Virtually the same? Examining the impact of the COVID-19 related shift to virtual lung cancer multidisciplinary team meetings in the UK National Health Service: a mixed methods study.

OBJECTIVES: To evaluate the impact of the shift to virtual lung cancer multidisciplinary team meetings (MDTMs) in response to the COVID-19 pandemic, specifically in relation to the magnitude of information technology (IT) issues and distractions and MDT members'/managers' perceptions and experiences of this shift. DESIGN: A mixed methods study comprising real-time observations of IT issues/distractions within virtual MDTM case discussions held between April and July 2021 and qualitative data from interviews/surveys. SETTING: Eight hospital organisations in Southern England. PARTICIPANTS: Team members (respiratory physicians, surgeons, oncologists, radiologists, pathologists, palliative care professionals, nurses and MDT coordinators) and managers (n=190) across 8 local MDTs. RESULTS: MDTM observations (n=1664) highlighted significant variation between teams regarding IT functionality. IT issues and other distractions relating to the virtual MDTM format were observed 465 times affecting 20.6% of case discussions, most of which were audio issues (18.1%). Case discussions that had audio issues were, on average, 26 s longer (t(1652)=-2.77, p<0.01). A total of 73 MDT members and managers participated in the survey and 41 participated in interviews, with all 8 teams being represented. Increased flexibility, reduced travel time and easier real-time access to patient information were seen as the main advantages of virtual MDTMs. Views regarding the impact on relational aspects and communication differed. In line with observational findings, concerns were raised in relation to IT, including having inappropriate equipment, insufficient bandwidth (impairing image sharing and video communication) and an overarching theme that virtual meeting platforms provided were not fit for purpose. CONCLUSIONS: Despite the potential benefits of virtual MDTMs, IT issues can waste valuable MDTM time. If hospital organisations plan to continue virtual MDTMs, a functioning infrastructure is required, necessitating appropriate resource and investment.

Investigating the efficiency of lung multi-disciplinary team meetings-A mixed methods study of eight lung multi-disciplinary teams.

BACKGROUND: Multidisciplinary team meetings (MDTMs), where treatment recommendations are discussed and agreed, are fundamental to effective cancer care. The increasing volume and complexity of caseloads has led to the need to transform MDTM pathways to improve efficiency and allow sufficient time for discussion of complex cases. Understanding of current functioning and inefficiencies is required to inform such transformation. METHODS: A mixed-methods observational study of all lung cancer MDTMs in one UK cancer network over 12 weeks (n = 8 MDTs, 96 MDT meetings). Data were collected on meeting attendance and on each discussed case using a validated MDT tool. Semi-structured interviews were conducted with a range of MDT members and cancer service managers to gain understanding of perceived influences on the efficiency of MDTMs. RESULTS: In total, 1671 case discussions were observed. Models of MDT working, including referral and diagnostic pathway management, varied within the network. Attendance was quorate in only 21% of the observed MDTMs, most often lacking palliative care specialists. Over a third (37%) of observed cases were repeat discussions pre-diagnosis. Treatment recommendations were agreed in 48% of case discussions but deferred for a quarter (24%) of discussed cases, most commonly due to awaiting results. Information about patients' fitness for treatment and/or performance status score was available for 60% of cases discussed overall (30%-75% by MDT). Interviews (n = 56) identified addressing clinical and administrative workforce shortages, less reliance on the MDTM for pre-diagnostic decision-making and better availability of key clinical information about patients discussed in the MDTM as factors critical to improved MDT function. CONCLUSIONS: Inefficiencies were prevalent in all MDTMs; improvements would require an individualised approach due to the variation in ways of working. Local, regional and national support is needed for lung MDTs to develop their diagnostic workforce and facilities, and clinical and administrative resource.

Irisin concentration in infant formulas and breast milk.

BACKGROUND: Irisin is a newly discovered myokine with antiobesity 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 for 30 days period after delivery. A significant increase of irisin concentration in natural milk 4 weeks postdelivery 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.

Inflammasome function in monocyte subsets and a risk of late-onset sepsis in preterm very low birth weight neonates.

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-1ß (IL-1ß) expression were analyzed using flow cytometry. Inflammasome function, defined as level of IL-1ß 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-1ß 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-1ß 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-1ß within classical MO of the before-LOS group may be an independent risk factor for LOS development.

Over-the-counter antipyretics use among children from Southeastern Poland.

BACKGROUND: Over-the-counter (OTC) drugs are becoming increasingly popular. However, little is known about parents' practices concerning the use of OTC antipyretics in children. This paper aimed to study the habits and knowledge of parents regarding the use of OTC antipyretics in their offspring, considering the demographic and socioeconomic characteristics of the families. MATERIAL AND METHODS: A multiple-purpose survey was conducted anonymously among 229 parents of patients hospitalised in the Department of Paediatrics, University Children's Hospital, Krakow. Each parent answered 23 questions regarding OTC antipyretics use in his/her hospitalised child throughout the whole child's life. The data was statistically analysed. RESULTS: OTC antipyretics are administered to their children by 92% of parents. In the vast majority (87%), health care professionals or a leaflet were the sources of information on the drug and its dosage. Parents also used information from TV or the Internet (27%) and friends and family (30%), especially those in the younger age group. Families with high socioeconomic status were more likely to use health care professionals' advice for drug knowledge. Parents of children with allergic diseases made less use of nonmedical sources of knowledge. CONCLUSIONS: The majority of parents use OTC antipyretic drugs in their children. However, a high percentage of people using nonmedical sources of information is of concern. It is necessary to educate caregivers and to build the parents' awareness that they take an active role in their child's treatment. It would be useful to create generally available recommendations for home treatment.

Living life in limbo: experiences of healthcare professionals during the HCPC fitness to practice investigation process in the UK.

BACKGROUND: It is the responsibility of healthcare regulators to ensure healthcare professionals remain fit for practice in healthcare settings. If there are concerns about an individual healthcare professional they may undergo a fitness to practice investigation. This process is known to be hugely stressful for doctors and social workers, but little is known about the impact of this experience on other professions. This study explores the experiences of registrants going through the process of being reported to the UK's Health and Care Professions Council (HCPC) and attending fitness to practice (FTP) hearings. We discuss the implications of this process on registrants' wellbeing and, from our findings, present recommendations based on registrants experiences. In doing so we articulate the structural processes of the HCPC FTP process and the impact this has on individuals. METHODS: This study uses semi-structured interviews and framework analysis to explore the experiences of 15 registrants who had completed the FTP process. Participants were sampled for maximum variation and were selected to reflect the range of possible processes and outcomes through the FTP process. RESULTS: The psychological impact of undergoing a FTP process was significant for the majority of participants. Their stories described influences on their wellbeing at both a macro (institutional/organisational) and micro (individual) level. A lack of information, long length of time for the process and poor support avenues were macro factors impacting on the ability of registrants to cope with their experiences (theme 1). These macro factors led to feelings of powerlessness, vulnerability and threat of ruin for many registrants (theme 2). Suggested improvements (theme 3) included better psychological support (e.g. signposting or provision); proportional processes to the incident (e.g. mediation instead of hearings); and taking context into account. CONCLUSIONS: Findings suggest that improvements to both the structure and conduct of the FTP process are warranted. Implementation of better signposting for support both during and after a FTP process may improve psychological wellbeing. There may also be value in considering alternative ways of organising the FTP process to enable greater consideration of and flexibility for registrants' context and how they are investigated.

Exploring the macro-level, meso-level and micro-level barriers and facilitators to the provision of good quality early inflammatory arthritis (EIA) care in England and Wales.

BACKGROUND: Evidence from a national clinical audit of early inflammatory arthritis (EIA) shows considerable variability between hospitals in performance, unexplained by controlling for case-mix. OBJECTIVE: To explore the macro-level, meso-level and micro-level barriers and facilitators to the provision of good quality EIA care. METHODS: A qualitative study within 16 purposively sampled rheumatology units across England and Wales. Quality was assessed in relation to 11 quality indicators based on clinical opinion, evidence and variability observed in the data. Data from semi-structured interviews with staff (1-5 from each unit, 56 in total) and an online questionnaire (n=14/16 units) were integrated and analysed using the framework method for thematic analysis using a combined inductive and deductive approach (underpinned by an evidence-based framework of healthcare team effectiveness), and constant comparison of data within and between units and its relationship with the quality criteria. FINDINGS: Quality of care was influenced by an interplay between macro, meso and micro domains. The macro (eg, shared care arrangements and relationships with general practitioners) and meso (eg, managerial support and physical infrastructure) factors were found to act as crucial enablers of and barriers to higher quality service provision at the micro (team) level. These organisational factors directly influenced team structure and function, and thereby EIA care quality. CONCLUSIONS: Variability in quality of EIA care is associated with an interplay between macro, meso and micro service features. Tackling macro and meso barriers is likely to have a significant impact on quality of EIA service, and ultimately patient experience and outcomes.

Findings from a mixed-methods pragmatic cluster trial evaluating the impact of ethics education interventions on residential care-givers.

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.

Barriers and facilitators to uptake and retention of inner-city ethnically diverse women in a postnatal weight management intervention: a mixed-methods process evaluation within a feasibility trial in England.

OBJECTIVES: To understand the barriers and facilitators to uptake and retention of postnatal women randomised to a commercial group weight management intervention using the COM-B (capability, opportunity, motivation and behaviour) behaviour change model. DESIGN: Concurrent mixed-methods (qualitative dominant) process evaluation nested within a feasibility randomised controlled trial, comprising questionnaires and interviews at 6 and 12 months postbirth. SETTING: One National Health Service maternity unit in an inner city area in the south of England. PARTICIPANTS: 98 postnatal women with body mass indices>25 kg/m2 (overweight/obese) at pregnancy commencement. INTERVENTION: Twelve-week Slimming World (SW) commercial group weight management programme, commencing anytime from 8 to 16 weeks postnatally. PRIMARY AND SECONDARY OUTCOME MEASURES: Data regarding uptake and retention from questionnaires and interviews conducted 6 and 12 months postbirth analysed thematically and mapped to the COM-B model. RESULTS: Barriers to SW uptake mostly concerned opportunity issues (eg, lack of time or childcare support) though some women also lacked motivation, not feeling that weight reduction was a priority, and a few cited capability issues such as lacking confidence. Weight loss aspirations were also a key factor explaining retention, as were social opportunity issues, particularly in relation to factors such as the extent of group identity and relationship with the group consultant; and physical opportunity such as perceived support from and fit with family lifestyle. In addition, barriers relating to beliefs and expectations about the SW programme were identified, including concerns regarding compatibility with breastfeeding and importance of exercise. Women's understanding of the SW approach, and capability to implement into their lifestyles, appeared related to level of attendance (dose-response effect). CONCLUSIONS: Uptake and retention in commercial weight management programmes may be enhanced by applying behaviour change techniques to address the barriers impacting on women's perceived capability, motivation and opportunity to participate. TRIAL REGISTRATION NUMBER: ISRCTN39186148.

Transcriptome analysis reveals dysregulation of genes involved in oxidative phosphorylation in a murine model of retinopathy of prematurity.

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.

Pulmonary vascular disease is evident in gene regulation of experimental bronchopulmonary dysplasia.

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.

Short- and long-term impact of hyperoxia on the blood and retinal cells' transcriptome in a mouse model of oxygen-induced retinopathy.

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.

Immune System Regulation Affected by a Murine Experimental Model of Bronchopulmonary Dysplasia: Genomic and Epigenetic Findings.

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.

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia.

BACKGROUND: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. METHODS: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(-) groups, according to the development of BPD. RESULTS: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. CONCLUSIONS: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

Lung ultrasound in the diagnosis of neonatal respiratory failure prior to patient transport.

PURPOSE: Lung ultrasound (LUS) at the point-of-care is a new method that is increasingly used in neonatology. The aim of this study was to determine the utility of the addition of LUS prior to the interhospital transport of neonates with respiratory failure. METHODS: LUS was performed on 50 newborns with respiratory failure prior to transport to a tertiary neonatal intensive care unit. We analyzed the performance of LUS for diagnosing the cause of respiratory failure, the concordance between LUS, chest X-ray (CXR) and final clinical diagnosis, and the impact of LUS on clinical decision making before transport. RESULTS: LUS sensitivity for the diagnosis of respiratory distress syndrome was 91.3% (95%CI: 70.5-98.5%), and specificity was 92.6% (95%CI: 74.2-98.7%), whereas sensitivity and specificity of CXR were 69.6% (95%CI: 47.0-85.9%) and 81.5% (95%CI: 61.2-92.9%), respectively. For the recognition of pneumothorax (PTX) LUS had a sensitivity of 83.3% (95%CI: 36.5-99.1%) and a specificity of 100% (95%CI: 89.9-100%). For CXR, sensitivity was 16.7% (95%CI: 0.01-63.5%) and specificity was 97.7% (95%CI: 86.4-99.9%). The agreement between LUS and CXR in diagnosing the cause of respiratory failure was substantial (κ of 0.57 [95%CI: 0.40-0.74]) and the agreement between LUS and the final clinical diagnosis was very good (κ of 0.86 [95%CI: 0.74-0.98]). In 42% of the patients, a LUS examination prior to transport indicated the need for endotracheal tube repositioning or PTX decompression. CONCLUSION: LUS may be a reliable imaging technique for differentiating the causes of respiratory failure before neonatal transport. Use of LUS may optimize the care of infants during transport.

Does type of feeding affect body composition in very low birth weight infants? - A prospective cohort study.

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 < 0.01), while fat mass (% FM) was higher (16.4% vs.14.5%; p < 0.01) in group A compared to full-term newborns. There were no such differences in FFM (84.3% vs. 85.5%; p = 0.13) or FM (15.7% vs. 14.5%; p = 0.13) between group B and control. CONCLUSION: To sum up, the VLBW infants fed with breast milk shared similar body composition with the full-term infants, while the formula-fed VLBW developed higher amounts of adipose tissue and lower amounts of fat-free mass. This is the first study to expose differences in fat tissue content attributed to type of provided nutrition, which has become significant as early as estimated time of birth despite the comparable weight.

An iTRAQ-Based Quantitative Proteomic Analysis of Plasma Proteins in Preterm Newborns With Retinopathy of Prematurity.

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.

Evaluation of irisin and visfatin levels in very low birth weight preterm newborns compared to full term newborns-A prospective cohort study.

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.

Hyperoxia induces epigenetic changes in newborn mice lungs.

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-ß signaling pathway (p = 0.0013). The hypermethylated genes included Tgfbr1, Crebbp, and Creb1, which play central roles in the TGF-ß 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-ß pathway genes in lung tissue reaction to hyperoxia. The data also suggest that hyperoxia may be a programming factor in newborn mice.

Analysis of selected aspects of inflammasome function in the monocytes from neonates born extremely and very prematurely.

BACKGROUND: Inflammasomes regulate activation of caspase-1, which cleaves and activates interleukin (IL)-1ß 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. METHODS: 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-1ß expression and supernatant concentration of IL-1ß and IL-18. Secondary blood samples were collected within 24h of late-onset sepsis (LOS) development and analysed as above. RESULTS: 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-1ß 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. CONCLUSIONS: 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.