Intra-NICU Patient Transfers: A Study of Frequency and Family and Staff Perceptions.

AIMS: (a) Quantify frequency of patient moves within a NICU with single patient and semi-private rooms (SPR). (b) Compare staff and parent perceptions of these moves. METHODS: A hospital administrative database was evaluated to quantify the frequency of moves. A Room Change Questionnaire was devised to evaluate perceptions from NICU families and staff. RESULTS: Most families reported experiencing at least 1 patient move (92 percent), with the majority reporting at least 3 moves (58 percent). Staff perceived moves as negative significantly more than parents (p < .01), and overreported negative family perceptions (p < .01). Overall, moves did not bother families (52 percent); however, most families who moved 3 or more times reported at least 1 negative perception (63 percent). CONCLUSION: SFRs increase the number of patient moves. NICU staff's perception is significantly more negative than family's perception; however, most families who were moved frequently reported at least 1 negative perception.

Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high-fat diet in male and female mice.

The hypothalamus is essential for regulation of energy homeostasis and metabolism. Feeding hypercaloric, high-fat (HF) diet induces hypothalamic arcuate nucleus injury and alters metabolism more severely in male than in female mice. The site(s) and extent of hypothalamic injury in male and female mice are not completely understood. In the paraventricular nucleus (PVN) of the hypothalamus, single-minded family basic helix-loop helix transcription factor 1 (Sim1) neurons are essential to control energy homeostasis. We tested the hypothesis that exposure to HF diet induces injury to Sim1 neurons in the PVN of male and female mice. Mice expressing membrane-bound enhanced green fluorescent protein (mEGFP) in Sim1 neurons (Sim1-Cre:Rosa-mEGFP mice) were generated to visualize the effects of exposure to HF diet on these neurons. Male and female Sim1-Cre:Rosa-mEGFP mice exposed to HF diet had increased weight, hyperleptinemia, and developed hepatosteatosis. In male and female mice exposed to HF diet, expression of mEGFP was reduced by > 40% in Sim1 neurons of the PVN, an effect paralleled by cell apoptosis and neuronal loss, but not by microgliosis. In the arcuate nucleus of the Sim1-Cre:Rosa-mEGFP male mice, there was decreased alpha-melanocyte-stimulating hormone in proopiomelanocortin neurons projecting to the PVN, with increased cell apoptosis, neuronal loss, and microgliosis. These defects were undetectable in the arcuate nucleus of female mice exposed to the HF diet. Thus, injury to Sim1 neurons of the PVN is a shared feature of exposure to HF diet in mice of both sexes, while injury to proopiomelanocortin neurons in arcuate nucleus is specific to male mice. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Enrolment in paediatric oncology early-phase clinical trials: The health-care professionals' perspective.

AIM: Approximately 20-30% of children/adolescents with cancer will not respond to standard therapies. These children are usually offered experimental treatment in the form of an early-phase clinical trial. We examined the perspectives of health-care professionals (HCPs) regarding obtaining informed consent for early-phase trials in paediatric oncology. METHODS: We collected survey data from 87 HCPs working in paediatric cancer centres across Australia and New Zealand. RESULTS: HCPs were, on average, 44 years old (range = 25-74), with 15.8 years' experience in paediatric oncology (range = 1-40). Few HCPs (17.4%) received training for early-phase trial consent; however, most were willing to attend training (77.9%). HCPs (61.6%) reported that they informed families about early-phase trials without any attempt to influence their decision. However, 23.3% of HCPs reported that they informed families that their child would benefit. HCPs' main obstacle in obtaining consent was their perception of parents' eagerness to 'try anything' (52.3%). HCPs perceived that many parents misunderstood key clinical trials concepts, with 25.2% of HCPs believing that not being given clear information influenced parents' decisions. Physicians were more likely than social workers/nurses to inform families that other children will benefit from enrolment in the study. Social workers/nurses appeared to rate the chance of benefits for the patient higher than physicians. CONCLUSIONS: HCPs may experience difficulty conducting early-phase trial consultations and obtaining valid informed consent. Our study highlights the need for formal training for HCPs and additional patient education tools.

Delphi Study: ASPAN Adult Patient Pain and Comfort Practices.

PURPOSE: The American Society of PeriAnesthesia Nurses (ASPAN) is responsible for establishing evidence-based standards to guide perianesthesia nursing practice. The ASPAN model for evidence-based practice acknowledges the potential for the Delphi technique to identify priorities for perianesthesia research. The purpose of this Delphi study was to generate a consensus on pain and comfort among a panel of experts. DESIGN: ASPAN convened a panel of experts to provide recommendations based on seven categories, this led to the development of a questionnaire to build consensus. METHODS: Survey conducted among panel of experts to obtain consensus. Two survey rounds were completed. FINDINGS: A consensus was obtained reaching a 70% benchmark for an acceptance. CONCLUSIONS: The results found a consensus on topics required for education and competency among perianesthesia nurses including transfer and discharge criteria related to pain and comfort, resources for perianesthesia nurses, policy guidelines, and the management of the special needs of perianesthesia patients.

Lipid stress inhibits endocytosis of melanocortin-4 receptor from modified clathrin-enriched sites and impairs receptor desensitization.

Melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor expressed in the brain's hypothalamus where it regulates energy homeostasis. MC4R agonists function to lower food intake and weight. In this respect, although obesity promotes hyperlipidemia and hypothalamic injury, MC4R agonists are nevertheless more effective to reduce food intake within hours of administration in overweight, rather than lean, mice. MC4R undergoes constitutive internalization and recycling to the plasma membrane with agonist binding inducing receptor retention along the intracellular route and, under prolonged exposure, desensitization. Here, we found that, in neuronal cells, lipid stress by exposure to elevated palmitate leaves unchanged the rate by which MC4R and transferrin receptor are constitutively excluded from the cell surface. However, lipid stress disrupted later steps of MC4R and transferrin receptor internalization to endosomes as well as traffic of agonist-occupied MC4R to lysosomes and MC4R desensitization. In the lipid-stressed cells, MC4R and clathrin were redistributed to the plasma membrane where they colocalized to sites that appeared by super-resolution microscopy to be modified and to have higher clathrin content than those of cells not exposed to elevated palmitate. The data suggest that lipid stress disrupts steps of endocytosis following MC4R localization to clathrin-coated sites and exclusion of the receptor from the extracellular medium. We conclude that increased effectiveness of MC4R agonists in obesity may be an unexpected outcome of neuronal injury with disrupted clathrin-dependent endocytosis and impaired receptor desensitization.

Quantitative analysis of anxiety levels of nursing students studying bioscience in Australia.

Nursing students traditionally find bioscience difficult and anxiety provoking. This has important ramifications, as anxiety can hinder comprehension and lead to poor exam performance. The aim of the present study was to assess whether there was any difference between the anxiety levels of nursing students during their bioscience laboratory classes compared to their clinical laboratory classes. Students were recruited from a first year Bachelor of Nursing program. The self-report State-Trait Anxiety Inventory (short form) was administered at the start of all classes throughout the semester. Anxiety scores of students between the units were compared using paired t-tests, and repeated-measures analysis of variance was used to measure anxiety scores within units over time. There were no significant differences in anxiety scores in the bioscience and clinical classes; however, the students were significantly more anxious in the theory classes. These findings suggest that nursing students do not find the subject of bioscience any more anxiety provoking than other nursing subjects. Bioscience educators should continue to focus on the integration of bioscience with nursing practice, while broader anxiety-reduction strategies throughout the curriculum should be implemented.

Localised intravascular coagulation complicating venous malformations in children: Associations and therapeutic options.

Venous malformations are slow-flow congenital vascular malformations that enlarge as the child ages and may be associated with localised intravascular coagulation, a consumptive coagulopathy characterised by elevated D-dimer and decreased fibrinogen levels. The authors review the known correlations between localised intravascular coagulation and venous malformation number, size and planes involved, and call attention to the concept of the progression of localised intravascular coagulopathy as the child ages and their venous malformations enlarge. The authors also discuss the identified therapeutic options for its investigation, management and treatment, including compression garments, anti-coagulation therapy, sclerotherapy, endovascular laser, surgical excision and sirolimus (rapamycin). Evidence for protocol improvements that may be instigated for the optimal physical and medical therapy of venous malformations complicated by localised intravascular coagulopathy is reviewed.

Haematopoietic stem cell transplantation for primary immunodeficiency syndromes: A 5-year single-centre experience.

AIM: Haematopoietic stem cell transplantation (HSCT) is a central therapy in the treatment of primary immunodeficiency diseases (PIDs). Over the past 5 years, outcomes have been greatly improved due to earlier diagnosis, improved donor availability, advancements in graft manipulation and the use of less toxic preparative regimens. We present a 5-year audit of HSCT for PID at a single Australian tertiary hospital. METHODS: Retrospective case note review identified diagnosis, pre-transplant medical morbidity, transplant protocol, engraftment, adverse events, post-transplant immune reconstitution and general health. RESULTS: A total of 22 patients with PID underwent 24 HSCTs at our institution between 2012 and 2016. The most common indications were severe combined immunodeficiency, chronic granulomatous disease and familial haemophagocytic lymphohistiocytosis, with a genetic diagnosis in all but two patients. Reduced intensity or reduced toxicity conditioning was used in 91% of cases, and 75% of the donors were unrelated. Transplant-related mortality at day +100 was 9.5%, and cumulative overall survival was 86%. There were three mortalities, all secondary to viral infection, one of which occurred in the context of graft failure. Two patients remained on immune support, with the remainder achieving adequate immune reconstitution. CONCLUSIONS: The outcomes for HSCT for PIDs performed at Sydney Children's Hospital were in line with the world's best practice. HSCT should be considered a potential therapeutic option for all Australian PID patients with a valid disease indication.

The legacy of gender-based violence and HIV/AIDS in the postgenocide era: Stories from women in Rwanda.

Drawing on qualitative interviews with 22 Rwandan women, we describe the lived experiences of women survivors of gender-based violence (GBV) more than a decade and a half after the 1994 Genocide. We argue that the intersection between GBV and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) has long-term implications: the majority of women interviewed continue to endure trauma, stigma, social isolation, and economic hardship in the postgenocide era and are in need of expanded economic and mental health support. Our findings have implications for the importance of providing integrated psychosocial support to survivors of GBV postconflict contexts.

Systematic identification of tRNAome and its dynamics in Lactococcus lactis.

Transfer RNAs (tRNAs) through their abundance and modification pattern significantly influence protein translation. Here, we present a systematic analysis of the tRNAome of Lactococcus lactis. Using the next-generation sequencing approach, we identified 40 tRNAs which carry 16 different post-transcriptional modifications as revealed by mass spectrometry analysis. While small modifications are located in the tRNA body, hypermodified nucleotides are mainly present in the anticodon loop, which through wobbling expand the decoding potential of the tRNAs. Using tRNA-based microarrays, we also determined the dynamics in tRNA abundance upon changes in the growth rate and heterologous protein overexpression stress. With a fourfold increase in the growth rate, the relative abundance of tRNAs cognate to low abundance codons decrease, while the tRNAs cognate to major codons remain mostly unchanged. Significant changes in the tRNA abundances are observed upon protein overexpression stress, which does not correlate with the codon usage of the overexpressed gene but rather reflects the altered expression of housekeeping genes.

Platelet glycoprotein Ib-IX as a regulator of systemic inflammation.

OBJECTIVE: The platelet glycoprotein Ib-IX (GP Ib-IX) receptor is a well-characterized adhesion receptor supporting hemostasis and thrombosis via interactions with von Willebrand factor. We examine the GP Ib-IX/von Willebrand factor axis in murine polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP). APPROACH AND RESULTS: Genetic absence of the GP Ib-IX ligand, von Willebrand factor, prolongs survival after CLP, but absence of the receptor, GP Ib-IX, does not. Because absence of either von Willebrand factor or GP Ib-IX significantly impairs hemostasis and thrombosis, we sought to define additional GP Ib-IX-dependent pathways impacting survival in the CLP model. We document that the absence of GP Ib-IX leads to reduced platelet-neutrophil and platelet-monocyte interactions. Twenty-four hours after CLP, absence of GP Ib-IX coincides with an alteration in cytokine levels, such as tumor necrosis factor-α secreted by monocytes, and increased macrophage-1 antigen expression by neutrophils. CONCLUSIONS: In contrast to the well-characterized proinflammatory properties of platelets, we describe in the CLP model an anti-inflammatory property associated with platelet GP Ib-IX. Thus, a single platelet receptor displays a dual modulatory role in both the thrombotic and inflammatory pathways associated with polymicrobial sepsis. In sharing leucine-rich motifs with toll-like receptors, platelet GP Ib-IX can be considered a multifunctional participant in hemostasis, thrombosis, and the inflammatory cascade. The results highlight a dynamic role for platelets in systemic inflammation and add to the complex pathophysiologic events that occur during the dysregulated coagulation and inflammation associated with sepsis.

Wnt coreceptor Lrp5 is a driver of idiopathic pulmonary fibrosis.

RATIONALE: Wnt/ß-catenin signaling has been implicated in lung fibrosis, but how this occurs and whether expression changes in Wnt pathway components predict disease progression is unknown. OBJECTIVES: To determine whether the Wnt coreceptor Lrp5 drives pulmonary fibrosis in mice and is predictive of disease severity in humans. METHODS: We examined mice with impaired Wnt signaling caused by loss of the Wnt coreceptor Lrp5 in models of lung fibrosis induced by bleomycin or an adenovirus encoding an active form of transforming growth factor (TGF)-ß. We also analyzed gene expression in peripheral blood mononuclear cells (PBMC) from patients with idiopathic pulmonary fibrosis (IPF). MEASUREMENTS AND MAIN RESULTS: In patients with IPF, analysis of peripheral blood mononuclear cells revealed that elevation of positive regulators, Lrp5 and 6, was independently associated with disease progression. LRP5 was also associated with disease severity at presentation in an additional cohort of patients with IPF. Lrp5 null mice were protected against bleomycin-induced pulmonary fibrosis, an effect that was phenocopied by direct inhibition of ß-catenin signaling by the small molecular inhibitor of ß-catenin responsive transcription. Transplantation of Lrp5 null bone marrow cells into wild-type mice did not limit fibrosis. Instead, Lrp5 loss was associated with reduced TGF-ß production by alveolar type 2 cells and leukocytes. Consistent with a role of Lrp5 in the activation of TGF-ß, Lrp5 null mice were not protected against lung fibrosis induced by TGF-ß. CONCLUSIONS: We show that the Wnt coreceptor, Lrp5, is a genetic driver of lung fibrosis in mice and a marker of disease progression and severity in humans with IPF. Evidence that TGF-ß signaling can override a loss in Lrp5 has implications for patient selection and timing of Wnt pathway inhibitors in lung fibrosis.

Transforming LEND leadership training curriculum through the maternal and child health leadership competencies.

The purpose of this article is to describe how the Maternal and Child Health (MCH) Leadership Competencies (v 3.0) were used to examine and improve an MCH Leadership Education in Neurodevelopmental and Related Disabilities (LEND) training curriculum for New Hampshire and Maine. Over 15 % of the nation's children experience neurodevelopmental disabilities or special health care needs and estimates suggest 1 in every 68 children is diagnosed with an autism spectrum disorder. Across the Unites States critical shortages of qualified MCH professionals exist, particularly in poor and rural areas. A continued investment in training interdisciplinary leaders is critical. The MCH Leadership Competencies provide an effective foundation for leadership training through identification of requisite knowledge, skills, and dispositions required of MCH leaders. This paper describes a three-step process, which began in 2010 and included utilizing the MCH Leadership Competencies as a tool to reflect on, develop, and evaluate the NH LEND leadership curriculum. Curriculum development was further supported through participation in a multi-state learning collaborative. Through a series of intentional decisions, the curriculum design of NH LEND utilized the competencies and evidence-based principles of instruction to engage trainees in the development of specific MCH content knowledge and leadership skills. The LEND network specifically, and MCH leadership programs more broadly, may benefit from the intentional use of the MCH competencies to assist in curriculum development and program evaluation, and as a means to support trainees in identifying specific leadership goals and evaluating their leadership skill development.

Transplant-related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25-year retrospective review.

BACKGROUND: Over the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased. PROCEDURE: A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984-31/8/1992, Period 2: 1/9/1992-30/4/2001, Period 3: 1/5/2001-31/12/2009). RESULTS: Despite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6-64.8%, P = 0.0027; OS 41.8-78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time. CONCLUSION: EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement.

Agmatidine, a modified cytidine in the anticodon of archaeal tRNA(Ile), base pairs with adenosine but not with guanosine.

Modification of the cytidine in the first anticodon position of the AUA decoding tRNA(Ile) (tRNA2(Ile)) of bacteria and archaea is essential for this tRNA to read the isoleucine codon AUA and to differentiate between AUA and the methionine codon AUG. To identify the modified cytidine in archaea, we have purified this tRNA species from Haloarcula marismortui, established its codon reading properties, used liquid chromatography-mass spectrometry (LC-MS) to map RNase A and T1 digestion products onto the tRNA, and used LC-MS/MS to sequence the oligonucleotides in RNase A digests. These analyses revealed that the modification of cytidine in the anticodon of tRNA2(Ile) adds 112 mass units to its molecular mass and makes the glycosidic bond unusually labile during mass spectral analyses. Accurate mass LC-MS and LC-MS/MS analysis of total nucleoside digests of the tRNA2(Ile) demonstrated the absence in the modified cytidine of the C2-oxo group and its replacement by agmatine (decarboxy-arginine) through a secondary amine linkage. We propose the name agmatidine, abbreviation C(+), for this modified cytidine. Agmatidine is also present in Methanococcus maripaludis tRNA2(Ile) and in Sulfolobus solfataricus total tRNA, indicating its probable occurrence in the AUA decoding tRNA(Ile) of euryarchaea and crenarchaea. The identification of agmatidine shows that bacteria and archaea have developed very similar strategies for reading the isoleucine codon AUA while discriminating against the methionine codon AUG.

Functional characterization of the YmcB and YqeV tRNA methylthiotransferases of Bacillus subtilis.

Methylthiotransferases (MTTases) are a closely related family of proteins that perform both radical-S-adenosylmethionine (SAM) mediated sulfur insertion and SAM-dependent methylation to modify nucleic acid or protein targets with a methyl thioether group (-SCH(3)). Members of two of the four known subgroups of MTTases have been characterized, typified by MiaB, which modifies N(6)-isopentenyladenosine (i(6)A) to 2-methylthio-N(6)-isopentenyladenosine (ms(2)i(6)A) in tRNA, and RimO, which modifies a specific aspartate residue in ribosomal protein S12. In this work, we have characterized the two MTTases encoded by Bacillus subtilis 168 and find that, consistent with bioinformatic predictions, ymcB is required for ms(2)i(6)A formation (MiaB activity), and yqeV is required for modification of N(6)-threonylcarbamoyladenosine (t(6)A) to 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A) in tRNA. The enzyme responsible for the latter activity belongs to a third MTTase subgroup, no member of which has previously been characterized. We performed domain-swapping experiments between YmcB and YqeV to narrow down the protein domain(s) responsible for distinguishing i(6)A from t(6)A and found that the C-terminal TRAM domain, putatively involved with RNA binding, is likely not involved with this discrimination. Finally, we performed a computational analysis to identify candidate residues outside the TRAM domain that may be involved with substrate recognition. These residues represent interesting targets for further analysis.

Australian Paediatric Surveillance Unit study of haemoglobinopathies in Australian children.

AIM: The aims of this study were to determine the incidence and types of haemoglobinopathies in Australian children and their distribution among ethnic groups, and to collect information on timing of diagnosis of haemoglobinopathies in Australia. METHODS: Between January 2004 and March 2006, the Australian Paediatric Surveillance Unit asked paediatricians to report all children under 15 years of age with a newly diagnosed haemoglobinopathy. A questionnaire requesting further information was forwarded to those clinicians. Carrier states such as thalassaemia minor were excluded. RESULTS: Eighty-four notifications of haemoglobinopathy were received by the Australian Paediatric Surveillance Unit, with 59 confirmed cases giving a national incidence of 0.74 per 100,000 children < 15 years of age per annum. Of 59 cases, 42 (71%) were Australian born. Twenty-nine (35.6%) children had sickle cell disease, 17 (28.8%) had Hb H disease, six (10.2%) had beta-thalassaemia major and 15 (25.4%) had compound heterozygous conditions. One child died from sickle cell disease. Of Australian born children, at least 10 mothers (23.8%) and 11 fathers (26.2%) were unaware of their carrier status pre-partum (information unavailable for 13 mothers and 17 fathers). Only 11 parents (18.6%) had risks of haemoglobinopathy discussed with them antenatally and only three cases (5.1%) were diagnosed antenatally. CONCLUSIONS: We found that a small but significant number of children with haemoglobinopathies are being born in Australia despite existing programmes of testing at-risk groups and neonatal screening. Haemoglobinopathies were also diagnosed in recent immigrants. Greater awareness of these conditions and enhancements of screening and detection programmes may be needed as the genetic diversity of the Australian population continues to develop.