Impact of Outpatient vs Inpatient ABSSSI Treatment on Outcomes: A Retrospective Observational Analysis of Medical Charts Across US Emergency Departments

Background The objective of this study was to characterize treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and describe the association between hospital admission and emergency department (ED) visits or readmissions within 30 days after initial episode of care (IEC). Methods This was a retrospective, observational, cohort study of adults with ABSSSI who presented to an ED between July 1, 2012, and June 30, 2013. Patient, health care facility, and treatment characteristics, including unplanned ED visits or readmissions, were obtained through manual chart review and abstraction. Adjusted logistic regression analysis examined likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients. Results Records from 1527 ED visits for ABSSSI from 40 centers were reviewed (admitted, n = 578 [38%]; nonadmitted, n = 949 [62%]). Admitted patients were typically older (mean age, 52.2 years vs 43.0 years), more likely to be morbidly obese (body mass index \u3e 40 kg/m2; 17.3% vs 9.1%), and had more comorbidities (Charlson Comorbidity Index ≥ 4; 24.4% vs 6.8%) compared with those not admitted. In the primary analysis, adjusted logistic regression, controlling for comorbidities and severity of illness, demonstrated that there was a similar likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients (odds ratio, 1.03; 95% confidence interval, 0.74–1.43; P = .87). Conclusions ABSSSI treatment pathways leveraging outpatient treatment vs hospital admission support similar likelihood of unplanned 30-day ED visits or readmissions, an important clinical outcome and quality metric at US hospitals. Further research regarding the decision criteria around hospital admission to avoid potentially unnecessary hospitalizations is warranted

Aggregatibacter Actinomycetemcomitans Leukotoxin Utilizes a Cholesterol Recognition/Amino Acid Consensus Site for Membrane Association

Background: A repeats-in-toxin (RTX) leukotoxin and its integrin receptor aggregate in cholesterol-rich lipid rafts. Results: The affinity of the toxin to cholesterol is driven by a cholesterol recognition/amino acid consensus (CRAC) motif. Conclusion: Leukotoxin cytotoxicity is regulated by the CRAC motif. Significance: Other RTX toxins contain this CRAC motif, suggesting a role for cholesterol recognition in RTX cytolysis. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc

Membrane Association and Destabilization by Aggregatibacter Actinomycetemcomitans Leukotoxin Requires Changes in Secondary Structures

Aggregatibacter actinomycetemcomitans is a common inhabitant of the upper aerodigestive tract of humans and non-human primates and is associated with disseminated infections, including lung and brain abscesses, pediatric infective endocarditis in children, and localized aggressive periodontitis. A. actinomycetemcomitans secretes a repeats-in-toxin protein, leukotoxin, which exclusively kills lymphocyte function-associated antigen-1-bearing cells. The toxin\u27s pathological mechanism is not fully understood; however, experimental evidence indicates that it involves the association with and subsequent destabilization of the target cell\u27s plasma membrane. We have long hypothesized that leukotoxin secondary structure is strongly correlated with membrane association and/or destabilization. In this study, we tested this hypothesis by analyzing lipid-induced changes in leukotoxin conformation. Upon incubation of leukotoxin with lipids that favor leukotoxin-membrane association, we observed an increase in leukotoxin α-helical content that was not observed with lipids that favor membrane destabilization. The change in leukotoxin conformation after incubation with these lipids suggests that membrane binding and membrane destabilization have distinct secondary structural requirements, suggesting that they are independent events. These studies thus provide insight into the mechanism of cell damage that leads to disease progression by A. actinomycetemcomitans

Drug Interactions with New and Investigational Antiretrovirals

More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat)

Aggregatibacter Actinomycetemcomitans Leukotoxin Causes Activation of Lymphocyte Function-Associated Antigen 1

Repeats-in-toxin leukotoxin (LtxA) produced by the oral bacterium Aggregatibacter actinomycetemcomitans kills human leukocytes in a lymphocyte function-associated antigen 1 (LFA-1, integrin α L /β 2 )-dependent manner, although the mechanism for this interaction has not been identified. The LtxA internalisation by LFA-1-expressing cells was explored with florescence resonance energy transfer (FRET) microscopy using a cell line that expresses LFA-1 with a cyan fluorescent protein-tagged cytosolic α L domain and a yellow fluorescent protein-tagged β 2 domain. Phorbol 12-myristate 13-acetate activation of LFA-1 caused transient cytosolic domain separation. However, addition of LtxA resulted in an increase in FRET, indicating that LtxA brings the cytosolic domains closer together, compared with the inactive state. Unlike activation, this effect was not transient, lasting more than 30 min. Equilibrium constants of LtxA binding to the cytoplasmic domains of both α L and β 2 were determined using surface plasmon resonance. LtxA has a strong affinity for the cytosolic domains of both the α L and β 2 subunits (K d = 15 and 4.2 nM, respectively) and a significantly lower affinity for the cytoplasmic domains of other integrin α M , α X , and β 3 subunits (K d = 400, 180, and 230 nM, respectively), used as controls. Peptide fragments of α L and β 2 show that LtxA binds membrane-proximal domain of α L and intermediate domain of β 2 . © 2018 John Wiley & Sons Lt

Nurses\u27 Alumnae Association Bulletin - Volume 7 Number 11

Anna M. Shafer Barton Memorial Division Births Changes in the Ophthalmology Division Change of Address Clara Melville Fund Continental Tour Deceased Digest of Meetings Inter-County Hospitalization Plan Katherine Childs\u27 Letter Lost Members Marriages Miscellaneous Nursing Home Committee\u27s Report Physical Advantages President James L. Kauffman\u27s Letter President\u27s Greeting Private Duty Section Prizes Relief Fund School Nursing Silhouette of a Public Health Nurse Rooming-in of Infant with Mother Staff Activities The Student White Haven Divisio

Developing a collaborative framework for naturalistic visual search

While much research has investigated the mechanisms of visual search behaviour in laboratory-based computer tasks, there has been relatively little work on whether these results generalise to more naturalistic search tasks and thus how well existing theories explain real-world search behaviour. In addition, work relating to this question has often been carried out by researchers working in very different disciplines, including not just vision science but also fields such as consumer behaviour, sports science and medical science, making it more difficult to get an overview of the progress made and open questions remaining. We present findings from a systematic review of real-world visual search, showing that we can group the current literature into theoretical and applied approaches, and that there are certain well-studied topics (e.g., X-ray screening) but that there are relatively few links made across different search tasks and/or search contexts. We also present preliminary work detailing our development of a “naturalistic search task battery”, which aims to provide a suite of open source, reproducible and standardised real-world search tasks, thus enabling the generation of comparable data across multiple studies and aiding theory and modelling in this area

Inhibition of LtxA Toxicity by Blocking Cholesterol Binding With Peptides

The leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. The interaction of LtxA with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. In the initial encounter with the host cell, LtxA associates with lymphocyte function-associated antigen-1 (LFA-1), a cell surface adhesion glycoprotein. However, we have also demonstrated that the toxin associates strongly with the plasma membrane lipids, specifically cholesterol. This association with cholesterol is regulated by a cholesterol recognition amino acid consensus (CRAC) motif, with a sequence of 334LEEYSKR340, in the N-terminal region of the toxin. Here, we have demonstrated that removal of cholesterol from the plasma membrane or mutation of the LtxA CRAC motif inhibits the activity of the toxin in THP-1 cells. To inhibit LtxA activity, we designed a short peptide corresponding to the CRAC336 motif of LtxA (CRAC336WT). This peptide binds to cholesterol and thereby inhibits the toxicity of LtxA in THP-1 cells. Previously, we showed that this peptide inhibits LtxA toxicity against Jn.9 (Jurkat) cells, indicating that peptides derived from the cholesterol-binding site of LtxA may have a potential clinical applicability in controlling infections of RTX-producing organisms

Aggregatibacter Actinomycetemcomitans Leukotoxin Cytotoxicity Occurs Through Bilayer Destabilization

The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, is a common inhabitant of the human upper aerodigestive tract. The organism produces an RTX (Repeats in ToXin) toxin (LtxA) that kills human white blood cells. LtxA is believed to be a membrane-damaging toxin, but details of the cell surface interaction for this and several other RTX toxins have yet to be elucidated. Initial morphological studies suggested that LtxA was bending the target cell membrane. Because the ability of a membrane to bend is a function of its lipid composition, we assessed the proficiency of LtxA to release of a fluorescent dye from a panel of liposomes composed of various lipids. Liposomes composed of lipids that form nonlamellar phases were susceptible to LtxA-induced damage while liposomes composed of lipids that do not form non-bilayer structures were not. Differential scanning calorimetry demonstrated that the toxin decreased the temperature at which the lipid transitions from a bilayer to a nonlamellar phase, while 31P nuclear magnetic resonance studies showed that the LtxA-induced transition from a bilayer to an inverted hexagonal phase occurs through the formation of an isotropic intermediate phase. These results indicate that LtxA cytotoxicity occurs through a process of membrane destabilization