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Item 1735. The Pig Skin Commensal D. incerta Exhibits Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus(Oxford University Press, 2022) Wei, Monica; Knight, Simon; Flowers, Laurice; Walsh, Jasmine; Grice, Elizabeth A.; Medicine, School of MedicineBackground: Methicillin-resistant Staphylococcus aureus (MRSA) infections occur commonly on skin and cause significant healthcare burden. MRSA can also stably colonize the skin and nasal passages, contributing to community spread. This colonization results in long-term interaction with the skin microbiome, which harbors a diverse community of bacteria that often use antimicrobial molecules to compete for ecologic niches. We hypothesize that the skin microbiome contains bacteria that secrete novel antimicrobial agents against MRSA. Methods: Pigs are an established model organism for skin whose microbiome is not well explored. We mined the pig skin microbiome for bacterial species that inhibited MRSA via a modified disc diffusion assay. Results: We find that the novel pig skin commensal D. incerta inhibits USA300 strain MRSA via a secreted antimicrobial protein that can be isolated from cell-free supernatant. Analysis of the D. incerta genome shows little homology to known antimicrobial genes clusters. The identity of the antimicrobial molecule and whether its antimicrobial activity persists in the context of MRSA skin infection remain unclear. We characterize the identity of this antimicrobial molecule via parallel genomic and biochemical approaches. Finally, we propose to test the ability of D. incerta to impede MRSA colonization and improve healing of MRSA-mediated skin infection, two clinically important skin conditions. Conclusion: We screened the pig skin microbiome and successfully identified bacterial inhibitors of MRSA. Preliminary data suggest that the pig skin commensal D. incerta secretes a novel antimicrobial protein. Our current efforts focus on identifying this antimicrobial molecule and investigating its therapeutic potential in animal models of skin.Item Data of NODDI diffusion metrics in the brain and computer simulation of hybrid diffusion imaging (HYDI) acquisition scheme(Elsevier, 2016-06) Kodiweera, Chandana; Wu, Yu-Chien; Department of Radiology and Imaging Sciences, IU School of MedicineThis article provides NODDI diffusion metrics in the brains of 52 healthy participants and computer simulation data to support compatibility of hybrid diffusion imaging (HYDI), "Hybrid diffusion imaging"[1] acquisition scheme in fitting neurite orientation dispersion and density imaging (NODDI) model, "NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain"[2]. HYDI is an extremely versatile diffusion magnetic resonance imaging (dMRI) technique that enables various analyzes methods using a single diffusion dataset. One of the diffusion data analysis methods is the NODDI computation, which models the brain tissue with three compartments: fast isotropic diffusion (e.g., cerebrospinal fluid), anisotropic hindered diffusion (e.g., extracellular space), and anisotropic restricted diffusion (e.g., intracellular space). The NODDI model produces microstructural metrics in the developing brain, aging brain or human brain with neurologic disorders. The first dataset provided here are the means and standard deviations of NODDI metrics in 48 white matter region-of-interest (ROI) averaging across 52 healthy participants. The second dataset provided here is the computer simulation with initial conditions guided by the first dataset as inputs and gold standard for model fitting. The computer simulation data provide a direct comparison of NODDI indices computed from the HYDI acquisition [1] to the NODDI indices computed from the originally proposed acquisition [2]. These data are related to the accompanying research article "Age Effects and Sex Differences in Human Brain White Matter of Young to Middle-Aged Adults: A DTI, NODDI, and q-Space Study" [3].Item Global white matter microstructural abnormalities associated with addiction liability score in drug naïve youth(Springer Nature, 2018-02) Hulvershorn, Leslie; Hummer, Tom; Wu, Yu-Chien; Tarter, Ralph; Rea, Parker; Anand, Amit; Andrew Chambers, R.; Finn, Peter; Psychiatry, School of MedicineAbnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naïve 10-14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naïve youths.Item The heat released during catalytic turnover enhances the diffusion of an enzyme(Nature Publishing Group, 2015-01-08) Riedel, Clement; Gabizon, Ronen; Wilson, Christian A. M.; Hamadani, Kambiz; Tsekouras, Konstantinos; Marqusee, Susan; Pressé, Steve; Bustamante, Carlos; Department of Cellular & Integrative Physiology, IU School of MedicineRecent studies have shown that the diffusivity of enzymes increases in a substrate-dependent manner during catalysis,. Although this observation has been reported and characterized for several different systems–, the precise origin of this phenomenon is unknown. Calorimetric methods are often used to determine enthalpies from enzyme-catalysed reactions and can therefore provide important insight into their reaction mechanisms,. The ensemble averages involved in traditional bulk calorimetry cannot probe the transient effects that the energy exchanged in a reaction may have on the catalyst. Here we obtain single-molecule fluorescence correlation spectroscopy data and analyse them within the framework of a stochastic theory to demonstrate a mechanistic link between the enhanced diffusion of a single enzyme molecule and the heat released in the reaction. We propose that the heat released during catalysis generates an asymmetric pressure wave that results in a differential stress at the protein–solvent interface that transiently displaces the centre-of-mass of the enzyme (chemoacoustic effect). This novel perspective on how enzymes respond to the energy released during catalysis suggests a possible effect of the heat of reaction on the structural integrity and internal degrees of freedom of the enzyme.Item An in-vitro evaluation on the biocompatibility of resilon by the microbiota of the infected root canal utilizing an agar disc diffusion assay(2012) Whatley, Jenny J. (Jenny Johnson), 1982-; Spolnik, Kenneth Jacob, 1950-; Vail, Mychel Macapagal, 1969-; Gregory, Richard L.; Legan, Joseph J.; Zunt, Susan L., 1951-; Ehrlich, YgalResilon is a resin-based obturation material that claims to create a monoblock through bonding of RealSeal sealer to the dentin walls and to the core material. Resilon is comprised of a biodegradable polymer, polycaprolactone, and inorganic fillers. Resilon has been shown to undergo enzymatic hydrolysis by bacterial enzymes such as lipase. This study aims to demonstrate if bacteria found within the infected root canal system are capable of degrading Resilon utilizing an agar disc hydrolysis method. A 0.1-percent Resilon emulsion and a gutta-percha emulsion were prepared with Tryptic Soy Agar in plates. Several bacterial species were inoculated in eight spots each on the Resilon and gutta-percha agar plates and the plates were observed for the formation of hydrolytic halos surrounding bacteria signifying their ability to degrade the material. The bacterial enzyme Lipase PS served as a positive control. P. intermedia, P. aeruginosa, P. assacharoylitica, S. epidermidis and S. aureus all demonstrated hydrolytic halos, clear zones, at each of the eight inoculation locations (100%, 95%CI 63%-100%) on the Resilon plates. The halos were similar to those seen in the positive lipase control. No halos were seen with E. faecalis, F. nucleatum, S. mutans, S. sanguis, or P. gingivalis at any of the eight inoculation spots (0%, 95%CI 0%-37%) on the Resilon plates. No hydrolytic halos were seen around any bacterial colonies or the Lipase PS on the gutta-percha plates. The results of this study indicate that bacteria found in endodontic infections can hydrolize Resilon dispersed into an emulsion. The potential exists for Resilon degradation after its use as an obturation material in infected root canal systems. Given that root canal therapy does not render a canal void of microorganisms, it is prudent to obturate the root canal system with a material that cannot be degraded by bacteria and their enzymes.Item The ion release behaviours and water sorption of novel resin-based calcium phosphate cement(2010) AlZain, Afnan Omar, 1981-; Chu, Tien-Min Gabriel; Lund, Melvin R., 1922-; Cochran, Michael A. (Michael Alan), 1944-; Martinez Mier, Esperanza de los A. (Esperanza de los Angeles), 1967-; Cook, Norman Blaine, 1954-Calcium phosphate-filled restorative materials were developed to provide calcium (Ca) and phosphate (PO4) ions, which have been proposed to enhance remineralization of demineralized tooth structure. Recently, tricalcium phosphate (TCP)-filled restorative materials were introduced as an alternative to amorphous calcium phosphate. The TCP filler has a more crystalline structure than ACP and is therefore potentially stronger. The aim of the present study was to examine TCP-filled restorative resins at different concentration levels at different time intervals to characterize the concentrations of Ca and PO4 ions released, and to measure the water sorption (WS) of these resins. An in vitro study was conducted by formulating resin composite using TCP as the filler mixed with EBPADMA, HmDMA, and HEMA as the resin matrix. One-hundred- sixty samples were prepared, 40 samples of each filler concentration (30 percent, 40 percent, 50 percent, and 60 percent) by weight. From each filler concentration, 5 samples of each of the 8 time points (time intervals of 4 h, 8 h, 12 h, 24 h, 3 d, 7 d, 14 d, and 21 d) were immersed in 100-ml deionized water. Calcium and PO4 ions were measured using atomic absorption spectroscopy and light spectroscopy, respectively. Water sorption (WS) was measured according to ISO 4049 specification and then the WS and the diffusion coefficient were calculated. The significance level was set at p = 0.001. The results indicated that Ca and PO4 ion release increased with increasing filler level at a rate faster than being linear. In addition, WS results were very high and failed to meet the ISO 4049 specification requirement. Diffusion coefficient results were also high. One-way ANOVA test for only 21-day data revealed that there is a statistically significant difference in filler level percent, and two-way ANOVA testing revealed that there is a statistically significant interaction between time and filler level percent on the Ca, PO4 released and WS. It can be concluded that the concentrations of Ca and PO4 released and WS were affected by composition of the monomers, filler level and type, dispersion, and the absence of coupling agent. Although this TCP-filled restorative material may release Ca and PO4, it cannot serve as a restorative material due to high WS values. Further study is needed to improve the material and evaluate its ability in promoting remineralization of the tooth structure in order for it to serve its purpose.Item Parcellation of Human Amygdala Subfields Using Orientation Distribution Function and Spectral K-means Clustering(Springer, 2016-10) Wen, Qiuting; Stirling, Brian D.; Sha, Long; Shen, Li; Whalen, Paul J.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of MedicineAmygdala plays an important role in fear and emotional learning, which are critical for human survival. Despite the functional relevance and unique circuitry of each human amygdaloid subnuclei, there has yet to be an efficient imaging method for identifying these regions in vivo. A data-driven approach without prior knowledge provides advantages of efficient and objective assessments. The present study uses high angular and high spatial resolution diffusion magnetic resonance imaging to generate orientation distribution function, which bears distinctive microstructural features. The features were extracted using spherical harmonic decomposition to assess microstructural similarity within amygdala subfields are identified via similarity matrices using spectral k-mean clustering. The approach was tested on 32 healthy volunteers and three distinct amygdala subfields were identified including medial, posterior-superior lateral, and anterior-inferior lateral.Item Pre-Exposure Prophylaxis (PrEP) Dissemination: Adapting Diffusion Theory to Examine PrEP Adoption(Springer, 2021) Schuyler, Ashley; Alidina, Zainab; Dolcini, M. Margaret; Harper, Gary; Fortenberry, J. Dennis; Singh, Ryan; Jamil, Omar; Pollack, Lance; Catania, Joseph; Pediatrics, School of MedicinePrEP adoption among African-American men-who-have-sex-with-men (AAMSM) remains low. We applied Diffusion-of-Innovations (DOI) theory to understand PrEP adoption processes among young HIV-negative/status unknown AAMSM (AAYMSM; N = 181; 17-24 years). Quantitative and qualitative analyses were used to examine predictors of PrEP diffusion stages. Most AAYMSM were in the persuasion stage (PrEP-aware, hadn't adopted; 72.4%). Our results suggest that model antecedents are DOI stage-specific. PrEP awareness (knowledge stage) was associated with lower levels of social stigma (p < .03) and greater health literacy (p < .05), while sexual risk (p < .03) and education (p < .03) predicted PrEP adoption (12.2%). PrEP efficacy and side effects were primary innovation characteristics influencing adoption receptivity in the persuasion stage. Interventions to improve PrEP diffusion should be tailored to stage-specific antecedents depending on how a community is stratified across the DOI stages.Item State of Science: Bridging the Science-Practice Gap in Aging, Dementia and Mental Health(Wiley, 2018-04) Callahan, Christopher M.; Bateman, Daniel R.; Wang, Sophia; Boustani, Malaz A.; Medicine, School of MedicineThe workforce available to care for older adults has not kept pace with the need. In response to workforce limitations and the growing complexity of healthcare, scientists have tested new models of care that redesign clinical practice. This article describes why new models of care in aging, dementia, and mental health diffuse inadequately into the healthcare systems and communities where they might benefit older adults. We review a general framework for the diffusion of innovations and highlight the importance of other features of innovations that deter or facilitate diffusion. Although scientists often focus on generating evidence-based innovations, end-users apply their own criteria to determine an innovation's value. In 1962, Rogers suggested six features of an innovation that facilitate or deter diffusion suggested: relative advantage, compatibility with the existing environment, ease or difficulty of implementation, trial-ability or ability to "test drive", adaptability, and observed effectiveness. We describe examples of models of care in aging, dementia and mental health that enjoy a modicum of diffusion into practice and place the features of these models in the context of deterrents and facilitators for diffusion. Developers of models of care in aging, dementia, and mental health typically fail to incorporate the complexities of health systems, the barriers to diffusion, and the role of emotion into design considerations of new models. We describe agile implementation as a strategy to facilitate the speed and scale of diffusion in the setting of complex adaptive systems, social networks, and dynamic macroenvironments.