Plasma levels of osteopontin from birth to adulthood

Aim Osteopontin (OPN) has been investigated as a biomarker for cancer and nonmalignant diseases during the last decades. Data about OPN as a potential biomarker in childhood diseases are still sparse, and reference values are not available in children. We aimed to establish reference values for children from birth to young adulthood and evaluate whether there are age‐, gender‐, and weight‐specific differences. Method Umbilical cord blood and blood plasma samples of 117 children were collected in the Children's Hospital of Saarland University in Homburg/Saar. OPN levels were measured by ELISA, and statistical analysis was performed using SPSS software. Results Neonates, infants, toddlers, young children, adolescents, and adults were divided into the following six age groups: newborns (birth), infancy and toddlers (0‐24 months), early childhood (3‐6 years), middle childhood (7‐11 years), adolescence (12‐18 years), and adults (> 18 years). Highest blood OPN levels were found in the group of 0‐1 years of age. OPN blood levels declined significantly with age (Spearman r = −0.874; P < 0.001). Conclusion Our work is the first prospective and systematic study analyzing OPN cord blood and blood plasma levels in children of all ages. It is the first study yielding reference values for different age groups from birth to young adulthood. Our data give insight on how OPN in umbilical cord blood and OPN in blood plasma are physiologically influenced during childhood development and growth with high OPN levels after birth and a constant age‐related decline until the age of 14, when OPN levels reach similar values to those measured in adults

Novel modified Peyton's approach for knowledge retention on newborn life support training in medical students

Aim We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four‐step approach (P4S). Methods Newborn life support (NLS) training was performed in a simulation‐based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow‐up assessment). Results Both groups showed similar scorings in the initial, follow‐up assessment and in mean change. On initial megacode, time to start with initial inflation and post‐resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow‐up assessment. Only time until start with post‐resuscitation care shows a significant group difference in mean change between initial and follow‐up with increasing time in the control and decreasing time span in intervention group. Conclusion Both methods showed equal levels of knowledge acquisition and long‐term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease

Background Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. Method In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. Results MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). Conclusion MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker

Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p &lt; 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p &lt; 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p &lt; 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS

Patterns of volatile organic compounds in excrements of preterm neonates

Background: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples. Methods: We performed a feasibility study to investigate whether ambient airindependent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH). Results: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p<0.05. Conclusions: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates

Bedside Measurement of Volatile Organic Compounds in the Atmosphere of Neonatal Incubators Using Ion Mobility Spectrometry

Background: Early and non-invasive diagnosis of common diseases is of great importance in the care of preterm infants. We hypothesized that volatile organic compounds (VOC) can be successfully measured in the neonatal incubator atmosphere. Methods: This is a feasibility study to investigate whether the discrimination of occupied and unoccupied neonatal incubators is possible by bedside measurement of volatile organic compounds (VOCs) on the neonatal intensive care unit. VOC profiles were measured in the incubator air using ion mobility spectrometry coupled to multi-capillary columns (BreathDiscovery B&S Analytik GmbH, Dortmund, Germany). Results: Seventeen incubators occupied by preterm infants (50 measurements) and nine unoccupied neonatal incubators were sampled, using 37 room air measurements as controls. Three VOC signals that allow the discrimination between occupied and unoccupied incubators were identified. The best discrimination was reached by peak P20 exhibiting a sensitivity, specificity, positive predictive value and negative predictive value of 94.0, 88.9, 97.3, and 72.3%, respectively. Use of a decision tree improved these values to 100.0, 88.9, 98.0, and 100.0%, respectively. Discussion: A bedside method that allows the characterization of VOC profiles in the neonatal incubator atmosphere using ion mobility spectrometry was established. Occupied and unoccupied incubators could be discriminated by characterizing VOC profiles. This technique has the potential to yield results within minutes. Thus, future studies are recommended to test the hypothesis that VOCs within neonatal incubators are useful biomarkers for non-invasive diagnostics in preterm neonates

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice.

BACKGROUND:Oxygen supply as a lifesaving intervention is frequently used to treat preterm infants suffering additionally from possible prenatal or perinatal pathogen features. The impact of oxygen and/or physical lung injury may influence the morphological lung development, leading to a chronic postnatal lung disease called bronchopulmonary dysplasia (BPD). At present different experimental BPD models are used. However, there are no systematic comparative studies regarding different influences of oxygen on morphological lung maturation. OBJECTIVE:We investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on morphological lung maturation based on stereological parameters, to find out which model best reflects morphological changes in lung development comparable with alterations found in BPD. METHODS:Pregnant mice were exposed to normoxia, the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore, pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all pups at 14 days after birth. RESULTS:Compared to controls (No/No) 1) the lung volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the volume weighted mean volume of the parenchymal airspaces was significantly higher in the Hypo/Hyper group, 3) the total air space volume was significantly lower in the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall thickness of septa showed the highest values in the Hypo/Hyper group without reaching significance, 6) the volume density and the volume weighted mean volume of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly lower in the Hypo/Hyper group. CONCLUSION:Prenatal hypoxia and postnatal hyperoxia differentially influence the maturation of lung parenchyma. In 14 day old mice a significant retardation of morphological lung development leading to BPD-like alterations indicated by different parameters was only seen after hypoxia and hyperoxia

Lung parenchyma of 14 day old mice.

<p>Sections were stained with toluidine blue. a) Control lungs (No/No) exhibit well developed formed septa, alveoli and ductus alveolares. b) Prenatal hypoxia induced lungs (Hypo/No) show lung parenchyma without clearly visible alterations compared to controls. c) Postnatal hyperoxia induced lungs (No/Hyper) indicate more expanded airspaces with fewer septa than controls. d) Lungs exposed to prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper) display enlarged parenchymal airspaces surrounded by more or less thick septa.</p

Stereological parameters characterizing Alveolar Epithelial cells type II (AEII) and lamellar bodies (Lb).

<p>Controls (normoxia group, No/No), after prenatal hypoxia and postnatal normoxia (Hypo/No group), after prenatal normoxia and postnatal hyperoxia ((No/Hyper group) and after prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper group). Mean ± SD, *p<0.05, **p<0.01, ***p<0.001 compared to controls. a) The volume density of AEII showed a more or less pronounced variance in all groups. b) The volume weighted mean volume of AEII showed the significantly highest values compared to controls in the double hit model. c) Volume densities of Lb show comparable values in the one hit models, but significantly lower values in the Hypo/Hyper group. d) The volume weighted mean volume of Lb is comparable with control values in the Hypo/No and in the No/Hyper group. Significantly lower values were found in the double hit group.</p