The Impact of Antihypertensive Drugs on the Number and Risk of Death, Stroke and Myocardial Infarction in the United States

Estimating the value of medical innovation is a continual challenge. In this research, we quantify the impact of antihypertensive therapy on U.S. blood pressures, risk and number of heart attacks, strokes, and deaths. We also consider the potential for further improvements. We estimate the value of innovation using equations relating blood pressure to adverse outcomes from the Framingham Heart Study. Our results show that without antihypertensive therapy, 1999-2000 average blood pressure for the U.S. population age 40 plus would have been 10-13 percent higher. 86,000 excess premature deaths from cardiovascular disease (2001), and 833,000 hospital discharges for stroke and heart attacks (2002) would have occurred. Life expectancy would be 0.5 (men) and 0.4 (women) years lower. At guideline care, there would have been 89,000 fewer premature deaths (2001) and 420,000 fewer hospital discharges for stroke and heart attack (2002) than observed. Our analysis suggests that antihypertensive therapy has had a significant impact on cardiovascular health outcomes but that mortality gains would have been approximately twice as high if guideline care had been achieved for all.

Retrospective Determination of Prognostic Factors in BRAF-V600E Melanoma Brain Metastases​

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Tissue tropisms opt for transmissible reassortants during avian and swine influenza A virus co-infection in swine

Genetic reassortment between influenza A viruses (IAVs) facilitate emergence of pandemic strains, and swine are proposed as a “mixing vessel” for generating reassortants of avian and mammalian IAVs that could be of risk to mammals, including humans. However, how a transmissible reassortant emerges in swine are not well understood. Genomic analyses of 571 isolates recovered from nasal wash samples and respiratory tract tissues of a group of co-housed pigs (influenza-seronegative, avian H1N1 IAV–infected, and swine H3N2 IAV– infected pigs) identified 30 distinct genotypes of reassortants. Viruses recovered from lower respiratory tract tissues had the largest genomic diversity, and those recovered from turbinates and nasal wash fluids had the least. Reassortants from lower respiratory tracts had the largest variations in growth kinetics in respiratory tract epithelial cells, and the cold temperature in swine nasal cells seemed to select the type of reassortant viruses shed by the pigs. One reassortant in nasal wash samples was consistently identified in upper, middle, and lower respiratory tract tissues, and it was confirmed to be transmitted efficiently between pigs. Study findings suggest that, during mixed infections of avian and swine IAVs, genetic reassortments are likely to occur in the lower respiratory track, and tissue tropism is an important factor selecting for a transmissible reassortant

Exploratory use of fluorescent SmartProbes for the rapid detection of microbial isolates causing corneal ulcer

PURPOSE:To explore the use of optical SmartProbes for the rapid evaluation of corneal scrapes from patients with suspected microbial keratitis, as a clinical alternative to Gram stain. DESIGN:Experimental study with evaluation of a diagnostic technology. METHODS:Corneal scrapes were collected from 267 patients presenting with microbial keratitis at a referral cornea clinic in South India. Corneal scrapes were flooded with SmartProbes (BAC One or BAC Two) and evaluated by fluorescence microscopy (without the need for sample washing or further processing). The SmartProbe labelled samples were scored as bacteria/fungi/none (BAC One) or gram-negative bacteria/none (BAC Two) and compared to Gram stain results. RESULTS:Compared to Gram stain, BAC One demonstrated sensitivity and specificity of 80.0 and 87.5 percent respectively, positive and negative predictive values (PPV, NPV) of 93.8 and 65.1 percent, and an accuracy of 82.2. BAC Two demonstrated sensitivity and specificity of 93.3 and 84.8 percent respectively, a NPV of 99.2 percent and an accuracy of 85.6 percent. When the corresponding culture results were compared to the Gram stain result, the sensitivity and specificity were 73.4 and 70.7 percent, the PPV and NPVs were 86.5 and 51.0 percent, and an overall accuracy of 72.6. CONCLUSIONS:Fluorescent SmartProbes offer a comparative method to Gram stain for delineating gram-positive or gram-negative bacteria or fungi within corneal scrapes. We demonstrate equivalent or higher sensitivity, specificity, PPV and NPVs, and accuracy than culture to Gram stain. Our approach has scope for point-of-care clinical application to aid in the diagnosis of microbial keratitis

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

ReviewHuman biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.Supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032]info:eu-repo/semantics/publishedVersio

A systematic approach synergizing toxicological and epidemiological knowledge

Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032 ]. Authors acknowledge the editorial assistance of Richard Davies. Publisher Copyright: © 2023 The Author(s)Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.publishersversionpublishe

Form and function within a phylogenetic framework: Locomotory habits of extant predators and some Miocene Sparassodonta (Metatheria)

In this study, we analysed locomotory habits in extant predators and Sparassodonta species through geometric morphometric techniques and discriminant analyses of the distal humerus in anterior view, proximal ulna in lateral view, and tibia in proximal view. We included a wide sample of extant predators, and considered the phylogenetic and allometric structure in the data sets. We also included some Sparassodonta, a group of carnivorous metatherians that inhabited South America during the Cenozoic, and inferred their locomotory habits. Results suggest the presence of a close relationship between shape and locomotory habits, even after removing the shape component explained by phylogeny in the three postcranial elements. Terrestrial habits were inferred for Arctodictis sinclairi, Borhyaena tuberata, 'Lycopsis' longirostrus, and Thylacosmilus atrox. Some degree of cursoriality was highlighted in B. tuberata and T. atrox, and climbing abilities in 'L.' longirostrus, and to a lesser degree in B. tuberata. Scansorial habits were inferred for Cladosictis patagonica, Sipalocyon gracilis, Prothylacynus patagonicus, and Pseudonotictis pusillus, and in the case of C. patagonica, some digging ability was also tentatively inferred. © 2012 The Linnean Society of London.Fil: Ercoli, Marcos Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Prevosti, Francisco Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Alvarez, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Facultad de Ciencias Naturales y Museo, Universidad Nacional de la Plata; Argentin