Does self-directed learning address gaps in nursing student knowledge of Alzheimer's disease?

In the past two decades, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from age-related Alzheimer's disease (AD) have increased. Future nurses will be caring for the rapidly escalating number of older adults facing increased AD risk, yet nursing students' knowledge has been shown to be limited regarding the age-related disease of Alzheimer's (and the most common dementia type) (Aljezawi et al., 2022; Mattos et al., 2015). In this pilot study, a quasi-experimental approach was used to examine undergraduate baccalaureate nursing students' basic knowledge about AD among two cohorts (N = 146). Testing occurred following an assigned self-directed learning activity as a means of providing the most current information regarding dementia. Pearson correlation and t-tests were applied in comparing student results in pre- and posttest surveys and investigating possible correlations between sociodemographic variables. Students in the 2020 group scored lower on ten of the thirty test items than the earlier 2018 cohort, suggesting that the method of self-directed learning, despite offering the most recent information, may be inadequate. To prepare nursing students to care for the increasing numbers of older adults at risk for Alzheimer's disease, curricula that are inclusive of the most recent advances in science surrounding dementia-related illnesses, and supplemented by faculty lectures, is recommended. This requires faculty themselves to be knowledgeable of the most recent advances in dementia risk, prevention, detection and management.

Preliminary Characterization of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity.

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug-resistant fungi, toxicity, and drug-drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida, Aspergillus, and Cryptococcus, as well as others. NP339 was designed based on endogenous cationic human defense peptides, which are constituents of the cornerstone of immune defense against pathogenic microbes. NP339 specifically targets the fungal cell membrane through a charge-charge-initiated membrane interaction and therefore possesses a differentiated safety and toxicity profile to existing antifungal classes. NP339 is rapidly fungicidal and does not elicit resistance in target fungi upon extensive passaging in vitro. Preliminary analyses in murine models indicate scope for therapeutic application of NP339 against a range of systemic and mucocutaneous fungal infections. Collectively, these data indicate that NP339 can be developed into a highly differentiated, first-in-class antifungal candidate for poorly served invasive and other serious fungal diseases.

Improved Methods for Assessing Therapeutic Potential of Antifungal Agents against Dermatophytes and Their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate.

Onychomycosis is a common, difficult-to-treat nail infection that is mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects. The development of treatments for onychomycosis is challenging because standard in vitro tests are not predictive of antifungal efficacy within the nail. We have developed a new antifungal agent, NP213, for the treatment of onychomycosis. NP213 is based on endogenous host defense peptides produced within the nail. We compared the in vitro activity of NP213 and existing antifungal agents using conventional antimicrobial susceptibility test (AST) systems and more physiologically relevant models based on the human nail. We observed that the standard in vitro AST methodologies failed to predict the efficacy of antifungal agents within the nail. To address that, we present a more physiologically relevant modified AST method. This method, alongside other standard in vitro assessments of activity (including mechanism-of-action and time-of-kill studies), better reflected the activity of NP213 and other antifungal agents within the nail than standard in vitro AST methods. NP213 is a rapidly acting, fungicidal peptide that is superior to existing antifungal agents in vitro It penetrated the nail more effectively than other antifungals, as confirmed by using an optimized in vitro nail infection model. The data presented here support the current clinical development status of NP213 as a novel agent for treating onychomycosis. We propose that the modified tests developed and applied for NP213 characterization are the most relevant to use for screening any potential therapeutic candidates for onychomycosis.

Novel fluorinated lipopeptides from Bacillus sp. CS93 via precursor-directed biosynthesis.

While attempting to improve production of fluoro-iturin A in Bacillus sp. CS93 new mono- and di-fluorinated fengycins were detected in culture supernatants by (19)F NMR and tandem mass spectrometry, after incubation of the bacterium with 3-fluoro-L-tyrosine. The fluorinated amino acid was presumably incorporated in place of one or both of the tyrosyl residues in fengycin. Investigations to generate additional new fluorinated derivatives were undertaken using commercially available fluorinated phenylalanines and 2-fluoro- and 2,3-difluoro-tyrosine that were synthesised by Negishi cross-coupling of iodoalanine and fluorinated bromo-phenols. The anti-fungal activity of the fluorinated lipopeptides was assayed against Trichophyton rubrum and found to be similar to that of the non-fluorinated metabolites.

Azole antifungals induce up-regulation of SAP4, SAP5 and SAP6 secreted proteinase genes in filamentous Candida albicans cells in vitro and in vivo.

OBJECTIVES: Expression of fungal virulence factors can be influenced by exposure to antifungal agents. To test this hypothesis, we determined the effects of subinhibitory concentrations of three antifungal agents on expression of three secreted proteinase genes associated with virulence in filamentous forms of Candida albicans. METHODS: GFP-SAP promoter constructs and fluorescence measurement, transcript profiling and RT-PCR in vitro and in an animal model of disseminated Candida infection. RESULTS: Exposure of C. albicans to subinhibitory concentrations of fluconazole in RPMI 1640 in the absence of serum led to up-regulation of the virulence-associated genes SAP4, SAP5 and SAP6 in hyphae and long pseudohyphae. Measurements with green fluorescent protein (GFP)-tagged promoters showed that the fluorescence of SAP4 and SAP6 under these conditions was strongest in the apical tip compartments of these filamentous cells and declined in compartments more proximal to the parent yeast cell. By contrast, SAP5-GFP fluorescence was expressed at similar levels in all cell compartments. Exposure to fluconazole led to significant increases in GFP-SAP4 and -SAP6 fluorescence in the filaments; itraconazole exposure also significantly increased GFP-SAP4 fluorescence, whereas flucytosine had no effect on any of the constructs. In experimentally infected animals, fluorescence of the GFP-SAP promoter fungal cells in kidney tissues was greater than that was seen in vitro for all four SAP constructs: treatment of animals with fluconazole did not significantly increase SAP promoter expression as measured by GFP fluorescence. CONCLUSIONS: Azole antifungal agents stimulated up-regulation of SAP4 and SAP6 genes in filamentous C. albicans cells in vitro and may therefore influence virulence as well as growth of the fungus. However, such effects appear to be transient in vivo.

Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism.

Eukaryotic cells from fungal hyphae to neurites that grow by polarized extension must coordinate cell growth and cell orientation to enable them to exhibit growth tropisms and to respond to relevant environmental cues. Such cells generally maintain a tip-high Ca(2+) cytoplasmic gradient, which is correlated with their ability to exhibit polarized tip growth and to respond to growth-directing extracellular signals. In yeast and other fungi, the polarisome, exocyst, Arp2/3, and Spitzenkörper protein complexes collectively orchestrate tip growth and cell polarity, but it is not clear whether these molecular complexes also regulate cell orientation or whether they are influenced by cytoplasmic Ca(2+) gradients. Hyphae of the human pathogenic fungus Candida albicans reorient their growth axis in response to underlying surface topography (thigmotropism) and imposed electric fields (galvanotropism). The establishment and maintenance of directional growth in relation to these environmental cues was Ca(2+) dependent. Tropisms were attenuated in media containing low Ca(2+), or calcium-channel blockers, and in mutants where calcium channels or elements of the calcium signaling pathway were deleted. Therefore galvanotropism and thigmotropism may both be mediated by localized Ca(2+) influx at sites of polarized growth via Ca(2+) channels that are activated by appropriate environmental signals.