Search

Rationale: The positive reinforcing effects of alcohol (ethanol) drive repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanol's reinforcing properties is unclear., Objective: This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanol's reinforcing effects in male C57BL/6 J mice., Results: Sucrose-sweetened ethanol self-administration (0.81 g/kg/day) increased AMPAR GluA2 protein expression in the AcbC, without effect on GluA1, compared to sucrose-only controls. Infusion of myristoylated Pep2m in the AcbC, which blocks GluA2 binding to N-ethylmaleimide-sensitive fusion protein (NSF) and reduces GluA2-containing AMPAR activity, reduced ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Antagonizing GluA2-lacking AMPARs, through AcbC infusion of NASPM, had no effect on ethanol self-administration. AcbC neurons receiving projections from the basolateral amygdala (BLA) showed increased sEPSC area under the curve (a measurement of charge transfer) and slower decay kinetics in ethanol self-administering mice as compared to sucrose. Optogenetic activation of these neurons revealed an ethanol-enhanced AMPA/NMDA ratio and significantly reduced paired-pulse ratio, suggesting elevated GluA2 contributions specifically within the BLA➔AcbC pathway., Conclusions: Ethanol use upregulates GluA2 protein expression in the AcbC and AMPAR synaptic activity in AcbC neurons receiving BLA projections and enhances synaptic plasticity directly within the BLA➔AcbC circuit. GluA2-containing AMPAR activity in the AcbC regulates the positive reinforcing effects of ethanol through an NSF-dependent mechanism, highlighting a potential therapeutic target in AUD., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale : The positive reinforcing effects of alcohol (ethanol) drive its repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanol's reinforcing properties is unclear. Objective: This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanol's reinforcing effects in male C57BL/6J mice. Results: Sucrose-sweetened ethanol self-administration (0.81 g/kg/day) increased AMPAR GluA2 protein expression in the AcbC, without effect on GluA1, compared to sucrose-only controls. Infusion of myristoylated Pep2m in the AcbC, which blocks GluA2 binding to N-ethylmaleimide-sensitive fusion protein (NSF) and reduces GluA2-containing AMPAR activity, reduced ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Antagonizing GluA2-lacking AMPARs, through AcbC infusion of NASPM, had no effect on ethanol self-administration. AcbC neurons receiving projections from the basolateral amygdala (BLA) showed increased sEPSC area under the curve (a measurement of charge transfer) and slower decay kinetics in ethanol self-administering mice as compared to sucrose. Optogenetic activation of these neurons revealed an ethanol-enhanced AMPA/NMDA ratio and significantly reduced paired-pulse ratio, suggesting elevated GluA2 contributions specifically within the BLA→AcbC pathway. Conclusions: Ethanol use upregulates GluA2 protein expression in the AcbC and AMPAR synaptic activity in AcbC neurons receiving BLA projections and enhances synaptic plasticity directly within the BLA→AcbC circuit. GluA2-containing AMPAR activity in the AcbC regulates the positive reinforcing effects of ethanol through an NSF-dependent mechanism, highlighting a potential therapeutic target in AUD.

Background: Community health workers (CHWs) connect individuals to community resources and build individual competence in an effort to improve overall community/public health. There is a need for more research on how community health nurse (CHN)-led training programs are needed to help train and support CHWs., Purpose: The purpose was to describe the development and evaluation of a series of CHN-led CHW trainings on CHW role, boundaries, and motivational interviewing; diabetes; mental health and long COVID; sexually transmitted infections; and lead poisoning prevention and treatment., Design: This study utilized a one-group pretest-posttest design in which quantitative and qualitative data were collected., Methods: The sample consisted of CHWs representing White/Caucasian, Black/African American, Hispanic/Latinx, and Asian American populations who for each topic, completed a pretest one week prior to the training, the training, and a posttest one week after the training. The quantitative and qualitative data collected during winter and spring/summer 2023 underwent statistical and thematic analysis, respectively., Findings: The results suggest that the CHW trainings were effective overall at increasing participants' knowledge and confidence in their knowledge levels, as well as comfort with educating community members on various public health topics. Information learned and found most helpful, and application and utilization plans for this knowledge in their work were revealed., Conclusions: CHWs are important for disseminating health communication and education among members of their communities, and play a key role in reducing health disparities among at-risk populations., Clinical Evidence: CHN-led educational intervention is a strategy to improve CHWs' knowledge, confidence, and comfort.

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior., (© 2024. The Author(s).)

Background: The American Heart Association has a call to action to reduce hospital acquired venous thromboembolism (HA-VTE) by 20% by the year 2030. There is increasing recognition that quality improvement initiatives for VTE reduction should focus on reducing potentially preventable HA-VTE. The objective of our study was to determine what proportion of HA-VTE events are potentially preventable. Methods: This was a retrospective, single center pilot study of 50 patients with HA-VTE. Seven preventability factors were identified with a focus on VTE prescription and administration. Data were extracted through chart review using a systematic data collection form. The primary endpoint was the proportion of patients with potentially preventable HA-VTE. Descriptive statistics were used. Results: The median age was 66 years with an admission VTE risk level of moderate-high in 94%. Potentially preventable HA-VTE was found in 40% of cases. Missed doses occurred in 29.8% with a median of 2 missed doses and a range of 1 to 20. Patient refusal was the most common reason for missed doses in 71%. Delays in initiation occurred in 12.7%. Sixty percent of those on mechanical prophylaxis only had nonadherence. Conclusion: Forty percent of HA-VTE cases were potentially preventable. Missed doses was the most common preventability factor identified with patient refusal accounting for most missed doses., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose: The purpose of this research study was to determine the effectiveness of an innovative online COVID-19 educational module among community health nursing students., Design: Mixed-methods study., Methods: The sample ( N  = 86) consisted of prelicensure and postlicensure community health nursing students, who completed a pretest, COVID-19 educational intervention, and posttest., Findings: The majority of participants' scores increased from pretest to posttest, and most participants strongly agreed that the COVID-19 educational module was effective. Strategies to address vaccine hesitancy, information learned and found most helpful, and plans for application and utilization of this knowledge were revealed., Conclusions: An online COVID-19 community health nursing educational intervention was effective at improving participants' knowledge, confidence, and attitudes regarding COVID-19., Clinical Evidence: Online COVID-19 community health nursing education was an effective strategy for increasing preparation for this pandemic and the format can be useful to utilize for future public health emergencies.

Background: Virtual reality (VR) simulation in nursing education, especially about non-acute care including community health, is an emerging learning strategy; more research is needed about its effectiveness. Purpose: This study aimed to evaluate the effectiveness of an innovative community health nursing VR simulation on prelicensure students' knowledge about social determinants of health and cultural competence, with a goal of enhancing students' preparation for practice. Methods: In a convergent mixed methods study, 100 prelicensure nursing students in a community health nursing course at a Midwestern U.S., urban, public university completed a pretest, a VR simulation, a posttest, and an evaluation. Pre- and posttests containing content questions adapted from leading community health nursing text faculty resources were used to assess learning, and the Simulation Effectiveness Tool-Modified (SET-M) was used to assess perceived effectiveness of the intervention. Results: The majority of participants' posttest scores were higher than their pretest scores. Most participants strongly agreed that the VR simulation was effective, and reported on new knowledge/skills learned, material found most helpful, and benefit to their nursing practice. Conclusions: The community health nursing VR simulation was effective at increasing participants' knowledge and their confidence in their knowledge and abilities.

Rationale: The development and progression of alcohol use disorder (AUD) are widely viewed as maladaptive neuroplasticity. The transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) regulatory protein γ8 (TARP γ-8) is a molecular mechanism of neuroplasticity that has not been evaluated in AUD or other addictions., Objective: To address this gap in knowledge, we evaluated the mechanistic role of TARP γ-8 bound AMPAR activity in the basolateral amygdala (BLA) and ventral hippocampus (vHPC) in the positive reinforcing effects of alcohol, which drive repetitive alcohol use throughout the course of AUD, in male C57BL/6 J mice. These brain regions were selected because they exhibit high levels of TARP γ-8 expression and send glutamate projections to the nucleus accumbens (NAc), which is a key nucleus in the brain reward pathway., Methods and Results: Site-specific pharmacological inhibition of AMPARs bound to TARP γ-8 in the BLA via bilateral infusion of the selective negative modulator JNJ-55511118 (0-2 µg/µl/side) significantly decreased operant alcohol self-administration with no effect on sucrose self-administration in behavior-matched controls. Temporal analysis showed that reductions in alcohol-reinforced response rate occurred > 25 min after the onset of responding, consistent with a blunting of the positive reinforcing effects of alcohol in the absence of nonspecific behavioral effects. In contrast, inhibition of TARP γ-8 bound AMPARs in the vHPC selectively decreased sucrose self-administration with no effect on alcohol., Conclusions: This study reveals a novel brain region-specific role of TARP γ-8 bound AMPARs as a molecular mechanism of the positive reinforcing effects of alcohol and non-drug rewards., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Virtual reality simulation in postlicensure nursing education, including community health, is an emerging instructional approach, and more research is needed on its effectiveness. The goal of this study was to evaluate the effectiveness of an innovative, computer-based community health nursing virtual reality simulation among postlicensure nursing students., Method: This mixed methods study consisted of 67 postlicensure community health nursing students who completed a pretest, computer-based virtual reality simulation, and a posttest and evaluation., Results: The majority of participant scores increased from pretest to posttest, and most participants agreed that the computer-based virtual reality simulation was effective; new knowledge and skills learned, the material that was found to be most helpful, and benefits to nursing practice were identified., Conclusion: This community health nursing computer-based virtual reality simulation was effective at increasing participants' knowledge and confidence with learning. [ J Contin Educ Nurs. 2023;54(3):109-116.] .

Of 65 cases during a human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in West Virginia (2019-2021), 61 (94%) had hepatitis C diagnosed a median of 46 months prior to HIV diagnosis. Hepatitis C diagnosis among PWID should trigger improved access to prevention and treatment services., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Aim: To describe the process of engaging underserved communities of color that designs, conducts, and evaluates community-engaged COVID-19 Community Health Navigator training on COVID-19: Vaccination, Prevention, and Contact Tracing., Subject and Methods: The project used a mixed-methods design; 18 community health navigators (CHNs) representing Asian American, Arab American, Black/African American, and Hispanic/Latinx communities completed the pretest, training, and post-test. Demographic characteristics, along with knowledge and confidence level questions regarding COVID-19 issues, were gathered in pre- and post-tests. Qualitative data were collected via open-ended questions in post-tests., Results: Findings suggest that the community health navigator training successfully increased participants' knowledge of COVID-19-related topic areas and confidence in educating community members regarding COVID-19 vaccination and prevention. Qualitative evaluation contained information learned and found most helpful, and application and utilization plans for CHNs' follow-up work., Conclusion: The process of community health navigator training and evaluation results adds important insights to the current COVID-19 pandemic workforce literature and can inform future trainings., Competing Interests: Conflicts of interest/competing interestsThe authors declare that they have no conflicts of interest/competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To evaluate the effectiveness of an online human trafficking awareness program for healthcare providers., Design: Mixed-methods study., Methods: Sample ( N =141) consisted of community health nursing students, who completed a pretest, watched one three-minute video a day for 20 days, and completed a posttest., Findings: Participants indicated their knowledge of human trafficking increased, attitudes toward victims improved, and competence and confidence engaging with victims increased. Satisfaction with program, and information utilization plans for practice were revealed., Conclusions: Human trafficking awareness program was effective in increasing participants' knowledge, competence and confidence, and improving attitudes., Clinical Evidence: Educational intervention is a strategy to improve students' knowledge of human trafficking.

Complementary and alternative medicine therapies can be used as adjuvant or preventive therapy, and have newer applications: cryotherapy, halotherapy, floatation therapy, and compression therapy. Nurse practitioners need to know about these therapies and their applicability to patient populations. Appropriate integration of these therapies is part of holistic care, which they strive to provide., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the effectiveness of a community/public health nursing virtual simulation. Design: Mixed-methods study. Methods: Sample ( N = 121) consisted of community health nursing students, who completed a pretest, virtual simulation, posttest, and satisfaction and self-confidence in learning scale. Findings: Majority of participants' scores increased from pretest to posttest, and most participants agreed or strongly agreed with statements regarding satisfaction and self-confidence in learning; material learned and found most helpful, as well as knowledge application/utilization plans for practice were revealed. Conclusions: Community/public health nursing virtual simulation was effective at increasing participants' knowledge, and satisfaction and self-confidence in learning. Clinical Evidence: Virtual simulation is a strategy to improve students' knowledge of community/public health nursing.

Purpose: To evaluate the effectiveness of a virtual interprofessional collaboration in public health educational intervention., Design: Mixed-methods study., Methods: Sample ( N =171) consisted of community health nursing students, who completed an assessment after watching six videos, illustrating how various disciplines collaborate in a public health department., Findings: Participants felt their interprofessional awareness, understanding, and collaboration intention increased; clarified discipline misconceptions, and application/utilization plans for this knowledge in practice were revealed., Conclusions: Interprofessional collaboration in public health educational intervention was effective in increasing participants' interprofessional awareness, understanding, and intent to collaborate., Clinical Evidence: Educational intervention is a strategy to improve students' knowledge of interprofessional collaboration in public health.

Addiction is viewed as maladaptive glutamate-mediated neuroplasticity that is regulated, in part, by calcium-permeable AMPA receptor (CP-AMPAR) activity. However, the contribution of CP-AMPARs to alcohol-seeking behavior remains to be elucidated. We evaluated CP-AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self-administration in C57BL/6J mice. Operant self-administration of sweetened alcohol increased spontaneous EPSC frequency in BLA neurons that project to the nucleus accumbens as compared with behavior-matched sucrose controls indicating an alcohol-specific upregulation of synaptic activity. Bath application of the CP-AMPAR antagonist NASPM decreased evoked EPSC amplitude only in alcohol self-administering mice indicating alcohol-induced synaptic insertion of CP-AMPARs in BLA projection neurons. Moreover, NASPM infusion in the BLA dose-dependently decreased the rate of operant alcohol self-administration providing direct evidence for CP-AMPAR regulation of alcohol reinforcement. As most CP-AMPARs are GluA1-containing, we asked if alcohol alters the activation state of GluA1-containing AMPARs. Immunocytochemistry results showed elevated GluA1-S831 phosphorylation in the BLA of alcohol as compared with sucrose mice. To investigate mechanistic regulation of alcohol self-administration by GluA1-containing AMPARs, we evaluated the necessity of GluA1 trafficking using a TET-ON AAV encoding a dominant-negative GluA1 c-terminus (GluA1ct) that blocks activity-dependent synaptic delivery of native GluA1-containing AMPARs. GluA1ct expression in the BLA reduced alcohol self-administration with no effect on sucrose controls. These results show that CP-AMPAR activity and GluA1 trafficking in the BLA mechanistically regulate the reinforcing effects of sweetened alcohol. Pharmacotherapeutic targeting these mechanisms of maladaptive neuroplasticity may aid medical management of alcohol use disorder., (© 2021 Society for the Study of Addiction.)

Anthropogenic disturbances associated with urban ecosystems can create favorable conditions for populations of some invasive plant species. Light pollution is one of these disturbances, but how it affects the growth and establishment of invasive plant populations is unknown. Cheatgrass ( Bromus tectorum ) is a problematic invasive species where it has displaced native grassland communities in the United States, but to our knowledge, there have been no studies of the ecological factors that affect cheatgrass presence in urban ecosystems. We conducted field surveys in urban alleys in Denver, Colorado, to compare the presence of cheatgrass at sites with and without artificial light at night (hereafter artificial light) from streetlights. These streetlights are mounted on utility poles, which cause ground disturbance when installed in alleys; we were able to test the independent effect of poles on cheatgrass establishment because not all poles have streetlights on them. We found that cheatgrass was positively associated with the presence of streetlights and to a lesser extent poles. In addition to cheatgrass, we also found that other plants were positively associated with the presence of both poles and streetlights. Our results suggest that artificial light may benefit the occurrence of cheatgrass and other plant species in urban settings. While invasive populations of cheatgrass in wild habitats attract the most attention from managers, we suggest more consideration for this grass in urban environments where its growth and establishment benefit from anthropogenic changes., Competing Interests: None declared., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: A prominent therapeutic indication for alcohol use disorder (AUD) is reduction in chronic repetitive alcohol use. Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) regulate chronic alcohol self-administration in preclinical models. Recent evidence indicates that the expression and function of AMPARs require the transmembrane AMPAR regulatory protein γ-8 (TARP γ-8). This study evaluated the preclinical efficacy of JNJ-55511118, a novel, selective, high-affinity inhibitor of TARP γ-8-bound AMPARs, in reducing chronic operant alcohol self-administration., Methods: Separate groups of male and female C57BL/6J mice (n = 8/sex/group) were trained to lever press for sweetened alcohol (9% v/v + sucrose 2% w/v) or sucrose only (2% w/v) in operant conditioning chambers using an FR-4 schedule of reinforcement. After a 40-day baseline, JNJ-55511118 (0, 1, and 10 mg/kg, p.o.) was administered in randomized order 1 h before self-administration sessions. Parameters of operant behavior including response rate, total reinforcers, and head entries in the drinking troughs were computer recorded., Results: During baseline, responding to alcohol, but not sucrose, was greater in female than male mice. In male mice, both doses of JNJ-55511118 decreased multiple parameters of alcohol self-administration but did not reduce behavior-matched sucrose-only self-administration. JNJ-55511118 had no effect on sweetened alcohol or sucrose self-administration in female mice. Subsequent tests of motor function showed that the lowest effective dose of JNJ-55511118 (1 mg/kg) had no effect on open-field activity in male mice., Conclusions: This study shows for the first time that TARP γ-8-bound AMPARs regulate a behavioral pathology associated with addiction. The preclinical efficacy of JNJ-55511118 in reducing alcohol self-administration in male mice suggests that inhibition of TARP γ-8-bound AMPARs is a novel and highly significant neural target for developing medications to treat AUD and other forms of addiction., (© 2021 Research Society on Alcoholism.)

Abstract: Public health departments exemplify interprofessional collaboration. Nursing and public health education students are required to complete practicum hours or an internship respectively in community health, yet placements at health departments are limited and competitive. This study evaluated the effects of an interprofessional education intervention on community health nursing and health education students' current interprofessional awareness and understanding, and intent to collaborate interprofessionally. Results showed that the majority of participants felt that their interprofessional awareness, understanding, and intent to collaborate increased. This intervention helped bring an example of the health department experience to students and demonstrate its interprofessional nature., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2020 National League for Nursing.)

The challenges of managing an academic/grade grievance can be taxing on nursing faculty. Therefore, it is essential that faculty are well-equipped for these experiences. The purpose of this article is to enable nursing faculty to understand how to navigate a student academic/grade grievance. In this article, three nursing faculty with varying levels of teaching experience will share insightful information on the prevention, preparation, and processes for successfully navigating student academic/grade grievances. They will discuss steps for addressing an academic/grade grievance and lessons learned with helpful tips for nursing faculty to put into their toolbox for future use., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The title compound, {[CuI(bpe)]·0.25(bpe)} n , was synthesized similarly to (CuI) 2 (bpe) [Neal et al. (2019 ▸). IUCrData , 4 , x190122] with red crystals grown from aceto-nitrile solutions of CuI and the bpe ligand [bpe = 1,2-bis-(pyridin-4-yl)ethene, C 12 H 10 N 2 ]. The structure of the title compound is a type 1 complex in the Graham nomenclature [Graham et al. (2000 ▸). Inorg. Chem . 39 , 5121-5132], having rhombic dimers of Cu 2 I 2 that are bridged by two bpe ligands, to form oligomeric ribbons arranged as stairsteps. The step height is 2.8072 (11) Å, which is the Cu-I i distance of the dimer [symmetry code (i): 1 -  x , 2 -  y , 1 -  z ]. The resulting polymer displays a two-dimensional honeycomb framework along the (01) plane, and disordered free bpe mol-ecules fill the voids in the crystal., (© Hoffman et al. 2020.)

Adolescent and young adult females are at increased risk for STDs/STIs and their complications. It is imperative that the sexual health education provided to this vulnerable population is effective. This mixed methods study assessed the impact of an online educational intervention on knowledge of sexual health and STDs/STIs, and impact on behavioral intent among sexually active, young adult females 18-22 years of age. Results showed that the online educational intervention was effective. Scores increased from pretest to posttest and responses included what participants learned and found most helpful, and changes they plan to make as a result of the educational intervention.

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1, IFE-3) that bind 7-methylguanosine (m7G) mRNA caps during Caenorhabditis elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline and localizes to germ granules, but is distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression in spermatocytes of IFE-1, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E-binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The transition between student and new nurse practitioner (NP) can be challenging. Survival guides given to student NPs may help ease the transition and make it a successful one. This study evaluates the effectiveness of survival guides in two student NP cohorts in the fall 2015 and fall 2016 semesters. Students completed a brief online survey at graduation, and three and six months after graduation. Results support the inclusion of survival guides in NP curricula as a creative way to positively support the transition from student to new NP and improve preparation for NP practice.

A high proportion of patients with breast cancer in the Philippines present at an advanced stage and have a rapid, unfavorable outcome. Providing breast cancer education and early detection to this population is important to help reduce this health disparity. This article describes the impact of a train-the-trainer program, with mission groups traveling to the Philippines to promote female residents' breast cancer awareness, knowledge, and intent for future screening.

Metabotropic glutamate receptor subtype-5 (mGluR5) activity regulates a variety of behavioral pathologies associated with alcohol addiction. The main goal of this study was to determine if mGluR5 regulates the induction of ethanol-induced locomotor sensitization, which is a model of experience-dependent plasticity following initial exposure to drugs of abuse. The extracellular signal-regulated kinase (ERK 1/2 ) pathway is downstream of mGluR5 and implicated in alcohol addiction; however, its role in sensitization remains unexplored. We sought to determine if mGluR5-mediated changes in ethanol-induced sensitization are associated with changes in ERK 1/2 phosphorylation (pERK 1/2 ) in specific brain regions. Adult male DBA/2 J mice were tested for acute locomotor response to ethanol (0 or 2 g/kg, IP) followed by a 9-day induction period in which the mGluR5 antagonist MPEP (0 or 30 mg/kg, IP) was administered prior to ethanol (0 or 2.5 g/kg, IP). One day later, ethanol (2 g/kg) produced a robust within- and between-group increase in locomotor activity, indicating sensitization in mice that received MPEP (0 mg/kg) during induction. MPEP (30 mg/kg) treatment during induction resulted in locomotor response to ethanol (2 g/kg) challenge that was equivalent to an acute response, indicating full blockade of sensitization. Sensitization was associated with increased pERK 1/2 immunoreactivity (IR) in nucleus accumbens shell (AcbSh) and a reduction in lateral habenula (LHb), both of which were blocked by MPEP treatment during induction. Sensitization was also associated with mGluR5-independent increases in pERK 1/2 IR in the nucleus accumbens core and decreases in the dentate gyrus and lateral septum. These data indicate that mGluR5 activity is required for the induction of ethanol locomotor sensitization and associated changes in ERK 1/2 phosphorylation in the AcbSh and LHb, which raises the hypothesis that mGluR5-mediated cell signaling in these brain regions may mediate the induction of sensitization. Elucidating mechanisms of sensitization may increase understanding of how ethanol hijacks behavioral functions during the development of addiction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Students in health care today are very different than those of past generations. Health care education requires both innovation and creativity to meet the changing needs of students. Soft skills such as leadership, communication, nursing informatics, technology, and professionalism can sometimes be lost in pursuit of scientific knowledge. The purpose of this descriptive pilot study was to evaluate the effectiveness of a product designed to assist in the development of soft skills in a bachelor of science in nursing curriculum. This research did not support the additive value of this particular product but recommended further research at other curricular levels.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that nondependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology. We first evaluated the impact of voluntary 24-h, two-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the AD-associated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wild-type mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol-free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aβ 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex, medial prefrontal cortex, and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late-stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer's pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex. Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice., (© 2019 Elsevier Inc. All rights reserved.)

Objectives: To identify patient characteristics, bleed management, and bleed outcomes in patients experiencing an apixaban major bleeding event and to identify opportunities to improve the safe use of apixaban., Methods: This retrospective single health-system study identified apixaban patients experiencing a major bleeding event between January 2013 and May 2016 through electronic medical record review. Patient characteristics, bleed management, and outcomes were extracted in those with a confirmed major bleed assessed by the International Society on Thrombosis and Haemostasis criteria., Results: Fifty major bleeding events occurred in 49 patients (79 ± 9.8 years). Patient characteristics included history of hypertension (94%), anemia (68%), and concomitant antiplatelet use (68%). Gastrointestinal bleeding occurred in 72% of patients and intracranial hemorrhage in 14% of patients. Packed red blood cells (PRBCs) were utilized in 82% of patients and reversal agents were administered to 6% of patients. Mortality during the hospital admission for the bleed was 0%. Anticoagulation was held at discharge in 64% of patients and remained held at 30 days in the majority of patients. Of those on concurrent aspirin therapy, an appropriate indication was not found in 64.7% of patients., Conclusions: Patients with major bleeding were elderly and frequently on inappropriate concomitant antiplatelet therapy. The majority of patients were managed with PRBC transfusion. More than half of patients had anticoagulation therapy held at discharge. Concerns with prescribing and patient management were identified leading to recommendations for improving the safe use of apixaban therapy.

Rivaroxaban, the first oral direct factor Xa inhibitor, was approved for stroke prevention in nonvalvular atrial fibrillation in 2011. Limited data are available regarding major bleeding in a clinical practice setting. The purpose of this study is to describe the patient characteristics, management, and outcomes of major bleeding events in patients receiving rivaroxaban for atrial fibrillation. This retrospective, single health system study identified patients with rivaroxaban having a major bleeding event between July 2011 and June 2014. Patients were identified through adverse event reporting or by cross-referencing rivaroxaban with International Classification of Diseases, Ninth Revision diagnosis codes for atrial fibrillation and hemorrhage, with and without transfusion. A total of 60 patients were identified. The mean age of patients was 80.3 ± 7.4 years. The most common bleed sites were gastrointestinal (63.3%) and intracranial (26.7%). Higher dose than recommended based on renal function was present in 35% of patients and concurrent antiplatelet therapy occurred in 70%. Activated prothrombin complex concentrate was utilized in 30% of patients and recombinant factor VIIa in 6.7%. A procedure or surgery was performed for bleed management in 10 patients. Anticoagulation was held at discharge in 76% of patients. A total of 6 patients died during hospital admission, 5 of whom experienced an intracranial hemorrhage. In conclusion, patients experiencing a rivaroxaban major bleeding event were elderly, often renally impaired, and receiving concurrent antiplatelet therapy. In-hospital mortality was 10%. The majority of patients (76%) had anticoagulation therapy held at discharge.

Objectives: We validate a machine learning-based sepsis-prediction algorithm ( InSight ) for the detection and prediction of three sepsis-related gold standards, using only six vital signs. We evaluate robustness to missing data, customisation to site-specific data using transfer learning and generalisability to new settings., Design: A machine-learning algorithm with gradient tree boosting. Features for prediction were created from combinations of six vital sign measurements and their changes over time., Setting: A mixed-ward retrospective dataset from the University of California, San Francisco (UCSF) Medical Center (San Francisco, California, USA) as the primary source, an intensive care unit dataset from the Beth Israel Deaconess Medical Center (Boston, Massachusetts, USA) as a transfer-learning source and four additional institutions' datasets to evaluate generalisability., Participants: 684 443 total encounters, with 90 353 encounters from June 2011 to March 2016 at UCSF., Interventions: None., Primary and Secondary Outcome Measures: Area under the receiver operating characteristic (AUROC) curve for detection and prediction of sepsis, severe sepsis and septic shock., Results: For detection of sepsis and severe sepsis, InSight achieves an AUROC curve of 0.92 (95% CI 0.90 to 0.93) and 0.87 (95% CI 0.86 to 0.88), respectively. Four hours before onset, InSight predicts septic shock with an AUROC of 0.96 (95% CI 0.94 to 0.98) and severe sepsis with an AUROC of 0.85 (95% CI 0.79 to 0.91)., Conclusions: InSight outperforms existing sepsis scoring systems in identifying and predicting sepsis, severe sepsis and septic shock. This is the first sepsis screening system to exceed an AUROC of 0.90 using only vital sign inputs. InSight is robust to missing data, can be customised to novel hospital data using a small fraction of site data and retains strong discrimination across all institutions., Competing Interests: Competing interests: All authors who have affiliations listed with Dascena (Hayward, California,USA) are employees or contractors of Dascena. CB reports receiving consulting fees from Dascena. CB, LS, DS and GF report receiving grant funding from Dascena., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Technological innovation has become a driver of educational and leadership development practices that place students at the center of learning and leadership development experiences., (© 2017 Wiley Periodicals, Inc., A Wiley Company.)

Rationale: Chronic alcohol exposure is associated with impaired decision making skills, cognitive deficits, and poor performance on tasks requiring behavioral flexibility. Although oral routes of alcohol administration are commonly used to examine effects of alcohol on various behaviors in rodents, only a few investigations have used intragastric exposures to evaluate ethanol's effects on behavioral flexibility in the adult rat., Objectives: The aim of the current series of experiments was to determine if behavioral flexibility impairments would be demonstrated across a variety of procedural factors, including route of administration [intraperitoneal injection (i.p.), intragastric gavage (i.g.)], ethanol dose (3-5 g/kg), number of daily exposures (once/day, twice/day), duration of exposure (2-6 weeks), or length of abstinence (5-7 days)., Methods: Adult male Sprague-Dawley rats were exposed to chronic intermittent ethanol (CIE) or vehicle and evaluated for behavioral intoxication, blood ethanol concentrations (BEC), and performance on a reversal learning odor discrimination task., Results: While all rats displayed behavioral intoxication and elevated BECs, CIE i.p. rats had prolonged elevation in BECs and made the most errors during the reversal learning task. Unexpectedly, CIE i.g. exposures failed to produce deficits during reversal learning tasks regardless of ethanol dose, frequency/duration of exposure, or length of abstinence., Conclusions: Behavioral flexibility deficits resulting from CIE i.p. exposures may be due to the severity and chronicity of alcohol intoxication. Elucidating the impact of ethanol on behavioral flexibility is critical for developing a better understanding of the behavioral consequences of chronic alcohol exposure.

Background: Clinical decision support systems are used to help predict patient stability and mortality in the Intensive Care Unit (ICU). Accurate patient information can assist clinicians with patient management and in allocating finite resources. However, systems currently in common use have limited predictive value in the clinical setting. The increasing availability of Electronic Health Records (EHR) provides an opportunity to use medical information for more accurate patient stability and mortality prediction in the ICU., Objective: Develop and evaluate an algorithm which more accurately predicts patient mortality in the ICU, using the correlations between widely available clinical variables from the EHR., Methods: We have developed an algorithm, AutoTriage , which uses eight common clinical variables from the EHR to assign patient mortality risk scores. Each clinical variable produces a subscore, and combinations of two or three discretized clinical variables also produce subscores. A combination of weighted subscores produces the overall score. We validated the performance of this algorithm in a retrospective study on the MIMIC III medical ICU dataset., Results: AutoTriage 12 h mortality prediction yields an Area Under Receiver Operating Characteristic value of 0.88 (95% confidence interval 0.86 to 0.88). At a sensitivity of 80%, AutoTriage maintains a specificity of 81% with a diagnostic odds ratio of 16.26., Conclusions: Through the multidimensional analysis of the correlations between eight common clinical variables, AutoTriage provides an improvement in the specificity and sensitivity of patient mortality prediction over existing prediction methods.

Objective: To develop high-performance early sepsis prediction technology for the general patient population., Methods: Retrospective analysis of adult patients admitted to the intensive care unit (from the MIMIC II dataset) who were not septic at the time of admission., Results: A sepsis early warning algorithm, InSight, was developed and applied to the prediction of sepsis up to three hours prior to a patient's first five hour Systemic Inflammatory Response Syndrome (SIRS) episode. When applied to a never-before-seen set of test patients, InSight predictions demonstrated a sensitivity of 0.90 (95% CI: 0.89-0.91) and a specificity of 0.81 (95% CI: 0.80-0.82), exceeding or rivaling that of existing biomarker detection methods. Across predictive times up to three hours before a sustained SIRS event, InSight maintained an average area under the ROC curve of 0.83 (95% CI: 0.80-0.86). Analysis of patient sepsis risk showed that contributions from the coevolution of multiple risk factors were more important than the contributions from isolated individual risk factors when making predictions further in advance., Conclusions: Sepsis can be predicted at least three hours in advance of onset of the first five hour SIRS episode, using only nine commonly available vital signs, with better performance than methods in standard practice today. High-order correlations of vital sign measurements are key to this prediction, which improves the likelihood of early identification of at-risk patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Regulated mRNA translation is vital for germ cells to produce new proteins in the spatial and temporal patterns that drive gamete development. Translational control involves the de-repression of stored mRNAs and their recruitment by eukaryotic initiation factors (eIFs) to ribosomes. C. elegans expresses five eIF4Es (IFE-1-IFE-5); several have been shown to selectively recruit unique pools of mRNA. Individual IFE knockouts yield unique phenotypes due to inefficient translation of certain mRNAs. Here, we identified mRNAs preferentially translated through the germline-specific eIF4E isoform IFE-1. Differential polysome microarray analysis identified 77 mRNAs recruited by IFE-1. Among the IFE-1-dependent mRNAs are several required for late germ cell differentiation and maturation. Polysome association of gld-1, vab-1, vpr-1, rab-7 and rnp-3 mRNAs relies on IFE-1. Live animal imaging showed IFE-1-dependent selectivity in spatial and temporal translation of germline mRNAs. Altered MAPK activation in oocytes suggests dual roles for IFE-1, both promoting and suppressing oocyte maturation at different stages. This single eIF4E isoform exerts positive, selective translational control during germ cell differentiation., (© 2015. Published by The Company of Biologists Ltd.)

Background: The University HealthSystem Consortium (UHC), a national hospital engagement network (HEN), establishes health-system metrics to assess and improve quality of care. In 2012, a metric for inpatient anticoagulant hemorrhage was developed. The utility of this metric to improve anticoagulation care has not been assessed., Objective: To identify opportunities to improve anticoagulation safety through the use of a HEN metric for inpatient anticoagulant-associated hemorrhage., Methods: This was a single-center, retrospective, observational study of metric identified patients with presumed inpatient anticoagulant hemorrhage. Records were reviewed to confirm anticoagulant hemorrhage and identify bleed site and severity. A structured process was used to assess bleed preventability and subsequently identify opportunities for improving care. Each bleed was reviewed by 2 investigators., Results: Anticoagulant hemorrhage was confirmed in 85.9% (61/71) with heparin infusion the most common anticoagulant. Patients were primarily medical, with a mean age of 72.7 ± 15 years. The most common bleed sites were gastrointestinal (24.6%) and retroperitoneal (21.3%). Major bleeding occurred in 60.7% (37/61). Anticoagulant hemorrhage was preventable in 18% (11/61) of cases with heparin protocol noncompliance the most common cause of a preventable bleed. Several opportunities for improving heparin infusion therapy were recognized and protocol changes were implemented., Conclusions: The UHC metric accurately captures inpatient anticoagulant-associated hemorrhage the majority of time. The UHC metric on anticoagulant-associated hemorrhage can be a useful part of a health system's overall plan for the safe use of anticoagulants in the hospital setting., (© The Author(s) 2015.)

Unsteady flows in the marine environment can affect the stability and locomotor costs of animals. For fish swimming at shallow depths, waves represent a form of unsteady flow. Waves consist of cyclic oscillations, during which the water moves in circular or elliptical orbits. Large gravity waves have the potential to displace fish both cyclically and in the direction of wave celerity for animals floating in the water column or holding station on the bottom. Displacement of a fish can exceed its stability control capability when the size of the wave orbit is equivalent to the size of the fish. Previous research into compensatory behaviors of fishes to waves has focused on pelagic osteichthyan fishes with laterally compressed bodies. However, dorsoventrally compressed batoid rays must also contend with waves. Examination of rays subjected to waves showed differing strategies for stability between pelagic and demersal species. Pelagic cownose rays (Rhinoptera bonasus) would glide through or be transported by waves, maintaining a positive dihedral of the wing-like pectoral fins. Demersal Atlantic stingrays (Dasyatis sabina) and freshwater rays (Potamotrygon motoro) maintained contact with the bottom and performed compensatory fin motions and body postures. The ability to limit displacement due to wave action by the demersal rays was also a function of the bottom texture. The ability of rays to maintain stability due to wave action suggests mechanisms to compensate for the velocity flux of the water impinging on the large projected area of the enlarged pectoral fins of rays., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

Data comparing the patient characteristics, management and outcomes for dabigatran versus warfarin major bleeding in the practice setting are limited. We performed a retrospective single health system study of atrial fibrillation patients with dabigatran or warfarin major bleeding from October 2010 through September 2012. Patient identification occurred through both an internal adverse event reporting system and a structured stepwise data filtering approach using the International Classification of Diseases diagnosis codes. Thirty-five dabigatran major bleeding patients were identified and compared to 70 warfarin major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older (79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30 mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an excessive dose based on renal function. More dabigatran patients required a procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs. 11.4 %, p = 0.28). In a single hospital center practice setting, as compared to warfarin, patients with dabigatran major bleeding were more likely to be older, have renal impairment, require a procedure for bleed management and receive a hemostatic agent. Patients with dabigatran major bleeding had an excessive dose for renal function in more than one-third of cases.

We previously demonstrated a unique protective role for the transient receptor potential, melastatin-2 (TRPM2) cation channel in breast cancer cells. In the present study, we investigated the chemotherapeutic effects elicited by inhibiting this protective role in metastatic breast adenocarcinoma cells. TRPM2 inhibition led to dose-dependent increases in MDA-MB-231 breast adenocarcinoma cell death after treatment with doxorubicin or the DNA-methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. Similar results were observed after RNAi silencing of TRPM2 in these cells after doxorubicin treatment. However, TRPM2 RNAi silencing also led to increased MCF-7 breast adenocarcinoma cell death after tamoxifen treatment, yet not in non-cancerous human mammary epithelial cells. These results thus revealed that TRPM2 inhibition selectively increased cytotoxicity in a triple-negative and an estrogen receptor-positive breast cancer cell line, with minimal deleterious effects in non-cancerous breast cells. Analysis of DNA damage revealed enhanced DNA damage levels in MCF-7 cells treated with doxorubicin due to TRPM2 inhibition. Analysis of cell death demonstrated that inhibition of apoptosis, caspase-independent cell death or autophagy failed to significantly reduce cell death induced by TRPM2 inhibition and chemotherapy. These results indicate that TRPM2 inhibition activates alternative pathways of cell death in breast cancer cells. Taken together, our results provide significant evidence that TRPM2 inhibition is a potential strategy to induce triple-negative and estrogen receptor-positive breast adenocarcinoma cell death via alternative cell death pathways. This is expected to provide a basis for inhibiting TRPM2 for the improved treatment of breast cancer, which potentially includes treating breast tumors that are resistant to chemotherapy due to their evasion of apoptosis.

Molecular characterization of events is an integral part of the advancement process during genetically modified (GM) crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR) and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS), utilizing sequence capture coupled with next-generation sequencing (NGS) technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA). Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence) that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment., (© 2015 The Authors.)

Patients with single ventricle physiology face significant morbidity and mortality following the Fontan procedure resulting in the need for additional cardiac reinterventions. Online patient education resources provide limited information on the reinterventions performed in single ventricle patients following the Fontan procedure. We sought to determine cardiac surgical and percutaneous reintervention rates and factors affecting reinterventions following the Fontan procedure. Databases from a single tertiary care center were retrospectively reviewed for all patients who underwent a Fontan procedure between 1978 and 2002. The number and type of cardiac surgical and percutaneous interventions following the Fontan procedure were determined, and relationships between need for reintervention and clinical variables were sought. A total of 91 patients (55 males) underwent the Fontan procedure at a median age of 5.50 years (IQR: 3.33-9.50 years). Median age at last follow-up, death, or transplant was 21.89 years (IQR: 10.87-25.51 years). Following the Fontan procedure, 60 (66%) patients required an additional 144 median sternotomies and 61 (67%) required 139 percutaneous cardiac interventions. Pacemaker system placement/replacement was the most common intervention following the Fontan procedure. The median time to first cardiac surgery following the Fontan was 1.96 years (IQR: 0.06-8.42 years) while the median time to the first percutaneous intervention was 7.63 years (IQR: 0.65-15.89 years). Families of single ventricle patients should be counseled on the likelihood of requiring additional cardiac interventions following the Fontan procedure.

Isolated coarctation of the aorta (CoA) occurs in 6-8 % of patients with congenital heart disease. After successful relief of obstruction, patients remain at risk for aortic aneurysm formation at the site of the repair. We sought to determine the diagnostic utility of echocardiography compared with advanced arch imaging (AAI) in diagnosing aortic aneurysms in pediatric patients after CoA repair. The Congenital Heart Databases from 1996 and 2009 were reviewed. All patients treated for CoA who had AAI defined by cardiac magnetic resonance imaging (MRI), computed tomography (CT), or catheterization were identified. Data collected included the following: type, timing, and number of interventions, presence and time to aneurysm diagnosis, and mortality. Patients were subdivided into surgical and catheterization groups for analysis. Seven hundred and fifty-nine patients underwent treatment for CoA during the study period. Three hundred and ninety-nine patients had at least one AAI. Aneurysms were diagnosed by AAI in 28 of 399 patients at a mean of 10 ± 8.4 years after treatment. Echocardiography reports were available for 380 of 399 patients with AAI. The sensitivity of echocardiography for detecting aneurysms was 24 %. The prevalence of aneurysms was significantly greater in the catheterization group (p < 0.05) compared with the surgery group. Aneurysm was also diagnosed earlier in the catheterization group compared with the surgery group (p = 0.02). Multivariate analysis showed a significantly increased risk of aneurysm diagnosis in patients in the catheterization subgroup and in patients requiring more than three procedures. Aortic aneurysms continue to be an important complication after CoA repair. Although serial echocardiograms are the test of choice for following-up most congenital cardiac lesions in pediatrics, our data show that echocardiography is inadequate for the detection of aneurysms after CoA repair. Because the time to aneurysm diagnosis was shorter and the risk greater in the catheterization group (particularly for patients requiring more than one procedure), surveillance with cardiac MRI or CT should begin earlier in these patients.