Acute Natural Cocoa Consumption Improves Cerebral Vasodilatory Capacity in Obese Individuals

Obesity increases the risk for cardio and cerebral vascular diseases including hypertension, coronary artery disease, and stroke. Our preliminary data indicate that obese individuals (Obese) have attenuated cerebral vasodilatory capacity compared to age / sex matched lean individuals (Lean). This study tested the hypothesis that natural cocoa (NC) consumption (13g NC, The Hershey Company) would restore cerebral vasodilatory capacity in Obese. 15 lean (BMI \u3c 25) and 15 obese (BMI \u3e 30) subjects underwent a rebreathing protocol while cerebral blood velocity (CBFV) was measured before and 2 hr post consumption of a NC-containing drink or a NC-free placebo (randomized order, single-blinded). Cerebral vascular conductance (CVCI) was calculated as CBFV / MAP. The response to rebreathing was expressed as % of baseline CVCI (% CVCI). Prior to beverage consumption, the range of % CVCI and the maximal increase in CVCI in response to rebreathing-induced hypercapnia was attenuated in Obese (P0.05 pre vs. post), such that the baseline differences between groups were eliminated (P\u3e0.05). The placebo beverage had no effect on any indices of cerebral vascular function in either cohort (P\u3e0.05 for all variables). These data support the hypothesis that NC consumption can acutely augment cerebral vasodilatory capacity in Obese

A hymenopterists' guide to the hymenoptera anatomy ontology: utility, clarification, and future directions

Hymenoptera exhibit an incredible diversity of phenotypes, the result of ~240 million years of evolution and the primary subject of more than 250 years of research. Here we describe the history, development, and utility of the Hymenoptera Anatomy Ontology (HAO) and its associated applications. These resourc¬es are designed to facilitate accessible and extensible research on hymenopteran phenotypes. Outreach with the hymenopterist community is of utmost importance to the HAO project, and this paper is a direct response to questions that arose from project workshops. In a concerted attempt to surmount barriers of understanding, especially regarding the format, utility, and development of the HAO, we discuss the roles of homology, “preferred terms”, and “structural equivalency”. We also outline the use of Universal Resource Identifiers (URIs) and posit that they are a key element necessary for increasing the objectivity and repeatability of science that references hymenopteran anatomy. Pragmatically, we detail a mechanism (the “URI table”) by which authors can use URIs to link their published text to the HAO, and we describe an associated tool (the “Analyzer”) to derive these tables. These tools, and others, are available through the HAO Portal website (http://portal.hymao.org). We conclude by discussing the future of the HAO with respect to digital publication, cross-taxon ontology alignment, the advent of semantic phenotypes, and community-based curation.Katja C. Seltmann... Andrew D. Austin... John T. Jennings... et al

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Taxonomy based on science is necessary for global conservation

Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Bacterial Cyclic AMP-Phosphodiesterase Activity Coordinates Biofilm Formation

<div><p>Biofilm-related infections are a major contributor to human disease, and the capacity for surface attachment and biofilm formation are key attributes for the pathogenesis of microbes. <i>Serratia marcescens</i> type I fimbriae-dependent biofilms are coordinated by the adenylate cyclase, CyaA, and the cyclic 3′,5′-adenosine monophosphate (cAMP)-cAMP receptor protein (CRP) complex. This study uses <i>S. marcescens</i> as a model system to test the role of cAMP-phosphodiesterase activity in controlling biofilm formation. Herein we describe the characterization of a putative <i>S. marcescens</i> cAMP-phosphodiesterase gene (SMA3506), designated as <i>cpdS</i>, and demonstrated to be a functional cAMP-phosphodiesterase both <i>in vitro</i> and <i>in vivo</i>. Deletion of <i>cpdS</i> resulted in defective biofilm formation and reduced type I fimbriae production, whereas multicopy expression of <i>cpdS</i> conferred a type I fimbriae-dependent hyper-biofilm. Together, these results support a model in which bacterial cAMP-phosphodiesterase activity modulates biofilm formation.</p></div

Oligonucleotide primers used in this study.

a<p>Lower case base pairs target recombination and upper case base pairs direct amplification.</p

CpdS exhibits cAMP-PDE activity <i>in vitro</i>.

<p><b>A.</b> Thin layer chromatography to examine cAMP-PDE activity from purified CpdA from <i>E. coli</i>, CpdS, and CpdS-N94A mixed with cAMP. HK  =  indicates heat killed protein before being mixed with cAMP. <b>B.</b> cAMP-PDE assay shows dose responsive activity by CpdS and positive controls CpdA and PA4969 (CpdA from <i>P. aeruginosa</i>), but not by the CpdS-N94A mutant or a mock purified protein.</p

Strains used in this study.

<p>Strains used in this study.</p

Role of cAMP-phosphodiesterase activity in biofilm formation and identification of a cAMP-phosphodiesterase gene in the <i>S. marcescens</i> genome.

<p><b>A.</b> Model for cAMP metabolism and inhibitory effect on biofilm production. Adenylate cyclase (AC) catalyzes synthesis of cAMP from ATP, whereas cyclic-AMP phosphodiesterase (cAMP-PDE) catalyzes hydrolysis of cAMP to 5′-AMP. <b>B.</b> Crystal violet stained biofilms on the side of test tubes formed under high-sheer conditions. Shown is a wild-type <i>S. marcescens</i> strain with either the empty vector or the vector with a wild-type copy of the <i>E. coli</i> cAMP-PDE gene, <i>cpdA</i>. <b>C.</b> Genomic context of the <i>S. marcescens cpdS</i> gene, a candidate cAMP-PDE gene.</p