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Coronavirus disease 2019 (COVID-19), the clinical syndrome associated with infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted nearly every country in the world. Despite an unprecedented focus of scientific investigation, there is a paucity of evidence-based pharmacotherapies against this disease. Because of this lack of data-driven treatment strategies, broad variations in practice patterns have emerged. Observed hypercoagulability in patients with COVID-19 has created debate within the critical care community on the therapeutic utility of heparin. We seek to provide an overview of the data supporting the therapeutic use of heparin, both unfractionated and low molecular weight, as an anticoagulant for the treatment of SARS-CoV-2 infection. Additionally, we review preclinical evidence establishing biological plausibility for heparin and synthetic heparin-like drugs as therapies for COVID-19 through antiviral and anti-inflammatory effects. Finally, we discuss known adverse effects and theoretical off-target effects that may temper enthusiasm for the adoption of heparin as a therapy in COVID-19 without confirmatory prospective randomized controlled trials. Despite previous failures of anticoagulants in critical illness, plausibility of heparin for COVID-19 is sufficiently robust to justify urgent randomized controlled trials to determine the safety and effectiveness of this therapy.

Introduction Many patients who present to E/D with low or intermediate risk cardiac presentations can be safely managed with out-patient ambulatory diagnostics strategy. The lack of definitive outpatient pathways to safely manage these patients has a significant impact on admissions and length of stay adding to the current bed crisis and overcrowding of Emergency Department (E/D). A novel collaborative approach to this problem involved the implementation of a Cardiology ANP led Virtual Clinic outpatient ambulatory pathway which facilitates the referral of non ACS chest discomfort, rate controlled atrial fibrillation/flutter/pSVT, stable heart failure, HTN, incidental murmur, low risk collapse/syncope from the ED and provides patients with rapid access to a comprehensive range of outpatient cardiology diagnostics prior to referral to OPD when necessary. Aims/Objectives To determine the benefit of an ANP-led Virtual Cardiology Clinic to the patient and the organisation. Methodology Clinic referrals from January 2017 - December 2017 were audited. Data was collected prospectively as patients were referred to the service and those referred patients underwent case review (History/exam/Bloods/CXR/ECG) and when required, were contacted by phone. If indicated, appropriate diagnostics were requested, results reviewed then referred on to consultant clinic only if indicated. Results/Discussion 894 patients were referred. 9 patients (1%) recalled to ED. A significant 254 (28%) were deemed not to require diagnostics and discharged to GP. 732 diagnostic tests were performed on 640 patients including 201 functional stress tests (13 abnormal), 38 coronary day case angiograms (10 of which required PCI), 292 Holters, 97 ECHOs (13 minor abnormalities), 68 CTCA, 12 DCCV, 73 24 hour BP. 186 patients were subsequently referred to cardiology OPD. There were 2,145 acute beds saved (based on 2.4 LOS) with estimated savings of €2,4000,000. Conclusion The Cardiology ANP led Virtual Clinic is a safe and efficient pathway that pre – filters ED referrals resulting in reduced waiting time in the Emergency Department, unnecessary travel back to the hospital (further reducing travel time, costs, waiting times), unnecessary referral to cardiology outpatients (reducing outpatient department overcrowding and waiting times). In a 12-month period, this initiative has saved Beaumont Hospital an estimated 2.4 million Euro and 2,145 acute hospital bed days. Implications Cardiology ANP led Virtual Clinics have the potential for a significant impact around the country with regards to the appropriate and efficient management of acute cardiology presentations to E/D with early access to outpatient cardiology ambulatory diagnostics and appropriate referral to outpatient consultant cardiology clinics or d/c to GP.

Patients with inflammatory bowel disease have a unique inflammatory response to infection given the pathogenesis of these diseases and the common use of immunosuppressive therapy.The goal of this study is to determine severe sepsis outcomes in a subgroup of visits with the comorbidities of inflammatory bowel disease.The 2012 National Inpatient Sample database was used to identify patients with explicitly coded diagnoses of severe sepsis or septic shock. Visits with chronic inflammatory bowel disease and other inflammatory diagnoses were identified using ICD-9 codes. Sepsis outcomes of interest were identified using ICD-9 codes.There were 92,296 visits for severe sepsis or septic shock in the analysis. In the control group, the in-hospital mortality rate was 26.5%. Ulcerative colitis visits had a higher mortality rate (34.9%) while Crohn disease visits had lower mortality (19.6%). After adjusting for potential confounders, ulcerative colitis was independently associated with higher mortality (odds ratio [OR] 1.61, 95% CI 1.35-1.93). Conversely, Crohn disease was independently associated with lower mortality (OR 0.78, 95% CI 0.63-0.97).Sepsis visits with Crohn disease had improved outcomes compared with the control group. Conversely, visits with ulcerative colitis had markedly worsened sepsis-related outcomes. Further investigation is needed to determine the mechanisms underlying these clinical differences.

The microcirculation is a series of arterioles, capillaries, and venules that performs essential functions of oxygen and nutrient delivery, customized to the unique physiologic needs of the supplied organ. The homeostatic microcirculatory response to infection can become harmful if overactive and/or dysregulated. Pathologic microcirculatory dysfunction can be directly visualized by intravital microscopy or indirectly measured via detection of circulating biomarkers. Although several treatments have been shown to protect the microcirculation during sepsis, they have not improved patient outcomes when applied indiscriminately. Future outcomes-oriented studies are needed to test sepsis therapeutics when personalized to a patient's microcirculatory dysfunction.

BackgroundSevere acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown.ObjectiveWe hypothesized that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission.DesignRetrospective, propensity score matched cohort study.ParticipantsWe identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI.Main measuresThe predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge.ResultsAKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 [95% CI, 2.43-8.45]; pConclusionAmong patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge.

The endothelial glycocalyx is a heparan sulfate (HS)-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenous mechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncture mediated) endothelial glycocalyx degradation. We used mass spectrometry, surface plasmon resonance, and in vitro studies of human and mouse samples to determine the structure of HS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulating HS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1-mediated glycocalyx reconstitution.

The vagus nerve contains primary visceral afferents that convey sensory information from cardiovascular, pulmonary, and gastrointestinal tissues to the nucleus tractus solitarii (NTS). The heterogeneity of vagal afferents and their central terminals within the NTS is a common obstacle for evaluating functional groups of afferents. To determine whether different anterograde tracers can be used to identify distinct subpopulations of vagal afferents within NTS, we injected cholera toxin B subunit (CTb) and isolectin B4 (IB4) into the vagus nerve. Confocal analyses of medial NTS following injections of both CTb and IB4 into the same vagus nerve resulted in labeling of two exclusive populations of fibers. The ultrastructural patterns were also distinct. CTb was found in both myelinated and unmyelinated vagal axons and terminals in medial NTS, whereas IB4 was found only in unmyelinated afferents. Both tracers were observed in terminals with asymmetric synapses, suggesting excitatory transmission. Because glutamate is thought to be the neurotransmitter at this first primary afferent synapse in NTS, we determined whether vesicular glutamate transporters (VGLUTs) were differentially distributed among the two distinct populations of vagal afferents. Anterograde tracing from the vagus with CTb or IB4 was combined with immunohistochemistry for VGLUT1 or VGLUT2 in medial NTS and evaluated with confocal microscopy. CTb-labeled afferents contained primarily VGLUT2 (83%), whereas IB4-labeled afferents had low levels of vesicular transporters, VGLUT1 (5%) or VGLUT2 (21%). These findings suggest the possibility that glutamate release from unmyelinated vagal afferents may be regulated by a distinct, non-VGLUT, mechanism.

Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability.

Background and Objective Infectious complications after ischemic stroke are frequent and lead to neurological deterioration, poor functional outcomes, and higher mortality. Local and systemic inflammatory responses to brain ischemia differ between males and females, but little is known about differences in poststroke susceptibility to infection by sex. The purpose of this study was to compare sex-related differences in the risk of hospital-acquired sepsis and pneumonia after acute ischemic stroke (AIS). Materials and Methods This is a retrospective, secondary analysis of the 2010-2011 California State Inpatient Database. Previously validated International Classification of Disease, Ninth Revision (ICD-9) codes were used to identify adult hospitalizations for AIS. The primary outcome was hospital-acquired sepsis or pneumonia, also identified using ICD-9 codes. Associations between sex and hospital-acquired sepsis or pneumonia were adjusted for baseline characteristics and comorbidities using multivariable logistic regression. Results There were 91,643 hospitalizations for AIS included in this analysis, of which 1027 had hospital-acquired sepsis and 1225 had hospital-acquired pneumonia. The in-hospital mortality without infection was 4.6%; the presence of hospital-acquired infections was associated with higher mortality for sepsis (32.7%) and pneumonia (21.9%). Female (versus male) sex was associated with lower adjusted odds of hospital-acquired sepsis (odds ratio [OR] .74, 95% confidence interval [CI] .65-.84) and pneumonia (OR .69, 95% CI .62-.78). This difference was similar across age strata. Among hospitalizations with either hospital-acquired sepsis or pneumonia, sex did not influence mortality. Conclusions Female sex was associated with a lower risk of hospital-acquired sepsis and pneumonia after AIS. Further investigation is needed to determine the mechanisms underlying this clinical observation.

A well maintained orchard floor is critical for insuring year-round orchard access and a clean almond harvest operation. This study compared three methods of orchard floor vegetation management over a 4-year period. The objective of this study was to evaluate cost effective vegetation management programs for difficult to control summer annual weeds while maintaining the population of desirable winter annual species. Common purslane (Portulaca oleracea) can be a major summer weed problem that interferes with almond harvesting operations. A low rate residual herbicide program controlled purslane more consistently than mechanical or chemical mowing programs. Desirable winter weed cover was preserved in all three management systems. The costs for each program were similar; however, there was a reduction in the number of operations required for both chemical mowing and low rate residual programs compared to the mechanical mowing program.

Plasmid NAH7 was transferred from Pseudomonas putida PpG7 to P. putida R20 [R20(NAH7)], an antagonist of Pythium ultimum . The plasmid did not affect growth or survival of R20(NAH7) and was stably maintained under nonselective conditions in broth and soil and on sugar beet seeds. Plasmid NAH7 conferred to R20(NAH7) the ability to utilize salicylate in culture, agricultural field soil, and on sugar beet seeds. The metabolic activity of R20(NAH7), but not the wild-type R20, was greatly increased in soil by amendment with salicylate (250 μg/g) as measured by induced respiration. Population densities of R20(NAH7) were also enhanced in salicylate-amended soil, increasing from approximately 1 × 10 5 CFU/g to approximately 3 × 10 8 CFU/g after 35 h of incubation. In contrast, population densities of R20(NAH7) in nonamended soil were approximately 3 × 10 6 CFU/g of soil after 35 h of incubation. The concentration of salicylate in soil affected the rate and extent of population increase by R20(NAH7). At 50 to 250 μg of salicylate per g of soil, population densities of R20(NAH7) increased to approximately 10 8 CFU/g of soil by 48 h of incubation, with the fastest increase at 100 μg/g. A lag phase of approximately 24 h occurred before the population density increased in the presence of salicylate at 500 μg/g; at 1,000 μg/g, population densities of R20(NAH7) declined over the time period of the experiment. Population densities of R20(NAH7) on sugar beet seeds in soils amended with 100 μg of salicylate per g were not increased while ample carbon was present in the spermosphere. However, after carbon from the seed had been utilized, population densities of R20(NAH7) decreased significantly less ( P = 0.005) on sugar beet seeds in soil amended with salicylate than in nonamended soil.

Sodium salicylate (1,000 μg/ml) was delivered through a drip irrigation system to agricultural field soils planted to tomato and infested with Pseudomonas putida PpG7, the host of the salicylate catabolic plasmid NAH7. In nonfumigated soils infested with approximately 10 3 CFU of PpG7 per g in the top 30 cm, population densities were increased up to 112-fold within 14 days of the initial application of salicylate compared with the densities in the respective nonamended soils. Mean season-long population densities of PpG7 in the top 30 cm of soil were significantly increased ( P < 0.01) from 216 CFU/g in nonamended soils to 1,370 CFU/g in salicylate-amended soils. In the respective rhizosphere soils, mean population densities of PpG7 were significantly increased ( P < 0.01) from 92 to 2,066 CFU/cm of root. Soil fumigation interacted ( P < 0.01) with salicylate amendment and further increased the mean population densities of PpG7 in nonrhizosphere soil by an additional 5,689 CFU/g of soil. This fumigation effect was not detected in rhizosphere soils. The effect of salicylate in increasing population densities of PpG7 in soil also was affected by inoculum level, field site, and soil depth. Proportionate differences were greater in soils infested with approximately 10 3 CFU of PpG7 per g than in comparable soils infested with 10 5 CFU/g. In low-inoculum soils, increases from salicylate amendments were 26- and 29-fold in rhizosphere and nonrhizosphere soils, respectively, and in high-inoculum soils, the respective increases were 5.6- and 5-fold. No increases of fungi able to utilize salicylate were detected in soils amended with salicylate. However, soil fumigation with metham-sodium significantly reduced ( P < 0.01) population densities of fungal salicylate utilizers in rhizosphere and nonrhizosphere soils.

International audience; Cette revue de littérature pluridisciplinaire (management, économie, sociologie, sciences de l'information) s'intéresse aux caractéristiques, aux pratiques et aux rôles d'un acteur spécifique du champ de l'industrie culturelle : la critique de presse. Cette synthèse vise à soulever trois problématiques principales. Tout d'abord, nous proposons au lecteur une réflexion critique sur la nature spécifique de la critique de presse et sur les enjeux liés à son appartenance à l'industrie des médias. La deuxième problématique à laquelle s'intéresse cette synthèse est celle de la formation du discours critique : comment les critiques évaluent-ils les œuvres ? Enfin, la dernière problématique abordée ici est celle des multiples rôles exercés par la critique de presse : on s'y interroge sur la manière dont les divers acteurs de l'industrie culturelle s'approprient (ou non) cette forme d'expertise indépendante.

The purpose of this article is to come up with an individual measure of brand equity, based on consumers preferences and choices. Using the customer-based brand equity definition and valuation method, initially proposed by Park and Srinivasan, the authors put forwards two improvements, one conceptual, the other methodological. A survey-based results on 32 brands, comparing laboratory data and panel data, shows that the revised method has a better internal and external validity. The corrected brand equity construct is indeed better correlated to other constructs related to brand strength, such as market share and distribution indices. Last but not least, the Logit model, elaborated upon the revised construct, leads to a satisfactory prediction of choice shares, attesting that the proposed approach has a good predictive validity., Cet article développe une méthode de mesure individuelle du capital marque, fondée sur les préférences et les choix du consommateur. Prenant appui sur les travaux de Park et Srinivasan, les auteurs proposent deux améliorations, à la fois conceptuelle et méthodologique. Une expérimentation, confrontant des données de laboratoire et de panels sur 32 marques différentes, atteste de la meilleure validité interne et externe de la méthode révisée. Le construit de capital marque corrigé se révèle effectivement plus fortement corrélé à d’autres indicateurs de la force de la marque, tels que la part de marché, la distribution numérique et la distribution valeur. Enfin, le modèle de prévision, élaboré à partir du construit, conduit à une bonne estimation des parts de choix, témoignant ainsi de la validité prédictive de la mesure.