Discovery and mapping of the Triton seep site, Redondo Knoll: fluid flow and microbial colonization within an oxygen minimum zone

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Wagner, J. K. S., Smart, C., & German, C. R. Discovery and mapping of the Triton seep site, Redondo Knoll: fluid flow and microbial colonization within an oxygen minimum zone. Frontiers in Marine Science, 7, (2020): 108, doi:10.3389/fmars.2020.00108.This paper examines a deep-water (∼900 m) cold-seep discovered in a low oxygen environment ∼30 km off the California coast in 2015 during an E/V Nautilus telepresence-enabled cruise. This Triton site was initially detected from bubble flares identified via shipboard multibeam sonar and was then confirmed visually using the remotely operated vehicle (ROV) Hercules. High resolution mapping (to 1 cm resolution) and co-registered imaging has provided us with a comprehensive site overview – both of the geologic setting and the extent of the associated microbial colonization. The Triton site represents an active cold-seep where microorganisms can act as primary producers at the base of a chemosynthesis-driven food chain. But it is also located near the core of a local oxygen minimum zone (OMZ), averaging 100 m across the seafloor, dominate the site, while typical seep-endemic macro-fauna were noticeably absent from our co-registered photographic and high-resolution mapping surveys – especially when compared to all adjacent seep sites within the same California Borderlands region. While such absences of abundant macro-fauna could be attributable to variations in the availability of dissolved oxygen in the overlying water column this need not necessarily be the case. An alternate possibility is that the zonation in microbial activity that is readily observable at the seafloor at Triton reflects, instead, a concentric pattern of radially diminishing fluxes of reductants from the underlying seafloor. This unusual but readily accessible discovery, in close proximity to Los Angeles harbor, provides an intriguing new natural laboratory at which to examine biogeochemical and microbiological interactions associated with the functioning of cold seep ecosystems within an OMZ.Ship time was funded by NOAA – Office of Exploration and Research and the Ocean Exploration Trust. This material is based upon work supported by a National Science Foundation Graduate Research Fellowship (to JW), the Office of Naval Research (to CS), and NASA’s Astrobiology program (to CG)

Impact of obesity on acyclovir-induced nephrotoxicity

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Triamcinolone acetonide (TA), an intermediate acting corticosteroid, is used in the treatment of posterior ocular diseases, such as inflammation, posterior uveitis, and diabetic macular edema. The objective of this investigation was to prepare TA-loaded solid lipid nanoparticles (TA-SLNs) and in situ gel (TA-SLN-IG) formulations for delivery into the deeper ocular tissues through the topical route. TA-SLNs were prepared by hot homogenization and ultrasonication method using glyceryl monostearate and Compritol® 888ATO as solid lipids and Tween®80 and Pluronic® F-68 as surfactants. TA-SLNs were optimized and converted to TA-SLN-IG by the inclusion of gellan gum and evaluated for their rheological properties.In vitro transcorneal permeability and in vivo ocular distribution of the TA-SLNs and TA-SLN-IG were studied using isolated rabbit corneas and New Zealand albino rabbits, respectively, and compared with TA suspension, used as control (TA-C). Particle size, PDI, zeta potential, assay, and entrapment efficiency of TA-SLNs were in the range of 200–350 nm, 0.3–0.45, −52.31 to −64.35 mV, 70–98%, and 97–99%, respectively. TA-SLN-IG with 0.3% gellan gum exhibited better rheological properties. The transcorneal permeability of TA-SLN and TA-SLN-IG was 10.2 and 9.3-folds higher compared to TA-C. TA-SLN-IG showed maximum tear concentration at 2 h, indicating an improved pre-corneal residence time, as well as higher concentrations in aqueous humor, vitreous humor and cornea at 6 h, suggesting sustained delivery of the drug into the anterior and posterior segment ocular tissues, when compared to TA-SLN and TA-C. The results, therefore, demonstrate that the lipid based nanoparticulate system combined with the in situ gelling agents can be a promising drug delivery platform for the deeper ocular tissues

Fluoroquinolone versus nonfluoroquinolone treatment of bloodstream infections caused by chromosomally mediated ampc‐producing enterobacteriaceae

Objectives: Chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) display high susceptibility to fluoroquinolones; minimal clinical data exist supporting comparative clinical outcomes. The objective of this study was to compare treatment outcomes between fluoroquinolone and nonfluoroquinolone definitive therapy of bloodstream infections caused by CAE. Methods: This retrospective cohort assessed adult patients with positive blood cultures for CAE that received inpatient treatment for 48 hours. The primary outcome was difference in clinical failure between patients who received fluoroquinolone (FQ) versus non‐FQ treatment. Secondary endpoints included microbiological cure, infection‐related length of stay, 90‐day readmission, and all‐cause inpatient mortality. Results: 56 patients were included in the study (31 (55%) received a FQ as definitive therapy; 25 (45%) received non‐FQ). All non‐FQ patients received a beta‐lactam (BL). Clinical failure occurred in 10 (18%) patients, with 4 (13%) in the FQ group and 6 (24%) in the BL group (p = 0.315). Microbiological cure occurred in 55 (98%) patients. Median infection‐related length of stay was 10 (6–20) days, with a significantly longer stay occurring in the BL group (p = 0.002). There was no statistical difference in 90‐day readmissions between groups (7% FQ vs. 17% BL; p = 0.387); one patient expired. Conclusion: These results suggest that fluoroquinolones do not adversely impact clinical outcomes in patients with CAE. When alternatives to beta‐lactam therapy are needed, fluoroquinolones may provide an effective option

Impact of Obesity in Patients with Candida Bloodstream Infections: A Retrospective Cohort Study

© 2020, The Author(s). Background: Candida species are responsible for 15% of bloodstream infections, leading to prolonged hospitalizations and increased mortality. With the rise in obesity, antifungal dosing is unclear. The purpose of this study was to determine differences in clinical outcomes between obese versus non-obese patients with Candida bloodstream infections. Methods: This retrospective cohort included adult patient’s first episode of Candida bloodstream infection treated with ≥ 48 h of antifungal therapy between 1 June 2013 and 31 August 2019. Patients were excluded for: dual systemic antifungal therapy, polymicrobial infections, or chronic candidiasis. The primary outcome was infection-related length of stay. Secondary outcomes included: time to candidemia resolution, 30-day readmission rates, and in-hospital mortality. Results: Eighty patients were included (28 obese; 52 non-obese). Most were male (55%); median age was 54 years. Median BMI and weight were 36.3 kg/m2 and 103 kg versus 20.4 kg/m2 and 61 kg, respectively (p \u3c 0.01). Baseline characteristics were comparable. C. albicans was isolated in 37.5% of cultures and C. glabrata in 30%. Micafungin was utilized empirically in 72.5% of patients; obese patients received definitive micafungin more frequently (57.1% vs. 21.2%; p \u3c 0.01) and were treated longer (13 versus 10 days; p = 0.04). Infection-related length of stay was 19 days in the obese patients and 13 days in the non-obese patients (p = 0.05). Non-obese patients had a shorter duration of candidemia (5 versus 6 days; p = 0.02). In-hospital mortality was numerically higher in obese patients (21.4% versus 13.5%; p = 0.36). There were no differences in 30-day readmissions between groups. Conclusions: Worse clinical outcomes were observed for obese versus non-obese patients. Further clinical research is warranted

The transcriptomic evolution of mammalian pregnancy:gene expression innovations in endometrial stromal fibroblasts

The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call the latter cell type “neo-ESF” in contrast to “paleo-ESF” which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo-ESF), and cow (secondarily nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario, where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation

Population-Based Correlates of Covid-19 infection: an analysis From the Dfw Covid-19 Prevalence Study

BACKGROUND: COVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population. METHODS: The DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18-89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data. RESULTS: Of 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings. CONCLUSION: Over 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence

Very-high energy gamma-ray astronomy: A 23-year success story in high-energy astroparticle physics

Very-high energy (VHE) gamma quanta contribute only a minuscule fraction - below one per million - to the flux of cosmic rays. Nevertheless, being neutral particles they are currently the best "messengers" of processes from the relativistic/ultra-relativistic Universe because they can be extrapolated back to their origin. The window of VHE gamma rays was opened only in 1989 by the Whipple collaboration, reporting the observation of TeV gamma rays from the Crab nebula. After a slow start, this new field of research is now rapidly expanding with the discovery of more than 150 VHE gamma-ray emitting sources. Progress is intimately related with the steady improvement of detectors and rapidly increasing computing power. We give an overview of the early attempts before and around 1989 and the progress after the pioneering work of the Whipple collaboration. The main focus of this article is on the development of experimental techniques for Earth-bound gamma-ray detectors; consequently, more emphasis is given to those experiments that made an initial breakthrough rather than to the successors which often had and have a similar (sometimes even higher) scientific output as the pioneering experiments. The considered energy threshold is about 30 GeV. At lower energies, observations can presently only be performed with balloon or satellite-borne detectors. Irrespective of the stormy experimental progress, the success story could not have been called a success story without a broad scientific output. Therefore we conclude this article with a summary of the scientific rationales and main results achieved over the last two decades.Comment: 45 pages, 38 figures, review prepared for EPJ-H special issue "Cosmic rays, gamma rays and neutrinos: A survey of 100 years of research

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Nonviral Approaches for Neuronal Delivery of Nucleic Acids

The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cost of large-scale formulation. Nonviral vectors are an attractive alternative in that they offer improved safety profiles compared to viruses, are less expensive to produce, and can be targeted to specific neuronal subpopulations. However, most nonviral vectors suffer from significantly lower transfection efficiencies than neurotropic viruses, severely limiting their utility in neuron-targeted delivery applications. To realize the potential of nonviral delivery technology in neurons, vectors must be designed to overcome a series of extra- and intracellular barriers. In this article, we describe the challenges preventing successful nonviral delivery of nucleic acids to neurons and review strategies aimed at overcoming these challenges