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Background: This study provides a comprehensive analysis of Acinetobacter baumannii in aquatic environments and fish microbiota by integrating culture-dependent methods, 16S metagenomics, and antibiotic resistance profiling., Methods: A total of 83 A. baumannii isolates were recovered using culture-dependent methods from intra-hospital infections (IHI) and wastewater (WW) and surface water (SW) samples from two southern Romanian cities in August 2022. The antibiotic susceptibility was screened using disc diffusion, microdilution, PCR, and Whole Genome Sequencing assays., Results: The highest microbial load in the analyzed samples was found in Glina, Bucharest, for both WW and SW samples across all investigated phenotypes. For Bucharest isolates, the resistance levels corresponded to fluoroquinolones > aminoglycosides > β-lactam antibiotics. In contrast, A. baumannii from upstream SW samples in Târgoviște showed the highest resistance to aminoglycosides. The bla OXA-23 gene was frequently detected in IHI, WW, and SW isolates in Bucharest, but was absent in Târgoviște. Molecular phylogeny revealed the presence of ST10 in Târgoviște isolates and ST2 in Bucharest isolates, while other minor STs were not specifically correlated with a sampling point. Using 16S rRNA sequencing, significant differences in microbial populations between the two locations was identified. The low abundance of Alphaproteobacteria and Actinobacteria in both locations suggests environmental pressures or contamination events., Conclusions: These findings indicate significant fecal contamination and potential public health risks, emphasizing the need for improved water quality monitoring and management.

New discoveries in catalysis by earth-abundant materials can be guided by leveraging knowledge across two sub-disciplines of heterogeneous catalysis: electrocatalysis and thermocatalysis. Cobalt sulfide has been reported to be a highly active electrocatalyst for the oxygen evolution reaction (OER). Under these oxidative conditions, cobalt sulfide forms oxidized surfaces that outperform directly prepared cobalt oxide in OER catalysis. We postulated that the catalytic activity of oxidized cobalt sulfide for OER could reflect a more general ability to catalyze O-transfer reactions. Herein, we show that cobalt sulfide (CoS x ) indeed catalyzes the epoxidation of cyclooctene, a thermal O-transfer reaction. Similarly to OER, the surface-oxidized CoS x formed under reaction conditions outperformed the directly prepared cobalt oxide, hydroxide, and oxyhydroxide for epoxidation catalysis. Another notable phenomenological parallel to OER was revealed by the electron paramagnetic resonance (EPR) analysis of all spent Co-based catalysts that showed significant structural changes and the formation of paramagnetic Co(ii) and Co(iv) species. Mechanistic investigations suggest that a higher density of Co(ii) and/or an easier formation of high-valent Co species in the case of surface-oxidized cobalt sulfide is responsible for its high activity as an epoxidation catalyst. Our results provide important insight into the surface chemistry of Co-based catalysts and show the potential of oxidized CoS x as an earth-abundant catalyst for O-transfer reactivity beyond OER. This work highlights the utility of bridging electrocatalysis and thermocatalysis for the development of more sustainable chemical processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A major shortcoming associated with the application of enzymes in drug synergism originates from the lack of site-specific, multifunctional nanomedicine. This study introduces catalytic nanocompartments (CNCs) made of a mixture of PDMS- b -PMOXA diblock copolymers, decorated with glycooligomer tethers comprising eight mannose-containing repeating units and coencapsulating two enzymes, providing multifunctionality by their in situ parallel reactions. Beta-glucuronidase (GUS) serves for local reactivation of the drug hymecromone, while glucose oxidase (GOx) induces cell starvation through glucose depletion and generation of the cytotoxic H 2 O 2 . The insertion of the pore-forming peptide, melittin, facilitates diffusion of substrates and products through the membranes. Increased cell-specific internalization of the CNCs results in a substantial decrease in HepG2 cell viability after 24 h, attributed to simultaneous production of hymecromone and H 2 O 2 . Such parallel enzymatic reactions taking place in nanocompartments pave the way to achieve efficient combinatorial cancer therapy by enabling localized drug production along with reactive oxygen species (ROS) elevation.

To address the research hypothesis that the Alberta Infant Motor Scale (AIMS) completed following complex cardiac surgery (CCS) is a useful outcomes measure this study determined: (1) AIMS scores at age 8 months after CCS; (2) predictive validity of AIMS at 8 months for Bayley Scales of Infant and Toddler Development-III Gross Motor-scaled scores (GMSS) and diagnosis of cerebral palsy (CP) at 21 months; and (3) predictive demographic and surgical variables of AIMS scores. A prospective cohort study of 250/271 (92.3%) surviving children from Northern Alberta (born 2009-2020) who had CCS at age < 6 months determined AIMS scores at age mean (SD) 8.6 (2.4) and the GMSS at 21.9 (3.8) months. Gross motor delay was defined as AIMS < 5th percentile and GMSS as < 4 (-2SD). Predictions using multiple logistic regressions were expressed as Odds Ratios (OR) and 95% Confidence Interval (CI). Of children, 100/250 (40%) had AIMS < 5th predicting GMSS < 4 (n = 43); sensitivity, specificity, positive, and negative predictive values were 88%, 71%, 40%, and 97%. Hospitalization days were independently associated with AIMS < 5th, OR 1.02 (95% CI 1.007, 1.032; p = 0.005). Excluding hospital days, ventilation days independently predicted AIMS < 5th, OR 1.08 (95% CI 1.038, 1.125, p < 0.001. Gross motor delay determine by AIMS scores of < 5th percentile occurred in 40% of survivors with good prediction of continued delay. Delay determined by AIMS was predicted by longer hospitalization and ventilation; further investigations about the causes are required. AIMS results provide opportunity for early motor intervention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To determine whether gross motor scores of toddlers after complex cardiac surgery were different from fine motor scores and were adequately represented by motor composite scores and, whether acute care predictors and chronic childhood health markers of gross motor scores differed from those of fine motor., Methods: This prospective inception-cohort outcomes study included 171 toddlers after complex cardiac surgery with cardiopulmonary bypass at age <6 months, born in Northern Alberta from 2009 to 2019, and without known chromosomal abnormalities. At a mean (standard deviation) age of 21.7 (3.7) months, the Bayley Scales of Infant and Toddler Development-III determined motor composite and scaled scores (normative values, 100 (15), 10 (3), respectively). The same variables from surgery and assessment were analysed using multivariate regression to predict gross and fine motor scores; results expressed as effect size (95% confidence interval) with % variance., Results: Composite, fine, and gross motor scores were 89.7 (14.2), 9.4 (2.5), and 7.2 (2.7), respectively. Predictive variables accounted for 21.2% of the variance for fine motor, and 36.9% for gross motor. Multivariate analysis for gross motor scores included toddlers need for cardiac medication, effect size (95% confidence interval) -0.801 (-1.62, -0.02), gastrostomy, -1.35 (-2.39, -0.319), and single ventricle, -0.93 (-1.71, -0.15). These same variables did not predict fine motor scores., Conclusion: Gross motor skills commonly were lower than fine motor skills for toddlers after complex cardiac surgery. Predictors for gross motor scores differed from fine motor scores. Separate reporting of gross motor scores could lead to improved identification of predictors of delay and to optimised early intervention.

Polymeric nano- and microscale materials bear significant potential in manifold applications related to biomedicine. This is owed not only to the large chemical diversity of the constituent polymers, but also to the various morphologies these materials can achieve, ranging from simple particles to intricate self-assembled structures. Modern synthetic polymer chemistry permits the tuning of many physicochemical parameters affecting the behavior of polymeric nano- and microscale materials in the biological context. In this Perspective, an overview of the synthetic principles underlying the modern preparation of these materials is provided, aiming to demonstrate how advances in and ingenious implementations of polymer chemistry fuel a range of applications, both present and prospective., (© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Tailor-made poly(vinyl alcohol)-b-poly(styrene) copolymers (PVA-b-PS) for separation membranes are synthesized by the combination of reversible-deactivation radical polymerization techniques. The special features of these di-block copolymers are the high molecular weight (>70 kDa), the high PVA content (>80 wt%), and the good film-forming property. They are soluble only in hot dimethyl sulfoxide, but by the "solvent-switch" technique, they self-assemble in aqueous media to form micelles. When the self-assembled micelles are cast on a porous substrate, thin-film membranes with higher water permeance than that of PVA homopolymer are obtained. Thus, by using these tailor-made PVA-b-PS copolymers, it is demonstrated that chemical cross-linkers and acid catalysts can no longer be needed to produce PVA membranes, since the PS nanodomains within the PVA matrix act as cross-linking points. Lastly, subsequent thermal annealing of the thin film enhances the membrane selectivity due to the improved microphase separation., (© 2023 Wiley-VCH GmbH.)

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b -PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Major congenital heart disease (CHD) is associated with impaired neurodevelopment (ND), partly from prenatal insults. In this study we explore associations between 2nd and 3rd trimester umbilical (UA) and middle cerebral artery (MCA) pulsatility index (PI = systolic-diastolic velocities/mean velocity) in fetuses with major CHD and 2-year ND and growth outcomes. Eligible patients included those with a prenatal diagnosis of CHD from 2007 to 2017 without a genetic syndrome who underwent previously defined cardiac surgeries and 2-year biometric and ND assessments in our program. UA and MCA-PI Z-scores at fetal echocardiography were examined for relationships with 2-year Bayley Scales of Infant and Toddler Development and biometric Z-scores. Data from 147 children was analyzed. Second and 3rd trimester fetal echocardiograms were performed at 22.4 ± 3.7 and 34.7 ± 2.9 weeks (mean ± SD), respectively. Multivariable regression analysis showed an inverse relationship between 3rd trimester UA-PI for all CHD and cognitive - 1.98 (- 3.37, - 0.59), motor - 2.57 (- 4.15, - 0.99), and language - 1.67 (- 3.3, - 0.03) (effect size and 95th confidence interval) ND domains (p < 0.05), with the strongest relationships in the single ventricle and hypoplastic left heart syndrome subgroups. No association was found for 2nd trimester UA-PI or any trimester MCA-PI and ND or between UA or MCA-PI and 2-year growth parameters. Increased 3rd trimester UA-PI, reflecting an altered late gestation fetoplacental circulation, relates to worse 2-year ND in all domains., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: In infants with single-ventricle congenital heart disease, prematurity and low weight at the time of the Norwood operation are risk factors for mortality. Reports assessing outcomes (including neurodevelopment) post Norwood palliation in infants ≤2.5 kg are limited., Methods: All infants who underwent a Norwood-Sano procedure between 2004 and 2019 were identified. Infants ≤2.5 kg at the time of the operation (cases) were matched 3:1 with infants >3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and perioperative characteristics, survival, and functional and neurodevelopmental outcomes were compared., Results: Twenty-seven cases (mean ± standard deviation: weight 2.2 ± 0.3 kg and age 15.6 ± 14.1 days at surgery) and 81 comparisons (3.5 ± 0.4 kg and age 10.9 ± 7.9 days at surgery) were identified. Post-Norwood, cases had a longer time to lactate ≤2 mmol/L (33.1 ± 27.5 vs 17.9 ± 12.2 hours, P  < .001), longer duration of ventilation (30.5 ± 24.5 vs 18.6 ± 17.5 days, P  = .005), greater need for dialysis (48.1% vs 19.8%, P  = .007), and greater need for extracorporeal membrane oxygenation support (29.6% vs 12.3%, P  = .004). Cases had significantly greater postoperative (in-hospital) (25.9% vs 1.2%, P  < .001) and 2-year (59.2% vs 11.1%, P  < .001) mortality. Neurodevelopmental assessment showed the following for cases versus comparisons, respectively: cognitive delay (18.2% vs 7.9%, P  = .272), language delay (18.2% vs 11.1%, P  = .505), and motor delay (27.3% vs 14.3%, P  = .013)., Conclusions: Infants ≤2.5 kg at Norwood-Sano palliation have significantly increased postoperative morbidity and mortality up to 2-year follow-up. Neurodevelopmental motor outcomes were worse in these infants. Additional studies are warranted to assess the outcome of alternative medical and interventional treatment plans in this patient population., (© 2023 The Author(s).)

Cell-derived vesicles retain the cytoplasm and much of the native cell membrane composition. Therefore, they are attractive for investigations of membrane biophysics, drug delivery systems, and complex molecular factories. However, their fragility and aggregation limit their applications. Here, the mechanical properties and stability of giant plasma membrane vesicles (GPMVs) are enhanced by decorating them with a specifically designed diblock copolymer, cholesteryl-poly[2-aminoethyl methacrylate-b-poly(ethylene glycol) methyl ether acrylate]. When cross-linked, this polymer brush enhances the stability of the GPMVs. Furthermore, the pH-responsiveness of the copolymer layer allows for a controlled cargo loading/release, which may enable various bioapplications. Importantly, the cross-linked-copolymer GPMVs are not cytotoxic and preserve in vitro membrane integrity and functionality. This effective strategy to equip the cell-derived vesicles with stimuli-responsive cross-linkable copolymers is expected to open a new route to the stabilization of natural membrane systems and overcome barriers to biomedical applications., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Polymer assemblies on the nanoscale represent a powerful toolbox for the design of theranostic systems when combined with both therapeutic compounds and diagnostic reporting ones. Here, recent advances in the design of theranostic systems for various diseases, containing-in their architecture-either polymers or polymer assemblies as one of the building blocks are presented. This review encompasses the general principles of polymer self-assembly, from the production of adequate copolymers up to supramolecular assemblies with theranostic functionality. Such polymer nanoassemblies can be further tailored through the incorporation of inorganic nanoparticles to endow them with multifunctional therapeutic and/or diagnostic features. Systems that change their architecture or properties in the presence of stimuli are selected, as responsivity to changes in the environment is a key factor for enhancing efficiency. Such theranostic systems are based on the intrinsic properties of copolymers or one of the other components. In addition, systems with a more complex architecture, such as multicompartments, are presented. Selected systems indicate the advantages of such theranostic approaches and provide a basis for further developments in the field., (© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

The pesticide pollution of surface water and wastewater has been recognized as a major worldwide concern due to their persistence in the aquatic environment and the potential adverse effects on human, flora, and fauna health. Apart from pesticides, bio-contamination with various bacterial populations leads to waterborne diseases. Hence, it becomes vital to remove the above-mentioned pollutants from water using a suitable process. Consequently, our study emphasized the potential benefits of a highly porous, chemically cross-linked 3D chitosan (CSGA) cryogel in the removal of pesticides and bacteria. The CSGA sponges were prepared using a facile and cost-effective approach that consisted of a three-step cryogenic process: (i) freezing at -18 °C, (ii) storage in a frozen state for a certain period, and (iii) thawing at room temperature. Batch adsorption experiments were performed under different environments, where the effects of several parameters, such as pH, contact time, and initial pollutant concentration were evaluated to identify the appropriate adsorption conditions for maximum pesticide removal. The CSGA-based cryogel sponges exhibited a theoretical maximum adsorption capacity of 160.82 mg g -1 for the Fastac 10EC pesticide and very good recyclability at room temperature. In addition, the antibacterial activities of these sponges were also investigated against various bacterial pathogens. The rates of killing Escherichia coli , Listeria monocytogenes , and Staphylococcus aureus were close to 82%, 100%, and 99%, respectively. These results demonstrated that CSGA cryogels could be efficiently used in water remediation and find applications in the removal of pesticides and disinfection.

Glucuronidation is a metabolic pathway that inactivates many drugs including hymecromone. Adverse effects of glucuronide metabolites include a reduction of half-life circulation times and rapid elimination from the body. Herein, we developed synthetic catalytic nanocompartments able to cleave the glucuronide moiety from the metabolized form of hymecromone in order to convert it to the active drug. By shielding enzymes from their surroundings, catalytic nanocompartments favor prolonged activity and lower immunogenicity as key aspects to improve the therapeutic solution. The catalytic nanocompartments (CNCs) consist of self-assembled poly(dimethylsiloxane)- block -poly(2-methyl-2-oxazoline) diblock copolymer polymersomes encapsulating β-glucuronidase. Insertion of melittin in the synthetic membrane of these polymersomes provided pores for the diffusion of the hydrophilic hymecromone-glucuronide conjugate to the compartment inside where the encapsulated β-glucuronidase catalyzed its conversion to hymecromone. Our system successfully produced hymecromone from its glucuronide conjugate in both phosphate buffered solution and cell culture medium. CNCs were non-cytotoxic when incubated with HepG2 cells. After being taken up by cells, CNCs produced the drug in situ over 24 hours. Such catalytic platforms, which locally revert a drug metabolite into its active form, open new avenues in the design of therapeutics that aim at prolonging the residence time of a drug.

Precisely timed initiation of reactions and stability of the catalysts are fundamental in catalysis. We introduce here an efficient closing-opening method for nanocompartments that contain sensitive catalysts and so achieve a controlled and extended catalytic activity. We developed a chemistry-oriented approach for modifying a pore-forming membrane protein which allows for a stimuli-responsive pore opening within the membrane of polymeric nanocompartments. We synthesized a diol-containing linker that selectively binds to the pores, blocking them completely. In the presence of an external stimulus (periodate), the linker is cleaved allowing the diffusion of substrate through the pores to the nanocompartment interior where it sets off the in situ enzymatic reaction. Besides the precise initiation of catalytic activity by opening of the pores, oxidation by periodate guarantees the cleavage of the linker under mild conditions. Accordingly, this kind of responsive nanocompartment lends itself to harboring a large variety of sensitive catalysts such as proteins and enzymes.

Herein, we entrapped Thymus vulgaris essential oil (EO) within the physically cross-linked sponge-like architecture of cryogels by ice template-assisted freeze-drying. Their 3D cryogenically-structured network was built through hydrogen bonding formed by blending two naturally-derived polysaccharides, chitosan and dextrin. The embedment of EOs within the cryogel matrix generates porous films with an increased elasticity that allows their fast shape recovery after full compression. Thus, the swollen EOs-loaded cryogel films exhibited an elastic modulus of 3.00 MPa, which is more than 40 times higher than that of polysaccharide films without EOs (an elastic modulus of only 0.07 MPa). In addition, the encapsulation of bioactive compounds endows the bio-based films with both antioxidant and antifungal properties, showing a radical scavenging activity of 65% and a zone inhibition diameter of 40 mm for Candida parapsilosis fungi. Our results recommend the entrapment of EOs into bio-based cryogel carriers as a straightforward approach to provide 'green' polysaccharide-based films having both improved physicochemical properties and remarkable antifungal activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Children with congenital heart disease (CHD) are at risk of adverse long-term neurodevelopmental outcomes, believed to be, in part, secondary to prenatal insults. Placental pathology and altered fetal middle cerebral arterial (MCA) flow suggestive of brain sparing have been documented in fetal CHD. In the present study we investigated the relationship between MCA and umbilical arterial (UA) flow patterns in fetal transposition of the great arteries (d-TGA) and hypoplastic left heart syndrome (HLHS) and growth and 2-year neurodevelopmental outcomes., Methods: We included children with d-TGA and HLHS who had third-trimester fetal echocardiograms between 2004 and 2014, at which time umbilical artery (UA) and MCA pulsatility indices (PIs) were measured, and who underwent 2-year growth and neurodevelopmental assessments., Results: We identified 24 children with d-TGA and 36 with HLHS. Mean age at fetal echocardiography was 33.8 ± 3.5 weeks. At 2-year follow-up, head circumference z score (standard deviation [SD]) was -0.09 (1.07) and 0.17 (1.7) for the d-TGA and HLHS groups, respectively. Bayley III mean (SD) cognitive, language, and motor scores were 97.7 (10.8), 94.7 (13.4), and 98.6 (8.6) for the d-TGA group and 90.3 (13.9), 87.2 (17.5), and 85.3 (16.2) for the HLHS group. On multivariate linear regression analysis, UA-PI was associated (effect sizes [95% CI]) with length (-1.45 [-2.7, -0.17], P = 0.027), weight (-1.46 [-2.6 to -0.30], P = 0.015) and cognitive scores (-14.86 [-29.95 to 0.23], P = 0.05) at 2 years of age. MCA PI showed no statistically significant correlation., Conclusions: In fetal d-TGA and HLHS, a higher UA-PI in the third trimester, suggestive of placental insufficiency-but not MCA-PI-is associated with worse 2-year growth and neurodevelopment., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Compared with those born at term gestation, infants with complex congenital heart defects (CCHD) who were delivered before 37 weeks gestational age and received neonatal open-heart surgery (OHS) have poorer neurodevelopmental outcomes in early childhood. We aimed to describe the growth, disability, functional, and neurodevelopmental outcomes in early childhood of preterm infants with CCHD after neonatal OHS. Prediction models were evaluated at various timepoints during hospitalization which could be useful in the management of these infants. Study Design: We studied all preterm infants with CCHD who received OHS within 6 weeks of corrected age between 1996 and 2016. The Western Canadian Complex Pediatric Therapies Follow-up Program completed multidisciplinary comprehensive neurodevelopmental assessments at 2-year corrected age at the referral-site follow-up clinics. We collected demographic and acute-care clinical data, standardized age-appropriate outcome measures including physical growth with calculated z- scores; disabilities including cerebral palsy, visual impairment, permanent hearing loss; adaptive function (Adaptive Behavior Assessment System-II); and cognitive, language, and motor skills (Bayley Scales of Infant and Toddler Development-III). Multiple variable logistic or linear regressions determined predictors displayed as Odds Ratio (OR) or Effect Size (ES) with 95% confidence intervals. Results: Of 115 preterm infants (34 ± 2 weeks gestation, 2,339 ± 637 g, 64% males) with CCHD and OHS, there were 11(10%) deaths before first discharge and 21(18%) deaths by 2-years. Seven (6%) neonates had cerebral injuries, 7 had necrotizing enterocolitis; none had retinopathy of prematurity. Among 94 survivors, 9% had cerebral palsy and 6% had permanent hearing loss, with worse outcomes in those with syndromic diagnoses. Significant predictors of mortality included birth weight z- score [OR 0.28(0.11,0.72), P = 0.008], single-ventricle anatomy [OR 5.92(1.31,26.80), P = 0.021], post-operative ventilation days [OR 1.06(1.02,1.09), P = 0.007], and cardiopulmonary resuscitation [OR 11.58 (1.97,68.24), P = 0.007]; for adverse functional outcome in those without syndromic diagnoses, birth weight 2,000-2,499 g [ES -11.60(-18.67, -4.53), P = 0.002], post-conceptual age [ES -0.11(-0.22,0.00), P = 0.044], post-operative lowest pH [ES 6.75(1.25,12.25), P = 0.017], and sepsis [ES -9.70(-17.74, -1.66), P = 0.050]. Conclusions: Our findings suggest preterm neonates with CCHD and early OHS had significant mortality and morbidity at 2-years and were at risk for cerebral palsy and adverse neurodevelopment. This information may be important for management, parental counseling and the decision-making process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheung, Hajihosseini, Dinu, Switzer, Joffe, Bond and Robertson.)

Objective: To demonstrate feasibility of a music medicine intervention trial in pediatric intensive care and to obtain information on sedation and analgesia dose variation to plan a larger trial., Material and Methods: Pilot randomized controlled trial (RCT) was conducted at the Stollery Children's Hospital general and cardiac intensive care units (PICU/PCICU). The study included children 1 month to 16 years of age on mechanical ventilation and receiving sedation drugs. Patients were randomized in a 1:1:1 ratio to music, noise cancellation or control. The music group received classical music for 30 min three times/day using headphones. The noise cancellation group received the same intervention but with no music. The control group received usual care., Results: A total of 60 patients were included. Average enrollment rate was 4.8 patients/month, with a consent rate of 69%. Protocol adherence was achieved with patients receiving > 80% of the interventions. Overall mean (SD) daily Sedation Intensity Score was 52.4 (30.3) with a mean (SD) sedation frequency of 9.75 (7.21) PRN doses per day. There was a small but statistically significant decrease in heart rate at the beginning of the music intervention. There were no study related adverse events. Eighty-eight percent of the parents thought the headphones were comfortable; 73% described their child more settled during the intervention., Conclusions: This pilot RCT has demonstrated the feasibility of a music medicine intervention in critically ill children. The study has also provided the necessary information to plan a larger trial.

Enzymes are essential biocatalysts and very attractive as therapeutics. However, their functionality is strictly related to their stability, which is significantly affected by the environmental changes occurring during their usage or long-term storage. Therefore, maintaining the activity of enzymes is essential when they are exposed to high temperature during usage or when they are stored for extended periods of time. Here, we stabilize and protect enzymes by coencapsulating them with trehalose into polymersomes. The anhydrobiotic disaccharide preserved up to about 81% of the enzyme's original activity when laccase/trehalose-loaded nanoreactors were kept desiccated for 2 months at room temperature and 75% of its activity when heated at 50 °C for 3 weeks. Moreover, the applicability of laccase/trehalose-loaded nanoreactors as catalysts for bleaching of the textile dyes orange G, toluidine blue O, and indigo was proven. Our results demonstrate the advantages of coencapsulating trehalose within polymersomes to stabilize enzymes in dehydrated state for extended periods of time, preserving their activity even when heated to elevated temperature.

Combining ion-imprinting technology with pH-dependent adsorptive features of acid- or salt-activated zeolites brings up the opportunity to develop composite polymer materials with 'desired' sorption properties and performances. In this respect, we present here Co 2+ -imprinted composite cryo-beads with switching on/off selectivity towards the template ions, engineered by selecting the appropriate zeolite-treatment conditions and/or controlling the initial sorption pH values. Co 2+ chelating efficiency of all cryo-beads was investigated either at pH 4 or 6 depending on zeolite conditioning strategy. The maximum sorption capacity values of ion-imprinted cryo-beads were from about 5 up to 7 times higher compared with those of non-imprinted ones. Under competitive conditions (Cu 2+ , Ni 2+ , Fe 2+ and Cd 2+ ions), the change of pH value from 4 to 6 resulted in a remarkable quenching of Co 2+ selectivity generated by the zeolite shift from the H + -form to the Na + -form. The presence of zeolites within cryogel matrix generated composites with outstanding elasticity that allows the instant recovery of gels after full compression. These results indicate that the cryogel-type composites can be successfully re-used in separation processes for several times without losing their features., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: There is limited information about HRQL after pediatric heart transplantation at a young age., Methods: Prospective follow-up study of children who received a heart transplant at age ≤4 years. HRQL was assessed using the PedsQL TM 4.0 at age 4.5 years. This cohort was compared with healthy children, children with CHD, and with chronic conditions. Peri-operative factors associated with HRQL were also explored., Results: Of 66 eligible patients, 15 (23%) died prior to the HRQL assessment and 2 (3%) were lost to follow-up, leaving 49 patients. Indication for transplantation was CHD in 27 (55%) and CMP in 22 (45%). Median age (IQR) at transplant was 9 (5-31) months. HRQL was significantly lower in transplanted children compared to population norms (65.3 vs 87.3, P < .0001), children with chronic conditions (65.3 vs 76.1, P = .001), and children with CHD (65.3 vs 81.1, P < .0001). Transplanted children with CHD had lower HRQL than those with a prior diagnosis of CMP (59.5 vs 72.5, P-value = .020). Higher creatinine pretransplant and higher lactate post-operatively were associated with lower HRQL., Conclusion: Children after heart transplant had significantly lower HRQL, as reported by their parents, than the normative population, children with chronic conditions, and children with CHD., (© 2020 Wiley Periodicals LLC.)

Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications.

Self-organized nano- and microscale polymer compartments such as polymersomes, giant unilamellar vesicles (GUVs), polyion complex vesicles (PICsomes) and layer-by-layer (LbL) capsules have increasing potential in many sensing applications. Besides modifying the physicochemical properties of the corresponding polymer building blocks, the versatility of these compartments can be markedly expanded by biomolecules that endow the nanomaterials with specific molecular and cellular functions. In this review, we focus on polymer-based compartments that preserve their structure, and highlight the key role they play in the field of medical diagnostics: first, the self-assembling abilities that result in preferred architectures are presented for a broad range of polymers. In the following, we describe different strategies for sensing disease-related signals (pH-change, reductive conditions, and presence of ions or biomolecules) by polymer compartments that exhibit stimuli-responsiveness. In particular, we distinguish between the stimulus-sensitivity contributed by the polymer itself or by additional compounds embedded in the compartments in different sensing systems. We then address necessary properties of sensing polymeric compartments, such as the enhancement of their stability and biocompatibility, or the targeting ability, that open up new perspectives for diagnostic applications.

Background: We aimed to describe school-entry age neurocognitive, functional, and HRQL outcomes and their predictors after liver transplant done at age <6 years., Methods: A prospective cohort of all (n = 69) children surviving liver transplant from 1999 to 2014 were assessed at age 55.4 (SD 7.2) months and 38.6 (12.4) months after transplant. Assessment included: the Wechsler Preschool and Primary Scales of Intelligence, Beery-Buktenica Developmental Test of VMI, Adaptive Behavior Assessment System caregiver-completed questionnaire, and PedsQL 4.0 Generic Core Scales. Univariate and multiple linear regression determined predictors of outcomes at P < .05., Results: Neurocognitive and functional outcomes were on average within 1 SD of population norms, although shifted to the left (P ≤ .03), with more patients than expected having scores >2 (3.7-5.9 times more, P ≤ .007) SD below population norms. Total and Summary HRQL scores were statistically significantly lower than the healthy normative population (P ≤ .02) and a congenital heart disease group (P ≤ .02), but similar to children with other chronic health conditions; differences often exceeded the MCID and were lowest in the School functioning domain. There were few predictors on multiple linear regressions, and we could not confirm previous studies that suggested various inconsistent predictors of outcomes. Neurocognitive and functional outcomes scores were highly correlated with HRQL scores except for the School functioning domain, but did not fully explain them., Conclusions: Long-term follow-up of this vulnerable population is important in order to facilitate support for the patient and family, and early intervention for any difficulties identified., (© 2019 Wiley Periodicals, Inc.)

Background: Stress induced by pain and anxiety is common in pediatric intensive care unit (PICU) patients. Sedation/analgesia in PICU is usually achieved through various analgesics and sedatives. Excessive use of these drugs can put patients at risk for hemodynamic/respiratory instability, prolonged ventilation, withdrawal, delirium, and critical illness polyneuromyopathy.The use of non-pharmacologic interventions has been recommended by sedation guidelines. However, non-pharmacological measures in PICU, including music and noise reduction, have been inadequately studied., Methods: The Music Use for Sedation in Critically ill Children (MUSiCC trial) pilot study is an investigator-initiated, three-arm, randomized controlled trial (RCT) on the use of music for sedation in PICU. The main goal of the study is to demonstrate feasibility of a music trial in PICU and to obtain the necessary information to plan a larger trial. The study compares music versus noise cancelation versus control in sedated and mechanically ventilated children admitted to PICU. In the music group, children receive the music (modified classical music) three times a day for 30 min at a time. Music is delivered with noise cancelation headphones. The noise cancelation group receives the same intervention but with a no music (sham playlist). The control group receives usual care with no specific intervention. Children remain in the study until extubation or a maximum of 7 days. The primary outcomes of the study are feasibility and sedation/analgesia requirements. Secondary outcomes include change in vital signs before and during the intervention, ICU delirium, and adverse effects related to the intervention. The estimated sample size is 20 subjects per group for a total of 60 children., Discussion: Despite being recommended by current guidelines, evidence to support the use of music in PICU is lacking. Music has the potential to reduce sedation requirements and their negative side effects. This pilot RCT will demonstrate feasibility and provide the necessary information to plan a larger trial focusing on the effectiveness of the intervention., Trial Registration: The study was registered at ClinicalTrials.gov (NCT03497559) on April 13, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Background: Urea cycle disorders (UCD) and organic acid disorders classically present in the neonatal period. In those who survive, developmental delay is common with continued risk of regression. Liver transplantation improves the biochemical abnormality and patient survival is good. We report the neurocognitive and functional outcomes post-transplant for nine UCD, three maple syrup urine disease, and one propionic acidemia patient., Methods: Thirteen inborn errors of metabolism (IEM) patients were individually one-to-two matched to 26 non-IEM patients. All patients received liver transplant. Wilcoxon rank sum test was used to compare full-scale intelligence-quotient (FSIQ) and Adaptive Behavior Assessment System-II General Adaptive Composite (GAC) at age 4.5 years. Dichotomous outcomes were reported as percentages., Results: FSIQ and GAC median [IQR] was 75 [54, 82.5] and 62.0 [47.5, 83] in IEM compared with 94.5 [79.8, 103.5] and 88.0 [74.3, 97.5] in matched patients ( P -value <.001), respectively. Of IEM patients, 6 (46%) had intellectual disability (FSIQ and GAC <70), 5 (39%) had autism spectrum disorder, and 1/13 (8%) had cerebral palsy, compared to 1/26 (4%), 0, 0, and 0% of matched patients, respectively. In the subgroup of nine with UCDs, FSIQ (64[54, 79]), and GAC (56[45, 75]) were lower than matched patients (100.5 [98.5, 101] and 95 [86.5, 99.5]), P = .005 and .003, respectively., Conclusion: This study evaluated FSIQ and GAC at age 4.5 years through a case-comparison between IEM and matched non-IEM patients post-liver transplantation. The neurocognitive and functional outcomes remained poor in IEM patients, particularly in UCD. This information should be included when counselling parents regarding post-transplant outcome., Competing Interests: Shailly Jain‐Ghai has participated in advisory boards and received honoraria and travel grants from Sanofi‐Genzyme, Horizon Pharmaceutical, Amicus, BioMarin and Shire. Ari R Joffe, Gwen Y Bond, Komudi Siriwardena, Alicia Chan, Jason Y K Yap, Morteza Hajihosseini, Irina A Dinu, Bryan V Acton and Charlene MT Robertson have no conflicts of interest to declare., (© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Copper, nickel, zinc, chromium, and iron ions are the prevailing contaminants in the aqueous effluents resulting from the photo-etching industry. In this context, we investigate here the metal ion sorption performance of an ion-imprinted cryogel (IIC), consisting of low-cost materials coming from renewable resources, towards multi-component metal ion solutions. The IIC sorbent, which is based on a chitosan matrix embedding a natural zeolite, was synthesized using a straightforward strategy by coupling copper-imprinting and unidirectional ice-templating methods. As consequence, the 1D-orientation and the interconnectivity of flow-channels sustain the fast metal ion diffusion within the IIC anisotropic structure. The removal efficiency of IIC sorbent reached 50% after 30 min, and the sorption equilibrium was attained within 150 min. For assessing the successful formation of imprinted cavities with well-defined sizes controlled by the radius of copper ions used as template, selectivity studies were performed on binary, ternary, and five-component synthetic mixtures. The efficiency of IIC as sorbent was further evaluated on real-life aqueous effluents discharged from photo-etching processes; thus, an IIC dosage of 6 g L -1 was found to remove 98.89% of Cu 2+ , 94.56% of Fe 3+ , 91.67% of Ni 2+ , 92.24% of Zn 2+ , and 82.76% of Cr 3+ ions from this type of industrial wastewaters., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Currently, biosorption is considered a leading-edge environmentally-friendly method for the low-cost remediation of wastewaters contaminated with metal ions. However, the safe disposal of metal-loaded biosorbents is still a challenging issue. In this context, our major objective was to explore the possibility of "waste minimization" by reusing the metal-loaded biosorbents in further environmental applications, particularly into the oxidative catalysis of dyes. Thus, the decolourisation efficiency (DE) of Methyl Orange (MO) in aqueous solutions under ambient light using copper-imprinted chitosan-based composites in comparison to non-imprinted ones was investigated in this work. The MO degradation was established first in the absence of any co-catalyst, when a DE value of 95.3% was achieved by the ion-imprinted catalysts within 360 min of reaction, compared to only 67.4% attained by the non-imprinted ones. Under Fenton-like conditions, the apparent degradation rate constant was seventy times higher, the DE increasing within 40 min to about 98.6%, and 70.5% respectively, whereas the content of co-catalyst (H 2 O 2 ) was significantly lowered compared to other reported studies. The straightforward preparation of copper-loaded composites, along with their excellent stability and high efficiency even after four consecutive reaction runs support our ion-imprinted systems as potential catalysts for dye removal by oxidative decolourisation treatments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To reduce bilateral delayed-onset progressive sensory permanent hearing loss using a systems-wide quality improvement project with adherence to best practice for the administration of furosemide., Design: Prospective cohort study with regular audiologic follow-up assessment of survivors both before and after a 2007-2008 quality improvement practice change., Setting: The referral center in Western Canada for complex cardiac surgery, with comprehensive multidisciplinary follow-up by the Complex Pediatric Therapies Follow-up Program., Patients: All consecutive patients having single-ventricle palliative cardiac surgery at age 6 weeks old or younger., Interventions: A 2007-2008 quality improvement practice change consisted of a Parenteral Drug Monograph revision indicating slow IV administration of furosemide, an educational program, and an evaluation., Measurements and Main Results: The outcome measure was the prevalence of permanent hearing loss by 4 years old. Firth multiple logistic regression compared pre (1996-2008) to post (2008-2012) practice change occurrence of permanent hearing loss, adjusting for confounding variables, including all hospital days, extracorporeal membrane oxygenation, cardiopulmonary bypass time, age at first surgery, dialysis, and sepsis. From 1996 to 2012, 259 infants had single-ventricle palliative surgery at age 6 weeks old or younger, with 173 (64%) surviving to age 4 years. Of survivors, 106 (61%) were male, age at surgery was 11.6 days (9.0 d), and total hospitalization days by age 4 years were 64 (42); 18 (10%) had cardiopulmonary resuscitation and 38 (22%) had sepsis at any time. All 173 (100%) had 4-year follow-up. Pre- to postpractice change permanent hearing loss dropped from 17/100 (17%) to 0/73 (0%) of survivors. On Firth multiple logistic regression, the only variable statistically associated with permanent hearing loss was the pre- to postpractice change time period (odds ratio, 0.03; 95% CI, 0-0.35; p = 0.001)., Conclusions: A practice change to ensure slow IV administration of furosemide eliminated permanent hearing loss. Centers caring for critically ill infants, particularly those with single-ventricle anatomy or hypoxia, should review their drug administration guidelines and adhere to best practice for administration of IV furosemide.

Background: We aimed to determine predictors of, and outcomes after, veno-arterial extracorporeal membrane oxygenation instituted within 48 h after cardiac surgery (early ECMO) in young infants., Methods: Patients ≤ 6 weeks old having cardiac surgery from 2003 to 2012 were enrolled prospectively. Patients cannulated pre-operatively, intra-operatively, or ≥ 48 h post-operatively were excluded. Variables at p  ≤ 0.1 on univariate regression were entered into multiple logistic regression to predict early ECMO. Early-ECMO cases were matched 1:2 for six demographic variables, and death by age 2 years old (determined using conditional logistic regression; presented as odds ratio (OR), 95% confidence interval (CI)) and General Adaptive Composite scores at age 2 years (determined using Wilcoxon rank sum) were compared; p  ≤ 0.05 was considered statistically significant., Results: Of 565 eligible patients over the 10-year period, 20 had early ECMO instituted at a mean (standard deviation) of 12.4 (11.4) h post-operatively, 10 of whom had extracorporeal cardiopulmonary resuscitation. Of early-ECMO patients, 8 (40%) were found to have residual anatomic defects requiring intervention with catheterization ( n  = 1) and/or surgery ( n  = 7). On multiple regression, the post-operative day 1 highest vasoactive-inotrope score (OR 1.02; 95%CI 1.06,1.08; p  < 0.001), highest lactate (OR 1.2; 95%CI 1.06,1.35; p  = 0.003), and lowest base deficit (OR 0.82; 95%CI 0.71,0.94; p  = 0.004), CPB time (OR 1.01; 95%CI 1.00,1.02; p  = 0.002), and single-ventricle anatomy (OR 5.35; 95%CI 1.66,17.31; p  = 0.005) were associated with early ECMO. Outcomes at 2 years old compared between early-ECMO and matched patients were mortality 11/20 (55%) vs 11/40 (28%) (OR 3.22, 95%CI 0.98,10.63; p  = 0.054) and General Adaptive Composite median 65 [interquartile range (IQR) 58, 81.5] in 9 survivors vs 93 [IQR 86.5, 102.5] in 29 survivors ( p  = 0.02)., Conclusions: The identified risk factors for, and outcomes after, having early ECMO may aid decision making in the acute period and confirm that neurodevelopmental follow-up for these children is necessary. The hypothesis that earlier institution of ECMO may improve long-term outcomes requires further study., Competing Interests: The Health Research Ethics Board of the University of Alberta approved this study [Pro00001030]. All parents/guardians signed an informed consent form.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Children requiring heart transplantation (HTx) for congenital heart disease (CHD) or failing anatomically normal hearts (CMP) face different challenges pre-HTx. We compared the neurocognitive capabilities in pre-school-age children receiving HTx for CHD vs CMP and determined factors predicting outcomes., Methods: Data were collected within a prospective multi-provincial project from children who underwent HTx ≤4 years of age between 1999 and 2011. At age 54 ± 3 months, we obtained scores from the Wechsler Preschool and Primary Scales of Intelligence for full-scale intelligence quotient (FSIQ) verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ), and from the Beery-Buktenica Developmental Test for visual-motor integration (VMI). Possible predictive factors were collected prospectively from transplant listing., Results: Of the 76 patients included in the study, 61 survived to assessment, 2 were lost to follow-up and 4 were excluded for genetic disorders or heart-lung transplant. The CHD patients (n = 32) had significantly more previous surgeries, more severe kidney injuries, more days on ventilator and in intensive care, broader human leukocyte antigen (HLA) sensitization, longer cardipulmonary bypass (CPB) times and higher inotropic scores than CMP patients (n = 23). Mean IQ scores for the HTx children were below population norms and significantly lower in children with CHD. Intellectual disability (FSIQ <70) was more common in the CHD group (p = 0.036). The lower VMI in CHD patients approached significance. Lower FSIQ and VMI were independently associated with higher pre-HTx creatinine and lactate, longer stay in intensive care and lower socioeconomic status., Conclusions: Children post-HTx showed IQ and VMI scores within the borderline to low-average range, with CHD children ranging significantly lower. Low scores are associated with a more difficult pre- and peri-transplant course. Careful follow-up is required to warrant early detection of deficits and introduction of interventions and supportive measures., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Functional abilities are needed for activities of daily living. In general, these skills expand with age. We hypothesised that, in contrast to what is normally expected, children surviving the Fontan may have deterioration of functional abilities, and that peri-Fontan stroke is associated with this deterioration. All children registered in the Western Canadian Complex Pediatric Therapies Follow-up Program who survived a Fontan operation in the period 1999-2016 were eligible for inclusion. At the age of 2 years (pre-Fontan) and 4.5 years (post-Fontan), the Adaptive Behavior Assessment System-II general adaptive composite score was determined (population mean: 100, standard deviation: 15). Deterioration of functional abilities was defined as ⩾1 standard deviation decrease in pre- to post-Fontan scores. Perioperative strokes were identified through chart review. Multivariable logistic regression analysis determined predictors of deterioration of functional abilities. Of 133 children, with a mean age at Fontan of 3.3 years (standard deviation 0.8) and 65% male, the mean (standard deviation) general adaptive composite score was 90.6 (17.5) at 2 years and 88.3 (19.1) at 4.5 years. After Fontan, deterioration of functional abilities occurred in 34 (26%) children, with a mean decline of 21.8 (7.1) points. Evidence of peri-Fontan stroke was found in 10 (29%) children who had deterioration of functional abilities. Peri-Fontan stroke (odds ratio 5.00 (95% CI 1.74, 14.36)) and older age at Fontan (odds ratio 1.67 (95% CI 1.02, 2.73)) predicted functional deterioration. The trajectory of functional abilities should be assessed in this population, as more than 25% experience deterioration. Efforts to prevent peri-Fontan stroke, and to complete the Fontan operation at an earlier age, may lead to reduction of this deterioration.

An original strategy is proposed here to design chitosan-based ion-imprinted cryo-composites (II-CCs) with pre-organized recognition sites and tailored porous structure by combining ion-imprinting and ice-templating techniques. The cryo-composites showed a tube-like porous morphology with interconnected parallel micro-channels, the distance between the channel walls being around 15 μm. Both the entrapment of a natural zeolite and the presence of carboxylate groups, generated by partial hydrolysis of amide moieties, led to II-CCs with controlled swelling ratios (25-40 g/g, depending on pH) and enhanced overall chelating efficiency (260 mg Cu 2+ /g composite). To point out the importance of introducing Cu 2+ recognition sites, sorption experiments using mixtures of Cu 2+ and other competing ions (Co 2+ , Ni 2+ , Zn 2+ or/and Pb 2+ ) were also carried out. The higher values of selectivity coefficients obtained for the II-CCs compared to those of non-imprinted ones highlight the remarkable potential of our sorbents for decontamination of wastewaters and recycling of Cu 2+ ions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To describe noise levels in a pediatric cardiac intensive care unit, and to determine the relationship between sound levels and patient sedation requirements., Materials and Methods: Prospective observational study at a pediatric cardiac intensive care unit (PCICU). Sound levels were measured continuously in slow A weighted decibels dB(A) with a sound level meter SoundEarPro® during a 4-week period. Sedation requirement was assessed using the number of intermittent (PRNs) doses given per hour. Analysis was conducted with autoregressive moving average models and the Granger test for causality., Results: 39 children were included in the study. The average (SD) sound level in the open area was 59.4 (2.5) dB(A) with a statistically significant but clinically unimportant difference between day/night hours (60.1 vs. 58.6; p-value < 0.001). There was no significant difference between sound levels in the open area/single room (59.4 vs. 60.8, p-value = 0.108). Peak noise levels were > 90 dB. There was a significant association between average (p-value = 0.030) and peak sound levels (p-value = 0.006), and number of sedation PRNs., Conclusion: Sound levels were above the recommended values with no differences between day/night or open area/single room. High sound levels were significantly associated with sedation requirements., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Remote ischemic preconditioning involves providing a brief ischemia-reperfusion event to a tissue to create subsequent protection from a more severe ischemia-reperfusion event to a different tissue/organ. The few pediatric remote ischemic preconditioning studies in the literature show conflicting results., Aim: We conducted a pilot randomized controlled trial to determine the feasibility of conducting a larger trial and to gather provisional data on the effect of early and late remote ischemic preconditioning on outcomes of infants after surgery for congenital heart disease., Methods: This single-center, double-blind randomized controlled trial of remote ischemic preconditioning vs control (sham-remote ischemic preconditioning) in young infants going for surgery for congenital heart disease at the Stollery Children's Hospital. Remote ischemic preconditioning was performed at 24-48 h preoperatively and immediately prior to cardiopulmonary bypass. Remote ischemic preconditioning stimulus was performed with blood pressure cuffs around the thighs. Primary outcomes were feasibility and peak blood lactate level on day 1 postoperatively., Results: Fifty-two patients were randomized but seven patients became ineligible after randomization leaving 45 patients included in the study. In the included patients, 7 (15%) had protocol deviations (five infants did not have the preoperative intervention and two did not receive the intervention in the operating room). From a comfort point of view, only one subject in the control group and two in the Remote ischemic preconditioning group received sedation during the preoperative intervention. There were no study-related adverse events and no complications to the limbs subjected to preconditioning. There were no significant differences between the Remote ischemic preconditioning group and the control group in the highest blood lactate level on day 1 postoperatively (mean difference, 1.28; 95%CI, -0.22, 2.78; P-value = 0.093)., Conclusion: In infants who underwent surgery for congenital heart disease, our pilot randomized controlled trial on early and late remote ischemic preconditioning proved to be feasible but did not find any significant difference in acute outcomes. A larger trial may be necessary., (© 2017 John Wiley & Sons Ltd.)

Background: Strong recommendations have been made for the periodic developmental surveillance, screening, and evaluation of children with CHD. This supports similar calls for all at-risk children in order to provide timely, structured early developmental intervention that may improve outcomes. The aim of this study was to determine the accuracy of screening for language delay after life-saving therapies using the parent-completed vocabulary screen of the language Development Survey, by comparing screening with the individually administered language scores of the Bayley Scales of Infant and Toddler Development, Third edition., Method: In total, 310 (92.5%) of 335 eligible term-born children, born between 2004 and 2011, receiving complex cardiac surgery, heart or liver transplantation, or extracorporeal membrane oxygenation in infancy, were assessed at 21.5 (2.8) months of age (lost, 25 (7.5%)), through developmental/rehabilitation centres at six sites as part of the Western Canadian Complex Pediatric Therapies Follow-up Group., Results: Vocabulary screening delay was defined as scores ⩽15th percentile. Language delay defined as scores >1 SD below the mean was calculated for language composite score, receptive and expressive communication scores of the Bayley-III. Delayed scores for the 310 children were as follows: vocabulary, 144 (46.5%); language composite, 125 (40.3%); receptive communication, 98 (31.6%); and expressive communication, 124 (40%). Sensitivity, specificity, positive predictive values, and negative predictive values of screened vocabulary delay for tested language composite delay were 79.2, 75.7, 68.8, and 84.3%, respectively., Conclusion: High rates of language delay after life-saving therapies are concerning. Although the screening test appears to over-identify language delay relative to the tested Bayley-III, it may be a useful screening tool for early language development leading to earlier referral for intervention.

The development of advanced stimuli-responsive systems for medicine, catalysis, or technology requires compartmentalized reaction spaces with triggered activity. Only very few stimuli-responsive systems preserve the compartment architecture, and none allows a triggered activity in situ. We present here a biomimetic strategy to molecular transmembrane transport by engineering synthetic membranes equipped with channel proteins so that they are stimuli-responsive. Nanoreactors with triggered activity were designed by simultaneously encapsulating an enzyme inside polymer compartments, and inserting protein "gates" in the membrane. The outer membrane protein F (OmpF) porin was chemically modified with a pH-responsive molecular cap to serve as "gate" producing pH-driven molecular flow through the membrane and control the in situ enzymatic activity. This strategy provides complex reaction spaces necessary in "smart" medicine and for biomimetic engineering of artificial cells.

Objective: Extracorporeal Cardiopulmonary Resuscitation (E-CPR) is the initiation of extracorporeal life support during active chest compressions. There are no studies describing detailed neurocognitive outcomes of this population. We aim to describe the survival and neurocognitive outcomes of children who received E-CPR., Methods: Prospective cohort study. Children who received E-CPR at the Stollery Children's Hospital between 2000 and 2010 were included. Neurocognitive follow-up, including Wechsler Preschool and Primary Scales of Intelligence, was completed at the age of 4.5 years, and at a minimum of 6 months after the E-CPR admission., Results: Fifty-five patients received E-CPR between 2000 and 2010. Children with cardiac disease had a 49% survival to hospital discharge and 43% survival at age 5-years, with no survivors (n=4) in those with non-cardiac disease. Pediatric E-CPR survivors had a mean (SD) Full Scale Intelligence quotient (FSIQ) score of 76.5 (15.9); with 4 children (24%) having intellectual disability (defined as FSIQ over 2 standard deviations below the population mean; i.e., <70). Multiple Cox regression analysis found that mechanical ventilation prior to E-CPR, open chest CPR, longer duration of CPR, low pH and more red blood cells given on the first day of ECMO, and longer time for lactate to normalize on ECMO were associated with higher mortality at age 5-years., Conclusion: Pediatric patients with cardiac disease who required E-CPR had 43% survival at age 5 years. Of concern, the intelligence quotient in E-CPR survivors was significantly lower than the population mean, with 24% having intellectual disability., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Biomimetic polymer nanocompartments (polymersomes) with preserved architecture and ion-selective membrane permeability represent cutting-edge mimics of cellular compartmentalization. Here it is studied whether the membrane thickness affects the functionality of ionophores in respect to the transport of Ca 2+ ions in synthetic membranes of polymersomes, which are up to 2.6 times thicker than lipid membranes (5 nm). Selective permeability toward calcium ions is achieved by proper insertion of ionomycin, and demonstrated by using specific fluorescence markers encapsulated in their inner cavities. Preservation of polymersome architecture is shown by a combination of light scattering, transmission electron microscopy, and fluorescence spectroscopy. By using a combination of stopped-flow and fluorescence spectroscopy, it is shown that ionomycin can function and transport calcium ions across polymer membranes with thicknesses in the range 10.7-13.4 nm (7.1-8.9 times larger than the size of the ionophore). Thicker membranes induce a decrease in transport, but do not block it due to the intrinsic flexibility of these synthetic membranes. The design of ion selective biomimetic nanocompartments represents a new path toward the development of cellular ion nanosensors and nano-reactors, in which calcium sensitive biomacromolecules can be triggered for specific biological functions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Objectives: Little is known about chronic neuromotor disability (CND) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery (CCS). We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors., Methods: This prospective follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age. Groups included those with only 1 CCS, mostly biventricular CHD, and those with >1 CCS, predominantly single ventricle defects. At 4.5 years of age, 420 (94.6%) children received multidisciplinary assessment. Frequency of CND is given as percentage of assessed survivors. Predictors of CND were analyzed using multiple logistic regression analysis., Results: CND occurred in 6% (95% confidence interval [CI] 3.7%-8.2%) of 4.5-year survivors; for 1 CCS, 4.2% (CI 2.3%-6.1%) and >1, 9.8% (CI 7%-12.6%). CND presentation showed: hemiparesis, 72%; spasticity, 80%; ambulation, 72%; intellectual disability, 44%; autism, 16%; epilepsy, 12%; permanent vision and hearing impairment, 12% and 8%, respectively. Overall, 32% of presumed causative events happened before first CCS. Independent odds ratio for CND are age (days) at first CCS, 1.08 (CI 1.04-1.12; P < .001); highest plasma lactate before first CCS (mmol/L), 1.13 (CI 1.03-1.23; P = 0.008); and >1 CCS, 3.57 (CI 1.48-8.9; P = .005)., Conclusions: CND is not uncommon among CCS survivors. The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population. Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND., (Copyright © 2015 by the American Academy of Pediatrics.)

In nature there are various specific reactions for which highly selective detection or support is required to preserve their bio-specificity or/and functionality. In this respect, mimics of cell membranes and bio-compartments are essential for developing tailored applications in therapeutic diagnostics. Being inspired by nature, we present here biomimetic nanocompartments with ion-selective membrane permeability engineered by insertion of ionomycin into polymersomes with sizes less than 250 nm. As a marker to assess the proper insertion and functionality of ionomycin inside the synthetic membrane, we used a Ca(2+)-sensitive dye encapsulated inside the polymersome cavity prior to inserting the biopore. The calcium sensitive dye, ionomycin, and Ca(2+) did not influence the architecture and the size of polymersomes. Successful ionomycin functionality inside the synthetic membrane with a thickness of 10.7 nm was established by a combination of fluorescence spectroscopy and stopped-flow spectroscopy. Polymersomes equipped with ion selective membranes are ideal candidates for the development of medical applications, such as cellular ion nanosensors or nanoreactors in which ion exchange is required to support in situ reactions.

Background: The purpose of this study was to determine whether a clinical outcome score derived from early postoperative events is associated with Bayley-III scores at 18 to 24 months among infants undergoing cardiopulmonary bypass surgery., Methods: Included were infants aged 6 weeks or less who underwent surgery between 2005 and 2009, all of whom were referred for neurodevelopmental evaluation at 18 to 24 months. We excluded children with chromosomal abnormalities. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal life support were assigned a score of 7., Results: One hundred and ninety-nine subjects were included. Surgical procedures were arterial switch (72), Norwood (60), repair of total anomalous pulmonary venous connection (29), and other (38). Nine subjects had postoperative extracorporeal life support. Mean clinical outcome score in the Norwood group was 4.0 ± 1.4 versus the arterial switch group (2.6 ± 1.5, p < 0.001), total anomalous pulmonary venous connection group (2.8 ± 1.8, p < 0.01), and other group (4.0 ± 1.8, p = not significant). Among children who had a clinical outcome score of 4 or greater, there was a decrease in Bayley-III cognitive score of 5.7 (95% confidence interval: 1.5 to 9.9, p = 0.009), a decrease in language score of 10.0 (95% confidence interval: 4.9 to 15.1, p < 0.001), and a decrease in motor score of 9.7 (95% confidence interval: 4.8 to 14.5, p < 0.001). Time until lactate of 2.0 mmol/L or less and highest 24-hour inotrope score increased with increasing clinical outcome score (p < 0.0001)., Conclusions: Clinical outcome scores of 4 or greater were associated with significantly lower Bayley-III scores at 18 to 24 months. This score may be valuable as an endpoint when evaluating novel potential therapies for this high-risk population., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Survival after pediatric cardiac extracorporeal life support (ECLS) is guarded, and neurological morbidity varies widely. Our objective is to report our 10-year experience with cardiac ECLS, including survival and kindergarten entry neurocognitive outcomes; to identify predictors of mortality or adverse neurocognitive outcomes; and to compare 2 eras, before and after 2005., Methods and Results: From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Sixty-four patients (65%) survived to hospital discharge, and 50 (51%) survived ≤5 years of age. Neurocognitive follow-up of survivors was completed at mean (SD) age of 52.9 (8) months using Wechsler Preschool and Primary Scale of Intelligence. Logistic regression analysis found the longer time (hours) for lactate to fall below 2 mmol/L on ECLS (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84; P=0.022), and the amount of platelets (mL/kg) given in the first 48 hours (hazard ratio, 1.18; 95% confidence interval, 1.06, 1.32; P=0.002) was independently associated with higher in-hospital mortality. Receiving ECLS after the year 2005 was independently associated with lower risk of in-hospital mortality (hazard ratio, 0.36; 95% confidence interval, 0.13, 0.99; P=0.048). Extracorporeal cardiopulmonary resuscitation was not independently associated with mortality or neurocognitive outcomes. Era was not independently associated with neurocognitive outcomes. The full-scale intelligence quotient of survivors without chromosomal abnormalities was 79.7 (16.6) with 25% below 2 SD of the population mean., Conclusions: Mortality has improved over time; time for lactate to fall on ECLS and volume of platelets transfused are independent predictors of mortality. Extracorporeal cardiopulmonary resuscitation and era were not independently associated with neurocognitive outcomes., (© 2015 American Heart Association, Inc.)

Objective: To assess the health-related quality of life of children who received cardiac extracorporeal life support. We hypothesized that extracorporeal life support survivors have lower health-related quality-of-life scores when compared with a healthy sample, with children with chronic conditions, and with children who had surgery for congenital heart disease and did not receive extracorporeal life support., Design: Prospective cohort study., Setting: Stollery Children's Hospital and Complex Pediatric Therapies Follow-up Program clinics., Patients: Children less than or 5 years old with diagnosis of cardiac disease (congenital or acquired) who received extracorporeal life support at the Stollery Children's Hospital from 1999 to 2009., Interventions: None., Measurements and Main Results: Health-related quality of life was assessed using the PedsQL 4.0 Generic Core Scales completed by the children's parents at the time of follow-up. Forty-seven cardiac extracorporeal life support survivors had their health-related quality of life assessed at a median age of 4 years. Compared with a healthy sample, children who received venoarterial extracorporeal life support have significantly lower PedsQL (64.9 vs 82.2; p < 0.0001). The PedsQL scores of children who received extracorporeal life support were also significantly lower than those of children with chronic health conditions (64.9 vs 73.1; p = 0.007). Compared with children with congenital heart disease who underwent cardiac surgery early in infancy and who did not receive extracorporeal life support, extracorporeal life support survivors had significantly lower PedsQL scores (64.9 vs 81.1; p < 0.0001). Multiple linear regression analysis found an independent association between both higher inotrope score in the first 24 hours of extracorporeal life support and longer hospital length of stay, with lower PedsQL scores., Conclusions: Pediatric cardiac extracorporeal life support survivors showed lower health-related quality of life than healthy children, children with chronic conditions, and children with congenital heart disease who did not receive extracorporeal life support.