SARS‑CoV‑2 entry into and evolution within a skilled nursing facility

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the facility multiple times without establishing an interfacility transmission chain, followed by a single introduction that infected many individuals within a week. This largescale introduction by a single genotype then persisted in the facility. SARS-CoV-2 sequences were investigated at both the consensus and intra-host variation levels. Understanding the variability in SARS-CoV-2 during transmission chains will assist in understanding the spread of this disease and can ultimately inform best practices for mitigation strategies

ranacapa: An R package and Shiny web app to explore environmental DNA data with exploratory statistics and interactive visualizations.

Environmental DNA (eDNA) metabarcoding is becoming a core tool in ecology and conservation biology, and is being used in a growing number of education, biodiversity monitoring, and public outreach programs in which professional research scientists engage community partners in primary research. Results from eDNA analyses can engage and educate natural resource managers, students, community scientists, and naturalists, but without significant training in bioinformatics, it can be difficult for this diverse audience to interact with eDNA results. Here we present the R package ranacapa, at the core of which is a Shiny web app that helps perform exploratory biodiversity analyses and visualizations of eDNA results. The app requires a taxonomy-by-sample matrix and a simple metadata file with descriptive information about each sample. The app enables users to explore the data with interactive figures and presents results from simple community ecology analyses. We demonstrate the value of ranacapa to two groups of community partners engaging with eDNA metabarcoding results

Health Care Use and Costs Among Patients With Nonalcoholic Steatohepatitis With Advanced Fibrosis Using the Fibrosis-4 Score

Limited evidence exists on the clinical and economic burden of advanced fibrosis in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) due to the invasiveness of liver biopsies for accurately staging liver disease. The fibrosis-4 (FIB-4) score allows for noninvasive assessment of liver fibrosis by using clinical and laboratory data alone. This study aimed to characterize the comorbidity burden, health care resource use (HCRU), and costs among patients with NAFLD/NASH with FIB-4-defined F3 (bridging fibrosis) and F4 (compensated cirrhosis) fibrosis. Using the Optum Research Database, a retrospective cohort study was conducted among 251,725 commercially insured adult patients with ≥1 NAFLD/NASH diagnosis from January 1, 2008, to August 31, 2016, and laboratory data required to calculate FIB-4 scores. Five criteria using varying FIB-4 score cutoffs were identified based on expert clinical opinion and published literature. Date of the first valid FIB-4 score marked the index date. Mean annual HCRU and costs were calculated during the pre-index and post-index periods. The prevalence of FIB-4-based F3 and F4 fibrosis was 0.40%-2.72% and 1.03%-1.61%, respectively. Almost 50% of patients identified with FIB-4-based F3 or F4 had type 2 diabetes, cardiovascular disease, or renal impairment. Total all-cause health care costs increased significantly from pre-index to post-index for patients with FIB-4-based F3 fibrosis across most criteria (17%-29% increase) and patients with FIB-4-based F4 fibrosis across all criteria (47%-48% increase). Inpatient costs were the primary drivers of this increment

Access to

Dehydroquinate synthase (DHQS) catalyses the second step of the shikimate pathway to aromatic compounds. DHQS from the archaeal hyperthermophile Pyrococcus furiosus was insoluble when expressed in Escherichia coli but was partially solubilised when KCl was included in the cell lysis buffer. A purification procedure was developed, involving lysis by sonication at 30 • C followed by a heat treatment at 70 • C and anion exchange chromatography. Purified recombinant P. furiosus DHQS is a dimer with a subunit Mr of 37,397 (determined by electrospray ionisation mass spectrometry) and is active over broad pH and temperature ranges. The kinetic parameters are K M (3-deoxy-D-arabino-heptulosonate 7-phosphate) 3.7 μM and k cat 3.0 sec −1 at 60 • C and pH 6.8. EDTA inactivates the enzyme, and enzyme activity is restored by several divalent metal ions including (in order of decreasing effectiveness) Cd 2+ , Co 2+ , Zn 2+ , and Mn 2+ . High activity of a DHQS in the presence of Cd 2+ has not been reported for enzymes from other sources, and may be related to the bioavailability of Cd 2+ for P. furiosus. This study is the first biochemical characterisation of a DHQS from a thermophilic source. Furthermore, the characterisation of this hyperthermophilic enzyme was carried out at elevated temperatures using an enzyme-coupled assay

Implementation Of The Eighth Joint National Committee Guidelines Of Hypertension By The Primary Care Provider

Hypertension is a widespread disease process and well-known risk factor for coronary artery disease, stroke, heart failure, and renal failure. Proper diagnosis and treatment of hypertension is crucial to reducing these adverse patient outcomes. The Eighth Joint National Committee (JNC 8) released their most recent guidelines of the diagnosis and management of hypertension in December 2013 with implementation to take effect in January 2014. The JNC 8 guidelines of hypertension include the following: proper diagnosis of hypertension (\u3e140/90 for patients \u3c 60 years of age and those with diabetes and/or chronic kidney disease and \u3e150/90 in patients \u3e 60 years of age), lifestyle modifications to be initiated with every hypertensive patient, and newly diagnosed hypertensive patients should follow-up one-month after initial diagnosis and treatment. It is important for primary care providers to abide by these recommendations because of the evidence-based research behind the guidelines released by the Eighth Joint National Committee. This study is significant to education, nursing, and further research because of the prevalence of hypertension. This study was a quantitative, retrospective chart review that analyzed electronic medical records of adult patients newly diagnosed with hypertension with or without diabetes and/or chronic kidney disease. Following approval by the Institutional Review Board (IRB), a standardized data collection tool and legend was used to collect information such as: age, gender, race/ethnicity, blood pressure classification according to the JNC 8 guidelines, diagnosed comorbidities of diabetes and/or chronic kidney disease, pharmacologic management of hypertension, one-month follow-up with the primary care provider, documented need of lifestyle modifications, type of primary care provider and insurance of the patient. A total of 328 patients’ charts met the researchers’ criteria of 18 years of age or older and newly diagnosed with hypertension after January 1, 2014 for inclusion in the study. After compiling the data, the researchers determined the majority of primary care providers do follow the JNC 8 guidelines to diagnose and treat hypertension. Also, in congruence with the JNC 8 guidelines, pharmacological therapy was initiated for each patient diagnosed with hypertension. There was significant statistical difference in recommendation of lifestyle modifications in patients with comorbidities, and diet modifications was the most common lifestyle modification utilized by primary care providers. While primary care providers are likely to follow the JNC 8 guidelines in diagnosing and initiating pharmacological treatment in hypertensive patients, this study concluded that primary care providers do not educate on all recommended lifestyle modifications of the JNC 8 guidelines which include healthy diet, weight control, regular exercise, and smoking cessatio

Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.

Type II NADH:quinone oxidoreductase (NDH-2) is a proposed drug-target of major pathogenic microorganisms such as Mycobacterium tuberculosis and Plasmodium falciparum. Many NDH-2 inhibitors have been identified, but rational drug development is impeded by the lack of information regarding their mode of action and associated inhibitor-bound NDH-2 structure. We have determined the crystal structure of NDH-2 complexed with a quinolone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). HQNO is nested into the slot-shaped tunnel of the Q-site, in which the quinone-head group is clamped by Q317 and I379 residues, and hydrogen-bonds to FAD. The interaction of HQNO with bacterial NDH-2 is very similar to the native substrate ubiquinone (UQ1) interactions in the yeast Ndi1-UQ1 complex structure, suggesting a conserved mechanism for quinone binding. Further, the structural analysis provided insight how modifications of quinolone scaffolds improve potency (e.g. quinolinyl pyrimidine derivatives) and suggests unexplored target space for the rational design of new NDH-2 inhibitors

Recent Applications of Space Weather Research to NASA Space Missions

Marshall Space Flight Center s Space Environments Team is committed to applying the latest research in space weather to NASA programs. We analyze data from an extensive set of space weather satellites in order to define the space environments for some of NASA s highest profile programs. Our goal is to ensure that spacecraft are designed to be successful in all environments encountered during their missions. We also collaborate with universities, industry, and other federal agencies to provide analysis of anomalies and operational impacts to current missions. This presentation is a summary of some of our most recent applications of space weather data, including the definition of the space environments for the initial phases of the Space Launch System (SLS), acquisition of International Space Station (ISS) frame potential variations during geomagnetic storms, and Nascap-2K charging analyses

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

Gram-negative bacteria ubiquitously produce and release nano-size, non-replicative outer membrane vesicles (OMVs). In the gastrointestinal (GI-) tract, OMVs generated by members of the intestinal microbiota are believed to contribute to maintaining the intestinal microbial ecosystem and mediating bacteria–host interactions, including the delivery of bacterial effector molecules to host cells to modulate their physiology. Bacterial OMVs have also been found in the bloodstream although their origin and fate are unclear. Here we have investigated the interactions between OMVs produced by the major human gut commensal bacterium, Bacteroides thetaiotaomicron (Bt), with cells of the GI-tract. Using a combination of in vitro culture systems including intestinal epithelial organoids and in vivo imaging we show that intestinal epithelial cells principally acquire Bt OMVs via dynamin-dependent endocytosis followed by intracellular trafficking to LAMP-1 expressing endo-lysosomal vesicles and co-localization with the perinuclear membrane. We observed that Bt OMVs can also transmigrate through epithelial cells via a paracellular route with in vivo imaging demonstrating that within hours of oral administration Bt OMVs can be detected in systemic tissues and in particular, the liver. Our findings raise the intriguing possibility that OMVs may act as a long-distance microbiota–host communication system

Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype‐up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrom