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1.
Early Hum Dev ; 162: 105462, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34511288

RESUMO

For the preterm infant with respiratory insufficiency requiring supplemental oxygen, tight control of oxygen saturation (SpO2) is advocated, but difficult to achieve in practice. Automated control of oxygen delivery has emerged as a potential solution, with six control algorithms currently embedded in commercially-available respiratory support devices. To date, most clinical evaluations of these algorithms have been short-lived crossover studies, in which a benefit of automated over manual control of oxygen titration has been uniformly noted, along with a reduction in severe SpO2 deviations and need for manual FiO2 adjustments. A single non-randomised study has examined the effect of implementation of automated oxygen control with the CLiO2 algorithm as standard care for preterm infants; no clear benefits in relation to clinical outcomes were noted, although duration of mechanical ventilation was lessened. The results of randomised controlled trials are awaited. Beyond the gathering of evidence regarding a treatment effect, we contend that there is a need for a better understanding of the function of contemporary control algorithms under a range of clinical conditions, further exploration of techniques of adaptation to individualise algorithm performance, and a concerted effort to apply this technology in low resource settings in which the majority of preterm infants receive care. Attainment of these goals will be paramount in optimisation of oxygen therapy for preterm infants globally.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33963005

RESUMO

OBJECTIVE: To evaluate the performance of a rapidly responsive adaptive algorithm (VDL1.1) for automated oxygen control in preterm infants with respiratory insufficiency. DESIGN: Interventional cross-over study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking periods of manual control (12 hours each). SETTING: Neonatal intensive care unit. PARTICIPANTS: Preterm infants receiving non-invasive respiratory support and supplemental oxygen; median birth gestation 27 weeks (IQR 26-28) and postnatal age 17 (12-23) days. INTERVENTION: Automated oxygen titration with the VDL1.1 algorithm, with the incoming SpO2 signal derived from a standard oximetry probe, and the computed inspired oxygen concentration (FiO2) adjustments actuated by a motorised blender. The desired SpO2 range was 90%-94%, with bedside clinicians able to make corrective manual FiO2 adjustments at all times. MAIN OUTCOME MEASURES: Target range (TR) time (SpO2 90%-94% or 90%-100% if in air), periods of SpO2 deviation, number of manual FiO2 adjustments and oxygen requirement were compared between automated and manual control periods. RESULTS: In 60 cross-over studies in 35 infants, automated oxygen titration resulted in greater TR time (manual 58 (51-64)% vs automated 81 (72-85)%, p<0.001), less time at both extremes of oxygenation and considerably fewer prolonged hypoxaemic and hyperoxaemic episodes. The algorithm functioned effectively in every infant. Manual FiO2 adjustments were infrequent during automated control (0.11 adjustments/hour), and oxygen requirements were similar (manual 28 (25-32)% and automated 26 (24-32)%, p=0.13). CONCLUSION: The VDL1.1 algorithm was safe and effective in SpO2 targeting in preterm infants on non-invasive respiratory support. TRIAL REGISTRATION NUMBER: ACTRN12616000300471.

4.
Chembiochem ; 22(1): 193-202, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32964667

RESUMO

Penicillin-binding proteins (PBPs) are a family of bacterial enzymes that are key components of cell-wall biosynthesis and the target of ß-lactam antibiotics. Most microbial pathogens contain multiple structurally homologous PBP isoforms, making it difficult to target individual PBPs. To study the roles and regulation of specific PBP isoforms, a panel of bioorthogonal ß-lactone probes was synthesized and compared. Fluorescent labeling confirmed selectivity, and PBPs were selectively enriched from Streptococcus pneumoniae lysates. Comparisons between fluorescent labeling of probes revealed that the accessibility of bioorthogonal reporter molecules to the bound probe in the native protein environment exerts a more significant effect on labeling intensity than the bioorthogonal reaction used, observations that are likely applicable beyond this class of probes or proteins. Selective, bioorthogonal activity-based probes for PBPs will facilitate the activity-based determination of the roles and regulation of specific PBP isoforms, a key gap in knowledge that has yet to be filled.


Assuntos
Antibacterianos/metabolismo , Lactonas/metabolismo , Sondas Moleculares/metabolismo , Proteínas de Ligação às Penicilinas/análise , Streptococcus pneumoniae/química , Antibacterianos/química , Lactonas/química , Conformação Molecular , Sondas Moleculares/química , Proteínas de Ligação às Penicilinas/metabolismo , Espectrometria de Fluorescência , Coloração e Rotulagem , Streptococcus pneumoniae/metabolismo
5.
Front Pediatr ; 8: 570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042915

RESUMO

Apnoea, a pause in respiration, is almost ubiquitous in preterm infants born before completing 30 weeks gestation. Apnoea often begets hypoxemia and/or bradycardia, and has the potential to result in adverse neurodevelopmental consequences. Our current inability to predict apnoeic events in preterm infants requires apnoea to first be detected by monitoring device/s in order to trigger an intervention by bedside (medical or nursing) staff. Such a reactive management approach is laborious, and makes the consequences of apnoeic events inevitable. Recent technological advances and improved signal processing have allowed the possibility of developing prediction models for apnoeic events in preterm infants. However, the development of such models has numerous challenges and is only starting to show potential. This paper identifies requisite components and current gaps in developing prediction models for apnoeic events, and reviews previous studies on predicting apnoeic events in preterm infants.

6.
Curr Opin Chem Biol ; 57: 155-165, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32799037

RESUMO

Molecular imaging methods to visualize myriad biochemical processes in bacteria have traditionally been dependent upon molecular biology techniques to incorporate fluorescent biomolecules (e.g., fusion proteins). Such methods have been instrumental in our understanding of how bacteria function but are not without drawbacks, including potential perturbation to native protein expression and function. To overcome these limitations, the use of fluorescent small-molecule probes has gained much attention. Here, we highlight examples from the recent literature that showcase the utility of small-molecule probes for the fluorescence imaging of bacterial cells, including electrophilic, metabolic, and enzyme-activated probes. Although the use of these types of compounds for bacterial imaging is still relatively new, the selected examples demonstrate the exciting potential of these critical tools in the exploration of bacterial physiology.


Assuntos
Bactérias/isolamento & purificação , Corantes Fluorescentes/química , Imagem Óptica/métodos , Animais , Bactérias/enzimologia , Infecções Bacterianas/microbiologia , Humanos , Imagem Molecular/métodos
7.
J Nat Prod ; 83(1): 159-163, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31904955

RESUMO

Ion mobility spectrometry was utilized to corroborate the identity of streptorubin B (2) as the natural product produced by Streptomyces coelicolor. Natural product 2 was initially assigned as butylcycloheptylprodigiosin (3), and only relatively recently was this assignment clarified. We present additional evidence of this assignment by comparing collisional cross sections (Ω) of synthetic standards of 2, 3, and metacycloprodigiosin (4) to the cyclic prodiginine produced by S. coelicolor. Calculated theoretical Ω values demonstrate that cyclic prodiginines could be identified without standards. This work highlights ion mobility as an efficient tool for the dereplication of natural products.


Assuntos
Prodigiosina/análogos & derivados , Streptomyces coelicolor/química , Produtos Biológicos , Espectrometria de Mobilidade Iônica , Estrutura Molecular , Prodigiosina/química
8.
Pediatr Pulmonol ; 54(11): 1712-1721, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31313528

RESUMO

BACKGROUND: The factors influencing the severity of apnea-related hypoxemia and bradycardia are incompletely characterized, especially in infants receiving noninvasive respiratory support. OBJECTIVES: To identify the frequency and predictors of physiological instability (hypoxemia-oxygen saturation (SpO2 ) <80%, or bradycardia-heart rate (HR) < 100 bpm) following respiratory pauses in infants receiving noninvasive respiratory support. METHODS: Respiratory pause duration, derived from capsule pneumography, was measured in 30 preterm infants of gestation 30 (24-32) weeks [median (interquartile range)] receiving noninvasive respiratory support and supplemental oxygen. For identified pauses of 5 to 29 seconds duration, we measured the magnitude and duration of SpO2 and HR reductions over a period starting at the pause onset and ending 60 seconds after resumption of breathing. Temporally clustered pauses (<60 seconds separation) were analyzed separately. The relative contribution of respiratory pauses to overall physiological instability was determined, and predictors of instability were sought in regression analysis, including demographic, clinical and situational variables as inputs. RESULTS: In total, 17 105 isolated and 9180 clustered pauses were identified. Hypoxemia and bradycardia were more likely after longer duration and temporally-clustered pauses. However, the majority of such episodes occurred after 5 to 9 second pauses given their numerical preponderance, and short-lived pauses made a substantial contribution to physiological instability overall. Birth gestation, hemoglobin concentration, form of respiratory support, caffeine treatment, respiratory pause duration and temporal clustering were identified as predictors of instability. CONCLUSIONS: Brief respiratory pauses, especially when clustered, contribute substantially to hypoxemia and bradycardia in preterm infants.


Assuntos
Apneia/fisiopatologia , Bradicardia/etiologia , Hipóxia/etiologia , Doenças do Prematuro/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Apneia/complicações , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Recém-Nascido , Estudos Prospectivos , Respiração
9.
J Med Syst ; 41(9): 134, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28755269

RESUMO

Imaging systems have applications in patient respiratory monitoring but with limited application in neonatal intensive care units (NICU). In this paper we propose an algorithm to automatically detect the torso in an image of a preterm infant during non-invasive respiratory monitoring. The algorithm uses normalised cut to segment each image into clusters, followed by two fuzzy inference systems to detect the nappy and torso. Our dataset comprised overhead images of 16 preterm infants in a NICU, with uncontrolled illumination, and encompassing variations in poses, presence of medical equipment and clutter in the background. The algorithm successfully identified the torso region for 15 of the 16 images, with a high agreement between the detected torso and the torso identified by clinical experts.


Assuntos
Tronco , Algoritmos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal
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