pCO 2 445-1747 μatm) or a static pH 8.14 (pCO 2 432 μatm) treatment. Mussels underwent a haemolymph acidosis of 0.1-0.2 pH units in the fluctuating treatments, alongside two-fold increases in the superoxide dismutase activity and DNA damage induced by copper, compared to those induced by copper under static pH conditions. Conversely, ragworms experienced an alkalosis of 0.3 pH units under fluctuating pH/pCO 2 , driven by a two-fold increase in coelomic fluid bicarbonate. This mitigated the copper-induced oxidative stress to slightly reduce both antioxidant activity and DNA damage, relative to the static pH + copper treatment. These opposing responses suggest that differences in species acid-base physiology were more important in determining toxicity responses than the pH-induced speciation change. With variability in seawater chemistry predicted to increase as climate change progresses, understanding how fluctuating conditions interact with the toxicity of pH-sensitive contaminants will become more crucial in predicting their risk to coastal biota., 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 © 2020 Elsevier B.V. All rights reserved.)