scholarly journals Antibody-Mediated Killing of Carbapenem-Resistant ST258Klebsiella pneumoniaeby Human Neutrophils

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Scott D. Kobayashi ◽  
Adeline R. Porter ◽  
Brett Freedman ◽  
Ruchi Pandey ◽  
Liang Chen ◽  
...  

ABSTRACTCarbapenem-resistantKlebsiella pneumoniaeis a problem worldwide. A carbapenem-resistantK. pneumoniaelineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenicwzydeletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serumin vitro. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics.IMPORTANCEInfections caused by carbapenem-resistantK. pneumoniaeare difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrug-resistant bacteria. A strain of carbapenem-resistantK. pneumoniae, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistantK. pneumoniaelineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistantK. pneumoniaeinfections is feasible and has merit.

2019 ◽  
Vol 47 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Juli M. Bollinger ◽  
Abhi Sanka ◽  
Lena Dolman ◽  
Rachel G. Liao ◽  
Robert Cook-Deegan

Accessing BRCA1/2 data facilitates the detection of disease-associated variants, which is critical to informing clinical management of risks. BRCA1/2 data sharing is complex and many practices exist. We describe current BRCA1/2 data-sharing practices, in the United States and globally, and discuss obstacles and incentives to sharing, based on 28 interviews with personnel at U.S. and non-U.S. clinical laboratories and databases. Our examination of the BRCA1/2 data-sharing landscape demonstrates strong support for and robust sharing of BRCA1/2 data around the world, increasing global accesses to diverse data sets.


2011 ◽  
Vol 23 (4) ◽  
pp. 186-191 ◽  
Author(s):  
Malini Ratnasingam ◽  
Lee Ellis

Background. Nearly all of the research on sex differences in mass media utilization has been based on samples from the United States and a few other Western countries. Aim. The present study examines sex differences in mass media utilization in four Asian countries (Japan, Malaysia, South Korea, and Singapore). Methods. College students self-reported the frequency with which they accessed the following five mass media outlets: television dramas, televised news and documentaries, music, newspapers and magazines, and the Internet. Results. Two significant sex differences were found when participants from the four countries were considered as a whole: Women watched television dramas more than did men; and in Japan, female students listened to music more than did their male counterparts. Limitations. A wider array of mass media outlets could have been explored. Conclusions. Findings were largely consistent with results from studies conducted elsewhere in the world, particularly regarding sex differences in television drama viewing. A neurohormonal evolutionary explanation is offered for the basic findings.


2020 ◽  
Vol 2 (4) ◽  
pp. 32-54
Author(s):  
Silvia Spitta

Sandra Ramos (b. 1969) is one of the few artists to reflect critically on both sides of the Cuban di-lemma, fully embodying the etymological origins of the word in ancient Greek: di-, meaning twice, and lemma, denoting a form of argument involving a choice between equally unfavorable alternatives. Throughout her works she shines a light on the dilemmas faced by Cubans whether in Cuba or the United States, underlining the bad personal and political choices people face in both countries. During the hard 1990s, while still in Havana, the artist focused on the traumatic one-way journey into exile by thousands, as well as the experience of profound abandonment experienced by those who were left behind on the island. Today she lives in Miami and operates a studio there as well as one in Havana. Her initial disorientation in the USA has morphed into an acerbic representation and critique of the current administration and a deep concern with the environmental collapse we face. A buffoonlike Trumpito has joined el Bobo de Abela and Liborio in her gallery of comic characters derived from the rich Cuban graphic arts tradition where she was formed. While Cuba is now represented as a rotten cake with menacing flies hovering over it ready to pounce, a bombastic Trumpito marches across the world stage, trampling everything underfoot, a dollar sign for a face.


Author(s):  
Jakub J. Grygiel ◽  
A. Wess Mitchell ◽  
Jakub J. Grygiel ◽  
A. Wess Mitchell

From the Baltic to the South China Sea, newly assertive authoritarian states sense an opportunity to resurrect old empires or build new ones at America's expense. Hoping that U.S. decline is real, nations such as Russia, Iran, and China are testing Washington's resolve by targeting vulnerable allies at the frontiers of American power. This book explains why the United States needs a new grand strategy that uses strong frontier alliance networks to raise the costs of military aggression in the new century. The book describes the aggressive methods which rival nations are using to test American power in strategically critical regions throughout the world. It shows how rising and revisionist powers are putting pressure on our frontier allies—countries like Poland, Israel, and Taiwan—to gauge our leaders' commitment to upholding the American-led global order. To cope with these dangerous dynamics, nervous U.S. allies are diversifying their national-security “menu cards” by beefing up their militaries or even aligning with their aggressors. The book reveals how numerous would-be great powers use an arsenal of asymmetric techniques to probe and sift American strength across several regions simultaneously, and how rivals and allies alike are learning from America's management of increasingly interlinked global crises to hone effective strategies of their own. The book demonstrates why the United States must strengthen the international order that has provided greater benefits to the world than any in history.


2008 ◽  
Vol 12 (1) ◽  
Author(s):  
Anthony G Picciano ◽  
Robert V. Steiner

Every child has a right to an education. In the United States, the issue is not necessarily about access to a school but access to a quality education. With strict compulsory education laws, more than 50 million students enrolled in primary and secondary schools, and billions of dollars spent annually on public and private education, American children surely have access to buildings and classrooms. However, because of a complex and competitive system of shared policymaking among national, state, and local governments, not all schools are created equal nor are equal education opportunities available for the poor, minorities, and underprivileged. One manifestation of this inequity is the lack of qualified teachers in many urban and rural schools to teach certain subjects such as science, mathematics, and technology. The purpose of this article is to describe a partnership model between two major institutions (The American Museum of Natural History and The City University of New York) and the program designed to improve the way teachers are trained and children are taught and introduced to the world of science. These two institutions have partnered on various projects over the years to expand educational opportunity especially in the teaching of science. One of the more successful projects is Seminars on Science (SoS), an online teacher education and professional development program, that connects teachers across the United States and around the world to cutting-edge research and provides them with powerful classroom resources. This article provides the institutional perspectives, the challenges and the strategies that fostered this partnership.


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