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The model organism Escherichia coli K-12 has one of the most extensively annotated genomes in terms of functional characterization, yet a significant number of genes, ∼35%, are still considered poorly characterized. Initially genes without known functional understanding were given 'y' gene names. However, due to inconsistency in changing 'y' names to non-'y' names over the years, gene name alone does not provide sufficient information as to the characterization level of genes. Attempts to characterize y-ome genes, i.e. those that lack experimental evidence for function, are ongoing, and recent categorization based on the level of experimental evidence has helped clarify those genes that are well characterized versus uncharacterized. EcoCyc, the most comprehensive, curated genome database for E. coli K-12 substr. MG1655, has updated this approach by expanding the categories to include Partially characterized genes using a set of computational rules that includes keywords, experimental evidence codes and Gene Ontology terms. Approximately half of the previously categorized y-ome genes are now categorized as Partially characterized, leaving 15.5% (738) as Uncharacterized genes in EcoCyc. This new categorization scheme is searchable in the EcoCyc database, will be updated as new experimental evidence is curated and provides important information for research decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

There are limited well-studied treatments for migraine in the pediatric population. Calcitonin gene-related peptide (CGRP) inhibitors are an established safe and effective treatment in adults, and use may be appropriate for pediatric patients in certain clinical situations. We describe migraine pathophysiology as it relates to CGRP, provide an overview of available medications, and discuss clinical usage in this population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lisa Moore declares no conflicts of interest. Ann Pakalnis has received a research grant from Amgen., (Published by Elsevier Inc.)

Objective:  Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals., Study Design:  This is a secondary analysis of the nuMom2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be) study. Dietary ω-6 and ω-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via Doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square test., Results:  For PI > 1.6, odds ratio for the unfavorable FA quartile compared with remaining quartiles for the exposures were 0.96 to 1.25, p  = 0.157 (ω-6 FA); 0.97 to 1.26, p  = 0.124 (ω-3 FA); 0.87 to 1.14, p  = 1.00 (ω-6:ω-3 FA ratio)., Conclusion:  No significant associations between self-reported maternal preconception ω-6 and ω-3 FA intake and uterine artery Doppler indices measured during the second trimester were observed., Key Points: · Maternal diet impacts pregnancy health/fetal outcomes.. · ω-3 and ω-6 FA intake influences cardiovascular health.. · FA intake may affect blood flow to fetoplacental unit.. · Results are limited by inadequate adherence to dietary recommendations.., Competing Interests: None declared., (Thieme. All rights reserved.)

Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The Lieutenant Governor's Challenge 2.0, Wellness Award Initiative, is an opportunity for everyone to drive change and to elevate the well-being, productivity, and prosperity among communities in Delaware. The 2.0 reference is rooted in the mission of former Lieutenant Governor, and now Governor, John Carney to address physical activity and fitness levels of youth and adults. The Lieutenant Governor's Challenge 2.0 presents the opportunity to unite the entire state in an ongoing effort to create an overall healthier population. Mobilizing communities to get healthier, promote better health outcomes, and lower health care costs are the goals of this statewide initiative., (2024 The journal and its content is copyrighted by the Delaware Academy of Medicine / Delaware Public Health Association (Academy/DPHA).)

Chronic Disease, Health Equity, & COVID-19 ("Advancing Healthy Lifestyles" or "AHL") is a statewide initiative launched in January 2021 by the Delaware Department of Health and Social Services, Division of Public Health (DPH). DPH's Physical Activity, Nutrition and Obesity Prevention Program (PANO) introduced the initiative as Coronavirus 2019 (COVID-19) swept through the state, exacerbating health burdens already faced by many Delawareans. The PANO Program provides administrative staff support to the Delaware Cancer Consortium's Cancer Risk Reduction Committee (CRRC). In December 2019, the CRRC launched the Healthy Lifestyles Subcommittee (HLSC) in response to Governor John Carney's request to develop actionable policy recommendations to positively influence healthy lifestyles in Delaware. The HLSC efforts led to the recommendation of 14 policy recommendations for action in three population health strategic focus areas: 1) birth to age 18; 2) employee health and wellness; and 3) community wellness. The AHL initiative builds from the work of the HLSC and promotes the use of policy, systems, and environmental change (PSE) strategies to reduce obesity and other chronic conditions among Delawareans across the lifespan. Ideally, the AHL initiative is categorized into three component strategies: school, community, and workplace. This article highlights both completed and ongoing projects under the AHL Initiative that aim to address the burden of obesity in Delaware., (2024 The journal and its content is copyrighted by the Delaware Academy of Medicine / Delaware Public Health Association (Academy/DPHA).)

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices., Competing Interests: ND has a financial interest in Turing Medical Inc. and may financially benefit if the company is successful in marketing FIRMM motion monitoring software products, may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc, and is a co-founder of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. AH reports lecture fees for Boston Scientific and is a consultant for FxNeuromodulation and Abbott. RG is an employee of Rune Labs. JO'K is CEO and Founder of Machine Medicine Technologies. W-JN received honoraria for consulting from InBrain – Neuroelectronics that is a neurotechnology company and honoraria for talks from Medtronic that is a manufacturer of deep brain stimulation devices unrelated to this manuscript. SL has received speaking honoraria from Medtronic and is a consultant for Iota Biosciences. SS is a consultant for Zimmer Biomet, Neuropace, Koh Young, Boston Scientfic, Sensoria Therapeutics, Varian Medical; co-founder for Motif Neurotech. LM is an employee of Boston Scientific. AF has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB, Sunovion, and he has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer. AH-B and RR are employees of Medtronic Inc. LM is an employee of Boston Scientific. YP is an employee of Abbott. DG is an employee of NeuroPace, owns NeuroPace stock, and has NeuroPace stock options. SM is a founder and shareholder of Newronika SpA. LK is the CEO of Newronika. MP-N has received speaker honoraria/travel costs from Medtronic, Boston Scientific, Abbott, Bial, and Abbvie and study reimbursements from Zambon, Licher, Boston Scientific, and Abbott. LC has received research support from National Institutes of Health and the National Network of Depression Centers and serves on the Board of Directors for the International Neuroethics Society (unpaid) as well as on the Advisory Council for the Institute of Neuroethics think and do thank (unpaid). CM is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, BrainDynamics, CereGate, Cardionomic, Enspire DBS. NH is a co-founder of Surgical Information Sciences (SIS), Inc. HM received consulting and IP licensing fees from Abbott Laboratories. AK has stock options in Neurawell and Big Health and is a consultant for Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda. NP is a consultant for Abbott and Sensoria Therapeutics. PS receives free research devices from Medtronic and fellowship support funding from Medtronic and BSCI and no personal income from anyone. KF reports receiving research support and fellowship support from Medtronic and Boston Scientific and research support from Functional Neuromodulation. MO serves as Medical Advisor the Parkinson's Foundation, and has received research grants from NIH, Parkinson's Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MO is an associate editor for New England Journal of Medicine Journal, Watch Neurology, and JAMA Neurology. MO has participated in CME and educational activities (past 12-24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not MO receives grants from industry. MO has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Johnson, Dosenbach, Gordon, Welle, Wilkins, Bronte-Stewart, Voon, Morishita, Sakai, Merner, Lázaro-Muñoz, Williamson, Horn, Gilron, O'Keeffe, Gittis, Neumann, Little, Provenza, Sheth, Fasano, Holt-Becker, Raike, Moore, Pathak, Greene, Marceglia, Krinke, Tan, Bergman, Pötter-Nerger, Sun, Cabrera, McIntyre, Harel, Mayberg, Krystal, Pouratian, Starr, Foote, Okun and Wong.)

CyanoCyc is a web portal that integrates an exceptionally rich database collection of information about cyanobacterial genomes with an extensive suite of bioinformatics tools. It was developed to address the needs of the cyanobacterial research and biotechnology communities. The 277 annotated cyanobacterial genomes currently in CyanoCyc are supplemented with computational inferences including predicted metabolic pathways, operons, protein complexes, and orthologs; and with data imported from external databases, such as protein features and Gene Ontology (GO) terms imported from UniProt. Five of the genome databases have undergone manual curation with input from more than a dozen cyanobacteria experts to correct errors and integrate information from more than 1,765 published articles. CyanoCyc has bioinformatics tools that encompass genome, metabolic pathway and regulatory informatics; omics data analysis; and comparative analyses, including visualizations of multiple genomes aligned at orthologous genes, and comparisons of metabolic networks for multiple organisms. CyanoCyc is a high-quality, reliable knowledgebase that accelerates scientists' work by enabling users to quickly find accurate information using its powerful set of search tools, to understand gene function through expert mini-reviews with citations, to acquire information quickly using its interactive visualization tools, and to inform better decision-making for fundamental and applied research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Moore, Caspi, Campbell, Casey, Crevecoeur, Lea-Smith, Long, Omar, Paley, Schmelling, Torrado, Zehr and Karp.)

EcoCyc is a bioinformatics database available online at EcoCyc.org that describes the genome and the biochemical machinery of Escherichia coli K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the E. coli cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of E. coli . EcoCyc is an electronic reference source for E. coli biologists and for biologists who work with related microorganisms. The database includes information pages on each E. coli gene product, metabolite, reaction, operon, and metabolic pathway. The database also includes information on the regulation of gene expression, E. coli gene essentiality, and nutrient conditions that do or do not support the growth of E. coli . The website and downloadable software contain tools for the analysis of high-throughput data sets. In addition, a steady-state metabolic flux model is generated from each new version of EcoCyc and can be executed online. The model can predict metabolic flux rates, nutrient uptake rates, and growth rates for different gene knockouts and nutrient conditions. Data generated from a whole-cell model that is parameterized from the latest data on EcoCyc are also available. This review outlines the data content of EcoCyc and of the procedures by which this content is generated.

Neurologic manifestations of mpox (monkeypox) infection are common. Rarely, transverse myelitis has been associated with mpox infection. We describe a case of longitudinally extensive transverse myelitis in a patient with recently diagnosed mpox, presenting as acute flaccid paraplegia. The patient underwent an extensive work-up that included serological and cerebrospinal fluid (CSF) testing and magnetic resonance imaging (MRI). They were treated with tecoviromat, high dose steroids, and intravenous immunoglobulin, followed by plasma exchange. Despite these interventions, there was minimal neurologic improvement. This case underscores the importance of instituting measures designed to prevent mpox infection, including public education initiatives., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

The negative impact of nutritional deficits in the development of bronchopulmonary dysplasia is well recognized, yet mechanisms by which nutrition alters lung outcomes and nutritional strategies that optimize development and protect the lung remain elusive. Here, we use a rat model to assess the isolated effects of postnatal nutrition on lung structural development without concomitant lung injury. We hypothesize that postnatal growth restriction (PGR) impairs lung structure and function, critical mediators of lung development, and fatty acid profiles at postnatal day 21 in the rat. Rat pups were cross-fostered at birth to rat dams with litter sizes of 8 (control) or 16 (PGR). Lung structure and function, as well as serum and lung tissue fatty acids, and lung molecular mediators of development, were measured. Male and female PGR rat pups had thicker airspace walls, decreased lung compliance, and increased tissue damping. Male rats also had increased lung elastance, increased lung elastin protein abundance, and lysol oxidase expression, and increased elastic fiber deposition. Female rat lungs had increased conducting airway resistance and reduced levels of docosahexaenoic acid in lung tissue. We conclude that PGR impairs lung structure and function in both male and female rats, with sex-divergent changes in lung molecular mediators of development., (© 2023 American Association for Anatomy.)

Plastic pollution is a serious global problem, with more than 12 million tonnes of plastic waste entering the oceans every year. Plastic debris can have considerable impacts on microbial community structure and functions in marine environments, and has been associated with an enrichment in pathogenic bacteria and antimicrobial resistance (AMR) genes. However, our understanding of these impacts is largely restricted to microbial assemblages on plastic surfaces. It is therefore unclear whether these effects are driven by the surface properties of plastics, providing an additional niche for certain microbes residing in biofilms, and/or chemicals leached from plastics, the effects of which could extend to surrounding planktonic bacteria. Here, we examine the effects of polyvinyl chloride (PVC) plastic leachate exposure on the relative abundance of genes associated with bacterial pathogenicity and AMR within a seawater microcosm community. We show that PVC leachate, in the absence of plastic surfaces, drives an enrichment in AMR and virulence genes. In particular, leachate exposure significantly enriches AMR genes that confer multidrug, aminoglycoside and peptide antibiotic resistance. Additionally, enrichment of genes involved in the extracellular secretion of virulence proteins was observed among pathogens of marine organisms. This study provides the first evidence that chemicals leached from plastic particles alone can enrich genes related to microbial pathogenesis within a bacterial community, expanding our knowledge of the environmental impacts of plastic pollution with potential consequences for human and ecosystem health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There are questions about how well small-animal models for tissue-engineered vascular grafts (TEVGs) translate to clinical patients. Most TEVG studies used grafting times ≤6 months where conduits from generally biocompatible materials like poly(ε-caprolactone) (PCL) perform well. However, longer grafting times can result in significant intimal hyperplasia and calcification. This study tests the hypothesis that differences in pro-inflammatory response from pure PCL conduits will be consequential after long-term grafting. It also tests the long-term benefits of a peritoneal pre-implantation strategy on rodent outcomes. Electrospun conduits with and without peritoneal pre-implantation, and with 0 % and 10 % (w/w) collagen/PCL, were grafted into abdominal aortae of rats for 10 months. This study found that viability of control grafts without pre-implantation was reduced unlike prior studies with shorter grafting times, confirming the relevance of this model. Importantly, pre-implanted grafts had a 100 % patency rate. Further, pre-implantation reduced intimal hyperplasia within the graft. Differences in response between pure PCL and collagen/PCL conduits were observed (e.g., fewer CD80 + and CD3 + cells for collagen/PCL), but only pre-implantation had an effect on the overall graft viability. This study demonstrates how long-term grafting in rodent models can better evaluate viability of different TEVGs, and the benefits of the peritoneal pre-implantation step., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Adolescence is a critical period of social and neural development. Brain regions which process social information develop throughout adolescence as young people learn to navigate social environments. Studies investigating brain structural connectivity (indexed by white matter (WM) integrity), and social connectedness in adolescents have been limited until recently, with literature stemming mostly from adult samples, broad age ranges within adolescence or based on social network characteristics as opposed to social connectedness. This cross-sectional study of 12-year-olds (N = 73) explored the relationship between social connectedness (SCS) and structural connectivity in early adolescence, to gauge how this snapshot of WM development is associated with social behaviour. Whole brain voxel-wise diffusion tensor imaging was undertaken to determine correlations between SCS and fractional anisotropy (FA), radial (RD) and axial (AD) diffusivity of clusters within WM tracts. Significant negative relationships between FA and SCS scores were found in clusters within 11 WM tracts, with significant positive correlations between SCS and both RD and AD across clusters within 13 and 8 clusters, respectively. Clusters within the genu of the corpus callosum (CCgn) showed strong correlations for all three metrics, and regression models that included gender, age, and psychological distress, revealed SCS to be the only significant predictor of CCgn FA, RD and AD values. Overall, these findings suggest that those with lower social connectedness had a WM profile suggestive of reduced axonal density and/or coherence. Longitudinal research is needed to track such WM profiles during adolescent development and determine the associations with mental health and well-being outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intra-articular bone marrow concentrate (BMC) and aspirate (BMA) injections have been used with mixed results to treat osteoarthritis (OA). Given the various aspiration and concentration methods available for preparing bone marrow, more data are needed to identify the optimal bone marrow harvesting techniques to treat OA., Methods: This retrospective cohort study examined the effect of using low-volume BMAs harvested using the Marrow Cellution™ (MC) device on 160 patients (262 knees) suffering from pain due to knee OA, KL grades 2-4, that did not respond to conservative treatment. Changes in visual analog scores (VAS) for overall daily activity were examined over a six-month time frame in these patients (63.5 ± 0.97 years of age; 48.1% male). In addition, changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Patient Global Impression of Change (PGIC scores) were examined over the same time frame in a smaller subset of patients (95 patients including 172 knees)., Results: There was a statistically significant improvement in VAS scores for overall daily activity 6 months postprocedure in the study population, 7.29 ± 0.27 vs. 3.76 ± 0.34 ( p < 0.0001), as well as statistically significant improvements in WOMAC scores, 49.3 ± 4.27 vs. 66.3 ± 4.08 ( p < 0.0001). On the individual level, 71% of the cases displayed VAS improvements and 61% of the cases displayed WOMAC improvements that exceeded levels previous studies determined to be the minimal clinically important difference (MCID) for knee OA treatments. The improvements in WOMAC scores were also seen in both the WOMAC pain subscore, 52.2 ± 4.39 vs. 72.2 ± 4.36 ( p < 0.0001) and the WOMAC function subscore, 51.6 ± 4.67 vs. 69.0 ± 4.36 ( p < 0.0001). In addition, the PGIC scores measuring patient satisfaction improved from 4.03 ± 0.26 at 6 weeks postprocedure to 4.65 ± 0.28 at 6 months postprocedure ( p < 0.0001)., Conclusions: Knee OA patients treated with MC BMA intra-articular injections exhibited significant reductions in VAS pain scores and significant improvements in WOMAC scores that exceeded the minimal clinically important difference thresholds. In addition, reductions in VAS pain scores and improvements in WOMAC scores correlated with higher PGIC scores., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Daniel Kuebler et al.)

Background: Each year, approximately 9.5 million metric tons of plastic waste enter the ocean with the potential to adversely impact all trophic levels. Until now, our understanding of the impact of plastic pollution on marine microorganisms has been largely restricted to the microbial assemblages that colonize plastic particles. However, plastic debris also leaches considerable amounts of chemical additives into the water, and this has the potential to impact key groups of planktonic marine microbes, not just those organisms attached to plastic surfaces., Results: To investigate this, we explored the population and genetic level responses of a marine microbial community following exposure to leachate from a common plastic (polyvinyl chloride) or zinc, a specific plastic additive. Both the full mix of substances leached from polyvinyl chloride (PVC) and zinc alone had profound impacts on the taxonomic and functional diversity of our natural planktonic community. Microbial primary producers, both prokaryotic and eukaryotic, which comprise the base of the marine food web, were strongly impaired by exposure to plastic leachates, showing significant declines in photosynthetic efficiency, diversity, and abundance. Key heterotrophic taxa, such as SAR11, which are the most abundant planktonic organisms in the ocean, also exhibited significant declines in relative abundance when exposed to higher levels of PVC leachate. In contrast, many copiotrophic bacteria, including members of the Alteromonadales, dramatically increased in relative abundance under both exposure treatments. Moreover, functional gene and genome analyses, derived from metagenomes, revealed that PVC leachate exposure selects for fast-adapting, motile organisms, along with enrichment in genes usually associated with pathogenicity and an increased capacity to metabolize organic compounds leached from PVC., Conclusions: This study shows that substances leached from plastics can restructure marine microbial communities with the potential for significant impacts on trophodynamics and biogeochemical cycling. These findings substantially expand our understanding of the ways by which plastic pollution impact life in our oceans, knowledge which is particularly important given that the burden of plastic pollution in the marine environment is predicted to continue to rise. Video Abstract., (© 2022. The Author(s).)

Spinal cord stimulation enhanced restoration of motor function following spinal cord injury (SCI) in unblinded studies. To determine whether training combined with transcutaneous electrical spinal cord stimulation (tSCS), with or without systemic serotonergic treatment with buspirone (busp), could improve hand function in individuals with severe hand paralysis following SCI, we assessed ten subjects in a double-blind, sham-controlled, crossover study. All treatments-busp, tSCS, and the busp plus tSCS-reduced muscle tone and spasm frequency. Buspirone did not have any discernible impact on grip force or manual dexterity when administered alone or in combination with tSCS. In contrast, grip force, sinusoidal force generation and grip-release rate improved significantly after 6 weeks of tSCS in 5 out of 10 subjects who had residual grip force within the range of 0.1-1.5 N at the baseline evaluation. Improved hand function was sustained in subjects with residual grip force 2-5 months after the tSCS and buspirone treatment. We conclude that tSCS combined with training improves hand strength and manual dexterity in subjects with SCI who have residual grip strength greater than 0.1 N. Buspirone did not significantly improve the hand function nor add to the effect of stimulation., (© 2022. The Author(s).)

Antenatal administration of glucocorticoids such as betamethasone (BMZ) during the late preterm period improves neonatal respiratory outcomes. However, glucocorticoids may elicit programming effects on immune function and gene regulation. Here, we test the hypothesis that exposure to antenatal BMZ alters cord blood immune cell composition in association with altered DNA methylation and alternatively expressed Exon 1 transcripts of the glucocorticoid receptor (GR) gene in cord blood CD4 + T-cells. Cord blood was collected from 51 subjects in the Antenatal Late Preterm Steroids Trial: 27 BMZ, 24 placebo. Proportions of leukocytes were compared between BMZ and placebo. In CD4+ T-cells, methylation at CpG sites in the GR promoter regions and expression of GR mRNA exon 1 variants were compared between BMZ and placebo. BMZ was associated with an increase in granulocytes (51.6% vs. 44.7% p = 0.03) and a decrease in lymphocytes (36.8% vs. 43.0% p = 0.04) as a percent of the leukocyte population vs. placebo. Neither GR methylation nor exon 1 transcript levels differed between groups. BMZ is associated with altered cord blood leukocyte proportions, although no associated alterations in GR methylation were observed., (© 2022. Society for Reproductive Investigation.)

Sustaining impactful research within the field of perinatal biology requires training and retention of the next generations of physician-scientists and basic-scientists. Professional societies such as the Perinatal Research Society (PRS) have a unique role to play in training and retention of perinatal biologists. Here we report outcomes for an innovative Young Investigator Training Workshop created for the PRS. The PRS Workshop uses immersive, active-writing, and active-oral presentation design, with one-on-one feedback from NIH-funded faculty-mentors drawn from the PRS membership. Young investigator data were collected by anonymous surveys of young investigators, NIH RePORTER, and individual young investigator follow-up. Ninety-seven young investigators attended the Workshops over the period 2013-2018. Young investigators were physician- (73%) and PhD- (27%) scientists at the rank of clinical fellow/postdoctoral fellow (27%) or instructor/assistant professor (73%). Participation by underrepresented minority (URM) young investigators was 14%. Young investigators received NIH and non-NIH funding, with 80% of young investigators receiving new funding since the Workshop that they attended. NIH funding was received by 31% of young investigators in the form of K-series awards, R01 equivalents, and other NIH awards. In conclusion, our PRS young investigator Workshop serves as a model to facilitate training of emerging physician- and basic-scientists by scientific societies., (© 2022. Society for Reproductive Investigation.)

Marine cyanobacteria are key primary producers, contributing significantly to the microbial food web and biogeochemical cycles by releasing and importing many essential nutrients cycled through the environment. A subgroup of these, the picocyanobacteria (Synechococcus and Prochlorococcus), have colonised almost all marine ecosystems, covering a range of distinct light and temperature conditions, and nutrient profiles. The intra-clade diversities displayed by this monophyletic branch of cyanobacteria is indicative of their success across a broad range of environments. Part of this diversity is due to nutrient acquisition mechanisms, such as the use of high-affinity ATP-binding cassette (ABC) transporters to competitively acquire nutrients, particularly in oligotrophic (nutrient scarce) marine environments. The specificity of nutrient uptake in ABC transporters is primarily determined by the peripheral substrate-binding protein (SBP), a receptor protein that mediates ligand recognition and initiates translocation into the cell. The recent availability of large numbers of sequenced picocyanobacterial genomes indicates both Synechococcus and Prochlorococcus apportion >50% of their transport capacity to ABC transport systems. However, the low degree of sequence homology among the SBP family limits the reliability of functional assignments using sequence annotation and prediction tools. This review highlights the use of known SBP structural representatives for the uptake of key nutrient classes by cyanobacteria to compare with predicted SBP functionalities within sequenced marine picocyanobacteria genomes. This review shows the broad range of conserved biochemical functions of picocyanobacteria and the range of novel and hypothetical ABC transport systems that require further functional characterisation., (© 2021 The Author(s).)

Survival of patients with metastatic melanoma varies widely. Melanoma is a highly proliferative, chemo-resistant disease. With the recent availability of immunotherapies such as checkpoint inhibitors, durable response rates have improved but are often still limited to 2-3 years. Response rates to treatment range from 30 to 45% with combination therapy however no improvement in overall survival is frequently observed. Of the available therapies, many have targeted the BRAFV600E mutation that results in abnormal MAPK pathway activation which is important for regulating cell proliferation. Immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 offer better success but response rates are still low. Identifying biomarkers to better target those who will respond and identify the right combination of treatment is the best approach. In this study, we utilize data from the Cancer Cell Line Encyclopedia (CCLE), including 62 samples, to examine features of gene expression (19K+) and copy number (20K+) in the melanoma cell lines. We perform a clustering analysis on the feature set to assess genetically similarity among the cell lines. We then discover which specific genes and combinations thereof maximize cluster density. We design a feature selection approach for high-dimensional datasets that integrates multiple disparate machine learning techniques into one cohesive pipeline. Our approach provides a small subset of genes that can accurately distinguish between the clusters of melanoma cell lines across multiple types of classifiers. In particular, we find only the 15 highest ranked genes among the original 19 K are necessary to achieve perfect or near-perfect test split classification performance. Of these 15 genes, some are known to be linked to melanoma or other cancer progressions, while others have not previously been linked to melanoma and are of interest for further examination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kutt, Burdorf, Bain, Cameron, Pearah, Subasi, Carroll, Moore and Subasi.)

Microbial contamination of wounds is a significant problem that delays healing, particularly when bacterial biofilms are present. A novel combination of pectinic acid (PG) + caprylic acid (CAP) was previously found in vitro to be highly effective in eradicating various pathogens in biofilms with minimal cytotoxicity. In this study, a novel wound ointment was formulated with PG + CAP and first assessed in vitro using a well-established biofilm eradication model. In vitro, the PG + CAP ointment was shown to be efficacious in reducing the microbial biofilms. This ointment was then tested in vivo in two pilot porcine wound healing models, with and without Staphylococcus aureus microbial challenge. Ointments were applied to each wound daily, and healing by wound closure area measurement was assessed weekly over 4 weeks. After 4 weeks, pigs were sacrificed and wounds were scored for reepithelialization, inflammation, granulation tissue, and collagen deposition. We compared PG + CAP to hydroxyethylcellulose + glycerol ointment base (control) and MediHoney (comparator). In the porcine microbial challenge model, the novel antimicrobial PG + CAP wound ointment rapidly eradicated bacterial organisms embedded in wounds, was safe and well-tolerated, and was associated with enhanced healing compared to ointment base and MediHoney. Specifically, the cumulative histopathology, reepithelialization of epidermis, and mature granulation tissue in the wound bed was significantly better with PG + CAP than with control and MediHoney treatments. This ointment warrants further study as a non-antibiotic ointment for use in treating a wide array of infected wounds., (© 2021 The Wound Healing Society.)

Background: The authors draw upon their experience with a successful, enterprise-level, telemedicine program implementation to present a "How To" paradigm for other academic health centers that wish to rapidly deploy such a program in the setting of the COVID-19 pandemic. The advent of social distancing as essential for decreasing viral transmission has made it challenging to provide medical care. Telemedicine has the potential to medically undistance health care providers while maintaining the quality of care delivered and fulfilling the goal of social distancing. Methods: Rather than simply reporting enterprise telemedicine successes, the authors detail key telemedicine elements essential for rapid deployment of both an ambulatory and inpatient telemedicine solution. Such a deployment requires a multifaceted strategy: (1) determining the appropriateness of telemedicine use, (2) understanding the interface with the electronic health record, (3) knowing the equipment and resources needed, (4) developing a rapid rollout plan, (5) establishing a command center for post go-live support, (6) creating and disseminating reference materials and educational guides, (7) training clinicians, patients, and clinic schedulers, (8) considering billing and credentialing implications, (9) building a robust communications strategy, and (10) measuring key outcomes. Results: Initial results are reported, showing a telemedicine rate increase to 45.8% (58.6% video and telephone) in just the first week of rollout. Over a 5-month period, the enterprise has since conducted over 119,500 ambulatory telemedicine evaluations (a 1,000-fold rate increase from the pre-COVID-19 time period). Conclusion: This article is designed to offer a "How To" potential best practice approach for others wishing to quickly implement a telemedicine program during the COVID-19 pandemic.

Marine plastic pollution is a growing concern worldwide and has the potential to impact marine life via leaching of chemicals, with zinc (Zn), a common plastic additive, observed at particularly high levels in plastic leachates in previous studies. At this time, however, little is known regarding how elevated Zn affects key groups of marine primary producers. Marine cyanobacterial genera Prochlorococcus and Synechococcus are considered to be some of the most abundant oxygenic phototrophs on earth, and together contribute significantly to oceanic primary productivity. Here we set out to investigate how two Prochlorococcus (MIT9312 and NATL2A) and two Synechococcus (CC9311 and WH8102) strains, representative of diverse ecological niches, respond to exposure to high Zn concentrations. The two genera showed differences in the timing and degree of growth and physiological responses to elevated Zn levels, with Prochlorococcus strains showing declines in their growth rate and photophysiology following exposure to 27 µg l -1 Zn, while Synechococcus CC9311 and WH8102 growth rates declined significantly on exposure to 52 and 152 µg l -1 Zn, respectively. Differences were also observed in each strain's capacity to maintain cell wall integrity on exposure to different levels of Zn. Our results indicate that excess Zn has the potential to pose a challenge to some marine picocyanobacteria and highlights the need to better understand how different marine Prochlorococcus and Synechococcus strains may respond to increasing concentrations of Zn in some marine regions.

The placenta represents a critical node in fetal lipid acquisition, yet the mechanisms by which the placenta handles lipids under normal and pathologic conditions are incompletely understood. A key player in placental lipid handling is peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ influences global gene expression via its regulation of the epigenetic modifier lysine methyltransferase 5A (KMT5A), which places a methyl group on histone 4 lysine 20 (H4K20me) of target genes. Here we test the hypothesis that KMT5A is present in both the human and rat placentas and is affected by uteroplacental insufficiency (UPI) in the rat in association with increased placental lipid accumulation. We assessed levels and localization of KMT5A, as well as lipid droplet accumulation, in human placental tissue collected from maternal donors after delivery by planned cesarean section. Using a rat model of UPI, we also evaluated the effects of UPI on lipid accumulation, PPARγ, KMT5A, and H4K20me in the rat placenta. In this study, we show for the first time the presence and activity of KMT5A, in human and in rat placentas. We also demonstrate that in the rat placenta, UPI increases hypoxia, KMT5a expression, and activity in association with increased lipid accumulation in placenta supporting male fetuses. Placental PPARγ-KMT5A axis may be an important mediator of placental lipid handling.

Purpose: Obesity and high-fat (HF) diet are associated with over activation of the endocannabinoid system (ECS). We have demonstrated that maternal HF diet induces early obesity and modulates cannabinoid signaling in visceral (VIS) and subcutaneous (SUB) white adipose tissue (WAT) in weanling rat offspring. We hypothesized that perinatal maternal HF diet would program the expression of ECS in adipose tissue in a long-term way in parallel to alterations in epigenetic markers and sex hormone signaling., Methods: Progenitor female rats received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) for 8 weeks before mating, gestation, and lactation. All pups were weaned to C diet and they were euthanized at 180 days old., Results: Maternal HF diet induced overweight and increased SUB WAT mass of male and female adult offspring. Maternal HF diet induced hypertrophy of VIS and SUB adipocytes only in female offspring associated with increased type 1 cannabinoid receptor protein (CB1) and mRNA (Cnr1) levels. These changes were associated with increased estrogen receptor α binding to Cnr1 promoter in SUB WAT of adult female offspring, which may contribute to higher expression of Cnr1., Conclusion: Increased CB1 signaling in adipose tissue might contribute to higher adiposity programmed by maternal HF diet because endocannabinoids stimulate the accumulation of fat in the adipose tissue. Our findings provide molecular insights into sex-specific targets for anti-obesity therapies based on the endocannabinoid system.

In the midst of the COVID-19 pandemic, Remote Patient Monitoring technologies are highly important for clinicians and researchers. These connected-health technologies enable monitoring of patients and facilitate remote clinical trial research while reducing the potential for the spread of the novel coronavirus. There is a growing requirement for monitoring of the full 24 h spectrum of behaviours with a single research-grade sensor. This research describes a free-living and supervised protocol comparison study of the Verisense inertial measurement unit to assess physical activity and sleep parameters and compares it with the Actiwatch 2 actigraph. Fifteen adults (11 males, 23.4 ± 3.4 years and 4 females, 29 ± 12.6 years) wore both monitors for 2 consecutive days and nights in the free-living study while twelve adults (11 males, 23.4 ± 3.4 years and 1 female, 22 ± 0 years) wore both monitors for the duration of a gym-based supervised protocol study. Agreement of physical activity epoch-by-epoch data with activity classification of sedentary, light and moderate-to-vigorous activity and sleep metrics were evaluated using Spearman's rank-order correlation coefficients and Bland-Altman plots. For all activity, Verisense showed high agreement for both free-living and supervised protocol of r = 0.85 and r = 0.78, respectively. For physical activity classification, Verisense showed high agreement of sedentary activity of r = 0.72 for free-living but low agreement of r = 0.36 for supervised protocol; low agreement of light activity of r = 0.42 for free-living and negligible agreement of r = -0.04 for supervised protocol; and moderate agreement of moderate-to-vigorous activity of r = 0.52 for free-living with low agreement of r = 0.49 for supervised protocol. For sleep metrics, Verisense showed moderate agreement for sleep time and total sleep time of r = 0.66 and 0.54, respectively, but demonstrated high agreement for determination of wake time of r = 0.83. Overall, our results showed moderate-high agreement of Verisense with Actiwatch 2 for assessing epoch-by-epoch physical activity and sleep, but a lack of agreement for activity classifications. Future validation work of Verisense for activity cut-point potentially holds promise for 24 h continuous remote patient monitoring.

A synthesis of phenotypic and quantitative genomic traits is provided for bacteria and archaea, in the form of a scripted, reproducible workflow that standardizes and merges 26 sources. The resulting unified dataset covers 14 phenotypic traits, 5 quantitative genomic traits, and 4 environmental characteristics for approximately 170,000 strain-level and 15,000 species-aggregated records. It spans all habitats including soils, marine and fresh waters and sediments, host-associated and thermal. Trait data can find use in clarifying major dimensions of ecological strategy variation across species. They can also be used in conjunction with species and abundance sampling to characterize trait mixtures in communities and responses of traits along environmental gradients.

Maternal tobacco smoke exposure (MTS) affects fetal acquisition of long-chain polyunsaturated fatty acids (LCPUFA) and increases the risk of obesity and cardio-metabolic disease in the offspring. Alterations in fetal LCPUFA acquisition in maternal smoking are mediated by the placenta. The handling of LCPUFA by the placenta involves protein-mediated transfer and storage. Molecular mediators of placental LCPUFA handling include PPARγ and the fatty acid transport proteins. We previously demonstrated, in a rat model, that MTS results in programming of adult-onset obesity and metabolic disease in male, but not female, offspring. In this study, we test the hypothesis that in utero MTS exposure alters placental structure, placental LCPUFA handling, and fetal fatty acid levels, in a sex-divergent manner. We exposed pregnant rats to tobacco smoke from embryonic day 11 to term gestation. We measured placental and fetal fatty acid profiles, the systolic/diastolic ratio (SD ratio), placental histology, and expression of molecular mediators in the placenta. Our primary finding is that MTS alters fatty acid profiles in male, but not female fetuses and placenta, including increasing the ratio of omega-6 to omega-3 fatty acids. MTS also increased SD ratio in male, but not female placenta. In contrast, the expression of PPARγ and FATPs was upregulated in female, but not male placenta. We conclude that MTS causes sex-divergent changes in placental handling of LCPUFA in the rat. We speculate that our results demonstrate an adaptive response to MTS by the female placenta.

Plastic pollution is a global threat to marine ecosystems. Plastic litter can leach a variety of substances into marine environments; however, virtually nothing is known regarding how this affects photosynthetic bacteria at the base of the marine food web. To address this, we investigated the effect of plastic leachate exposure on marine Prochlorococcus , widely considered the most abundant photosynthetic organism on Earth and vital contributors to global primary production and carbon cycling. Two strains of Prochlorococcus representing distinct ecotypes were exposed to leachate from common plastic items: high-density polyethylene bags and polyvinyl chloride matting. We show leachate exposure strongly impairs Prochlorococcus in vitro growth and photosynthetic capacity and results in genome-wide transcriptional changes. The strains showed distinct differences in the extent and timing of their response to each leachate. Consequently, plastic leachate exposure could influence marine Prochlorococcus community composition and potentially the broader composition and productivity of ocean phytoplankton communities., Competing Interests: The authors declare no competing interests.

Maternal nutritional imbalances trigger developmental adaptations involving early epigenetic mechanisms associated with adult chronic disease. Maternal high-fat (HF) diet promotes obesity and hypothalamic leptin resistance in male rat offspring at weaning and adulthood. Leptin resistance is associated with over activation of the endocannabinoid system (ECS). The ECS mainly consists of endocannabinoids derived from n-6 fatty acids and cannabinoid receptors (CB1 coded by Cnr1 and CB2 coded by Cnr2). The CB1 activation in hypothalamus stimulates feeding and appetite for fat while CB2 activation seems to play an immunomodulatory role. We demonstrated that maternal HF diet increases hypothalamic CB1 in male offspring while increases CB2 in female offspring at birth, prior to obesity development. However, the molecular mechanisms behind these changes remain unexplored. We hypothesized that maternal HF diet would down-regulate leptin signaling and up-regulate Cnr1 mRNA levels in the hypothalamus of the offspring at birth, associated with sex-specific changes in epigenetic markers and sex steroid signaling. To test our hypothesis, we used progenitor female rats that received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) from 8 weeks before mating until delivery. Blood, hypothalamus and carcass from C and HF male and female offspring were collected for biochemical and molecular analyses at birth. Maternal HF diet down-regulated the transcriptional factor STAT3 in the hypothalamus of male and female offspring, but induced hypoleptinemia only in males and decreased phosphorylated STAT3 only in female offspring. Because leptin acts through STAT3 pathway to inhibit central ECS, our results suggest that leptin pathway impairment might contribute to increased levels of Crn1 mRNA in hypothalamus of both sex offspring. Besides, maternal HF diet increased the histone acetylation percentage of Cnr1 promoter in male offspring and increased the androgen receptor binding to the Cnr1 promoter, which can contribute to higher expression of Cnr1 in newborn HF offspring. Maternal HF diet increased plasma n6 to n3 fatty acid ratio in male offspring, which is an important risk factor to metabolic diseases and might indicate an over activation of endocannabinoid signaling. Thus, although maternal HF diet programs a similar phenotype in adult offspring of both sexes (obesity, hyperphagia and higher preference for fat), here we showed that molecular mechanisms involving leptin signaling, ECS, epigenetic markers and sex hormone signaling were modified prior to obesity development and can differ between newborn male and female offspring. These observations may provide molecular insights into sex-specific targets for anti-obesity therapies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The tropical marine environments of northern Australia encompasses a diverse range of geomorphological and oceanographic conditions and high levels of productivity and nitrogen fixation. However, efforts to characterize phytoplankton assemblages in these waters have been restricted to studies using microscopic and pigment analyses, leading to the current consensus that this region is dominated by large diatoms, dinoflagellates, and the marine cyanobacterium Trichodesmium . During an oceanographic transect from the Arafura Sea through the Torres Strait to the Coral Sea, we characterized prokaryotic and eukaryotic phytoplankton communities in surface waters using a combination of flow cytometry and Illumina based 16S and 18S ribosomal RNA amplicon sequencing. Similar to observations in other marine regions around Australian, phytoplankton assemblages throughout this entire region were rich in unicellular picocyanobacterial primary producers while picoeukaryotic phytoplankton formed a consistent, though smaller proportion of the photosynthetic biomass. Major taxonomic groups displayed distinct biogeographic patterns linked to oceanographic and nutrient conditions. Unicellular picocyanobacteria dominated in both flow cytometric abundance and carbon biomass, with members of the Synechococcus genus dominating in the shallower Arafura Sea and Torres Strait where chlorophyll a was relatively higher (averaging 0.4 ± 0.2 mg m -3 ), and Prochlorococcus dominating in the oligotrophic Coral Sea where chlorophyll a averaged 0.13 ± 0.07 mg m -3 . Consistent with previous microscopic and pigment-based observations, we found from sequence analysis that a variety of diatoms (Bacillariophyceae) exhibited high relative abundance in the Arafura Sea and Torres Strait, while dinoflagellates (Dinophyceae) and prymnesiophytes (Prymnesiophyceae) were more abundant in the Coral Sea. Ordination analysis identified temperature, nutrient concentrations and water depth as key drivers of the region's assemblage composition. This is the first molecular and flow cytometric survey of the abundance and diversity of both prokaryotic and picoeukaryotic phytoplankton in this region, and points to the need to include the picocyanobacterial populations as an essential oceanic variable for sustained monitoring in order to better understand the health of these important coastal waters as global oceans change.

Ascorbate (vitamin C) is critical as a first line of defense antioxidant within the brain, and specifically within the synapse. Ascorbate is released by astrocytes during glutamate clearance and disruption of this exchange mechanism may be critical in mediating glutamate toxicity within the synapse. This is likely even more critical in neurodegenerative disorders with associated excitotoxicity and seizures, in particular Alzheimer's disease, in which ascorbate levels are often low. Using Gulo -/- mice that are dependent on dietary ascorbate, we established that low brain ascorbate increased sensitivity to kainic acid as measured via behavioral observations, electroencephalography (EEG) measurements, and altered regulation of several glutamatergic system genes. Kainic acid-induced immobility was improved in wild-type mice following treatment with ceftriaxone, which upregulates glutamate transporter GLT-1. The same effect was not observed in ascorbate-deficient mice in which sufficient ascorbate is not available for release. A single, mild seizure event was sufficient to disrupt performance in the water maze in low-ascorbate mice and in APP SWE /PSEN1 dE9 mice. Together, the data support the critical role of brain ascorbate in maintaining protection during glutamatergic hyperexcitation events, including seizures. The study further supports a role for mild, subclinical seizures in cognitive decline in Alzheimer's disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls ( P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa ( P < 0.007 and P < 0.001, respectively), and lower radial alveolar count ( P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.

Objectives: To determine the effect of maternal age (MA) and paternal age (PA) on the risk of gestational hypertension, preeclampsia, and eclampsia in women who delivered on the Texas-Mexico border., Methods: A cohort study using birth certificate data (singleton pregnancies, years 2005-2010) from El Paso County, Texas, was conducted. Six parental age-exposure categories were created with MA 20 to 34 years and PA younger than 35 years serving as the referent. A directed acyclic graph was created. Adjusted risk ratios for the composite outcome of gestational hypertension, preeclampsia, or eclampsia were calculated using Poisson regression., Results: A total of 85,114 records were identified, with a majority of the mothers being of Hispanic ethnicity (89.2%). The incidence of the composite outcome ranged from 2.8% in the MA 20 to 34 years old and PA 35 years and older group to 4.4% in the MA younger than 20 years old and PA 35 years and older group. Compared to the MA 20 to 34 years old and PA younger than 35 years group, women in the MA 35 years and older and PA 35 years and older groups were more likely to experience the outcome (adjusted risk ratio 1.57, 95% confidence interval 1.39-1.77, P < 0.0001)., Conclusions: Couples in which both parents are 35 years old and older should be counseled on the increased risk of gestational hypertension or preeclampsia/eclampsia.

Engineered vascular grafts have shown promise as arteriovenous shunts, but they have not yet progressed to clinical trials for coronary arteries <4 mm in diameter such as the coronary arteries. Control over initial biomaterial properties and remodeling are necessary to generate viable grafts. In this study, we blended collagen with a synthetic material, poly(ε-caprolactone), to modulate the post-grafting inflammatory response while avoiding aneurysmal-like dilation and failure that can occur with pure collagen grafts. We also used pre-implantation in an "in vivo bioreactor" to recruit autologous cells and improve patency after grafting. Electrospun conduits were pre-implanted within rat peritoneal cavities and then grafted autologously into abdominal aortae. Conduit collagen percentages and pre-implantation were tested for their impact on graft remodeling and patency. Burst pressures >2000 mmHg, reproducible expansion with systole/diastole, and maintenance of mechanical integrity were observed. More importantly, peritoneal pre-implantation reduced overall lipid oxidation, intimal layer thickness, and expression of an M1 macrophage marker. The condition with the most collagen, 25%, exhibited the lowest expression of macrophage markers but also resulted in a thicker intimal layer. Overall, the 10% collagen/PCL with peritoneal pre-implantation condition appeared to exhibit the best combination of responses, and may result in improved clinical graft viability., Statement of Significance: This manuscript describes a rodent study to systematically determine the benefits of both pre-implantation in the peritoneal cavity and specific ratios of collagen on engineered vascular graft viability. We show that pre-implantation had a significant benefit, including decreasing the expression of macrophage markers and reducing lipid oxidation after grafting. This study is the first time that the benefits of peritoneal pre-implantation have been compared to an "off the shelf," directly grafted control condition. We also demonstrated the importance of specific collagen ratio on the response after grafting. Overall, we feel that this article will be of interest to the field and it has the potential to address a significant clinical need: a graft for coronary arteries <4 mm in diameter., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate the frequency and the quantity of polyhydramnios attributable to diabetes in pregnancy., Methods: The charts of patients with a four-quadrant amniotic fluid index (AFI) ≥ 20 cm and either a diagnosis of diabetes or a diabetes screening test during the index pregnancy were retrospectively reviewed. AFI was stratified into 5 categories and the frequency of diabetes was evaluated for each group. The frequency of polyhydramnios attributable to diabetes was compared to the frequency of polyhydramnios in the setting of fetal anomalies or no known cause., Results: One thousand five hundred and forty-five patients were included in the study. Eight point five percent ( n = 131) had diabetes and no other cause for polyhydramnios. Eleven point two percent (173) had antenatally diagnosed anomalies. For all categories of AFI except the largest (> 40.9 cm) the most common cause of polyhydramnios was idiopathic. In patients with diabetes the AFI was most likely to be between 26 cm and 35.9 cm., Conclusion: The rate of polyhydramnios in this study is 8.5%. Patients with diabetes most commonly have mild polyhydramnios between 26 and 35.9 cm of fluid on a four-quadrant AFI., Competing Interests: Conflict-of-interest statement: The author has no conflicts of interest related to the manuscript.

Background: The large-scale analysis of phenomic data (i.e., full phenotypic traits of an organism, such as shape, metabolic substrates, and growth conditions) in microbial bioinformatics has been hampered by the lack of tools to rapidly and accurately extract phenotypic data from existing legacy text in the field of microbiology. To quickly obtain knowledge on the distribution and evolution of microbial traits, an information extraction system needed to be developed to extract phenotypic characters from large numbers of taxonomic descriptions so they can be used as input to existing phylogenetic analysis software packages., Results: We report the development and evaluation of Microbial Phenomics Information Extractor (MicroPIE, version 0.1.0). MicroPIE is a natural language processing application that uses a robust supervised classification algorithm (Support Vector Machine) to identify characters from sentences in prokaryotic taxonomic descriptions, followed by a combination of algorithms applying linguistic rules with groups of known terms to extract characters as well as character states. The input to MicroPIE is a set of taxonomic descriptions (clean text). The output is a taxon-by-character matrix-with taxa in the rows and a set of 42 pre-defined characters (e.g., optimum growth temperature) in the columns. The performance of MicroPIE was evaluated against a gold standard matrix and another student-made matrix. Results show that, compared to the gold standard, MicroPIE extracted 21 characters (50%) with a Relaxed F1 score > 0.80 and 16 characters (38%) with Relaxed F1 scores ranging between 0.50 and 0.80. Inclusion of a character prediction component (SVM) improved the overall performance of MicroPIE, notably the precision. Evaluated against the same gold standard, MicroPIE performed significantly better than the undergraduate students., Conclusion: MicroPIE is a promising new tool for the rapid and efficient extraction of phenotypic character information from prokaryotic taxonomic descriptions. However, further development, including incorporation of ontologies, will be necessary to improve the performance of the extraction for some character types.

Background: Preterm birth and respiratory support with invasive mechanical ventilation frequently leads to bronchopulmonary dysplasia (BPD). A hallmark feature of BPD is alveolar simplification. For our preterm lamb model of BPD, invasive mechanical ventilation is associated with postnatal feeding intolerance (reduced nutrition) and sedation. In contrast, preterm lambs managed by noninvasive support (NIS) have normal alveolar formation, appropriate postnatal nutrition, and require little sedation. We used the latter, positive-outcome group to discriminate the contribution of reduced nutrition vs. sedation on alveolar simplification. We hypothesized that, restricted nutrition, but not sedation with pentobarbital, contributes to impaired indices of alveolar formation in preterm lambs managed by NIS., Methods: Preterm lambs managed by NIS for 21d were randomized into three groups: NIS control, NIS plus restricted nutrition, and NIS plus excess sedation with pentobarbital. We quantified morphological and biochemical indices of alveolar formation, as well as mesenchymal cell apoptosis and proliferation., Results: Restricted nutrition impaired morphological and biochemical indices of alveolar formation, and reduced mesenchymal cell apoptosis and proliferation. Excess sedation with pentobarbital did not alter these indices, although mesenchymal cell apoptosis was less., Conclusion: Our results demonstrate that restricted nutrition, but not excess sedation, contributes to impaired alveolar formation during the evolution of BPD in chronically ventilated preterm lambs.

Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Background: MicrO is an ontology of microbiological terms, including prokaryotic qualities and processes, material entities (such as cell components), chemical entities (such as microbiological culture media and medium ingredients), and assays. The ontology was built to support the ongoing development of a natural language processing algorithm, MicroPIE (or, Microbial Phenomics Information Extractor). During the MicroPIE design process, we realized there was a need for a prokaryotic ontology which would capture the evolutionary diversity of phenotypes and metabolic processes across the tree of life, capture the diversity of synonyms and information contained in the taxonomic literature, and relate microbiological entities and processes to terms in a large number of other ontologies, most particularly the Gene Ontology (GO), the Phenotypic Quality Ontology (PATO), and the Chemical Entities of Biological Interest (ChEBI). We thus constructed MicrO to be rich in logical axioms and synonyms gathered from the taxonomic literature., Results: MicrO currently has ~14550 classes (~2550 of which are new, the remainder being microbiologically-relevant classes imported from other ontologies), connected by ~24,130 logical axioms (5,446 of which are new), and is available at (http://purl.obolibrary.org/obo/MicrO.owl) and on the project website at https://github.com/carrineblank/MicrO. MicrO has been integrated into the OBO Foundry Library (http://www.obofoundry.org/ontology/micro.html), so that other ontologies can borrow and re-use classes. Term requests and user feedback can be made using MicrO's Issue Tracker in GitHub. We designed MicrO such that it can support the ongoing and future development of algorithms that can leverage the controlled vocabulary and logical inference power provided by the ontology., Conclusions: By connecting microbial classes with large numbers of chemical entities, material entities, biological processes, molecular functions, and qualities using a dense array of logical axioms, we intend MicrO to be a powerful new tool to increase the computing power of bioinformatics tools such as the automated text mining of prokaryotic taxonomic descriptions using natural language processing. We also intend MicrO to support the development of new bioinformatics tools that aim to develop new connections between microbial phenotypes and genotypes (i.e., the gene content in genomes). Future ontology development will include incorporation of pathogenic phenotypes and prokaryotic habitats.