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Background: The aim of the study was to analyse body composition of preterm infants fed with either breast milk or formula compared to a control group of full-term newborns. Methods: Fifty-three newborns were enrolled: a group of 34 very low birth weight (VLBW) preterm newborns subdivided into a formula-fed (n = 23; group A) and breast milk-fed (n = 11; group B) group, and a control group of 19 full-term infants (group C). Their body composition was assessed by a bioelectrical impedance analysis (BIA) either at the estimated time of birth in the VLBW group or during the 1st week of life in the full-term group. Results: There was no difference in body weight or length between any of the three studied groups. However, we discovered that fat free mass (% FFM) was lower (83.5% vs. 85.5%; p

There has been little previous research regarding the effectiveness of ethics education interventions for residential care-givers. The Researching Interventions to Promote Ethics in social care project responded to the question: Which is the most effective ethics education intervention for care-givers in residential social care? A pragmatic cluster trial explored the impact of three ethics education interventions for: (a) interactive face-to-face ethics teaching; (b) reflective ethics discussion groups; and (c) an immersive simulation experience. There was also a control arm (d). 144 trial participants were recruited from 39 residential care homes for older people in southern England. Change scores compared across intervention arms showed a significant reduction in work-related moral stress in the teaching arm compared with control group (p = .03); there were no significant differences between control and intervention arms in change scores for moral sensitivity, interpersonal reactivity (empathy) or ethical leadership. Qualitative data themes were as follows: ethical care; care challenges; and ethical care inhibitors. Overall findings stimulate reflection on the value of three different ethics education interventions and the most appropriate means to evaluate their impact. Findings suggest the complexity and diverse nature of ethical competence in care. We suggest a way forward for research evaluating ethics education.

Introduction This research set out to understand the context and explore the reasons for the disproportionate number of complaints raised against paramedics to the United Kingdom professional regulator – the Health and Care Professions Council – relative to other health professions. Methods This paper reports on qualitative findings from one aspect of a mixed-methods study which included a case analysis, Delphi study and literature review. One-to-one semi-structured interviews conducted with 15 stakeholders drawn from practitioners, educators, representatives and regulators, and three focus groups held with 16 practitioners and service users were used to gain an in-depth understanding of the possible reasons for complaints about paramedic practice. Results Five themes were generated from a thematic analysis of the data: the impact of public perceptions and expectations; the challenges of day-to-day practice; the effect of increasingly pressurised services; the organisational and cultural climate which impacts paramedics’ work; and the evolving nature of the profession. Conclusion This study highlights the complex and changing nature of paramedic practice. It provides an insight into the ways in which the character, practice and environment of the profession contribute to a disproportionate number of complaints.

This article examines the nature of, and reasons for, the disproportionately high rates of fitness to practise referrals of social workers in England to the Health and Care Professions Council (HCPC), compared with other professions regulated by HCPC during 2014–2016. In 2014–2015, the rate of referrals for social workers was 1.42 per cent of registrants, compared with an average for the sixteen professions regulated by HCPC of 0.66 per cent. Drawing on published statistics and unique analysis of a sample of 232 case files undertaken as part of a research project in 2016–2017, the article highlights relatively high rates of inappropriate referrals from ‘members of the public’ (mainly service users) particularly in relation to child placements and contact. A detailed picture is offered of the variety of referrals dealt with at each stage of the fitness to practise process (from initial triage to final hearings), with recommendations for how to prevent inappropriate referrals, whilst focusing concern on the most serious cases of incompetence and misconduct. This research is of significance at a time of increasing pressure for social workers, social services and service users under conditions of austerity and managerialism; on-going concerns about standards in social work; and recent changes in social work regulation.

Paramedics have been regulated in the UK since 2003. Analysis shows that the profession has had consistently higher rates of self-referral to its regulator compared with other health and care professions. Between 2013 and 2016, the percentage of paramedics who self-referred averaged 50% of all cases, compared with 6% across all other health professions regulated by the Health and Care Professions Council (HCPC) and 10% across social workers in England. This article reports on possible reasons underlying this trend. Using a mixed-methods approach including a literature review, interviews, focus groups and case analysis, the study identified a number of possible contributory factors. These included pressurised work environments, variable guidance and support from employers, and work cultures of fear and conflict. The evolving nature of the profession was also cited. The research found that there was a cohort of cases that appeared inappropriate—where the referral was for a matter that did not require reporting. Actions are being taken to reduce such self-referrals to avoid the emotional distress and resource implications for those involved.

Background Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease. Methods Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses. Results The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM-receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer's, Parkinson's and Huntington's disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression. Conclusions Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

Objective: To examine the gene expression regarding pulmonary vascular disease in experimental bronchopulmonary dysplasia in young mice. Premature delivery puts babies at risk of severe complications. Bronchopulmonary dysplasia (BPD) is a common complication of premature birth leading to lifelong affection of pulmonary function. BPD is recognized as a disease of arrested alveolar development. The disease process is not fully described and no complete cure or prevention is known. The focus of interest in the search for treatment and prevention of BPD has traditionally been at airspace level; however, the pulmonary vasculature is increasingly acknowledged in the pathology of BPD. The aim of the investigation was to study the gene expression in lungs with BPD with regards to pulmonary vascular disease (PVD). Methods: We employed a murine model of hyperoxia-induced BPD and gene expression microarray technique to determine the mRNA expression in lung tissue from young mice. We combined gene expression pathway analysis and analyzed the biological function of multiple single gene transcripts from lung homogenate to study the PVD relevant gene expression. Results: There were n = 117 significantly differentially regulated genes related to PVD through down-regulation of contractile elements, up- and down-regulation of factors involved in vascular tone and tissue-specific genes. Several genes also allowed for pinpointing gene expression differences to the pulmonary vasculature. The gene Nppa coding for a natriuretic peptide, a potent vasodilator, was significantly down-regulated and there was a significant up-regulation of Pde1a (phosphodiesterase 1A), Ptger3 (prostaglandin e receptor 3), and Ptgs1 (prostaglandin-endoperoxide synthase one). Conclusion: The pulmonary vasculature is affected by the arrest of secondary alveolarization as seen by differentially regulated genes involved in vascular tone and pulmonary vasculature suggesting BPD is not purely an airspace disease. Clues to prevention and treatment may lie in the pulmonary vascular system.

Health and Care Professionals Council (HCPC) as compared with the other health care professionals regulated by HCPC. This paper discusses findings from interviews and focus groups that formed part of a mixed methods study that aimed to find out the reasons for complaints and the strategies that may reduce complaints. Four themes were identified: social work as an evolving profession; social work involves challenging practice; social work takes place in a pressurised environment; and public perceptions and expectations of social work are often negative and unrealistic. Findings highlight explanations that focus on organisational culture and public responses to social workers’ control functions. We argue that, at a time of change for the profession, there is a need for public education regarding the role and function of social workers and for regulators to have more proactive engagement with registrants and employers.

Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Objectives To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost‐effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post‐birth. Design Two‐arm feasibility trial, with nested mixed‐methods process evaluation. Setting Inner‐city unit, south England. Population Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5–24.9 kg/m2) identified with excessive gestational weight gain at 36 weeks of gestation. Methods Randomised to standard care plus commercial weight management sessions commencing 8–16 weeks postnatally or standard care only. Main outcomes Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. Results In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. Conclusion It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out‐of‐trial costs and benefits in a future trial. A definitive trial is an important next step. Tweetable abstract A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease.Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses.The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM-receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer's, Parkinson's and Huntington's disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression.Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

The first report about the discovery of new, previously unknown immune cells named IRA B cells (innate response activator B cells) appeared in 2012. So far, their presence has been verified in both mice and humans. However, IRA B cells belong to the family of B lymphocytes and have a number of characteristics unique to this group of cells. IRA B cells are formed from activated B1a lymphocytes after their contact with a pathogen. B1a lymphocytes mainly reside within body cavities. Activated by the pathogen, they move on into secondary lymphoid organs (spleen, lymph nodes) where they differentiate into IRA B cells. IRA B cells are a rich source of granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF can stimulate IRA B cells in an autocrine manner for the secretion of intracellular stocks of immunoglobulin M (IgM), which can facilitate pathogens' phagocytosis by neutrophils. GM-CSF also stimulates neutrophils into active phagocytosis. Rapid eradication of the pathogen can prevent the development of an excessive inflammatory response, which can be dangerous for the organism. Until now the involvement of IRA B lymphocytes in the pathogenesis of sepsis and pneumonia has been proven, as well as their role in the progression of atherosclerotic lesions in mice. There is research in progress on the possibility of increasing the number of IRA B cells, for example by intravenous supply of modified immunoglobulins. It is necessary to characterize human IRA B cells and to determine their role in the functioning of the immune system.

Background: Bronchopulmonary dysplasia (BPD) is a common cause of abrupted lung development after preterm birth. BPD may lead to increased rehospitalization, more severe and frequent respiratory infections, and life-long reduced lung function. The gene regulation in lungs with BPD is complex, with various genetic and epigenetic factors involved. Objectives: The aim of this study was to examine the regulatory relation between gene expression and the epigenome (DNA methylation) relevant for the immune system after hyperoxia followed by a recovery period in air using a mouse model of BPD. Methods: Newborn mice pups were subjected to an immediate hyperoxic condition from birth and kept at 85% O2 levels for 14 days followed by a 14-day period in room air. Next, mice lung tissue was used for RNA and DNA extraction with subsequent microarray-based assessment of lung transcriptome and supplementary methylome analysis. Results:The immune system-related transcriptomeregulation was affected in mouse lungs after hyperoxia. A high proportion of genes relevant in the immune system exhibited significant expression alterations, e.g., B cell-specific genes central to the cytokine-cytokine receptor interaction, the PI3K-AKT, and the B cell receptor signaling pathways. The findings were accompanied by significant DNA hypermethylation observed in the PI3K-AKT pathway and immune system-relevant genes. Conclusions: Oxygen damage could be partly responsible for the increased susceptibility and abnormal response to respiratory viruses and infections seen in premature babies with BPD through dysregulated genes.

Within the regulatory community, there has been increasing interest in the issue of proportionality in regulation — that is, using the right amount and right types of regulatory interventions to achieve the primary mandate of the regulatory community in order to serve and to protect. The Health and Care Professions Council (HCPC) in the United Kingdom, one of the largest health-care regulatory bodies in the world, recently commissioned a study examining the disproportionately large number of complaints against paramedics in the UK and social workers in England. The objective of the study was to examine the nature of, and to better understand the reasons behind, this disproportionality, and to identify options and opportunities from a regulatory perspective that could be taken to address this issue. The study involved a systematic multi-methods research approach involving four key interrelated research elements:A systematic literature reviewA Delphi consultation with international expertsInterviews (n=26) and four focus groups (n=23) with UK experts, including service users and caregiversA review of a random sample (n=284) of fitness-to-practice cases over two years across the three stages of the process (initial complaint, Investigating Committee Panel, and final hearing) Findings from this study highlight the evolving nature of both professions and the influence of a binary model of complaints adjudication that may not be sufficiently nuanced to balance public protection with practitioners' learning needs. A non-binary option for understanding complaints against practitioners is suggested in this paper, offering a process that involves and engages both employers and practitioners in a more meaningful manner.

BACKGROUND Irisin is a newly discovered myokine with anti-obesity properties. The delivery of irisin with the breast milk or formula is an emerging concept that myokine present at human milk influences postnatal energy balance and developmental parameters. The aim of the study was to evaluate irisin concentration in breast milk of mothers with term and preterm babies and in infant formulas. METHODS A total of 49 lactating mothers were enrolled in the study: 31 mothers of very low birth weight preterm infants and 18 mothers of term infants. Milk samples were collected twice: during the first week after delivery and after 4 weeks of delivery. Irisin concentration was determined using ELISA kits both in human milk and in samples of 14 different infant formulas. RESULTS There were no differences in milk irisin levels between preterm and full-term milk samples during both the 1st and the 4th week after delivery. There were also no differences in irisin concentration between transitional milk and mature milk in both tested groups. Irisin concentrations in preterm and full-term milk were significantly higher than in formulas during 30 days period after delivery. A significant increase of irisin concentration in natural milk 4 weeks post-delivery in comparison to 1st week after delivery was observed (mean difference 0.362 μg/ml; p=0.0063). CONCLUSIONS This study provides evidence that irisin is present in infant formulas, although in less amount than in human milk. Further research is needed to assess, if children fed with infant formulas may disadvantage from lower irisin supply.

Background Immature immune systems predispose very low birth weight (VLBW) neonates to systemic infections in early life. Defective inflammasome function may increase a neonate's susceptibility to late-onset sepsis (LOS). Methods Blood samples were taken on the 5th day of life (DOL) for all VLBW neonates (non-LOS and before-LOS groups; n=76), and within 24 hours of sepsis onset (LOS group; n=39). Monocyte (MO) subsets and intracellular interleukin-1β (IL-1β) expression were analysed using flow cytometry. Inflammasome function, defined as level of IL-1β and interleukin-18 (IL-18) was measured with enzyme-linked immunosorbent assay. IRA B cells were reported as a fraction of all B cells. Results Stimulation of classical MO in non-LOS cells demonstrated a higher expression of intracellular IL-1β in comparison to MO from before-LOS group. Serum from the LOS group revealed a higher level of IL-18. Stimulation of mononuclear cultures from samples taken during LOS resulted in significantly increased supernatant level of IL-1β and IL-18 in comparison to samples taken on 5th DOL. No changes in the levels of IRA B cells were detected with the onset of sepsis. Conclusions We did not observe a difference in the functioning of the inflammasome within monocytes taken on 5th DOL from premature VLBW neonates. Furthermore, there was no observable change in the IRA B cells of the septic and non-septic groups. The decreased expression of intracellular IL-1β within classical MO of the before-LOS group may be an independent risk factor for LOS development.

Inflammasomes regulate activation of caspase-1, which cleaves and activates interleukin (IL)-1β and IL-18, the cytokines that trigger pro-inflammatory and antimicrobial responses. There is very little known about inflammasome function in the subsets of monocytes (MO) isolated from preterm neonates born extremely and very prematurely.A group of 76 very low birth weight patients without early-onset sepsis was divided into extremely preterm (28 gestational week) or very preterm (28-32 gestational week) neonates. The first blood sample was collected on the 5th day of life (5th DOL) to analyse MO subsets as well as the intracellular IL-1β expression and supernatant concentration of IL-1β and IL-18. Secondary blood samples were collected within 24h of late-onset sepsis (LOS) development and analysed as above.On the 5th DOL, the extremely preterm neonates were characterized by a significantly higher absolute count of MO, in particular in the classical and intermediate subsets, as compared to the very preterm group. The counts of the intermediate and non-classical MO subsets increased during LOS in all neonates. We did not observe significant differences in the intracellular IL-1β expression between the analysed groups. Furthermore, the levels of the analysed cytokines in the MO supernatants were comparable between the extremely and very preterm neonates on the 5th DOL. Finally, a higher level of IL-18 was observed in the supernatant of the extremely preterm group during LOS.During LOS, extremely preterm neonates excrete a higher level of IL-18 cytokines compared to very preterm neonates. Further studies are required to determine whether this observation is a result of a higher count of the circulating MO or is a true reflection of increased inflammasome function in this particular group of newborns.

Premature infants represent one of the groups with increased risk for metabolic syndrome. Our study is the first one to evaluate irisin and visfatin levels, associated with the metabolic syndrome, both in blood of preterm and full-term infants, as well as in the breastmilk of their mothers. A total of 72 newborns was enrolled in the study, including 53 very low birth weight preterm infants and a control group of 19 term infants. The levels of irisin and visfatin were determined by a commercial enzyme-linked immunoabsorbent assay both in the baby serum and maternal milk twice, first during the 1st week of life and then 4 weeks later. Preterm infants had significantly lower serum irisin levels compared to the term infants. Overall, serum irisin level during the 1st week of life was positively correlated with several anthropometric measurements at birth, as well as during 5th weeks of age. In contrast, serum visfatin levels during 5th week of life were negatively correlated with z-scores of birth weight, weight and head circumference during 5th week of age. We found a strong negative correlation between serum irisin and serum visfatin levels at both analyzed time points. The level of milk visfatin was significantly higher in the mothers of the preterm group during 5th week of life. In conclusion, our results provide further evidence that irisin and visfatin may play physiologic roles in development of both preterm and full-term newborns during their first month after birth. Observed differences in irisin and visfatin serum and breastmilk concentrations during the earliest stages of life may contribute to development of catch up growth, but also, they might eventually lead to a higher risk for metabolic syndrome in prematurely born children in later years.

Purpose Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease. Methods The cord and peripheral blood of neonates (≤30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (PMA), respectively. Blood samples were retrospectively subdivided into ROP(+) and ROP(-) groups, according to the development of ROP. Results The quantitative analysis of plasma proteome at both time points revealed 30 protein abundance changes between ROP(+) and ROP(-) groups. After standardization to gestational age, children who developed ROP were characterized by an increased C3 complement component and fibrinogen level at both analyzed time points. Conclusions Higher levels of the complement C3 component and fibrinogen, present in the cord blood and persistent to 36 PMA, may indicate a chronic low-grade systemic inflammation and hypercoagulable state that may play a role in the development of ROP.

Supplemental oxygen exposure is a risk factor for the development of bronchopulmonary dysplasia (BPD). Reactive oxygen species may damage lung tissue, but hyperoxia also has the potential to alter genome activity via changes in DNA methylation. Understanding the epigenetic potential of hyperoxia would enable further improvement of the therapeutic strategies for BPD. Here we aimed to identify hyperoxia-related alterations in DNA methylation, which could affect the activity of crucial genetic pathways involved in the development of hyperoxic lung injury. Newborn mice (n = 24) were randomized to hyperoxia (85% O2) or normoxia groups for 14 days, followed by normoxia for the subsequent 14 days. The mice were sacrificed on day 28, and lung tissue was analyzed using microarrays developed for the assessment of genome methylation and expression profiles. The mean DNA methylation level was higher in the hyperoxia group than the normoxia group. The analysis of specific DNA fragments revealed hypermethylation of > 1000 gene promoters in the hyperoxia group, confirming the presence of the DNA-hypermethylation effect of hyperoxia. Further analysis showed significant enrichment of the TGF-β signaling pathway (p = 0.0013). The hypermethylated genes included Tgfbr1, Crebbp, and Creb1, which play central roles in the TGF-β signaling pathway and cell cycle regulation. Genome expression analysis revealed in the hyperoxia group complementary downregulation of genes that are crucial for cell cycle regulation (Crebbp, Smad2, and Smad3). These results suggest the involvement of the methylation of TGF-β pathway genes in lung tissue reaction to hyperoxia. The data also suggest that hyperoxia may be a programming factor in newborn mice.

Purpose This paper aims to examine the suitability of a social enterprise model for community health promotion organisations working in disadvantaged neighbourhoods. It focuses on organisational culture, social resources and capacity as pre-requisites for entrepreneurial activities. Design/methodology/approach This paper is based on ethnographic case studies in England, including semi-structured interviews with the organisations’ staff, trustees and external stakeholders; participant observation; creative method workshops with staff; and feedback meetings with staff and trustees. Findings The paper provides empirical insights into the potential for, and the consequences of, introducing entrepreneurial ways of working to community health promotion organisations. It suggests that pre-existing capacity, competencies and skills, as well as the ability to manage cultural hybridity, are key factors. Research limitations/implications Studying three organisations allowed comparative analysis, but time constraints limited access to some stakeholders and meant that the researcher could not be continuously present. Fieldwork generated a series of “snapshots” of each organisation at several time points. Practical/implications Community health promotion organisations should be mindful of the social and cultural implications of following the entrepreneurial route to income generation. Policymakers need to be more aware of the challenges community health promotion organisations face in taking on entrepreneurial ways of working. Originality/value This paper contributes new empirical insights into the process of community health promotion organisations adopting entrepreneurial ways of working. This is underpinned by Bourdieu’s concept of habitus, which provides a new theoretical lens for examining the social and cultural aspects of this transition.

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome.

Background: The long-term impact of prematurity on cardiac structure and function has not yet been fully discovered. Objectives: To assess long-term cardiac complications in the regional cohort of extremely low birth weight (ELBW) children born in 2002-2004. Material and Methods: Eighty-one children born as ELBW infants (91% of the available cohort) with a median birth weight of 890 g (25-75th percentile: 760-950) were evaluated at the mean age of 6.7 years. The control group included 40 children born full-term, selected from one general practice in the district. Echocardiography and 24-hour ambulatory blood pressure measurements (ABPM) were performed. The primary outcome variable was the presence of cardiac complications such as left ventricular hypertrophy (LVH), diastolic dysfunction or systolic dysfunction. Results: LVH was diagnosed in 4/81 ELBW children and 2/40 control children (p = 1.0). Concentric remodeling was detected in 8 (10%) subjects from the ELBW group and in 2 (5%) from the control group (p = 0.49). There were no patients with diastolic or systolic dysfunction in either group. After having expressed the results of M-mode echocardiography as z-scores for body surface area (BSA), statistically significant differences were observed for right-ventricle dimension in diastole (-1.49 ± 1.25 vs. -0.31 ± 0.91; p < 0.001), LV inner dimension in diastole (-0.53 ± 1.26 vs. 0.13 ± 0.94; p = 0.01) and left atrium (-0.93 ± 1.07 vs. -0.15 ± 1.02; p < 0.01). Heart rate (HR) was significantly faster in ELBW children (92.9 ± 8.4 vs. 86.7 ± 7.4 bpm; p = 0.01 adjusted for BSA) and they also had significantly higher night-time blood pressure [mean (z-score): 1.15 vs. 0.2; p = 0.02] without nocturnal dipping (night-time dipping Conclusions: No differences were found between the groups in the occurrence of cardiac complications. Ex-preterm ELBW children at age 6 may have a faster HR, smaller cardiac dimensions on echocardiography and higher nocturnal blood pressure. The clinical relevance of these findings is unknown.

There has been little previous scholarship regarding the aims, options and impact of ethics education on residential care-givers. This manuscript details findings from a pragmatic cluster trial evaluating the impact of three different approaches to ethics education. The focus of the article is on one of the interventions, an immersive simulation experience. The simulation experience required residential care-givers to assume the profile of elderly care-recipients for a 24-hr period. The care-givers were student nurses. The project was reviewed favourably by a university ethics committee, and participants provided informed consent. Data from six postsimulation experience focus groups were analysed thematically and three themes were identified: the experience of vulnerability, dignity in care and the organisation of care. Findings suggest that the immersive simulation experience had a powerful immediate impact as participants described epiphanous insights relating to their care experiences. It is suggested that reflecting on and recording epiphanous events has the potential to sustain ethical care practices. Further research is required to evaluate the impact of different ethics education interventions in different cultural contexts. Exploration is also required regarding the meaning and significance of care epiphanies, those “most delicate and evanescent of moments,” for the sustainability of ethical care.

Children born with extremely low birth weight (ELBW) have more respiratory tract complications during childhood. Little is known about respiratory and allergy problems in ELBW children at the threshold of adolescence.A follow-up study was conducted at the age of 11 among ELBW children (n=65) and age-matched controls (n=36). The primary outcomes in the study were the occurrence of respiratory and allergy problems and the rate of hospitalization due to respiratory complications at the age of 11 years, assessed with a questionnaire. Secondary outcome variables were serum levels of immunoglobulin classes.ELBW children had more respiratory tract infections (31 vs.11%, p = 0.03), but less allergies (3 vs. 22%, p0.01) compared with controls and had lower level of serum tIgE (geometric mean: 46.5 vs. 89.3 kU/l, p = 0.02). The risk factors for the occurrence of respiratory tract disorders in the ELBW group were: low gestational age, need for surfactant therapy and length of ventilatory support in the neonatal period.ELBW children have more frequent respiratory tract complications, but fewer allergies at the age of 11 years compared with children born at term. Lower respiratory tract problems decrease in ELBW children with age. Respiratory tract infections are not connected with deficiency in humoral immunity.

We assessed the long-term renal complications in a regional cohort of extremely low birth weight (ELBW) children born in 2002–2004. The study group, comprising 78 children born as ELBW infants (88% of the available cohort), was evaluated with measurement of serum cystatin C, urinary albumin excretion, renal ultrasound, and 24-h ambulatory blood pressure measurements. The control group included 38 children born full-term selected from one general practice in the district. Study patients were evaluated at a mean age of 6.7 years, and had a median birthweight of 890 g (25th–75th percentile: 760–950 g) and a median gestational age of 27 weeks (25th–75th percentile: 26–29 weeks). Mean serum cystatin C levels were significantly higher (0.64 vs. 0.59 mg/l; p = 0.01) in the ELBW group. Hypertension was diagnosed in 8/78 ELBW and 2/38 of the control children (p = 0.5). Microalbuminuria (>20 mg/g of creatinine) was detected only in five ELBW children (p = 0.17). The mean renal volume was significantly lower in the ELBW group (absolute kidney volume 81 ml vs. 113 ml; p

New three-component photoinitiating systems consisting of a cyanine dye, borate salt, and a 1,3,5-triazine derivative were investigated by measuring their photoinitiation activities and through fluorescence quenching experiments. Polymerization kinetic studies based on the microcalorimetric method revealed a significant increase in polymerization rate when the concentration of n-butyltriphenylborate salt or the 1,3,5-triazine derivative were increased. The photo-induced electron transfer process between electron donor and electron acceptor was studied by means of fluorescence quenching and SrEt change of the fluorescence intensity. The experiments performed documented that an increase of the n-butyltriphenylborate salt concentration dramatically increases the rate of dye fluorescence quenching, whereas the increasing of the 1,3,5-triazine derivative concentration slows down the consumption of the dye. We conclude that the primary photochemical reaction involves an electron transfer from the n-butyltriphenylborate anion to the excited singlet state of the dye, followed by the reaction of the 1,3,5-triazine derivative with the resulting dye radical to regenerate the original dye. This reaction simultaneously produces a triazinyl radical anion derived from the 1,3,5-triazine, which undergoes the carbon-halogen bond cleavage yielding radicals active in initiation of a free radical polymerization chain.

Introduction: Neuroblastoma (NB), Hirschsprung disease (HSCR), Congenital Central Hypoventilation Syndrome (CCHS), clinically referred as the NB-HSCR-CCHS cluster, is genetic disorders linked to mutations in the PHOX2B gene on chromosome 4p12. Specific aim: The specific aim of this project is to define the PHOX2B gene mutations as the genomic basis for the clinical manifestations of the NB-HSCR-CCHS cluster. Patient: A one day old male patient presented to the JUMC neonatal ICU due to abdominal distention, vomiting, and severe apneic episodes. With the preliminary diagnosis of the NB-HSCR-CCHS, the blood and tissue samples were acquired from the child, as well as from the child’s parents. All procedures were pursued in accordance with the Declaration of Helsinki, with the patient’s Guardian Informed Consent and the approval from the Institutional Review Board. Genetic/genomic methods: Karyotyping was analyzed based upon Giemsa banding. The patient’s genomic DNA was extracted from peripheral blood and amplified by polymerase chain reaction. Direct microfluidic Sanger sequencing was performed on the genomic DNA amplicons. These procedures were pursued in addition to the routine clinical examinations and tests. Results: G-banding showed the normal 46 XY karyotype. However, genomic sequencing revealed a novel, heterozygous deletion (8 nucleotides (c.699-706, del8) in exon 3 of the PHOX2B gene on chromosome 4. This led to the frame-shift mutation and malfunctioning gene expression product. Conclusion: Herein, we report a novel PHOX2B gene mutation in the patient diagnosed with the NB-HSCRCCHS cluster. The resulting gene expression product may be a contributor to the clinical manifestations of these genetic disorders. It adds to the library of the mutations linked to this syndrome. Consequently, we suggest that screening for the PHOX2B mutations becomes an integral part of genetic counseling, prenatal screening, and preparing supportive therapy upon delivery.

Kawasaki disease is the number one cause of acquired heart disease among children in developed countries.The aim of the study was a retrospective analysis of the factors that may influence the persistence of coronary artery abnormalities in patients with Kawasaki disease.Analyzing the medical records of patients hospitalized in the University Children's Hospital of Krakow in the years 2005-2011 we collected the data of 28 patients diagnosed with Kawasaki disease. The group was divided into two subgroups, depending on the duration of the persistence of changes in the coronary arteries - A (n = 17) for up to 6 months, B (n = 11) - for more than 6 months. Both groups were analyzed for the presence of factors that may influence the course of the disease.There were more boys in group A (11 boys (65%), 6 girls (35%)), whereas in group B the distribution was more uniform (6 boys (55%), 5 girls (45%)). The age of onset in group A was 37.9 months (SD 30.8), in group B 39.5 months (SD 16.7). 17.6% of patients in group A and 36.4% in group B were treated with glucocorticoids.In the group of patients in which coronary artery abnormalities disappeared more quickly, male and slightly older children dominated. The only difference observed between the 2 groups related to the frequency of the use of glucocorticoids, they were used more often in children, in whom coronary artery abnormalities persisted longer.

To expand the knowledge about the consecutive expression of genes involved in the immune system development in preterm neonates and to verify if the environment changes the gene expression after birth we conducted a prospective study that included three cohorts: (A) extremely (gestational age (GA): 23–26 weeks;n=41), (B) very (GA: 27–29 weeks;n=39), and (C) moderately preterm infants (GA: 30–32 weeks;n=33). Blood samples were drawn from the study participants on the 5th and 28th day of life (DOL). The mRNA samples were evaluated for gene expression with the use of GeneChip Human Gene 1.0ST microarrays. Differential expression analysis revealed small subsets of genes that presented positive or negative monotone trends in both the 5th (138 genes) and 28th DOL (308 genes) in the three subgroups of patients. Based on pathway enrichment analysis, we found that most of the pathways that revealed a positive monotone trend were involved in host immunity. The most significantly GA dependent pathways were T-cell receptor signaling pathway and intestinal immune network for IgA production. Overall 4431 genes were differentially expressed between the 5th and 28th DOL. Despite differences in gestational age, patients with the same postconceptional age have a very similar expression of genes.

Aim Assessment of long-term cardiac complications in the regional cohort of extremely low birth weight (ELBW) children born in 2002–2004. Material and Methods The study group comprising 81 children born as ELBW infants with the median birthweight of 890g (25 th –75 th percentile: 760–950) were evaluated at the mean age of 7 years. The control group included 40 children born full term. Echocardiography and 24-hour ambulatory blood pressure measurements were performed. Results Conclusions The former ELBW children have smaller heart’s diameters and to reach the same cardiac index their heart rate is faster. Moreover, the former ELBW children have higher blood pressure comparing to their peers.