Hybrid Graphenene Oxide/Cellulose Nanofillers to Enhance Mechanical and Barrier Properties of Chitosan-Based Composites.

Chitosan-based hybrid nanocomposites, containing cellulose nanocrystals (CNCs), graphene oxide (GO), and borate as crosslinking agents, were successfully prepared by solution-casting technique. The synergistic effect of the two fillers, and the role of the cross-linker, in enhancing the structural and functional properties of the chitosan polymer, was investigated. XPS results confirm the chemical interaction between borate ions and hydroxyl groups of chitosan, GO, and CNCs. The morphological characterization shows that the GO sheets are oriented along the casting surface, whereas the CNC particles are homogenously distributed in the sample. Results of tensile tests reveal that the presence of graphene oxide enhances the elastic modulus, tensile strength, elongation at break, and toughness of chitosan, while cellulose and borate induce an increase in the elastic modulus and stress at the yield point. In particular, the borate-crosslinked chitosan-based sample containing 0.5 wt% of GO and 0.5 wt% of CNCs shows an elongation at a break value of 30.2% and a toughness value of 988 J*m-3 which are improved by 124% and 216%, respectively, compared with the pristine chitosan. Moreover, the water permeability results show that the presence of graphene oxide slightly increases the water barrier properties, whereas the borate and cellulose nanocrystals significantly reduce the water vapor permeability of the polymer by about 50%. Thus, by modulating the content of the two reinforcing fillers, it is possible to obtain chitosan-based nanocomposites with enhanced mechanical and water barrier properties which can be potentially used in various applications such as food and electronic packaging.

Tuning of polyurethane foam mechanical and thermal properties using ball-milled cellulose.

Cystalline-Cc and ultra-milled Amorphous-Ca cellulose were used as reactive filler to tune the performances of composite polyurethane-cellulose-foams, PUC. The effect of Cc and Ca on chemo-physical and mechanical properties of PUC was analysed through FTIR, morphological analysis, thermal conductivity and compression measurements. FTIR results show that, both Cc and Ca react with isocyanate through the OH functional groups contributing to the formation of a tough cellulose-polyurethane network. Morphological observations show that the addition of both Cc and Ca induces a decrease of average cell-size compared to the pristine-PU, thus confirming that they act as nucleating agent. In addition, the better dispersion of the Ca in the polyol, with respect to Cc induces, a finer cell leading to a reduction of the thermal conductivity around 33 % (for the composite loaded with 20 %wt-Ca) with respect to pristine-PU. Finally, the addition of Ca highly reactive modifies the mechanical behaviour from rigid-brittle to semi-rigid.

Optimization of dye adsorption capacity and mechanical strength of chitosan aerogels through crosslinking strategy and graphene oxide addition.

Chitosan (CS) aerogels were prepared by freeze-drying as potential adsorbents for water purification, and the effect of the strategy of crosslinking was investigated by varying the amount of crosslinker (glutaraldehyde) and the sequence of steps for the preparation of the aerogel. Two procedures were compared, in which the crosslinking step was carried out before or after the freeze-drying of the starting CS solution. When crosslinking was postponed after the freeze-drying step, the adsorption capacity towards an anionic dye, such as indigo carmine, considerably increased (up to +45%), reaching values as high as 534.4 ± 30.5 mg g-1. The same crosslinking strategy ensured a comparable improvement also in nanocomposite aerogels containing graphene oxide (GO), which was added to enhance the mechanical strength and provide adsorption capacity towards cationic dyes. Besides possessing good mechanical strength (compressive modulus higher than 1 MPa), the CS/GO aerogels were able to bind also cationic pollutants such as methylene blue. The maximum uptake capacity increased from 4.3 ± 1.6 to 168.6 ± 9.6 mg of cationic dye adsorbed per gram of adsorbent with respect to pristine CS aerogels.

Different concentration of human cord blood HMGB1 according to delivery and labour: A pilot study.

OBJECTIVE: Oxidative stress is involved in several maternal conditions characterized both by an increase in free radicals synthesis and a parallel decrease in the antioxidant activity. Parturition induces considerable oxidative stress and many inflammatory mediators, among which HMGB1, are involved from the beginning of pregnancy to the birth of the infant. We evaluated serum cord blood HMGB1 levels in a population of neonates to investigate correlation with mode of delivery, as well as the influence of labour. SETTING AND PATIENTS: The study subjects were 325 neonates delivered at University Hospital "G. Martino" of Messina over an 18-month period. Following cord separation, venous blood sampling was performed on umbelical cords. RESULTS: In the cord venous blood, we found HMGB1 values significantly more elevated in spontaneous vaginal group when compared to elective or emergency caesarean section group. Regarding labour, umbilical cord venous blood HMGB1 levels were significantly higher in the spontaneous and induced labour group, compared to non-labouring women. CONCLUSION: These results could highlight a possible role of HMGB1 during birth time related to mode of delivery and labour.

Pain perception in NICU: a pilot questionnaire.

PURPOSE: Neonatal pain management has made a great step forward over the last several years. Despite the drafting of International guidelines, an under-treatment of neonatal pain is still reported. MATERIALS AND METHODS: Medical and paramedical personnel working in five Italian NICUs were asked to complete a questionnaire about pain management. The questionnaire was comprised of three sections: (i) brief explanation of the purpose; (ii) demographic information, including age, profession, religious beliefs, and hospital level; (iii) questionnaire about pain management and prevention. RESULTS: One-hundred and forty caregivers participated in this study. Non-pharmacological analgesia during heel prick or venipuncture was used by 64% and 60% of them, respectively; topical analgesia was performed in 13% of venipunctures; no analgesia was used in 30% of cases for both heel prick and venipuncture. In the case of lumbar puncture, 35% of participants used topical analgesia, 15% non-pharmacological approach, 10% opioids, and 6% intravenous paracetamol. While 65% of participants gave a score of 4 out of 5 about the importance of pain treatment, 39% of them reported that in their department no pain scales were used. CONCLUSIONS: Pain treatment in these NICUs is still far to be optimal. This nonetheless reflects a worldwide trend, which requires more attention on pain prevention, assessment, and treatment.

Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery.

OBJECTIVE: Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. METHODS: A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. RESULTS: In total, 61 neonates were included, median gestational age at 39 weeks (range 31-42) and weight at 3000 grams (1400-4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. CONCLUSION: Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.

Randomized trial of early erythropoietin supplementation after preterm birth: Iron metabolism and outcome.

BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30.0weeks). OUTCOME MEASURES: The iron status, postnatal morbidities and follow-up at the age of two years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants were recruited. A requirement of red blood cell transfusions during first 28days was similar between the study groups. EPO treatment decreased total serum iron concentration (p=0.035). EPO supplementation had no significant effect on serum transferrin receptors or reactive non-protein-bound iron. There were no differences in neonatal morbidity or in survival without major neurological abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the iron load in preterm infants. There was no change in reactive, non-protein bound iron plasma levels and no influence on the outcomes during early childhood. Whether the neurocognitive effects of early EPO treatment can be detectable later in childhood remained to be verified.

Maternal obesity and perinatal oxidative stress: the strength of the association.

Maternal obesity is a chronic inflammatory state, which has been shown to induce increased levels of free fatty acids, reactive oxygen species and inflammatory cells. Recent evidence reveals increased levels of lipid peroxidation products in the plasma of obese women during pregnancy. The aim of this study was to test the hypothesis that maternal overweight or obesity is associated with increased oxidative stress (OS) in offspring. Two hundred and forty-five pregnant women and their newborns were prospectively enrolled. Mothers were divided in two groups: lean control - LC (n=175, Group I); overweight or obese (n=70, Group II) according to BMI ≥ 25 before pregnancy. Cord blood F2-isoprostanes (F2-IsoPs), as reliable markers of OS, were measured in all newborns. Lower 1 minute APGAR score and higher weight at discharge were found in Group II neonates, compared to those of Group I (p less than 0.05). Small for gestational age (SGA) newborns of both groups showed increased levels of F2-IsoPs than appropriate (AGA) or large (LGA) for gestational age (GA) (p less than 0.01). SGA newborns of Group II had higher F2-IsoPs levels compared to SGA of Group I (p less than 0.01), which were significantly correlated to maternal BMI at the end of pregnancy (r=0.451, p less than 0.01). Multivariate regression analysis corrected for confounding factors, showed that maternal overweight or obesity was significantly associated with high F2-IsoPs levels in SGA offspring (p less than 0.01). Maternal overweight or obesity is associated with increased OS in their SGA newborns. Data suggest the need of antioxidant protection for both mothers during pregnancy and infants soon after birth.

Oxidative Stress as a Physiological Pain Response in Full-Term Newborns.

This research paper aims to investigate if oxidative stress biomarkers increase after a painful procedure in term newborns and if nonpharmacological approaches, or sex, influence pain degree, and the subsequent OS. 83 healthy term newborns were enrolled to receive 10% oral glucose or sensorial saturation (SS) for analgesia during heel prick (HP). The ABC scale was used to score the pain. Advanced oxidation protein products (AOPP) and total hydroperoxides (TH) as biomarkers of OS were measured at the beginning (early-sample) and at the end (late-sample) of HP. The early-sample/late-sample ratio for AOPP and TH was used to evaluate the increase in OS biomarkers after HP. Higher levels of both AOPP and TH ratio were observed in high degree pain (4-6) compared with low degree pain score (0-3) (AOPP: p = 0.049; TH: p = 0.001). Newborns receiving SS showed a significantly lower pain score (p = 0.000) and AOPP ratio levels (p = 0.021) than those without. Males showed higher TH levels at the end of HP (p = 0.005) compared to females. The current study demonstrates that a relationship between pain degree and OS exists in healthy full-term newborns. The amount of OS is gender related, being higher in males. SS reduces pain score together with pain-related OS in the newborns.

Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery.

With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2-Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects.

A comparative study on oxidative stress role in nasal breathing impairment and obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a sleep disorder that leads to metabolic abnormalities and increased cardiovascular risk. This study aimed to define the expression and clinical significance of biomarkers involved in oxidative stress in patients with OSAS. A prospective study was designed to compare outcomes of oxidative stress laboratory tests in three groups of subjects. The study involved the recruitment of three groups of subjects, 10 patients with obstructive sleep apnoea syndrome with AHI > 30; 10 patients suffering from snoring at night with AHI < 15; 10 patients with nasal respiratory impairment with AHI < 5. Patients were subjected to skin prick tests for common aero-allergens, nasal endoscopy, active anterior rhinomanometry, fibrolaryngoscopy and polysomnography; and extra-routine diagnostic tests and procedures; analysis of oxidative and antioxidant (plasma thiol groups) biomarkers in blood and urine samples. No statistical differences in age, sex distribution or body mass index were present between the three groups (p > 0.05). There were significant differences in AHI among the three groups of patients (p < 0.05). No statistical significance was found in the Analysis of Variance (ANOVA) test (p > 0.05) between the levels of biomarkers of oxidative stress in the three populations studied. The results of our study show that the nose can play a role in the pathogenesis of OSAS through the production of biomarkers of oxidative stress.

How painful is a heelprick or a venipuncture in a newborn?

OBJECTIVE: Neonates undergo many painful procedures daily, in particular venipunctures and heelpricks. Our aim was to assess how painful these procedures actually are, and how effective are the common analgesic strategies to blunt this pain. METHODS: We performed a MEDLINE/PubMed research from 1999 to 2013. We retrieved all papers in English language that evaluated pain during neonatal heelprick or venipuncture and that used as score the Premature Infant Pain Profile (PIPP), a widely used scale for evaluate acute pain in term and preterm babies. RESULTS: Fifteen papers met the inclusion criteria, using different analgesic methods. Just in one case two studies used the same analgesic method. Most analgesic procedures show a relevant level of pain. We didn't find univocal difference between heelprick and venipuncture. Topic creams, systemic analgesics, posture and oral glucose 10% have scarce analgesic effectiveness. The most effective procedures are the use of oral sweet solutions (sucrose or glucose) at concentrations greater than 20%, multisensory stimulations and non-nutritive sucking used along with 10% glucose. CONCLUSIONS: A large amount of analgesic methods was used, making comparisons difficult. Nevertheless, in the absence of analgesic treatment, heelpricks and venipunctures are moderately-severely painful, and among the proposed analgesic procedures, few seem to be effective.

Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air.

AIM: The starting fraction of inspired oxygen for preterm resuscitation is a matter of debate, and the use of room air in full-term asphyxiated infants reduces oxidative stress. This study compared oxidative stress in preterm infants randomised for resuscitation with either 100% oxygen or room air titrated to internationally recommended levels of preductal oxygen saturations. METHODS: Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room air (n = 59). Oxidative stress markers, including advanced oxidative protein products (AOPP) and isoprostanes (IsoP), were measured with high-performance liquid chromatography and mass spectrometry. RESULTS: Significantly higher levels of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations were significantly higher in the 100% oxygen group. CONCLUSION: Initial resuscitation with room air versus 100% oxygen was associated with lower protein oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels between two and 12 hours of life. Correlations with clinical outcomes will be vital to optimise the use of oxygen in preterm resuscitation.

Proton nuclear magnetic resonance spectroscopy of urine samples in preterm asphyctic newborn: a metabolomic approach.

In order to highlight differences in the metabolic profile of healthy (control) compared with asphyxiated newborns, by using untargeted metabolomic approach coupled with (1)H NMR spectroscopy, we evaluated the effects of asphyxia on newborn urine metabolites. Our results showed that lactate, glucose and TMAO, together with threonine plus 3-hydroxyisovalerate are the metabolites more characterizing the asphyxiated group; lower contribute to discrimination is related to other metabolites such as dimethylglycine, dimethylamine, creatine, succinate, formate, urea and aconitate. After 24-48h from resuscitation preterm asphyctic neonates showed their recovery pattern that still can be differentiated by the controls.

Lipid and protein oxidation in newborn infants after lutein administration.

OBJECTIVES: To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period. METHODS: A randomized controlled, double-blinded clinical trial was conducted among 150 newborns divided into control group, not supplemented (n = 47), and test group, supplemented with lutein on the first day postpartum (n = 103). Blood Samples were collected at birth from cord and at 48 hrs postpartum while routine neonatal metabolic screenings were taking place. Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and biological antioxidant potential (BAP) were measured by spectrophotometry and data were analyzed by Wilcoxon rank sum test and by multivariate logistic regression analysis. RESULTS: Before lutein supplementation, the mean blood concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and 2361.04 umol/L in the test group. After lutein supplementation, significantly higher BAP increment (0.17 ± 0.22 versus 0.06 versus ± 0.46) and lower TH increment (0.46 ± 0.54 versus 0.34 ± 0.52) were observed in the test group compared to controls. CONCLUSION: Neonatal supplementation with lutein in the first hours of life increases BAP and reduces TH in supplemented babies compared to those untreated. The generation of free radical-induced damage at birth is reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

MMT-supported Ag nanoparticles for chitosan nanocomposites: structural properties and antibacterial activity.

Multifunctional bionanocomposites have been prepared by loading chitosan matrix with silver-montmorillonite antimicrobial nanoparticles obtained by replacing Na(+) ions of natural montmorillonite with silver ions. This filler has been chosen for its twofold advantage to serve as silver supporting material and to confer new and better performance to the obtained material. It has been proved that the achievement of the intercalation of chitosan into the silicate galleries of montomorillonite as well as the interaction between chitosan and Ag ions and silver particles lead to an enhancement of the thermal stability, to an improvement of mechanical strengths and to a reduction of the liquid water uptake of the obtained bionanocomposites. Results also show that silver ions are released in a steady and prolonged manner providing, after 24 h, a significant reduction in the microbial growth of Pseudomonas spp.

C-reactive protein: a marker of neonatal stress?

AIM: To assess whether blood values of C-reactive protein (CRP) in healthy term newborns, are influenced by stress. MATERIAL AND METHODS: Since different types of delivery (vaginal delivery [VD], emergency C-section [EMCS] and elective C-section [ELCS]) are notoriously characterized by different levels of stress for the baby, these three groups were used as models of different levels of stress. The mean CRP values of the three groups obtained in the first hours of life were compared. RESULTS: We retrieved 1012 babies. Median values (3rd-97th ct) were: 0.05 (0.01-0.46), 0.17 (0.02-1.54), 0.30 (0.04-1.77), 0.43 (0.05-1.31), 0.40 (0.04-1.13) at 12, 24, 48, 72 and 96 h, respectively. Mean values in babies born after VD were statistically higher than those born after C-section, and higher CRP values were present in EMCS with respect to ELCS. CONCLUSION: This study described normal blood CRP values in a wide population of term babies. An influence of the type of delivery on blood CRP is evident, and this may be explained by the different amount of perinatal stress induced by anyone of the three types of delivery we considered.

Intramuscular injections in newborns: analgesic treatment and sex-linked response.

AIM: To compare the analgesic effect of three treatments to relieve the pain produced by intramuscular injections (IMI) in term newborns, and to assess sex-linked differences in their response to pain. MATERIAL AND METHODS: We studied 62 babies. Each baby received antibiotic IMIs for clinical aims. During each IMI, one of the following analgesic treatments was utilized: oral 33% glucose (OG), sensorial saturation (SS), or topic anesthetic cream (TAC). SS is a validated analgesic method, based on the combination of three stimulations (tactile, acoustic and gustative). During the IMI, pain level was assessed with the use of the DAN scale, a validated neonatal pain scale. All babies who received three distinct analgesic procedures for three distinct IMIs were enrolled. Mean pain scores of the three analgesic treatment groups were compared. We then compared mean pain scores of females vs males in the whole cohort and within each treatment group. RESULTS: The 95% Confidence Intervals of pain scores were 5.6-6.5 for TAC, 1.4-2.3 for OG and 0.6-1.2 for SS: when treated with TAC, babies' pain scores were significantly higher than with OG or SS (p <0.0001); when treated with OG, babies' pain scores were higher than SS (p = 0.002). Females' mean pain score was significantly higher than males' mean pain score: (95% CI: 2.9-4.1 vs 2.0-3.1; p = 0.01). OG and SS produced significantly higher mean DAN scores in females than in males. Also in the TAC group females' mean DAN scores were higher than males, though this last difference was not statistically significant. CONCLUSION: This is the first study to show the effectiveness of nonpharmacologic analgesia in relieving IMI pain. It is also the first study to clearly show that the sex differences in pain perception are present since birth.

Use of fetal analgesia during prenatal surgery.

OBJECTIVE: Recent progresses in fetal surgery have raised concern on fetal pain, its long-term consequences and the risks of sudden fetal movements induced by pain. In several studies, surgeons have directly administered opioids to the fetus, while others have considered sufficient the maternally administered analgesics. We performed a review of the literature to assess the state of the art. METHODS: We performed a PubMed search to retrieve the papers that in the last 10 years reported studies of human fetal surgery and that described whether any fetal analgesia was administered. RESULTS: We retrieved 34 papers. In three papers, the procedure did not hurt the fetus, being performed on fetal annexes, in two papers, it was performed in the first half of pregnancy, when pain perception is unlikely. In 10 of the 29 remaining papers, fetal surgery was performed using direct fetal analgesia, while in 19, analgesia was administered only to the mother. In most cases, fetal direct analgesia was obtained using i.m. opioids, and muscle relaxant. Rare drawbacks on either fetuses or mothers due to fetal analgesia were reported. CONCLUSION: Fetal direct analgesia is performed only in a minority of cases and no study gives details about fetal reactions to pain. More research is needed to assess or exclude its possible long-term drawbacks, as well as the actual consequences of pain during surgery.