Clinical applications of photoplethysmography in paediatric intensive care

Objective: The photoplethysmographic wave is displayed by most pulse oximeters. It may be used as anon-invasive alternative to invasive arterial blood pressure trace analysis for continuous haemodynamic monitoring in selected situations. Patients and setting: Four cardiac patients treated in atertiary neonatal-paediatric intensive care unit. Measurements: Simultaneous monitoring of the photoplethysmographic wave, ECG, and invasive blood pressure. Results and conclusions: Photoplethysmography allows for monitoring pulse rate in patients with (possible) heart rate/pulse rate dissociation (pacemaker dependency, pulsatile ventricular assist device); monitoring sudden changes in heart beat volume, which are unrelated to respiration (pulseless electrical activity, pulsus alternans); and monitoring respiratory-dependent fluctuations of the plethysmographic wave (heart failure, hypovolaemia, asthma, upper airway obstruction, pericardial effusion). Deterioration, slowly evolving over time, may be detected by this metho

The targeted delivery of IL17 to the mouse tumor neo-vasculature enhances angiogenesis but does not reduce tumor growth rate

There has been a long controversy as to whether interleukin-17 (IL17) has an impact on tumor growth. In order to assess whether IL17 may affect tumor growth, it would be convenient to achieve high levels of this pro-inflammatory cytokine at the tumor neo-vasculature, since IL17 is known to promote angiogenesis. Here, we have generated and tested in vivo a fusion protein, consisting of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker of angiogenesis) and of murine IL17 (mIL17). The resulting immunocytokine (termed F8-mIL17) was shown to selectively localize at the tumor neo-vasculature and to vigorously promote tumor angiogenesis, without however reducing or enhancing tumor growth rate both in immunocompetent and in immunodeficient mic

Synthesis of small molecules for skin cancer treatment with plasma and non-plasma application

This dissertation deals with the synthesis of small molecules for use in skin cancers with possible plasma application. First, N-glycosylated oxindoles and N-glycosylated isatins bearing electron-withdrawing substituents were synthesized. Furthermore, highly functionalized synthetic building blocks were synthesized in regio- and chemo selective palladium-catalyzed coupling reactions with various boronic acids and alkynes, which then reacted to form heterocycles by acid-mediated cycloisomerization or alkyne-carbonyl metathesis.Die vorliegende Dissertation befasst sich mit der Modifizierung und Herstellung von small molecules für den Einsatz bei Hautkrebserkrankungen mit möglicher Plasmaanwendung. Zunächst wurden N-glykosylierte Oxindole und N-glykosylierte Isatine mit elektronenziehenden Substituenten synthetisiert. Weiterhin wurden Synthesebausteine in regio- und chemoselektiven palladiumkatalysierten Kupplungsreaktionen mit verschiedenen Boronsäuren und Alkinen synthetisiert, die dann durch Brønsted-Säure-vermittelte Zykloisomerisierung oder Alkin-Carbonyl-Metathese zu Heterozyklen umgesetzt wurden

Bestimmung der Zytokine Interleukin 15, Interleukin 16 und Interleukin 18 im Vaginalsekret bei Frauen mit Candidose und gesunder Kontrollgruppe

Mittels ELISA bestimmten wir in unserer Studie die Konzentration der Interleukine IL-15, IL-16 und IL-18 in 71 Scheidenproben von Patientinnen mit nachgewiesener vulvovaginaler Candidainfektion. Als Vergleichsgruppe diente das Scheidensekret von 147 (IL-15 und IL-16) bzw. 139 (IL-18) objektiv und subjektiv gesunden, eubiotischen, nicht schwangeren Probandinnen. Bezüglich der Konzentration von IL-15 und IL-16 im Vaginalsekret zeigte sich kein Unterschied zwischen gesunden und erkrankten Probandinnen. Bei der quantitativen Bestimmung von IL-18 ergab sich ein signifikanter Unterschied zwischen den untersuchten Gruppen. So sind die IL-18 Werte bei Patientinnen mit Candidose höher als bei gesunden Probandinnen

Bestimmung der Zytokine Interleukin 15, Interleukin 16 und Interleukin 18 im Vaginalsekret bei Frauen mit Candidose und gesunder Kontrollgruppe

Mittels ELISA bestimmten wir in unserer Studie die Konzentration der Interleukine IL-15, IL-16 und IL-18 in 71 Scheidenproben von Patientinnen mit nachgewiesener vulvovaginaler Candidainfektion. Als Vergleichsgruppe diente das Scheidensekret von 147 (IL-15 und IL-16) bzw. 139 (IL-18) objektiv und subjektiv gesunden, eubiotischen, nicht schwangeren Probandinnen. Bezüglich der Konzentration von IL-15 und IL-16 im Vaginalsekret zeigte sich kein Unterschied zwischen gesunden und erkrankten Probandinnen. Bei der quantitativen Bestimmung von IL-18 ergab sich ein signifikanter Unterschied zwischen den untersuchten Gruppen. So sind die IL-18 Werte bei Patientinnen mit Candidose höher als bei gesunden Probandinnen

Tumour-targeting properties of antibodies specific to MMP-1A, MMP-2 and MMP-3

Purpose: Matrix metalloproteinases (MMPs), a group of more than 20 zinc-containing endopeptidases, are upregulated in many diseases, but several attempts to use radiolabelled MMP inhibitors for imaging tumours have proved unsuccessful in mouse models, possibly due to the limited specificity of these agents or their unfavourable pharmacokinetic profiles. In principle, radiolabelled monoclonal antibodies could be considered for the selective targeting and imaging of individual MMPs. Methods: We cloned, produced and characterized high-affinity monoclonal antibodies specific to murine MMP-1A, MMP-2 and MMP-3 in SIP (small immunoprotein) miniantibody format using biochemical and immunochemical methods. We also performed comparative biodistribution analysis of their tumour-targeting properties at three time points (3h, 24h, 48h) in mice bearing subcutaneous F9 tumours using radioiodinated protein preparations. The clinical stage L19 antibody, specific to the alternatively spliced EDB domain of fibronectin, was used as reference tumour-targeting agent for in vivo studies. Results: All anti-MMP antibodies and SIP(L19) strongly stained sections of F9 tumours when assessed by immunofluorescence methods. In biodistribution experiments, SIP(SP3), specific to MMP-3, selectively accumulated at the tumour site 24 and 48h after intravenous injection, but was rapidly cleared from other organs. By contrast, SIP(SP1) and SIP(SP2), specific to MMP-1A and MMP-2, showed no preferential accumulation at the tumour site. Conclusion: Antibodies specific to MMP-3 may serve as vehicles for the efficient and selective delivery of imaging agents or therapeutic molecules to sites of diseas

Animal, fungi, and plant genome sequences harbour different non-canonical splice sites

Frey K, Pucker B. Animal, fungi, and plant genome sequences harbour different non-canonical splice sites. Cells. 2020;9(2): 458.Most protein encoding genes in eukaryotes contain introns which are interwoven with exons. After transcription, introns need to be removed in order to generate the final mRNA which can be translated into an amino acid sequence by the ribosome. Precise excision of introns by the spliceosome requires conserved dinucleotides which mark the splice sites. However, there are variations of the highly conserved combination of GT at the 5' end and AG at the 3' end of an intron in the genome. GC-AG and AT-AC are two major non-canonical splice site combinations which are known for many years. During the last few years, various minor non-canonical splice site combinations were detected with all possible dinucleotide permutations. Here we expand systematic investigations of non-canonical splice site combinations in plant genomes to all eukaryotes by analysing fungal and animal genome sequences. Comparisons of splice site combinations between these three kingdoms revealed several differences such as a substantially increased CT-AC frequency in fungal genomes. In addition, high numbers of GA-AG splice site combinations were observed in two animal species. In depth investigation of splice site usage based on RNA-Seq read mappings indicates a generally higher flexibility of the 3' splice site compared to the 5' splice site

Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Calcitonin Gene-Related Peptide (CGRP)-I and Procalcitonin (Pro-CT) Production in Human Adipocytes

Context: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. Objective: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. Design and Participants: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. Results: Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P > 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P > 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P > 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P > 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P > 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. Conclusion: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations

A Field Experiment in Motivating Employee Ideas

We study a field experiment at a large technology company. Employees were encouraged to submit ideas on process and product improvements. The company randomly assigned nineteen teams into treatment and control groups. Treatment team employees received rewards if their ideas were approved. Nothing changed for control team employees. Our main finding is that rewards substantially increased the quality of ideas. Rewards increased participation in the suggestion system but decreased ideas per participating employee, with no net effect on the quantity of ideas. Broader participation persisted after the reward was discontinued, suggesting habituation. We find no evidence for motivational crowding out

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44weeks and 50-55weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95% CI 1.167-1.230) at 40-44weeks. Alpha changed significantly (p=0.001) at 50-55weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromis