Dopplersonographische Normalwerte für Blutflussparameter der Niere bei gesunden Neugeborenen am ersten und dritten Lebenstag: Dopplersonographische Normalwerte für Blutflussparameter der Nierebei gesunden Neugeborenen am ersten und dritten Lebenstag

Eine Vielzahl von Faktoren können am Lebensanfang eine ausreichende Perfusion der Niere gefährden und ihre Funktion beeinträchtigen. Umgekehrt spiegelt eine suffiziente Nierendurchblutung meist auch eine stabile systemische Hämodynamik des Neugeborenen wieder. Laborwerte sind in diesem Alter wenig aussagefähig bezüglich der Nierenfunktion. Ziel dieser Studie war die Erstellung von dopplersonographischen Normalwerten der Blutflussparameter beim gesunden Neugeborenen am ersten und dritten Lebenstag. Es wurden Mittelwerte für die systolische, mittlere und diastolische arterielle Flussgeschwindigkeit in der A. renalis am ersten und dritten Lebenstag beim gesunden Neugeborenen durch dopplersonographische Messung bestimmt. Es konnten dopplersonographische Referenzparameter der Durchblutung der Niere ermittelt werden, die als unkompliziert messbare Parameter in der neonatologischen Praxis zur Einschätzung systemisch hämodynamischer Veränderungen sowie funktioneller Störungen der Niere bis zum akuten Nierenversagen benutzt werden können

EuroScore and IL-6 predict the course in ICU after cardiac surgery.

BACKGROUND Despite modern advances in intensive care medicine and surgical techniques, mortality rates in cardiac surgical patients are still about 3%. Considerable efforts were made to predict morbidity and mortality after cardiac surgery. In this study, we analysed the predictive properties of EuroScore and IL-6 for mortality in ICU, prolonged postoperative mechanical ventilation, and prolonged stay in ICU. METHODS We enrolled 2972 patients undergoing cardiac surgery. The patients either underwent aortic valve surgery (AV), mitral valve surgery (MV), coronary artery bypass grafting (CABG), and combined operations of aortic valve and coronary artery bypass grafting (AV + CABG) or of mitral and tricuspid valve (MV + TV). Different laboratory and clinical parameters were analysed. RESULTS EuroScore as well as IL-6 were associated with increased mortality after cardiac surgery. Furthermore, a higher EuroScore and elevated levels of IL-6 were predictors for prolonged mechanical ventilation and a longer stay in ICU. Especially, highly significant elevated IL-6 levels and an increased EuroScore showed a strong association. Statistics suggested superiority when both parameters were combined in a single model. CONCLUSION Our results suggest that EuroScore and IL-6 are helpful in predicting the course in ICU after cardiac surgery, and therefore, the use of intensive care resources. Especially, the combination of highly elevated levels of IL-6 and EuroScore may prove to be excellent predictors for an unfortunate postoperative course in ICU

EPIDEMIOLOGY AND CLINICAL CHARACTERISTICS OF HUMAN METAPNEUMOVIRUS INFECTIONS IN HOSPITALIZED CHILDREN IN TWO CONSECUTIVE POSTPANDEMIC YEARS.

We assessed human metapneumovirus infections in children hospitalized between 2011 and 2023 and compared the strongest pre- and postpandemic seasons. After the COVID-19 pandemic, we observed offseason cases and loss of the alternating pattern of the human metapneumovirus season magnitude. Incidence rate ratio of 0- to 11-month-old versus 12- to 23-month-old children was 2.1 (95% CI: 1.0-4.8) before and 1.3 (95% CI: 0.6-2.9) after the pandemic

Short-Term Effects of Elexacaftor/Tezacaftor/Ivacaftor Combination on Glucose Tolerance in Young People With Cystic Fibrosis—An Observational Pilot Study

BACKGROUND: The effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on glucose tolerance and/or cystic-fibrosis-related diabetes (CFRD) is not well understood. We performed an observational study on the short-term effects of ELX/TEZ/IVA on glucose tolerance. METHODS: Sixteen adolescents with CF performed oral glucose tolerance tests (OGTT) before and 4–6 weeks after initiating ELX/TEZ/IVA therapy. A continuous glucose monitoring (CGM) system was used 3 days before until 7 days after starting ELX/TEZ/IVA treatment. RESULTS: OGTT categories improved after initiating ELX/TEZ/IVA therapy (p = 0.02). Glucose levels of OGTT improved at 60, 90, and 120 min (p < 0.05), whereas fasting glucose and CGM measures did not change. CONCLUSION: Shortly after initiating ELX/TEZ/IVA therapy, glucose tolerance measured by OGTT improved in people with CF. This pilot study indicates that ELX/TEZ/IVA treatment has beneficial effects on the endocrine pancreatic function and might prevent or at least postpone future CFRD

Stochastic IMT (insulator-metal-transition) neurons: An interplay of thermal and threshold noise at bifurcation

Artificial neural networks can harness stochasticity in multiple ways to enable a vast class of computationally powerful models. Electronic implementation of such stochastic networks is currently limited to addition of algorithmic noise to digital machines which is inherently inefficient; albeit recent efforts to harness physical noise in devices for stochasticity have shown promise. To succeed in fabricating electronic neuromorphic networks we need experimental evidence of devices with measurable and controllable stochasticity which is complemented with the development of reliable statistical models of such observed stochasticity. Current research literature has sparse evidence of the former and a complete lack of the latter. This motivates the current article where we demonstrate a stochastic neuron using an insulator-metal-transition (IMT) device, based on electrically induced phase-transition, in series with a tunable resistance. We show that an IMT neuron has dynamics similar to a piecewise linear FitzHugh-Nagumo (FHN) neuron and incorporates all characteristics of a spiking neuron in the device phenomena. We experimentally demonstrate spontaneous stochastic spiking along with electrically controllable firing probabilities using Vanadium Dioxide (VO$_2$) based IMT neurons which show a sigmoid-like transfer function. The stochastic spiking is explained by two noise sources - thermal noise and threshold fluctuations, which act as precursors of bifurcation. As such, the IMT neuron is modeled as an Ornstein-Uhlenbeck (OU) process with a fluctuating boundary resulting in transfer curves that closely match experiments. As one of the first comprehensive studies of a stochastic neuron hardware and its statistical properties, this article would enable efficient implementation of a large class of neuro-mimetic networks and algorithms.Comment: Added sectioning, Figure 6, Table 1, and Section II.E Updated abstract, discussion and corrected typo

Informed interpretation of metagenomic data by StrainPhlAn enables strain retention analyses of the upper airway microbiome.

Shotgun metagenomic sequencing has the potential to provide bacterial strain-level resolution which is of key importance to tackle a host of clinical questions. While bioinformatic tools that achieve strain-level resolution are available, thorough benchmarking is needed to validate their use for less investigated and low biomass microbiomes like those from the upper respiratory tract. We analyzed a previously published data set of longitudinally collected nasopharyngeal samples from Bangladeshi infants (Microbiota and Health study) and a novel data set of oropharyngeal samples from Swiss children with cystic fibrosis. Data from bacterial cultures were used for benchmarking the parameters of StrainPhlAn 3, a bioinformatic tool designed for strain-level resolution. In addition, StrainPhlAn 3 results were compared with metagenomic assemblies derived from StrainGE and newly derived whole-genome sequencing data. After optimizing the analytical parameters, we compared StrainPhlAn 3 results to culture gold standard methods and achieved sensitivity values of 87% (Streptococcus pneumoniae), 80% (Moraxella catarrhalis), 75% (Haemophilus influenzae), and 57% (Staphylococcus aureus) for 420 nasopharyngeal and 75% (H. influenzae) and 46% (S. aureus) for 260 oropharyngeal samples. Comparing the phylogenetic tree of the core genome of 50 S. aureus isolates with a corresponding marker gene tree generated by StrainPhlAn 3 revealed a striking similarity in tree topology for all but three samples indicating adequate strain resolution. In conclusion, a comparison of StrainPhlAn 3 results to data from bacterial cultures revealed that strain-level tracking of the respiratory microbiome is feasible despite the high content of host DNA when parameters are carefully optimized to fit low biomass microbiomes.IMPORTANCEThe usage of 16S rRNA gene sequencing has become the state-of-the-art method for the characterization of the microbiota in health and respiratory disease. The method is reliable for low biomass samples due to prior amplification of the 16S rRNA gene but has limitations as species and certainly strain identification is not possible. However, the usage of metagenomic tools for the analyses of microbiome data from low biomass samples is not straight forward, and careful optimization is needed. In this work, we show that by validating StrainPhlAn 3 results with the data from bacterial cultures, the strain-level tracking of the respiratory microbiome is feasible despite the high content of host DNA being present when parameters are carefully optimized to fit low biomass microbiomes. This work further proposes that strain retention analyses are feasible, at least for more abundant species. This will help to better understand the longitudinal dynamics of the upper respiratory microbiome during health and disease

Nasal Resistome Development in Infants With Cystic Fibrosis in the First Year of Life

Polymicrobial infections of the respiratory tract due to antibiotic resistant bacteria are a great concern in patients with cystic fibrosis (CF). We therefore aimed at establishing a functional metagenomic method to analyze the nasal resistome in infants with CF within the first year of life. We included samples from patients before antibiotic treatment, which allowed obtaining information regarding natural status of the resistome. In total, we analyzed 130 nasal swabs from 26 infants with CF and screened for β-lactams (ampicillin, amoxicillin-clavulanic acid, and cefuroxime) and other classes of antibiotic resistances (tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole). For 69 swabs (53% of total), we found at least one non-susceptible phenotype. Analyses of the inserts recovered from non-susceptible clones by nanopore MinION sequencing revealed a large reservoir of resistance genes including mobile elements within the antibiotic naïve samples. Comparing the data of the resistome with the microbiota composition showed that the bacterial phyla and operational taxonomic units (OTUs) of the microbiota rather than the antibiotic treatment were associated with the majority of non-susceptible phenotypes in the resistome. Future studies will reveal if characterization of the resistome can help in clinical decision-making in patients with CF

Respiratory symptoms do not reflect functional impairment in early CF lung disease.

BACKGROUND Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known. METHODS We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life. RESULTS We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms. CONCLUSIONS We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone

Exposure to moderate air pollution and associations with lung function at school-age: A birth cohort study

Adverse effects of higher air pollution levels before and after birth on subsequent lung function are often reported in the literature. We assessed whether low-to-moderate levels of air pollution during preschool-age impact upon lung function at school-age.; In a prospective birth cohort of 304 healthy term-born infants, 232 (79%) completed lung function at follow-up at six years. Using spatial-temporal models, levels of individual air pollution (nitrogen dioxide (NO; 2; ) and ozone (O; 3; ), particulate matter with a diameter <10 μm (PM; 10; )) were estimated for the time windows pregnancy, first up to the sixth year of life separately, and birth until follow-up at six years. Time window means were compared to World Health Organization (WHO) guideline limits. Associations of exposure windows with spirometry and body plethysmography indices were analyzed using regression models, adjusting for potential confounders. For subgroup analysis, air pollution exposure was categorized into quartiles (four groups of 52 children).; Mean NO; 2; level from birth until follow-up was [mean (range)] [11.8 (4.9 to 35.9 μg/m; 3; )], which is almost 4-times lower than the WHO suggested limit of 40 μg/m; 3; . In the whole population, increased air pollution levels from birth until follow-up were associated with reduced lung function at six years. In the subgroup analysis, the 52 children exposed to NO; 2; levels from the highest quartile during pregnancy, the first and second years of life and from birth until follow-up, had a significant decrease in forced expiratory volume in 1 s (FEV; 1; ). Per interquartile range increase of NO; 2; , FEV; 1; decreased by [z-score change (95% confidence interval)] [-1.07 (-1.67 to -0.47)], [-1.02 (-1.66 to -0.39)], [-0.51 (-0.86 to -0.17)] and [-0.80 (-1.33 to -0.27)], respectively. Air pollution exposure during pregnancy and childhood resulted in a non-significant decrease in lung volume at six years, as assessed by functional residual capacity measured by body plethysmography (FRC; pleth; ).; Our results suggest that exposure to higher NO; 2; levels, which are still much lower than WHO guideline limits, especially during the sensitive period of early lung development, may be associated with reduced lung function at school-age. These findings support the concept of age and dose-dependent pollution effects on lung function in healthy school-aged children and underline the importance of pollution reduction measures

Nasal resistome development in infants with cystic fibrosis in the first year of life

Polymicrobial infections of the respiratory tract due to antibiotic resistant bacteria are a great concern in patients with cystic fibrosis (CF). We therefore aimed at establishing a functional metagenomic method to analyze the nasal resistome in infants with CF within the first year of life. We included samples from patients before antibiotic treatment, which allowed obtaining information regarding natural status of the resistome. In total, we analyzed 130 nasal swabs from 26 infants with CF and screened for β-lactams (ampicillin, amoxicillin-clavulanic acid, and cefuroxime) and other classes of antibiotic resistances (tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole). For 69 swabs (53% of total), we found at least one non-susceptible phenotype. Analyses of the inserts recovered from non-susceptible clones by nanopore MinION sequencing revealed a large reservoir of resistance genes including mobile elements within the antibiotic naïve samples. Comparing the data of the resistome with the microbiota composition showed that the bacterial phyla and operational taxonomic units (OTUs) of the microbiota rather than the antibiotic treatment were associated with the majority of non-susceptible phenotypes in the resistome. Future studies will reveal if characterization of the resistome can help in clinical decision-making in patients with CF