Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City.

Highly pathogenic avian influenza viruses of the H5N1 clade 2.3.4.4b were detected in North America in the winter of 2021/2022. These viruses have spread across the Americas, causing morbidity and mortality in both wild and domestic birds as well as some mammalian species, including cattle. Many surveillance programs for wildlife as well as commercial poultry operations have detected these viruses. In this study, we conducted surveillance of avian species in the urban environment in New York City. We detected highly pathogenic H5N1 viruses in six samples from four different bird species and performed whole-genome sequencing. Sequencing analysis showed the presence of multiple different genotypes. Our work highlights that the interface between animals and humans that may give rise to zoonotic infections or even pandemics is not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers.IMPORTANCEWhile surveillance programs for avian influenza viruses are often focused on migratory routes and their associated stop-over locations or commercial poultry operations, many bird species-including migratory birds-frequent or live in urban green spaces and wetlands. This brings them into contact with a highly dense population of humans and pets, providing an extensive urban animal-human interface in which the general public may have little awareness of circulating infectious diseases. This study focuses on virus surveillance of this interface, combined with culturally responsive science education and community outreach.

Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City.

Highly pathogenic avian influenza viruses of the H5N1 clade 2.3.4.4b arrived in North America in the winter of 2021/2022. These viruses have spread across the Americas causing morbidity and mortality in both wild and domestic birds as well as some mammalian species, including cattle. Many surveillance programs in wildlife as well as commercial poultry operations have detected these viruses. Here we conducted surveillance of avian species in the urban environment in New York City. We detected highly pathogenic H5N1 viruses in six samples from four different bird species and performed full genome sequencing. Sequence analysis showed the presence of multiple different genotypes. Our work highlights that the interface between animals and humans that may give rise to zoonotic infections or even pandemics is not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers.

Application of three-dimensional printed biomodels in endoscopic spinal surgery.

Background: Three-dimensional printing (3DP) is increasingly used to individualise surgery and may be an effective tool for representing patient anatomy. Current literature on patient-specific anatomical models (biomodels) for minimally invasive spinal surgery is a limited number of case series and cohort studies. However, studies investigating 3DP in other specialties have reported multiple benefits. Methods: This prospective study considered a series of patients (n=33) undergoing elective endoscopic spinal surgery, including combinations of microdiscectomy (n=27), foraminotomy (n=7), and laminectomy (n=3). These surgeries were conducted at vertebral levels ranging from L2/3 to L5/S1. The surgeon then recorded the impact on preoperational planning, intraoperative decision-making and accelerating the learning curve with a qualitative questionnaire. Results: There were benefits to planning in 54.5% of cases (n=18), improved intraoperative decision-making in 60.6% of cases (n=20). These benefits were reported more frequently earlier in the cases, with improvements to learning reported in 60% of the first five cases and not in subsequent cases. The surgeon commented that the biomodels were more useful on. Conclusions: The rates of preoperative and intraoperative benefits are consistent with existing studies, and the early benefit to the learning curve may be suitable for applications to surgical training. Additional research is required to determine the practicality of biomodels and their impact on patient outcomes for endoscopic spinal surgery.

Cigarette smoke stimulates clonal expansion of Jak2V617F and Tet2-/- cells.

Introduction: Somatic mutations in myeloid growth factor pathway genes, such as JAK2, and genes involved in epigenetic regulation, such as TET2, in hematopoietic stem cells (HSCs) leads to clonal hematopoiesis of indeterminate potential (CHIP) which presents a risk factor for hematologic malignancy and cardiovascular disease. Smoking behavior has been repeatedly associated with the occurrence of CHIP but whether smoking is an environmental inflammatory stressor in promoting clonal expansion has not been investigated. Methods: We performed in vivo smoke exposures in both wildtype (WT) mice and transplanted mice carrying Jak2V617F mutant and Tet2 knockout (Tet-/-) cells to determine the impact of cigarette smoke (CS) in the HSC compartment as well as favoring mutant cell expansion. Results: WT mice exposed to smoke displayed increased oxidative stress in long-term HSCs and suppression of the hematopoietic stem and progenitor compartment but smoke exposure did not translate to impaired hematopoietic reconstitution in primary bone marrow transplants. Gene expression analysis of hematopoietic cells in the bone marrow identified an imbalance between Th17 and Treg immune cells suggesting a local inflammatory environment. We also observed enhanced survival of Jak2V617F cells exposed to CS in vivo and cigarette smoke extract (CSE) in vitro. WT bone marrow hematopoietic cells from WT/Jak2V617F chimeric mice exposed to CS demonstrated an increase in neutrophil abundance and distinct overexpression of bone marrow stromal antigen 2 (Bst2) and retinoic acid early transcript 1 (Raet1) targets. Bst2 and Raet1 are indicative of increased interferon signaling and cellular stress including oxidative stress and DNA damage, respectively. In chimeric mice containing both WT and Tet2-/- cells, we observed an increased percentage of circulating mutant cells in peripheral blood post-cigarette smoke exposure when compared to pre-exposure levels while this difference was absent in air-exposed controls. Conclusion: Altogether, these findings demonstrate that CS results in an inflamed bone marrow environment that provides a selection pressure for existing CHIP mutations such as Jak2V617F and Tet2 loss-of-function.

Quality of Information for Post-Prostatectomy Incontinence Treatments on YouTube.

OBJECTIVE: To assess the quality of information on YouTube regarding post-prostatectomy incontinence treatments. The 2019 American Urological Association(AUA)/(SUFU) Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction guidelines recommend the placement of a male sling or artificial urinary sphincter. Patient education is essential for appropriate expectations and patient satisfaction. METHODS: The top 100 most relevant (default setting) YouTube videos searched with terms "post-prostatectomy incontinence" and "male stress incontinence" were assessed using the validated DISCERN instrument, Patient Education Materials Assessment Tool for Audiovisual Materials, and a misinformation Likert Scale. Videos with poor video/audio quality, duplicates, and non-English videos were excluded. Four independent raters were randomly assigned such that each video had 2 raters. Data was analyzed using multivariate linear regression, and inter-rater reliability was measured using Cohen's kappa. RESULTS: The median DISCERN score was 2.5 with 71% of videos scoring <=3. The median PEMAT Actionability and Understandability scores were 64.6 (range 0-100) and 79.9 (range 52-100), respectively. The median misinformation Likert score was 1 range (1-4). Less than half of the videos discussed realistic treatment outcomes or the risks (39% and 24%, respectively). PEMAT Actionability and risk discussion significantly predicted average DISCERN score (p < .001). There were no significant disagreements between raters. CONCLUSION: Our study shows most videos on post-prostatectomy incontinence had moderate to low quality information and were published by medical professionals. The majority did not sufficiently discuss realistic outcomes and risks, which are hallmarks of informed decision making. This provides an opportunity for the urologic community to create educational materials that adequately supplement shared-decision making for patients treated for post-prostatectomy incontinence.

Mental Health of Emergency Department Healthcare Workers During COVID-19 in Brooklyn, New York.

Background: Maintaining good mental health among Emergency Department healthcare workers (ED HCW) is paramount to well-functioning healthcare. We measured mental health and COVID-19 symptoms in ED HCW at a COVID-19 epicenter. Methods: A cross-sectional, convenience sample of adult (≥18 years) ED HCW in Brooklyn, New York, USA, who were employed at ≥50% of a full-time effort, was surveyed September-December, 2020 with reference period March-May 2020. An anonymous email-distributed survey assessed gender, age, race, healthcare worker status (clinical versus non-clinical), SARS-CoV-2 testing, number of people to talk to, COVID-19-related home problems, mental health care interruption during COVID-19, loneliness, and survey date. Outcomes included symptoms of depression, psychological distress, perceived stress, post-traumatic stress disorder (PTSD), anxiety, and resilience measured using validated scales. Results: Of 774 HCW, 247 (31.9%) responded (mean age 38.2±10.8 years; 59.4% White; 52.5% men; 80.1% clinical; 61.6% SARS-CoV-2 tested). Average mental health scores were significantly higher among clinical vs non-clinical HCW (P's<0.0001-0.019). The proportion reporting a clinically-relevant psychological distress symptom burden was higher among clinical vs non-clinical HCW (35.8% vs 13.8%, p=0.019); and suggested for depression (53.9% clinical vs 35.7% non-clinical, p=0.072); perceived stress (63.6% clinical vs 44.8% non-clinical, p=0.053); and PTSD (18.2% clinical vs 3.6% non-clinical, p=0.064). Compared to non-clinical staff, Medical Doctors and Doctors of Osteopathy reported 4.8-fold higher multivariable-adjusted odds of clinically-relevant perceived stress (95%CI 1.8-12.9, p=0.002); Emergency Medical Technicians reported 15.5-fold higher multivariable-adjusted odds of clinically-relevant PTSD (95%CI 1.6-150.4, p=0.018). Increasing age, number of COVID-19-related home problems and people to talk to, loneliness and mental health care interruption were adversely associated with mental health; being male and SARS-CoV-2 testing were beneficial. Conclusions: COVID-19-related mental health burden was high among ED HCW in Brooklyn. Mental health support services are essential for ED HCW.

Nanocrystalline Yttria-Stabilized Zirconia Ceramics for Cranial Window Applications.

Transparent yttria-stabilized zirconia (YSZ) ceramics are promising for cranial window applications because of their good mechanical and optical properties as well as biocompatibility. YSZ discs with different yttria concentrations were either processed via current-activated pressure-assisted densification (CAPAD) using commercial nanoparticles or densified via spark plasma sintering (SPS) using pyrolysis-synthesized nanoparticles in-house. This study provided critical results to screen composition, processing, microstructure, and cytocompatibility of transparent YSZ discs for cranial window applications. CAPAD-processed YSZ discs with 6 or 8 mol % yttria (6YSZ and 8YSZ) and SPS-densified YSZ discs with 4 mol % yttria (4YSZ_P) showed 200-350 nm polycrystalline grains containing 20-30 nm crystallite domains. SPS-densified YSZ discs with 8 mol % yttria (8YSZ_P) showed larger polycrystalline grains of 819 ± 155 nm with 29 ± 5 nm crystallite domains. CAPAD-processed YSZ discs with 3 mol % yttria (3YSZ) showed 39 ± 9 nm grains. Bone-marrow-derived stem cells (BMSCs) on the polished YSZ discs showed statistically higher spreading areas than those on the unpolished YSZ discs of the same compositions. Generally, polished 8YSZ, 4YSZ_P, and 8YSZ_P discs and unpolished 8YSZ_R, 4YSZ_PR, and 8YSZ_PR discs had lower average cell adhesion densities than other YSZ discs under direct contact conditions. Under indirect contact conditions, all the YSZ disc groups showed similar average cell adhesion densities to the Cell-only control. The groups of polished 4YSZ_P and 8YSZ_P discs, unpolished 4YSZ_PR and 8YSZ_PR discs, and particle control of 8YSZ_Pnp showed higher Y3+ ion concentrations than other groups. No mineral deposition was detected on the polished YSZ discs after cell culture. Considering multiple factors such as cytocompatibility, cell adhesion density, Y3+ ion release, mineral deposition, and optical transparency collectively, 8YSZ may be the best candidate for the cranial window applications. Further studies are needed to evaluate the long-term transparency and biocompatibility of YSZ discs.

Definitive treatment choice among Black immigrants with prostate cancer: Analysis of patient surveys distributed at a single safety-net institution.

BACKGROUND: Large-scale prostate cancer (PCa) database reviews have found a consistent discrepancy in the mortality rate in Black patients compared to their White counterparts. Furthermore, differences in PCa treatment and outcomes among Black men of different ethnic origins have also been identified. Due to the heterogeneity of PCa-impacted communities and the unclear impact of patient immigration status on treatment outcomes, we sought to determine the demographic factors associated with treatment choice for definitive treatment of PCa in our single institution's patient population of Black immigrants. METHODS: We distributed surveys to all patients in the Kings County Hospital Center urologic oncology clinic from February 2019 to February 2020 and collected relevant health information via EMR. The survey collected demographic information regarding age, education, health insurance, employment status, socioeconomic status, country of birth, and years living in the United States (US). RESULTS: Out of the 253 patients surveyed, the majority of patients surveyed were Black and foreign born. There were no significant differences in demographic data between US-born and foreign-born patients except number of years living in the United States. In the intermediate risk group, patients living in the United States for <10 years chose surgery significantly more often than US-born patients (90.9% vs. 50.0%, p = 0.036). On multivariate analysis, patients that chose surgery were more likely to be older when diagnosed (odds ratio [OR] = 1.21) and less likely to be born in the United States than in African or Caribbean countries (OR = 0.054). CONCLUSIONS: In our study of a majority-Black population, we found that patients born in the United States were less likely than their foreign counterparts to opt for surgery, as previous studies have shown. The choice of definitive treatment modality for Black men with intermediate risk PCa was found to be influenced by age at diagnosis and immigration status.

Association between pregnancy and nocturia: A National Health and Nutrition Examination Survey analysis.

AIMS: This study aimed to determine the impact of pregnancy and pregnancy-associated characteristics on nocturia. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) database from 2005/06 to 2017/18, we analyzed women who completed the "Reproductive Health" and "Kidney Conditions-Urology" questionnaires by sorting them into three groups: nulligravida, previously pregnant (nonpregnant with prior pregnancies), and currently pregnant. After excluding patients with pre-existing conditions impacting nocturia or with incomplete data, we weighed and matched the groups for age, race, BMI, and number of pregnancies. The relationships of nocturia to pregnancy in all groups and pregnancy-associated characteristics (gestational diabetes mellitus [GDM], history of multiple pregnancies, and trimesters of pregnancy) in currently pregnant women were assessed. RESULTS: Of 8330 women that indicated pregnancy status, 1544 women (age range: 20-44 years; 523 nulligravida, 498 previously pregnant, 523 currently pregnant women) were included in analysis. Currently, pregnant women had a higher prevalence of nocturia than previously pregnant and nulligravida women (56.4% vs. 22.5% vs. 16.1%, p < 0.001) and had the highest odds of nocturia (OR: 6.82, p < 0.001). GDM or history of multiple pregnancies showed no associations in currently pregnant women. Increasing trimesters were associated with nocturia, with the third trimester showing the highest odds (OR: 10.35, p < 0.001) and a greater average of nighttime voids than the first and second trimesters (2.40 ± 1.42 vs. 1.56 ± 1.31 and 1.88 ± 1.32, p < 0.001). CONCLUSIONS: The association noted between pregnancy and nocturia, which strengthened with increasing trimesters, demonstrates that nocturia can significantly impact quality of life and therefore must be addressed during pregnancy.

Analysis of Twitter Engagement in a Progressively More Competitive Urology Match: A Mixed Methods Study.

OBJECTIVE: To analyze Twitter engagement in response to the urology match during the COVID-19 pandemic. METHODS: Tweets containing the hashtags "#uromatch" or "#AUAmatch" during the 2021 and 2022 Match Week were reviewed. Date, author type and number of followers, general content, and engagement with each Tweet was collected. Differences in engagement between author type and content were analyzed using the Kruskal-Wallis H test. Tweet characteristics were compared between the 2021 and 2022 Match Cycles using the Chi-Square test. RESULTS: There were 656 Tweets in total, with 272 (43.5%) from 2021 and 353 (56.5%) from 2022. Medical students' and residency programs' posts received significantly more Tweet engagement than those by residents/fellows, attendings, or the AUA (P <.05). Tweets focusing on announcing a new residency class and personal announcements of match results received significantly more engagements than other content categories (P <.05). In 2022, there was a significantly higher percentage of Tweets about advice for unmatched applicants (2.2 vs 12.5; P <.001), match statistics (0.4 vs 2.9; P = .028) and focus on underrepresented groups in urology (0.7 vs 3.4; P = .029). CONCLUSION: The Twitter response to the urology match between 2021 and 2022 mirrored the increase in competitiveness, with greater participation and an increasing focus on the difficulty of matching. During Match Week, Twitter is a readily available source of information for programs, matched students, and unmatched students alike. As we continue to embrace virtual platforms, we believe that Twitter will remain a major source of match-related information and can be an instrumental tool for broader networking in our field.

Leaving No Stone Unturned: Factors Associated With Overturning Insurance Claim Denials for Urological Conditions in New York State.

INTRODUCTION: Denied health claims in New York State may be appealed by external review. After appeal, the denial can either be upheld or overturned. Regardless, an appeal process results in delays in care and can negatively impact patient health and practice efficiency. This study aimed to describe the epidemiology of New York State urological external appeals and assess factors associated with successful appeals. METHODS: The New York State External Appeals database was queried for 2019-2021 urological cases (N=408). Patient age, gender, decision year, appeal reason, diagnosis, treatment, and reference to American Urological Association were extracted. Annual appeal volume was analyzed by linear regression. Relationships between appeal outcomes and characteristics were analyzed by χ2 tests. Multivariate logistic regression analysis was used to identify factors related to overturns. RESULTS: Overall, 39.5% of denials in this data set were overturned. Appeal volume increased annually, with overturned cases increasing 244% (mean 29.5, P = .068). Of reviewers, 15.6% referenced American Urological Association guidelines in their decision. Appeals mostly involved ages 40-59 years (32.4%), inpatient stays (63.5%), and infections (32.4%). Female sex, age 80+, diagnosis of incontinence/lower urinary tract symptoms, treatment with home health care, medications, or surgical services, and not referencing American Urological Association guidelines were significantly associated with successful appeal. Referencing American Urological Association guidelines had 70% decreased odds of overturning denials. CONCLUSIONS: Our findings suggest that upon appeal of denied claims, practices may have a high chance of overturning an initial denial and this trend is rising. These findings will help serve as a reference for future external appeals research and urology policy and advocacy groups.

Scale Can Improve the Clinical Value of Radiology Practices.

Radiology is participating in the recent consolidation trend. Larger practices can invest in the infrastructure and teams to help improve the clinical value of the services they deliver. An example of national practice is provided that leverages its scale to promote clinical best practices aimed at reducing variability in the recommendations radiologists make for common imaging findings. This is accomplished by promoting the culture of learning and collaboration. In some initiatives, developing a machine learning tool to facilitate the application of clinical algorithms at the point of dictation facilitates the adoption of the recommendations. Regular feedback on practice and individual performance promotes improvement in performance and personal satisfaction of the clinicians. Cost savings through the reduction of unnecessary imaging studies or invasive procedures as well as improved outcomes through evidence-based follow-up have been achieved. In some cases, reductions in the rupture rate of abdominal aortic aneurysms have been realized through clinical follow-up programs. Embracing a culture of continuous learning through peer learning can lay the foundation for sharing clinical best practices. Having access to the benefits of scale in the form of investment in data, analytics, project management, and machine learning tools can facilitate the process of creating clinical value for our patients.

Predicting Protein-Polymer Block Copolymer Self-Assembly from Protein Properties.

Protein-polymer bioconjugate self-assembly has attracted a great deal of attention as a method to fabricate protein nanomaterials in solution and the solid state. To identify protein properties that affect phase behavior in protein-polymer block copolymers, a library of 15 unique protein-b-poly(N-isopropylacrylamide) (PNIPAM) copolymers comprising 11 different proteins was compiled and analyzed. Many attributes of phase behavior are found to be similar among all studied bioconjugates regardless of protein properties, such as formation of micellar phases at high temperature and low concentration, lamellar ordering with increasing temperature, and disordering at high concentration, but several key protein-dependent trends are also observed. In particular, hexagonal phases are only observed for proteins within the molar mass range 20-36 kDa, where ordering quality is also significantly enhanced. While ordering is generally found to improve with increasing molecular weight outside of this range, most large bioconjugates exhibited weaker than predicted assembly, which is attributed to chain entanglement with increasing polymer molecular weight. Additionally, order-disorder transition boundaries are found to be largely uncorrelated to protein size and quality of ordering. However, the primary finding is that bioconjugate ordering can be accurately predicted using only protein molecular weight and percentage of residues contained within ß sheets. This model provides a basis for designing protein-PNIPAM bioconjugates that exhibit well-defined self-assembly and a modeling framework that can generalize to other bioconjugate chemistries.

SANS partial structure factor analysis for determining protein-polymer interactions in semidilute solution.

The interaction between proteins and polymers in solution contributes to numerous important technological processes, including protein crystallization, biofouling, and the self-assembly of protein-polymer bioconjugates. To quantify these interactions, three different polymers-PNIPAM, POEGA, and PDMAPS-were each blended with a model protein mCherry and studied using contrast variation small angle neutron scattering (SANS). This technique allows for the decomposition of the SANS scattering intensity into partial structure factors corresponding to interactions between two polymer chains, interactions between two proteins, and interactions between a polymer chain and a protein, even for concentrations above the overlap concentration. Examining correlations between each component offers insight into the interactions within the system. In particular, mCherry-PNIPAM interactions are consistent with a depletion interaction, and mCherry-POEGA interactions suggest a considerable region of polymer enrichment close to the protein surface, indicative of attractive forces between the two. Interactions between mCherry and PDMAPS are more complex, with possible contributions from both depletion forces and electrostatic forces.

Osseous Loading by a Volume-Reduced Tongue During Muscle Contractions.

PURPOSE: To investigate how tongue volume reduction affects loads on surrounding bone surfaces produced by neuromuscular stimulation of the tongue. MATERIALS AND METHODS: Of each pair of same-gender minipig siblings, 1 received tongue reduction and 1 underwent sham surgery. Either immediately (acute, 6 pairs) or 1 month (chronic, 5 pairs) after surgery, bone surface and/or suture strains and pressures were recorded from the following locations when the hypoglossal nerve trunk, hypoglossal nerve medial branch, hypoglossal nerve lateral branch, genioglossus, and styloglossus (SG) were electrically stimulated: 1) three rosette strain gauges on the premaxillary palatal surface (premaxilla [PM]) and lingual surfaces of the mandibular alveolus at anterior (mandibular incisor [MI]) and posterior (mandibular molar [MM]) locations; 2) two single-element strain gauges over the palatal surface of the premaxillary-maxillary suture and the lingual surface of the mandibular symphysis; and 3) two pressure transducers on the palatal surface of the maxilla (palatal process) and the lingual surface of the mandibular alveolus (mandibular corpus). RESULTS: Compared with the sham animals in the acute study, reduction animals showed significantly decreased PM and MI strains, as well as palatal process pressure. With muscle contractions, mandibular symphysis and MM strains were enhanced significantly with a more dorsal orientation. In the chronic study, reduction animals showed decreased PM and increased MM strains. On comparison of chronic versus acute studies, PM, MI, and MM strains under SG stimulation were significantly smaller whereas MM strain was significantly larger under hypoglossal nerve trunk, hypoglossal nerve lateral branch, and SG stimulations. CONCLUSIONS: Muscle contractions from a volume-reduced tongue produce lower and higher loads in the anterior and posterior mouth, respectively. However, although the effects on reducing loads in the anterior mouth are persisting over time, compensatory load enhancement in the posterior mouth diminishes owing to surgical healing.

The integrated stress response in hypoxia-induced diffuse white matter injury.

Currently no treatments exist for preterm infants with diffuse white matter injury (DWMI) caused by hypoxia. Due to improved care of preterm neonates and increased recognition by advanced imaging techniques, the prevalence of DWMI is increasing. A better understanding of the pathophysiology of DWMI is therefore of critical importance. The integrated stress response (ISR), a conserved eukaryotic response to myriad stressors including hypoxia, may play a role in hypoxia-induced DWMI and may represent a novel target for much needed therapies. In this study we utilize in vitro and in vivo hypoxic models of DWMI to investigate whether the ISR is involved in DWMI. We demonstrate that hypoxia activates the ISR in primary mouse oligodendrocyte precursor cells (OPCs) in vitro and that genetically inhibiting the ISR in differentiating OPCs increases their susceptibility to in vitro hypoxia. We also show that a well-established in vivo mild chronic hypoxia (MCH) mouse model and a new severe acute hypoxia (SAH) mouse model of DWMI activates the initial step of the ISR. Nonetheless, genetic inhibition of the ISR has no detectable effect on either MCH or SAH-induced DWMI. In addition, we demonstrate that genetic enhancement of the ISR does not ameliorate MCH or SAH-induced DWMI. These studies suggest that while the ISR protects OPCs from hypoxia in vitro, it does not appear to play a major role in either MCH or SAH-induced DWMI and is therefore not a likely target for therapies aimed at improving neurological outcome in preterm neonates with hypoxia-induced DWMI.SIGNIFICANCE STATEMENTDiffuse white matter injury (DWMI) caused by hypoxia is a leading cause of neurological deficits following premature birth. An increased understanding of the pathogenesis of this disease is critical. The integrated stress response (ISR) is activated by hypoxia and protects oligodendrocyte lineage cells in other disease models. This has led to an interest in the potential role of the ISR in DWMI. Here we examine the ISR in hypoxia-induced DWMI and show that while the ISR protects oligodendrocyte lineage cells from hypoxia in vitro, genetic inhibition or enhancement of the ISR has no effect on hypoxia-induced DWMI in vivo suggesting that the ISR does not play a major role in, and is not a likely therapeutic target for, DWMI.

Neonatal Hypoxia Results in Peripheral Nerve Abnormalities.

Although the adverse effects of neonatal hypoxia associated with premature birth on the central nervous system are well known, the contribution of hypoxic damage to the peripheral nervous system (PNS) has not been addressed. We demonstrate that neonatal hypoxia results in hypomyelination and delayed axonal sorting in mice leading to electrophysiological and motor deficits that persist into adulthood. These findings support a potential role for PNS hypoxic damage in the motor impairment that results from premature birth and suggest that therapies designed to protect the PNS may provide clinical benefit.

Kinetic Effects on Self-Assembly and Function of Protein-Polymer Bioconjugates in Thin Films Prepared by Flow Coating.

The self-assembly of nanostructured globular protein arrays in thin films is demonstrated using protein-polymer block copolymers based on a model protein mCherry and the polymer poly(oligoethylene glycol acrylate) (POEGA). Conjugates are flow coated into thin films on a poly(ethylene oxide) grafted Si surface, forming self-assembled cylindrical nanostructures with POEGA domains selectively segregating to the air-film interface. Long-range order and preferential arrangement of parallel cylinders templated by selective surfaces are demonstrated by controlling relative humidity. Long-range order increases with coating speed when the film thicknesses are kept constant, due to reduced nucleation per unit area of drying film. Fluorescence emission spectra of mCherry in films prepared at <25% relative humidity shows a small shift suggesting that proteins are more perturbed at low humidity than high humidity or the solution state.