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Plant genomes encode hundreds of secreted peptides; however, relatively few have been characterised. We report here an uncharacterised, stress-induced family of plant signalling peptides, which we call CTNIPs. Based on the role of the common co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) in CTNIP-induced responses, we identified in Arabidopsis thaliana the orphan receptor kinase HAESA-LIKE 3 (HSL3) as the CTNIP receptor via a proteomics approach. CTNIP-binding, ligand-triggered complex formation with BAK1, and induced downstream responses all involve HSL3. Notably, the HSL3-CTNIP signalling module is evolutionarily conserved amongst most extant angiosperms. The identification of this novel signalling module will further shed light on the diverse functions played by plant signalling peptides and will provide insights into receptor-ligand co-evolution.

In plants, antimicrobial immune responses involve the cellular release of anions and are responsible for the closure of stomatal pores. Detection of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) induces currents mediated via slow-type (S-type) anion channels by a yet not understood mechanism. Here, we show that stomatal closure to fungal chitin is conferred by the major PRRs for chitin recognition, LYK5 and CERK1, the receptor-like cytoplasmic kinase PBL27, and the SLAH3 anion channel. PBL27 has the capacity to phosphorylate SLAH3, of which S127 and S189 are required to activate SLAH3. Full activation of the channel entails CERK1, depending on PBL27. Importantly, both S127 and S189 residues of SLAH3 are required for chitin-induced stomatal closure and anti-fungal immunity at the whole leaf level. Our results demonstrate a short signal transduction module from MAMP recognition to anion channel activation, and independent of ABA-induced SLAH3 activation.

Pathogens modulate plant cell structure and function by secreting effectors into host tissues. Effectors typically function by associating with host molecules and modulating their activities. This study aimed to identify the host processes targeted by the RXLR class of host-translocated effectors of the potato blight pathogen Phytophthora infestans. To this end, we performed an in planta protein-protein interaction screen by transiently expressing P. infestans RXLR effectors in Nicotiana benthamiana leaves followed by coimmunoprecipitation and liquid chromatography-tandem mass spectrometry. This screen generated an effector-host protein interactome matrix of 59 P. infestans RXLR effectors x 586 N. benthamiana proteins. Classification of the host interactors into putative functional categories revealed over 35 biological processes possibly targeted by P. infestans. We further characterized the PexRD12/31 family of RXLR-WY effectors, which associate and colocalize with components of the vesicle trafficking machinery. One member of this family, PexRD31, increased the number of FYVE positive vesicles in N. benthamiana cells. FYVE positive vesicles also accumulated in leaf cells near P. infestans hyphae, indicating that the pathogen may enhance endosomal trafficking during infection. This interactome dataset will serve as a useful resource for functional studies of P. infestans effectors and of effector-targeted host processes.

Parasitic plants of the genus Cuscuta penetrate shoots of host plants with haustoria and build a connection to the host vasculature to exhaust water, solutes and carbohydrates. Such infections usually stay unrecognized by the host and lead to harmful host plant damage. Here, we show a molecular mechanism of how plants can sense parasitic Cuscuta. We isolated an 11 kDa protein of the parasite cell wall and identified it as a glycine-rich protein (GRP). This GRP, as well as its minimal peptide epitope Crip21, serve as a pathogen-associated molecular pattern and specifically bind and activate a membrane-bound immune receptor of tomato, the Cuscuta Receptor 1 (CuRe1), leading to defense responses in resistant hosts. These findings provide the initial steps to understand the resistance mechanisms against parasitic plants and further offer great potential for protecting crops by engineering resistance against parasitic plants.

Plant immunity consists of two arms: pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), induced by surface-localized receptors, and effector-triggered immunity (ETI), induced by intracellular receptors. Despite the little structural similarity, both receptor types activate similar responses with different dynamics. To better understand phosphorylation events during ETI, we employed a phosphoproteomic screen using an inducible expression system of the bacterial effector avrRpt2 in Arabidopsis thaliana, and identified 109 differentially phosphorylated residues of membrane-associated proteins on activation of the intracellular RPS2 receptor. Interestingly, several RPS2-regulated phosphosites overlap with sites that are regulated during PTI, suggesting that these phosphosites may be convergent points of both signaling arms. Moreover, some of these sites are residues of important defense components, including the NADPH oxidase RBOHD, ABC-transporter PEN3, calcium-ATPase ACA8, noncanonical Gα protein XLG2 and H+ -ATPases. In particular, we found that S343 and S347 of RBOHD are common phosphorylation targets during PTI and ETI. Our mutational analyses showed that these sites are required for the production of reactive oxygen species during both PTI and ETI, and immunity against avirulent bacteria and a virulent necrotrophic fungus. We provide, for the first time, large-scale phosphoproteomic data of ETI, thereby suggesting crucial roles of common phosphosites in plant immunity.

The Saffman-Delbrück hydrodynamic model for lipid-bilayer membranes is modified to account for the periodic boundary conditions commonly imposed in molecular simulations. Predicted lateral diffusion coefficients for membrane-embedded solid bodies are sensitive to box shape and converge slowly to the limit of infinite box size, raising serious doubts for the prospects of using detailed simulations to accurately predict membrane-protein diffusivities and related transport properties. Estimates for the relative error associated with periodic boundary artifacts are 50% and higher for fully atomistic models in currently feasible simulation boxes. MARTINI simulations of LacY membrane protein diffusion and LacY dimer diffusion in DPPC membranes and lipid diffusion in pure DPPC bilayers support the underlying hydrodynamic model.

Lipid areas (Aℓ), bilayer area compressibilities (KA), bilayer bending constants (KC), and monolayer spontaneous curvatures (c0) from simulations using the CHARMM36 force field are reported for 12 representative homogenous lipid bilayers. Aℓ (or their surrogate, the average deuterium order parameter in the "plateau region" of the chain) agree very well with experiment, as do the KA. Simulated KC are in near quantitative agreement with vesicle flicker experiments, but are somewhat larger than KC from X-ray, pipette aspiration, and neutron spin echo for saturated lipids. Spontaneous curvatures of bilayer leaflets from the simulations are approximately 30% smaller than experimental values of monolayers in the inverse hexagonal phase.

The bilayer bending modulus (Kc) is one of the most important physical constants characterizing lipid membranes, but precisely measuring it is a challenge, both experimentally and computationally. Experimental measurements on chemically identical bilayers often differ depending upon the techniques employed, and robust simulation results have previously been limited to coarse-grained models (at varying levels of resolution). This Communication demonstrates the extraction of Kc from fully atomistic molecular dynamics simulations for three different single-component lipid bilayers (DPPC, DOPC, and DOPE). The results agree quantitatively with experiments that measure thermal shape fluctuations in giant unilamellar vesicles. Lipid tilt, twist, and compression moduli are also reported.

This article evaluates the pediatric cardiology (PC) workforce and forecasts its future supply. Produced as part of a supplement in Pediatrics, this effort represents a collaboration among the American Board of Pediatrics Foundation, the University of North Carolina at Chapel Hill's Carolina Health Workforce Research Center, the Strategic Modeling and Analysis Ltd., and members of the pediatric subspecialty community. PC is a complex subspecialty including care from fetal life through adulthood and in practice settings that range from the outpatient clinic to procedural settings to the cardiac ICU. Complex subdisciplines include imaging, electrophysiology, heart failure, and interventional and critical care. Using American Board of Pediatrics data, US Census Bureau data, and data from the modeling project, projections were created to model the subspecialty workforce through 2040. Across all modeling scenarios considered, there is considerable projected growth in the supply of pediatric cardiologists by 2040. However, there is significant regional variation in the projected supply of trainees relative to demand in terms of local population growth, with evidence of a likely mismatch between areas surrounding training centers versus areas of greatest workforce need. In addition, this article highlights areas for future focus, including efforts to attract more residents to the subspecialty in general, particularly underrepresented minority members; increased support, more part-time career options, and improved academic career advancement for women in PC; and the development of better "real-time" workforce data to guide trainees and training programs in decisions regarding sub-subspecialty job availability., (Copyright © 2024 by the American Academy of Pediatrics.)

Entrustable professional activities (EPAs) are "observable essential tasks expected to be performed by a physician for safe patient care in practice." Six Pediatric Cardiology (PC) EPAs and their level of supervision (LOS) scales were developed by medical educators in PC using a modified Delphi process and reviewed by the Subspecialty Pediatrics Investigator Network (SPIN). However, their general use in assessment for PC fellows for graduation requirements has yet to be studied. The objective of this study was to determine the minimum LOS required for PC fellows to graduate and compare it with the minimum LOS expected for safe and effective practice for the six PC EPAs, from the perspective of the PC Fellowship Program Directors(FPD). All Fellowship Program Directors(FPD) of ACGME-accredited PC fellowships were surveyed through SPIN between April 2017 and August 2017. For each of the PC EPAs, the FPDs were asked to indicate the minimum LOS expected for graduation and whether they would allow a fellow to graduate if this level was not achieved and the minimum LOS expected for a practicing pediatric cardiologist to provide safe and effective patient care. The minimum LOS was defined as the LOS for which no more than 20% of FPDs would want a lower level. The survey response rate was 80% (47/59). The majority of the FPDs did not require a minimum LOS of five corresponding to unsupervised practice in any of the six PC EPAs at graduation. For EPAs related to imaging, arrhythmia management, and management of cardiac problems, the minimum LOS for graduation was 3, corresponding to being "trusted to perform a task with indirect supervision for most simple and a few complex cases." For the EPAs related to interventional cardiology, heart failure pulmonary hypertension, and cardiac intensive care, the minimum LOS for graduation was 2, corresponding to being "trusted to perform a task only with direct supervision and coaching." The minimum LOS considered necessary for safe and effective practice for all but one EPA was 3. For the EPA related to the management of cardiac problems, the minimum LOS for safe practice was 4, corresponding to being "trusted to execute tasks independently except for few complex and critical cases." Most PC FPDs reported they would not require fellows to achieve the highest entrustment level for any of the six PC EPAs for graduation. It is crucial that educational programs evolve to address these essential activities during training better and that stakeholders ensure that graduating PC fellows have adequate resources and infrastructure to continue professional development as early career pediatric cardiologists., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Repaired tetralogy of Fallot (RTOF) patients will develop right ventricular (RV) dysfunction from chronic pulmonary regurgitation (PR). Cardiac magnetic resonance sequences such as four-dimensional flow can demonstrate altered vorticity and flow energy loss (FEL); however, they are not as available as conventional echocardiography (echo). The study determined whether a novel, vendor-independent Doppler velocity reconstruction (DoVeR) could measure RV intracardiac flow in conventional echo of RTOF patients. The primary hypothesis was that DoVeR could detect increased vorticity and diastolic FEL in RTOF patients., Methods: Repaired tetralogy of Fallot patients with echo were retrospectively paired with age-/size-matched controls. Doppler velocity reconstruction employed the stream function-vorticity equation to approximate intracardiac flow fields from color Doppler. A velocity field of the right ventricle was reconstructed from the apical 4-chamber view. Vortex strength (VS, area integral of vorticity) and FEL were derived from DoVeR. Cardiac magnetic resonance and exercise stress parameters (performed within 1 year of echo) were collected for analysis., Results: Twenty RTOF patients and age-matched controls were included in the study. Mean regurgitant fraction was 40.5% ± 7.6%, and indexed RV end-diastolic volume was 158 ± 36 mL/m 2 . Repaired tetralogy of Fallot patients had higher total, mean diastolic, and peak diastolic VS (P = .0013, P = .0012, P = .0032, respectively) and higher total, mean diastolic, and peak diastolic body surface area-indexed FEL (P = .0016, P = .0022, P < .001, respectively). Peak diastolic indexed FEL and peak diastolic VS had weak-to-moderate negative correlation with RV ejection fraction (r = -0.52 [P = .019] and r = -0.49 [P = .030], respectively) and left ventricular ejection fraction (r = -0.47 [P = .034] and r = -0.64 [P = .002], respectively). Mean diastolic indexed FEL and VS had moderate-to-strong negative correlation with percent predicted maximal oxygen consumption (r = -0.69 [P = .012] and r = -0.75 [P = .006], respectively)., Conclusions: DoVeR can detect alterations to intracardiac flow in RTOF patients from conventional color Doppler imaging. Echo-based measures of diastolic VS and FEL correlated with ventricular function. DoVeR has the potential to provide serial evaluation of abnormal flow dynamics in RTOF patients., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic., Objectives: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children., Methods: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum., Results: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04)., Conclusion: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth., Methods: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions., Results: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25)., Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, highlighting concerns regarding the inequities in access to cardiac care and the need for multidisciplinary care. We also recognize the problems of transparency in outcomes reporting and the promising application of telehealth. Finally, we highlight the training of providers, measures of productivity, diversity in the workforce, and the importance of patient-family centered organizations in advocating for patients. Although all of these issues remain relevant to many subspecialties in medicine, this article attempts to illustrate the unique needs of this population and highlight ways in which to work together to address important opportunities for change in the cardiac care community and beyond. This article provides a framework for policy and advocacy efforts for the next decade.

Objective: Medical education experienced widespread disruption during the first peak of the COVID-19 pandemic. In response, members of the Society of Pediatric Cardiology Training Program Directors (SPCTPD) created a series of live, Zoom-based lectures for pediatric cardiology fellows. The goals were to support fellow didactic education and connect fellows and faculty during the pandemic. We sought to determine the impact of the lecture series on pediatric cardiology fellows around the country., Methods: Pediatric cardiology experts from across the country volunteered to give lectures in the Pediatric Cardiology National Education Series (PC-NES). Lectures were held online once or twice weekly for 3 months during Spring 2020, while many fellows had modified clinical responsibilities. Fellows voluntarily completed an online survey before and after the lecture series., Results: On the initial survey, a majority of fellows responded they would benefit from more didactic education while their training was impacted by COVID-19. After the series concluded, almost all (95%) fellows responded that PC-NES lectures were valuable supplements to their training during COVID-19. They included quality of lectures, board-relevance, and a way to connect to the pediatric cardiology community as key reasons for participating in PC-NES, and 100% responded they felt PC-NES should continue in some capacity., Conclusion: The PC-NES was a low-cost, simple way to deliver high-quality supplemental education to pediatric cardiology fellows, help trainees build a network of peers and learn from experts outside their home institution. Similar models could connect other pediatric trainees at local, regional, or national levels, and provide valuable supplemental education opportunities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

Successfully matching into a pediatric cardiology fellowship program is difficult, and there is currently a paucity of helpful material for prospective applicants. To address this gap and to guide pediatric cardiology fellowship applicants in navigating this process, three fellowship program directors have compiled a list of recommendations on how residents can improve their chances for a successful match. Detailed descriptions of the following recommendations are provided: become a great pediatrician, show consistent interest in pediatric cardiology, complete a research project, ensure great letters of recommendation, don't botch the personal statement, and apply wisely and interview effectively.

Objective: To test whether children with epilepsy have impairments in myocardial mechanics compared to controls without epilepsy., Methods: Children with refractory epilepsy with epilepsy duration of at least 3 years underwent echocardiography including conventional measurements and speckle tracking to assess longitudinal and circumferential strain. Parent-completed surveys, capturing critical aspects of the children's seizure history and cardiac risk factors, complemented retrospective chart reviews, which also included antiepileptic drug history. Normal echocardiograms from controls, matched for age and gender, were obtained from our institutional database and evaluated for strain., Results: Forty-one patients (median age = 10 years, interquartile range [IQR] = 5-15; 58.5% male) were enrolled. Epilepsy etiology included genetic (n = 26), structural (n = 6), genetic and structural (n = 5), infection (n = 3), and unknown (n = 1). No cardiac structural abnormalities were identified. Both longitudinal and circumferential strain were impaired (P < .03) in patients compared to controls (median [IQR] = 22.7% [21.2-24.2] vs 23.6% [22.2-26.1] and 22.0% [20.3-25.4] vs 24.5% [22.3-27.0], respectively), indicating decreased myocardial deformation/contraction. Shortening fraction was higher in patients (37.6% [35.7-39.7] vs 34.9% [32.5-38.7], P = .009); mitral valve E wave inflow velocity (84.8 cm/s [78.4-92.8] vs 97.2 cm/s [85.9-105.8], P = .005) and tissue Doppler lateral E' wave (13.9 cm/s [12.3-16.1] vs 17.3 cm/s [15.4-18.5], P < .001) were decreased compared to controls. Findings were similar in the pairs with epilepsy patients distinguished by the ability to independently ambulate. There was no difference between patients and controls in ejection fraction. Among the epilepsy patients, there were no associations between cardiac measurements and epilepsy characteristics, including seizure type and frequency and cardiotoxic antiseizure medication exposure after correction for multiple comparisons., Significance: Children with refractory epilepsy had impaired systolic ventricular strain compared to controls, not correlated with epilepsy history. Further studies are needed to determine the significance of these changes., (© 2020 International League Against Epilepsy.)

We conducted a retrospective study to identify electrocardiogram (ECG) and echocardiogram utilization among patients presenting for a follow-up cardiology evaluation with innocent heart murmur between 2012 and 2014. The 2014 echocardiogram Appropriate Use Criteria was applied. We observed high rates of ordering ECGs and echocardiograms on follow-up visits (79% and 36%); only 1 patient had an appropriate indication for echocardiogram while the rest had rarely appropriate indication. Having had an ECG done did not affect echocardiogram ordering behavior. Older patient age was the only factor associated with a higher likelihood for ordering echocardiograms on follow-up visit (odds ratio = 1.016, P = .021). In this small sample study, we noticed high rates of test utilization and low-probability utilization of echocardiogram in the recurrent evaluation of children with innocent heart murmur. A larger, multicenter prospective study to investigate patterns and drivers of test utilization in children with innocent heart murmur presenting for a follow-up cardiology visit is needed.

A 17-year-old male subject with a history of deep venous thrombosis presented with acute unilateral severe chest pain. His examination was nonspecific, and vital signs were normal. His initial laboratory evaluation revealed mild thrombocytopenia, elevated troponin levels, and critically elevated activated partial thromboplastin time. A computed tomography angiogram of the chest revealed a pulmonary embolus, and anticoagulation therapy was initiated. His course was complicated by the development of multiple thrombi and respiratory failure. Extensive evaluation revealed a rare, underlying diagnosis in time for life-saving treatment to be initiated., (Copyright © 2017 by the American Academy of Pediatrics.)

Objectives: Alterations in myocardial strain can identify cardiac dysfunction and can be measured in the mid-gestation fetus. This study evaluates feasibility of strain measurements in early fetuses and establishes normal early fetal strain values., Methods: Normal fetal echocardiograms were reviewed for image adequacy for strain measurements in 12- to 14-week gestation fetuses. Two readers performed independent strain measurements. Values were compared with data from 40 normal second trimester fetuses., Results: Strain evaluation could be attempted in 36 of 53 (68%) of first trimester echocardiograms (mean gestation 13.4 weeks); excessive motion or inadequate imaging planes precluded tracking analysis in the remainder. Strain measurements were feasible in 19 of 53 fetuses (36%, or 53% of those in whom tracking was attempted). Peak systolic global longitudinal left ventricular (RV) and right ventricular (LV) strain were similar (LV = -13.9 ± 5.7%, RV = -14.4 ± 5.5%, p = 0.7). RV strain was higher in first trimester fetuses compared with second trimester normals (p = 0.003). Intraobserver and interobserver agreement were moderate to strong for peak global LV and RV strain but poor for regional basal and mid-septal segments., Conclusions: Strain measurements were feasible in one-third of retrospectively assessed early fetal echocardiograms. Global longitudinal strain may be higher in earlier than mid-gestation fetuses. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Objectives: Unplanned admissions to the pediatric cardiac ICU may be a large and high-risk group. Our study describes the frequency of unplanned pediatric cardiac ICU admissions, their admission data, and outcomes., Design: All admissions to a pediatric cardiac ICU over 2 years were reviewed and those that were unplanned were identified for a detailed chart abstraction. Demographic, laboratory, diagnostic, and outcome data were collected. Readmission or admission for adverse event was noted., Setting: Single, tertiary, pediatric cardiac center., Patients: All patients admitted unexpectedly to the pediatric cardiac critical care unit between May 2008 and May 2010., Interventions: None., Measurements and Main Results: There were 1,203 admissions to the cardiac ICU, and 426 (35%) were unplanned. The most common reasons for admission were new heart disease (25%), infection (19%), arrhythmia (13%), and congestive heart failure (11%). The majority of unplanned admissions (62%) occurred at night. Shock was present at admission in 18.5% of patients. Structural heart disease was present in 79%, and 39% of those were patients with single ventricle. Overall mortality among unplanned admissions was 7.3%, which is higher than that reported for elective surgical admissions. Mortality for the subset of patients readmitted within 30 days was 5.5%. Mean creatinine at admission was higher among nonsurvivors (0.7) than survivors (0.5)., Conclusions: Unplanned admissions accounted for over one third of all admissions and had a high mortality rate. The majority of these occur at night, which may affect staffing models. Acute deterioration leading to unplanned admission, rather than readmission status, may be the driving factor in increased mortality. However, the risk of readmission, lower renal function, or other indices may identify patients at higher risk of an unplanned admission. Continued efforts to identify patients at risk for unplanned admissions are warranted given the outcomes in this cohort.

Background: Patients with Kawasaki disease (KD) are at risk for developing coronary artery lesions, but the association of noncoronary changes such as mitral regurgitation (MR) and/or pericardial effusion (PE) with cardiac mechanics in the acute phase of KD has not been previously described. The aim of this study was to test the hypothesis that these noncoronary markers for carditis are associated with abnormalities in strain (ε) and strain rate (SR) in patients with MR or PE not appreciated by conventional echocardiography., Methods: Longitudinal and circumferential ε and SR analyses were retrospectively performed on patients with KD. Patients with and without MR or PE were compared. Strain values were also compared between patients with and without coronary artery lesions. Values for ejection fraction, shortening fraction, and clinical laboratory parameters were correlated with MR or PE. Follow-up echocardiographic outcomes were recorded at the first encounter after initial diagnosis. Follow-up ε and SR data were also obtained in the group with MR or PE and altered ventricular mechanics at diagnosis., Results: Of the 110 patients reviewed, 92 had appropriate image quality for either longitudinal ε and SR or circumferential ε and SR analysis. Twenty-eight patients (30%) had either MR or PE. Longitudinal ε and SR were significantly decreased in patients with MR or PE compared with patients without MR or PE (ε: -16.4 ± 4.0% vs -19.0 ± 3.7%, P = .004; SR: -1.3 ± 0.7 vs -1.6 ± 0.4 sec(-1), P = .03). No significant difference in longitudinal ε or SR was noted between patients with and without coronary artery lesions (ε: -17.9 ± 4.1% vs -17.8 ± 3.8%, P = .50; SR: -1.5 ± 0.3 vs -1.6 ± 0.8 sec(-1), P = .50). In the group with abnormal coronary arteries, presence of MR or PE was correlated with decreased longitudinal ε (-16.1 ± 3.6% vs -18.9 ± 3.4%, P = .02), without a significant difference in longitudinal SR (-1.6 ± 0.4 vs -1.5 ± 0.4 sec(-1), P = .20). At approximately 3-week follow-up (21.3 ± 15.8 days), longitudinal ε and SR for the group with MR or PE had increased significantly compared with diagnosis (ε: -16.4 ± 4.3% vs -18.6 ± 0.5%, P = .03; SR: -1.3 ± 0.6 vs -1.8 ± 0.4 sec(-1), P = .008), coincident with resolution of MR or PE. In both groups, erythrocyte sedimentation rate and C-reactive protein were elevated (85.3 ± 36.2 mm/h vs 75.1 ± 33.1 mm/h [P = .34] and 12.3 ± 6.7 vs 11.7 ± 8.2 mg/dL [P = .83]), but only modest correlations were noted between longitudinal ε and elevated erythrocyte sedimentation rate (r = 0.52, P = .01; confidence interval, 0.10-0.80) and C-reactive protein (r = 0.50, P = .02; confidence interval, 0.10-0.80) in patients with MR or PE. Shortening fraction and ejection fraction were within the normal range in both groups., Conclusions: Patients presenting with KD with MR or PE at diagnosis are likely to have altered ventricular mechanics compared with patients with KD without MR or PE despite normal conventional echocardiographic measures of function. There is no significant difference in ventricular mechanics when comparing patients with KD with coronary ectasia or aneurysms and those without coronary lesions. Presence of abnormal ε in patients with KD with altered ventricular mechanics correlates modestly with laboratory inflammatory markers. Peak systolic longitudinal ε and SR increased significantly at 3-week follow-up compared with initial diagnosis, coincident with resolution of MR or PE., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Transesophageal echocardiographic imaging of small infants has been limited because of equipment size. A newer miniaturized transducer has allowed for the imaging of even the smallest patients but has been limited by intermittent poor image quality because of hardware durability. A second generation of the transducer was developed to address this problem. The aim of this study was to evaluate the performance and durability of the second-generation transducer over multiple uses and to compare the image quality from the modified transducer and new software preset to the original transducer., Methods: Patients undergoing transesophageal echocardiography (TEE) based on clinical indications with the original or second-generation transducers were included in the study. All studies were reviewed for image quality and unacceptable image degradation, which was defined as imaging quality inadequate for clinical use. Study review was performed by two echocardiographers., Results: Using the original transducer, 37 studies were performed with a mean patient weight of 3.46±0.89 kg (range 2.1-5.7). Using the second-generation transducer, 65 studies were performed with a mean patient weight of 4.87±2.05 kg (range 2.2-13.8). Image quality was clinically inadequate in 8 of the 35 studies with the original transducer and in zero with the second generation (P<.0001)., Conclusions: The second-generation transducer allows for effective use of TEE even in the smallest infants and avoids the mechanical failures associated with the first-generation release., (© The Author(s) 2014.)

Objective: Sepsis is common in children and often results in cardiac dysfunction. Assessment of patients with sepsis-associated myocardial depression using ejection fraction and fractional shortening with conventional echocardiography is load dependent and often reveals cardiac dysfunction only after clinical deterioration has occurred. Speckle tracking imaging is a novel technology that can assess deformation and strain by tracking displacement of acoustic markers in the myocardium. We hypothesize that speckle tracking imaging will detect cardiac impairments during sepsis that are not appreciated by conventional echocardiography., Design: Retrospective, observational study., Setting: A large, tertiary-care pediatric intensive care unit., Patients: Fifteen pediatric patients with septic shock, and 30 age- and gender-matched healthy controls., Interventions: Transthoracic echocardiograms from subjects with septic shock (by American College of Chest Physicians/Society of Critical Care Medicine consensus criteria) and controls were evaluated. Speckle tracking imaging was used to obtain tissue displacement, velocity, strain, and strain rate in radial, longitudinal, and circumferential planes. Ejection fraction and fractional shortening were determined by conventional methods. Comparisons between groups were made using a paired t test., Measurements and Main Results: Compared to control subjects, children with septic shock demonstrated impaired myocardial performance as quantified by speckle tracking imaging. Significant differences were seen in circumferential and longitudinal strain (p < .001), strain rate (p < .05), radial displacement (p < .001), and rotational velocity and displacement (p < .01). There was no significant difference in ejection fraction and fractional shortening between septic patients and controls., Conclusions: Speckle tracking imaging detected a number of significantly impaired measures of ventricular performance in children with sepsis, not appreciated by conventional echocardiography. This technology may improve our understanding and identification of myocardial depression in the critically ill septic child.

Background: The authors conducted an ultrasound interrogation of a mutant mouse model with a Dnah5 mutation to determine whether cardiac mechanics may be affected by reversal of cardiac situs. This mutant is a bona fide model of primary ciliary dyskinesia, with surviving homozygous mice showing either situs solitus (SS) or situs inversus totalis (SI)., Methods: High-frequency ultrasound interrogations of 27 neonatal and infant Dnah5 mutant mice, 16 with SS and 11 with SI, were conducted using an ultra-high-frequency biomicroscope. Electrocardiographic and respiratory gating were used to reconstruct high-resolution two-dimensional cines at 1,000 Hz, with speckle-tracking echocardiography used to further analyze midchamber and apical rotation., Results: All SS mice exhibited the expected counterclockwise apical rotation as viewed caudocranially, and surprisingly, the same counterclockwise motion was also observed in SI mice. Speckle-tracking analysis confirmed counterclockwise systolic rotation in both SS and SI mice, and this increased in magnitude from the subepicardium to the endocardium and from the papillary muscles to the apex. The magnitude of apical endocardial rotation was not different for SS and SI mice (5.64+/-0.75 degrees and 5.76+/-1.90 degrees, respectively, P=.93). The anatomic segments responsible for the largest components of apical endocardial systolic rotation differed between the SS and SI hearts (P=.004). In both, the two largest contributors to rotation were offset 180 degrees from each other, but the anatomic regions differed between them. In SS hearts, maximal regional rotation occurred at the anterior mid-septum and posterolateral free wall, while in SI hearts, it was derived from the posterior septum and the anterolateral free wall. Analysis by episcopic fluorescence image capture histology of representative SI and SS mice showed normal intracardiac and segmental anatomy ({S,D,S} or {I,L,I}) without intracardiac defects., Conclusions: These results show that mirror-image cardiac looping did not result in mirror-image rotation of the morphologic left ventricle. These findings suggest that further studies are warranted to evaluate whether fiber orientation and cardiac mechanics may be abnormal in individuals with reversal of cardiac situs. The results of this study indicate that cardiac looping and myofiber orientation may be independently regulated., (Copyright (c) 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The amnioserosa is an extraembryonic, epithelial tissue that covers the dorsal side of the Drosophila embryo. The initial development of the amnioserosa is controlled by the dorsoventral patterning genes. Here we show that a group of genes, which we refer to as the U-shaped-group (ush-group), is required for maintenance of the amnioserosa tissue once it has differentiated. Using several molecular markers, we examined amnioserosa development in the ush-group mutants: u-shaped (ush), hindsight (hnt), serpent (srp) and tail-up (tup). Our results show that the amnioserosa in these mutants is specified correctly and begins to differentiate as in wild type. However, following germ-band extension, there is a premature loss of the amnioserosa. We demonstrate that this cell loss is a consequence of programmed cell death (apoptosis) in ush, hnt and srp, but not in tup. We discuss the role of the ush-group genes in maintaining the amnioserosa's viability. We also discuss a possible role for the amnioserosa in germ-band retraction in light of these mutants' unretracted phenotype.

We have constructed six new P-element-based Drosophila melanogaster transformation vectors that specifically allow for the high-level accumulation of any RNA of interest in the developing egg and pre-blastoderm embryo. Such specificity results, in part, from the inclusion in the vectors of an enhancer active exclusively in nurse cells, the principal providers of RNA to the egg and early embryo. The nurse cell enhancer was derived from the hsp26 heat-shock (HS) gene, but its activity was neither dependent on nor sensitive to HS. In addition to the nurse cell enhancer, two of the vectors contain sequences from the K10 gene that promote the early transfer of RNAs from nurse cells into the oocyte; RNAs that contain the K10 sequence are transferred into the oocyte during the early to middle stages of oogenesis (i.e., during stages 2-9), while RNAs that lack such sequences are stored in nurse cells until stage 11. All of the vectors contain a tsp and a multiple cloning site (MCS) immediately downstream from the hsp26 nurse cell enhancer. In three of the vectors, the MCS is preceded by an ATG start codon. A wild-type copy of the white gene is included in all of the vectors as a selectable marker for transformation. The specificity of the vectors was demonstrated by the analysis of the expression patterns of lacZ derivatives.

The highly organized structure of the Drosophila ovary makes it an ideal system for studying mechanisms of differential gene expression. Here we report the identification of a 171 bp sequence from the 5' end of the hsp26 gene that functions as a female germ-line-specific transcriptional regulator when linked in two copies to a basal promoter. The regulator is active only in nondividing cells of the germ line, i.e., only in nurse cells and oocytes. It is not active in any examined tissue or cell type outside of the female germ line. Copper nuclease footprinting studies show that the germ line regulator contains two binding sites for each of two different ovarian nuclear factors. Point mutations in the DNA target sites of either nuclear factor abolish in vitro binding and in vivo transcriptional activity, indicating that each factor is a positive activator of nurse cell/oocyte transcription. The two factors may represent different classes of activator proteins, since an increase in the copy number of one factor's DNA target site cannot compensate for a decrease in the copy number of the other factor's target site.