Search

The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer1-3. The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here we present a comprehensive, spatiotemporal map of human proteomic heterogeneity by integrating proteomics at subcellular resolution with single-cell transcriptomics and precise temporal measurements of individual cells in the cell cycle. We show that around one-fifth of the human proteome displays cell-to-cell variability, identify hundreds of proteins with previously unknown associations with mitosis and the cell cycle, and provide evidence that several of these proteins have oncogenic functions. Our results show that cell cycle progression explains less than half of all cell-to-cell variability, and that most cycling proteins are regulated post-translationally, rather than by transcriptomic cycling. These proteins are disproportionately phosphorylated by kinases that regulate cell fate, whereas non-cycling proteins that vary between cells are more likely to be modified by kinases that regulate metabolism. This spatially resolved proteomic map of the cell cycle is integrated into the Human Protein Atlas and will serve as a resource for accelerating molecular studies of the human cell cycle and cell proliferation.

The understanding of how spatio-temporal patterns of neural activity may arise in the cortex of the brain has advanced with the development and analysis of neural field models. Replicating this suc...

Supplemental Digital Content is available in the text., Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in cardiovascular prevention have recently been demonstrated in a large randomized, controlled trial. In addition, n-3 PUFAs serve as the substrate for the synthesis of specialized proresolving mediators, which are known by their potent beneficial anti-inflammatory, proresolving, and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and specialized proresolving mediators on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA–derived specialized proresolving mediators in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe−/− mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in noncalcified regions compared with calcified regions. Liquid chromatography tandem mass spectrometry–based lipid mediator lipidomics identified that the n-3 PUFA–derived specialized proresolving mediator resolvin E1 was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe−/− mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tg×Apoe−/−), which enables the endogenous synthesis of n-3 PUFA and increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization, and improved echocardiographic parameters. Finally, abrogation of the resolvin E1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived resolvin E1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.

The causes of chronic pelvic pain (CPP) in women can be multifactorial and significantly affect quality of life. Finding the cause(s) for CPP often takes a multidisciplinary approach. One commonly overlooked cause of CPP is pelvic venous disease (PVD). The causal relationship between PVD and CPP has been well-documented in the literature, but with limited assessment or treatment guidelines to advise health care providers, there continues to be a limited understanding of PVD. This article aims to ensure nurse practitioners are well equipped to recognize women presenting with symptoms suggestive of PVD and expedite referral when needed for further evaluation.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

Prenatal prediction of postnatal univentricular versus biventricular circulation in patients with borderline left ventricle (bLV) remains challenging. This study investigated prenatal fetal echocardiographic parameters and postnatal outcome of patients with a prenatally diagnosed bLV. We report a retrospective study of bLV patients at four prenatal centers with a follow-up of one year. BLV was defined as z-scores of the left ventricle (LV) between -2 and -4. Single-ventricle palliation (SVP), biventricular repair (BVR), and no surgical or catheter-based intervention served as the dependent outcome. Prenatal ultrasound parameters were used as independent variables. Cut-off values from receiver operating characteristic curves (ROC) were determined for significant discrimination between outcomes. A total of 54 patients were diagnosed with bLV from 2010 to 2018. All were live births. Out of the entire cohort, 8 (15 %) received SVP, 34 (63 %) BVR, and 12 (22 %) no intervention. There was no significant difference with regard to genetic or extracardiac anomalies. There were significantly more patients with endocardial fibroelastosis (EFE) in the SVP group compared to the BVR group (80 % vs. 10 %), (p 0.001). Apex-forming LV (100 % vs. 70 %) and lack of retrograde arch flow (20 % vs. 80 %) were associated with no intervention (p 0.001). With respect to BVR vs. SVP, the LV sphericity index provided the highest specificity (91.7 %) using a cutoff value of ≤ 0.5. The majority of bLV patients maintained biventricular circulation. EFE, retrograde arch flow, and LV sphericity can be helpful parameters for counseling parents and further prospective studies can be developed.ZIEL: Die pränatale Vorhersage eines postnatal univentrikulären versus biventrikulären Kreislaufs bei Föten mit grenzwertigem linkem Ventrikel (bLV, “borderline left ventricle”) bleibt eine Herausforderung. Diese Studie untersuchte pränatale fetale echokardiografische Parameter und den postnatalen Outcome von Patienten mit einer pränatal diagnostizierten bLV. Wir berichten über eine retrospektive Studie von Föten mit bLV an 4 Pränatalzentren mit einer Nachverfolgung von einem Jahr. BLV wurde definiert als z-Scores des linken Ventrikels (LV) zwischen –2 und –4. Als abhängiger Outcome dienten die Einzelventrikel-Palliation (SVP), die biventrikuläre Korrektur (BVR) und keine chirurgische oder Katheter-basierte Intervention. Die pränatalen Ultraschallparameter wurden als unabhängige Variablen verwendet. Die Cut-off-Werte aus den Receiver-Operating-Characteristic (ROC) -Kurven wurden für eine signifikante Diskriminierung zwischen den Outcomes ermittelt. Von 2010–2018 wurden insgesamt 54 Patienten mit bLV diagnostiziert. Alle waren Lebendgeburten. Von der gesamten Kohorte erhielten 8 (15 %) SVP, 34 (63 %) BVR und 12 (22 %) keine Intervention. Es gab keinen signifikanten Unterschied in Bezug auf genetische oder extrakardiale Anomalien. Es gab signifikant mehr Patienten mit endokardialer Fibroelastose (EFE) in der SVP- im Vergleich zu BVR-Gruppe (80 % vs. 10 %; p 0,001). Ein an der Herzspitzenbildung beteiligter LV (100 % vs. 70 %) und fehlender retrograder Bogenfluss (20 % vs. 80 %) waren mit keiner Intervention assoziiert (p 0,001). Für die Differenzierung von BVR vs. SVP lieferte der LV-Sphärizitätsindex bei einem Cut-off-Wert von ≤ 0,5 die höchste Spezifität (91,7 %). Die Mehrheit der bLV-Patienten hielt einen biventrikulären Kreislauf aufrecht. EFE, retrograder Bogenfluss und LV-Sphärizität können hilfreiche Parameter bei der Beratung der Eltern und der Entwicklung weiterer prospektiver Studien sein.

Cardiac alternans, in which the membrane potential and the intracellular calcium concentration exhibit alternating durations and peak amplitudes at consecutive beats, constitute a precursor to fatal cardiac arrhythmia such as sudden cardiac death. A crucial question therefore concerns the onset of cardiac alternans. Typically, alternans are only reported when they are fully developed. Here, we present a modelling approach to explore recently discovered microscopic alternans, which represent one of the earliest manifestations of cardiac alternans. In this case, the regular periodic dynamics of the local intracellular calcium concentration is already unstable, while the whole-cell behaviour suggests a healthy cell state. In particular, we use our model to investigate the impact of calcium diffusion in both the cytosol and the sarcoplasmic reticulum on the formation of microscopic calcium alternans. We find that for dominant cytosolic coupling, calcium alternans emerge via the traditional period doubling bifurcation. In contrast, dominant luminal coupling leads to a novel route to calcium alternans through a saddle-node bifurcation at the network level. Combining semi-analytical and computational approaches, we compute areas of stability in parameter space and find that as we cross from stable to unstable regions, the emergent patterns of the intracellular calcium concentration change abruptly in a fashion that is highly dependent upon position along the stability boundary. Our results demonstrate that microscopic calcium alternans may possess a much richer dynamical repertoire than previously thought and further strengthen the role of luminal calcium in shaping cardiac calcium dynamics.

Objectives To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). Methods We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 ( 30 weeks). Results 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. Conclusion TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Background and study aims The demand for screening colonoscopy has continued to rise over the past two decades. As a result, the current workforce of gastroenterologists is unable to meet the needs for colorectal cancer (CRC) screening. Therefore, solutions are needed to improve this disparity, with non-physician endoscopists being a potential option. However, current literature on the performance of non-physicians in endoscopy is limited. The aim of this study was to assess the quality of colonoscopy performed by three gastrointestinal fellowship-trained nurse practitioners (NPs). Methods This was a retrospective study performed at a single tertiary academic medical center. Colonoscopies performed by three gastrointestinal-specialized NPs after having completed training of at least 140 supervised colonoscopies were reviewed for analysis. Inclusion criteria were patients undergoing colonoscopy for colorectal cancer screening purposes. Outcomes included colonoscopy quality indicators as defined by the American Society for Gastrointestinal Endoscopy/American College of Gastroenterology Taskforce (ASGE/ACG) Taskforce. Results The study included 1,012 subjects (mean age 56.2 years, female 51.5 %, African American 73.9 %) who underwent screening colonoscopies by three NPs. Cecal intubation was successful in 997 subjects (98.5 %). Mean adenoma detection rate was 35.6 %. Mean withdrawal time was 18.9 minutes. There were no adverse events including colonic perforations or delayed post-polypectomy bleeding. Conclusions Three fellowship-trained NPs in colonoscopy in the United States satisfied the quality indicators proposed by the ASGE/ACG Task force, demonstrating that adequately trained NPs can perform colonoscopy safely and effectively. With the demand for colonoscopy exceeding the supply, non-physicians could be part of the solution to meet the demands for CRC screening.

BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clinical worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11-1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01-2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

Publications on the paediatric Berlin Heart EXCOR ventricular assist device have revealed that low body weight10 kg is a significant risk factor for mortality with children weighing5 kg being at the highest risk. However, these studies are limited to implantation periods prior to 2011. Since then, progress has been made in the optimization of patient selection and management. This study investigated whether the survival of children weighing10 kg supported with the EXCOR assist device has improved in recent years and sought to determine the risk factors for mortality.The Berlin Heart EXCOR prospective registry (n = 1832) was retrospectively reviewed between 2000 and 2017 to compare the outcomes of different weight cohorts: A (5 kg; n = 204), B (5-10 kg; n = 633) and C (10 kg; n = 995) in different eras [era 1: January 2000-December 2012 (n = 1089) and era 2: January 2013-June 2017 (n = 743)].Overall survival in groups A and B significantly increased from era 1 to era 2 (group A 51% vs 65%, P 0.001; group B 74% vs 78%, P = 0.001), whereas it remained stable in group C (78% vs 73%). In era 2, the survival of group B was not significantly different from group C. On the multivariable analysis of children weighing5 kg, congenital heart disease, preoperative extracorporeal life support and biventricular support were independently associated with increased mortality in era 1 [hazard ratio 2.04 (95% confidence interval 1.18-3.53); 2.44 (1.36-4.37) and 1.93 (1.11-3.34), respectively] but not in era 2.Paediatric EXCOR ventricular assist device therapy has significantly improved for patients weighing10 kg. Withholding a ventricular assist device is not justified on the basis of the body weight alone.

Salivary biomarkers may offer a noninvasive and easy sampling alternative in cardiovascular risk evaluation. The aim of the present study was to establish associations of salivary potassium, sodium, calcium, and phosphate levels with the cardiovascular phenotype determined by carotid ultrasound and carotid-femoral pulse wave velocity and to identify possible covariates for these associations. N=241 samples of nonstimulated whole buccal saliva were obtained from subjects with (n=143; 59%) or without (n=98; 41%) hypertension. The potassium concentrations were 10-fold higher in saliva compared with plasma, whereas sodium concentrations exhibited the reverse relation between saliva and blood. There were no significant correlations between the levels of sodium, potassium, or calcium in saliva and plasma. All salivary electrolytes, except sodium, were significantly associated with age. In age-adjusted analyses, salivary potassium was significantly associated with carotid artery intima media thickness (cIMT) and carotid-femoral pulse wave velocity, and these associations were at the limit of significance in multivariate analyses including prevalent cardiovascular disease and risk factors. Body mass index was a significant confounder for salivary potassium. Salivary phosphate was significantly associated with cIMT in the multivariate analysis. Salivary potassium, calcium, and phosphate levels were significantly associated with heart rate in the univariate age-adjusted as well as in two different multivariate models, whereas no significant associations between sodium and heart rate were observed. In conclusion, the differential association of salivary electrolytes with cardiovascular phenotypes indicates that these electrolytes should be further studied for their predictive value as noninvasive biomarkers for cardiovascular risk evaluation.

Visual Abstract, Highlights • Specialized lipid mediators transduce the resolution of inflammation by means of the ALX/FPR2. • Human AAA exhibited decreased ALX/FPR2 expression. • Genetic disruption of the murine ALX/FPR2 ortholog exacerbated AAA and increased inflammation. • The ALX/FPR2 agonist ATL induced pro-resolving signaling in bone marrow-derived murine cells. • Pro-resolving signaling by means of the ALX/FPR2 receptor may decrease the progression of AAA., Summary An abdominal aortic aneurysm (AAA) is a progressive aortic dilation that may lead to rupture, which is usually lethal. This study identifies the state of failure in the resolution of inflammation by means of decreased expression of the pro-resolving receptor A lipoxin/formyl peptide receptor 2 (ALX/FPR2) in the adventitia of human AAA lesions. Mimicking this condition by genetic deletion of the murine ALX/FPR2 ortholog in hyperlipidemic mice exacerbated the aortic dilation induced by angiotensin II infusion, associated with decreased vascular collagen and increased inflammation. The authors also identified key roles of lipoxin formation through 12/15-lipoxygenase and neutrophil p38 mitogen-activated protein kinase. In conclusion, this study established pro-resolving signaling by means of the ALX/FPR2 receptor in aneurysms and vascular inflammation.

The aim of our retrospective evaluation was to compare the outcome of patients with prenatal and postnatal diagnosis of Tetralogy of Fallot (TOF) and to analyze prenatal echocardiographic parameters predicting intervention within 30 days postnatal. We evaluated 142 patients in our pediatric heart center and prenatal diagnosis center and prenatal practice Praenatal plus in Cologne between 01/08-06/16. Within the prenatal diagnosis group, 6/74 fetuses (8.1 %) had TOF with pulmonary atresia (TOF-PA), and 6 (8.1 %) had absent pulmonary valve syndrome (TOF-APVS). 14 (18.9 %) had an abnormal karyotype including 9/14 (64.3 %) with microdeletion 22q11.2. 25 (33.8 %) had extracardiac malformation. 4 (5.4 %) had agenesis of ductus arteriosus (DA), 22 (29.7 %) had right aortic arch (RAA) and 9 (12.2 %) had major aortopulmonary collateral arteries (MAPCAs). Within the postnatal diagnosis group, no patient had TOF-PA, 4/68 (5.9 %) had TOF-APVS. 12 (17.6 %) had extracardiac malformations, 9 (13.2 %) had an abnormal karyotype including 2/9 with microdeletion 22q11.2. 10 (14.7 %) had RAA, 9 (13.2 %) had MAPCAs. There were no cases with agenesis of DA. Increasing z-score values of the left/right pulmonary artery (LPA/RPA) prenatally were associated with a lower probability for early postnatal intervention (RPA: p = 0.017; LPA: p = 0.013). Within the prenatal diagnosis group, 12 of 41 (29.3 %) live-born patients with follow-up and intention to treat needed early intervention versus 7 (10.3 %) in the postnatal diagnosis group (p = 0.02). Within the postnatal diagnosis group, there were no deaths, while 2 (4.9 %) post-intervention deaths occurred in the prenatal diagnosis group. There are no significant differences concerning post-intervention survival in the prenatal diagnosis group versus the postnatal diagnosis group. Complex cases may be underrepresented in the postnatal diagnosis group. Smaller RPA/LPA values prenatally seem to be associated with early postnatal intervention.ZIEL: Ziel unserer retrospektiven Auswertung war der Outcome-Vergleich von Patienten mit pränatal und postnatal diagnostizierter Fallot-Tetralogie (TOF) sowie die Auswertung fetaler Echokardiografie-Parameter im Hinblick auf Prädiktion einer Intervention innerhalb 30 Tage postnatal. Ausgewertet wurden 142 Patienten, die von 01/08–06/16 in unserem Kinderherz-Zentrum, unserer Pränataldiagnostik oder in der Praxis Praenatal plus in Köln vorstellig waren. In der Pränatal-Diagnose-Gruppe waren 6 von 74 (8,1 %) mit TOF und Pulmonalatresie (TOF-PA), 6 (8,1 %) mit absent-pulmonary-valve-syndrome (TOF-APVS). 14 (18,9 %) hatten einen auffälligen Karyotyp, darunter 9/14 mit Mikrodeletion 22q11.2 (64,3 %). 25 (33,8 %) hatten extrakardiale Fehlbildungen. 4 (5,4 %) hatten eine Ductus arteriosus (DA) -Agenesie, 22 (29,7 %) einen rechten Aortenbogen (RAA), 9 (12,2 %) hatten aortopulmonale Kollateralen (MAPCAs). In der Postnatal-Diagnose-Gruppe waren keine Patienten mit TOF-PA, 4 von 68 (5,9 %) hatten TOF-APVS. 12 (17,6 %) hatten extrakardiale Fehlbildungen, 9 (13,2 %) hatten einen auffälligen Karyotyp, darunter 2/9 mit Mikrodeletion 22q11.2. 10 (14,7 %) hatten ein RAA, 9 (13,2 %) hatten MAPCAs. Es gab keine DA-Agenesien. Pränatal höhere z-Werte der linken/rechten Pulmonalarterie (LPA/RPA) waren mit einer niedrigeren Wahrscheinlichkeit für eine frühe postnatale Intervention assoziiert (RPA: p = 0,017; LPA: p = 0,013). Innerhalb der Pränatal-Diagnose-Gruppe benötigten 12 von 41 (29,3 %) Lebendgeburten mit follow-up und Intention-to-treat eine frühe Intervention versus 7 von 68 (10,3 %) innerhalb der Postnatal-Diagnose-Gruppe (p = 0,02). In der Postnatal-Diagnose-Gruppe gab es keine Todesfälle, in der Pränatal-Diagnose-Gruppe gab es 2/41 (4,9 %) Todesfälle postinterventionell. Es zeigten sich keine Unterschiede hinsichtlich post-interventionellem Überleben in der Pränatal-Diagnose-Gruppe versus Postnatal-Diagnose-Gruppe. Komplexe Fälle könnten in der Postnatal-Diagnose-Gruppe unterrepräsentiert sein. Pränatal kleinere RPA/LPA-Werte scheinen mit einer frühen postnatalen Intervention assoziiert zu sein.

Supplemental Digital Content is available in the text., Background: In addition to enhanced proinflammatory signaling, impaired resolution of vascular inflammation plays a key role in atherosclerosis. Proresolving lipid mediators formed through the 12/15 lipoxygenase pathways exert protective effects against murine atherosclerosis. n-3 Polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), serve as the substrate for the formation of lipid mediators, which transduce potent anti-inflammatory and proresolving actions through their cognate G-protein–coupled receptors. The aim of this study was to identify signaling pathways associated with EPA supplementation and lipid mediator formation that mediate atherosclerotic disease progression. Methods: Lipidomic plasma analysis were performed after EPA supplementation in Apoe−/− mice. Erv1/Chemr23−/−xApoe−/− mice were generated for the evaluation of atherosclerosis, phagocytosis, and oxidized low-density lipoprotein uptake. Histological and mRNA analyses were done on human atherosclerotic lesions. Results: Here, we show that EPA supplementation significantly attenuated atherosclerotic lesion growth induced by Western diet in Apoe−/− mice and was associated with local cardiovascular n-3 enrichment and altered lipoprotein metabolism. Our systematic plasma lipidomic analysis identified the resolvin E1 precursor 18-monohydroxy EPA as a central molecule formed during EPA supplementation. Targeted deletion of the resolvin E1 receptor Erv1/Chemr23 in 2 independent hyperlipidemic murine models was associated with proatherogenic signaling in macrophages, increased oxidized low-density lipoprotein uptake, reduced phagocytosis, and increased atherosclerotic plaque size and necrotic core formation. We also demonstrate that in macrophages the resolvin E1–mediated effects in oxidized low-density lipoprotein uptake and phagocytosis were dependent on Erv1/Chemr23. When analyzing human atherosclerotic specimens, we identified ERV1/ChemR23 expression in a population of macrophages located in the proximity of the necrotic core and demonstrated augmented ERV1/ChemR23 mRNA levels in plaques derived from statin users. Conclusions: This study identifies 18-monohydroxy EPA as a major plasma marker after EPA supplementation and demonstrates that the ERV1/ChemR23 receptor for its downstream mediator resolvin E1 transduces protective effects in atherosclerosis. ERV1/ChemR23 signaling may represent a previously unrecognized therapeutic pathway to reduce atherosclerotic cardiovascular disease.

In the present study arsenic contaminated simulated water and groundwater was treated by the combination of biological oxidation of tri-valent arsenite [As (III)] to penta-valent arsenate [As (V)] in presence of Acidothiobacillus ferrooxidans bacteria and its removal by adsorptive filtration in a bioreactor system. This method includes the immobilisation of A.ferrooxidans on Granulated Activated Carbon (GAC) capable of oxidising ferrous [Fe (II)] to ferric [Fe (III)]. The Fe (III) significantly converts the As (III) to As (V) and ultimately removed greater than 95% by the bed of GAC, limestone, and sand. The significant influence of Fe (II) concentration (0.1–1.5 gL−1), flowrate (0.06–0.18 Lh−1), and initial As (III) concentration (100–1000 µgL−1) on the arsenic removal efficiency was investigated. The simulated water sample containing the different concentration of As (III) and other ions was used in the study. The removal of other co-existing ions present in contaminated water was also investiga...

The aim of this investigation was to determine the efficiency of arsenic removal present in acidic water using the biochemical method in presence of Acidothiobacillus ferrooxidans bacteria and ferrous ions. The process includes the bio-oxidation of ferrous to ferric by bacteria with simultaneous conversion of arsenite to arsenate and its removal by chemical method. The experiments were carried out in shake flasks with or without A.ferrooxidans culture. The variables of the pH, temperature, cell density and initial concentration of ferrous ions in the growth medium of A.ferrooxidans bacteria were examined in the laboratory to determine how they affect the removal of arsenic. It was found that the maximum arsenic removal (80%–85%) occurred at ferrous ions concentration of 2 gL−1 at the temperature of 35 °C with the initial cell density of 3.66 × 107 cells/mL and initial pH value of 2.5 with 70%–75% bio-oxidation of ferrous ions. The results of scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses have confirmed the growth of bacteria and identify the nature of precipitate generated by the bacteria. The finding showed that arsenic can be removed considerably in this process in an efficient and greener way, but also removing efficiency was much more ( 80 % ) in acidic wastewater. The ANOVA and LSD statistical analysis were performed to assess any significant differences occurred among the four different levels of each variable. This study verified that combination of bio-oxidation with filtration improves the removal efficiency of arsenic.

Nursing care of the neonate in the neonatal intensive care unit (NICU) is complex, due in large part to various physiological challenges. A newer and less well-known physiological consideration is the neonatal microbiome, the community of microorganisms, both helpful and harmful, that inhabit the human body. The neonatal microbiome is influenced by the maternal microbiome, mode of infant birth, and various aspects of NICU care such as feeding choice and use of antibiotics. The composition and diversity of the microbiome is thought to influence key health outcomes including development of necrotizing enterocolitis, late-onset sepsis, altered physical growth, and poor neurodevelopment. Nurses in the NICU play a key role in managing care that can positively influence the microbiome to promote more optimal health outcomes in this vulnerable population of newborns.

Background Different lipid mediators may have opposing effects on vascular inflammation. For example, whereas leukotriene B4 (LTB4) transduces inflammation, resolvin D1 (RvD1), which is synthesized from the omega-3 fatty acid docosahexaenoic acid, facilitates the resolution of inflammation. The aim of this study was to determine the association of the RvD1/LTB4 ratio with subclinical atherosclerosis. Methods Saliva samples and ultrasound measurements of the intima media thickness of the carotid artery was obtained for 254 participants. The lipid mediators RvD1 and LTB4 were measured by enzyme-linked immunosorbent assay. Results Participants with a salivary RvD1/LTB4 ratio >1 had a significantly lower intima media thickness than those in whom LTB4 prevailed. The salivary RvD1/LTB4 ratio independently predicted carotid intima media thickness. Conclusions The ratio between the proresolving and proinflammatory salivary lipid mediators RvD1 and LTB4 may serve as a biomarker of non-resolving inflammation and its relation to intima media thickness in cardiovascular disease.

This study aimed to compare the blood pressure responses in normotensive-trained men following resistance training (RT) experimental sessions with loads of 60% and 80% of a one-repetition maximum. Ten participants underwent three experimental condition: (P60) – session adjusted with 60%, (P80) – session adjusted with 80% of 1 repetition maximum (1RM) and, (CONT) – only blood pressure assessments in rest condition for 60 min (intervals of 10 min). The resistance training design was adjusted with 3-sets, 3-min rest interval length between sets and exercises. Blood pressure was measured before, and at 10, 20, 30, 40, 50, and 60 min after the training session. The results showed that both protocols induce post-exercise hypotension ( p p

Cardiac transplantation for children with end-stage cardiac disease with no other medical or surgical options is now standard. The number of children in need of cardiac transplant continues to exceed the number of donors considered "acceptable." Therefore, there is an urgent need to understand which recipients are in greatest need of transplant before becoming "too ill" and which "marginal" donors are acceptable in order to reduce waitlist mortality. This article reviewed primarily pediatric studies reported over the last 15 years on waitlist mortality around the world for the various subgroups of children awaiting heart transplant and discusses strategies to try to reduce the cardiac waitlist mortality.

During a single heartbeat, muscle cells in the heart contract and relax. Under healthy conditions, the behaviour of these muscle cells is almost identical from one beat to the next. However, this regular rhythm can be disturbed giving rise to a variety of cardiac arrhythmias including cardiac alternans. Here, we focus on so-called microscopic calcium alternans and show how their complex spatial patterns can be understood with the help of the master stability function. Our work makes use of the fact that cardiac muscle cells can be conceptualised as a network of networks, and that calcium alternans correspond to an instability of the synchronous network state. In particular, we demonstrate how small changes in the coupling strength between network nodes can give rise to drastically different activity patterns in the network.

Background. The absolute number of patients presenting with failure of the hemi-Fontan or Fontan circulation for cardiac transplantation (cTx) will continuously rise. We aimed to analyze the intraoperative differences in patients undergoing cTx for a failing hemi-Fontan or Fontan circulation (group A) with those undergoing cTx for cardiomyopathy and congenital heart disease (group B). Methods. Data of patients undergoing cTx during a 10-year period were compared between group A and group B patients. Results. cTx was performed in 83 patients (group A, n = 21; group B, n = 62). Surgical times including median incision-suture time (549 minutes vs 386 minutes, P < .05) and median organ ischemia time (305 minutes vs 233 minutes, P < .05) were longer in group A patients. After weaning off cardiopulmonary bypass a higher median modified Vasoactive Inotropic Score (16 vs 10, P < .05) was necessary in group A patients. During surgery more fresh frozen plasma (44 mL/kg vs 20 mL/kg, P < .05), platelet concentrates (20 mL/kg vs 14 mL/kg, P < .05), and coagulation factor concentrates were given in group A patients. Mortality during the first 90 days after cTx was higher in group A (23.8% vs 6.5%, P < .05). Conclusion. Patients undergoing cTx for a failing hemi-Fontan or Fontan circulation are challenging. They require an intensive vasoactive and inotropic support; furthermore, special attention should be paid to the management of bleeding complications. cTx for this group of patients is associated with higher 90 days mortality.

BACKGROUND Neonatal management of patients with hypoplastic left heart syndrome and complex remains a challenging task, whereby the "hybrid" palliation is often reserved for high-risk patients as a "rescue" procedure. AIM This study documents the anesthetic challenges and potential complications associated with the Giessen hybrid stage I approach. METHODS The Giessen hybrid stage I approach is focused on surgical bilateral pulmonary artery banding. Retrospective perioperative data were analyzed. Contrary to a stable group A, inotropic treatment before surgery for treatment of postnatal shock classified patients as unstable (Group B). Clinical outcomes considered were inhospital mortality, duration of postoperative mechanical ventilation, postoperative time at the intensive care unit, perioperative vasoactive medication requirements, and red blood cell transfusion. RESULTS From June 1998 to December 2015, 185 patients were allocated to Group A (n = 165) and Group B (n = 20). The inhospital mortality was 2.2% with no difference between the groups. There was also no difference in the postoperative time on mechanical ventilation and the time in the intensive care unit. Vasoactive medication was more often required in Group B (100%) compared to Group A (19%). In Group B, more red blood cells were transfused 6.0 ± 8.3 vs 2.0 ± 5.8 mL/kg in Group A (P

BACKGROUND Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. METHODS Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). RESULTS LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (β = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. CONCLUSIONS Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

Comprehensive stage II is the advanced surgical part of the staged treatment of a newborn with hypoplastic left heart syndrome (HLHS) palliated initially by a Giessen-Hybrid approach. We report an almost ideal course following comprehensive stage II operation with focus on postoperative intensive care strategy. Following a short introduction of the postnatally performed Giessen-Hybrid approach, in which the surgical part is focused on bilateral pulmonary banding and duct stenting as well as manipulation of the atrial septum is postponed to transcatheter approach, it should be emphasized, that the quality of inter-stage I is eminently important for the success of the following comprehensive stage II. Furthermore, the interplay of the responsible surgeon, anesthesiologist, cardiologist and intensivist is mandatory for working as a team with a similar pathophysiological background. Presupposed a sophisticated surgical and anesthesiologic management, the immediate post-operative intensive care is crucial for the patient's final outcome, not only in terms of mortality but even morbidity (long-term neurological condition). Detailed treatment strategies are presented by pathophysiological reasonable hypotheses and the current pharmacological knowledge. Aiming to improve systemic and regional oxygen delivery and lowering oxygen consumption, as a sine qua none for a favorable patient's outcome.

The Cell Atlas, part of the Human Protein Atlas project, systematically investigate the spatiotemporal subcellular distribution of human proteins. This is our standard protocol for indirect immunostaining of cells cultured in 96-well glass bottom plates.

Aim This study was conducted to find out the relationship of prepartum udder and teat measurements with subsequent milk production traits in primiparous Nili-Ravi buffaloes. Materials and methods A total of 12 Nili-Ravi buffalo heifers were selected from Buffalo Farm, Central Institute for Research on Buffaloes, Regional Station- Bir Dosanjh, Nabha, Patiala, Punjab. The udder length (UL), udder width (UW), udder depth, teat length (TL), teat diameter (TD), and teat distances were measured at fortnightly interval from 60 days prepartum until calving. After calving, 60 days total milk yield (TDMY), peak yield (PY), and days taken to attain PY (DPY) were also recorded. The correlation coefficients of various prepartum udder and teat measurements since 60 days prepartum to calving with 60 days TDMY, PY, and DPY were calculated to find out the relationship between the traits in primiparous Nili-Ravi buffaloes. Results The result envisaged that all udder and teat measurements were increased gradually toward the date of calving in primiparous buffaloes. The UL, UW, left fore (LF) and right rear (RR)TL, RRTD, and the distance between LF to left rear (LR) teat were positively correlated with 60 days TDMY. The UL and UW depicted positive but nonsignificant correlation with PY. Fore TLs showed positive correlation where as TDs and teat distances had a negative correlation with the DPY in primiparous Nili-Ravi buffaloes. Conclusion It was concluded that milk production performance could be assessed on the basis of prepartum udder and teat measurements in primiparous Nili-Ravi buffaloes.

Objective Clinical assessments that rely on behavioral responses to differentiate Disorders of Consciousness are at times inapt because of some patients’ motor disabilities. To objectify patients’ conditions of reduced consciousness the present study evaluated the use of electroencephalography to measure residual brain activity. Methods We analyzed entropy values of 18 scalp EEG channels of 15 severely brain-damaged patients with clinically diagnosed Minimally-Conscious-State (MCS) or Unresponsive-Wakefulness-Syndrome (UWS) and compared the results to a sample of 24 control subjects. Permutation entropy (PeEn) and symbolic transfer entropy (STEn), reflecting information processes in the EEG, were calculated for all subjects. Participants were tested on a modified active own-name paradigm to identify correlates of active instruction following. Results PeEn showed reduced local information content in the EEG in patients, that was most pronounced in UWS. STEn analysis revealed altered directed information flow in the EEG of patients, indicating impaired feed-backward connectivity. Responses to auditory stimulation yielded differences in entropy measures, indicating reduced information processing in MCS and UWS. Conclusions Local EEG information content and information flow are affected in Disorders of Consciousness. This suggests local cortical information capacity and feedback information transfer as neural correlates of consciousness. Significance The utilized EEG entropy analyses were able to relate to patient groups with different Disorders of Consciousness.

Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of maternal tasks, including labor, lactation, and infant bonding, has also been hypothesized to have a role in postpartum depression. Women are routinely given synthetic oxytocin to induce or augment labor and to prevent postpartum hemorrhage. The aim of this study was to review the quality and reliability of literature that examines potential relationships between OT and PPD to determine if there is sufficient data to reliably assess the strength of these relationships. We conducted a literature search in December of 2018 using five databases (PubMed, Web of Science, Embase, PsycInfo, and CINAHL). Eligible studies were identified, selected, and appraised using the Newcastle-Ottawa quality assessment scale and Cochrane Collaboration’s tool for assessing risk of bias, as appropriate. Sixteen studies were included in the analysis and broken into two categories: correlations of endogenous OT with PPD and administration of synthetic OT with PPD. Depressive symptoms were largely measured using the Edinburgh Postnatal Depression Scale. OT levels were predominately measured in plasma, though there were differences in laboratory methodology and control of confounders (primarily breast feeding). Of the twelve studies focused on endogenous oxytocin, eight studies suggested an inverse relationship between plasma OT levels and depressive symptoms. We are not able to draw any conclusions regarding the relationship between intravenous synthetic oxytocin and postpartum depression based on current evidence due to the heterogeneity and small number of studies (n = 4). Considering limitations of the current literature and the current clinical prevalence of synthetic OT administration, we strongly recommend that rigorous studies examining the effects of synthetic OT exposure on PPD should be performed as well as continued work in defining the relationship between endogenous OT and PPD.