Dynamic Antimicrobial Poly(disulfide) Coatings Exfoliate Biofilms On Demand Via Triggered Depolymerization.

Bacterial biofilms are notoriously problematic in applications ranging from biomedical implants to ship hulls. Cationic, amphiphilic antibacterial surface coatings delay the onset of biofilm formation by killing microbes on contact, but they lose effectiveness over time due to non-specific binding of biomass and biofilm formation. Harsh treatment methods are required to forcibly expel the biomass and regenerate a clean surface. Here, a simple, dynamically reversible method of polymer surface coating that enables both chemical killing on contact, and on-demand mechanical delamination of surface-bound biofilms, by triggered depolymerization of the underlying antimicrobial coating layer, is developed. Antimicrobial polymer derivatives based on α-lipoic acid (LA) undergo dynamic and reversible polymerization into polydisulfides functionalized with biocidal quaternary ammonium salt groups. These coatings kill >99.9% of Staphylococcus aureus cells, repeatedly for 15 cycles without loss of activity, for moderate microbial challenges (≈105 colony-forming units (CFU) mL-1, 1 h), but they ultimately foul under intense challenges (≈107 CFU mL-1, 5 days). The attached biofilms are then exfoliated from the polymer surface by UV-triggered degradation in an aqueous solution at neutral pH. This work provides a simple strategy for antimicrobial coatings that can kill bacteria on contact for extended timescales, followed by triggered biofilm removal under mild conditions.

Time series based road traffic accidents forecasting via SARIMA and Facebook Prophet model with potential changepoints.

Road traffic accident (RTA) is a critical global public health concern, particularly in developing countries. Analyzing past fatalities and predicting future trends is vital for the development of road safety policies and regulations. The main objective of this study is to assess the effectiveness of univariate Seasonal Autoregressive Integrated Moving Average (SARIMA) and Facebook (FB) Prophet models, with potential change points, in handling time-series road accident data involving seasonal patterns in contrast to other statistical methods employed by key governmental agencies such as Ghana's Motor Transport and Traffic Unit (MTTU). The aforementioned models underwent training with monthly RTA data spanning from 2013 to 2018. Their predictive accuracies were then evaluated using the test set, comprising monthly RTA data from 2019. The study employed the Box-Jenkins method on the training set, yielding the development of various tentative time series models to effectively capture the patterns in the monthly RTA data. SARIMA(0,1,1)×(1,0,0)12 was found to be the suitable model for forecasting RTAs with a log-likelihood value of -266.28, AIC value of 538.56, AICc value of 538.92, BIC value of 545.35. The findings disclosed that the SARIMA(0,1,1)×(1,0,0)12 model developed outperforms FB-Prophet with a forecast accuracy of 93.1025% as clearly depicted by the model's MAPE of 6.8975% and a Theil U1 statistic of 0.0376 compared to the FB-Prophet model's respective forecasted accuracy and Theil U1 statistic of 84.3569% and 0.1071. A Ljung-Box test on the residuals of the estimated SARIMA(0,1,1)×(1,0,0)12 model revealed that they are independent and free from auto/serial correlation. A Box-Pierce test for larger lags also revealed that the proposed model is adequate for forecasting. Due to the high forecast accuracy of the proposed SARIMA model, the study recommends the use of the proposed SARIMA model in the analysis of road traffic accidents in Ghana.

Early Postnatal Expression of Tgfß-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with white matter injury (WMI) and reduced neurogenesis. IVH commonly arises from the germinal matrix, a highly cellular, transient structure, where all precursor cells are born, proliferate, and migrate during brain development. IVH leads to reduced progenitor cell proliferation and maturation and contributes to WMI. Interruption of oligodendrocyte lineage (OL) proliferation and maturation after IVH will prevent myelination. We evaluated whether unrestricted somatic stem cells (USSCs) could recover OL lineage, as USSC release multiple relevant growth factors and cytokines. The effects of USSC infusion at 24 hours after IVH were assessed in the periventricular zone by analysis of OL lineage-specific progression (PDGFR+, OLIG2+, NKX2.2+ with Ki67), and this was correlated with growth factors TGFß1, FGF2 expression. The early OL cell lineage by immunofluorescence and cell density quantitation showed significant reduction after IVH (P < .05 both PDGFR+, OLIG2+ at day 3); with significant recovery after injection of USSCs (P < .05 both PDGFR+, OLIG2+ at day 3). CSF protein and tissue mRNA levels of TGFß1 were reduced by IVH and recovered after USSC (P < .05 for all changes). FGF2 showed an increased mRNA after USSC on day3 (P < .05). Cell cyclin genes were unaffected except for the cycle inhibitor P27Kip1 which increased after IVH but returned to normal after USSC on day 3. Our findings demonstrated a plausible mechanism through which USSCs can aid in developmental myelination by recovery of OL proliferation and maturation along with correlative changes in growth factors during brain development.

Baseline comparative analysis and review of election forensics: Application to Ghana's 2012 and 2020 presidential elections.

Many allegations have been levelled against the electoral process of many countries across the world by most opposition leaders, especially when they lose a presidential election e.g. Ghana in 2012 and 2020. Therefore, the need to apply election forensic techniques to the certified election results data of valid votes count to statistically verify if some suspected or possible anomalies and irregularities exist in the voting pattern. This paper seeks to provide a comprehensive review of election forensics techniques and make a comparative analysis of Benford's Second-order test of conformity (using the first two digits) and Hartigans' dip test of unimodality to examine the existence of possible anomalies and irregularities in the 2012 and 2020 presidential elections held in Ghana. The findings of the two tests suggest that the electoral process produced possible anomalous data in the 2012 presidential election results (with an overall 16.67% suspected anomalies), whilst possible non-anomalous data was produced in the 2020 presidential election results (with an overall 0% suspected anomaly) of valid votes count. Therefore, the study recommends that for better statistical data analysis on election anomaly detection, Benford's test of conformity and Hartigans' dip test of unimodality should serve as baseline tests (initial screening tools), highlighting areas that may require further investigation or more rigorous analysis and progressively dig deeper into the application of finite mixture fraud models and machine learning techniques. In spite of the promising results Benford's Law, dip test, machine learning algorithms, and network analysis have produced in detecting irregularities in election data, real-world applications remain challenging, particularly when dealing with complex and evolving forms of fraud. Therefore, there is the need for continuous research and innovation to improve the accuracy and effectiveness of these methods and promote transparency and accountability in democratic societies.

Development of a Slow-Degrading Polymerized Curcumin Coating for Intracortical Microelectrodes.

Intracortical microelectrodes are used with brain-computer interfaces to restore lost limb function following nervous system injury. While promising, recording ability of intracortical microelectrodes diminishes over time due, in part, to neuroinflammation. As curcumin has demonstrated neuroprotection through anti-inflammatory activity, we fabricated a 300 nm-thick intracortical microelectrode coating consisting of a polyurethane copolymer of curcumin and polyethylene glycol (PEG), denoted as poly(curcumin-PEG1000 carbamate) (PCPC). The uniform PCPC coating reduced silicon wafer hardness by two orders of magnitude and readily absorbed water within minutes, demonstrating that the coating is soft and hydrophilic in nature. Using an in vitro release model, curcumin eluted from the PCPC coating into the supernatant over 1 week; the majority of the coating was intact after an 8-week incubation in buffer, demonstrating potential for longer term curcumin release and softness. Assessing the efficacy of PCPC within a rat intracortical microelectrode model in vivo, there were no significant differences in tissue inflammation, scarring, neuron viability, and myelin damage between the uncoated and PCPC-coated probes. As the first study to implant nonfunctional probes with a polymerized curcumin coating, we have demonstrated the biocompatibility of a PCPC coating and presented a starting point in the design of poly(pro-curcumin) polymers as coating materials for intracortical electrodes.

Biocidal Potency of Polymers with Bulky Cations.

The performance of antimicrobial polymers depends sensitively on the type of cationic species, charge density, and spatial arrangement of cations. Here we report antimicrobial polymers bearing unusually bulky tetraaminophosphonium groups as the source of highly delocalized cationic charge. The bulky cations drastically enhanced the biocidal activity of amphiphilic polymers, leading to remarkably potent activity in the submicromolar range. The cationic polynorbornenes with pendent tetraaminophosphonium groups killed over 98% E. coli at a concentration of 0.1 µg/mL and caused a 4-log reduction of E. coli within 2 h at a concentration of 2 µg/mL, showing very rapid and potent bactericidal activity. The polymers are also highly hemolytic at similar concentrations, indicating a biocidal activity profile. Polymers of a similar chemical structure but with more flexible backbones were made to examine the effects of the flexibility of polymer chains on their activity, which turned out to be marginal. We also explore variants with different spacer arm groups separating the cations from the backbone main chain. The antibacterial activity was comparably potent in all cases, but the polymers with shorter spacer arm groups showed more rapid bactericidal kinetics. Interestingly, pronounced counterion effects were observed. Tightly bound PF6- counteranions showed poor activity at high concentrations due to gross aggregate formation and precipitation from the assay media, whereas loosely bound Cl- counterions resulted in very potent activity that monotonically increased with increasing concentration. In this paper, we reveal that bulky phosphonium cations are associated with markedly enhanced biocidal activity, which provides an innovative strategy to develop more effective self-disinfecting materials.

Poly(pro-curcumin) Materials Exhibit Dual Release Rates and Prolonged Antioxidant Activity as Thin Films and Self-Assembled Particles.

Curcumin is a natural polyphenol that exhibits remarkable antioxidant and anti-inflammatory activities; however, its clinical application is limited in part by its physiological instability. Here, we report the synthesis of curcumin-derived polyesters that release curcumin upon hydrolytic degradation to improve curcumin stability and solubility in physiological conditions. Curcumin was incorporated in the polymer backbone by a one-pot condensation polymerization in the presence of sebacoyl chloride and polyethylene glycol (PEG, Mn = 1 kDa). The thermal and mechanical properties, surface wettability, self-assembly behavior, and drug-release kinetics all depend sensitively on the mole percentage of curcumin incorporated in these statistical copolymers. Curcumin release was triggered by the hydrolysis of phenolic esters on the polymer backbone, which was confirmed using a PEGylated curcumin model compound, which represented a putative repeating unit within the polymer. The release rate of curcumin was controlled by the hydrophilicity of the polymers. Burst release (2 days) and extended release (>8 weeks) can be achieved from the same polymer depending on curcumin content in the copolymer. The materials can quench free radicals for at least 8 weeks and protect primary neurons from oxidative stress in vitro. Further, these copolymer materials could be processed into both thin films and self-assembled particles, depending on the solvent-based casting conditions. Finally, we envision that these materials may have potential for neural tissue engineering application, where antioxidant release can mitigate oxidative stress and the inflammatory response following neural injury.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

BACKGROUND AND OBJECTIVES: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study. Kidney function, urine albumin, and BP were measured at 2-year (24±2 months) corrected gestational age. We compared outcomes across gestational age categories and evaluated associations between kidney-related outcomes and neonatal and maternal characteristics. The primary outcome was eGFR <90 ml/min per 1.73 m2 (CKD); secondary outcomes were spot urine albumin-creatinine ratio ≥30 mg/g (albuminuria) and either systolic BP or diastolic BP >90th percentile for height, age, and sex. RESULTS: A total of 832 survived to 2 years, and 565 (68%) had at least one outcome measured. Overall, 297 (53%) had one abnormal kidney outcome; 61 (18%) had an eGFR <90 ml/min per 1.73 m2, 155 (36%) had albuminuria, 65 (22%) had elevated systolic BP, and 128 (44%) had elevated diastolic BP. Gestational age (odds ratio, 0.94; 95% confidence interval, 0.89 to 0.99), birth weight z-score (odds ratio, 0.92; 95% confidence interval, 0.85 to 0.98), and prenatal steroids (odds ratio, 1.23; 95% confidence interval, 1.08 to 1.39) were associated with an eGFR <90 ml/min per 1.73 m2. An elevated systolic BP was associated with indomethacin use (odds ratio, 1.18; 95% confidence interval, 1.04 to 1.33) and Black race (odds ratio, 1.19; 95% confidence interval, 1.01 to 1.39); elevated diastolic BP was associated with male sex (odds ratio, 1.29; 95% confidence interval, 1.12 to 1.49), severe AKI (odds ratio, 1.24; 95% confidence interval, 1.04 to 1.48), and indomethacin use (odds ratio, 1.16; 95% confidence interval, 1.01 to 1.33). CONCLUSIONS: Approximately 18% of extremely low gestational age neonates have CKD, 36% have albuminuria, 22% have an elevated systolic BP, and 44% have an elevated diastolic BP at 2 years of age. Gestational age, birthweight z-score, and prenatal steroids were associated with CKD. Male sex, Black race, indomethacin use, and severe AKI were associated with elevated BP. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_19_CJN15011121.mp3.

Emerging therapies for brain recovery after IVH in neonates: Cord blood derived Mesenchymal Stem Cells (MSC) and Unrestricted Somatic Stem Cells (USSC).

In this report, we summarize evidence on mechanisms of injury after intraventricular hemorrhage resulting in post-hemorrhagic white matter injury and hydrocephalus and correlate that with the possibility of cellular therapy. We describe how two stem cell lines (MSC & USSC) acting in a paracrine fashion offer promise for attenuating the magnitude of injury in animal models and for improved functional recovery by: lowering the magnitude of apoptosis and neuronal cell death, reducing inflammation, and thus, mitigating white matter injury that culminates in improved motor and neurocognitive outcomes. Animal models of IVH are analyzed for their similarity to the human condition and we discuss merits of each approach. Studies on stem cell therapy for IVH in human neonates is described. Lastly, we offer suggestions on what future studies are needed to better understand mechanisms of injury and recovery and argue that human trials need to be expanded in parallel to animal research.

Virucidal N95 Respirator Face Masks via Ultrathin Surface-Grafted Quaternary Ammonium Polymer Coatings.

N95 respirator face masks serve as effective physical barriers against airborne virus transmission, especially in a hospital setting. However, conventional filtration materials, such as nonwoven polypropylene fibers, have no inherent virucidal activity, and thus, the risk of surface contamination increases with wear time. The ability of face masks to protect against infection can be likely improved by incorporating components that deactivate viruses on contact. We present a facile method for covalently attaching antiviral quaternary ammonium polymers to the fiber surfaces of nonwoven polypropylene fabrics that are commonly used as filtration materials in N95 respirators via ultraviolet (UV)-initiated grafting of biocidal agents. Here, C12-quaternized benzophenone is simultaneously polymerized and grafted onto melt-blown or spunbond polypropylene fabric using 254 nm UV light. This grafting method generated ultrathin polymer coatings which imparted a permanent cationic charge without grossly changing fiber morphology or air resistance across the filter. For melt-blown polypropylene, which comprises the active filtration layer of N95 respirator masks, filtration efficiency was negatively impacted from 72.5 to 51.3% for uncoated and coated single-ply samples, respectively. Similarly, directly applying the antiviral polymer to full N95 masks decreased the filtration efficiency from 90.4 to 79.8%. This effect was due to the exposure of melt-blown polypropylene to organic solvents used in the coating process. However, N95-level filtration efficiency could be achieved by wearing coated spunbond polypropylene over an N95 mask or by fabricating N95 masks with coated spunbond as the exterior layer. Coated materials demonstrated broad-spectrum antimicrobial activity against several lipid-enveloped viruses, as well as Staphylococcus aureus and Escherichia coli bacteria. For example, a 4.3-log reduction in infectious MHV-A59 virus and a 3.3-log reduction in infectious SuHV-1 virus after contact with coated filters were observed, although the level of viral deactivation varied significantly depending on the virus strain and protocol for assaying infectivity.

Depression complexity prevalence and outcomes among veterans affairs patients in integrated primary care.

INTRODUCTION: The Veterans Health Administration (VA) Primary Care-Mental Health Integration (PC-MHI) initiative targets depression (MDD), anxiety/posttraumatic stress disorder (PTSD) and alcohol misuse (AM) for care improvement. In primary care, case finding often relies on depression screening. Whereas clinical practice guidelines solely inform management of depression, minimal information exists to guide treatment when psychiatric symptom clusters coexist. We provide descriptive clinical information for care planners about VA PC patients with depression alone, depression plus alcohol misuse, and depression with complex psychiatric comorbidities (PTSD and/or probable bipolar disorder). METHOD: We examined data from a VA study that used a visit-based sampling procedure to screen 10,929 VA PC patients for depression; 761 patients with probable major depression completed baseline measures of health and care engagement. Follow-up assessments were completed at 7 months. RESULTS: At baseline, 53% of patients evidenced mental health conditions in addition to depression; 10% had concurrent AM, and 43% had psychiatrically complex depression (either with or without AM). Compared with patients with depression alone or depression with AM, those with psychiatrically complex depression evinced longer standing and more severe mood disturbance, higher likelihood of suicidal ideation, higher unemployment, and higher levels of polypharmacy. Baseline depression complexity predicted worse mental health status and functioning at follow-up. DISCUSSION: A substantial proportion of VA primary care patients with depression presented with high medical multimorbidity and elevated safety concerns. Psychiatrically complex depression predicted lower treatment effectiveness, suggesting that PC-MHI interventions should co-ordinate and individualize care for these patients. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Bacteria - derived short chain fatty acids restore sympathoadrenal responsiveness to hypoglycemia after antibiotic-induced gut microbiota depletion.

The microbiome co-evolved with their mammalian host over thousands of years. This commensal relationship serves a pivotal role in various metabolic, physiological, and immunological processes. Recently we discovered impaired adrenal catecholamine stress responses in germ-free mice suggesting developmental modification of the reflex arc or absence of an ongoing microbiome signal. To determine whether maturational arrest or an absent bacteria-derived metabolite was the cause, we tested whether depleting gut microbiome in young adult animals could also alter the peripheral stress responses to insulin-induced hypoglycemia. Groups of C57Bl6 male mice were given regular water (control) or a cocktail of non-absorbable broad-spectrum antibiotics (Abx) in the drinking water for two weeks before injection with insulin or saline. Abx mice displayed a profound decrease in microbial diversity and abundance of Bacteroidetes and Firmicutes, plus a markedly enlarged caecum and no detectable by-products of bacterial fermentation (sp. short chain fatty acids, SCFA). Tonic and stress-induced epinephrine levels were attenuated. Recolonization (Abx + R) restored bacterial diversity, but not the sympathoadrenal system responsiveness or caecal acetate, propionate and butyrate levels. In contrast, corticosterone (HPA) and glucagon (parasympathetic) resting values and responses to hypoglycemia remained similar across all conditions. Oral supplementation with SCFA improved epinephrine responses to hypoglycaemia. Whole genome shotgun sequence profiling of fecal samples from control, Abx and Abx + R cohorts identified nine microbes (SCFA producers) absent from both Abx and Abx + R groups. These results implicate gut microbiome depletion plus its attendant reduction in SCFA signalling in adversely affecting the release of epinephrine in response to hypoglycemia. We speculate that regardless of postnatal age, a mutable microbiome messaging system exists throughout life. Unravelling these mechanisms could lead to new therapeutic possibilities through controlled manipulation of the gut microbiota and its ability to alter systemic neurotransmitter responsiveness.

Unexpected Enhancement of Antimicrobial Polymer Activity against Staphylococcus aureus in the Presence of Fetal Bovine Serum.

Cationic and amphiphilic polymers are known to exert broad-spectrum antibacterial activity by a putative mechanism of membrane disruption. Typically, nonspecific binding to hydrophobic components of the complex biological milieu, such as globular proteins, is considered a deterrent to the successful application of such polymers. To evaluate the extent to which serum deactivates antibacterial polymethacrylates, we compared their minimum inhibitory concentrations in the presence and absence of fetal bovine serum. Surprisingly, we discovered that the addition of fetal bovine serum (FBS) to the assay media in fact enhances the antimicrobial activity of polymers against Gram-positive bacteria S. aureus, whereas the opposite is the case for Gram-negative E. coli. Here, we present these unexpected trends and develop a hypothesis to potentially explain this unusual phenomenon.

Posttraumatic stress disorder collaborative care: A quality improvement study in veterans affairs primary care.

Introduction: Collaborative care improves depression and anxiety outcomes. In this naturalistic, observational case study, we adapted an evidence-based depression collaborative care protocol for the assessment and treatment of posttraumatic stress disorder (PTSD) and sought to demonstrate that the protocol could be implemented in Veterans Affairs (VA) primary care. Method: Based on feedback from a content expert panel, clinical stakeholders, and a pilot study conducted in a postdeployment clinic, the original depression collaborative care protocol was modified to include PTSD assessment and support for PTSD medication adherence, self-management, and engagement in evidence-based PTSD care. Results: The modified program was implemented from November 2012 to March 2017, and 239 patients with PTSD were referred. Nearly two thirds (n = 185) enrolled, and they participated in the program for an average of 4 to 5 months and completed calls approximately once per month. Among patients with more than one assessment of clinical outcomes, 53.4% (n = 94) reported clinically significant improvement in depression on the Patient Health Questionnaire-9 (≥ 5-point decrease), and 42.2% (n = 35) reported clinically significant improvement on the PTSD Checklist (≥ 10-point decrease). Veterans and clinical staff described the modified collaborative care program positively in qualitative interviews. Discussion: Our findings suggest that a depression collaborative care program can be modified to support treatment of PTSD in primary care. The modified program was acceptable to both veterans and clinical staff and showed potential for positive clinical change in an uncontrolled quality improvement study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with cerebral palsy, intellectual disability, and commonly, accumulation of cerebrospinal fluid (CSF). Histologically, IVH leads to subependymal gliosis, fibrosis, and disruption of the ependymal wall. Importantly, expression of aquaporin channels 1 and 4 (AQP1 and AQP4) regulating respectively, secretion and absorption of cerebrospinal fluids is altered with IVH and are associated with development of post hemorrhagic hydrocephalus. Human cord blood derived unrestricted somatic stem cells (USSCs), which we previously demonstrated to reduce the magnitude of hydrocephalus, as having anti-inflammatory, and beneficial behavioral effects, were injected into the cerebral ventricles of rabbit pups 18 h after glycerol-induced IVH. USSC treated IVH pups showed a reduction in ventricular size when compared to control pups at 7 and 14 days (both, P < 0.05). Histologically, USSC treatment reduced cellular infiltration and ependymal wall disruption. In the region of the choroid plexus, immuno-reactivity for AQP1 and ependymal wall AQP4 expression were suppressed after IVH but were restored following USSC administration. Effects were confirmed by analysis of mRNA from dissected choroid plexus and ependymal tissue. Transforming growth factor beta (TGF-ß) isoforms, connective tissue growth factor (CTGF) and matrix metalloprotease-9 (MMP-9) mRNA, as well as protein levels, were significantly increased following IVH and restored towards normal with USSC treatment (P < 0.05). The anti-inflammatory cytokine Interleukin-10 (IL-10) mRNA was reduced in IVH, but significantly recovered after USSC injection (P < 0.05). In conclusion, USSCs exerted anti-inflammatory effects by suppressing both TGF-ß specific isoforms, CTGF and MMP-9, recovered IL-10, restored aquaporins expression towards baseline, and reduced hydrocephalus. These results support the possibility of the use of USSCs to reduce IVH consequences in prematurity.

Acute Dose-Dependent Neuroprotective Effects of Poly(pro-17ß-estradiol) in a Mouse Model of Spinal Contusion Injury.

17ß-Estradiol (E2) confers neuroprotection in preclinical models of spinal cord injury when administered systemically. The goal of this study was to apply E2 locally to the injured spinal cord for a sustained duration using poly(pro-E2) film biomaterials. Following contusive spinal cord injury in adult male mice, poly(pro-E2) films were implanted subdurally and neuroprotection was assessed using immunohistochemistry 7 days after injury and implantation. In these studies, poly(pro-E2) films modestly improved neuroprotection without affecting the inflammatory response when compared to the injured controls. To increase the E2 dose released, bolus-releasing poly(pro-E2) films were fabricated by incorporating unbound E2 into the poly(pro-E2) films. However, compared to the injured controls, bolus-releasing poly(pro-E2) films did not significantly enhance neuroprotection or limit inflammation at either 7 or 21 days post-injury. Future work will focus on developing poly(pro-E2) biomaterials capable of more precisely releasing therapeutic doses of E2.

Effect of ventilator modes on neonatal cerebral and peripheral oxygenation using near-infrared spectroscopy.

AIM: The effect of ventilator modes on regional tissue oxygenation in premature neonates with respiratory distress syndrome (RDS) has yet to be delineated. Previous studies have looked at global oxygen delivery and have not assessed the effects on regional tissue oxygenation. Our aim in this study was to assess such tissue oxygenation in premature babies with RDS in relation to differing modes of ventilation using near-infrared spectroscopy (NIRS). METHODS: In 24 stable preterm infants with RDS, undergoing elective wean in ventilator mode, cerebral and muscle tissue oxygenation were assessed using NIRS. Infants were weaned from high-frequency oscillator or jet ventilator to conventional invasive ventilation (CV) or extubated from CV to non-invasive mechanical ventilation. Data at 30 minutes prior and at one hour after change in ventilator mode were compared (paired t test). RESULTS: In babies changed from high-frequency oscillation to CV, jet to CV and CV to non-invasive ventilation, the differences in cerebral NIRS (mean ± SD) were 1.7 ± 9.9%, 2.3 ± 5.7% and 2.1 ± 8.4%, respectively. The concomitant changes in muscle NIRS were -2.9 ± 8.5%, 8.1 ± 9.7% and 3.6 ± 22.4%, respectively. No changes were statistically significant. CONCLUSION: Our data suggest that there is no alteration in regional tissue oxygenation related to ventilator mode in stable preterm infants with improving RDS.

Respiratory Severity Score greater than or equal to 2 at birth is associated with an increased risk of mortality in infants with birth weights less than or equal to 1250 g.

OBJECTIVE: Respiratory Severity Score (RSS), the product of mean airway pressure and the fraction of inspired oxygen may estimate the severity of neonatal lung disease. We aimed to determine if RSS on the first day of life is associated with mortality and/or comorbidities in infants born less than or equal to 1250 g. METHODS: Data were extracted from the NYS Perinatal Data System for premature inborn infants from 2006 to 2016 born between 400 and 1250 g (N = 730). RSS was divided into three categories: less than 2 (low, n = 310), 2-5 (moderate, n = 265), greater than 5 (high, n = 155). The primary outcome was mortality. Logistic regression determined associations with composite outcomes of death or respiratory morbidity (respiratory support after 36 weeks postmenstrual age), death or neurologic morbidity (periventricular leukomalacia) or high-grade intraventricular hemorrhage), and death/severe morbidity (death or neurologic morbidity or respiratory morbidity or stage ≥ III retinopathy of prematurity or necrotizing enterocolitis) by RSS category. RESULTS: Birthweight and gestational age were lower with the increasing RSS category (p < .001 for both). Mode of delivery, antenatal steroids, and maternal age did not differ by RSS. In adjusted analyses, there were increased odds of mortality in infants with moderate RSS (odds ratio [95% confidence intervals]: 3.1 (1.7-5.4) and high 4.5 (2.5-8.2). These groups had higher odds of death or respiratory morbidity, death or neurologic morbidity, and death/severe morbidity. CONCLUSION: Higher RSS (≥2) is associated with an increased risk of mortality and morbidities in infants born less than or equal to 1250 g.

Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure. Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions. Design, Setting, and Participants: The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019. Interventions: In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks. Main Outcomes and Measures: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein. Results: A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001). Conclusions and Relevance: These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.