Analysis of perinatal risk factors for massive pulmonary hemorrhage in very low birth weight infant: A nationwide large cohort database.

OBJECTIVE: To determine perinatal risk factors for Massive pulmonary hemorrhage (MPH) and MPH-caused mortality to guide clinicians in implementing preventive measures at the beginning of life for improving the survival of very low birth weight infant (VLBWIs). STUDY DESIGN: A total of 13,826 VLBWIs born between 2013 and 2020 in the Korean Neonatal Network database were included. RESULTS: MPH occurred in 870 (6.3 %) VLBWIs. Among infants with MPH, 162 (18.6 %) VLBWIs died due to MPH. In the multivariate logistic regression analysis, independent risk factors for MPH were identified as small for gestational age, multiple gestation, high CRIB-II score, use of surfactant, and symptomatic patent ductus arteriosus (sPDA) in VLBIWs. Independent risk factors for MPH-caused mortality were identified as multiple gestation in VLBWIs. Receiving a complete course of antenatal corticosteroids (ACS) was found to be a significant independent protective factor for MPH-caused mortality in VLBWIs. CONCLUSION: Proactive managements for reducing unnecessary use of pulmonary surfactant and for decreasing the risk of sPDA at the beginning of life could be recommended as preventive strategies to reduce the risk of MPH in extremely preterm infants. ACS therapy is highly recommended for women with a high likelihood of giving birth preterm to reduce the risk of mortality caused by MPH.

CS-UNet: Cross-scale U-Net with Semantic-position dependencies for retinal vessel segmentation.

Accurate retinal vessel segmentation is the prerequisite for early recognition and treatment of retina-related diseases. However, segmenting retinal vessels is still challenging due to the intricate vessel tree in fundus images, which has a significant number of tiny vessels, low contrast, and lesion interference. For this task, the u-shaped architecture (U-Net) has become the de-facto standard and has achieved considerable success. However, U-Net is a pure convolutional network, which usually shows limitations in global modelling. In this paper, we propose a novel Cross-scale U-Net with Semantic-position Dependencies (CS-UNet) for retinal vessel segmentation. In particular, we first designed a Semantic-position Dependencies Aggregator (SPDA) and incorporate it into each layer of the encoder to better focus on global contextual information by integrating the relationship of semantic and position. To endow the model with the capability of cross-scale interaction, the Cross-scale Relation Refine Module (CSRR) is designed to dynamically select the information associated with the vessels, which helps guide the up-sampling operation. Finally, we have evaluated CS-UNet on three public datasets: DRIVE, CHASE_DB1, and STARE. Compared to most existing state-of-the-art methods, CS-UNet demonstrated better performance.

Prophylaxis of Patent Ductus Arteriosus with Paracetamol in Extremely Low Gestational Age Newborns (ELGANs): A Single-Institution Observational Study in Vietnam.

INTRODUCTION: Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks' gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol's impact on sPDA interventions in ELGANs in an LMIC. METHODS: This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA (n = 104) with infants (n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA. RESULTS: In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort (p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation (p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%). CONCLUSIONS: Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies.

Joint domain symmetry and predictive balance for cross-dataset EEG emotion recognition.

BACKGROUND: Cross-dataset EEG emotion recognition is an extremely challenging task, since data distributions of EEG from different datasets are greatly different, which makes the universal models yield unsatisfactory results. Although there are many methods have been proposed to reduce cross-dataset distribution discrepancies, they still neglected the following two problems. (1) Label space inconsistency: emotional label spaces of subjects from different datasets are different; (2) Uncertainty propagation: the uncertainty of misclassified emotion samples will propagate between datasets. NEW METHOD: To solve these problems, we propose a novel method called domain symmetry and predictive balance (DSPB). For the problem of label space inconsistency, a domain symmetry module is designed to make label spaces of source and target domain to be the same, which randomly selects samples from the source domain and put into the target domain. For the problem of uncertainty propagation, a predictive balance module is proposed to reduce the prediction score of incorrect samples and then effectively reduce distribution differences between EEG from different datasets. RESULTS: Experimental results show that our method achieve 61.48% average accuracies on the three cross-dataset tasks. Moreover, we find that gamma is the most relevant to emotion recognition among the five frequency bands, and the prefrontal and temporal brain regions are the channels carrying the most emotional information among the 62 brain channels. COMPARISON WITH EXISTING METHODS: Compared with the partial domain adaptation method (SPDA) and the unsupervised domain adaptation (MS-MDA), our method improves average accuracies by 15.60% and 23.11%, respectively. CONCLUSION: Besides, data distributions of EEG from different datasets but with the same emotional labels have been well aligned, which demonstrates the effectiveness of DSPB.

Combination of sulfide-driven partial denitrification with anammox enhanced by zeolite powder for autotrophic nitrogen and sulfide removal from wastewater.

Sulfide-driven partial denitrification and anaerobic ammonia oxidizing (anammox) (SPDA) is a high-efficiency technology to achieve simultaneous nitrogen and sulfide removal. Nitrite accumulation from sulfide-driven partial denitrification is the key to achieve SPDA. Zeolite powder was added to strengthen the competition of anammox bacteria against nitrite. The nitrogen removal rate (NRR) and partial denitrification efficiency in reactor was 5.18 kg-N m-3d-1 and 92.3% during 180 days of operation, higher than those without zeolite powder, indicating an improving contribution of zeolite powder. Metabolomics analysis revealed zeolite powder addition enhanced the metabolisms of amino acids, nicotinate and porphyrin through increasing glutamate content, and improved EPS secretion, heme c content and particle size. Besides, high ammonia enriched by zeolite powder was conducive to improve anammox activity and NRR. This study provides the metabolic insights into the mechanism of zeolite powder enhancing SPDA, which is meaningful towards overcoming the limitations in practical application of SDPA.

YOLOv5s-DSD: An Improved Aerial Image Detection Algorithm Based on YOLOv5s.

Due to the challenges of small detection targets, dense target distribution, and complex backgrounds in aerial images, existing object detection algorithms perform poorly in aerial image detection tasks. To address these issues, this paper proposes an improved algorithm called YOLOv5s-DSD based on YOLOv5s. Specifically, the SPDA-C3 structure is proposed and used to reduce information loss while focusing on useful features, effectively tackling the challenges of small detection targets and complex backgrounds. The novel decoupled head structure, Res-DHead, is introduced, along with an additional small object detection head, further improving the network's performance in detecting small objects. The original NMS is replaced by Soft-NMS-CIOU to address the issue of neighboring box suppression caused by dense object distribution. Finally, extensive ablation experiments and comparative tests are conducted on the VisDrone2019 dataset, and the results demonstrate that YOLOv5s-DSD outperforms current state-of-the-art object detection models in aerial image detection tasks. The proposed improved algorithm achieves a significant improvement compared with the original algorithm, with an increase of 17.4% in mAP@0.5 and 16.4% in mAP@0.5:0.95, validating the superiority of the proposed improvements.

Analysis of Costs Associated with the Use of Personalized Automated Dosing Systems versus Manual Preparation in a Residential Center for the Elderly in Extremadura.

INTRODUCTION: During the SARS-CoV-2 pandemic, there has been a decrease in the supervision of the medication of subjects with chronic diseases. Customized automated dosing systems (SPDA) are devices that allow medication to be dispensed and administered, which have proven to be safe and effective for the patient and cost-effective for the healthcare system. METHODS: an intervention study was carried out on patients from January to December 2019 in a residential centre for the elderly with more than 100 beds. The economic costs derived from manual dosing were compared with those of an automated preparation (Robotik Technology®). RESULTS: Of the 198 patients included, 195 (97.47%) of them were polymedicated. Of the total of 276 active substances of registered medicinal products, it was possible to include them in the process of automating the preparation of the SPDA 105 active pharmaceutical ingredients. A cost reduction of EUR 5062.39 per year was found using SPDA. Taking into account the active ingredients of emblistable and non-emblistable medicines, the use of SPDA resulted in savings of EUR 6120.40 per year. The system contributed to the detection of cases of therapeutic duplication and reduced the time to prepare the medication. CONCLUSIONS: the use of SPDA is a useful and economically profitable strategy for its use in residential centres for the elderly.

Sustained Release of BMSC-EVs from 3D Printing Gel/HA/nHAP Scaffolds for Promoting Bone Regeneration in Diabetic Rats.

Extracellular vesicles (EVs) play an important role in intercellular communication, and the function of EVs mainly depends on the state of source cells. To determine the effect of diabetic microenvironment on EVs secreted by bone marrow mesenchymal stem cells (BMSCs), this work explores the effect of normal glucose (5.5 mm) cultured BMSCs derived EVs (NG-EVs) and high glucose (30 mm) cultured BMSCs derived EVs (HG-EVs) in regulating the migration, proliferation and osteoblastic differentiation of BMSCs in vitro. In order to improve the bioavailability of EVs, this work constructs a sustained release system of polydopamine (PDA) functionalized 3D printing gelatin/hyaluronic acid/nano-hydroxyapatite (Gel/HA/nHAP) scaffolds (S/PDA) and verifies its function in the calvarial defect model of diabetic rats. This work confirms that both NG-EVs and HG-EVs can promote proliferation and migration, inhibit apoptosis and promote osteogenic differentiation, but the function of HG-EVs is weaker than that of NG-EVs. Therefore, EVs secreted by autologous cells of diabetic patients are not suitable for self-repair. This work hopes that the 3D printing scaffold designed for sustained-release EVs will provide a new strategy for acellular tissue engineering bone repair in diabetic patients.

Effect of mirasol pathogen reduction technology system on immunomodulatory molecules of apheresis platelets.

Pathogen inactivation for platelets by riboflavin system (MIRASOL) efficiently reduces transfusion related pathogen transmission. However little is known about its impact on platelets' immunomodulatory biochemical profile. We aimed was to assess the effects of MIRASOL treatment on platelet quality parameters and immunomodulatory molecules CD62P, RANTES, and CD40L in Single Donor Platelets (SDPs) resuspended in plasma (SDP-P) or T-PAS and additive solution (SDP-A). Twenty nine SDPs (15 SDP-P and 14 SDP-A) were included in the study. Samples were collected before, after MIRASOL treatment and just before transfusion. P-selectin (CD62P), RANTES, and CD40L were tested by ELISA. Platelet products quality assays were also performed. Platelet count/unit decreased after Mirasol treatment by 13 %. The pH of all units decreased over the 5-day storage period but remained above expected limits and the swirling test was positive throughout storage. P-selectin levels were not different between the three different time points in both SDPs-P and SDPs-A while RANTES levels were found to differ statistically significantly at the three different time points in all units and in the SPD-A subgroup. CD40L levels in all SDP products increased slightly during storage but this was not statistically significant. CD62P, RANTES, and CD40L in all time points were elevated in SDPs-A compared to SDPs-P but not at a statistically significant level. In conclusion MIRASOL treatment apart from RANTES increase does not seem to substantially affect platelets associated other cytokines and immunomodulatory molecules namely P-selectin and sCD40L which are implicated in immune transfusion reactions.

Extracellular polymeric substances trigger microbial immigration from partial denitrification (PD) to anammox biofilms in a long-term operated PD/anammox process in low-strength wastewater.

The immigration of microbial communities in a synergistic partial denitrification/anammox (SPDA) system was investigated in a moving bed biofilm reactor (MBBR) inoculated with partial denitrification (PD) and anaerobic ammonium oxidation (anammox) biofilms. The SPDA system was operated at 25 ± 1 °C over 260 days. The total nitrogen (TN) of the effluent was only 3.71 ± 0.92 mg·L-1 in the stable phase with a TN removal efficiency of 95.23%. The anammox process was the dominant nitrogen removal pathway with an average contribution of 74.31% to TN removal. The results of the in situ activity and key enzymatic activity revealed that the nitrate-reducing bacteria tended to immigrate to anammox biofilms. Correspondingly, the abundance of the genus Thauera, the second most dominant bacteria in anammox biofilms, quickly increased from 0.78 to 10.69% on day 50 and eventually to 16.45% on day 221 according to the Illumina MiSeq sequencing data. The microbial immigration might be caused by different extracellular polymeric substance (EPS)-mediated mechanisms in PD and anammox biofilms. For fast-growing denitrifiers, PD biofilms tend to increase the ability of mass transfer by excreting more polysaccharides to form loosely-bound EPS at the expense of the ability to harbor the nitrate-reducing bacteria. However, for the slow-growing anaerobic ammonium oxidizing bacteria (AnAOB), the anammox biofilms tend to increase the retention of AnAOB by excreting more proteins to form enhanced tightly-bound EPS at the expense of the mass transfer ability, thereby causing the detached nitrate-reducing bacteria to immigrate into anammox biofilms.

Nanometer-Scale Precision Polymer Patterning of PDMS: Multiscale Insights into Patterning Efficiency Using Alkyldiynamines.

Most high-resolution interfacial patterning approaches are restricted to crystalline inorganic interfaces. Recently, we have shown that it is possible to generate 1 nm resolution functional patterns on soft materials, such as polydimethylsiloxane (PDMS), by creating highly structured striped patterns of functional alkyldiacetylenes on a hard crystalline surface, photopolymerizing to set the molecular pattern as a striped-phase polydiacetylene (sPDA), and then covalently transferring the sPDAs to PDMS. Transfer depends on the diacetylene polymerization, making it important to understand design principles for efficient sPDA polymerization and cross-linking to PDMS. Here, we combine single-molecule and fluorescence-based metrics for sPDA polymerization and transfer, first to characterize sPDA polymerization of amine striped phases, and then to develop a probabilistic model that describes the transfer process in terms of sPDA-PDMS cross-linking reaction efficiency and number of reactions required for transfer. We illustrate that transferred patterns of alkylamines can be used to direct both adsorption of CdSe nanocrystals with alkyl ligand shells and covalent reactions with fluorescent dyes, highlighting the utility of functional patterning of the PDMS surface.

Ductus Arteriosus of Extremely Preterm Twins is More Resistant to Cyclooxygenase Inhibitors Than Those of Singletons.

Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm infants, as closure of the ductus arteriosus using cyclooxygenase inhibitors is often difficult. A recent study using a preterm sheep model showed that intimal thickening-required for anatomical closure of the ductus arteriosus-is less developed in twins than in singletons. Therefore, this study primarily aimed to prove that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of extremely preterm singletons. Its secondary aim was to assess whether the resistance against cyclooxygenase inhibitors differed according to chorionicity. In this retrospective case-control study, medical records of 162 extremely preterm infants (gestational age < 28 weeks) were reviewed, and the treatment course of sPDA was subsequently compared between singletons (n = 131) and twins (n = 31). The median indomethacin doses for sPDA and the necessity for surgical ligation were significantly higher in twins than in singletons (5 vs 2 [p < 0.001] and 42% vs 21% [p = 0.018], respectively). No significant differences in sPDA treatment, including the number of indomethacin doses and the necessity for surgical ligation, were observed between monochorionic diamniotic and dichorionic diamniotic twins. This study confirms that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of singletons. However, there was no significant difference in sPDA treatment by chorionicity.

Artificial intelligence model comparison for risk factor analysis of patent ductus arteriosus in nationwide very low birth weight infants cohort.

Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Exploring the NT-proBNP expression in Premature Infants with Patent Ductus Arteriosus (PDA) by Echocardiography.

OBJECTIVES: To investigate the correlation between echocardiographic indicators and the expression level of N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants (PIs) with patent ductus arteriosus (PDA) and the value of NT-proBNP in diagnosing symptomatic PDA (sPDA) in PIs whose gestational age (GA) was less than 32 weeks. METHODS: Ninty premature infants were selected as the research objects, including 52 in the non-PDA group and 38 in the PDA group (26 sPDA cases and 12 cases with asymptomatic PDA (asPDA)) from February 2019 to March 2020. The general information of these infants was recorded, including gender, delivery method, maternal infection, and serum NT-proBNP level on the 3rd day after birth. They were screened by echocardiographic indicators under an artificial intelligence convolutional neural network (AI-CNN). The Receiver Operating Characteristic (ROC) curves were illustrated to decide serum NT-proBNP expression levels, thereby determining specificity and sensitivity of sPDA and the correlation between serum sPDA NT-proBNP expression and echocardiographic indicators. RESULTS: The expression level of serum NT-proBNP in the sPDA group was greater than that in the asPDA group and the non-PDA group (P<0.001). The serum NT-proBNP expression level was positively correlated with the diameter of the ductus arteriosus in the sPDA group (r=0.462, P<0.001); it was also positively correlated with the ratio of left atrium/aorta (LA/AO) (r=0.573, P<0.001), but was not correlated with left ventricular ejection fraction (LVEF) (r=-0.015, P=0.747). CONCLUSION: The combination of serum NT-proBNP expression and echocardiography had clinical values in early diagnosis of PDA.

Evidence for an arginine-dependent route for the synthesis of NO in the model filamentous fungus Aspergillus nidulans.

Nitric oxide (NO) is a signalling molecule in eukaryotic and prokaryotic organisms. NO levels transiently boost upon induction of conidiation in Aspergillus nidulans. Only one pathway for NO synthesis involving nitrate reductase has been reported in filamentous fungi so far, but this does not satisfy all the NO produced in fungal cells. Here we provide evidence for at least one additional biosynthetic pathway in A. nidulans involving l-arginine or an intermediate metabolite as a substrate. Under certain growth conditions, the addition of l-arginine to liquid media elicited a burst of NO that was not dependent on any of the urea cycle genes. The NO levels were controlled by the metabolically available arginine, which was regulated by mobilization from the vacuoles and during development. In vitro assays with protein extracts and amino acid profiling strongly suggested the existence of an arginine-dependent NO pathway analogous to the mammalian NO synthase. Addition of polyamines induced NO synthesis, and mutations in the polyamine synthesis genes puA and spdA reduced the production of NO. In conclusion, here we report an additional pathway for the synthesis of NO in A. nidulans using urea cycle intermediates.

Effect of irradiation of silicon photodiode arrays for ITER radial x-ray camera investigated by measuring response and current-voltage characteristics.

The response and current-voltage (I-V) characteristics of irradiated and non-irradiated silicon photodiode arrays (SPDAs) for use in the International Thermonuclear Experimental Reactor camera are measured and compared. Irradiation experiments are carried out using a uranium-zirconium hydride pulsed reactor. The total equivalent 1 MeV neutron fluence with energy above 0.01 MeV is ∼9.89 × 1013 n cm-2. The output signal of the irradiated SPDA (XD2) shows a nonlinear trend during the irradiation experiment. The final signal is about 5.6% of the original one in the visible light region. Tests on the Experimental Advanced Superconducting Tokamak (EAST) show that the XD2 signal is 70%-80% of that of a non-irradiated SPDA (XD3). This indicates that irradiated SPDAs can still observe plasma radiation after exposure to 9.89 × 1013 n cm-2 neutron fluence. However, because the neutron fluence of external camera detectors will reach 1.4 × 1016 n cm-2 in D-T phase, the SPDAs might become unusable at some point. The responsivity ratio of irradiated and non-irradiated SPDAs is about 4%-20% from 7 to 13 keV. The degradation of responsivity is related to the energy level. After irradiation, the reversed dark current rises from 0.1 to 10 nA to a level of around 1 µA. In terms of tests of XD2 on EAST, zero bias is a good working condition for irradiated SPDAs.

Exploration and verification of the feasibility of sulfide-driven partial denitrification coupled with anammox for wastewater treatment.

Anaerobic ammonia oxidation (anammox) is a well-developed biotechnology for treating high-strength ammonium wastewaters. Recently, partial denitrification has been considered as an alternative to supply anammox with the required nitrite. In this study, a process of sulfide-driven partial denitrification and anammox (SPDA) was developed and operated continuously in an upflow anaerobic sludge blanket (UASB) reactor for 392 days. This reactor was fed with synthetic wastewater containing 100 mgN/L nitrate, 80 mgN/L ammonium and 20-80 mgS/L sulfide. After 160 days of operation, the reactor reached stable performance, and the nitrogen removal efficiency and rate were maintained at 80% and 0.29 kgN/(m³â€¢d), respectively. The estimated nitrogen removal via anammox and sulfide-driven denitrification were 87.2% and 12.8%. Additional batch experiments were conducted to investigate the effects of sulfide on anammox and the mechanisms of nitrogen removal in the SPDA system. The following results were obtained: (1) sulfide had an inhibitory effect on the specific anammox activity with IC50 of 9.7 mgS-H2S/L. (2) The rapid oxidation of sulfide by sulfur-oxidizing bacteria (SOB) could relieve the toxic effects of sulfide on the anammox in the SPDA system. (3) Sulfide bio-oxidation was a two-step reaction with biologically produced elemental sulfur (BPS0) as the intermediate, and the second step using BPS0 as the electron donor, can efficiently produce nitrite via partial denitrification (NO3- → NO2-) as a supply for anammox. Finally, a high-throughput sequencing analysis identified Thiobacillus and Sulfurimonas as the dominant genera of SOB in the SPDA system, and Candidatus Kuenenia as the dominant anammox bacteria. Overall, this research gives the foundation for the practical application of sulfide-driven partial denitrification and anammox process in the future.

Toward rational management of patent ductus arteriosus: ductal disease staging and first line paracetamol.

AIMS: To study paracetamol (PCM) use as first line therapy for significant patent ductus arteriosus (sPDA) closure, stratified by echocardiography. METHODS: In this retrospective observational study, a prepublished score comprising PDA size and velocity, PDA:left pulmonary artery ratio, diastolic flow in main and LPA, LA:Ao ratio and left ventricular:aortic ratio were included for shunt severity. Successful closure was defined a priori as closure or ≥50% reduction in score. Comparisons were made between infants with sPDA who were treated and not treated. RESULTS: During November 2017-2018, 227 infants from 23 to 31+6 weeks' gestational age (GA) were admitted; 50 (22%) infants were diagnosed with PDA, 32 treated with PCM, overall treatment rate of 32/227 (14%). Successful therapy was noted in 23/32 (72%) and was higher when treated at ≤7 days (80 versus 68%, p = .68), in infants >26 weeks GA (62.5 versus 100%, p = .07) and BW >1000 g (65.4 versus 100%, p = .14). Univariate analysis noted statistical significance only for GA. Eighteen infants were managed conservatively. Treated infants had a lower GA and BW, higher composite ECHO score (14.4 ± 0.5 versus 19 ± 0.4, p < .001). CONCLUSIONS: Composite scoring helped reduce exposure, and focus more on infants with lower GA and BW with greater shunt severity.

High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity.

OBJECTIVE: Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. STUDY DESIGN: Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. RESULTS: In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. CONCLUSION: HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

pH-Responsive Micelles From an Oleic Acid Tail and Propionic Acid Heads Dendritic Amphiphile for the Delivery of Antibiotics.

The aim of this study was to synthesize a novel biocompatible pH-responsive oleic acid-based dendritic lipid amphiphile (OLA-SPDA) which self-assembled into stable micelles (OLA-SPDA -micelles) with a relatively low critical micelle concentration (CMC) of 5.6 × 10-6 M. The formulated micelles had particle size, polydispersity index (PDI) and zeta potential (ZP) of 84.16 ± 0.184 nm, 0.199 ± 0.011 and -42.6 ± 1.98 mV, respectively, at pH 7.4. The vancomycin (VCM) encapsulation efficiency was 78.80 ± 3.26%. The micelles demonstrated pH-responsiveness with an increase in particle size to 141.1 ± 0.0707 nm and a much faster release profile at pH 6.0, as compared to pH 7.4. The minimum inhibitory concentration (MIC) of VCM-OLA-SPDA-micelle against methicillin-resistant staphylococcus aureus (MRSA) was 8-fold lower compared to bare VCM, and the formulation had a 4-fold lower MIC at pH 6.0 when compared to the formulation's MIC at pH 7.4. MRSA viability assay showed the micelles had a percentage killing of 93.39% when compared bare-VCM (58.21%) at the same MIC (0.98 µg/mL). In vivo mice (BALB/c) skin infection models showed an 8-fold reduction in MRSA burden after treatment with VCM-OLA-SPDA-micelles when compared with bare VCM. The above results suggest that pH-responsive VCM-OLA-SPDA-micelles has the potential to be an effective carrier to enhance therapeutic outcomes against infections characterised by low pH.