Microcirculation of the Newborn

Appropriate regulation of microvascular blood flow in the neonate is crucial for cardiorespiratory stability and survival in the period immediately following birth. Inappropriate microvascular dilatation in the first few days of extrauterine life is associated with poor outcomes in preterm neonates. Male very preterm neonates (≤28 weeks completed gestation) have significantly higher flows than females of the same gestational age. This is of clinical importance as preterm males are twice as likely to die as females. Very little is known about the mechanisms underlying microvascular tone regulation in the perinatal period. Previous studies suggest a role for the gasotransmitters nitric oxide and carbon monoxide; however, differences in levels of these molecules do not account for all the variation observed, suggesting another player. In this chapter, the role of the third gasotransmitter—hydrogen sulphide—as a potential mediator of microvascular (dys)function in the preterm is explored

“Robots cannot drink coffee or real ale”:the undeniable spark of face-to-face teaching moments in digital learning journeys

The purpose of this study is to evaluate student perceptions of a yearly workshop, held as part of the Master’s in Industrial Project Management programme at the University of Birmingham. This study employed action research methods to understand how the use of technology to deliver fully online and hybrid teaching during the COVID-19 pandemic (2020/21) and its immediate aftermath (2022) impacted on student experience. A mix of technological tools was used, most notably the virtual world environment Virbela, MS Teams, the digital collaboration platform Miro, and telepresence robots. The data indicates that students generally preferred the hybrid teaching mode, which combines face-to-face interactions with remote learning. While fully online teaching offered higher flexibility in a time of crisis, the hybrid approach optimised both digital resources and in-person engagement, leading to enhanced student satisfaction, particularly for the social aspects of learning and community building.<br/

“Robots cannot drink coffee or real ale”:the undeniable spark of face-to-face teaching moments in digital learning journeys

The purpose of this study is to evaluate student perceptions of a yearly workshop, held as part of the Master’s in Industrial Project Management programme at the University of Birmingham. This study employed action research methods to understand how the use of technology to deliver fully online and hybrid teaching during the COVID-19 pandemic (2020/21) and its immediate aftermath (2022) impacted on student experience. A mix of technological tools was used, most notably the virtual world environment Virbela, MS Teams, the digital collaboration platform Miro, and telepresence robots. The data indicates that students generally preferred the hybrid teaching mode, which combines face-to-face interactions with remote learning. While fully online teaching offered higher flexibility in a time of crisis, the hybrid approach optimised both digital resources and in-person engagement, leading to enhanced student satisfaction, particularly for the social aspects of learning and community building.<br/

Interactions of the Gasotransmitters Contribute to Microvascular Tone (Dys)regulation in the Preterm Neonate

Background & Aims Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. Methods 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. Results No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. Conclusions The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.The authors would like to acknowledge the parents of the neonates enrolled in the 2CANS study for their participation, the staff of the Kaleidoscope Neonatal Intensive Care Unit at the John Hunter Children’s Hospital, and Kimberly-Clark Australia for providing the diapers used in this stud

Sequence Stratigraphy and the Interpretation of Neoproterozoic Earth History

The application of sequence stratigraphy to Neoproterozoic successions is important for improving the resolution of time-correlation within individual sedimentary basins and potentially at a global scale. The methodology is illustrated in this paper by reference to two contrasting examples from the Flinders Ranges (Adelaide geosyncline) of South Australia, where the younger part of the Neoproterozoic to earliest Cambrian succession (∼ 770 Ma to ∼ 540 Ma) has been divided into thirteen unconformity-bounded depositional sequences. One of the most prominent sequence boundaries, at or near the base of the Wonoka Formation, is characterized by a series of buried canyons as much as 1 km deep. High-resolution sequence-stratigraphic studies at Umberatana syncline continue to support the view that the canyons were cut subaerially and filled by fluvial and shallow-water sediments. In contrast to the Wonoka canyons, sequence boundaries interpreted at the base of the Nuccaleena Formation/Seacliff Sandstone and near the top of the ABC Range Quartzite are relatively subtle, with only limited evidence for erosion and valley incision. Four sequence boundaries, at the level of the Sturtian and Marinoan (Varanger?) glacial deposits and in the vicinity of the Precambrian-Cambrian boundary, are thought to correlate with surfaces in the Amadeus basin of central Australia. Other prominent sequence boundaries, including the Wonoka canyons and surfaces within the upper part of the Wonoka Formation and at the base of the Ediacara Member of the Rawnsley Quartzite, correspond with a relatively condensed section in the Amadeus basin, and their lateral persistence beyond the Adelaide geosyncline is therefore difficult to evaluate. Given the lack of precision in biostratigraphy and isotope geochemistry in Neoproterozoic rocks, and in a marked departure from Phanerozoic practice, we recommend placement of a terminal Proterozoic GSSP at a sequence boundary. A prime candidate in Australia is the sequence boundary at the base of the Nuccaleena Formation/Seacliff Sandstone, immediately above the Marinoan glacial rocks in the Adelaide geosyncline, and its likely correlative at or near the base of the Gaylad Sandstone in the Amadeus basin

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment

Videomicroscopy as a tool for investigation of the microcirculation in the newborn

The perinatal period remains a time of significant risk of death or disability. Increasing evidence suggests that this depends on microcirculatory behavior. Sidestream dark-field orthogonal polarized light videomicroscopy (OPS) has emerged as a useful assessment of adult microcirculation but the values derived are not delineated for the newborn. We aimed to define these parameters in well term newborn infants. Demographic details were collected prospectively on 42 healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h of age. Stored video was analyzed by a masked observer using proprietary software. There were no significant differences between the sexes for any structural parameters at any time point. There was a significant increase over time in small vessel perfusion in female infants only (P = 0.009). A number of 6- and 72-h measurements were significantly correlated, but differed from the 24-h values. These observations confirm the utility of the ear conch for neonatal microvascular videomicroscopy. They provide a baseline for studies into the use of OPS videomicroscopy in infants. The changes observed are comparable with previous studies of term infants using these and other microvascular techniques. It is recommended that studies for examining the mature neonatal microvascular structure be delayed until 72 h of life, but studies of the physiology of cardiovascular transition should include the 24-h time point after delivery

Development of materials to support parents whose babies cry excessively: findings and health service implications

Aim: To develop evidence-based materials which provide information and support for parents who are concerned about their baby's excessive crying. As well as meeting these parents' needs, the aim was to develop a package of materials suitable for use by the UK National Health Service (NHS). Background: Parents report that around 20% of 1-4 month-old infants in western countries cry excessively without apparent reason. Traditionally, research has focused on the crying and its causes. However, evidence is growing that how parents evaluate and respond to the crying needs to receive equal attention. This focus encompasses parental resources, vulnerabilities, wellbeing, and mental health. At present, the UK NHS lacks a set of routine provisions to support parents who are concerned about their baby's excessive crying. The rationales, methods and findings from a study developing materials for this purpose are reported. Method: Following a literature review, 20 parents whose babies previously cried excessively took part in focus groups or interviews. They provided reports on their experiences and the supports they would have liked when their baby was crying excessively. In addition, they identified their preferred delivery methods and devices for accessing information and rated four example support packages identified by the literature review. Findings: During the period their baby cried excessively, most parents visited a health service professional and most considered these direct contacts to have provided helpful information and support. Websites were similarly popular. Telephones and tablets were the preferred means of accessing online information. Groups to meet other parents were considered an important additional resource by all the parents. Three package elements - a Surviving Crying website, a printed version of the website, and a programme of Cognitive Behaviour Therapy-based support sessions delivered to parents by a qualified practitioner, were developed for further evaluation

Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period