Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants

To assess the regional respiratory time constants of lung volume changes during stepwise lung recruitment before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. A stepwise oxygenation-guided recruitment procedure was performed before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. Electrical impedance tomography was used to continuously record changes in lung volume during the recruitment maneuver. Time constants were determined for all incremental and decremental pressure steps, using one-phase exponential decay curve fitting. Data were analyzed for the whole cross section of the chest and the ventral and dorsal lung regions separately. Before surfactant treatment, the time constants of the incremental pressure steps were significantly longer (median 27.3 s) than those in the decremental steps (16.1 s). Regional analysis showed only small differences between the ventral and dorsal lung regions. Following surfactant treatment, the time constants during decremental pressure steps almost tripled to 44.3 s. Furthermore, the time constants became significantly (p <0.01) longer in the dorsal (61.2 s) than into the ventral (40.3 s) lung region. Lung volume stabilization during stepwise oxygenation-guided lung recruitment in high-frequency oscillatory ventilated preterm infants with respiratory distress syndrome is usually completed within 5 min and is dependent on the position of ventilation on the pressure volume curve, the surfactant status, and the region of interest of the lun

Elective high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: an individual patient data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Despite the considerable amount of evidence from randomized controlled trials and meta-analyses, uncertainty remains regarding the efficacy and safety of high-frequency oscillatory ventilation as compared to conventional ventilation in the early treatment of respiratory distress syndrome in preterm infants. This results in a wide variation in the clinical use of high-frequency oscillatory ventilation for this indication throughout the world. The reasons are an unexplained heterogeneity between trial results and a number of unanswered, clinically important questions. Do infants with different risk profiles respond differently to high-frequency oscillatory ventilation? How does the ventilation strategy affect outcomes? Does the delay – either from birth or from the moment of intubation – to the start of high-frequency oscillation modify the effect of the intervention? Instead of doing new trials, those questions can be addressed by re-analyzing the individual patient data from the existing randomized controlled trials.</p> <p>Methods/Design</p> <p>A systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of the original individual data from each infant included in each randomized controlled trial addressing this question.</p> <p>The study objective is to estimate the effect of high-frequency oscillatory ventilation on the risk for the combined outcome of death or bronchopulmonary dysplasia or a severe adverse neurological event. In addition, it will explore whether the effect of high-frequency oscillatory ventilation differs by the infant's risk profile, defined by gestational age, intrauterine growth restriction, severity of lung disease at birth and whether or not corticosteroids were given to the mother prior to delivery. Finally, it will explore the importance of effect modifying factors such as the ventilator device, ventilation strategy and the delay to the start of high-frequency ventilation.</p> <p>Discussion</p> <p>An international collaborative group, the PreVILIG Collaboration (Prevention of Ventilator Induced Lung Injury Group), has been formed with the investigators of the original randomized trials to conduct this systematic review. In the field of neonatology, individual patient data meta-analysis has not been used previously. Final results are expected to be available by the end of 2009.</p

Crystal Structure of a Novel Esterase Rv0045c from Mycobacterium tuberculosis

There are at least 250 enzymes in Mycobacterium tuberculosis (M. tuberculosis) involved in lipid metabolism. Some of the enzymes are required for bacterial survival and full virulence. The esterase Rv0045c shares little amino acid sequence similarity with other members of the esterase/lipase family. Here, we report the 3D structure of Rv0045c. Our studies demonstrated that Rv0045c is a novel member of α/β hydrolase fold family. The structure of esterase Rv0045c contains two distinct domains: the α/β fold domain and the cap domain. The active site of esterase Rv0045c is highly conserved and comprised of two residues: Ser154 and His309. We proposed that Rv0045c probably employs two kinds of enzymatic mechanisms when hydrolyzing C-O ester bonds within substrates. The structure provides insight into the hydrolysis mechanism of the C-O ester bond, and will be helpful in understanding the ester/lipid metabolism in M. tuberculosis

High frequency oscillatory ventilation and prone positioning in a porcine model of lavage-induced acute lung injury

BACKGROUND: This animal study was conducted to assess the combined effects of high frequency oscillatory ventilation (HFOV) and prone positioning on pulmonary gas exchange and hemodynamics. METHODS: Saline lung lavage was performed in 14 healthy pigs (54 ± 3.1 kg, mean ± SD) until the arterial oxygen partial pressure (PaO(2)) decreased to 55 ± 7 mmHg. The animals were ventilated in the pressure controlled mode (PCV) with a positive endexpiratory pressure (PEEP) of 5 cmH(2)O and a tidal volume (V(T)) of 6 ml/kg body weight. After a stabilisation period of 60 minutes, the animals were randomly assigned to 2 groups. Group 1: HFOV in supine position; group 2: HFOV in prone position. After evaluation of prone positioning in group 2, the mean airway pressure (P(mean)) was increased by 3 cmH(2)O from 16 to 34 cmH(2)O every 20 minutes in both groups accompanied by measurements of respiratory and hemodynamic variables. Finally all animals were ventilated supine with PCV, PEEP = 5 cm H(2)O, V(T )= 6 ml/kg. RESULTS: Combination of HFOV with prone positioning improves oxygenation and results in normalisation of cardiac output and considerable reduction of pulmonary shunt fraction at a significant (p < 0.05) lower P(mean )than HFOV and supine positioning. CONCLUSION: If ventilator induced lung injury is ameliorated by a lower P(mean), a combined treatment approach using HFOV and prone positioning might result in further lung protection

Secondary students' values and perceptions of science-related careers: responses to vignette-based scenarios

There has been concern about the attractiveness of science-based careers to many adolescent learners, and it has been suggested that school science may not always recognise or engage personal values that are important to young people in making life choices. The present study discusses interview comments made by upper secondary level students in England when 15 young people were asked to give their personal responses to brief vignettes describing scientific careers. Using an interview-about-scenarios approach, the students were asked about whether they would feel comfortable working in the scientific careers represented. The career areas were purposefully selected because they might be considered to potentially raise issues in relation to personal values or commitments that some students might hold. A range of student perceptions relating to the mooted careers were elicited (positive, negative and indifferent), but all of the participants raised issues that impacted on the acceptability or attractiveness of at least one of the mooted scientific careers, in terms of aspects of their own personal beliefs and values systems. It is recommended that teachers and career advisors should be aware of the range of value-related considerations that influence student views of science-related careers and should consider exploring aspects of science-based careers that link to values commonly shared by young people. This exploratory study also offers indications for directions for further research exploring how learners' value systems impact upon their perceptions of science and scientific work

Can Simply Answering Research Questions Change Behaviour? Systematic Review and Meta Analyses of Brief Alcohol Intervention Trials

BACKGROUND: Participant reports of their own behaviour are critical for the provision and evaluation of behavioural interventions. Recent developments in brief alcohol intervention trials provide an opportunity to evaluate longstanding concerns that answering questions on behaviour as part of research assessments may inadvertently influence it and produce bias. The study objective was to evaluate the size and nature of effects observed in randomized manipulations of the effects of answering questions on drinking behaviour in brief intervention trials. METHODOLOGY/PRINCIPAL FINDINGS: Multiple methods were used to identify primary studies. Between-group differences in total weekly alcohol consumption, quantity per drinking day and AUDIT scores were evaluated in random effects meta-analyses. Ten trials were included in this review, of which two did not provide findings for quantitative study, in which three outcomes were evaluated. Between-group differences were of the magnitude of 13.7 (-0.17 to 27.6) grams of alcohol per week (approximately 1.5 U.K. units or 1 standard U.S. drink) and 1 point (0.1 to 1.9) in AUDIT score. There was no difference in quantity per drinking day. CONCLUSIONS/SIGNIFICANCE: Answering questions on drinking in brief intervention trials appears to alter subsequent self-reported behaviour. This potentially generates bias by exposing non-intervention control groups to an integral component of the intervention. The effects of brief alcohol interventions may thus have been consistently under-estimated. These findings are relevant to evaluations of any interventions to alter behaviours which involve participant self-report

Challenging the Moral Status of Blood Donation

The World Health Organisation encourages that blood donation becomes voluntary and unremunerated, a system already operated in the UK. Drawing on public documents and videos, this paper argues that blood donation is regarded and presented as altruistic and supererogatory. In advertisements, donation is presented as something undertaken for the benefit of others, a matter attracting considerable gratitude from recipients and the collecting organisation. It is argued that regarding blood donation as an act of supererogation is wrongheaded, and an alternative account of blood donation as moral obligation is presented. Two arguments are offered in support of this position. First, the principle of beneficence, understood in a broad consequentialist framework obliges donation where the benefit to the recipient is large and the cost to the donor relatively small. This argument can be applied, with differing levels of normativity, to various acts of donation. Second, the wrongness of free riding requires individuals to contribute to collective systems from which they benefit. Alone and in combination these arguments present moral reasons for donation, recognised in communication strategies elsewhere. Research is required to evaluate the potential effects on donation of a campaign which presents blood donation as moral obligation, but of wider importance is the recognition that other-regarding considerations in relation to our own as well as others’ health result in a range not only of choices but also of obligations

Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen

Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC

Longitudinal study of adolescent tobacco use and tobacco control policies in India

Abstract Background This project will use a multilevel longitudinal cohort study design to assess whether changes in Community Tobacco Environmental (CTE) factors, measured as community compliance with tobacco control policies and community density of tobacco vendors and tobacco advertisements, are associated with adolescent tobacco use in urban India. India’s tobacco control policies regulate secondhand smoke exposure, access to tobacco products and exposure to tobacco marketing. Research data about the association between community level compliance with tobacco control policies and youth tobacco use are largely unavailable, and are needed to inform policy enforcement, implementation and development. Methods The geographic scope will include Mumbai and Kolkata, India. The study protocol calls for an annual comprehensive longitudinal population-based tobacco use risk and protective factors survey in a cohort of 1820 adolescents ages 12–14 years (and their parent) from baseline (Wave 1) to 36-month follow-up (Wave 4). Geographic Information Systems data collection will be used to map tobacco vendors, tobacco advertisements, availability of e-cigarettes, COTPA defined public places, and compliance with tobacco sale, point-of-sale and smoke-free laws. Finally, we will estimate the longitudinal associations between CTE factors and adolescent tobacco use, and assess whether the associations are moderated by family level factors, and mediated by individual level factors. Discussion India experiences a high burden of disease and mortality from tobacco use. To address this burden, significant long-term prevention and control activities need to include the joint impact of policy, community and family factors on adolescent tobacco use onset. The findings from this study can be used to guide the development and implementation of future tobacco control policy designed to minimize adolescent tobacco use.https://deepblue.lib.umich.edu/bitstream/2027.42/144539/1/12889_2018_Article_5727.pd