Tracking of marine predators to protect Southern Ocean ecosystems.

Southern Ocean ecosystems are under pressure from resource exploitation and climate change1,2. Mitigation requires the identification and protection of Areas of Ecological Significance (AESs), which have so far not been determined at the ocean-basin scale. Here, using assemblage-level tracking of marine predators, we identify AESs for this globally important region and assess current threats and protection levels. Integration of more than 4,000 tracks from 17 bird and mammal species reveals AESs around sub-Antarctic islands in the Atlantic and Indian Oceans and over the Antarctic continental shelf. Fishing pressure is disproportionately concentrated inside AESs, and climate change over the next century is predicted to impose pressure on these areas, particularly around the Antarctic continent. At present, 7.1% of the ocean south of 40°S is under formal protection, including 29% of the total AESs. The establishment and regular revision of networks of protection that encompass AESs are needed to provide long-term mitigation of growing pressures on Southern Ocean ecosystems.

Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

MUC5AC concentrations in lung lavage fluids are associated with acute lung injury after cardiac surgery.

Heart surgery may be complicated by acute lung injury and adult respiratory distress syndrome. Expression and release of mucins MUC5AC and MUC5B in the lungs has been reported to be increased in acute lung injury. The aim of our study was to [1] investigate the perioperative changes of MUC5AC, MUC5B and other biomarkers in mini-bronchoalveolar lavage (minBAL), and [2] relate these to clinical outcomes after cardiac surgery. In this prospective cohort study in 49 adult cardiac surgery patients pre- and post-surgery non-fiberscopic miniBAL fluids were analysed for MUC5AC, MUC5B, IL-8, human neutrophil elastase, and neutrophils. All measured biomarkers increased after surgery. Perioperative MUC5AC-change showed a significant negative association with postoperative P/F ratio (p = 0.018), and a positive association with ICU stay (p = 0.027). In conclusion, development of lung injury after cardiac surgery and prolonged ICU stay are associated with an early increase of MUC5AC as detected in mini-BAL.

The role of hemoadsorption in cardiac surgery - a systematic review.

BACKGROUND: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. METHODS: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. RESULTS: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. CONCLUSIONS: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.

Thoracic aortic atherosclerosis in patients with a bicuspid aortic valve; a case-control study.

INTRODUCTION: Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients. METHODS: Atherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006-2020), resulting in a total of 128 inclusions. RESULTS: Histopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 - 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 - 1.61); p = 0.014). CONCLUSION: Ascending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm.

Minimally Invasive Aortic Valve Replacement in Contemporary Practice: Clinical and Hemodynamic Performance from a Prospective Multicenter Trial.

BACKGROUND: The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate clinical outcomes and hemodynamic performance achieved with minimally invasive aortic valve replacement (MI-AVR) as compared with conventional AVR. METHODS: Patients who underwent surgical AVR with the Avalus bioprosthesis, as part of a prospective multicenter non-randomized trial, were included in this analysis. Surgical approach was left to the discretion of the surgeons. Patient characteristics and clinical outcomes were compared between MI-AVR and conventional AVR groups in the entire cohort (n = 1077) and in an isolated AVR subcohort (n = 528). Propensity score adjustment was performed to estimate the effect of MI-AVR on adverse events. RESULTS: Patients treated with MI-AVR were younger, had lower STS scores, and underwent concomitant procedures less often. Valve size implanted was comparable between the groups. MI-AVR was associated with longer procedural times in the isolated AVR subcohort. Postprocedural hemodynamic performance was comparable. There were no significant differences between MI-AVR and conventional AVR in early and 3-year all-cause mortality, thromboembolism, reintervention, or a composite of those endpoints within either the entire cohort or the isolated AVR subcohort. After propensity score adjustment, there remained no association between MI-AVR and the composite endpoint (hazard ratio: 0.86, 95% confidence interval: 0.47-1.55, p = 0.61). CONCLUSION: Three-year outcomes after MI-AVR with the Avalus bioprosthetic valve were comparable to conventional AVR. These results provide important insights into the overall ability to reduce the invasiveness of AVR without compromising outcomes.

Improving accuracy in diagnosing aortic stenosis severity: An in-depth analysis of echocardiographic measurement error through literature review and simulation study.

AIMS: The present guidelines advise replacing the aortic valve for individuals with severe aortic stenosis (AS) based on various echocardiographic parameters. Accurate measurements are essential to avoid misclassification and unnecessary interventions. The objective of this study was to evaluate the influence of measurement error on the echocardiographic evaluation of the severity of AS. METHODS AND RESULTS: A systematic review was performed to examine whether measurement errors are reported in studies focusing on the prognostic value of peak aortic jet velocity (Vmax ), mean pressure gradient (MPG), and effective orifice area (EOA) in asymptomatic patients with AS. Out of the 37 studies reviewed, 17 (46%) acknowledged the existence of measurement errors, but none of them utilized methods to address them. Secondly, the magnitude of potential errors was collected from available literature for use in clinical simulations. Interobserver variability ranged between 0.9% and 8.3% for Vmax and MPG but was higher for EOA (range 7.7%-12.7%), indicating lower reliability. Assuming a circular left ventricular outflow tract area led to a median underestimation of EOA by 23% compared to planimetry by other modalities. A clinical simulation resulted in the reclassification of 42% of patients, shifting them from a diagnosis of severe AS to moderate AS. CONCLUSIONS: Measurement errors are underreported in studies on echocardiographic assessment of AS severity. These errors can lead to misclassification and misdiagnosis. Clinicians and scientists should be aware of the implications for accurate clinical decision-making and assuring research validity.

Computed tomography follow-up after elective proximal aortic surgery: Less is more?

STUDY OBJECTIVE: The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of aorta-related complications and reinterventions detected during routine CT follow-up. METHODS: Data on 314 patients undergoing first time elective proximal aortic surgery between 2000 and 2015 were collected. The primary study end points were aorta-related complications and reinterventions, detected during routine CT follow-up. Secondary study endpoints included all aorta-related complications and reinterventions, irrespective of the mode of detection and survival. RESULTS: Median CT follow-up time was 6.8 (IQR 4.1-9.8) years, during which a total of 1303 routine follow-up CT-scans (median 4, IQR 3-5) were performed. During CT follow-up, aorta-related complications were detected in 18 (5.7%) patients, of which 6 (1.6%) underwent reintervention. In total, 28 aorta-related complications were observed in 23 (7.3%) patients, of which 9 led to reintervention. In order to detect 1 aorta-related complication leading to reintervention, 218 routine follow-up CT-scans were required. The unadjusted and EuroSCORE II adjusted hazard ratios of not undergoing CT follow-up on mortality were 1.260 (95% CI 0.705-2.251) and 0.830 (95% CI 0.430-1.605), respectively. CONCLUSIONS: Following first time elective proximal aortic surgery, aorta-related complications are uncommon, are not always detected during CT follow-up and, if detected, often do not result in reintervention. Therefore, a more conservative CT follow-up protocol could be considered in selected patients to reduce lifetime radiation burden and health care costs.

Perioperative Care Standards in Cardiac Surgery Patients Aiming at Enhancing Recovery: A Nationwide Survey in the Netherlands and Belgium.

OBJECTIVE: The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium. DESIGN: An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery. SETTING: The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium. PARTICIPANTS: A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%). CONCLUSIONS: The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population.

Robotic Mitral Valve Surgery.

Growing interest in minimalizing surgical trauma during heart procedures stimulated the development of robotic mitral valve surgery in the late 1990s. Initially, the new technology was slowly adopted in clinical practice. However, following encouraging results by teams that adopted robotic heart surgery early on, a growing interest in implementation of robotic mitral valve surgery has emerged. Of importance are the technical developments and possibilities that accompany robotic surgery. Robotic arms feature unique characteristics, allowing unparalleled range of motion and allowing complex mitral valve repair techniques to be performed without limitations related to limited surgical incisions. High-quality three-dimensional vision effectively compensates for the lack of tactile feedback. Several technical solutions have been developed to facilitate mitral valve repair in minimal invasive setting, including chordal guiding systems, now available with various annuloplasty rings. On the other hand, precise vision and movements allows accurate determination of the length of implanted neochordae, facilitating precise determination of the length of implanted neochords even without the use of chordal-guiding systems. With robotic mitral valve surgery, leaflet resection techniques can be performed without limitations, ensuring that no compromises of the surgical strategy are made. Nevertheless, careful preoperative planning with appropriate work-up and imaging is of utmost importance to prevent complications. Moreover, the drawbacks of the initial learning curve and higher procedural costs are counterbalanced by less surgical trauma, lower utilization of blood products, and faster patient recovery. Robotic mitral valve surgery is still a young field and evolving technology that is bound to become an important tool in the toolbox of surgical mitral valve approaches.

Peri-operative nutrition in cardiovascular surgery: current pitfalls and future directions.

In the field of cardiovascular surgery, many areas are frequently evaluated to improve patient outcomes. Even though cardiac surgery has advanced significantly, peri-operative nutrition remains an area needing special attention and is under-considered in patient results. The three portions of cardiac surgical nutrition optimization are pre-operative, intra-operative and post-operative. All these, merit important clinical intervention which when done properly can significantly improve patient recovery and reduce morbidity and mortality. Here we provide a narrative review and recommendations for peri-operative nutritional optimization in cardiac surgery.

Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD.

BACKGROUND: Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. METHODS: Children 7-15 years old were recruited for a case-control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). RESULTS: ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [ß = -0.147 (-0.27 to -0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. CONCLUSION: Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

Prosthesis-patient mismatch after mitral valve replacement: A pooled meta-analysis of Kaplan-Meier-derived individual patient data.

OBJECTIVE: The hemodynamic effect and early and late survival impact of prosthesis-patient mismatch (PPM) after mitral valve replacement remains insufficiently explored. METHODS: Pubmed, Embase, Web of Science, and Cochrane Library databases were searched for English language original publications. The search yielded 791 potentially relevant studies. The final review and analysis included 19 studies compromising 11,675 patients. RESULTS: Prosthetic effective orifice area was calculated with the continuity equation method in 7 (37%), pressure half-time method in 2 (10%), and partially or fully obtained from referenced values in 10 (53%) studies. Risk factors for PPM included gender (male), diabetes mellitus, chronic renal disease, and the use of bioprostheses. When pooling unadjusted data, PPM was associated with higher perioperative (odds ratio [OR]: 1.66; 95% confidence interval [CI]: 1.32-2.10; p < .001) and late mortality (hazard ratio [HR]: 1.46; 95% CI: 1.21-1.77; p < .001). Moreover, PPM was associated with higher late mortality when Cox proportional-hazards regression (HR: 1.97; 95% CI: 1.57-2.47; p < .001) and propensity score (HR: 1.99; 95% CI: 1.34-2.95; p < .001) adjusted data were pooled. Contrarily, moderate (HR: 1.01; 95% CI: 0.84-1.22; p = .88) or severe (HR: 1.19; 95% CI: 0.89-1.58; p = .24) PPM were not related to higher late mortality when adjusted data were pooled individually. PPM was associated with higher systolic pulmonary pressures (mean difference: 7.88 mmHg; 95% CI: 4.72-11.05; p < .001) and less pulmonary hypertension regression (OR: 5.78; 95% CI: 3.33-10.05; p < .001) late after surgery. CONCLUSIONS: Mitral valve PPM is associated with higher postoperative pulmonary artery pressure and might impair perioperative and overall survival. The relation should be further assessed in properly designed studies.

Impact of recurrent mitral regurgitation after mitral valve repair for functional mitral regurgitation: long-term analysis of competing outcomes.

AIMS: Recurrent mitral regurgitation (MR) has been reported after mitral valve repair for functional MR. However, the impact of recurrent MR on long-term survival remains poorly defined. In the present study, mortality-adjusted recurrent MR rates, the clinical impact of recurrent MR and its determinants were studied in patients after mitral valve repair with revascularization for functional MR in the setting of ischaemic heart disease. METHODS AND RESULTS: Long-term clinical and echocardiographic outcome was evaluated in 261 consecutive patients after restrictive mitral annuloplasty and revascularization for moderate to severe functional MR, between 2000 and 2014. The cumulative incidence of recurrent MR ≥ Grade 2, assessed by competing risk analysis, was 9.6 ± 1.8% at 1-year, 20.3 ± 2.5% at 5-year, and 27.6 ± 2.9% at 10-year follow-up. Cumulative survival was 85.8% [95% confidence interval (CI) 81.0-90.0] at 1-year, 67.3% (95% CI 61.1-72.6%) at 5-year, and 46.1% (95% CI 39.4-52.6%) at 10-year follow-up. Age, preoperative New York Heart Association Class III or IV, a history of renal failure, and recurrence of MR expressed as a time-dependent variable [HR 3.28 (1.87-5.75), P < 0.001], were independently associated with an increased mortality risk. Female gender, a history of ST-elevation myocardial infarction, a preoperative QRS duration ≥120 ms, a higher preoperative MR grade, and a higher indexed left ventricular end-systolic volume were independently associated with an increased likelihood of recurrent MR. CONCLUSION: Mitral valve repair for functional ischaemic MR resulted in a low incidence of recurrent MR with favourable clinical outcome up to 10 years after surgery. Presence of recurrent MR at any moment after surgery proved to be independently associated with an increased risk for mortality.

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Vasoplegia After Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation in Patients With Heart Failure.

OBJECTIVES: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. DESIGN: Retrospective. SETTING: University medical center, single institutional. PARTICIPANTS: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). MEASUREMENTS AND MAIN RESULTS: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. CONCLUSIONS: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology.

Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics.

Global forage-fish landings are increasing, with potentially grave consequences for marine ecosystems. Predators of forage fish may be influenced by this harvest, but the nature of these effects is contentious. Experimental fishery manipulations offer the best solution to quantify population-level impacts, but are rare. We used Bayesian inference to examine changes in chick survival, body condition and population growth rate of endangered African penguins Spheniscus demersus in response to 8 years of alternating time-area closures around two pairs of colonies. Our results demonstrate that fishing closures improved chick survival and condition, after controlling for changing prey availability. However, this effect was inconsistent across sites and years, highlighting the difficultly of assessing management interventions in marine ecosystems. Nevertheless, modelled increases in population growth rates exceeded 1% at one colony; i.e. the threshold considered biologically meaningful by fisheries management in South Africa. Fishing closures evidently can improve the population trend of a forage-fish-dependent predator-we therefore recommend they continue in South Africa and support their application elsewhere. However, detecting demographic gains for mobile marine predators from small no-take zones requires experimental time frames and scales that will often exceed those desired by decision makers.

The role of the microbiome for human health: from basic science to clinical applications.

The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.

Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs.

Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host- and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.