Publications by authors named "K E Kasza"

111 Publications

Challenges and solutions in polymer drug delivery for bacterial biofilm treatment: a tissue-by-tissue account.

Adv Drug Deliv Rev 2021 Sep 13:113973. Epub 2021 Sep 13.

Division of Molecular Therapeutics and Formulation, School of Pharmacy, University of Nottingham, NG7 2RD, UK. Electronic address:

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial communities (biofilms) are a particular concern in this context. Biofilms are responsible for most human infections and are inherently less susceptible to antibiotic treatments. Biofilms have been linked with several challenging chronic diseases, including implant-associated osteomyelitis and chronic wounds. The specific local environments present in the infected tissues further contribute to the rise in antibiotic resistance by limiting the efficacy of systemic antibiotic therapies and reducing drug concentrations at the infection site, which can lead to reoccurring infections. To overcome the shortcomings of systemic drug delivery, encapsulation within polymeric carriers has been shown to enhance antimicrobial efficacy, permeation and retention at the infection site. In this Review, we present an overview of current strategies for antimicrobial encapsulation within polymeric carriers, comparing challenges and solutions on a tissue-by-tissue basis. We compare challenges and proposed drug delivery solutions from the perspective of the local environments for biofilms found in oral, wound, gastric, urinary tract, bone, pulmonary, vaginal, ocular and middle/inner ear tissues. We will also discuss future challenges and barriers to clinical translation for these therapeutics. The following Review demonstrates there is a significant imbalance between the research focus being placed on different tissue types, with some targets (oral and wound biofims) being extensively more studied than others (vaginal and otitis media biofilms and endocarditis). Furthermore, the importance of the local tissue environment when selecting target therapies is demonstrated, with some materials being optimal choices for certain sites of bacterial infection, while having limited applicability in others.
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http://dx.doi.org/10.1016/j.addr.2021.113973DOI Listing
September 2021

Using optogenetics to link myosin patterns to contractile cell behaviors during convergent extension.

Biophys J 2021 Jul 20. Epub 2021 Jul 20.

Department of Mechanical Engineering, Columbia University, New York, New York. Electronic address:

Distinct patterns of actomyosin contractility are often associated with particular epithelial tissue shape changes during development. For example, a planar-polarized pattern of myosin II localization regulated by Rho1 signaling during Drosophila body axis elongation is thought to drive cell behaviors that contribute to convergent extension. However, it is not well understood how specific aspects of a myosin pattern influence the multiple cell behaviors, including cell intercalation, cell shape changes, and apical cell area fluctuations, that simultaneously occur during morphogenesis. Here, we developed two optogenetic tools, optoGEF and optoGAP, to activate or deactivate Rho1 signaling, respectively. We used these tools to manipulate myosin patterns at the apical side of the germband epithelium during Drosophila axis elongation and analyzed the effects on contractile cell behaviors. We show that uniform activation or inactivation of Rho1 signaling across the apical surface of the germband is sufficient to disrupt the planar-polarized pattern of myosin at cell junctions on the timescale of 3-5 min, leading to distinct changes in junctional and medial myosin patterns in optoGEF and optoGAP embryos. These two perturbations to Rho1 activity both disrupt axis elongation and cell intercalation but have distinct effects on cell area fluctuations and cell packings that are linked with changes in the medial and junctional myosin pools. These studies demonstrate that acute optogenetic perturbations to Rho1 activity are sufficient to rapidly override the endogenous planar-polarized myosin pattern in the germband during axis elongation. Moreover, our results reveal that the levels of Rho1 activity and the balance between medial and junctional myosin play key roles not only in organizing the cell rearrangements that are known to directly contribute to axis elongation but also in regulating cell area fluctuations and cell packings, which have been proposed to be important factors influencing the mechanics of tissue deformation and flow.
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http://dx.doi.org/10.1016/j.bpj.2021.06.041DOI Listing
July 2021

E-Cigarette Flavors and Frequency of E-Cigarette Use among Adult Dual Users Who Attempt to Quit Cigarette Smoking in the United States: Longitudinal Findings from the PATH Study 2015/16-2016/17.

Int J Environ Res Public Health 2021 04 20;18(8). Epub 2021 Apr 20.

Department of Health Behavior, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Potential mechanisms by which e-cigarette use may relate to combustible cigarette smoking cessation are not well-understood. We used U.S. nationally representative data to prospectively evaluate the relationship between e-cigarette flavor use and frequency of e-cigarette use among adult cigarette/e-cigarette dual users who attempted to quit smoking cigarettes. Analyses used Population Assessment of Tobacco and Health (PATH) Study data from adult dual users (2015/16) who attempted to quit smoking between 2015/16 and 2016/17 (Wave 3-Wave 4, = 685, including those who did/did not quit by 2016/17). E-cigarette flavor use (usual/last flavor, past 30-day flavor; assessed in 2015/16) was categorized into Only tobacco; Only menthol/mint; Only non-tobacco, non-menthol/mint; and Any combination of tobacco, menthol/mint, other flavor(s). The key outcome, evaluated at follow-up in 2016/17, was frequent e-cigarette use, which was defined as use on 20+ of past 30 days. Logistic regression was used to evaluate associations between e-cigarette flavor use in 2015/16 and frequent e-cigarette use at follow-up in 2016/17. Dual users who attempted to quit smoking had greater odds of frequent e-cigarette use at follow-up when they used only non-tobacco, non-menthol/mint flavor than when they used only tobacco flavor as their regular/last e-cigarette flavor (OR = 1.9, 95% CI: 1.1-3.4); findings were no longer significant when adjusted for factors including e-cigarette device type (AOR = 1.4, 95% CI: 0.7-2.8). Past 30-day e-cigarette flavor use results were generally similar, although frequent e-cigarette use at follow-up was highest among those who used any combination of tobacco, menthol/mint, or other flavors. Findings indicate that e-cigarette flavor use among dual users who attempt to quit smoking may be related to e-cigarette use frequency overall, which may indicate a mechanism underlying findings for e-cigarette use and smoking cessation. Further longitudinal research may help to disentangle how e-cigarette characteristics uniquely impact e-cigarette use frequency and smoking cessation/sustained use.
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http://dx.doi.org/10.3390/ijerph18084373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074329PMC
April 2021

Changes in Smoking and Vaping over 18 Months among Smokers and Recent Ex-Smokers: Longitudinal Findings from the 2016 and 2018 ITC Four Country Smoking and Vaping Surveys.

Int J Environ Res Public Health 2020 09 27;17(19). Epub 2020 Sep 27.

Department of Psychology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.

This descriptive study of smokers (smoked at least monthly) and recent ex-smokers (quit for ≤2 years) examined transitions over an 18 month period in their smoking and vaping behaviors. Data are from Waves 1 (W1: 2016) and 2 (W2: 2018) of the ITC Four Country Smoking and Vaping Survey, a cohort study of adult (≥18+) smokers, concurrent users (smoke and vape), and recent ex-smokers from Australia, Canada, England, and the United States (US). Respondents (N = 5016) were classified according to their smoking and vaping status, which resulted in eight subgroups: (1) exclusive daily smokers (2) exclusive non-daily smokers; (3-6) concurrent users (subdivided into four groups by each combination of daily/non-daily smoking and daily/non-daily vaping); (7) ex-smokers who vape; (8) ex-smokers not vaping. The analyses focused first on describing changes between groups from W1 to W2. Second, transition outcomes were assessed based on changes in smoking and vaping between W1 and W2. Transitions focused on smoking were: no change in smoking (continued smoking at the same frequency); decreased smoking; increased smoking; discontinued smoking; relapsed (ex-smokers at W1 who were smoking at W2). Transitions focused on vaping were: initiated vaping; switched from smoking to vaping. Overall, this study found that the vast majority of smokers were smoking 18 months later. Non-daily smokers were more likely than daily smokers to have discontinued smoking ( < 0.0001) and to have switched to exclusive vaping ( = 0.034). Exclusive non-daily smokers were more likely than exclusive daily smokers to have initiated vaping ( = 0.04). Among all W1 daily smokers, there were no differences in discontinued smoking between daily smokers who vaped (concurrent users) and exclusive daily smokers; however, concurrent users were more likely than exclusive daily smokers to have decreased to non-daily smoking ( < 0.001) or to have switched to vaping by W2 ( < 0.001). Among all W1 non-daily smokers, there were no significant differences in increased smoking or discontinued smoking between concurrent users or exclusive smokers. Most ex-smokers remained abstinent from smoking, and there was no difference in relapse back to smoking between those who vaped and those who did not.
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http://dx.doi.org/10.3390/ijerph17197084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579485PMC
September 2020
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