Modulation of La Crosse Virus Infection in Aedes albopictus Mosquitoes Following Larval Exposure to Coffee Extracts

The mosquito-borne La Crosse virus (LACV; Family Bunyaviridae) may cause encephalitis, primarily in children, and is distributed throughout much of the eastern United States. No antivirals or vaccines are available for LACV, or most other mosquito-borne viruses, and prevention generally relies on mosquito control. We sought to determine whether coffee extracts could interfere with LACV replication and vector mosquito development. Both regular and decaffeinated coffee demonstrated significant reductions in LACV replication in direct antiviral assays. This activity was not due to the presence of caffeine, which did not inhibit the virus life cycle. Aedes albopictus (Skuse; Diptera: Culicidae) mosquito larvae suffered near total mortality when reared in high concentrations of regular and decaffeinated coffee and in caffeine. Following larval exposure to sublethal coffee concentrations, adult A. albopictus mosquitoes had significantly reduced whole-body LACV titers 5 days post-infection, compared to larvae reared in distilled water. These results suggest that it may be possible to both control mosquito populations and alter the vector competence of mosquitoes for arthropod-borne viruses by introducing antiviral compounds into the larval habitat

Investing in People: Assessing the Economic Benefits of 1890 Institutions

The report examines the historical USDA funding levels of 1890 institutions; discusses the outcomes of these investments and potential measurable indicators of these outcomes; and outlines a conceptual model for estimating returns to investment in education tailored to particularities of the 1890's.1890s, land grant universities, human capital, extension service, agricultural research, research funding, Labor and Human Capital, Teaching/Communication/Extension/Profession,

Meiotic errors followed by two parallel postzygotic trisomy rescue events are a frequent cause of constitutional segmental mosaicism

Structural copy number variation (CNV) is a frequent cause of human variation and disease. Evidence is mounting that somatic acquired CNVs are prevalent, with mosaicisms of large segmental CNVs in blood found in up to one percent of both the healthy and patient populations. It is generally accepted that such constitutional mosaicisms are derived from postzygotic somatic mutations. However, few studies have tested this assumption. Here we determined the origin of CNVs which coexist with a normal cell line in nine individuals. We show that in 2/9 the CNV originated during meiosis. The existence of two cell lines with 46 chromosomes thus resulted from two parallel trisomy rescue events during postzygotic mitoses

Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.

Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma

Electronic health record data quality assessment and tools: A systematic review

OBJECTIVE: We extended a 2013 literature review on electronic health record (EHR) data quality assessment approaches and tools to determine recent improvements or changes in EHR data quality assessment methodologies. MATERIALS AND METHODS: We completed a systematic review of PubMed articles from 2013 to April 2023 that discussed the quality assessment of EHR data. We screened and reviewed papers for the dimensions and methods defined in the original 2013 manuscript. We categorized papers as data quality outcomes of interest, tools, or opinion pieces. We abstracted and defined additional themes and methods though an iterative review process. RESULTS: We included 103 papers in the review, of which 73 were data quality outcomes of interest papers, 22 were tools, and 8 were opinion pieces. The most common dimension of data quality assessed was completeness, followed by correctness, concordance, plausibility, and currency. We abstracted conformance and bias as 2 additional dimensions of data quality and structural agreement as an additional methodology. DISCUSSION: There has been an increase in EHR data quality assessment publications since the original 2013 review. Consistent dimensions of EHR data quality continue to be assessed across applications. Despite consistent patterns of assessment, there still does not exist a standard approach for assessing EHR data quality. CONCLUSION: Guidelines are needed for EHR data quality assessment to improve the efficiency, transparency, comparability, and interoperability of data quality assessment. These guidelines must be both scalable and flexible. Automation could be helpful in generalizing this process

Impact of Vitamin C on Endothelial Function and Exercise Capacity in Patients with a Fontan Circulation

Objective.  To evaluate the impact of antioxidant therapy on functional health status in Fontan‐palliated patients. Design.  Prospective, randomized, double‐blind, placebo‐controlled trial. Patients.  Fifty‐three generally asymptomatic Fontan patients. Interventions.  Patients were randomized to receive either high‐dose ascorbic acid (vitamin C) or placebo for 4 weeks. Outcome Measures.  Peripheral vascular function, as measured with endothelium‐dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. Results.  Twenty‐three vitamin C‐ and 21 placebo‐assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7–18.2) and 11.9 years (IQR 9.0–15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). Conclusions.  Short‐term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92126/1/j.1747-0803.2011.00605.x.pd

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant (P < .05) for duodenum (r = 0.42) and colon (r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant (P < .05) correlations were observed for crypt dilation (r = 0.42), lamina propria (LP) lymphocytes (r = 0.40), LP neutrophils (r = 0.45), mucosal fibrosis (r = 0.47), lacteal dilation (r = 0.39), and villus stunting (r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity

The Gamma-Ray Imager/Polarimeter for Solar Flares (GRIPS)

The balloon-borne Gamma-Ray Imager/Polarimeter for Solar flares (GRIPS) instrument will provide a near-optimal combination of high-resolution imaging, spectroscopy, and polarimetry of solar-flare gamma-ray/hard X-ray emissions from approximately 20 keV to greater than approximately 10 MeV. GRIPS will address questions raised by recent solar flare observations regarding particle acceleration and energy release, such as: What causes the spatial separation between energetic electrons producing hard X-rays and energetic ions producing gamma-ray lines? How anisotropic are the relativistic electrons, and why can they dominate in the corona? How do the compositions of accelerated and ambient material vary with space and time, and why? The spectrometer/polarimeter consists of sixteen 3D position-sensitive germanium detectors (3D-GeDs), where each energy deposition is individually recorded with an energy resolution of a few keV FWHM and a spatial resolution of less than 0.1 cubic millimeter. Imaging is accomplished by a single multi-pitch rotating modulator (MPRM), a 2.5-centimeter thick tungsten alloy slit/slat grid with pitches that range quasi-continuously from 1 to 13 millimeters. The MPRM is situated 8 meters from the spectrometer to provide excellent image quality and unparalleled angular resolution at gamma-ray energies (12.5 arcsec FWHM), sufficient to separate 2.2 MeV footpoint sources for almost all flares. Polarimetry is accomplished by analyzing the anisotropy of reconstructed Compton scattering in the 3D-GeDs (i.e., as an active scatterer), with an estimated minimum detectable polarization of a few percent at 150-650 keV in an X-class flare. GRIPS is scheduled for a continental-US engineering test flight in fall 2013, followed by long or ultra-long duration balloon flights in Antarctica

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function