Impact of dissolved inorganic carbon concentrations and pH on growth of the chemolithoautotrophic epsilonproteobacterium Sulfurimonas gotlandica GD1T

Epsilonproteobacteria have been found globally distributed in marine anoxic/sulfidic areas mediating relevant transformations within the sulfur and nitrogen cycles. In the Baltic Sea redox zones, chemoautotrophic epsilonproteobacteria mainly belong to the Sulfurimonas gotlandica GD17 cluster for which recently a representative strain, S. gotlandica GD1T, could be established as a model organism. In this study, the potential effects of changes in dissolved inorganic carbon (DIC) and pH on S. gotlandica GD1T were examined. Bacterial cell abundance within a broad range of DIC concentrations and pH values were monitored and substrate utilization was determined. The results showed that the DIC saturation concentration for achieving maximal cell numbers was already reached at 800 μmol L−1, which is well below in situ DIC levels. The pH optimum was between 6.6 and 8.0. Within a pH range of 6.6–7.1 there was no significant difference in substrate utilization; however, at lower pH values maximum cell abundance decreased sharply and cell-specific substrate consumption increased

Autonomic control in preterm infants - what we can learn from mathematical descriptions of vital signs

Background: Preterm birth is a major burden, affecting approximately 15 million infants each year. Recent advances in reproductive medicine increases that number even more. The population of preterm infants in particular suffers from autonomic dysregulation that manifests as temperature instability and poor control of heart rate and breathing. Thermal care, monitoring of vital signs in a neonatal intensive care unit, pharmacotherapy, and respiratory support over weeks to months is necessary. Improvements in neonatal care in the past years lead to a decrease in mortality, especially in very preterm infants. However, former preterm infants still are a high-risk population for acute and chronic sequelae as a result of the interruption of the physiological development. A better understanding of the pathophysiology of the autonomic dysregulation in that population would be very useful. Unfortunately, accurate diagnostic tools that objectively assess and quantify the immature autonomic control in neonates are lacking. Methods: In this PhD thesis we examined different effects of the immature autonomic control in very preterm infants under clinically relevant conditions. We conducted a prospective single center observational study, where we assessed fluctuations in body temperature, sleep behavior, and heart rate variability in very preterm infants. We described the different regulatory systems using distinct mathematical expressions, such as detrended fluctuation analysis and sample entropy. We assessed associations between these outcome parameters and relevant factors of the infant’s history, such as demographic parameters and co-morbidities. Besides that, we analyzed lung function measurements of preterm infants and healthy term controls at a comparable postconceptional age, to describe respiratory control. Results: This study is systematically assessing different physiological signals of autonomic dysregulation in preterm infants during their first days of life. We found associations between parameters describing the complexity of time series analysis and maturity or relevant co-morbidities of the infants. In the analysis of heart rate variability we even found that parameters derived from time series analysis, assessed during the infants first days of life, improve our ability to predict future evolution of the infants’ autonomic stability. Lastly, several weeks after the expected due date, tidal breathing pattern of preterm infants showed a different reaction in response to a sigh when compared to term born controls at equivalent postmenstrual age indicating that autonomic dysregulation in preterm infants is still present well beyond the expected due date. Conclusion: A better understanding about the resolution of autonomic dysregulation in this population is not only important for the infant and its family but has the potential to support resource allocation and identification of patients with elevated risk for future deterioration. We thus think that the insights about the immature autonomic control in preterm infants, gained through this PhD work, are of substantial scientific and clinical relevance

Respiratory rate estimation from multi-channel signals using auto-regulated adaptive extended Kalman filter

Background: Respiration rate (RR) is a major cause for false alarms in intensive care units (ICU) and is primarily impaired by the artifact prone signals from skin-attached electrodes. Catheter-integrated esophageal electrodes are an alternative source for multi-channel physiological signals from multiple organs such as the heart and the diaphragm. Nonlinear estimation and sensor fusion are promising techniques for extracting the respiratory activity from such multi-component signals, however, pathologic breathing patterns with rapid RR changes typically observed in patient populations such as premature infants, pose significant challenges. Methods: We developed an auto-regulated adaptive extended Kalman filter (AA-EKF), which iteratively adapts the system model and the noise parameters based on the respiratory pattern. AA-EKF was tested on neonatal esophageal observations (NEO), and also on simulated multi-components signals created using waveforms in CapnoBase and ETNA databases. Results: AA-EKF derived RR (RRAA-EKF) from NEO had lower median (inter-quartile range) error of 0.1 (10.6) breaths per minute (bpm) compared to contemporary neonatal ICU monitors (RRNICU): −3.8 (15.7) bpm (p <0.001). RRAA-EKF error of −0.2 (3.2) bpm was achieved for ETNA wave forms and a bias (95% LOA) of 0.1 (−5.6, 5.9) in breath count. Mean absolute error (MAE) of RRAA-EKF with Capnobase waveforms, as median (inter-quartile range), at 0.3 (0.2) bpm was comparable to the literature reported values. Discussion: The auto-regulated approach allows RR estimation on a broad set of clinical data without requiring extensive patient specific adjustments. Causality and fast response times of EKF based algorithms makes the AA-EKF suitable for bedside monitoring in the ICU setting

Effect of Mutations in GvpJ and GvpM on Gas Vesicle Formation of Halobacterium salinarum

The two haloarchaeal proteins, GvpM and GvpJ, are homologous to GvpA, the major gas vesicle structural protein. All three are hydrophobic and essential for gas vesicle formation. The effect of mutations in GvpJ and GvpM was studied in Haloferax volcanii transformants by complementing the respective mutated gene with the remaining gvp genes and inspecting the cells for the presence of gas vesicles (Vac⁺). In case of GvpJ, 56 of 66 substitutions analyzed yielded Vac⁻ ΔJ + Jmut transformants, indicating that GvpJ is very sensitive to alterations, whereas ten of the 38 GvpM variants resulted in Vac⁻ ΔM + Mmut transformants. The variants were also tested by split-GFP for their ability to interact with their partner protein GvpL. Some of the alterations leading to a Vac⁻ phenotype affected the J/L or M/L interaction. Also, the interactions J/A and J/M were studied using fragments to exclude an unspecific aggregation of these hydrophobic proteins. Both fragments of GvpJ interacted with the M1–25 and M60–84 fragments of GvpM, and fragment J1–56 of GvpJ interacted with the N-terminal fragment A1–22 of GvpA. A comparison of the results on the three homologous proteins indicates that despite their relatedness, GvpA, GvpJ, and GvpM have unique features and cannot substitute each other

Women in cardiology: past, present and future

In 2018, the Swiss Society of Cardiology celebrated its70thyear. Is this also a celebration for the achievement ofwomen in cardiology? Yes and no

Dynamics and complexity of body temperature in preterm infants nursed in incubators

Poor control of body temperature is associated with mortality and major morbidity in preterm infants. We aimed to quantify its dynamics and complexity to evaluate whether indices from fluctuation analyses of temperature time series obtained within the first five days of life are associated with gestational age (GA) and body size at birth, and presence and severity of typical comorbidities of preterm birth.; We recorded 3h-time series of body temperature using a skin electrode in incubator-nursed preterm infants. We calculated mean and coefficient of variation of body temperature, scaling exponent alpha (Talpha) derived from detrended fluctuation analysis, and sample entropy (TSampEn) of temperature fluctuations. Data were analysed by multilevel multivariable linear regression.; Data of satisfactory technical quality were obtained from 285/357 measurements (80%) in 73/90 infants (81%) with a mean (range) GA of 30.1 (24.0-34.0) weeks. We found a positive association of Talpha with increasing levels of respiratory support after adjusting for GA and birth weight z-score (p&lt;0.001; R2 = 0.38).; Dynamics and complexity of body temperature in incubator-nursed preterm infants show considerable associations with GA and respiratory morbidity. Talpha may be a useful marker of autonomic maturity and severity of disease in preterm infants

Sigh-induced changes of breathing pattern in preterm infants

Sighs are thought to play an important role in control of breathing. It is unclear how sighs are triggered, and whether preterm birth and lung disease influence breathing pattern prior to and after a sigh in infants. To assess whether frequency, morphology, size, and short-term variability in tidal volume (VT) before, during, and after a sigh are influenced by gestational age at birth and lung disease (bronchopulmonary dysplasia, BPD) in former preterm infants and healthy term controls measured at equivalent postconceptional age (PCA). We performed tidal breathing measurements in 143 infants during quiet natural sleep at a mean (SD) PCA of 44.8 (1.3) weeks. A total of 233 sighs were analyzed using multilevel, multivariable regression. Sigh frequency in preterm infants increased with the degree of prematurity and severity of BPD, but was not different from that of term controls when normalized to respiratory rate. After a sigh, VT decreased remarkably in all infants (paired t-test: P &lt; 0.001). There was no major effect of prematurity or BPD on various indices of sigh morphology and changes in VT prior to or after a sigh. Short-term variability in VT modestly increased with maturity at birth and infants with BPD showed an earlier return to baseline variability in VT following a sigh. In early infancy, sigh-induced changes in breathing pattern are moderately influenced by prematurity and BPD in preterm infants. The major determinants of sigh-related breathing pattern in these infants remain to be investigated, ideally using a longitudinal study design

The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

BackgroundSurvival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants.MethodsTwenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured.ResultsThe CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18–24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development.ConclusionOur data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome

The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

Funding Information: This study was funded by the Karolinska Institutet, the University Hospital of Iceland and the Swedish Society for Medical Research, the Swedish Brain Foundation (FO2019-0087 and FO2019-0006), Strategic Research Area Neuroscience (StratNeuro), Ehrling-Person Family Foundation, Axel Tielmans, Freemasons Children’s House, the Swedish National Heart and Lung (20180505) Foundations, the Swedish Research Council (2019-01157), and the Stockholm County Council (20190400). KJ received funding from the Swiss National Science Foundation (Postdoc Mobility Fellowship, P400PM_194474. The funders did not participate in the design or conduct of the study. Publisher Copyright: Copyright © 2022 Leifsdottir, Jost, Siljehav, Thelin, Lassarén, Nilsson, Haraldsson, Eksborg and Herlenius.Background: Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. Methods: Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. Results: The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18–24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. Conclusion: Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.Peer reviewe