The mechanistic basis and adaptive significance of cross-tolerance: a 'pre-adaptation' to a changing world?

Protective responses are pivotal in aiding organismal persistence in complex, multi-stressor environments. Multiple-stressor research has traditionally focused on the deleterious effects of exposure to concurrent stressors. However, encountering one stressor can sometimes confer heightened tolerance to a second stressor, a phenomenon termed 'cross-protection'. Cross-protection has been documented in a wide diversity of taxa (spanning the bacteria, fungi, plant and animal kingdoms) and habitats (intertidal, freshwater, rainforests and polar zones) in response to many stressors (e.g. hypoxia, predation, desiccation, pathogens, crowding, salinity, food limitation). Remarkably, cross-protection benefits have also been shown among emerging, anthropogenic stressors, such as heatwaves and microplastics. In this Commentary, we discuss the mechanistic basis and adaptive significance of cross-protection, and put forth the idea that cross-protection will act as a 'pre-adaptation' to a changing world. We highlight the critical role that experimental biology has played in disentangling stressor interactions and provide advice for enhancing the ecological realism of laboratory studies. Moving forward, research will benefit from a greater focus on quantifying the longevity of cross-protection responses and the costs associated with this protective response. This approach will enable us to make robust predictions of species' responses to complex environments, without making the erroneous assumption that all stress is deleterious.

Fire and rain: A systematic review of the impacts of wildfire and associated runoff on aquatic fauna.

Climate and land-use changes are expected to increase the future occurrence of wildfires, with potentially devastating consequences for freshwater species and ecosystems. Wildfires that burn in close proximity to freshwater systems can significantly alter the physicochemical properties of water. Following wildfires and heavy rain, freshwater species must contend with complex combinations of wildfire ash components (nutrients, polycyclic aromatic hydrocarbons, and metals), altered light and thermal regimes, and periods of low oxygen that together can lead to mass mortality events. However, the responses of aquatic fauna to wildfire disturbances are poorly understood. Here we provide a systematic review of available evidence on how aquatic animals respond to and recover from wildfire disturbance. Two databases (Web of Science and Scopus) were used to identify key literature. A total of 83 studies from across 11 countries were identified to have assessed the risk of wildfires on aquatic animals. We provide a summary of the main ecosystem-level changes associated with wildfires and the main responses of aquatic fauna to such disturbances. We pay special focus to physiological tools and biomarkers used to assess how wildfires impact aquatic animals. We conclude by providing an overview of how physiological biomarkers can further our understanding of wildfire-related impacts on aquatic fauna, and how different physiological tools can be incorporated into management and conservation plans and serve as early warning signs of wildfire disturbances.

Se espera que el cambio climático y el cambio en el uso de suelo aumentaran la ocurrencia de incendios forestales, con consecuencias potencialmente devastadoras para las especies de agua dulce y los ecosistemas. Los incendios forestales que arden cerca de los sistemas de agua dulce pueden alterar significativamente las propiedades fisicoquímicas del agua. Después de los incendios forestales y llueves fuertes, las especies de agua dulce lidian con combinaciones complejas de componentes de cenizas de incendios forestales (nutrientes, sedimentos, hidrocarburos aromáticos policíclicos y metales), regímenes de luz y térmicos alterados y períodos de bajo oxígeno que, en conjunto, pueden conducir a eventos de mortalidad masiva. Sin embargo, las respuestas de la fauna acuática a las perturbaciones de los incendios forestales son poco conocidas. Aquí proporcionamos una revisión sistemática de la evidencia disponible sobre cómo los animales acuáticos responden y se recuperan de la perturbación de los incendios forestales. Se utilizaron dos bases de datos (Web of Science y Scopus) para identificar la literatura clave. Se identificaron un total de 83 estudios de 11 países que habían evaluado el riesgo de incendios forestales en animales acuáticos. Proporcionamos un resumen de los principales cambios a nivel de ecosistema asociados con los incendios forestales y las principales respuestas de la fauna acuática a tales perturbaciones. Prestamos especial atención a las herramientas fisiológicas y los biomarcadores que se utilizan para evaluar cómo los incendios forestales afectan a los animales acuáticos. Concluimos proporcionando una descripción general de cómo los biomarcadores fisiológicos pueden mejorar nuestra comprensión de los impactos relacionados con los incendios forestales en la fauna acuática, y cómo se pueden incorporar diferentes herramientas fisiológicas en los planes de gestión y conservación y servir como señales de alerta temprana de las perturbaciones de los incendios forestales.

Exercise training does not affect heat tolerance in Chinook salmon (Oncorhynchus tshawytscha).

The progression of climate warming will expose ectotherms to transient heatwave events and temperatures above their tolerance range at increased frequencies. It is therefore pivotal that we understand species' physiological limits and the capacity for various controls to plastically alter these thresholds. Exercise training could have beneficial impacts on organismal heat tolerance through improvements in cardio-respiratory capacity, but this remains unexplored. Using juvenile Chinook salmon (Oncorhynchus tshawytscha), we tested the hypothesis that exercise training improves heat tolerance through enhancements in oxygen-carrying capacity. Fish were trained once daily at 60% of their maximum sustainable swim speed, UCRIT, for 60 min. Tolerance to acute warming was assessed following three weeks of exercise training, measured as the critical thermal maximum (CTMAX). CTMAX measurements were coupled with examinations of the oxygen carrying capacity (haematocrit, haemoglobin concentration, relative ventricle size, and relative splenic mass) as critical components of the oxygen transport cascade in fish. Contrary to our hypothesis, we found that exercise training did not raise the CTMAX of juvenile Chinook salmon with a mean CTMAX increase of just 0.35 °C compared to unexercised control fish. Training also failed to improve the oxygen carrying capacity of fish. Exercise training remains a novel strategy against acute warming that requires substantial fine-tuning before it can be applied to the management of commercial and wild fishes.

Stress history affects heat tolerance in an aquatic ectotherm (Chinook salmon, Oncorhynchus tshawytscha).

The stress history of an ectotherm may be a pivotal predictor of how they cope with rapid spikes in environmental temperature. An understanding of how stressors in habitats and commercial operations affect ectotherm heat tolerance is urgently required so that management actions can be informed by thermal physiology. We hypothesised that brief exposure to mild stress would heighten tolerance to subsequent heat stress, indicative of a cross-tolerance interaction, whereas exposure to severe stress would reduce heat tolerance, reflecting a cross-susceptibility interaction. To test this hypothesis, we assessed how three acute stressors (salinity shock [10 or 33 ppt for 2 h]), air exposure (1 or 5 min) and crowding [95.6 kg m-3 for 2 h]), commonly experienced by fish, affected the heat tolerance (measured as critical thermal maximum, CTMAX) in juvenile Chinook salmon (Oncorhynchus tshawytscha). Fish were exposed to one of the three stressors and left for 24 h of recovery prior to measuring CTMAX. Heat tolerance was improved by ∼0.6 °C in fish exposed to salinity shock (10 ppt) and air exposure (5 min) compared to unstressed controls, demonstrating cross-tolerance. However, the development of cross-tolerance was non-linear with stressor severity, and crowding stress had no effect on CTMAX. Together these results show that some forms of stress can heighten acute heat tolerance in ectotherms, but the development of cross-tolerance is highly specific to both stressor type and stressor severity.

Type III Kounis Syndrome Secondary to Ciprofloxacin-Induced Hypersensitivity.

Kounis syndrome (KS) is a rare syndrome characterized by the co-occurrence of acute coronary syndromes in the setting of mast cell and platelet activation in response to hypersensitivity reactions. It can be manifested as coronary vasospasms, acute myocardial infarction, or stent thrombosis triggered by drugs, vaccines, foods, coronary stents, and insect bites. It is a life-threatening condition that needs to be adequately recognized for early diagnosis and appropriate treatment. In this case report, we present a 71-year-old patient with a history of arterial hypertension and non-ST elevation myocardial infarction six months earlier that was treated percutaneously with angioplasty plus stent implantation in the circumflex artery, who subsequently presented to the emergency department due to generalized itching associated with tongue swelling, dyspnea, and chest pain after ingestion of ciprofloxacin for the treatment of a urogenital infection. An electrocardiogram showed ST elevation in II, III, and aVF leads, and positive troponin; thus, a coronary arteriography was performed that showed complete thrombotic stent occlusion in the circumflex artery. Consequently, diagnosis of type 4b inferolateral acute myocardial infarction secondary to ciprofloxacin-triggered type III Kounis syndrome was made. The aim of this report is to understand the relationship between the allergic reaction to ciprofloxacin and the acute coronary syndrome, and to create awareness of the importance of early diagnosis and treatment of this potentially fatal syndrome.

Syncope due to non-sustained episodes of Torsade de Pointes associated to androgen-deprivation therapy use: a case presentation.

BACKGROUND: Abiraterone is a medication frequently used for metastatic castrate-resistant prostate cancer. We report a case of non-sustained episodes of TdP associated with severe hypokalemia due to androgen-deprivation therapy. Few case presentations describe this association; the novelty lies in the potentially lethal cardiovascular events among cancer patients receiving hormonal therapy. CASE PRESENTATION: A 70-year-old male presented with recurrent syncope without prodrome. ECG revealed frequent ventricular ectopy, non-sustained episodes of TdP, and severe hypomagnesemia and hypokalemia. During potassium and magnesium infusion for repletion, the patient underwent temporary transvenous atrial pacing. As part of the work-up, coronary angiography revealed a mild coronary artery disease, and transthoracic echocardiogram showed a moderately depressed ejection fraction. After electrolyte disturbances were corrected, the QT interval normalized, and transvenous pacing was no longer necessary. Abiraterone was discontinued during the admission, and the patient returned to baseline. CONCLUSIONS: Cancer treatment is complex and requires a multidisciplinary approach. We presented a case of non-sustained TdP associated with androgen-deprivation therapy in an elderly patient with mild coronary artery disease and moderately reduced ejection fraction. Close follow-up and increased awareness are required in patients with hormonal treatment, especially in the setting of other cardiovascular risk factors.

Thermal acclimation offsets the negative effects of nitrate on aerobic scope and performance.

Rising temperatures are set to imperil freshwater fishes as climate change ensues unless compensatory strategies are employed. However, the presence of additional stressors, such as elevated nitrate concentrations, may affect the efficacy of compensatory responses. Here, juvenile silver perch (Bidyanus bidyanus) were exposed to current-day summer temperatures (28°C) or a future climate-warming scenario (32°C) and simultaneously exposed to one of three ecologically relevant nitrate concentrations (0, 50 or 100 mg l-1). We measured indicators of fish performance (growth, swimming), aerobic scope (AS) and upper thermal tolerance (CTmax) to test the hypothesis that nitrate exposure would increase susceptibility to elevated temperatures and limit thermal compensatory responses. After 8 weeks of acclimation, the thermal sensitivity and plasticity of AS and swimming performance were tested at three test temperatures (28, 32, 36°C). The AS of 28°C-acclimated fish declined with increasing temperature, and the effect was more pronounced in nitrate-exposed individuals. In these fish, declines in AS corresponded with poorer swimming performance and a 0.8°C decrease in CTmax compared with unexposed fish. In contrast, acclimation to 32°C masked the effects of nitrate; fish acclimated to 32°C displayed a thermally insensitive phenotype whereby locomotor performance remained unchanged, AS was maintained and CTmax was increased by ∼1°C irrespective of nitrate treatment compared with fish acclimated to 28°C. However, growth was markedly reduced in 32°C-acclimated compared with 28°C-acclimated fish. Our results indicate that nitrate exposure increases the susceptibility of fish to acute high temperatures, but thermal compensation can override some of these potentially detrimental effects.

Coping with climatic extremes: Dietary fat content decreased the thermal resilience of barramundi (Lates calcarifer).

Aquatic organisms, including important cultured species, are forced to contend with acute changes in water temperature as the frequency and intensity of extreme weather events worsen. Acute temperature spikes are likely to threaten aquaculture species, but dietary intervention may play an important protective role. Increasing the concentration of macronutrients, for example dietary fat content, may improve the thermal resilience of aquaculture species, however, this remains unexplored. To evaluate this hypothesis, we used two commercially available diets (20% versus 10% crude fat) to examine if dietary fat content improves the growth performance of juvenile barramundi (Lates calcarifer) while increasing their resilience to acute thermal stress. Fish were fed their assigned diets for 28-days before assessing the upper thermal tolerance (CTMAX) and the thermal sensitivity of swimming performance (UCRIT) and metabolism. We found that feeding fish a high fat diet resulted in heavier fish, but did not affect the thermal sensitivity of swimming performance or metabolism over an 18 °C temperature range (from 20 to 38 °C). Thermal tolerance was compromised in fish fed the high fat diet by 0.48 °C, showing significantly lower CTMAX. Together, these results suggest that while a high fat diet increases juvenile L. calcarifer growth, it does not benefit physiological performance across a range of relevant water temperatures and may even reduce fish tolerance of extreme water temperatures. These data may have implications for aquaculture production in a warming world, where episodic extremes of temperature are likely to become more frequent.

Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial.

AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.

Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial.

BACKGROUND: Vorapaxar inhibits platelet activation by antagonising thrombin-mediated activation of the protease-activated receptor 1 on human platelets. The effect of adding other antiplatelet drugs to aspirin for long-term secondary prevention of thrombotic events in stable patients with previous myocardial infarction is uncertain. We tested this effect in a subgroup of patients from the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial. METHODS: In TRA 2°P-TIMI 50--a randomised, placebo-controlled, parallel trial--we randomly assigned patients with a history of atherothrombosis to receive vorapaxar (2·5 mg daily) or matching placebo in a 1:1 ratio. Patients, and those giving treatment, assessing outcomes, and analysing results were masked to treatment allocation. Patients with a qualifying myocardial infarction within the previous 2 weeks to 12 months were analysed as a pre-defined subgroup. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke, analysed by intention to treat. We analysed events by Kaplan-Meier analysis and compared groups with a Cox proportional hazard model. TRA 2°P-TIMI 50 is registered at ClinicalTrials.gov (NCT00526474). FINDINGS: 17,779 of 26,449 patients had a qualifying myocardial infarction and were assigned treatment (8898 to vorapaxar and 8881 to placebo). Median follow-up was 2·5 years (IQR 2·0-2·9). Cardiovascular death, myocardial infarction, or stroke occurred in 610 of 8898 patients in the vorapaxar group and 750 of 8881 in the placebo group (3-year Kaplan-Meier estimates 8·1%vs 9·7%, HR 0·80, 95% CI 0·72-0·89; p<0·0001). Moderate or severe bleeding was more common in the vorapaxar group versus the placebo group (241/8880 [3·4%, 3-year Kaplan-Meier estimate] vs 151/8849 [2·1%, 3-year Kaplan-Meier estimate], HR 1·61, 95% CI 1·31-1·97; p<0·0001). Intracranial haemorrhage occurred in 43 of 8880 patients (0·6%, 3-year Kaplan-Meier estimate) with vorapaxar versus 28 of 8849 (0·4%, 3-year Kaplan-Meier estimate) with placebo (p=0·076). Other serious adverse events were equally distributed between groups. INTERPRETATION: For patients with a history of myocardial infarction, inhibition of protease-activated receptor 1 with vorapaxar reduces the risk of cardiovascular death or ischaemic events when added to standard antiplatelet treatment, including aspirin, and increases the risk of moderate or severe bleeding. FUNDING: Merck.

Risk of complications after a non-ST segment elevation acute myocardial infarction in a Latin-American cohort: An application of the ACTION ICU score.

BACKGROUND: European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (NSTEMI) recommend Intensive Care Unit (ICU) surveillance during the first 24-48 h. Interestingly, the in-hospital mortality of NSTEMI patients has consistently decreased, giving some patients the option to be managed in general hospital wards. The ACTION ICU score has been proposed to identify high-risk patients with NSTEMI and guide the selective risk-based need for ICU care. OBJECTIVE: To evaluate the usefulness of the ACTION ICU score to predict patients' risk of developing complications requiring ICU care in a Latin-American cohort with NSTEMI. METHODS: We applied the ACTION ICU score in a retrospective cohort. A composite primary outcome included: cardiorespiratory arrest, shock, high-grade atrio-ventricular block, respiratory failure, stroke, or death. The predictive performance of this model was estimated with a conditional multivariable logistic regression analysis. RESULTS: Of 1,062 patients with NSTEMI, the primary outcome was present in 75 patients (7.1%), and 1,019 (96%) were admitted to ICU. The most common event was respiratory failure (4.0%), followed by cardiogenic shock (3.7%), and cardiac arrest (1.7%). The presence of heart failure signs or symptoms had the highest association with the primary outcome (OR:2.16; 95%CI:1.61-2.92). The best cut-off point for this population was 3 (complications risk: 4.0%, SEN:96%, SP:15.4%, NPV:98.1%, PPV:7.9%). CONCLUSION: The ACTION ICU score may be a promising tool to identify the need for ICU care in Latin-American patients with NSTEMI. Furthermore, additional research is needed to evaluate the cost-effectiveness of this strategy.

Harnessing the potential of cross-protection stressor interactions for conservation: a review.

Conservation becomes increasingly complex as climate change exacerbates the multitude of stressors that organisms face. To meet this challenge, multiple stressor research is rapidly expanding, and the majority of this work has highlighted the deleterious effects of stressor interactions. However, there is a growing body of research documenting cross-protection between stressors, whereby exposure to a priming stressor heightens resilience to a second stressor of a different nature. Understanding cross-protection interactions is key to avoiding unrealistic 'blanket' conservation approaches, which aim to eliminate all forms of stress. But, a lack of synthesis of cross-protection interactions presents a barrier to integrating these protective benefits into conservation actions. To remedy this, we performed a review of cross-protection interactions among biotic and abiotic stressors within a conservation framework. A total of 66 publications were identified, spanning a diverse array of stressor combinations and taxonomic groups. We found that cross-protection occurs in response to naturally co-occurring stressors, as well as novel, anthropogenic stressors, suggesting that cross-protection may act as a 'pre-adaptation' to a changing world. Cross-protection interactions occurred in response to both biotic and abiotic stressors, but abiotic stressors have received far more investigation. Similarly, cross-protection interactions were present in a diverse array of taxa, but several taxonomic groups (e.g. mammals, birds and amphibians) were underrepresented. We conclude by providing an overview of how cross-protection interactions can be integrated into conservation and management actions and discuss how future research in this field may be directed to improve our understanding of how cross-protection may shield animals from global change.

Exposure to Nitrate Increases Susceptibility to Hypoxia in Fish.

AbstractAquatic hypoxic events are increasing in frequency and intensity as concentrations of nutrients, such as nitrate, continue to rise from human activities. Many fish species can alter their behavior and physiology to cope with drops in oxygen, but these compensatory strategies may be compromised under high levels of nitrate pollution. Hence, we investigated whether exposure to elevated nitrate concentrations affects key behavioral (avoidance and aquatic surface respiration [ASR]) and physiological (hemoglobin and hematocrit levels, ventilation frequency, and burst and prolonged swimming performance) responses of fish to mitigate the impacts of acute hypoxia. Juvenile silver perch (Bidyanus bidyanus) were exposed to one of three nitrate concentrations (0, 50, or 100 mg NO3- L-1) for 3 wk, after which behavioral and physiological responses of fish to progressive hypoxia were assessed. Fish exposed to nitrate utilized ASR at a higher threshold of partial pressure of oxygen during progressive hypoxia compared with control animals but did not alter behavioral avoidance of low oxygen levels. In these nitrate-exposed fish, the early onset of ASR behaviors is likely a behavioral, compensatory strategy to cope with nitrate-induced physiological disruptions, namely, increases in ventilation frequency and lower levels of hemoglobin and hematocrit. The physiological constraints placed by nitrate and acute hypoxia exposures manifested to lower the swimming performance of silver perch. Collectively, these data suggest that exposure to elevated nitrate is likely to disrupt key behavioral and physiological strategies used by fish to cope with short-term hypoxia.

Thermal plasticity of the cardiorespiratory system provides cross-tolerance protection to fish exposed to elevated nitrate.

Exposure to nitrate is toxic to aquatic animals due to the formation of methaemoglobin and a subsequent loss of blood-oxygen carrying capacity. Yet, nitrate toxicity can be modulated by other stressors in the environment, such as elevated temperatures. Acclimation to elevated temperatures has been shown to offset the negative effects of nitrate on whole animal performance in fish, but the mechanisms underlying this cross-tolerance interaction remain unclear. In this study, juvenile silver perch (Bidyanus bidyanus) were exposed to a factorial combination of temperature (28 °C or 32 °C) and nitrate concentrations (0, 50 or 100 mg NO3- L-1) treatments to test the hypothesis that thermal acclimation offsets the effects of nitrate via compensatory changes to the cardiorespiratory system (gills, ventricle and blood oxygen carrying capacity). Following 21 weeks of thermal acclimation, we found that fish acclimated to 32 °C experienced an expansion of gill surface area and an increase in ventricular thickness regardless of nitrate exposure concentration. Exposure to nitrate (both 50 and 100 mg NO3- L-1) reduced the blood oxygen carrying capacity of silver perch due to increases in methaemoglobin concentration and a right shift in oxygen-haemoglobin binding curves in fish from both thermal acclimation treatments. These results indicate that plasticity of the gills and ventricle of warm acclimated fish are potential mechanisms which may provide cross-tolerance protection to elevated nitrate concentrations despite nitrate induced reductions to oxygen transport.

Long-Term Results of Slipped Capital Femoral Epiphysis Treated with the Modified Dunn Procedure in a Colombian Cohort.

BACKGROUD: Slipped capital femoral epiphysis (SCFE) is a severe and catastrophic disorder that affects the hips of adolescents. Many reports about surgical procedures to treat this condition have been published, but to our knowledge, there are no published results of treatment in Latin American patients. This study describes the clinical and radiological results of the modified Dunn procedure with the surgical approach described by Ganz to treat mild to severe SCFE in a cohort of Colombian pediatric patients. METHODS: We retrospectively analyzed 21 patients (22 hips) with SCFE treated with surgical dislocation of the hip from 2005 to 2017. The same pediatric orthopedic surgeon performed all operations. Clinical outcome was assessed using the range of movement and Merle d'Aubigné score, while radiological measurements and assessment included the slip angle and Tönnis score. RESULTS: The average duration of follow-up was 29 months (range, 12-72 months). Of all cases, 17 presented with acute-on-chronic symptoms. Preoperatively, all 22 hips were classified as poor according to the Merle d'Aubigné score. Preoperative radiological classification showed compromise grade II or III in 20 hips. Last follow-up Merle d'Aubigné score rated 17 cases as good or excellent (p < 0.05). The postoperative radiological classification was grade I or II in all 22 cases, and the Tönnis score was stage II in 3 cases and stage III in 4 cases. CONCLUSIONS: Our results suggest that the modified Dunn osteotomy performed through the Ganz technique could be safely and effectively used to treat patients with mild to severe SCFE.

Double whammy: Nitrate pollution heightens susceptibility to both hypoxia and heat in a freshwater salmonid.

Species persistence in a changing world will depend on how they cope with co-occurring stressors. Stressors can interact in unanticipated ways, where exposure to one stressor may heighten or reduce resilience to another stressor. We examined how a leading threat to aquatic species, nitrate pollution, affects susceptibility to hypoxia and heat stress in a salmonid, the European grayling (Thymallus thymallus). Fish were exposed to nitrate pollution (0, 50 or 200 mg NO3- L-1) at two acclimation temperatures (18 °C or 22 °C) for eight weeks. Hypoxia- and heat-tolerance were subsequently assessed, and the gills of a subset of fish were sampled for histological analyses. Nitrate-exposed fish were significantly more susceptible to acute hypoxia at both acclimation temperatures. Similarly, in 18 °C- acclimated fish, exposure to 200 mg NO3- L- 1 caused a 1 °C decrease in heat tolerance (critical thermal maxima, CTMax). However, the opposite effect was observed in 22 °C-acclimated fish, where nitrate exposure increased heat tolerance by ~1 °C. Further, nitrate exposure induced some histopathological changes to the gills, which limit oxygen uptake. Our findings show that nitrate pollution can heighten the susceptibility of fish to additional threats in their habitat, but interactions are temperature dependent.

Living in polluted waters: A meta-analysis of the effects of nitrate and interactions with other environmental stressors on freshwater taxa.

Nutrient effluents from urban and agricultural inputs have resulted in high concentrations of nitrate in freshwater ecosystems. Exposure to nitrate can be particularly threatening to aquatic organisms, but a quantitative synthesis of the overall effects on amphibians, amphipods and fish is currently unavailable. Moreover, in disturbed ecosystems, organisms are unlikely to face a single stressor in isolation, and interactions among environmental stressors can enhance the negative effects of nitrate on organisms. Here, the effects of elevated nitrate on activity level, deformity rates, hatching success, growth and survival of three taxonomic groups of aquatically respiring organisms are documented. Effect sizes were extracted from 68 studies and analysed using meta-analytical techniques. The influence of nitrate on life-stages was also assessed. A factorial meta-analysis was conducted to examine the effect of nitrate and its interaction with other ecological stressors on organismal survival. Overall, the impacts of nitrate are biased towards amphibians (46 studies) and fish (13 studies), and less is known about amphipods (five studies). We found that exposure to nitrate translates to a 79% decrease in activity, a 29% decrease in growth, and reduces survival by 62%. Nitrate exposure also increases developmental deformities but does not affect hatching success. Nitrate exposure was found to influence all life-stages except embryos. Differences in the sensitivity of nitrate among taxonomic groups tended to be negligible. The factorial meta-analysis (14 amphibians and two amphipod studies) showed that nitrate in combination with other stressors affects survival in a non-additive manner. Our results indicate that nitrate can have strong effects on aquatic organisms and can interact with other environmental stressors which compound the negative effects on survival. Overall, the impacts of nitrate and additional stressors are complex requiring a holistic approach to better conserve freshwater biodiversity in the face of ongoing global change.

Simultaneous exposure to nitrate and low pH reduces the blood oxygen-carrying capacity and functional performance of a freshwater fish.

Human activities present aquatic species with numerous of environmental challenges, including excessive nutrient pollution (nitrate) and altered pH regimes (freshwater acidification). In isolation, elevated nitrate and acidic pH can lower the blood oxygen-carrying capacity of aquatic species and cause corresponding declines in key functional performance traits such as growth and locomotor capacity. These factors may pose considerable physiological challenges to organisms but little is known about their combined effects. To characterise the energetic and physiological consequences of simultaneous exposure to nitrate and low pH, we exposed spangled perch (Leiopotherapon unicolor) to a combination of nitrate (0, 50 or 100 mg L-1) and pH (pH 7.0 or 4.0) treatments in a factorial experimental design. Blood oxygen-carrying capacity (haemoglobin concentration, methaemoglobin concentrations and oxygen equilibrium curves), aerobic scope and functional performance traits (growth, swimming performance and post-exercise recovery) were assessed after 28 days of exposure. The oxygen-carrying capacity of fish exposed to elevated nitrate (50 and 100 mg L-1) was compromised due to reductions in haematocrit, functional haemoglobin levels and a 3-fold increase in methaemoglobin concentrations. Oxygen uptake was also impeded due to a right shift in oxygen-haemoglobin binding curves of fish exposed to nitrate and pH 4.0 simultaneously. A reduced blood oxygen-carrying capacity translated to a lowered aerobic scope, and the functional performance of fish (growth and swimming performance and increased post-exercise recovery times) was compromised by the combined effects of nitrate and low pH. These results highlight the impacts on aquatic organisms living in environments threatened by excessive nitrate and acidic pH conditions.

HEART, TIMI, and GRACE Scores for Prediction of 30-Day Major Adverse Cardiovascular Events in the Era of High-Sensitivity Troponin. / Os Escores HEART, TIMI e GRACE para Predição de Eventos Cardiovasculares Adversos Maiores no Período de 30 Dias na Era de Troponina I de Alta Sensibilidade.

BACKGROUND: Multiple scoring systems have been designed to calculate the risk of major adverse cardiovascular events (MACE) in patients with chest pain. There is no data on whether the HEART score outperforms TIMI and GRACE in the prediction of MACE, especially in the era of high-sensitivity troponin assay and in an exclusively Latin-American population. OBJECTIVE: To compare the performance of the HEART, TIMI, and GRACE scores for predicting major cardiovascular events at 30 days of follow-up, in patients who consult for chest pain in the emergency department. METHODS: HEART, TIMI, and GRACE scores were analyzed in 519 patients with chest pain at the emergency department. The primary endpoint was the occurrence of MACE within 30 days. The performance of the HEART score was compared with the TIMI and GRACE scores using the DeLong test with p values of 0.05 considered statistically significant. RESULTS: A total of 224 patients (43%) had MACE at 30 days. The C statistic for the HEART, TIMI, and GRACE score was 0.937, 0.844, and 0.797 respectively (p < 0.0001). A HEART score of 3 or less had a sensitivity of 99.5% and a negative predictive value of 99% to classify low risk patients correctly; both values were higher than those obtained by the other scores. CONCLUSION: The HEART score more effectively predicts cardiovascular events at 30 days of follow-up compared to the other scores. High-sensitivity troponins maintain this score's previously demonstrated superiority. This score offers more precise identification of low-risk patients. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: Múltiplos sistemas de pontuação têm sido elaborados para calcular o risco de eventos cardiovasculares adversos maiores (MACE) em pacientes com dor no peito. Não há dados que avaliem se o escore HEART tem um desempenho superior a TIMI e GRACE para a predição de MACE, especialmente na era de troponina I de alta sensibilidade e em uma população exclusivamente latino-americana. OBJETIVO: Comparar o desempenho dos escores HEART, TIMI e GRACE para a predição de MACE em 30 dias de acompanhamento, em pacientes atendidos com dor no peito no departamento de emergência. MÉTODOS: Os escores HEART, TIMI e GRACE foram analisados em 519 pacientes com dor no peito no departamento de emergência. O desfecho primário foi a ocorrência de MACE no período de 30 dias. O desempenho do escore HEART foi comparado com o dos escores TIMI e GRACE utilizando o teste de DeLong, considerando estatisticamente significativos os valores de p de 0,05. RESULTADOS: Um total de 224 pacientes (43%) apresentaram MACE no período de 30 dias. A estatística C para os escores HEART, TIMI e GRACE foi de 0,937, 0,844 e 0,797 respectivamente (p < 0,0001). Uma pontuação de 3 ou menos no escore HEART apresentou uma sensibilidade de 99,5% e um valor preditivo negativo de 99% para classificar pacientes de baixo risco de maneira correta; ambos os valores foram mais elevados do que aqueles obtidos pelos outros escores. CONCLUSÃO: O escore HEART, em um período de 30 dias, prediz eventos cardiovasculares, mais eficazmente, em comparação com os outros escores. Troponinas de alta sensibilidade mantêm a superioridade previamente demonstrada deste escore. Este escore oferece uma identificação mais precisa dos pacientes de baixo risco. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial.

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P=0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.