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Critical heart disease in the pediatric population is associated with high morbidity and mortality. Research around the most effective communication and decision-making strategies is lacking. This systematic review aims to summarise what is known about parent preference for communication and decision-making in children with critical heart disease. Database searches included key words such as family, pediatric heart disease, communication, and decision-making. A total of 10 studies fit our inclusion criteria: nine were qualitative studies with parent interviews and one study was quantitative with a parent survey. We found three main themes regarding physician-parent communication and decision-making in the context of paediatric heart disease: (1) amount, timing, and content of information provided to parents; (2) helpful physician characteristics and communication styles; and (3) reinforcing the support circle for families.

Background: Children with chronic critical illness (CCI), those children with repeated and prolonged hospitalizations along with technology-dependence or multiple organ system involvement, are increasing in number. The intensive daily needs of these children, during hospitalization and at home, affect both clinicians and families., Objective: To assess clinician experiences of burnout and clinician perceptions of family burnout in caring for children with CCI., Design: Semistructured interviews with 44 stakeholders known for pediatric CCI expertise were audio-recorded and transcribed. Participants characterized their experiences with provider and family burnout., Setting/subjects: Stakeholders were from five metropolitan areas, representing a variety of professions (i.e., inpatient/outpatient clinicians, home health providers, and policy professionals)., Measurements: Content analysis was performed on interview transcripts., Results: Participants reported that both clinicians and families caring for children with CCI experience some level of burnout, although stakeholders note that families may experience burnout differently than clinicians. Burnout results from the following: (1) escalating daily care needs; (2) intense relationships between clinicians and families; (3) uncertain outcomes; (4) feeling unprepared to care for children with complicated medical needs; and (5) the stress and emotional toll of caring for a child with CCI., Conclusions: Managing the medical needs of children with CCI can be associated with clinician and parent burnout. Strategies to support clinicians and families are needed to ensure high quality of care for these children, as well as maintain an appropriate number of clinical providers for this vulnerable subset of children with medical complexity.

Children in foster care are considered a “vulnerable population” in clinical care and research, with good reason. These children face multiple medical, psychological, and social risks that obligate the child welfare and healthcare systems to protect them from further harms. An unintended consequence of the “vulnerable population” designation for children in foster care is that it may impose barriers on tracking and studying their health that creates gaps in knowledge that are key to their receipt of medical care and good outcomes. These gaps in knowledge have implications for justice, beneficence, and maleficence and serve to undermine “protection” of this population. Here we review the challenges of research regarding children in foster care, particularly medically complex children, and offer specific recommendations to include children in foster care in medical research.

Objective: To develop a question prompt list tailored to the needs of parents of critically ill infants at risk of neurodevelopmental impairment., Study Design: Question content was derived from audio-recorded neonatal intensive care unit family meetings and interviews with parents of infants treated with therapeutic hypothermia. Question content was refined using clinician focus groups. Acceptability testing was performed with parents and clinicians caring for infants in the neonatal intensive care unit., Results: All clinicians and parents found the QPL content acceptable. Parents universally endorsed that the question prompt list was useful to them and would help them prepare for a meeting with their infant's healthcare team., Conclusion: This question prompt list, designed for parents of critically ill infants, is acceptable to parents and clinicians, and can be used in the acute neonatal course to facilitate parent engagement in family meetings.

Objective: Neonatal ICUs and PICUs increasingly admit patients with chronic critical illness: children whose medical complexity leads to recurrent and prolonged ICU hospitalizations. We interviewed participants who routinely care for children with chronic critical illness to describe their experiences with ICU care for pediatric chronic critical illness., Design: Semi-structured interviews. Interviews were transcribed and analyzed for themes., Setting: Stakeholders came from five regions (Seattle, WA; Houston, TX; Jackson, MS; Baltimore, MD; and Philadelphia, PA)., Subjects: Fifty-one stakeholders including: 1) interdisciplinary providers (inpatient, outpatient, home care, foster care) with extensive chronic critical illness experience; or 2) parents of children with chronic critical illness., Interventions: Telephone or in-person interviews., Measurements and Main Results: Stakeholders identified several key issues and several themes emerged after qualitative analysis. Issues around chronic critical illness patient factors noted that patients are often relocated to the ICU because of their medical needs. During extended ICU stays, these children require longitudinal relationships and developmental stimulation that outstrip ICU capabilities. Family factors can affect care as prolonged ICU experience leads some to disengage from decision-making. Clinician factors noted that parents of children with chronic critical illness are often experts about their child's disease, shifting the typical ICU clinician-parent relationship. Comprehensive care for children with chronic critical illness can become secondary to needs of acutely ill patients. Lastly, with regard to system factors, stakeholders agreed that achieving consistent ICU care goals is difficult for chronic critical illness patients., Conclusions: ICU care is poorly adapted to pediatric chronic critical illness. Patient, family, clinician, and system factors highlight opportunities for targeted interventions toward improvement in care.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Objectives: The past 2 decades have seen an expanding pediatric population that is chronically critically ill: children with repeated and prolonged hospitalizations and ongoing dependence on technologies to sustain vital functions. Although illness complexity prompts many hospitalizations, our goal with this study was to explore modifiable patient, family, and health system contributions to excess hospital days for children with chronic critical illness (CCI)., Methods: Semistructured interviews were conducted with 51 stakeholders known for their CCI expertise. Stakeholders were from 5 metropolitan areas and were either (1) interdisciplinary providers (inpatient and/or outpatient clinicians, home health providers, foster care affiliates, or policy professionals) or (2) parents of children with CCI. Interview transcripts were qualitatively analyzed for themes., Results: All stakeholders agreed that homelike settings are ideal care sites for children with CCI, yet in every region these children experience prolonged hospitalizations. The perceived causes of excess hospital days are (1) inadequate communication and coordination within health care teams and between clinicians and families, (2) widespread gaps in qualified pediatric home health services and durable medical equipment providers, (3) inconsistent parent support, and (4) policies that limit pediatric service eligibility, state-supported case management, and nonhospital care sites., Conclusions: Despite an expanding pediatric population with CCI, we lack an intentional care model to minimize their hospitalizations. In this study, we generate several hypotheses for exploring the potential impact of expanded access to home nursing, robust care coordination, and family and clinician support to reduce hospital days for this population of high health care utilizers., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

We describe three cases of newborns with complex CHD characterised by communication challenges. These communication challenges were categorised as patient, family, or system-related red flags. Strategies for addressing these red flags were proposed, for the goal of optimising care and improving quality of life in this vulnerable population.

The discovery of infectious particles that challenge conventional thoughts concerning "what is a virus" has led to the evolution a new field of study in the past decade. Here, we review knowledge and information concerning "giant viruses", with a focus not only on some of the best studied systems, but also provide an effort to illuminate systems yet to be better resolved. We conclude by demonstrating that there is an abundance of new host-virus systems that fall into this "giant" category, demonstrating that this field of inquiry presents great opportunities for future research.

Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing ≤ 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

This review considers a variety of perspectives on overweight and obesity (OW/obesity), including measurement and classification; prevalence and changes in prevalence in recent years; genetic, biological, medical, individual, and social correlates of OW/obesity; and treatment approaches. Despite increased attention, OW/obesity is escalating in prevalence worldwide, and the causes are exceedingly complex. A range of innovative studies, including basic research on gut microflora, dietary composition, pharmacologic interventions, and surgical procedures, is generating findings with potential for future prevention and treatment of OW/obesity. Social system changes such as school programs and the awareness of the roles of personal, family, health provider, and cultural experiences related to OW/obesity have also gained traction for vital prevention and treatment efforts over the past decade.

Purpose: Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used therapy for many patients with hematologic malignancies and other marrow failure or immune system disorders. The purpose of this study was to quantify and visualize both the demand and unmet need for HCT., Methods: HCT use for 2012 was described using the Center for International Blood and Marrow Transplant Research registry. Potential demand for HCT was calculated using 2012 SEER data and published literature for HCT-treatable conditions. Point locations of transplant centers were geocoded using geographic information system (GIS) software; Thiessen polygons were created to establish adult (age 20 to 74 years) and pediatric (age 0 to 19 years) market areas. Market-area population estimates were calculated using 2012 population estimates by age aggregated by census block., Results: US market areas for HCTs were identified separately for transplant centers treating adult (n = 62) and pediatric patients (n = 52). Overall HCT demand among adults was 16,096, with an unmet need for HCTs of 10,276 patients. For pediatric patients, the total demand was 4,561, with an unmet need of 3,213 potential recipients. Evaluation of adult and pediatric market areas indicated that the largest unmet needs tended to be in areas with large populations., Conclusion: Market-area maps and statistics developed using GIS will help communicate the unmet need for HCT, inform policy, and assist transplant centers in planning for the anticipated growth in HCT use., (Copyright © 2015 by American Society of Clinical Oncology.)

Background: Dinoflagellates are eukaryotes with unusual cell biology and appear to rely on translational rather than transcriptional control of gene expression. The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in regulating gene expression because eIF4E binding to the mRNA cap is a control point for translation. eIF4E is part of an extended, eukaryote-specific family with different members having specific functions, based on studies of model organisms. Dinoflagellate eIF4E diversity could provide a mechanism for dinoflagellates to regulate gene expression in a post-transcriptional manner. Accordingly, eIF4E family members from eleven core dinoflagellate transcriptomes were surveyed to determine the diversity and phylogeny of the eIF4E family in dinoflagellates and related lineages including apicomplexans, ciliates and heterokonts., Results: The survey uncovered eight to fifteen (on average eleven) different eIF4E family members in each core dinoflagellate species. The eIF4E family members from heterokonts and dinoflagellates segregated into three clades, suggesting at least three eIF4E cognates were present in their common ancestor. However, these three clades are distinct from the three previously described eIF4E classes, reflecting diverse approaches to a central eukaryotic function. Heterokonts contain four clades, ciliates two and apicomplexans only a single recognizable eIF4E clade. In the core dinoflagellates, the three clades were further divided into nine sub-clades based on the phylogenetic analysis and species representation. Six of the sub-clades included at least one member from all eleven core dinoflagellate species, suggesting duplication in their shared ancestor. Conservation within sub-clades varied, suggesting different selection pressures., Conclusions: Phylogenetic analysis of eIF4E in core dinoflagellates revealed complex layering of duplication and conservation when compared to other eukaryotes. Our results suggest that the diverse eIF4E family in core dinoflagellates may provide a toolkit to enable selective translation as a strategy for controlling gene expression in these enigmatic eukaryotes.

Dinoflagellates are unusual eukaryotes with large genomes and a reduced role for transcriptional regulation compared to other eukaryotes. The mRNA in dinoflagellates is trans -spliced with a 5'-spliced-leader sequence, yielding a 22-nucleotide 5'-sequence with a methylated nucleotide cap. Since the control of gene expression is primarily post-transcriptional, this study focuses on mRNA recruitment as a means for regulating gene expression and specifically on the diversity of eIF4E family members. Three novel clades related to the cap binding initiation factor eIF4E have been recognized in alveolates that are distinct from the three metazoan classes of eIF4E. We have analyzed the characteristics of five of the fourteen eIF4E family members from Karlodinium veneficum , four from clade 1 and one from clade 2. Members of each clade all bear the distinctive features of a cap-binding protein. We examined their ability to interact with the cap analogue, m 7 GTP using an in vitro bead-binding assay. We show that recombinant eIF4E-1 family members are able to bind the cap analogue m 7 GTP, but eIF4E-2b binds poorly. Overall, the eIF4E-1 family members may be serving as general cap-binding translation initiation factors, while the eIF4E-2 (and perhaps eIF4E-3) family members may serve a regulatory role in gene expression.

Obesity continues to affect African Americans in epidemic proportions, particularly among women and adolescent females. Perceptions, beliefs, behaviors, and body sizes of adolescents are associated with those of their mothers, yet little is known about the transgenerational meanings and experiences of obese African American adolescent girls and their mothers. An interpretive phenomenological study was conducted with seven African American adolescents between the ages of 11 and 17, and their adult female caregivers. Audio-taped interviews were transcribed and analyzed by a multicultural interpretive team. Two constitutive patterns and associated themes were identified. One pattern, 'Framing: sizing it up; sizing it down', with its three associated themes is presented. Mothers and daughters are engaged in multiple common practices in which they self-define body size, while protecting their self-esteem and self-image. This pattern illustrates how the women and girls created an image of their bodies as they confronted and acknowledged their self-perceptions, compared themselves to others in their environment, and evaluated themselves against specific parameters of acceptable size.

The entire mitochondrial genome of the striped bass Morone saxatilis was sequenced together with the mitochondrial (mt) control regions of the white bass Morone chrysops, white perch Morone americana, yellow bass Morone mississippiensis, spotted seabass Dicentrarchus punctatus, European seabass Dicentrarchus labrax and the Japanese seabass Lateolabrax japonicus. The resultant 17 580 base pair circular genome of M. saxatilis contains 38 genes (13 proteins, 23 transfer RNAs and two ribosomal RNAs) and a control region bordered by the proline and phenylalanine mitochondrial tRNAs. Gene arrangement was similar to other vertebrates, except that the mt-nd6 gene was found within the control region rather than the canonical position between the mt-nd5 and mt-cyb genes. This translocation was found in all the Morone and Dicentrarchus species studied without functional copies or pseudogenes in the ancestral position. In L. japonicus, the mt-nd6 gene was found in the canonical position without evidence of an mt-nd6 gene in the control region. A Bayesian analysis of these and published mt-nd6 sequences from 45 other Perciformes grouped the Morone and Dicentrarchus species monophyletically with a probability of 1·00 with respect to L. japonicus and all other perciforms, and placed the Dicentrarchus species in the basal position. These data reinforce current placement of L. japonicus outside the Moronidae and provide a clear evolutionary character to define this family. The phylogeny of the Moronidae presented here also supports the hypothesis of an anadromous common ancestor to this family that gave rise to the North American estuarine and freshwater species. A series of tandem repeats previously reported in M. saxatilis was found in the control region of all Morone species between the mt-nd6 and mt-rnr1 genes, but not in either Dicentrarchus species, which reinforces the continued use of these two separate genera., (© 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.)

Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1alpha and HIF-2alpha, and overexpression of HIF-2alpha in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2alpha during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1alpha versus HIF-2alpha must be elucidated. We demonstrate here that mice lacking HIF-2alpha in myeloid cells (Hif2aDelta/Delta mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2alpha directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2aDelta/Delta mice displayed reduced TAM infiltration in independent murine hepatocellular and colitis-associated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2alpha modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2alpha as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.

Objectives: Despite having potent activity against actively replicating Mycobacterium tuberculosis, isoniazid has very limited activity against dormant bacilli. In order to investigate the lack of bactericidal activity of this drug under conditions leading to mycobacterial dormancy, we studied the transcriptional pattern of M. tuberculosis in different physiological states following exposure to isoniazid., Methods: Global gene expression analysis was used to study M. tuberculosis treated with isoniazid in dormancy models of nutrient depletion and progressive hypoxia in vitro, as well as in an in vivo hollow fibre model of dormancy. Mycobacterial expression of the drug's putative transcriptional signature was investigated by RT-PCR in each dormancy model, and during the early and chronic phases of infection in the mouse aerosol model. Transcriptional responses were correlated with the bactericidal activity of isoniazid in the respective models., Results: A small group of genes directly relevant to the mechanism of action of isoniazid was confirmed to constitute a transcriptional signature of the drug, as differential regulation of these genes was abrogated in an isoniazid-resistant, katG-deficient M. tuberculosis strain following isoniazid exposure. Isoniazid-induced expression of this transcriptional signature was abolished in dormant bacilli which had acquired phenotypic tolerance to isoniazid, regardless of the specific conditions responsible for the induction of the dormancy phenotype. Quantitative RT-PCR revealed that expression of isoniazid-regulated genes (IRGs) is dramatically altered under conditions of nutrient depletion and progressive hypoxia in vitro. Although these IRGs are highly induced following drug exposure early in infection in the mouse hollow fibre and aerosol models, correlating with potent bactericidal activity of the drug, their expression levels are markedly diminished during late-stage infection in these two models, coinciding with the greatly reduced bactericidal activity of isoniazid against these organisms., Conclusions: The reduced susceptibility of bacilli to the bactericidal drug isoniazid, as well as lack of expression of IRGs upon exposure to the drug, may be defining features of M. tuberculosis dormancy.

Mycobacterium tuberculosis SigF is homologous to stress response and sporulation sigma factors in many bacteria. Consistent with a possible role in mycobacterial survival under stress conditions, M. tuberculosis sigF is strongly induced within cultured human macrophages and upon nutrient starvation, and SigF has been implicated in M. tuberculosis entry into stationary phase. On the other hand, SigF appears to contribute to the immune pathology of tuberculosis (TB), and a sigF-deficient mutant has altered cell membrane properties. Using an M. tuberculosis sigF deletion mutant, we show here that sigF is not required for bacillary survival under nutrient starvation conditions and within activated murine macrophages or for extracellular persistence in an in vivo granuloma model of latent TB infection. Using a chemically inducible recombinant strain to conditionally overexpress sigF, we did not observe arrest or retardation of growth in exponentially growing cultures or reduced susceptibility to rifampin and isoniazid. Consistent with our hypothesis that SigF may mediate TB immunopathogenesis by altering cell membrane properties, we found that overexpression of sigF resulted in the differential regulation of many cell wall-associated proteins, including members of the MmpL, PE, and PPE families, several of which have been shown to influence host-pathogen interactions. The most highly upregulated gene by quantitative reverse transcription-PCR at all time points following sigF induction was Rv3301c (phoY1), which encodes a probable transcriptional regulatory protein homologous to PhoU proteins involved in regulation of phosphate uptake. Using in vitro transcription analysis, we show that SigF directly regulates phoY1, whose proposed promoter sequence is GGATTG-N(16)-GGGTAT.

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.

The gene transfer efficiency into nonobese diabetic/severe combined immunodeficient (NOD/SCID)-repopulating cells (SRCs) derived from umbilical cord blood (UCB) (n = 11 NOD/SCID mice) and granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) (n = 64 NOD/SCID mice) was compared using a clinically relevant protocol and a retrovirus vector expressing the enhanced green fluorescent protein (EGFP). At 6-9 weeks after transplantation, the frequency of transduced human cells in the bone marrow (BM) (40.5% +/- 2.4% [mean +/- SE]) and spleen (SPL) (36.4% +/- 3.2%) in recipients of UCB cells was significantly higher (p < 0.001) than that observed in the BM (2.2% +/- 1.8%) and SPL (2.0% +/- 2.6%) in recipients of MPB. In subsequent studies, MPB was cultured for 2-8 days in cytokines prior to transduction to determine if longer prestimulation was required for optimal gene transfer. A significant increase in gene transfer into CD45(+) human cells and clonogenic cells derived from MPB SRCs was observed when cells were prestimulated for 6 days compared to 2 days prior to transduction (p = 0.019). However, even after 6 days of prestimulation, transduction was still significantly less than UCB. A substantial discrepancy exists in the ability to introduce genes effectively via retrovirus vectors into SRCs derived from MPB as compared to UCB.