Understanding the implementation and sustainability needs of evidence-based programs for racial and ethnic minoritized older adults in under-resourced communities with limited aging services.

Background: Evidence-based programs (EBPs) for older adults effectively improve health outcomes. However, there is a limited understanding of the unique needs of service providers as they consider adopting, implementing, and maintaining programs for older minority adults in low-income communities with limited aging services.

Methods: We conducted semi-structured interviews with key informants of community-based organizations (CBOs) to understand implementation and sustainability needs of CBOs within four racial and ethnically diverse Los Angeles County geographic areas.

Telavancin Is Active against Experimental Aortic Valve Endocarditis Caused by Daptomycin- and Methicillin-Resistant Staphylococcus aureus Strains.

We compared the efficacy of telavancin (TLV) and daptomycin (DAP) in an experimental rabbit endocarditis model caused by two clinically derived daptomycin-resistant (DAP) methicillin-resistant Staphylococcus aureus (MRSA) strains. TLV treatment significantly reduced MRSA densities in all target tissues and increased the percentage of these organs rendered culture negative compared to those with the untreated control or DAP-treated animals. These results demonstrate that TLV has potent in vivo efficacy against DAP MRSA isolates in this invasive endovascular infection model.

SSD1 is integral to host defense peptide resistance in Candida albicans.

Candida albicans is usually a harmless human commensal. Because inflammatory responses are not normally induced by colonization, antimicrobial peptides are likely integral to first-line host defense against invasive candidiasis. Thus, C.

The gamma-core motif correlates with antimicrobial activity in cysteine-containing kaliocin-1 originating from transferrins.

Kaliocin-1 is a 31-residue peptide derived from human lactoferrin, and with antimicrobial properties that recapitulate those of its 611 amino acid parent holoprotein. As kaliocin-1 is a cysteine-stabilized peptide, it was of interest to determine whether it contained a multidimensional gamma-core signature recently identified as common to virtually all classes of disulfide-stabilized antimicrobial peptides. Importantly, sequence and structural analyses identified an iteration of this multidimensional antimicrobial signature in kaliocin-1.

Modular determinants of antimicrobial activity in platelet factor-4 family kinocidins.

Mammalian platelets contain an array of antimicrobial peptides, termed platelet microbicidal proteins (PMPs). Human and rabbit PMPs include known chemokines, such as platelet factor-4 (hPF-4); PMP-1 is the rabbit orthologue of hPF-4. Chemokines that also exert direct antimicrobial activity have been termed kinocidins.

Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins.

Chemokines are small (8-12 kDa) effector proteins that potentiate leukocyte chemonavigation. Beyond this role, certain chemokines have direct antimicrobial activity against human pathogenic organisms; such molecules are termed kinocidins. The current investigation was designed to explore the structure-activity basis for direct microbicidal activity of kinocidins.

Antimicrobial peptides versus invasive infections.

It has been estimated that there are more microorganisms within and upon the human body than there are human cells. By necessity, every accessible niche must be defended by innate mechanisms to prevent invasive infection, and ideally that precludes the need for robust inflammatory responses. Yet the potential for pathogens to transcend the integument actively or passively and access the bloodstream emphasizes the need for rapid and potent antimicrobial defense mechanisms within the vascular compartment.

Structural congruence among membrane-active host defense polypeptides of diverse phylogeny.

A requisite for efficacious host defense against pathogens and predators has prioritized evolution of effector molecules thereof. A recent multidimensional analysis of physicochemical properties revealed a novel, unifying structural signature among virtually all classes of cysteine-containing antimicrobial peptides. This motif, termed the gamma-core, is seen in host defense peptides from organisms spanning more than 2.

Blockade of plasmid replication mediated by peptide nucleic acids.

Because peptide nucleic acids (PNAs) are capable of blocking amplification of deoxyribonucleic acid (DNA) by Taq DNA polymerase in vitro, we postulated that PNAs might be able to block replication in vivo. To explore this possibility, we assessed the ability of PNA to specifically block the replication of pUC19 plasmids by allowing a PNA, directed against segments of the Ampr sequence to bind to pUC19 prior to electroporation into Escherichia coli, strain DH10B. Colonies produced by this maneuver not only remained sensitive to ampicillin but were also incapable of blue color production on X-gal-containing media, thus demonstrating true blockade of pUC19 replication, rather than antisense activity.

New approaches to the prevention and treatment of severe S. aureus infections.

Staphylococcus aureus is a virulent pathogen that is currently a major cause of community-acquired infections, as well as infections in hospitalized patients. Morbidity and mortality due to S. aureus infections, such as sepsis, osteomyelitis, septic arthritis and infective endocarditis, remain high despite the use of newer antibiotics.

Linezolid: a new antibiotic.

The U.S. Food and Drug Administration recently approved linezolid for the treatment of patients with methicillin-resistant staphylococcal and vancomycin-resistant enterococcal infections.

Gemifloxacin.

Gemifloxacin is a novel antibiotic and the first fluoroquinolone with a pyrrolidine derivative at the C-7 position. Because of the added pyrrolidine substitute, gemifloxacin has an enhanced spectrum of activity against Gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus, in addition to its activity against Gram-negative bacteria. Like other fluoroquinolones, gemifloxacin's mechanism of action focuses on inhibiting DNA gyrase and topoisomerase, thus preventing cellular replication.

Diversity in antistaphylococcal mechanisms among membrane-targeting antimicrobial peptides.

Many antimicrobial peptides permeabilize the bacterial cytoplasmic membrane. However, it is unclear how membrane permeabilization and antimicrobial activity are related for distinct peptides. This study investigated the relationship between Staphylococcus aureus membrane permeabilization and cell death due to the following antistaphylococcal peptides: thrombin-induced platelet microbicidal protein 1 (tPMP-1), gramicidin D, and protamine.

The oxygen- and iron-dependent sigma factor pvdS of Pseudomonas aeruginosa is an important virulence factor in experimental infective endocarditis.

In Pseudomonas aeruginosa, pvdS, a key oxygen (O2)-dependent locus, regulates expression of a number of virulence genes, including toxA (which encodes exotoxin A production). To define the in vivo role of differing O2 tensions on pseudomonal virulence, 2 knockout mutants, DeltapvdS and DeltatoxA, were compared with their parental strain, PA01, in rabbit aortic and tricuspid endocarditis models (representing aerobic vs. microaerobic conditions in vivo, respectively).

Membrane permeabilization by thrombin-induced platelet microbicidal protein 1 is modulated by transmembrane voltage polarity and magnitude.

Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a small, cationic peptide generated from rabbit platelets when they are exposed to thrombin in vitro. It has potent microbicidal activity against a broad spectrum of bacterial and fungal pathogens, including Staphylococcus aureus. Previous in vitro studies involving whole staphylococcal cells and planar lipid bilayers (as artificial bacterial membrane models) suggested that membrane permeabilization by tPMP-1 is voltage dependent (S.

Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action.

Platelet microbicidal proteins (PMPs) are hypothesized to exert microbicidal effects via cytoplasmic membrane disruption. Transmission electron microscopy demonstrated a temporal association between PMP exposure, damage of the Staphylococcus aureus cytoplasmic membrane ultrastructure, and subsequent cell death. To investigate the mechanisms of action of PMPs leading to membrane damage, we used flow cytometry to compare the effects of two distinct PMPs (thrombin-induced PMP-1 [tPMP-1] or PMP-2) with human neutrophil defensin-1 (hNP-1) on transmembrane potential (Deltapsi), membrane permeabilization, and killing of S.

Staphylocidal action of thrombin-induced platelet microbicidal protein is influenced by microenvironment and target cell growth phase.

Thrombin-induced platelet microbicidal protein (tPMP) is a small, cationic peptide released from rabbit platelets following exposure to thrombin in vitro. This peptide exerts potent in vitro microbicidal activity against a broad spectrum of bloodstream pathogens, including Staphylococcus aureus. It is known that the microbicidal actions of other cationic antimicrobial peptides (e.

Staphylocidal action of thrombin-induced platelet microbicidal protein is not solely dependent on transmembrane potential.

Thrombin-induced platelet microbicidal protein (tPMP) is a small, cationic, antimicrobial peptide released from rabbit platelets when stimulated with thrombin. We studied the relationship between staphylococcal transmembrane potential (delta psi) and tPMP staphylocidal activity. A genetically related pair of Staphylococcus aureus strains, 6850 and JB1, which differ in delta psi generation (-143 and -97 mV, respectively) were used.

Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro.

Defensin NP-1, derived from the neutrophils of rabbits, was tested for its fungistatic and fungicidal activity against strains of Cryptococcus neoformans. The MICs for the encapsulated strains tested ranged from 3.75 to 15.

Subinhibitory concentration of octenidine and pirtenidine: influence on the lipid and sterol contents of Candida albicans.

The effect of subinhibitory concentrations of octenidine and pirtenidine on the lipid and sterol composition of Candida albicans was investigated. The total lipid and sterol contents of C. albicans grown in the presence of either octenidine or pirtenidine were reduced compared with control-grown cells.

What is the value of determining the presence and measuring the level of circulating immune complexes in children with kidney disease and what methods should be used for their measurement?

What is the value of determining the presence and measuring the level of circulating immune complexes in children with kidney disease and what methods should be used for their measurement?