RESUMEN
The Snf2 chromatin remodeler, DECREASE IN DNA METHYLATION 1 (DDM1) facilitates DNA methylation. In flowering plants, DDM1 mediates methylation in heterochromatin, which is targeted primarily by MET1 and CMT methylases and is necessary for silencing transposons and for proper development. DNA methylation mechanisms evolved throughout plant evolution, whereas the role of DDM1 in early terrestrial plants remains elusive. Here, we studied the function of DDM1 in the moss, Physcomitrium (Physcomitrella) patens, which has robust DNA methylation that suppresses transposons and is mediated by a MET1, a CMT, and a DNMT3 methylases. To elucidate the role of DDM1 in P. patens, we have generated a knockout mutant and found DNA methylation to be strongly disrupted at any of its sequence contexts. Symmetric CG and CHG sequences were affected stronger than asymmetric CHH sites. Furthermore, despite their separate targeting mechanisms, CG (MET) and CHG (CMT) methylation were similarly depleted by about 75%. CHH (DNMT3) methylation was overall reduced by about 25%, with an evident hyper-methylation activity within lowly-methylated euchromatic transposon sequences. Despite the strong hypomethylation effect, only a minute number of transposons were transcriptionally activated in Ppddm1. Finally, Ppddm1 was found to develop normally throughout the plant life cycle. These results demonstrate that DNA methylation is strongly dependent on DDM1 in a non-flowering plant; that DDM1 is required for plant-DNMT3 (CHH) methylases, though to a lower extent than for MET1 and CMT enzymes; and that distinct and separate methylation pathways (e.g. MET1-CG and CMT-CHG), can be equally regulated by the chromatin and that DDM1 plays a role in it. Finally, our data suggest that the biological significance of DDM1 in terms of transposon regulation and plant development, is species dependent.
Asunto(s)
Proteínas de Arabidopsis , Bryopsida , Metilación de ADN , Bryopsida/metabolismo , Cromatina/metabolismo , Metiltransferasas/genética , Heterocromatina/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Arabidopsis/genéticaRESUMEN
Cytosine (DNA) methylation in plants regulates the expression of genes and transposons. While methylation in plant genomes occurs at CG, CHG, and CHH sequence contexts, the comparative roles of the individual methylation contexts remain elusive. Here, we present Physcomitrella patens as the second plant system, besides Arabidopsis thaliana, with viable mutants with an essentially complete loss of methylation in the CG and non-CG contexts. In contrast to A. thaliana, P. patens has more robust CHH methylation, similar CG and CHG methylation levels, and minimal cross-talk between CG and non-CG methylation, making it possible to study context-specific effects independently. Our data found CHH methylation to act in redundancy with symmetric methylation in silencing transposons and to regulate the expression of CG/CHG-depleted transposons. Specific elimination of CG methylation did not dysregulate transposons or genes. In contrast, exclusive removal of non-CG methylation massively up-regulated transposons and genes. In addition, comparing two exclusively but equally CG- or CHG-methylated genomes, we show that CHG methylation acts as a greater transcriptional regulator than CG methylation. These results disentangle the transcriptional roles of CG and non-CG, as well as symmetric and asymmetric methylation in a plant genome, and point to the crucial role of non-CG methylation in genome regulation.
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Bryopsida/genética , Metilación de ADN/genética , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Mutación/genética , Elementos Transponibles de ADN/genética , Epigenoma , Silenciador del Gen , Modelos Genéticos , Regulación hacia Arriba/genéticaRESUMEN
The original version of this Article contained an error in Fig. 5, in which the evolutionary origin of DRM2 was incorrectly placed prior to the divergence between gymnosperms and angiosperms . The correct evolutionary origin of DRM2 should be in angiosperms. In addition, in the "Percent methylation change" section of the Methods, Equation 1 was incorrect. This has been corrected in both the PDF and HTML versions of the Article.An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
To properly regulate the genome, cytosine methylation is established by animal DNA methyltransferase 3 s (DNMT3s). While altered DNMT3 homologs, Domains rearranged methyltransferases (DRMs), have been shown to establish methylation via the RNA directed DNA methylation (RdDM) pathway, the role of true-plant DNMT3 orthologs remains elusive. Here, we profile de novo (RPS transgene) and genomic methylation in the basal plant, Physcomitrella patens, mutated in each of its PpDNMTs. We show that PpDNMT3b mediates CG and CHH de novo methylation, independently of PpDRMs. Complementary de novo CHG methylation is specifically mediated by the CHROMOMETHYLASE, PpCMT. Intragenomically, PpDNMT3b functions preferentially within heterochromatin and is affected by PpCMT. In comparison, PpDRMs target active-euchromatic transposons. Overall, our data resolve how DNA methylation in plants can be established in heterochromatin independently of RdDM; suggest that DRMs have emerged to target euchromatin; and link DNMT3 loss in angiosperms to the initiation of heterochromatic CHH methylation by CMT2.
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Bryopsida/fisiología , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN/fisiología , Heterocromatina/genética , Proteínas de Plantas/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , Evolución Molecular , Redes y Vías Metabólicas/fisiología , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Selección Genética/fisiologíaRESUMEN
The authors of this article are previous or current members of the Clinical Ethics Consultation Affairs (CECA) Committee, a standing committee of the American Society for Bioethics and Humanities (ASBH). The committee is composed of seasoned healthcare ethics consultants (HCECs), and it is charged with developing and disseminating education materials for HCECs and ethics committees. The purpose of this article is to describe the educational research and development processes behind our teaching materials, which culminated in a case studies book called A Case-Based Study Guide for Addressing Patient-Centered Ethical Issues in Health Care (hereafter, the Study Guide). In this article, we also enumerate how the Study Guide could be used in teaching and learning, and we identify areas that are ripe for future work.
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Eticistas/educación , Comités de Ética Clínica , Consultoría Ética/normas , Humanos , Objetivos Organizacionales , Sociedades Médicas , Estados UnidosRESUMEN
Myelomeningocele and gastroschisis, on their own, are both relatively common entities encountered in pediatric surgical care. Coexistence of these pathologies, however, is exceedingly rare. The authors report on 2 patients who presented with myelomeningocele and gastroschisis at birth. They obtained blood for whole-exome analysis for one of the patients and identified 3 mutations that could be related to the underlying anomalies: homozygous mutations in FAM171B and ABCA1 and a hemizygous (X-linked) mutation in COL4A5. Of these, FAM171B and ABCA1 both have function that may be related to the underlying disease.
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Gastrosquisis/complicaciones , Meningomielocele/complicaciones , Adolescente , Adulto , Femenino , Gastrosquisis/diagnóstico por imagen , Gastrosquisis/cirugía , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Meningomielocele/diagnóstico por imagen , Meningomielocele/cirugíaRESUMEN
Spina bifida is a neurodevelopmental disorder that results in a broad range of disability. Over the last few decades, there have been significant advances in diagnosis and treatment of this condition, which have raised concerns regarding how clinicians prognosticate the extent of disability, determine quality of life, and use that information to make treatment recommendations. From the selective treatment of neonates in the 1970s, to the advent of maternal-fetal surgery today, the issues that have been raised surrounding spina bifida intervention invoke principles of medical bioethics such as beneficence and nonmaleficence, while also highlighting how quality of life judgments may drive care decisions. Such changes in treatment norms are also illustrative of how disability is viewed both within the medical community and by society at large. An examination of the changes in spina bifida treatment provides a model through which to understand how ethically complex decisions regarding care for children with disabilities has evolved, and the challenges faced when medical information is combined with value-based judgments to guide medical decision making.
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Bioética/tendencias , Personas con Discapacidad/psicología , Calidad de Vida/psicología , Estigma Social , Disrafia Espinal/complicaciones , Eutanasia/tendencias , Humanos , Disrafia Espinal/epidemiología , Disrafia Espinal/mortalidadRESUMEN
Polycomb group (PcG) proteins are evolutionarily conserved chromatin modifiers that regulate developmental pathways in plants. PcGs form nuclear multi-subunit Polycomb Repressive Complexes (PRCs). The PRC2 complex mediates gene repression via methylation of lysine 27 on histone H3, which consequently leads to chromatin condensation. In Arabidopsis thaliana, several PRC2 complexes with different compositions were identified, each controlling a particular developmental program.The core subunit FIE is crucial for PRC2 function throughout the plant life cycle, yet accurate information on its spatial and temporal localization was absent. This study focused on identifying FIE accumulation patterns, using microscopy and biochemical approaches. Analysing endogenous FIE and transgenic gFIE-green fluorescent protein fusion protein (gFIE-GFP) showed that FIE accumulates in the nuclei of every cell type examined. Interestingly, gFIE-GFP, as well as the endogenous FIE, also localized to the cytoplasm in all examined tissues. In both vegetative and reproductive organs, FIE formed cytoplasmic high-molecular-mass complexes, in parallel to the nuclear PRC2 complexes. Moreover, size-exclusion chromatography and bimolecular fluorescence complementation assays indicated that in inflorescences FIE formed a cytoplasmic complex with MEA, a PRC2 histone methyltransferase subunit. In contrast, CLF and SWN histone methyltransferases were strictly nuclear. Presence of PRC2 subunits in cytoplasmic complexes has not been previously described in plants. Our findings are in agreement with accumulating evidence demonstrating cytoplasmic localization and function of PcGs in metazoa. The cytosolic accumulation of PRC2 components in plants supports the model that PcGs have alternative non-nuclear functions that go beyond chromatin methylation.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Citoplasma/metabolismo , Proteínas Represoras/metabolismo , Cromatina/metabolismo , Cromatografía en Gel , Inmunoprecipitación , Microscopía Confocal , Plantas Modificadas Genéticamente , Complejo Represivo Polycomb 2RESUMEN
Informed consent should be seen as an essential part of health care practice; parental permission and childhood assent is an active process that engages patients, both adults and children, in their health care. Pediatric practice is unique in that developmental maturation allows, over time, for increasing inclusion of the child's and adolescent's opinion in medical decision-making in clinical practice and research. This technical report, which accompanies the policy statement "Informed Consent in Decision-Making in Pediatric Practice" was written to provide a broader background on the nature of informed consent, surrogate decision-making in pediatric practice, information on child and adolescent decision-making, and special issues in adolescent informed consent, assent, and refusal. It is anticipated that this information will help provide support for the recommendations included in the policy statement.
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Toma de Decisiones Clínicas , Consentimiento Informado , Pediatría , Adolescente , Niño , Humanos , Consentimiento Informado/normas , Consentimiento por TercerosRESUMEN
Plants characteristically alternate between haploid gametophytic and diploid sporophytic stages. Meiosis and fertilization respectively initiate these two different ontogenies(1). Genes triggering ectopic embryo development on vegetative sporophytic tissues are well described(2,3); however, a genetic control of embryo development from gametophytic tissues remains elusive. Here, in the moss Physcomitrella patens we show that ectopic overexpression of the homeobox gene BELL1 induces embryo formation and subsequently reproductive diploid sporophytes from specific gametophytic cells without fertilization. In line with this, BELL1 loss-of-function mutants have a wild-type phenotype, except that their egg cells are bigger and unable to form embryos. Our results identify BELL1 as a master regulator for the gametophyte-to-sporophyte transition in P. patens and provide mechanistic insights into the evolution of embryos that can generate multicellular diploid sporophytes. This developmental innovation facilitated the colonization of land by plants about 500 million years ago(4) and thus shaped our current ecosystems.
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Bryopsida/genética , Genes Homeobox/genética , Bryopsida/embriología , Bryopsida/fisiología , Diploidia , Células Germinativas de las Plantas/fisiología , Haploidia , Reproducción AsexuadaRESUMEN
Packaging of eukaryotic DNA largely depends on histone modifications that affect the accessibility of DNA to transcriptional regulators, thus controlling gene expression. The Polycomb group (PcG) chromatin remodeling complex deposits a methyl group on lysine 27 of histone 3 leading to repressed gene expression. Plants encode homologs of the Enhancer of zeste (E(z)), a component of the PcG complex from Drosophila, one of which is a SET domain protein designated CURLY LEAF (CLF). Although this SET domain protein exhibits a strong correlation with the presence of the H3K27me3 mark in plants, the methyl-transferase activity and specificity of its SET domain have not been directly tested in-vivo. Using the evolutionary early-diverged land plant model species Physcomitrella patens we show that abolishment of a single copy gene PpCLF, as well as an additional member of the PcG complex, FERTILIZATION-INDEPENDENT ENDOSPERM (PpFIE), results in a specific loss of tri-methylation of H3K27. Using site-directed mutagenesis of key residues, we revealed that H3K27 tri-methylation is mediated by the SET domain of the CLF protein. Moreover, the abolishment of H3K27me3 led to enhanced expression of transcription factor genes. This in turn led to the development of fertilization-independent sporophyte-like structures, as observed in PpCLF and PpFIE null mutants. Overall, our results demonstrate the role of PpCLF as a SET protein in tri-methylation of H3K27 in-vivo and the importance of this modification in regulating the expression of transcription factor genes involved in developmental programs of P. patens.
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Bryopsida/crecimiento & desarrollo , Bryopsida/genética , N-Metiltransferasa de Histona-Lisina/fisiología , Histonas/metabolismo , Proteínas del Grupo Polycomb/fisiología , Secuencia de Aminoácidos , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/química , Proteínas de Homeodominio/fisiología , Lisina/metabolismo , Metilación , Datos de Secuencia Molecular , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Plantas Modificadas Genéticamente , Homología de Secuencia de AminoácidoAsunto(s)
Eticistas , Consultoría Ética , Comités de Ética , Ética Clínica , Ética Médica , Humanos , Derivación y ConsultaRESUMEN
DNA methylation has a crucial role in plant development regulating gene expression and silencing of transposable elements. Maintenance DNA methylation in plants occurs at symmetrical (m)CG and (m)CHG contexts ((m) = methylated) and is maintained by DNA METHYLTRANSFERASE 1 (MET1) and CHROMOMETHYLASE (CMT) DNA methyltransferase protein families, respectively. While angiosperm genomes encode for several members of MET1 and CMT families, the moss Physcomitrella patens, serving as a model for early divergent land plants, carries a single member of each family. To determine the function of P. patens PpMET we generated ΔPpmet deletion mutant which lost (m)CG and unexpectedly (m)CCG methylation at loci tested. In order to evaluate the extent of (m)CCG methylation by MET1, we reexamined the Arabidopsis thaliana Atmet1 mutant methylome and found a similar pattern of methylation loss, suggesting that maintenance of DNA methylation by MET1 is conserved through land plant evolution. While ΔPpmet displayed no phenotypic alterations during its gametophytic phase, it failed to develop sporophytes, indicating that PpMET plays a role in gametogenesis or early sporophyte development. Expression array analysis revealed that the deletion of PpMET resulted in upregulation of two genes and multiple repetitive sequences. In parallel, expression analysis of the previously reported ΔPpcmt mutant showed that lack of PpCMT triggers overexpression of genes. This overexpression combined with loss of (m)CHG and its pleiotropic phenotype, implies that PpCMT has an essential evolutionary conserved role in the epigenetic control of gene expression. Collectively, our results suggest functional conservation of MET1 and CMT families during land plant evolution. A model describing the relationship between MET1 and CMT in CCG methylation is presented.
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Bryopsida/genética , Bryopsida/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , Proteínas de Plantas/metabolismo , Oxidorreductasas de Alcohol , Secuencia de Bases , Bryopsida/crecimiento & desarrollo , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN/genética , ADN de Plantas/genética , ADN de Plantas/metabolismo , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Modelos Biológicos , Datos de Secuencia Molecular , Mutación , Proteínas de Plantas/genética , Plantas Modificadas GenéticamenteRESUMEN
As the culture of medical practice has evolved, so has the relationship between the physician and patient. This is decidedly true with regards to the introduction of innovative therapies, especially in the surgical arena. A critical challenge is identifying and defining innovative therapy. Is the proposed treatment an incremental change, a research proposal, or more commonly someplace in between? This gray area creates a transition zone commonly referred to as innovative therapy. Given the complexities of the current landscape of innovation, innovation therapy committees may provide a mechanism to help to guide both physicians and patients through such difficult topics as the process of informed consent, managing conflicts of interest, and how to evaluate the outcomes of innovative therapies. As surgical innovation remains critical to the advancement of care, it must occur in a transparent partnership with patients, under the eye of guiding entities, aimed at ultimately improving outcomes and care.
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Conflicto de Intereses , Consentimiento Informado/normas , Invenciones/normas , Evaluación de Procesos y Resultados en Atención de Salud/normas , Participación del Paciente , Procedimientos Quirúrgicos Operativos/normas , HumanosRESUMEN
C-5 DNA methylation is an essential mechanism controlling gene expression and developmental programs in a variety of organisms. Though the role of DNA methylation has been intensively studied in mammals and Arabidopsis, little is known about the evolution of this mechanism. The chromomethylase (CMT) methyltransferase family is unique to plants and was found to be involved in DNA methylation in Arabidopsis, maize and tobacco. The moss Physcomitrella patens, a model for early terrestrial plants, harbors a single homolog of the CMT protein family designated as PpCMT. Our phylogenetic analysis suggested that the CMT family is unique to embryophytes and its earliest known member PpCMT belongs to the CMT3 subfamily. Thus, P. patens may serve as a model to study the ancient functions of the CMT3 family. We have generated a ΔPpcmt deletion mutant which demonstrated that PpCMT is essential for P. patens protonema and gametophore development and is involved in CHG methylation as demonstrated at four distinct genomic loci. PpCMT protein accumulation pattern correlated with proliferating cells and was sub-localized to the nucleus as predicted from its function. Taken together, our results suggested that CHG DNA methylation mediated by CMT has been employed early in land plant evolution to control developmental programs during both the vegetative and reproductive haploid phases along the plant life cycle.
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Bryopsida/enzimología , ADN (Citosina-5-)-Metiltransferasas/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Secuencia de Aminoácidos , Evolución Biológica , Bryopsida/citología , Bryopsida/genética , Bryopsida/crecimiento & desarrollo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , Dosificación de Gen , Datos de Secuencia Molecular , Fenotipo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Proteínas Recombinantes de Fusión , Alineación de Secuencia , Análisis de Secuencia de ADN , Eliminación de Secuencia , TransgenesRESUMEN
Isolated fibrous gastric antral band in a neonate causing partial gastric obstruction and mimicking prepyloric antral web is not reported in the English literature, and we would like to report the first case. A premature neonate with feeding difficulties and bilious aspirate underwent upper gastrointestinal contrast examination. The upper gastrointestinal series showed a thin, radiolucent, circumferential band in the antrum with delayed gastric emptying. Radiographic diagnosis of prepyloric antral web with partial gastric obstruction was made. Intraoperatively, a circumferential fibrous cord was found in the muscle layer (tunica muscularis) of the antrum, which was completely divided. Clinically and radiographically, the 2 conditions could not be differentiated but require 2 separate surgical techniques for their management.
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Obstrucción de la Salida Gástrica/congénito , Enfermedades del Prematuro/diagnóstico , Antro Pilórico/anomalías , Vaciamiento Gástrico , Obstrucción de la Salida Gástrica/diagnóstico , Obstrucción de la Salida Gástrica/diagnóstico por imagen , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico por imagen , Enfermedades del Prematuro/patología , Enfermedades del Prematuro/cirugía , Recién Nacido Pequeño para la Edad Gestacional , Intubación Gastrointestinal , Laparotomía , Masculino , Músculo Liso/patología , RadiografíaRESUMEN
OBJECTIVE: The generalizability of palliative care intervention research is often limited by high rates of study attrition. This study examined factors associated with attrition from a randomized controlled trial comparing meaning-centered group psychotherapy (MCGP), an intervention designed to help advanced cancer patients sustain or enhance their sense of meaning to the supportive group psychotherapy (SGP), a standardized support group. METHODS: Patients with advanced solid tumor cancers (n = 153) were randomized to eight sessions of either the MCGP or SGP. They completed assessments of psychosocial, spiritual, and physical well-being pretreatment, midtreatment, and 2 months post-treatment. Attrition was assessed in terms of the percent of participants who failed to complete these assessments, and demographic, psychiatric, medical, and study-related correlates of attrition were examined for the participants in each of these categories. RESULTS: The rates of attrition at these time points were 28.1%, 17.7%, and 11.1%, respectively; 43.1% of the participants (66 of 153) completed the entire study. The most common reason for dropout was patients feeling too ill. Attrition rates did not vary significantly between study arms. The participants who dropped out pretreatment reported less financial concerns than post-treatment dropouts, and the participants who dropped out of the study midtreatment had poorer physical health than treatment completers. There were no other significant associations between attrition and any demographic, medical, psychiatric, or study-related variables. CONCLUSIONS: These findings highlight the challenge of maintaining advanced cancer patients in longitudinal research and suggest the need to consider alternative approaches (e.g., telemedicine) for patients who might benefit from group interventions but are too ill to travel.
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Neoplasias/psicología , Cuidados Paliativos/psicología , Pacientes Desistentes del Tratamiento , Psicoterapia de Grupo/métodos , Grupos de Autoayuda , Enfermo Terminal/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/patología , Neoplasias/terapia , Ciudad de Nueva York , Cooperación del Paciente/psicología , Cooperación del Paciente/estadística & datos numéricos , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad , Cuidado Terminal/métodos , Resultado del TratamientoRESUMEN
There is growing evidence for the efficacy of acceptance-based behavioral therapies, which aim to increase acceptance of internal experiences and values-consistent action. Further, experimental studies have demonstrated that acceptance decreases distress and increases willingness to engage in challenging tasks (e.g. Levitt, Brown, Orsillo, & Barlow, 2004). However, research demonstrating the positive effects of values articulation on psychological functioning is needed. The goal of the present study was to evaluate the efficacy of a brief intervention in reducing anxiety related to a stressful speech task. Contrary to predictions, engagement in values writing did not reduce anticipatory or posttask anxiety relative to engagement in a neutral writing task. However, self-esteem significantly predicted anxious response to the task. Experiential avoidance and valued living were also associated with anxious response to the task, although the contribution of these predictors was not statistically significant.
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Terapia Conductista/estadística & datos numéricos , Psicoterapia Breve/estadística & datos numéricos , Valores Sociales , Estrés Psicológico/terapia , Adolescente , Adulto , Terapia Conductista/métodos , Femenino , Humanos , Masculino , Ansiedad de Desempeño/complicaciones , Ansiedad de Desempeño/psicología , Ansiedad de Desempeño/terapia , Psicoterapia Breve/métodos , Autoimagen , Autoinforme , Estrés Psicológico/complicaciones , Estrés Psicológico/psicología , EscrituraRESUMEN
BACKGROUND: There has been increasing interest and concern raised in the surgical literature regarding changes in the culture of surgical training and practice, and the impact these changes may have on surgeon stress and the appeal of a career in surgery. We surveyed pediatric surgeons and their partners to collect information on career satisfaction and work-family balance. METHODS: The American Pediatric Surgical Association Task Force on Family Issues developed separate survey instruments for both pediatric surgeons and their partners that requested demographic data and information regarding the impact of surgical training and practice on the surgeon's opportunity to be involved with his/her family. RESULTS: We found that 96% of pediatric surgeons were satisfied with their career choice. Of concern was the lack of balance, with little time available for family, noted by both pediatric surgeons and their partners. CONCLUSION: The issues of work-family balance and its impact on surgeon stress and burnout should be addressed in both pediatric surgery training and practice. The American Pediatric Surgical Association is positioned to play a leading role in this effort.