Nano polydopamine crosslinked thiol-functionalized hyaluronic acid hydrogel for angiogenic drug delivery

Crosslinking of polymeric network using nanoparticles by physical or chemical method to obtain hydrogel is an emerging approach. Herein, we synthesized Polydopamine (PDA) nanoparticles via oxidative self-polymerization of dopamine in water-ethanol mixture. Thiol-functionalized hyaluronic acid was developed using cysteamine and hyaluronic acid (HA-Cys) via 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide - N-hydroxysuccinimide (EDC-NHS) crosslinking chemistry. Developed HA-Cys conjugate was cross-linked using PDA nanoparticles via Michael-type addition reaction. Synthesized nanoparticles were monodisperse with size of 124 +/- 8 nm and had spherical morphology. FTIR characterization confirmed successful synthesis of HA-Cys conjugate and subsequent crosslinking with PDA nanoparticles. Rheological characterization revealed that hydrogels were injectable in nature with good mechanical stability. Dimethyloxalylglycine (DMOG) loaded PDA nanoparticle showed sustained drug release for period of 7 days from composite hydrogel. Hydrogel microenvironment facilitated enhanced endothelial cell migration, proliferation and attachment. Furthermore, in response to release of DMOG from developed hydrogel, cells showed enhanced capillary tube formation in vitro. Overall, these results demonstrate that PDA cross-linked thiol-functionalized hydrogel was developed in a facile manner under physiological conditions. These developed hydrogels could be potentially used in tissue engineering and drug delivery

The development of the circadian heart rate rhythm (CHR) in Asian infants

Objective: To test the hypothesis that term-born Asian infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heart rate rhythm (CHR) at a later age than non-Asian term infants. Method: Repeated overnight heart rate (HR) traces obtained with a battery-operated Polar S810i heart-rate monitor at home in 17 Asian Torajan infants in Indonesia, were compared with those of 52 non-Asian infants monitored as part of the Collaborative Home Infant Monitoring Evaluation (CHIME). HR was determined using a moving window averaging technique. A comparison of median HR during quiet sleep (QS) episodes (identified by minimum HR variability), established the presence of CHR. Results: Seventy three percent of non-Asian CHIME infants ≤ 7 weeks exhibited CHR compared to 45% of Asian Torajan infants. Between 8 and 12. weeks, 94% of non-Asian CHIME infants exhibited CHR, compared to 33% of Asian Torajan infants (p \u3c 0.001). Forty seven and 56% of Asian Torajan infants exhibited the CHR at the age intervals of 16-20. weeks and 21-25. weeks respectively. Active wakefulness percentages as a function of the entire recording and median QS HR were not significantly different in the two groups. Conclusion: Despite the fact that Asian Torajan infants were on average a week older than non-Asian CHIME babies, between two and three months of age only one in three exhibited the CHR, compared to virtually all non-Asian CHIME infants. We speculate that the cause of this difference rests in the infants\u27 environment rather than their genetic origin. © 2011 Elsevier Ltd

A PHYSIOLOGIC REDUCED OXYGEN PROTOCOL DECREASES THE INCIDENCE OF THRESHOLD RETINOPATHY OF PREMATURITY

PURPOSE: To report the incidence of threshold retinopathy of prematurity (ROP) in very low birth weight premature infants from three neonatal intensive care units (NICUs) before and after implementation of a physiologic reduced oxygen protocol (PROP). METHODS: Prospective, observational study of data from three NICUs: Cedars-Sinai Medical Center (CSMC), Los Angeles; Good Samaritan Hospital (GSH), Los Angeles; and National University Hospital (NUH), Singapore. PROP was implemented to keep oxygen saturation values by pulse oximeter (SpO(2)) between 83% and 93% (as described in Pediatrics 2003;111:339–345). The incidence of threshold ROP in the year before and the year after implementation of PROP was compared. Data from the transition year were not included in the analysis. RESULTS: The incidence of threshold ROP decreased in each center: CSMC, 3.3% to 0.0% (3/92 to 0/88); GSH, 14.8% to 4.9% (8/54 to 2/41); and NUH, 6.7% to 0.0% (3/45 to 0/30). Overall, the incidence of threshold ROP decreased from 7.3% to 1.3%. (P <.05). The 95% confidence interval was 4.3% to 12% for the pre-PROP group and 0.05% to 4.76% for the post-PROP group. CONCLUSIONS: Physiologic hypoxia is the normal fetal state. Exposure of newborn premature infants to hyperoxia down-regulates retinal vascular endothelial growth factor. This arrests the normal retinal vascular migration and causes vaso-obliteration, the first phase of ROP. The hypothesis is that maintaining SpO(2) values between 83% and 93% in the immediate postgestation life, combined with strict control of oxygen fluctuations, prevents the early vaso-obliterative phase and subsequent development of severe ROP. Significant reduction of threshold disease after implementation of PROP in all three centers supports the hypothesis

Antistaphylococcal and neutrophil chemotactic injectable κ-carrageenan hydrogel for infectious wound healing

Staphylococcus aureus wound infection is a major concern due to the resistance of S. aureus to topical antibiotics and capacity to inhibit neutrophil migration at the infection site. To overcome these problems, we have developed 0.01% (v/v) octenidine dihydrochloride (Oct) and 0.5% (w/w) chitosan-treated serum (CTS) containing 1.5% (w/v) κ-carrageenan hydrogel (κC). Oct is an antiseptic agent, against which no resistance is reported so far, and CTS has neutrophilic attractant properties. The prepared Oct-CTS-κC hydrogel is injectable and biocompatible. Using in vitro experiments, we demonstrated CTS can induce the migration of polymorphonuclear neutrophils (PMNs) and fibroblasts that can facilitate tissue regeneration at a wound site. In vitro release studies revealed a sustained release of Oct and serum proteins from the Oct-CTS-κC hydrogel. Antibacterial properties of developed hydrogels were tested against S. aureus and its clinical isolates. Further, the in vivo antibacterial efficacy of the prepared hydrogel was evaluated in an S. aureus-infected Sprague-Dawley (SD) rat wound. Both in vitro and in vivo studies showed that the Oct-CTS-κC hydrogel inhibited S. aureus growth. Thus, the developed Oct-CTS-κC hydrogel can be potentially exploited for S. aureus-infected wound healing

Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multi-center prospective randomized controlled trial

Abstract Background Invasive mechanical ventilation (IMV) is associated with the development of adverse pulmonary and non-pulmonary outcomes in very premature infants. Various modes of non-invasive respiratory support are increasingly being used to decrease the incidence of bronchopulmonary dysplasia. The aim of this trial is to compare the effect of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary non-invasive ventilation support mode. Methods/design In this multi-center randomized controlled trial, 300 preterm infants born at a gestational age of 266/7 to 336/7 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. The study will be conducted in 18 tertiary neonatal intensive care units in China. The primary outcome is the need for IMV during the first 7 days after enrollment in preterm infants randomized to the two groups. The prespecified secondary outcomes include days of hospitalization, days on non-invasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for a surfactant, severe retinopathy of prematurity requiring laser treatment or surgery, patent ductus arteriosus needing ligation, bronchopulmonary dysplasia, abdominal distention, air leak syndromes, intraventricular hemorrhage (≥ grade 3), spontaneous intestinal perforation, necrotizing enterocolitis (≥II stage), and nasal trauma. Other secondary outcomes include Bayley Scales of Infant Development at 18–24 months of corrected age. Discussion In recent decades, several observational studies have compared the effects of NHFOV and NCPAP in neonates as a rescue mode or during weaning from IMV. To our knowledge, this will be the first multi-center prospective, randomized controlled trial to evaluate NHFOV as a primary mode in preterm infants with RDS in China or any other part of the world. Our trial may help to establish guidelines for NHFOV in preterm infants with RDS to minimize the need for IMV, and to decrease the significant pulmonary and non-pulmonary morbidities associated with IMV. Trial registration ClinicalTrials.gov, NCT03099694. Registered on 4 April 2017

Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants

To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (Fio(2)) adjustment in maintaining arterial oxygen saturation (Spo(2)) within an intended range for mechanically ventilated preterm infants with frequent episodes of decreased Spo(2). Thirty-two infants (gestational age [median and interquartile range]: 25 weeks [24-27 weeks]; age: 27 days [17-36 days]) were studied during 2 consecutive 24-hour periods, one with Fio(2) adjusted by clinical staff members (manual) and the other by an automated system (automated), in random sequence. Time with Spo(2) within the intended range (87%-93%) increased significantly during the automated period, compared with the manual period (40% ± 14% vs 32% ± 13% [mean ± SD]). Times with Spo(2) of >93% or >98% were significantly reduced during the automated period (21% ± 20% vs 37% ± 12% and 0.7% vs 5.6% [interquartile ranges: 0.1%-7.2% and 2.7%-11.2%], respectively). Time with Spo(2) of <87% increased significantly during the automated period (32% ± 12% vs 23% ± 9%), with more-frequent episodes with Spo(2) between 80% and 86%, whereas times with Spo(2) of <80% or <75% did not differ between periods. Hourly median Fio(2) values throughout the automated period were lower and there were substantially fewer manual Fio(2) changes (10 ± 9 vs 112 ± 59 changes per 24 hours; P < .001), compared with the manual period. In infants with fluctuations in Spo(2), automated Fio(2) adjustment improved maintenance of the intended Spo(2) range led to reduced time with high Spo(2) and more-frequent episodes with Spo(2) between 80% and 86%