Structure-property relationships in renewable composites of poly(lactic acid) reinforced by low amounts of micro- and nano-kraft-lignin.

We investigate the direct and indirect effects of micro- and nano-kraft lignin, kL and NkL, respectively, at a quite low amount of 0.5 wt%, in poly(lactic acid) (PLA)-based composites. These renewable composites were prepared via two routes, either simple melt compounding or in situ reactive extrusion. The materials are selected and prepared using targeted methods in order to vary two variables, i.e., the size of kL and the synthetic method, while maintaining constant polymer chain lengths, L-/D-lactide isomer ratio and filler amounts. The direct/indirect effects were respectively investigated in the amorphous/semicrystalline state, as crystallinity plays in general a dominant role in polymers. The investigation involves structural, thermal and molecular mobility aspects. Non-extensive polymer-lignin interactions were recorded here, whereas the presence of the fillers led to both enhancements and suppressions of properties, e.g., glass transition, crystallization, melting temperatures, etc. The local and segmental molecular dynamics map of the said systems was constructed and is shown here for the first time, demonstrating both expected and unexpected trends. An interesting discrepancy between the trends in the calorimetric measurement against the dielectric Tg is revealed, providing indications for 'dynamical heterogeneities' in the composites as compared to neat PLA. The reactive extrusion as compared to compounding-based systems was found to exhibit stronger effects on crystallizability and mobility, most, probably due to the severe enhancement of the chains' diffusion. In general, the effects are more pronounced when employing nano-lignin compared to micro-lignin, which is the expected beneficial behaviour of nanocomposites vs. conventional composites. Interestingly, the variety of these effects can be easily manipulated by the proper selection of the preparation method and/or the thermal treatment under relatively mild conditions. The latter capability is actually desirable for processing and targeted applications and is proved here, once again, as an advantage of biobased polyesters such as PLA.

Parvovirus B19 Intrauterine Infection and Eventration of the Diaphragm.

Parvovirus B19 infection in pregnancy may have a poor outcome for the fetus. Ocular anomalies, brain damage with hydrocephalus and central nervous system (CNS) scarring, cleft lip and hypospadias, as well myocarditis and congenital heart disease have been reported. We present a case of a preterm female neonate born with ascites, hydrothorax and congenital diaphragmatic eventration (CDE), with a prenatal diagnosis of congenital diaphragmatic hernia (CDH). The neonate was born prematurely at 32 weeks gestation with caesarean section due to a previous caesarean delivery. She was immediately intubated in the delivery room, transferred in the Neonatal Intensive Care Unit (NICU) and supported with high frequency oscillatory ventilation (HFOV). The diagnosis of CDH was sonographically estimated from the 20th week of gestation and surgical correction was decided. During surgery CDE was diagnosed instead of CDH and despite postoperatively care the neonate developed disseminated intravascular coagulation and finally died in the 40th hour of life. Along with the identification of parvovirus B19 in the pleural fluid by PCR, the biopsy of the diaphragm revealed connective tissue, full of vasculature and absence muscle tissue. Although only cytomegalovirus, rubella, and toxoplasmosis were considered to be associated with CDE, parvovirus B19 might also be related to this congenital diaphragmatic malformation. In CDE, the function of the lungs can be compromised as a consequence of the compression applied by the abdominal organs. The neonatologists should include this condition in their differential diagnosis for a more direct and effective management.

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection.

Development of pneumonia is the most lethal consequence of influenza, increasing mortality more than 50-fold compared with uncomplicated infection. The spread of viral infection from conducting airways to the alveolar epithelium is therefore a pivotal event in influenza pathogenesis. We found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly accelerated the spread of viral infection from the airways to alveoli compared with challenge with IAV alone, based on spatial and temporal analyses of viral nucleoprotein staining of lung tissue sections and dissociated lung cells. To better define the temporal relationship between KGF administration and susceptibility to IAV infection in vivo, we administered KGF 120, 48, 24, and 0 h before intrapulmonary IAV challenge and assessed the percentages of proliferating and IAV-infected, alveolar type II (AECII) cells in dispersed lung cell populations. Peak AECII infectivity coincided with the timing of KGF administration that also induced peak AECII proliferation. AECII from mice that were given intrapulmonary KGF before isolation and then infected with IAV ex vivo exhibited the same temporal pattern of proliferation and infectious susceptibility. KGF-induced increases in mortality, AECII proliferation, and enhanced IAV susceptibility were all reversed by pretreatment of the animals with the mTOR inhibitor rapamycin before mitogenic stimulation. Taken together, these data suggest mTOR signaling-dependent, mitogenic conditioning of AECII is a determinant of host susceptibility to infection with IAV.

Evaluation of cerebral oxygenation and perfusion in small for gestational age neonates and neurodevelopmental outcome at 24-36 months of age.

Objective To examine cerebral oxygenation and perfusion in small for gestational age (SGA) compared with appropriate for gestational age (AGA) neonates during the first postnatal week, and to investigate any association with neurodevelopmental outcomes at 24-36 months of age. Methods A prospective matched case-control study was conducted evaluating cerebral oxygenation and perfusion, using near-infrared spectroscopy (NIRS), between SGA and AGA neonates, during the first postnatal week. A neurodevelopmental assessment with Bayley-III was performed at 24-36 months of age. Results Forty-eight SGA and 48 AGA neonates of similar gestation (32.8 ± 2.1 vs. 32.5 ± 1.9) were enrolled. On the first postnatal day, the cerebral oxygenation was equal between SGA and AGA neonates (71 ± 7% vs. 72 ± 8%); however, in the subgroup analysis, males had higher oxygenation compared to female SGA neonates (73 ± 7% vs. 69 ± 7%, P = 0.04). Cerebral perfusion was significantly higher in SGA neonates on the first postnatal day (1.4 ± 0.6 vs. 1.1 ± 0.5, P = 0.04), but this difference was diminished on subsequent measurements. There were no significant differences between the SGA and AGA infants regarding the composite cognitive, communication and motor index scores. The length of mechanical ventilation and late-onset sepsis were significant risk factors affecting the cognitive and communication composite index scores, respectively. Conclusion Cerebral oxygenation was equal between SGA and AGA neonates, while cerebral perfusion was transiently increased in SGA neonates during the first postnatal day. There was no significant association of cerebral oxygenation and perfusion with neurodevelopmental outcomes.

Research questions to facilitate the future development of European long-term ecosystem research infrastructures: A horizon scanning exercise.

Distributed environmental research infrastructures are important to support assessments of the effects of global change on landscapes, ecosystems and society. These infrastructures need to provide continuity to address long-term change, yet be flexible enough to respond to rapid societal and technological developments that modify research priorities. We used a horizon scanning exercise to identify and prioritize emerging research questions for the future development of ecosystem and socio-ecological research infrastructures in Europe. Twenty research questions covered topics related to (i) ecosystem structures and processes, (ii) the impacts of anthropogenic drivers on ecosystems, (iii) ecosystem services and socio-ecological systems and (iv), methods and research infrastructures. Several key priorities for the development of research infrastructures emerged. Addressing complex environmental issues requires the adoption of a whole-system approach, achieved through integration of biotic, abiotic and socio-economic measurements. Interoperability among different research infrastructures needs to be improved by developing standard measurements, harmonizing methods, and establishing capacities and tools for data integration, processing, storage and analysis. Future research infrastructures should support a range of methodological approaches including observation, experiments and modelling. They should also have flexibility to respond to new requirements, for example by adjusting the spatio-temporal design of measurements. When new methods are introduced, compatibility with important long-term data series must be ensured. Finally, indicators, tools, and transdisciplinary approaches to identify, quantify and value ecosystem services across spatial scales and domains need to be advanced.

A new methodology for the measurement of the root canal curvature and its 3D modification after instrumentation.

OBJECTIVE: In this study, the three-dimensional (3D) modification of root canal curvature was measured, after the application of Reciproc instrumentation technique, by using cone beam computed tomography (CBCT) imaging and a special algorithm developed for the 3D measurement of the curvature of the root canal. MATERIALS AND METHODS: Thirty extracted upper molars were selected. Digital radiographs for each tooth were taken. Root curvature was measured by using Schneider method and they were divided into three groups, each one consisting of 10 roots, according to their curvature: Group 1 (0°-20°), Group 2 (21°-40°), Group 3 (41°-60°). CBCT imaging was applied to each tooth before and after its instrumentation, and the data were examined by using a specially developed CBCT image analysis algorithm. RESULTS: The instrumentation with Reciproc led to a decrease of the curvature by 30.23% (on average) in all groups. CONCLUSIONS: The proposed methodology proved to be able to measure the curvature of the root canal and its 3D modification after the instrumentation.

Chitosan Nanoparticles with Encapsulated Natural and UF-Purified Annatto and Saffron for the Preparation of UV Protective Cosmetic Emulsions.

The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and physicochemical properties were evaluated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and dynamic light scattering (DLS). Results showed that the prepared nanoparticles ranged from ~150 to ~500 nm and had a spherical or irregular shape. In the case of annatto and UF annatto, due to the formation of H-bonds, the sunscreen agents were amorphously dispersed within CS nanoparticles, while in the case of saffron and UF saffron, crystalline dispersion was observed. All encapsulated materials had good thermal stability as well as color stability. In a further step, sunscreen emulsions were prepared based on the formed CS-sunscreen nanoparticles and evaluated for their stability in terms of pH and viscosity, along with their ultraviolet (UV) radiation protection ability in terms of sun protection factor (SPF). All prepared emulsions showed low cytotoxicity and good storage stability for up to 90 days, while minimum sunscreen protection was observed with SPF values varying from 2.15 to 4.85.

Differential Ligand Binding Specificities of the Pulmonary Collectins Are Determined by the Conformational Freedom of a Surface Loop.

Lung surfactant proteins (SPs) play critical roles in surfactant function and innate immunity. SP-A and SP-D, members of the collectin family of C-type lectins, exhibit distinct ligand specificities, effects on surfactant structure, and host defense functions despite extensive structural homology. SP-A binds to dipalmitoylphosphatidylcholine (DPPC), the major surfactant lipid component, but not phosphatidylinositol (PI), whereas SP-D shows the opposite preference. Additionally, SP-A and SP-D recognize widely divergent pathogen-associated molecular patterns. Previous studies suggested that a ligand-induced surface loop conformational change unique to SP-A contributes to lipid binding affinity. To test this hypothesis and define the structural features of SP-A and SP-D that determine their ligand binding specificities, a structure-guided approach was used to introduce key features of SP-D into SP-A. A quadruple mutant (E171D/P175E/R197N/K203D) that introduced an SP-D-like loop-stabilizing calcium binding site into the carbohydrate recognition domain was found to interconvert SP-A ligand binding preferences to an SP-D phenotype, exchanging DPPC for PI specificity, and resulting in the loss of lipid A binding and the acquisition of more avid mannan binding properties. Mutants with constituent single or triple mutations showed alterations in their lipid and sugar binding properties that were intermediate between those of SP-A and SP-D. Structures of mutant complexes with inositol or methyl-mannose revealed an attenuation of the ligand-induced conformational change relative to wild-type SP-A. These studies suggest that flexibility in a key surface loop supports the distinctive lipid binding functions of SP-A, thus contributing to its multiple functions in surfactant structure and regulation, and host defense.

Assessing the impact of geogenic chromium uptake by carrots (Daucus carota) grown in Asopos river basin.

A methodology was developed to assess the impact of geogenic origin hexavalent chromium uptake by carrots, and the risk of human consumption of carrots grown in Asopos River basin in Greece. A field scale experiment was conducted with carrots cultivated in treatment plots, with and without compost amendment, in order to assess the impact of carbon in the mobility and uptake of chromium by plants. The results suggested that there is a trend for chromium mobilization and uptake in the surface and the leaves of the carrots cultivated in the treatment plot with the higher carbon addition, but not in the core of the carrots. Limited mobility of hexavalent chromium in the soil-plant-water system is presented due to the affinity of chromium to be retained in the solid phase and be uptaken by plants. Hexavalent chromium tolerant bacterial strains were isolated from the carrots. These endophytic bacteria, present in all parts of the plant, were able to reduce hexavalent chromium to trivalent form to levels below the detection limit. Finally, a site-specific risk assessment analysis suggested no adverse effects to human health due to the consumption of carrots. These findings are of particular importance since they confirm that carrots grown in soils with geogenic origin chromium does not pose any adverse risk for human consumption, but could also have the beneficial effect of the micronutrient trivalent chromium.

Evaluation of Cerebral Oxygenation in Neonates with Sepsis with Near-Infrared Spectroscopy.

Objective Neonates with sepsis have increased risk of cerebral injury. Our aim was to evaluate cerebral oxygenation in septic neonates using near-infrared spectroscopy. Study Design A prospective study was designed enrolling neonates with sepsis, as defined by the International Consensus Conference of Pediatric Sepsis criteria and matched controls. Three cerebral half-hourly measurements were performed during the first, third, and seventh day of the episode and the values of tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) were compared between the two groups. Result The study population consisted of 50 septic and 44 control neonates with similar characteristics. No differences on TOI and FTOE were recorded in the first and third day. However, on the seventh day, septic neonates had significantly decreased oxygenation (62.7 ± 7 vs. 71.4 ± 4.4%, p < 0.001) and increased oxygen extraction (0.35 ± 0.07 vs. 0.27 ± 0.05, p < 0.001), irrespectively of the severity of the infection. Conclusion Although septic neonates have normal cerebral oxygenation in the first and third day of the sepsis, they present decreased cerebral oxygenation in the seventh day independently of the infection severity.

Keratinocyte growth factor supports pulmonary innate immune defense through maintenance of alveolar antimicrobial protein levels and macrophage function.

Keratinocyte growth factor (KGF) is an epithelial mitogen that has been reported to protect the lungs from a variety of toxic and infectious insults. In prior studies we found that recombinant human KGF accelerates clearance of bacteria from the murine lung by augmenting the function of alveolar macrophages (AM). In this study we tested the hypothesis that endogenous KGF plays a role in the maintenance of innate pulmonary defense against gram-negative bacterial infections. KGF-deficient mice exhibited delayed clearance of Escherichia coli from the lungs, attenuated phagocytosis by AM, and decreased antimicrobial activity in bronchoalveolar lavage (BAL) fluid, due in part to reductions in levels of surfactant protein A, surfactant protein D, and lysozyme. These immune deficits were accompanied by lower alveolar type II epithelial cell counts and reduced alveolar type II epithelial cell expression of collectin and lysozyme genes on a per cell basis. No significant between-group differences were detected in selected inflammatory cytokines or BAL inflammatory cell populations at baseline or after bacterial challenge in the wild-type and KGF-deficient mice. A single intranasal dose of recombinant human KGF reversed defects in bacterial clearance, AM function, and BAL fluid antimicrobial activity. We conclude that KGF supports alveolar innate immune defense through maintenance of alveolar antimicrobial protein levels and functions of AM. Together these data demonstrate a role for endogenous KGF in maintenance of normal pulmonary innate immune function.

G-CSF drives a posttraumatic immune program that protects the host from infection.

Traumatic injury is generally considered to have a suppressive effect on the immune system, resulting in increased susceptibility to infection. Paradoxically, we found that thermal injury to the skin induced a robust time-dependent protection of mice from a lethal Klebsiella pneumoniae pulmonary challenge. The protective response was neutrophil dependent and temporally associated with a systemic increase in neutrophils resulting from a reprioritization of hematopoiesis toward myeloid lineages. A prominent and specific activation of STAT3 in the bone marrow preceded the myeloid shift in that compartment, in association with durable increases in STAT3 activating serum cytokines G-CSF and IL-6. Neutralization of the postburn increase in serum G-CSF largely blocked STAT3 activation in marrow cells, reversing the hematopoietic changes and systemic neutrophilia. Daily administration of rG-CSF was sufficient to recapitulate the changes induced by injury including hematopoietic reprioritization and protection from pulmonary challenge with K. pneumoniae. Analysis of posttraumatic gene expression patterns in humans reveals that they are also consistent with a role for G-CSF as a switch that activates innate immune responses and suppresses adaptive immune responses. Our findings suggest that the G-CSF STAT3 axis constitutes a key protective mechanism induced by injury to reduce the risk for posttraumatic infection.

Platelet Mass Predicts Intracranial Hemorrhage in Neonates With Gram-negative Sepsis.

Neonatal sepsis due to gram-negative bacteria is associated with severe hemorrhagic conditions, such as intracranial hemorrhage (ICH). The aim of the study was to investigate the significance of platelet (PLT) count and platelet mass (PM) in predicting promptly neonatal ICH. Demographics, species, PLT, PM, ICH, and outcome for neonates with gram-negative sepsis for the period 2005 to 2012 were retrospectively recorded. Eighty-four infants were enrolled with median gestational age 30 weeks, median birthweight 1481.5 g, and median age at sepsis diagnosis 23 days. The most frequently isolated bacteria were Enterobacter spp. (38.1%). ICH occurred in 16 neonates (19%), whereas the mortality rate was 25% (21 neonates). The median PLT count and PM at days 1, 2, and 3 after diagnosis of gram-negative sepsis was significantly associated with the presence of ICH. Regression analysis revealed the cutoff predictive value of 355 fL/nL for the PM at day 3 (area under the curve: 75, sensitivity 90%, P=0.002). PM levels could play an important role in predicting the occurrence of ICH in high-risk neonates.

Severe Extravasation Injuries in Neonates: A Report of 34 Cases.

INTRODUCTION: Extravasation injuries are a common and challenging problem in hospitalized newborns. Accidental infusion leakage into the surrounding tissues in immature infants may frequently result in skin necrosis, with significant risk of functional and cosmetic impairment. MATERIAL AND METHODS: In the present study we reviewed 34 cases of severe extravasation injuries occurring in 1,409 neonates hospitalized in a single neonatal unit over 24 months (incidence 2.4%). Total parenteral nutrition solutions were involved in most cases. All patients were treated within 30 minutes after the injury was recorded using a flush-out technique with normal saline irrigation and occlusive paraffin dressings of the infiltrated area. RESULTS: The majority of injuries affected preterm, low-birthweight infants (mean gestation 32 wks + 6 days, mean birth weight 1,885 g), with a mean age at the time of injury of 11.6 days and a mean weight of 2,045 g. Neither gestational age (p = 0.87) or birthweight significantly affected (p = 0.07) the incidence of extravasation injuries, although the incidence of skin necrosis had a significant correlation with gestational age (p = 0.009) and birthweight (p < 0.001). All patients responded well to treatment and their wounds healed uneventfully within a maximum of 25 days without the need for secondary surgery for skin coverage. CONCLUSION: Extravasation injuries in extremely preterm and low-birthweight infants are more likely to lead to skin necrosis. Peripheral venous catheterization should be performed with caution in these patients to prevent such injuries. Immediate irrigation with normal saline is recommended to reduce toxic sequelae in the infiltrated area.

Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses.

We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glycan-rich viral envelope proteins including hemagglutinin (HA). We now show that replacement of D325 with serine to create D325S+R343V provided equal or increased neutralizing activity compared with D325A+R343V. The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V). D325A+R343V and D325S+R343V also strongly inhibited HA activity, and markedly aggregated, the 1968 pandemic H3N2 strain, Aichi68. D325S+R343V significantly reduced viral loads and mortality of mice infected with Aichi68, whereas wild-type SP-D NCRD did not. The pandemic H1N1 strains of 1918 and 2009 have only one N-linked glycan side on the head region of the HA and are fully resistant to inhibition by native SP-D. Importantly, we now show that D325A+R343V and D325S+R343V inhibited Cal09 H1N1 and related strains, and reduced uptake of Cal09 by epithelial cells. Inhibition of Cal09 was mediated by the lectin activity of the NCRDs. All known human pandemic strains have at least one glycan attachment on the top or side of the HA head, and our results indicate that they may be susceptible to inhibition by modified host defense lectins.

Effects of olive mill wastewater on soil carbon and nitrogen cycling.

This study investigated the cycling of C and N following application of olive mill wastewater (OMW) at various rates (0, 42, 84, and 168 m(3)/ha). OMW stimulated respiration rate throughout the study period, but an increase in soil organic matter was observed only at the highest rate. Soil phenol content decreased rapidly within 2 weeks following application but neither phenol oxidase and peroxidase activity nor laccase gene copies could explain this response. Soil NH4 (+)-N content increased in response to OMW application rate, while an opposite trend observed for NO3 (-)-N, which attributed to immobilization. This decrease was in accordance with amoA gene copies of archaeal and bacterial ammonia oxidizers in the first days following OMW application. Afterwards, although amoA gene copies and potential nitrification rates recovered to values similar to or higher than those in the non-treated soils, NO3 (-)-N content did not change among the treatments. A corresponding increase in denitrifying gene copies (nirK, nirS, nosZ) during that period indicates that denitrification, stimulated by OMW application rate, was responsible for this effect; a hypothesis consistent with the decrease in total Kjeldahl nitrogen content late in the season. The findings suggest that land application of OMW is a promising practice for OMW management, even at rates approaching the soil water holding capacity.

Nutrient mitigation in a temporary river basin.

We estimate the nutrient budget in a temporary Mediterranean river basin. We use field monitoring and modelling tools to estimate nutrient sources and transfer in both high and low flow conditions. Inverse modelling by the help of PHREEQC model validated the hypothesis of a losing stream during the dry period. Soil and Water Assessment Tool model captured the water quality of the basin. The 'total daily maximum load' approach is used to estimate the nutrient flux status by flow class, indicating that almost 60% of the river network fails to meet nitrogen criteria and 50% phosphate criteria. We recommend that existing well-documented remediation measures such as reforestation of the riparian area or composting of food process biosolids should be implemented to achieve load reduction in close conjunction with social needs.

Outbreak of pan-susceptible Klebsiella pneumoniae in a neonatal intensive care unit.

We describe the outbreak of a pan-susceptible Klebsiella pneumoniae strain in a neonatal intensive care unit. A total of 7 neonates developed bacteraemia (37% attack rate), of whom 3 died (43% case fatality rate). A birth weight < 1500 g was the only statistically significant risk factor. Despite an extensive environmental investigation, the source was not identified.

Predicting response to rFVIIa in neonates with intractable bleeding or severe coagulation disturbances.

BACKGROUND: To date, clinical experience with recombinant factor VIIa (rFVIIa) in neonates is rather limited because of the lack of controlled studies. ΑIM: The objective of this study was to present further experience from our center with regard to the use of rFVIIa in newborns with severe bleeding or coagulopathy resistant to conventional therapy and to determine factors affecting the clinical outcome. METHODOLOGY: We performed a retrospective data analysis of 29 neonates with intractable bleeding or severe coagulation disturbances. All patients received 100 µg/kg of rFVIIa per dose bolus intravenously (maximum of 23 doses), as rescue procedure after other interventions had failed to achieve hemostasis. RESULTS: Fourteen neonates survived (group A), whereas 15 died (group B). There was no difference in birth weight, gestational age, and bleeding site and causes between the 2 groups. In the neonates who survived, rFVIIa had been administered earlier in the disease process (<24 h of beginning of bleeding) compared with those who died (P=0.009). In all 29 neonates, international normalized ratio was directly restored (from 2.99±1.4 before rFVIIa administration to 1.6±1.1 afterward, P<0.001) and prothrombin time and activated partial thromboplastin time were significantly decreased after administration of rFVIIa (from 28 to 16.4 and from 180 to 67, respectively; P=0.001 and 0.05, respectively). Blood products administered were significantly less in group A than in group B, as time from the beginning of bleeding to the administration of rFVIIa was significantly less in group A than in group B. Neither acute adverse events nor thromboembolic complications were observed. CONCLUSIONS: In this neonatal group with intractable bleeding and/or severe coagulation disturbances, rFVIIa was more effective in early intervention as rescue therapy, without any adverse events in all neonates. Upon failure to achieve hemostasis with initial administration of blood products, fast intervention with rFVIIa could be considered in neonates with serious bleeding and coagulation disorders.