Advancing Healthy Lifestyles:: A Multicomponent Initiative to Reduce the Burden of Obesity In Delaware.

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.

Lieutenant Governor's Challenge:: Motivating and Honoring Delawareans to Improve Their Health and Well-Being.

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.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

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.

CyanoCyc cyanobacterial web portal.

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.

Transverse myelitis associated with Mpox infection.

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.

Postnatal growth restriction impairs rat lung structure and function.

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.

The EcoCyc Database (2023).

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.

Plastic leachate exposure drives antibiotic resistance and virulence in marine bacterial communities.

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.

Peritoneal pre-conditioning impacts long-term vascular graft patency and remodeling.

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.

Structural connectivity and its association with social connectedness in early adolescence.

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.

Short-Term Efficacy of Using a Novel Low-Volume Bone Marrow Aspiration Technique to Treat Knee Osteoarthritis: A Retrospective Cohort Study.

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.

Plastic leachates impair picophytoplankton and dramatically reshape the marine microbiome.

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.

Symptomatic Vascular Compression of Brainstem May Be Managed Conservatively.

Medulla compression from vertebral artery abnormality is a very rare occurrence with few cases present in the literature. It has been documented to present with a very wide spectrum of clinical symptomatology ranging from asymptomatic to full hemiplegia. There is currently no treatment algorithm in place to guide clinicians encountering such patients but treatments have historically involved major posterior compartment surgical interventions. This case outlined a patient evaluated for dizziness without any other neurological symptoms or signs, found to have abnormal dilatation, elongation, and tortuosity of the vertebral artery with resultant compression of the medulla oblongata. The patient was managed conservatively after discussion of surgical options. This report outlined an important consideration for management of medullar compression by vertebral artery based on symptom severity with the possibility of postponing surgical or endovascular interventions and opting for conservative management with an anti-platelet regimen, particularly in the short term.

Minimal handgrip force is needed for transcutaneous electrical stimulation to improve hand functions of patients with severe spinal cord injury.

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.

Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing.

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.

Perinatal Research Society's Young Investigator Workshop Prepares the Next Generation of Investigators.

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.

Functional characterisation of substrate-binding proteins to address nutrient uptake in marine picocyanobacteria.

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.

Identification of Prognostic Biomarker Candidates Associated With Melanoma Using High-Dimensional Genomic Data.

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.