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This study investigates the efficacy and effects of Kolb's experiential learning (EL) model and students' scientific field groups on their innovativeness in business development. (1) Humanities and Social Science, and (2) Science and Technology are the scientific field groups. A quasi-experimental quantitative approach with a 2 x 2 factorial design was used in this study. This study's sample encompassed active Faculty of Teacher Training and Education of the University of Mataram enrolling for entrepreneurship courses which were taken using random sampling after commensuration processes. The data collection instrument used to collect data on students' innovativeness is a project-based assessment based on indicators of innovativeness in developing products and digital marketing. The results of the instrument test fulfilled the validity and reliability requirement. All data were analyzed statistically by descriptive statistics and comparative analysis using the ANOVA test, which was preceded by an analysis requirement test. The study results showed an interaction effect of the EL model and students' scientific field on students' innovativeness. In addition, Kolb's EL model also directly affects students' innovativeness, while the scientific field group does not. Nevertheless, the data showed that the Science and Technology group innovates better than the others. The theoretical implication of this study was that EL has a strong theoretical framework for entrepreneurial learning, so it needs to be expanded through further studies.

Giving educational stimulation in early childhood can be given through games. Traditional science-based games make an important contribution to supporting children's development. This study aimed to identify traditional games in Central Lombok Regency that can be played in early childhood and how to play traditional games to improve children's development. This research is survey research conducted at Central Lombok Regency. This research uses observation data collection methods, interviews, and documentation. The subjects of this study were six community leaders or cultural leaders and five teachers. Data analysis used descriptive qualitative analysis. The results showed that there were 28 identified traditional games. After being reviewed and verified based on the criteria for tools and materials used: playground, gender, age of players, number of players, and how to play, 23 traditional games were obtained: fort, bekel, ciwe, cepun, do mi gift, merchandise, long dragon snakes, marbles, playing rope, pese-pese'an, temeong-meong, gobak sodor, trumpets, cingkaleng, manuk brackets, splashing, temong-meong, school stones, playing moon, cupring, segem, playing war and coffee. Traditional games use tools, do not use tools, and use poetry/songs. How to play traditional games each game has steps similar to each others. Based on these criteria, traditional games can indirectly improve child development such as cognitive, language, social-emotional, religious and moral values, physical-motor, and artistic.

The plasminogen receptor, Plg-R KT, is a unique cell surface receptor that is broadly expressed in cells and tissues throughout the body. Plg-R KT localizes plasminogen on cell surfaces and promotes its activation to the broad-spectrum serine protease, plasmin. In this study, we show that overexpression of Plg-R KT protects mice from high fat diet (HFD)-induced adipose and metabolic dysfunction. During the first 10 weeks on the HFD, the body weights of mice that overexpressed Plg-R KT (Plg-R KT -OEX) were lower than those of control mice (CagRosaPlgRKT). After 10 weeks on the HFD, CagRosaPlgRKT and Plg-R KT -OEX mice had similar body weights. However, Plg-R KT -OEX mice showed a more metabolically favourable body composition phenotype. Plg-R KT -OEX mice also showed improved glucose tolerance and increased insulin sensitivity. We found that the improved metabolic functions of Plg-R KT -OEX mice were mechanistically associated with increased energy expenditure and activity, decreased proinflammatory adipose macrophages and decreased inflammation, elevated brown fat thermogenesis, and higher expression of adipose PPARγ and adiponectin. These findings suggest that Plg-R KT signalling promotes healthy adipose function via multiple mechanisms to defend against obesity-associated adverse metabolic phenotypes.

Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla-afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.

The plasminogen activation system regulates the activity of the serine protease, plasmin. The role of plasminogen receptors in cancer progression is being increasingly appreciated as key players in modulation of the tumor microenvironment. The interaction of plasminogen with cells to promote plasminogen activation requires the presence of proteins exposing C-terminal lysines on the cell surface. Plg-R KT is a structurally unique plasminogen receptor because it is an integral membrane protein that is synthesized with and binds plasminogen via a C-terminal lysine exposed on the cell surface. Here, we have investigated the expression of Plg-R KT in human breast tumors and human breast cancer cell lines. Breast cancer progression tissue microarrays were probed with anti-Plg-R KT mAB and we found that Plg-R KT is widely expressed in human breast tumors, that its expression is increased in tumors that have spread to draining lymph nodes and distant organs, and that Plg-R KT expression is most pronounced in hormone receptor (HR)-positive tumors. Plg-R KT was detected by Western blotting in human breast cancer cell lines. By flow cytometry, Plg-R KT cell surface expression was highest on the most aggressive tumor cell line. Future studies are warranted to address the functions of Plg-R KT in breast cancer.

Machine intelligence can convert raw clinical data into an informational source that helps make decisions and predictions. As a result, cardiovascular diseases are more likely to be addressed as early as possible before affecting the lifespan. Artificial intelligence has taken research on disease diagnosis and identification to another level. Despite several methods and models coming into existence, there is a possibility of improving the classification or forecast accuracy. By selecting the connected combination of models and features, we can improve accuracy. To achieve a better solution, we have proposed a reliable ensemble model in this paper. The proposed model produced results of 96.75% on the cardiovascular disease dataset obtained from the Mendeley Data Center, 93.39% on the comprehensive dataset collected from IEEE DataPort, and 88.24% on data collected from the Cleveland dataset. With this proposed model, we can achieve the safety and health security of an individual., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Bhanu Prakash Doppala et al.)

Background: Plg-R KT , a unique transmembrane plasminogen receptor, enhances the activation of plasminogen to plasmin, and localizes the proteolytic activity of plasmin on the cell surface., Objectives: We investigated the role of Plg-R KT in adipose function, metabolic homeostasis, and obesity., Methods: We used adipose tissue (AT) sections from bariatric surgery patients and from high fat diet (HFD)-induced obese mice together with immunofluorescence and real-time polymerase chain reaction to study adipose expression of Plg-R KT . Mice genetically deficient in Plg-R KT and littermate controls fed a HFD or control low fat diet (LFD) were used to determine the role of Plg-R KT in insulin resistance, glucose tolerance, type 2 diabetes, and associated mechanisms including adipose inflammation, fibrosis, and ectopic lipid storage. The role of Plg-R KT in adipogenesis was determined using 3T3-L1 preadipocytes and primary cultures established from Plg-R KT -deficient and littermate control mice., Results: Plg-R KT was highly expressed in both human and mouse AT, and its levels dramatically increased during adipogenesis. Plg-R KT -deficient mice, when fed a HFD, gained more weight, developed more hepatic steatosis, and were more insulin resistant/glucose intolerant than HFD-fed wild-type littermates. Mechanistically, these metabolic defects were linked with increased AT inflammation, AT macrophage and T-cell accumulation, adipose and hepatic fibrosis, and decreased insulin signaling in the AT and liver. Moreover, Plg-R KT regulated the expression of PPARγ and other adipogenic molecules, suggesting a novel role for Plg-R KT in the adipogenic program., Conclusions: Plg-R KT coordinately regulates multiple aspects of adipose function that are important to maintain efficient metabolic homeostasis., (© 2021 International Society on Thrombosis and Haemostasis.)

Plasminogen activation rates are enhanced by cell surface binding. We previously demonstrated that exogenous plasminogen binds to phosphatidylserine-exposing and spread platelets. Platelets contain plasminogen in their α-granules, but secretion of plasminogen from platelets has not been studied. Recently, a novel transmembrane lysine-dependent plasminogen receptor, Plg-RKT, has been described on macrophages. Here, we analyzed the pool of plasminogen in platelets and examined whether platelets express Plg-RKT. Plasminogen content of the supernatant of resting and collagen/thrombin-stimulated platelets was similar. Pretreatment with the lysine analog, ε-aminocaproic acid, significantly increased platelet-derived plasminogen (0.33 vs 0.08 nmol/108 platelets) in the stimulated supernatant, indicating a lysine-dependent mechanism of membrane retention. Lysine-dependent, platelet-derived plasminogen retention on thrombin and convulxin activated human platelets was confirmed by flow cytometry. Platelets initiated fibrinolytic activity in fluorescently labeled plasminogen-deficient clots and in turbidimetric clot lysis assays. A 17-kDa band, consistent with Plg-RKT, was detected in the platelet membrane fraction by western blotting. Confocal microscopy of stimulated platelets revealed Plg-RKT colocalized with platelet-derived plasminogen on the activated platelet membrane. Plasminogen exposure was significantly attenuated in thrombin- and convulxin-stimulated platelets from Plg-RKT-/- mice compared with Plg-RKT+/+ littermates. Membrane exposure of Plg-RKT was not dependent on plasminogen, as similar levels of the receptor were detected in plasminogen-/- platelets. These data highlight Plg-RKT as a novel plasminogen receptor in human and murine platelets. We show for the first time that platelet-derived plasminogen is retained on the activated platelet membrane and drives local fibrinolysis by enhancing cell surface-mediated plasminogen activation.

Wound healing is a complex physiologic process that proceeds in overlapping, sequential steps. Plasminogen promotes fibrinolysis and potentiates the inflammatory response during wound healing. We have tested the hypothesis that the novel plasminogen receptor, Plg-R KT , regulates key steps in wound healing. Standardized burn wounds were induced in mice and time dependence of wound closure was quantified. Healing in Plg-R KT -/- mice was significantly delayed during the proliferation phase. Expression of inflammatory cytokines was dysregulated in Plg-R KT -/- wound tissue. Consistent with dysregulated cytokine expression, a significant delay in wound healing during the proliferation phase was observed in mice in which Plg-R KT was specifically deleted in myeloid cells. Following wound closure, the epidermal thickness was less in Plg-R KT -/- wound tissue. Paradoxically, deletion of Plg-R KT , specifically in keratinocytes, significantly accelerated the rate of healing during the proliferation phase. Mechanistically, only two genes were upregulated in Plg-R KT -/- compared with Plg-R KT +/+ wound tissue, filaggrin, and caspase 14. Both filaggrin and caspase 14 promote epidermal differentiation and decrease proliferation, consistent with more rapid wound closure and decreased epidermal thickness during the remodeling phase. Fibrin clearance was significantly impaired in Plg-R KT -/- wound tissue. Genetic reduction of fibrinogen levels to 50% completely abrogated the effect of Plg-R KT deletion on the healing of burn wounds. Remarkably, the effects of Plg-R KT deletion on cytokine expression were modulated by reducing fibrinogen levels. In summary, Plg-R KT is a new regulator participating in different phases of cutaneous burn wound healing, which coordinately plays a role in the interrelated responses of inflammation, keratinocyte migration, and fibrinolysis.

Pharmaceuticals and pesticides are important analytes of interest in clinical, environmental, and food analyses for ensuring public health. Sample pretreatment steps are often prerequisites for the quantitative analysis of these compounds, which are generally present in low concentrations in samples with complex matrices. In compliance with the current trend towards green analytical chemistry, the replacement of conventional toxic organic solvents with ecofriendly and safe solvents has been pursued in developing sample pretreatment methods. Subsequent to several reports in 2017, deep eutectic solvents (DESs) have been increasingly applied as desirable alternative solvents in numerous types of sample pretreatment methods for the analysis of pharmaceuticals and pesticides. The present review summarizes analytical methods involving DESs as extraction solvents and as the reaction media or functional materials for preparing adsorbents to quantify pharmaceuticals and pesticides in various matrices.

Membrane-bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-R KT is expressed by immune cells, including monocytes and macrophages. Among monocytes and macrophages, distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-R KT by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Proinflammatory CD14 ++ CD16 + human monocytes and Ly6C high mouse monocytes expressed the highest levels of Plg-R KT and bound significantly more plasminogen compared with the other respective subsets. Proinflammatory human macrophages, generated by polarization with lipopolysaccharide and interferon-γ, showed significantly higher expression of Plg-R KT compared with alternatively activated macrophages, polarized with interleukin-4 and interleukin-13. Directional migration of proinflammatory monocytes was plasmin dependent and was abolished by anti-Plg-R KT monoclonal antibody, ε-amino-caproic acid, aprotinin, and the aminoterminal fragment of urokinase-type plasminogen activator. In an in vivo peritonitis model, significantly less Ly6C high monocyte recruitment was observed in Plg-R KT -/- compared with Plg-R KT +/+ mice. Immunohistochemical analysis of human carotid plaques and adipose tissue showed that proinflammatory macrophages also exhibited high levels of Plg-R KT in vivo. Our data demonstrate higher expression of Plg-R KT on proinflammatory monocyte and macrophage subsets that impacts their migratory capacity., (© 2019 by The American Society of Hematology.)

Inflammation resolution is an active process that functions to restore tissue homeostasis. Clearance of apoptotic leukocytes by efferocytosis at inflammatory sites plays an important role in inflammation resolution and induces remarkable macrophage phenotypic and functional changes. Here, we investigated the effects of deletion of either plasminogen (Plg) or the Plg receptor, Plg-R KT , on the resolution of inflammation. In a murine model of pleurisy, the numbers of total mononuclear cells recruited to the pleural cavity were significantly decreased in both Plg -/- and Plg-R KT -/- mice, a response associated with decreased levels of the chemokine CCL2 in pleural exudates. Increased percentages of M1-like macrophages were determined in pleural lavages of Plg -/- and Plg-R KT -/- mice without significant changes in M2-like macrophage percentages. In vitro , Plg and plasmin (Pla) increased CD206/Arginase-1 expression and the levels of IL-10/TGF-β (M2 markers) while decreasing IFN/LPS-induced M1 markers in murine bone-marrow-derived macrophages (BMDMs) and human macrophages. Furthermore, IL4-induced M2-like polarization was defective in BMDMs from both Plg -/- and Plg-R KT -/- mice. Mechanistically, Plg and Pla induced transient STAT3 phosphorylation, which was decreased in Plg -/- and Plg-R KT -/- BMDMs after IL-4 or IL-10 stimulation. The extents of expression of CD206 and Annexin A1 (important for clearance of apoptotic cells) were reduced in Plg -/- and Plg-R KT -/- macrophage populations, which exhibited decreased phagocytosis of apoptotic neutrophils (efferocytosis) in vivo and in vitro . Taken together, these results suggest that Plg and its receptor, Plg-R KT , regulate macrophage polarization and efferocytosis, as key contributors to the resolution of inflammation.

Approximately, 10-20% of newborns require breathing assistance at birth, which remains the cornerstone of neonatal resuscitation. Fortunately, the need for chest compression (CC) or medications in the delivery room (DR) is rare. About 0.1% of term infants and up to 15% of preterm infants receive these interventions, this will result in approximately one million newborn deaths annually worldwide. In addition, CC or medications (epinephrine) are more frequent in the preterm population (~15%) due to birth asphyxia. A recent study reported that only 6 per 10,000 infants received epinephrine in the DR. Further, the study reported that infants receiving epinephrine during resuscitation had a high incidence of mortality (41%) and short-term neurologic morbidity (57% hypoxic-ischemic encephalopathy and seizures). A recent review of newborns who received prolonged CC and epinephrine but had no signs of life at 10 min following birth noted 83% mortality, with 93% of survivors suffering moderate-to-severe disability. The poor prognosis associated with receiving CC alone or with medications in the DR raises questions as to whether improved cardiopulmonary resuscitation methods specifically tailored to the newborn could improve outcomes.

In preterm neonates we investigated cerebral hypoxia assessed with near-infrared-spectroscopy during immediate transition after birth and general movement optimality score assessed before discharge. General movement optimality score decreased with increasing cerebral hypoxia. Burden of cerebral hypoxia during immediate transition might be associated with impaired short-term neurological outcome in preterm neonates., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background Preterm birth is known to be a stressful and anxious situation for parents, which might have long-term impact on the psychological health of mothers and even on the development of their preterm infants. Objective The Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) was developed to assess parental stress after preterm birth through three subscales [1]. The aim of the present study was to examine the psychometric properties and the dimensionality of the German version of the PSS:NICU to develop a reliable German version of the PSS:NICU. Methods For the development (exploratory factor analysis) 100 parents of preterm infants answered the questionnaire. Results The Sights and Sounds subscale was removed from the German version of the PSS:NICU due to low number of items., A Pss: NICU_German/2-scales was developed consisting of 2 subscales: Infant Behavior and Appearance (7 Items, Cronbach's α=0,82) and Parental Role Alteration (6 Items, Cronbach's α=0,87). Conclusions The PSS:NICU_German/2-scales is a reliable and economic scale for the assessment of parental stress after preterm birth., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Substantial haemodynamic changes occur during the first minutes after birth. Currently, only heart rate (HR) and arterial oxygen saturation are routinely used to monitor haemodynamic transition after birth., Objectives: The aim of the present study was to continuously assess haemodynamic changes during transition in term infants for the first time by using electrical velocimetry (EV), a new method of non-invasive cardiac output monitoring (NICOM), based on impedance cardiography technology., Methods: In this prospective observational study, term neonates delivered by elective caesarean section underwent NICOM measurements within the first 15 min after birth. The beat-to-beat measurement over a 10-second period was used to calculate cardiac output (CO) for each minute after birth. The data of CO were only accepted when the signal quality index (SQI) remained >80% during the measurement period of 10 s., Results: 100 term neonates underwent 1,500 NICOM measurements. 1,143 (76.2%) measurements were excluded because of a SQI <80%. HR and CO showed a trend to increase within the first minutes, and decreased significantly from minute 3 (HR) and 4 (CO), until minute 12 and 10, respectively. Stroke volume remained stable during the observation period., Conclusion: The present study was the first using EV for NICOM during the transition period in a larger cohort of newborn infants. Results of NICOM were similar to available echocardiography data. The possibility of NICOM offers continuous CO measurement. The present study supports the idea that CO is closely related to HR in newborn infants., (© 2016 S. Karger AG, Basel.)

Background: Measurement of mean arterial blood pressure (MABP) is feasible during neonatal transition., Objective: The objective of this study was to investigate a potential influence of MABP on the cerebral regional oxygen saturation (crSO2) in preterm and term infants during the immediate neonatal transition., Materials and Methods: Preterm and term infants were included in this observational study. The crSO2 was measured by near-infrared spectroscopy with the INVOS 5100C (Somanetics Corp., Troy, MI, USA) during the immediate neonatal transition (15 min after birth). The near-infrared spectroscopy sensor was applied to the left forehead. Furthermore, a pulse oximeter was applied to monitor arterial oxygen saturation (SpO2) and heart rate (HR). Fifteen minutes after birth, blood pressure was measured noninvasively at the left upper arm. Cerebral fraction tissue oxygen extraction (cFTOE) was calculated from SpO2 and crSO2. To investigate a potential association between crSO2/cFTOE and MABP, we performed a correlation analysis., Results: A total of 462 preterm and term infants (186/292) were included. Mean gestational age was 31.0 ± 3.5 weeks for preterm infants and 38.9 ± 0.8 weeks for full term infants. Mean birth weight was 1.591 ± 630 g in preterm infants and 3.331 ± 461 g in term infants. There was a significant negative correlation between MABP and cFTOE (ρ = -0.19, p = 0.03) in preterm infants but not in term infants (ρ = 0.05, p = 0.39). There was no significant correlation between MABP and crSO2 in either group., Conclusion: MABP has an impact on cerebral oxygenation in preterm infants. Therefore, blood pressure monitoring during the immediate neonatal transition might be relevant for improving cerebral oxygenation especially in preterm infants., (© 2017 S. Karger AG, Basel.)

Background: Preterm birth is associated with increased parental stress, worry, and anxiety, and affects parental-child interactional behaviour., Aim: To evaluate the influence of length of antepartum hospital stay on maternal stress after the birth of a preterm infant., Methods: A prospective two-centre pilot case-control study was performed at two tertiary level Neonatal-Intensive-Care-Units (NICU). Mothers of preterm infants <36 +0 weeks of gestation admitted to the NICUs were included. The stress of mothers with length of antepartum hospital stay <12h (n=20) were case-matched and compared to that of mothers with length of antepartum hospital stay ≥12h (n=20). Maternal stress was assessed within three days after birth with the Parental-Stress-Scale:NICU (PSS:NICU) questionnaire measuring three scales: "relationship and parental role", "sights and sounds", and "baby looks and behaves". Maternal socio-demographic data were collected by questionnaire administered at the same time., Results: Both groups of mothers had similar socio-demographic data. Stress scale of "sights and sounds" was significantly increased in mothers with antepartum stay ≥12h (2.48±0.69) compared to mothers with antepartum stay <12h (1.95±0.73) (p=0.024). There was no significant difference between the two groups regarding the "looks and behaves" (2.73±0.80 vs. 2.72±0.91; p=0.962) and "relationship and parental role" scales (3.31±1.08 vs. 3.58±1.18; p=0.484)., Conclusions: Our study demonstrated higher levels of maternal stress after preterm birth in mothers, who had been admitted to hospital for longer periods of time before delivery. Interventional programmes starting in the antepartum period should be established in order to reduce the burden of stress and to improve parental-child interaction., (Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Aim: To analyze whether in term neonates during immediate transition after birth low cerebral activity measured by amplitude-integrated EEG (aEEG) is linked to cerebral regional oxygen saturation (crSO2) measured by near-infrared spectroscopy (NIRS). Additionally, the cerebral fractional tissue oxygen extraction (cFTOE) was calculated to analyze whether cerebral activity is linked to cFTOE., Methods: A total of 244 term neonates delivered by primary cesarean section were studied. In addition to routine monitoring with pulse oximetry, aEEG and NIRS measurements were performed during the first 15min after birth. The mean minimum (Vmin) and maximum (Vmax) amplitude of the cerebral activity as well as crSO2 and cFTOE for each minute was determined. Neonates with initial Vmin<5μV or Vmax<10μV, which normalized during transition (study group) were compared to neonates with normal aEEG values throughout the whole monitoring period (control group)., Results: 9 neonates fulfilled inclusion criteria to the study group and were compared to 50 neonates in the control group. Vmin, Vmax, crSO2, SpO2 and cFTOE were compared from the 4th to 15thmin after birth. During our study period, Vmin and Vmax were significantly lower in the study group than in the control group. crSO2 was significantly lower in the study group until minute 11, dropping below the 10th centile in minute 8. cFTOE was significantly higher in the study group until minute 10, rising above the 90th centile in minutes 8 and 9. SpO2 was within normal ranges in both groups. crSO2 and cFTOE were within normal ranges in the control group., Conclusion: The present study demonstrates that neonates with initially low cerebral activity during immediate transition after birth concurrently showed low crSO2 (<10th percentile), but increased cerebral oxygen extraction (cFTOE>90th percentile). Cerebral monitoring with aEEG and NIRS might provide useful information on the neonates' condition during immediate transition., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess if monitoring of cerebral regional tissue oxygen saturation (crSO2) using near-infrared spectroscopy (NIRS) to guide respiratory and supplemental oxygen support reduces burden of cerebral hypoxia and hyperoxia in preterm neonates during resuscitation after birth., Study Design: Preterm neonates <34(+0) weeks of gestation were included in a prospective randomized controlled pilot feasibility study at 2 tertiary level neonatal intensive care units. In a NIRS-visible group, crSO2 monitoring in addition to pulse oximetry was used to guide respiratory and supplemental oxygen support during the first 15 minutes after birth. In a NIRS-not-visible group, only pulse oximetry was used. The primary outcomes were burden of cerebral hypoxia (<10th percentile) or hyperoxia (>90th percentile) measured in %minutes crSO2 during the first 15 minutes after birth. Secondary outcomes were all cause of mortality and/or cerebral injury and neurologic outcome at term age. Allocation sequence was 1:1 with block-randomization of 30 preterm neonates at each site., Results: In the NIRS-visible group burden of cerebral hypoxia in %minutes, crSO2 was halved, and the relative reduction was 55.4% (95% CI 37.6-73.2%; P = .028). Cerebral hyperoxia was observed in NIRS-visible group in 3 neonates with supplemental oxygen and in NIRS-not-visible group in 2. Cerebral injury rate and neurologic outcome at term age was similar in both groups. Two neonates died in the NIRS-not-visible group and none in the NIRS-visible group. No severe adverse reactions were observed., Conclusions: Reduction of burden of cerebral hypoxia during immediate transition and resuscitation after birth is feasible by crSO2 monitoring to guide respiratory and supplemental oxygen support., Trial Registration: ClinicalTrials.gov: NCT02017691., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To analyse impact of delayed cord clamping (DCC60sec) on cerebral regional tissue oxygenation (crSO2) and fractional tissue oxygen extraction (cFTOE) in spontaneously breathing preterm neonates during the first 15 min after birth., Methods: Two-centre observational study, crSO2 and cFTOE was monitored in neonates with DCC60sec or early cord clamping (ECC < 30 s)., Results: Seventy-six infants (birth weight and gestational age 1736 ± 508 g and 31.8 ± 2.5 weeks) were included. DCC was associated with lower initial crSO2 and higher cFTOE and lower initial Apgar-score and heart rate., Conclusion: Attending practitioners should be aware that DCC might impact initial immediate transition in spontaneously breathing preterm neonates.

Background: Sustained lung inflations (SLI) during neonatal resuscitation may promote alveolar recruitment in preterm infants. While most of the studies focus on respiratory outcome, the impact of SLI on the brain hasn't been investigated yet., Objective: Do SLI affect cerebral blood volume (CBV) in preterm infants?, Methods: Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support (RS) were included in this randomized controlled pilot trial. Within the first 15 minutes after birth near-infrared spectroscopy (NIRS) measurements using 'NIRO-200-NX' (Hamamatsu, Japan) were performed to evaluate changes in CBV and cerebral tissue oxygenation. Two groups were compared based on RS: In SLI group RS was given by applying 1-3 SLI (30 cmH2O for 15 s) continued by respiratory standard care. Control group received respiratory standard care only., Results: 40 infants (20 in each group) with mean gestational age of 32 weeks one day (±2 days) and birth weight of 1707 (±470) g were included. In the control group ΔCBV was significantly decreasing, whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes. Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses (p = 0.051)., Conclusion: This is the first study demonstrating an impact of SLI on CBV. Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age. Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain., Trial Registration: German Clinical Trials Register DRKS00005161 https://drks-neu.uniklinik-freiburg.de/drks&#95;web/setLocale&#95;EN.do.

Objectives: To investigate the occurrence of peri/intraventricular haemorrhage (P/IVH) in preterm infants and its potential association with cerebral regional oxygen saturation (crSO2) during the immediate transition., Methods: In this two-centre prospective observational cohort study, crSO2 was measured with near-infrared spectroscopy in preterm infants (<32 weeks of gestational age) during the immediate neonatal transition (15 min). In addition, arterial oxygen saturation (SpO2) and heart rate (HR) were monitored with pulse oximetry. Cranial ultrasound scans were performed on day 4, day 7 and day 14 after birth and before discharge. Neonates with IVH of any grade (IVH group) were matched to the neonates without IVH (Non-IVH group) on gestational age (±1 week) and birth weight (±100 g). The duration and magnitude of deviation from the 10th centile in crSO2 during immediate transition was analysed and expressed in %minutes., Results: IVH was found in 12 of the included neonates, who were matched to 12 neonates without IVH. There was no difference in SpO2 and HR between these two groups. The duration and magnitude of centiles-deviation of crSO2 was significantly pronounced in the IVH group compared with the Non-IVH group (1870%min vs 456%min)., Conclusions: The neonates of the IVH group showed significantly lower crSO2 values during the immediate transition, although there was no difference concerning SpO2 and HR. The additional monitoring of crSO2 during the immediate transition could reveal neonates with higher risk of developing an IVH later in the course., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Non-invasive monitoring of the brain with near-infrared spectroscopy (NIRS) during immediate transition after birth is of growing interest., Objective: The aim of this work was to define reference ranges and centile charts for a regional cerebral tissue oxygenation index (cTOI), measured with the NIRO 200NX (NIRO, Hamamatsu, Japan), and cerebral fractional tissue oxygen extraction (cFTOE) during the first 15 min after birth in preterm and term neonates without any medical support., Methods: cTOI was measured with the NIRO 200NX during the first 15 min after delivery via Caesarean section in preterm and term infants. The NIRS-sensor was placed on the right forehead. Peripheral arterial oxygen saturation (SpO2) and heart rate were continuously measured by pulse oximetry. cFTOE was calculated out of cTOI and SpO2. Neonates with a requirement for any medical support were excluded., Results: A total of 230 neonates were enrolled, from which 90 had to be excluded. Therefore, 140 term neonates were included and data were used to define reference ranges and centile charts. The 50th centile (10th to 90th centiles) of cTOI was 56% (39-75) at 2 min, 66% (50-78) at 5 min, 75% (62-85) at 10 min and 73% (61-84) at 15 min after birth. The 50th centile of cFTOE was 0.24 (0.11-0.44) at 2 min, 0.20 (0.10-0.35) at 5 min, 0.21 (0.09-0.35) at 10 min and 0.24 (0.13-0.37) at 15 min after birth., Conclusion: The present observational study adds the reference ranges and centile charts of cTOI measured with the NIRO 200NX and cFTOE calculated out of cTOI and SpO2 in neonates during the immediate neonatal transition. Centiles for each instrument will be necessary for future clinical application, since the differences between cTOI and cerebral regional tissue oxygen saturation measured with INVOS 5100C change with increasing regional oxygenation., (© 2015 S. Karger AG, Basel.)

Background: The fetal-to-neonatal transition is a complex process that includes changes in cardiac and respiratory systems., Objective: The aim of this study is to review the different methods of cardiocirculatory monitoring during the immediate neonatal transition period., Methods: A systematic search of PubMed and Ovid Embase was performed using the following terms: infant, newborn, newborn infant, neonate, neonates, heart, cardiac, blood pressure, haemodynamic, hemodynamics, blood circulation, circulation, echocardiography, ultrasonography, sonography, electrocardiography, ECG, oximetry, pulse, pulse oximetry, monitoring, measurement, acclimatization, adaptation, transition, after birth and delivery room. Additional articles were identified by manual search of cited references. Only human studies describing cardiocirculatory monitoring during the first 15 min after birth were included., Results: Thirteen studies were identified that described heart rate (HR). Additional five studies were identified that measured blood pressure. Four studies performed functional echocardiography during neonatal transition; two in addition to blood pressure monitoring and three in addition to HR monitoring., Conclusion: Routine HR monitoring using electrocardiography or pulse oximetry is used to evaluate adequate hemodynamic transition, and reference ranges have been established. Measuring blood pressure noninvasively though noncontinuously might be of some value in future, considering that the normative data have been established recently. Echocardiographic monitoring during the immediate transition period will improve the knowledge about cardiac function changes, but introduction in clinical routine remains questionable., (© 2014 S. Karger AG, Basel.)

Background: Peripheral muscle near-infrared spectroscopy (NIRS) measurements are of increasing interest especially in the care of critically ill patients., Objective: The aim was to perform a systematic qualitative review on peripheral muscle NIRS measurements in the clinical care of term and preterm neonates., Methods: A systematic search of PubMed and Ovid Embase was performed using the following terms: neonate, neonates, newborn, newborns, infant, infants, near-infrared spectroscopy, NIRS, oxygenation, perfusion, oxygen extraction, peripheral, tissue, muscle, calf, forearm and thigh. Additional articles were identified by a manual search of the cited references. Only human studies were included., Results: Twenty-one studies were identified to use peripheral muscle NIRS measurements as a single method, 17 studies combined cerebral and peripheral muscle NIRS measurements and 1 study used multi-site NIRS measurements in human neonates. Two randomized studies were identified. Two additional publications were included because they provided important general information about peripheral muscle NIRS measurements., Conclusion: In the care of critically ill neonates peripheral muscle NIRS measurements alone or in combination with cerebral or multi-site NIRS measurements provide useful additional information about peripheral circulation and oxygenation. This method is a promising tool in the recognition of early states of centralization (compensated shock) in this vulnerable group of patients. However, before this method can be used in the clinical routine it has to be tested as monitoring to guide interventions in further studies., (© 2015 S. Karger AG, Basel.)

Background: Near-infrared spectroscopy (NIRS) enables non-invasive measurements of changes in the concentration of oxygenated (x0394;HbO2) and reduced (x0394;HbR) haemoglobin. Changes in total haemoglobin (x0394;HbT = x0394;HbO2 + x0394;HbR) provide information on changes in cerebral blood volume (CBV)., Objective: The aim was to evaluate the behaviour of CBV during immediate postnatal transition in term infants., Design: This observational study was conducted at the Medical University of Graz. NIRS measurements were carried out in term infants without need for respiratory support by using 'NIRO 200-NX' (Hamamatsu) over the first 15 min after birth., Results: 109 infants with a mean gestational age of 38 + 6 weeks (±7 days) and birth weight of 3,242 g (±481) were included. Related to a reference value at minute 15, a significant decrease of HbT was observed for each minute within the study period. The mean (±SD) decrease of HbT of 17 (±40) µmol/l from minutes 2 to 15 represents a decrease of CBV of 1.0 ml/100 g brain (±2.2)., Conclusions: In healthy newborns, CBV decreased over the whole study period. This likely reflects a physiological process. The impact and clinical relevance of different CBV behaviour during immediate transition needs to be investigated in further studies., (© 2015 S. Karger AG, Basel.)

Plasminogen (PLG) is the zymogen of plasmin, the major enzyme that degrades fibrin clots. In addition to its binding and activation on fibrin clots, PLG also specifically interacts with cell surfaces where it is more efficiently activated by PLG activators, compared with the reaction in solution. This results in association of the broad-spectrum proteolytic activity of plasmin with cell surfaces that functions to promote cell migration. Here, we review emerging data establishing a role for PLG, plasminogen receptors and the newly discovered plasminogen receptor, Plg-RKT, in macrophage recruitment in the inflammatory response, and we address mechanisms by which the interplay between PLG and its receptors regulates inflammation., (© 2014 Elsevier Inc. All rights reserved.)

Laser acupuncture (LA) becomes more and more relevant in neonates and infants. With near-infrared spectroscopy (NIRS), a continuous and noninvasive measurement of tissue oxygenation is possible. Aim was to investigate, whether the application of LA was associated with any changes in regional cerebral oxygen saturation (rcSO2) in term and preterm neonates. The study included 20 neonates (12 males, 8 females). The Large Intestine 4 acupuncture point (LI 4, Hegu) was stimulated by a microlaser needle (10 mW, 685 nm laser needle EG GmbH, Germany) for 5 minutes, bilaterally. All neonates underwent polygraphic recording during undisturbed daytime sleep, including heart rate (HR), peripheral oxygen saturation (SpO2), and measurement of nasal flow. Using NIRS, rcSO2 was measured continuously. Cerebral fractional tissue oxygen extraction (cFTOE) was calculated. We did not observe any significant changes in SpO2 and HR values during the whole observation period. However, there was a significant decrease in rcSO2 (P = 0.003) within postintervention period, accompanied by a significant increase in cFTOE (P = 0.010) in postintervention period.