Search results

Title: Predictive Computer Models for Biofilm Detachment Properties in Pseudomonas aeruginosa.
Creator: Cogan, Nick G, Harro, Janette M, Stoodley, Paul, Shirtliff, Mark E
Abstract/Description: Microbial biofilm communities are protected against environmental extremes or clearance by antimicrobial agents or the host immune response. They also serve as a site from which microbial populations search for new niches by dispersion via single planktonic cells or by detachment by protected biofilm aggregates that, until recently, were thought to become single cells ready for attachment. Mathematically modeling these events has provided investigators with testable hypotheses for further...
Show moreMicrobial biofilm communities are protected against environmental extremes or clearance by antimicrobial agents or the host immune response. They also serve as a site from which microbial populations search for new niches by dispersion via single planktonic cells or by detachment by protected biofilm aggregates that, until recently, were thought to become single cells ready for attachment. Mathematically modeling these events has provided investigators with testable hypotheses for further study. Such was the case in the recent article by Kragh et al. (K. N. Kragh, J. B. Hutchison, G. Melaugh, C. Rodesney, A. E. Roberts, Y. Irie, P. Ø. Jensen, S. P. Diggle, R. J. Allen, V. Gordon, and T. Bjarnsholt, mBio 7:e00237-16, 2016, http://dx.doi.org/10.1128/mBio.00237-16), in which investigators were able to identify the differential competitive advantage of biofilm aggregates to directly attach to surfaces compared to the single-celled planktonic populations. Therefore, as we delve deeper into the properties of the biofilm mode of growth, not only do we need to understand the complexity of biofilms, but we must also account for the properties of the dispersed and detached populations and their effect on reseeding.
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Date Issued: 2016-06-14
Identifier: FSU_pmch_27302761, 10.1128/mBio.00815-16, PMC4916383, 27302761, 27302761, mBio.00815-16
Format: Citation

Title: Cocaine-induced neurodevelopmental deficits and underlying mechanisms.
Creator: Martin, Melissa M, Graham, Devon L, McCarthy, Deirdre M, Bhide, Pradeep G, Stanwood, Gregg D
Abstract/Description: Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with...
Show moreExposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. Birth Defects Research (Part C) 108:147-173, 2016. © 2016 Wiley Periodicals, Inc.
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Date Issued: 2016-06-01
Identifier: FSU_pmch_27345015, 10.1002/bdrc.21132, PMC5538582, 27345015, 27345015
Format: Citation

Title: Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
Creator: Duclot, Florian, Perez-Taboada, Iara, Wright, Katherine N, Kabbaj, Mohamed
Abstract/Description: Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear...
Show moreOnly a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory.
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27343386, 10.1016/j.neuropharm.2016.06.022, PMC5017153, 27343386, 27343386, S0028-3908(16)30275-1
Format: Citation

Title: Critical and direct involvement of the CD23 stalk region in IgE binding.
Creator: Selb, Regina, Eckl-Dorna, Julia, Twaroch, Teresa E, Lupinek, Christian, Teufelberger, Andrea, Hofer, Gerhard, Focke-Tejkl, Margarete, Gepp, Barbara, Linhart, Birgit, Breiteneder...
Show moreSelb, Regina, Eckl-Dorna, Julia, Twaroch, Teresa E, Lupinek, Christian, Teufelberger, Andrea, Hofer, Gerhard, Focke-Tejkl, Margarete, Gepp, Barbara, Linhart, Birgit, Breiteneder, Heimo, Ellinger, Adolf, Keller, Walter, Roux, Kenneth H, Valenta, Rudolf, Niederberger, Verena
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Abstract/Description: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head...
Show moreThe low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed. A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23. Our results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
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Date Issued: 2017-01-01
Identifier: FSU_pmch_27343203, 10.1016/j.jaci.2016.04.015, PMC5321597, 27343203, 27343203, S0091-6749(16)30261-5
Format: Citation

Title: Function of Succinoglycan Polysaccharide in Sinorhizobium meliloti Host Plant Invasion Depends on Succinylation, Not Molecular Weight.
Creator: Mendis, Hajeewaka C, Madzima, Thelma F, Queiroux, Clothilde, Jones, Kathryn M
Abstract/Description: The acidic polysaccharide succinoglycan produced by the rhizobial symbiont Sinorhizobium meliloti 1021 is required for this bacterium to invade the host plant Medicago truncatula and establish a nitrogen-fixing symbiosis. S. meliloti mutants that cannot make succinoglycan cannot initiate invasion structures called infection threads in plant root hairs. S. meliloti exoH mutants that cannot succinylate succinoglycan are also unable to form infection threads, despite the fact that they make...
Show moreThe acidic polysaccharide succinoglycan produced by the rhizobial symbiont Sinorhizobium meliloti 1021 is required for this bacterium to invade the host plant Medicago truncatula and establish a nitrogen-fixing symbiosis. S. meliloti mutants that cannot make succinoglycan cannot initiate invasion structures called infection threads in plant root hairs. S. meliloti exoH mutants that cannot succinylate succinoglycan are also unable to form infection threads, despite the fact that they make large quantities of succinoglycan. Succinoglycan produced by exoH mutants is refractory to cleavage by the glycanases encoded by exoK and exsH, and thus succinoglycan produced by exoH mutants is made only in the high-molecular-weight (HMW) form. One interpretation of the symbiotic defect of exoH mutants is that the low-molecular-weight (LMW) form of succinoglycan is required for infection thread formation. However, our data demonstrate that production of the HMW form of succinoglycan by S. meliloti 1021 is sufficient for invasion of the host M. truncatula and that the LMW form is not required. Here, we show that S. meliloti strains deficient in the exoK- and exsH-encoded glycanases invade M. truncatula and form a productive symbiosis, although they do this with somewhat less efficiency than the wild type. We have also characterized the polysaccharides produced by these double glycanase mutants and determined that they consist of only HMW succinoglycan and no detectable LMW succinoglycan. This demonstrates that LMW succinoglycan is not required for host invasion. These results suggest succinoglycan function is not dependent upon the presence of a small, readily diffusible form. Sinorhizobium meliloti is a bacterium that forms a beneficial symbiosis with legume host plants. S. meliloti and other rhizobia convert atmospheric nitrogen to ammonia, a nutrient source for the host plant. To establish the symbiosis, rhizobia must invade plant roots, supplying the proper signals to prevent a plant immune response during invasion. A polysaccharide, succinoglycan, produced by S. meliloti is required for successful invasion. Here, we show that the critical feature of succinoglycan that allows infection to proceed is the attachment of a "succinyl" chemical group and that the chain length of succinoglycan is much less important for its function. We also show that none of the short-chain versions of succinoglycan is produced in the absence of two chain-cleaving enzymes.
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Date Issued: 2016-06-21
Identifier: FSU_pmch_27329751, 10.1128/mBio.00606-16, PMC4916376, 27329751, 27329751, mBio.00606-16
Format: Citation

Title: GABAergic mechanisms contributing to categorical amygdala responses to chemosensory signals.
Creator: Westberry, Jenne M, Meredith, Michael
Abstract/Description: Chemosensory stimuli from conspecific and heterospecific animals, elicit categorically different immediate-early gene response-patterns in medial amygdala in male hamsters and mice. We previously showed that conspecific signals activate posterior (MeP) as well as anterior medial amygdala (MeA), and especially relevant heterospecific signals such as chemosensory stimuli from potential predators also activate MeP in mice. Other heterospecific chemosignals activate MeA, but not MeP. Here we show...
Show moreChemosensory stimuli from conspecific and heterospecific animals, elicit categorically different immediate-early gene response-patterns in medial amygdala in male hamsters and mice. We previously showed that conspecific signals activate posterior (MeP) as well as anterior medial amygdala (MeA), and especially relevant heterospecific signals such as chemosensory stimuli from potential predators also activate MeP in mice. Other heterospecific chemosignals activate MeA, but not MeP. Here we show that male hamster amygdala responds significantly differentially to different conspecific signals, by activating different proportions of cells of different phenotype, possibly leading to differential activation of downstream circuits. Heterospecific signals that fail to activate MeP do activate GABA-immunoreactive cells in the adjacent caudal main intercalated nucleus (mICNc) and elicit selective suppression of MeP cells bearing GABA-Receptors, suggesting GABA inhibition in MeP by GABAergic cells in mICNc. Overall, work presented here suggests that medial amygdala may discriminate between important conspecific social signals, distinguish them from the social signals of other species and convey that information to brain circuits eliciting appropriate social behavior.
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Date Issued: 2016-09-07
Identifier: FSU_pmch_27329335, 10.1016/j.neuroscience.2016.06.020, PMC4955787, 27329335, 27329335, S0306-4522(16)30250-0
Format: Citation

Title: Region and strain-dependent diffusivities of glucose and lactate in healthy human cartilage endplate.
Creator: Wu, Yongren, Cisewski, Sarah E, Wegner, Nicholas, Zhao, Shichang, Pellegrini, Vincent D, Slate, Elizabeth H, Yao, Hai
Abstract/Description: The cartilage endplate (CEP) is implicated as the main pathway of nutrient supply to the healthy human intervertebral disc (IVD). In this study, the diffusivities of nutrient/metabolite solutes in healthy CEP were assessed, and further correlated with tissue biochemical composition and structure. The CEPs from non-degenerated human IVD were divided into four regions: central, lateral, anterior, and posterior. The diffusivities of glucose and lactate were measured with a custom diffusion cell...
Show moreThe cartilage endplate (CEP) is implicated as the main pathway of nutrient supply to the healthy human intervertebral disc (IVD). In this study, the diffusivities of nutrient/metabolite solutes in healthy CEP were assessed, and further correlated with tissue biochemical composition and structure. The CEPs from non-degenerated human IVD were divided into four regions: central, lateral, anterior, and posterior. The diffusivities of glucose and lactate were measured with a custom diffusion cell apparatus under 0%, 10%, and 20% compressive strains. Biochemical assays were conducted to quantify the water and glycosaminoglycan (GAG) contents. The Safranin-O and Ehrlich׳s hematoxylin and eosin staining and scanning electron microscopy (SEM) were performed to reveal the tissue structure of the CEP. Average diffusivities of glucose and lactate in healthy CEP were 2.68±0.93×10cm/s and 4.52±1.47×10cm/s, respectively. Solute diffusivities were region-dependent (p<0.0001) with the highest values in the central region, and mechanical strains impeded solute diffusion in the CEP (p<0.0001). The solute diffusivities were significantly correlated with the tissue porosities (glucose: p<0.0001, r=0.581; lactate: p<0.0001, r=0.534). Histological and SEM studies further revealed that the collagen fibers in healthy CEP are more compacted than those in the nucleus pulposus (NP) and annulus fibrosus (AF) and show no clear orientation. Compared to human AF and NP, much smaller solute diffusivities in human CEP suggested that it acts as a gateway for solute diffusion through the disc, maintaining the balance of nutritional environment in healthy human disc under mechanical loading and preventing the progression of disc degeneration.
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Date Issued: 2016-09-06
Identifier: FSU_pmch_27338525, 10.1016/j.jbiomech.2016.06.008, PMC5056135, 27338525, 27338525, S0021-9290(16)30664-9
Format: Citation

Title: Retinopathy and Uveitis Associated with Sofosbuvir Therapy for Chronic Hepatitis C Infection.
Creator: Chin-Loy, Katrina, Galaydh, Farah, Shaikh, Saad
Abstract/Description: We report a case of retinopathy and uveitis associated with sofosbuvir therapy for hepatitis C infection. Case report. A 57-year-old-male developed ocular inflammation and retinopathy four weeks after the administration of sofosbuvir for a hepatitis C infection. Hearing loss, rheumatologic disease, and essential tremor were also noted. The ophthalmic findings resolved with discontinuation of the drug. The authors report a case of sofosbuvir induced retinopathy and uveitis, the first...
Show moreWe report a case of retinopathy and uveitis associated with sofosbuvir therapy for hepatitis C infection. Case report. A 57-year-old-male developed ocular inflammation and retinopathy four weeks after the administration of sofosbuvir for a hepatitis C infection. Hearing loss, rheumatologic disease, and essential tremor were also noted. The ophthalmic findings resolved with discontinuation of the drug. The authors report a case of sofosbuvir induced retinopathy and uveitis, the first associated with this emerging therapy for hepatitis C. Ophthalmologists and other treating physicians should be aware of the ophthalmic side effects of this drug.
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Date Issued: 2016-05-03
Identifier: FSU_pmch_27335709, 10.7759/cureus.597, PMC4895080, 27335709, 27335709
Format: Citation

Title: Small caliber covered self-expanding metal stents in the management of malignant dysphagia.
Creator: Kucera, Stephen, Barthel, James, Klapman, Jason, Shridhar, Ravi, Hoffe, Sarah, Harris, Cynthia, Almhanna, Khaldoun, Meredith, Kenneth
Abstract/Description: Use of large caliber [≥18 mm body diameter (BD)] self-expanding metal stents (SEMS) for management of malignant dysphasia is associated with substantial adverse event (AE) and mortality rates (MRs). We sought to determine dysphagia response, stent migration rates, and AE and MRs, for small caliber covered SEMS (sccSEMS) with BDs between 10-16 mm in malignant dysphagia. Thirty-one patients underwent direct endoscopic placement of 50 sccSEMS between January 2008 and March 2011. Patients were...
Show moreUse of large caliber [≥18 mm body diameter (BD)] self-expanding metal stents (SEMS) for management of malignant dysphasia is associated with substantial adverse event (AE) and mortality rates (MRs). We sought to determine dysphagia response, stent migration rates, and AE and MRs, for small caliber covered SEMS (sccSEMS) with BDs between 10-16 mm in malignant dysphagia. Thirty-one patients underwent direct endoscopic placement of 50 sccSEMS between January 2008 and March 2011. Patients were monitored for change in dysphagia score (DS), stent migration, AEs, and death through May 2011. DS improved in 30 of 31 patients (97%). The median DS decreased from 3 to 2 (P<0.0001). The median effective duration of first sccSEMS placement was 116 (95% CI: 75-196) days. Major and minor AE rates were 6.5% and 19.4% respectively. No stent related deaths were encountered. The overall migration rate was 36% (18/50). The anticipated migration rate was 45.7% (16/35) and the unanticipated migration rate was 13.3% (2/15) (P=0.052). Positive effective clinical outcome occurred in 93.5% (29/31) of cases. In malignant dysphagia, direct endoscopic sccSEMS placement provided acceptable dysphagia control and migration rates with substantial reductions in stent related AEs and MRs compared to those reported for large caliber SEMS.
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Date Issued: 2016-06-01
Identifier: FSU_pmch_27284474, 10.21037/jgo.2015.12.03, PMC4880758, 27284474, 27284474, jgo-07-03-411
Format: Citation

Title: Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance.
Creator: Martinez, Jessica S, Schlenoff, Joseph B, Keller, Thomas C S
Abstract/Description: Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked,...
Show morePolyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion and migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as 'leader' cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as 'follower' cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization.
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Date Issued: 2016-08-01
Identifier: FSU_pmch_27292313, 10.1016/j.yexcr.2016.06.002, PMC4967014, 27292313, 27292313, S0014-4827(16)30143-4
Format: Citation

Title: The neurobiology of pair bond formation, bond disruption, and social buffering.
Creator: Lieberwirth, Claudia, Wang, Zuoxin
Abstract/Description: Enduring social bonds play an essential role in human society. These bonds positively affect psychological, physiological, and behavioral functions. Here, we review the recent literature on the neurobiology, particularly the role of oxytocin and dopamine, of pair bond formation, bond disruption, and social buffering effects on stress responses, from studies utilizing the socially monogamous prairie vole (Microtus ochrogaster).
Date Issued: 2016-10-01
Identifier: FSU_pmch_27290660, 10.1016/j.conb.2016.05.006, PMC5072360, 27290660, 27290660, S0959-4388(16)30065-4
Format: Citation

Title: Crystallization of spin superlattices with pressure and field in the layered magnet SrCu2(BO3)2.
Creator: Haravifard, S, Graf, D, Feiguin, A E, Batista, C D, Lang, J C, Silevitch, D M, Srajer, G, Gaulin, B D, Dabkowska, H A, Rosenbaum, T F
Abstract/Description: An exact mapping between quantum spins and boson gases provides fresh approaches to the creation of quantum condensates and crystals. Here we report on magnetization measurements on the dimerized quantum magnet SrCu2(BO3)2 at cryogenic temperatures and through a quantum-phase transition that demonstrate the emergence of fractionally filled bosonic crystals in mesoscopic patterns, specified by a sequence of magnetization plateaus. We apply tens of Teslas of magnetic field to tune the density...
Show moreAn exact mapping between quantum spins and boson gases provides fresh approaches to the creation of quantum condensates and crystals. Here we report on magnetization measurements on the dimerized quantum magnet SrCu2(BO3)2 at cryogenic temperatures and through a quantum-phase transition that demonstrate the emergence of fractionally filled bosonic crystals in mesoscopic patterns, specified by a sequence of magnetization plateaus. We apply tens of Teslas of magnetic field to tune the density of bosons and gigapascals of hydrostatic pressure to regulate the underlying interactions. Simulations help parse the balance between energy and geometry in the emergent spin superlattices. The magnetic crystallites are the end result of a progression from a direct product of singlet states in each short dimer at zero field to preferred filling fractions of spin-triplet bosons in each dimer at large magnetic field, enriching the known possibilities for collective states in both quantum spin and atomic systems.
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Date Issued: 2016-06-20
Identifier: FSU_pmch_27320787, 10.1038/ncomms11956, PMC4915149, 27320787, 27320787, ncomms11956
Format: Citation

Title: Fast Method for Computing Chemical Potentials and Liquid-Liquid Phase Equilibria of Macromolecular Solutions.
Creator: Qin, Sanbo, Zhou, Huan-Xiang
Abstract/Description: Chemical potential is a fundamental property for determining thermodynamic equilibria involving exchange of molecules, such as between two phases of molecular systems. Previously, we developed the fast Fourier transform (FFT)-based method for Modeling Atomistic Protein-crowder interactions (FMAP) to calculate excess chemical potentials according to the Widom insertion. Intermolecular interaction energies were expressed as correlation functions and evaluated via FFT. Here, we extend this...
Show moreChemical potential is a fundamental property for determining thermodynamic equilibria involving exchange of molecules, such as between two phases of molecular systems. Previously, we developed the fast Fourier transform (FFT)-based method for Modeling Atomistic Protein-crowder interactions (FMAP) to calculate excess chemical potentials according to the Widom insertion. Intermolecular interaction energies were expressed as correlation functions and evaluated via FFT. Here, we extend this method to calculate liquid-liquid phase equilibria of macromolecular solutions. Chemical potentials are calculated by FMAP over a wide range of molecular densities, and the condition for coexistence of low- and high-density phases is determined by the Maxwell equal-area rule. When benchmarked on Lennard-Jones fluids, our method produces an accurate phase diagram at 18% of the computational cost of the current best method. Importantly, the gain in computational speed increases dramatically as the molecules become more complex, leading to many orders of magnitude in speed up for atomistically represented proteins. We demonstrate the power of FMAP by reporting the first results for the liquid-liquid coexistence curve of γII-crystallin represented at the all-atom level. Our method may thus open the door to accurate determination of phase equilibria for macromolecular mixtures such as protein-protein mixtures and protein-RNA mixtures, that are known to undergo liquid-liquid phase separation, both in vitro and in vivo.
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Date Issued: 2016-08-25
Identifier: FSU_pmch_27327881, 10.1021/acs.jpcb.6b01607, PMC5011432, 27327881, 27327881
Format: Citation

Title: Electrostatic effects on the folding stability of FKBP12.
Creator: Batra, Jyotica, Tjong, Harianto, Zhou, Huan-Xiang
Abstract/Description: The roles of electrostatic interactions in protein folding stability have been a matter of debate, largely due to the complexity in the theoretical treatment of these interactions. We have developed computational methods for calculating electrostatic effects on protein folding stability. To rigorously test and further refine these methods, here we carried out experimental studies into electrostatic effects on the folding stability of the human 12-kD FK506 binding protein (FKBP12). This...
Show moreThe roles of electrostatic interactions in protein folding stability have been a matter of debate, largely due to the complexity in the theoretical treatment of these interactions. We have developed computational methods for calculating electrostatic effects on protein folding stability. To rigorously test and further refine these methods, here we carried out experimental studies into electrostatic effects on the folding stability of the human 12-kD FK506 binding protein (FKBP12). This protein has a close homologue, FKBP12.6, with amino acid substitutions in only 18 of their 107 residues. Of the 18 substitutions, 8 involve charged residues. Upon mutating FKBP12 residues at these 8 positions individually into the counterparts in FKBP12.6, the unfolding free energy (ΔGu) of FKBP12 changed by -0.3 to 0.7 kcal/mol. Accumulating stabilizing substitutions resulted in a mutant with a 0.9 kcal/mol increase in stability. Additional charge mutations were grafted from a thermophilic homologue, MtFKBP17, which aligns to FKBP12 with 31% sequence identity over 89 positions. Eleven such charge mutations were studied, with ΔΔGu varying from -2.9 to 0.1 kcal/mol. The predicted electrostatic effects by our computational methods with refinements herein had a root-mean-square deviation of 0.9 kcal/mol from the experimental ΔΔGu values on 16 single mutations of FKBP12. The difference in ΔΔGu between mutations grafted from FKBP12.6 and those from MtFKBP17 suggests that more distant homologues are less able to provide guidance for enhancing folding stability.
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Date Issued: 2016-08-01
Identifier: FSU_pmch_27381026, 10.1093/protein/gzw014, PMC4955870, 27381026, 27381026, gzw014
Format: Citation

Title: The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.
Creator: Khoshnevis, Sohail, Askenasy, Isabel, Johnson, Matthew C, Dattolo, Maria D, Young-Erdos, Crystal L, Stroupe, M Elizabeth, Karbstein, Katrin
Abstract/Description: DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S...
Show moreDEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked.
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Date Issued: 2016-06-09
Identifier: FSU_pmch_27280440, 10.1371/journal.pbio.1002480, PMC4900678, 27280440, 27280440, PBIOLOGY-D-16-00944
Format: Citation

Title: In Wrong Anticipation - Miscalibrated Beliefs between Germans, Israelis, and Palestinians.
Creator: Goerg, Sebastian J, Hennig-Schmidt, Heike, Walkowitz, Gari, Winter, Eyal
Abstract/Description: The reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners' behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an...
Show moreThe reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners' behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an investee/allocator. We found a notable constellation of calibrated and un-calibrated beliefs. Within each country, transfer standards exist, which investees correctly anticipate within their country. However, across countries these standards differ. By attributing the standard of their own environment to the other countries investees are remarkably bad in predicting foreign investors' behavior. The tendency to ignore this potential difference can be a source of misinterpreting motives in cross-country interaction. Foreigners might perceive behavior as unfavorable or favorable differentiation, even though-unknown to them-investors actually treat fellow-country people and foreigners alike.
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Date Issued: 2016-06-16
Identifier: FSU_pmch_27311066, 10.1371/journal.pone.0156998, PMC4911115, 27311066, 27311066, PONE-D-15-27349
Format: Citation

Title: Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer.
Creator: Vallega, Karin A, Liu, NingNing, Myers, Jennifer S, Yu, Kaixian, Sang, Qing-Xiang Amy
Abstract/Description: African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels...
Show moreAfrican American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.
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Date Issued: 2016-06-17
Identifier: FSU_pmch_27314854, 10.1371/journal.pone.0157741, PMC4912107, 27314854, 27314854, PONE-D-16-17121
Format: Citation

Title: Pre-Clovis occupation 14,550 years ago at the Page-Ladson site, Florida, and the peopling of the Americas.
Creator: Halligan, Jessi J, Waters, Michael R, Perrotti, Angelina, Owens, Ivy J, Feinberg, Joshua M, Bourne, Mark D, Fenerty, Brendan, Winsborough, Barbara, Carlson, David, Fisher,...
Show moreHalligan, Jessi J, Waters, Michael R, Perrotti, Angelina, Owens, Ivy J, Feinberg, Joshua M, Bourne, Mark D, Fenerty, Brendan, Winsborough, Barbara, Carlson, David, Fisher, Daniel C, Stafford, Thomas W, Dunbar, James S
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Abstract/Description: Stone tools and mastodon bones occur in an undisturbed geological context at the Page-Ladson site, Florida. Seventy-one radiocarbon ages show that ~14,550 calendar years ago (cal yr B.P.), people butchered or scavenged a mastodon next to a pond in a bedrock sinkhole within the Aucilla River. This occupation surface was buried by ~4 m of sediment during the late Pleistocene marine transgression, which also left the site submerged. Sporormiella and other proxy evidence from the sediments...
Show moreStone tools and mastodon bones occur in an undisturbed geological context at the Page-Ladson site, Florida. Seventy-one radiocarbon ages show that ~14,550 calendar years ago (cal yr B.P.), people butchered or scavenged a mastodon next to a pond in a bedrock sinkhole within the Aucilla River. This occupation surface was buried by ~4 m of sediment during the late Pleistocene marine transgression, which also left the site submerged. Sporormiella and other proxy evidence from the sediments indicate that hunter-gatherers along the Gulf Coastal Plain coexisted with and utilized megafauna for ~2000 years before these animals became extinct at ~12,600 cal yr B.P. Page-Ladson expands our understanding of the earliest colonizers of the Americas and human-megafauna interaction before extinction.
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Date Issued: 2016-05-13
Identifier: FSU_pmch_27386553, 10.1126/sciadv.1600375, PMC4928949, 27386553, 27386553, 1600375
Format: Citation

Title: Dehydration of chlorite explains anomalously high electrical conductivity in the mantle wedges.
Creator: Manthilake, Geeth, Bolfan-Casanova, Nathalie, Novella, Davide, Mookherjee, Mainak, Andrault, Denis
Abstract/Description: Mantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a...
Show moreMantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a suite of hydrous phases, including serpentine and chlorite. In this present study, we have measured the electrical conductivity of a natural chlorite at pressures and temperatures relevant for the subduction zone setting. In our experiment, we observe two distinct conductivity enhancements when chlorite is heated to temperatures beyond its thermodynamic stability field. The initial increase in electrical conductivity to ~3 × 10(-3) S/m can be attributed to chlorite dehydration and the release of aqueous fluids. This is followed by a unique, subsequent enhancement of electrical conductivity of up to 7 × 10(-1) S/m. This is related to the growth of an interconnected network of a highly conductive and chemically impure magnetite mineral phase. Thus, the dehydration of chlorite and associated processes are likely to be crucial in explaining the anomalously high electrical conductivity observed in mantle wedges. Chlorite dehydration in the mantle wedge provides an additional source of aqueous fluid above the slab and could also be responsible for the fixed depth (120 ± 40 km) of melting at the top of the subducting slab beneath the subduction-related volcanic arc front.
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Date Issued: 2016-05-06
Identifier: FSU_pmch_27386526, 10.1126/sciadv.1501631, PMC4928900, 27386526, 27386526, 1501631
Format: Citation

Title: Bioturbation by the Fungus-Gardening Ant, Trachymyrmex septentrionalis.
Creator: Tschinkel, Walter R, Seal, Jon N
Abstract/Description: Soil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of...
Show moreSoil invertebrates such as ants are thought to be important manipulators of soils in temperate and tropical ecosystems. The fungus gardening ant, Trachymyrmex septentrionalis, is an important agent of biomantling, that is, of depositing soil excavated from below onto the surface, and has been suggested as an agent of bioturbation (moving soil below ground) as well. The amount of bioturbation by this ant was quantified by planting queenright colonies in sand columns consisting of 5 layers of different colored sand. The amount of each color of sand deposited on the surface was determined from April to November 2015. In November, colonies were excavated and the color and amount of sand deposited below ground (mostly as backfill in chambers) was determined. Extrapolated to one ha, T. septentrionalis deposited 800 kg of sand per annum on the surface, and an additional 200 kg (17% of the total excavated) below ground. On average, this mixes 1.3% of the sand from other layers within the top meter of soil per millennium, but this mixing is unlikely to be homogeneous, and probably occurs as "hotspots" in both horizontal and vertical space. Such mixing is discussed as a challenge to sediment dating by optically stimulated luminescence (OSL).
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Date Issued: 2016-07-08
Identifier: FSU_pmch_27391485, 10.1371/journal.pone.0158920, PMC4938500, 27391485, 27391485, PONE-D-16-06201
Format: Citation

Title: Marijuana use and viral suppression in persons receiving medical care for HIV-infection.
Creator: Okafor, Chukwuemeka N, Zhou, Zhi, Burrell, Larry E, Kelso, Natalie E, Whitehead, Nicole E, Harman, Jeffery S, Cook, Christa L, Cook, Robert L
Abstract/Description: Marijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. We determined the association between marijuana use and HIV viral suppression among PLWH. Data came from five repeated cross-sections (2009-2013) of the Florida Medical Monitoring Project, a population-based sample of PLWH in Florida. Data were obtained via interview and medical record abstraction (MRA). Weighted logistic regression models were used to determine the...
Show moreMarijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. We determined the association between marijuana use and HIV viral suppression among PLWH. Data came from five repeated cross-sections (2009-2013) of the Florida Medical Monitoring Project, a population-based sample of PLWH in Florida. Data were obtained via interview and medical record abstraction (MRA). Weighted logistic regression models were used to determine the association between marijuana use (past 12 months) and durable viral suppression (HIV-1 RNA value of ≤ 200 copies/milliliter in all measurements within the past 12 months). Of the 1,902 PLWH receiving antiretroviral therapy, completed an interview, and had a linked MRA, 20% reported marijuana use (13% less than daily and 7% daily use) and 73% achieved durable viral suppression. In multivariable analysis, marijuana use was not significantly associated with durable viral suppression in daily [Adjusted Odds Ratio (AOR): 0.87, 95% confidence interval (CI): 0.58, 1.33] or in less than daily [AOR: 0.83, 95% CI: 0.51, 1.37] users as compared to non-users when adjusting for sociodemographic factors, time since HIV diagnosis, depressive symptoms, alcohol, cigarette and other substance use. In this sample of PLWH receiving medical care in Florida, there was no statistically significant association between marijuana use and viral suppression. However, as the limits of the confidence intervals include effects that may be considered to be clinically important, there is a need for additional evidence from other samples and settings that include more marijuana users.
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Date Issued: 2017-01-01
Identifier: FSU_pmch_27398989, 10.1080/00952990.2016.1191505, PMC5226929, 27398989, 27398989
Format: Citation

Title: Improving Adolescent Health Risk Assessment: A Multi-method Pilot Study..
Creator: Thompson, Lindsay A, Wegman, Martin, Muller, Keith, Eddleton, Katie Z, Muszynski, Michael, Rathore, Mobeen, De Leon, Jessica, Shenkman, Elizabeth A
Abstract/Description: Objectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement...
Show moreObjectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement an intervention in a practice-based research network delivering private, comprehensive HRAs via tablet (Phase II). Providers and adolescents received geo-coded community resources according to individualized risks. Following the point-of-care implementation , we collected patient-reported outcomes using post-visit quality surveys (Phase III). Patient-reported outcomes from intervention and comparison clinics were analyzed using a mixed-model, fitted separately for each survey domain. Results Stakeholders agreed upon an HIT-enhanced HRA (Phase I). Twenty-two academic and community practices in north-central Florida then recruited 609 diverse adolescents (14-18 years) during primary care visits over 6 months; (mean patients enrolled = 28; median = 20; range 1-116; Phase II). Adolescents receiving the intervention later reported higher receipt of confidential/private care and counseling related to emotions and relationships (adjusted scores 0.42 vs 0.08 out of 1.0, p < .01; 0.85 vs 0.57, p < .001, respectively, Phase III) than those receiving usual care. Both are important quality indicators for adolescent well-child visits. Conclusions Stakeholder input was critical to the acceptability of the HIT-enhanced HRA. Patient recruitment data indicate that the intervention was feasible in a variety of clinical settings and the pilot evaluation data indicate that the intervention may improve adolescents' perceptions of high quality care.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27406154, 10.1007/s10995-016-2070-5, PMC5124035, 27406154, 27406154, 10.1007/s10995-016-2070-5
Format: Citation

Title: Mining Twitter to Assess the Public Perception of the "Internet of Things".
Creator: Bian, Jiang, Yoshigoe, Kenji, Hicks, Amanda, Yuan, Jiawei, He, Zhe, Xie, Mengjun, Guo, Yi, Prosperi, Mattia, Salloum, Ramzi, Modave, François
Abstract/Description: Social media analysis has shown tremendous potential to understand public's opinion on a wide variety of topics. In this paper, we have mined Twitter to understand the public's perception of the Internet of Things (IoT). We first generated the discussion trends of the IoT from multiple Twitter data sources and validated these trends with Google Trends. We then performed sentiment analysis to gain insights of the public's attitude towards the IoT. As anticipated, our analysis indicates that...
Show moreSocial media analysis has shown tremendous potential to understand public's opinion on a wide variety of topics. In this paper, we have mined Twitter to understand the public's perception of the Internet of Things (IoT). We first generated the discussion trends of the IoT from multiple Twitter data sources and validated these trends with Google Trends. We then performed sentiment analysis to gain insights of the public's attitude towards the IoT. As anticipated, our analysis indicates that the public's perception of the IoT is predominantly positive. Further, through topic modeling, we learned that public tweets discussing the IoT were often focused on business and technology. However, the public has great concerns about privacy and security issues toward the IoT based on the frequent appearance of related terms. Nevertheless, no unexpected perceptions were identified through our analysis. Our analysis was challenged by the limited fraction of tweets relevant to our study. Also, the user demographics of Twitter users may not be strongly representative of the population of the general public.
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Date Issued: 2016-07-08
Identifier: FSU_pmch_27391760, 10.1371/journal.pone.0158450, PMC4938510, 27391760, 27391760, PONE-D-15-54733
Format: Citation

Title: A value proposition for early physical therapist management of neck pain: a retrospective cohort analysis..
Creator: Horn, Maggie E, Brennan, Gerard P, George, Steven Z, Harman, Jeffrey S, Bishop, Mark D
Abstract/Description: Neck pain is one of the most common reasons for entry into the healthcare system. Recent increases in healthcare utilization and medical costs have not correlated with improvements in health. Therefore there is a need to identify management strategies for neck pain that are effective for the patient, cost efficient for the payer and provided at the optimal time during an episode of neck pain. One thousand five hundred thirty-one patients who underwent physical therapist management with a...
Show moreNeck pain is one of the most common reasons for entry into the healthcare system. Recent increases in healthcare utilization and medical costs have not correlated with improvements in health. Therefore there is a need to identify management strategies for neck pain that are effective for the patient, cost efficient for the payer and provided at the optimal time during an episode of neck pain. One thousand five hundred thirty-one patients who underwent physical therapist management with a primary complaint of non-specific neck pain from January 1, 2008 to December 31, 2012 were identified from the Rehabilitation Outcomes Management System (ROMS) database at Intermountain Healthcare. Patients reporting duration of symptoms less than 4 weeks were designated as undergoing "early" management and patients with duration of symptoms greater than 4 weeks were designated as receiving "delayed" management. These groups were compared using binary logistic regression to examine odds of achieving Minimal Clinically Important Difference (MCID) on the Neck Disability Index (NDI) and Numerical Pain Rating Scale (NPRS). Separate generalized linear modeling examined the effect of timing of physical therapist management on the metrics of value and efficiency. Patients who received early physical therapist management had increased odds of achieving MCID on the NDI (aOR = 2.01, 95 % CI 1.57, 2.56) and MCID on the NPRS (aOR = 1.82, 95 % CI 1.42, 2.38), when compared to patients receiving delayed management. Patients who received early management demonstrated the greatest value in decreasing disability with a 2.27 percentage point change in NDI score per 100 dollars, best value in decreasing pain with a 0.38 point change on the NPRS per 100 dollars. Finally, patients receiving early management were managed more efficiently with a 3.44 percentage point change in NDI score per visit and 0.57 point change in NPRS score per visit. These findings suggest that healthcare systems that provide pathways for patients to receive early physical therapist management of neck pain may realize improved patient outcomes, greater value and higher efficiency in decreasing disability and pain compared to delayed management. Further research is needed to confirm this assertion.
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Date Issued: 2016-07-12
Identifier: FSU_pmch_27405318, 10.1186/s12913-016-1504-5, PMC4942887, 27405318, 27405318, 10.1186/s12913-016-1504-5
Format: Citation

Title: Combined DSEK and Transconjunctival Pars Plana Vitrectomy.
Creator: Sane, Mona, Shaikh, Naazli, Shaikh, Saad
Abstract/Description: We report here three patients who underwent combined Descemet's stripping with endothelial keratoplasty and transconjunctival pars plana vitrectomy for bullous keratopathy and posterior segment pathology. A surgical technique and case histories are described. Anatomic and visual outcomes of combined Descemet's stripping with endothelial keratoplasty and vitrectomy were excellent. Our experience provides technical guidelines and limitations. The combined minimally invasive techniques allow for...
Show moreWe report here three patients who underwent combined Descemet's stripping with endothelial keratoplasty and transconjunctival pars plana vitrectomy for bullous keratopathy and posterior segment pathology. A surgical technique and case histories are described. Anatomic and visual outcomes of combined Descemet's stripping with endothelial keratoplasty and vitrectomy were excellent. Our experience provides technical guidelines and limitations. The combined minimally invasive techniques allow for rapid anatomical recovery and return of function and visual acuity in a single sitting.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27413563, 10.1155/2016/9728035, PMC4927958, 27413563, 27413563
Format: Citation

Title: Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.
Creator: Dang, Xibei, Singh, Amar, Spetman, Brian D, Nolan, Krystal D, Isaacs, Jennifer S, Dennis, Jonathan H, Dalton, Stephen, Marshall, Alan G, Young, Nicolas L
Abstract/Description: Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free...
Show moreHistone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.
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Date Issued: 2016-09-02
Identifier: FSU_pmch_27431976, 10.1021/acs.jproteome.6b00414, PMC6261780, 27431976, 27431976
Format: Citation

Title: An insight into the thermodynamic characteristics of human thrombopoietin complexation with TN1 antibody.
Creator: Arai, Shigeki, Shibazaki, Chie, Adachi, Motoyasu, Honjo, Eijiro, Tamada, Taro, Maeda, Yoshitake, Tahara, Tomoyuki, Kato, Takashi, Miyazaki, Hiroshi, Blaber, Michael, Kuroki, Ryota
Abstract/Description: Human thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody-hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen-binding fragment (Fab) derived from the TN1 antibody (TN1-Fab). To clarify the mechanism by which hTPO is recognized by TN1-Fab the conformation of free TN1-Fab was determined to a resolution of 2.0 Å using X-ray...
Show moreHuman thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody-hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen-binding fragment (Fab) derived from the TN1 antibody (TN1-Fab). To clarify the mechanism by which hTPO is recognized by TN1-Fab the conformation of free TN1-Fab was determined to a resolution of 2.0 Å using X-ray crystallography and compared with the hTPO-bound form of TN1-Fab determined by a previous study. This structural comparison revealed that the conformation of TN1-Fab does not substantially change after hTPO binding and a set of 15 water molecules is released from the antigen-binding site (paratope) of TN1-Fab upon hTPO complexation. Interestingly, the heat capacity change (ΔCp) measured by ITC (-1.52 ± 0.05 kJ mol(-1) K(-1) ) differed significantly from calculations based upon the X-ray structure data of the hTPO-bound and unbound forms of TN1-Fab (-1.02 ∼ 0.25 kJ mol(-1) K(-1) ) suggesting that hTPO undergoes an induced-fit conformational change combined with significant desolvation upon TN1-Fab binding. The results shed light on the structural biology associated with neutralizing antibody recognition.
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27419667, 10.1002/pro.2985, PMC5029525, 27419667, 27419667
Format: Citation

Title: Examining Healthcare Utilization Patterns of Elderly Middle-Aged Adults in the United States.
Creator: Zayas, Cilia E, He, Zhe, Yuan, Jiawei, Maldonado-Molina, Mildred, Hogan, William, Modave, François, Guo, Yi, Bian, Jiang
Abstract/Description: Elderly patients, aged 65 or older, make up 13.5% of the U.S. population, but represent 45.2% of the top 10% of healthcare utilizers, in terms of expenditures. Middle-aged Americans, aged 45 to 64 make up another 37.0% of that category. Given the high demand for healthcare services by the aforementioned population, it is important to identify high-cost users of healthcare systems and, more importantly, ineffective utilization patterns to highlight where targeted interventions could be placed...
Show moreElderly patients, aged 65 or older, make up 13.5% of the U.S. population, but represent 45.2% of the top 10% of healthcare utilizers, in terms of expenditures. Middle-aged Americans, aged 45 to 64 make up another 37.0% of that category. Given the high demand for healthcare services by the aforementioned population, it is important to identify high-cost users of healthcare systems and, more importantly, ineffective utilization patterns to highlight where targeted interventions could be placed to improve care delivery. In this work, we present a novel multi-level framework applying machine learning (ML) methods (i.e., random forest regression and hierarchical clustering) to group patients with similar utilization profiles into clusters. We use a vector space model to characterize a patient's utilization profile as the number of visits to different care providers and prescribed medications. We applied the proposed methods using the 2013 Medical Expenditures Panel Survey (MEPS) dataset. We identified clusters of healthcare utilization patterns of elderly and middle-aged adults in the United States, and assessed the general and clinical characteristics associated with these utilization patterns. Our results demonstrate the effectiveness of the proposed framework to model healthcare utilization patterns. Understanding of these patterns can be used to guide healthcare policy-making and practice.
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Date Issued: 2016-05-01
Identifier: FSU_pmch_27430035, PMC4946167, 27430035, 27430035
Format: Citation

Title: Achalasia: A case report on its effect during surgical decision making for laparoscopic sleeve gastrectomy in the young morbidly obese patient..
Creator: Oviedo, Rodolfo J, Sofiak, Chase W, Dixon, Bruce M
Abstract/Description: Achalasia is a condition that occurs when the lower esophageal sphincter (LES) fails to properly relax, combined with slowing/failure of esophageal peristalsis. This is seen clinically by not allowing solids and liquids to pass easily into the stomach. Achalasia is not historically associated with morbid obesity, yet dual treatment of morbid obesity and achalasia is becoming more prominent due to the worldwide obesity epidemic. Achalasia is typically a disease that affects non-obese adults...
Show moreAchalasia is a condition that occurs when the lower esophageal sphincter (LES) fails to properly relax, combined with slowing/failure of esophageal peristalsis. This is seen clinically by not allowing solids and liquids to pass easily into the stomach. Achalasia is not historically associated with morbid obesity, yet dual treatment of morbid obesity and achalasia is becoming more prominent due to the worldwide obesity epidemic. Achalasia is typically a disease that affects non-obese adults over the age of 55, which makes the discussion of this case report unique in that our patient is a 23 year-old woman who successfully underwent per-oral endoscopic myotomy (POEM) in preparation for a future laparoscopic sleeve gastrectomy. There is sparse literature on combining laparoscopic Heller myotomy (LHM) and partial fundoplication versus POEM with either restrictive or malabsorptive minimally invasive bariatric procedures. LHM and partial fundoplication have long been considered the gold standard surgical treatment for achalasia by disrupting both the longitudinal and circular muscle layers of the LES. The newer, less invasive, POEM technique will be compared to the gold standard LHM and Dor fundoplication in this uncharacteristically young morbidly obese achalasia patient. The decision to pursue a laparoscopic sleeve gastrectomy over a laparoscopic Roux-en-Y gastric bypass was multifactorial due to the patient's concerns regarding malabsorption of vitamins and nutrients in the event of a future pregnancy. The patient has already undergone a POEM procedure, which was chosen to maintain the gastric fundus, cardia, and gastroesophageal junction (GEJ) architecture as opposed to a LHM with Dor fundoplication, which would have altered the anatomy, thus making a concomitant laparoscopic sleeve gastrectomy an unfeasible option.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27423062, 10.1016/j.ijscr.2016.06.046, PMC4949807, 27423062, 27423062, S2210-2612(16)30230-9
Format: Citation

Title: Postsynaptic Fmrp Regulates Synaptogenesis In Vivo In The Developing Cochlear Nucleus.
Creator: Wang, Xiaoyu, Zorio, Diego A. R., Schecterson, Leslayann, Lu, Yong, Wang, Yuan
Abstract/Description: A global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of...
Show moreA global loss of the fragile X mental retardation protein (FMRP; encoded by the Fmr1 gene) leads to sensory dysfunction and intellectual disabilities. One underlying mechanism of these phenotypes is structural and functional deficits in synapses. Here, we determined the autonomous function of postsynaptic FMRP in circuit formation, synaptogenesis, and synaptic maturation. In normal cochlea nucleus, presynaptic auditory axons form large axosomatic endbulb synapses on cell bodies of postsynaptic bushy neurons. In ovo electroporation of drug-inducible Fmr1-shRNA constructs produced a mosaicism of FMRP expression in chicken (either sex) bushy neurons, leading to reduced FMRP levels in transfected, but not neighboring nontransfected, neurons. Structural analyses revealed that postsynaptic FMRP reduction led to smaller size and abnormal morphology of individual presynaptic endbulbs at both early and later developmental stages. We further examined whether FMRP reduction affects dendritic development, as a potential mechanism underlying defective endbulb formation. Normally, chicken bushy neurons grow extensive dendrites at early stages and retract these dendrites when endbulbs begin to form. Neurons transfected with Fmr1 shRNA exhibited a remarkable delay in branch retraction, failing to provide necessary somatic surface for timely formation and growth of large endbulbs. Patch-clamp recording verified functional consequences of dendritic and synaptic deficits on neurotransmission, showing smaller amplitudes and slower kinetics of spontaneous and evoked EPSCs. Together, these data demonstrate that proper levels of postsynaptic FMRP are required for timely maturation of somatodendritic morphology, a delay of which may affect synaptogenesis and thus contribute to long-lasting deficits of excitatory synapses.
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Date Issued: 2018-07-18
Identifier: FSU_libsubv1_wos_000439698400004, 10.1523/JNEUROSCI.0665-18.2018
Format: Citation

Title: Open chromatin reveals the functional maize genome.
Creator: Rodgers-Melnick, Eli, Vera, Daniel L, Bass, Hank W, Buckler, Edward S
Abstract/Description: Cellular processes mediated through nuclear DNA must contend with chromatin. Chromatin structural assays can efficiently integrate information across diverse regulatory elements, revealing the functional noncoding genome. In this study, we use a differential nuclease sensitivity assay based on micrococcal nuclease (MNase) digestion to discover open chromatin regions in the maize genome. We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within...
Show moreCellular processes mediated through nuclear DNA must contend with chromatin. Chromatin structural assays can efficiently integrate information across diverse regulatory elements, revealing the functional noncoding genome. In this study, we use a differential nuclease sensitivity assay based on micrococcal nuclease (MNase) digestion to discover open chromatin regions in the maize genome. We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks. Although MNase HS regions map to less than 1% of the genome, they consistently explain a remarkably large amount (∼40%) of heritable phenotypic variance in diverse complex traits. MNase HS regions are therefore on par with coding sequences as annotations that demarcate the functional parts of the maize genome. These results imply that less than 3% of the maize genome (coding and MNase HS regions) may give rise to the overwhelming majority of phenotypic variation, greatly narrowing the scope of the functional genome.
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Date Issued: 2016-05-31
Identifier: FSU_pmch_27185945, 10.1073/pnas.1525244113, PMC4896728, 27185945, 27185945, 1525244113
Format: Citation

Title: The Role of Smoking-Specific Experiential Avoidance in the Relation Between Perceived Stress and Tobacco Dependence, Perceived Barriers to Cessation, and Problems during Quit Attempts Among Treatment-Seeking Smokers.
Creator: Garey, Lorra, Farris, Samantha G, Schmidt, Norman B, Zvolensky, Michael J
Abstract/Description: Despite the clinically-significant association between perceived stress and smoking, there is little understanding of the mechanisms underlying this relation. The present study examined smoking-specific experiential avoidance as an explanatory mechanism linking perceived stress and smoking, including nicotine dependence, perceived barriers to cessation, and problems reported during past quit attempts among treatment-seeking daily smokers ( = 365; 48.5% female; M = 38.02; = 13.10). Results...
Show moreDespite the clinically-significant association between perceived stress and smoking, there is little understanding of the mechanisms underlying this relation. The present study examined smoking-specific experiential avoidance as an explanatory mechanism linking perceived stress and smoking, including nicotine dependence, perceived barriers to cessation, and problems reported during past quit attempts among treatment-seeking daily smokers ( = 365; 48.5% female; M = 38.02; = 13.10). Results indicated that smoking-specific experiential avoidance had a significant, indirect effect on perceived stress and the studied smoking criterion variables. The present findings provide initial empirical support that smoking-specific experiential avoidance may help explain how perceived stress is associated with smoking. These data suggest that there may be merit to targeting smoking-specific experiential avoidance during smoking cessation among smokers with elevated perceived stress.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27231668, 10.1016/j.jcbs.2015.11.001, PMC4876877, 27231668, 27231668
Format: Citation

Title: The role of interpersonal personality traits and reassurance seeking in eating disorder symptoms and depressive symptoms among women with bulimia nervosa.
Creator: Mason, Tyler B, Lavender, Jason M, Wonderlich, Stephen A, Crosby, Ross D, Joiner, Thomas E, Mitchell, James E, Crow, Scott J, Klein, Marjorie H, Le Grange, Daniel, Bardone-Cone,...
Show moreMason, Tyler B, Lavender, Jason M, Wonderlich, Stephen A, Crosby, Ross D, Joiner, Thomas E, Mitchell, James E, Crow, Scott J, Klein, Marjorie H, Le Grange, Daniel, Bardone-Cone, Anna M, Peterson, Carol B
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Abstract/Description: The role of interpersonal factors has been proposed in various models of eating disorder (ED) psychopathology and treatment. We examined the independent and interactive contributions of two interpersonal-focused personality traits (i.e., social avoidance and insecure attachment) and reassurance seeking in relation to global ED psychopathology and depressive symptoms among women with bulimia nervosa (BN). Participants were 204 adult women with full or subclinical BN who completed a battery of...
Show moreThe role of interpersonal factors has been proposed in various models of eating disorder (ED) psychopathology and treatment. We examined the independent and interactive contributions of two interpersonal-focused personality traits (i.e., social avoidance and insecure attachment) and reassurance seeking in relation to global ED psychopathology and depressive symptoms among women with bulimia nervosa (BN). Participants were 204 adult women with full or subclinical BN who completed a battery of self-report questionnaires. Hierarchical multiple OLS regressions including main effects and interaction terms were used to analyze the data. Main effects were found for social avoidance and insecure attachment in association with global ED psychopathology and depressive symptoms. In addition, two-way interactions between social avoidance and reassurance seeking were observed for both global ED psychopathology and depressive symptoms. In general, reassurance seeking strengthened the association between social avoidance and global ED psychopathology and depressive symptoms. These results demonstrate the importance of reassurance seeking in psychopathology among women with BN who display personality features characterized by social avoidance.
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Date Issued: 2016-07-01
Identifier: FSU_pmch_27234198, 10.1016/j.comppsych.2016.04.013, PMC5293149, 27234198, 27234198, S0010-440X(16)30018-9
Format: Citation

Title: Complementary and Alternative Medicine Use for HIV Management in the State of Florida: Medical Monitoring Project..
Creator: Kelso-Chichetto, Natalie E, Okafor, Chukwuemeka N, Harman, Jeffrey S, Canidate, Shantrel S, Cook, Christa L, Cook, Robert L
Abstract/Description: The aims of this study were to describe complementary and alternative medicine (CAM) use and to assess the relationships between CAM use and antiretroviral therapy (ART) adherence and human immunodeficiency virus (HIV) RNA viral load suppression among a sample of persons living with HIV (PLWH) engaged in care in the state of Florida. The Florida Medical Monitoring Project (n = 803) collected repeated cross-sectional data for surveillance of clinical outcomes among PLWH from 2009 to 2010. Past...
Show moreThe aims of this study were to describe complementary and alternative medicine (CAM) use and to assess the relationships between CAM use and antiretroviral therapy (ART) adherence and human immunodeficiency virus (HIV) RNA viral load suppression among a sample of persons living with HIV (PLWH) engaged in care in the state of Florida. The Florida Medical Monitoring Project (n = 803) collected repeated cross-sectional data for surveillance of clinical outcomes among PLWH from 2009 to 2010. Past-year CAM use specifically for the management of HIV was measured via self-report. Logistic regression models were conducted to assess the effect of CAM use on ART adherence and viral load suppression, controlling for demographic and clinical factors using backwards stepwise deletion of factors with a p-value of >0.25. CAM use was reported in 53.3% (n = 428). In bivariate analysis, CAM use was the highest among those 40-49 years of age (61%; p < 0.05), males (56%; p < 0.01), whites (61%; p = 0.001), and those educated beyond high school (59%; p < 0.05). Among those using CAM, 63% and 37% reported one and two or more CAM modalities, respectively. CAM modalities included biologically based therapies (89%), mind-body medicine/manipulative body-based therapies (30%), spiritual healing (23%), energy therapies (6%), and whole medical systems (6%). In multivariable analyses, any CAM use and number of CAM methods used were not associated with ART adherence. Any CAM use was not associated with detectable viral load (adjusted odds ratio [aOR] 0.81; 95% confidence interval [CI] 0.58-1.12; p = 0.20). Those using two or more methods had significantly decreased risk for detectable viral load (aOR 0.60; 95% CI 0.39-0.92; p < 0.02). CAM use was not associated with negative effects on ART adherence. CAM users were less likely to have detectable viral load compared with non-users. Future research should focus on CAM use among PLWH not engaged in HIV care and the longitudinal patterns of CAM use and possible effects of long-term health outcomes.
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Date Issued: 2016-11-01
Identifier: FSU_pmch_27631385, 10.1089/acm.2016.0190, PMC5116687, 27631385, 27631385
Format: Citation

Title: The role of ΔfosB in the medial preoptic area: Differential effects of mating and cocaine history..
Creator: McHenry, Jenna A, Robison, Christopher L, Bell, Genevieve A, Vialou, Vincent V, Bolaños-Guzmán, Carlos A, Nestler, Eric J, Hull, Elaine M
Abstract/Description: The transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day...
Show moreThe transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of ΔFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase ΔFosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing ΔFosB, its dominant negative antagonist ΔJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. ΔFosB overexpression impaired copulation and promoted female-directed aggression, compared to ΔJunD and control males. These data suggest that ΔFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. (PsycINFO Database Record
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27657309, 10.1037/bne0000160, PMC5201202, 27657309, 27657309, 2016-45747-001
Format: Citation

Title: Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.
Creator: Venables, Noah C, Hicks, Brian M, Yancey, James R, Kramer, Mark D, Nelson, Lindsay D, Strickland, Casey M, Krueger, Robert F, Iacono, William G, Patrick, Christopher J
Abstract/Description: Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work...
Show moreThreat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology.
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Date Issued: 2017-05-01
Identifier: FSU_pmch_27671504, 10.1016/j.ijpsycho.2016.09.011, PMC5364073, 27671504, 27671504, S0167-8760(16)30704-8
Format: Citation

Title: The sequential pathway between trauma-related symptom severity and cognitive-based smoking processes through perceived stress and negative affect reduction expectancies among trauma exposed smokers.
Creator: Garey, Lorra, Cheema, Mina K, Otal, Tanveer K, Schmidt, Norman B, Neighbors, Clayton, Zvolensky, Michael J
Abstract/Description: Smoking rates are markedly higher among trauma-exposed individuals relative to non-trauma-exposed individuals. Extant work suggests that both perceived stress and negative affect reduction smoking expectancies are independent mechanisms that link trauma-related symptoms and smoking. Yet, no work has examined perceived stress and negative affect reduction smoking expectancies as potential explanatory variables for the relation between trauma-related symptom severity and smoking in a sequential...
Show moreSmoking rates are markedly higher among trauma-exposed individuals relative to non-trauma-exposed individuals. Extant work suggests that both perceived stress and negative affect reduction smoking expectancies are independent mechanisms that link trauma-related symptoms and smoking. Yet, no work has examined perceived stress and negative affect reduction smoking expectancies as potential explanatory variables for the relation between trauma-related symptom severity and smoking in a sequential pathway model. Methods The present study utilized a sample of treatment-seeking, trauma-exposed smokers (n = 363; 49.0% female) to examine perceived stress and negative affect reduction expectancies for smoking as potential sequential explanatory variables linking trauma-related symptom severity and nicotine dependence, perceived barriers to smoking cessation, and severity of withdrawal-related problems and symptoms during past quit attempts. As hypothesized, perceived stress and negative affect reduction expectancies had a significant sequential indirect effect on trauma-related symptom severity and criterion variables. Findings further elucidate the complex pathways through which trauma-related symptoms contribute to smoking behavior and cognitions, and highlight the importance of addressing perceived stress and negative affect reduction expectancies in smoking cessation programs among trauma-exposed individuals. (Am J Addict 2016;25:565-572).
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Date Issued: 2016-10-01
Identifier: FSU_pmch_27658236, 10.1111/ajad.12442, PMC5531681, 27658236, 27658236
Format: Citation

Title: First 101 Robotic General Surgery Cases in a Community Hospital.
Creator: Oviedo, Rodolfo J, Robertson, Jarrod C, Alrajhi, Sharifah
Abstract/Description: The general surgeon's robotic learning curve may improve if the experience is classified into categories based on the complexity of the procedures in a small community hospital. The intraoperative time should decrease and the incidence of complications should be comparable to conventional laparoscopy. The learning curve of a single robotic general surgeon in a small community hospital using the da Vinci S platform was analyzed. Measured parameters were operative time, console time, conversion...
Show moreThe general surgeon's robotic learning curve may improve if the experience is classified into categories based on the complexity of the procedures in a small community hospital. The intraoperative time should decrease and the incidence of complications should be comparable to conventional laparoscopy. The learning curve of a single robotic general surgeon in a small community hospital using the da Vinci S platform was analyzed. Measured parameters were operative time, console time, conversion rates, complications, surgical site infections (SSIs), surgical site occurrences (SSOs), length of stay, and patient demographics. Between March 2014 and August 2015, 101 robotic general surgery cases were performed by a single surgeon in a 266-bed community hospital, including laparoscopic cholecystectomies, inguinal hernia repairs; ventral, incisional, and umbilical hernia repairs; and colorectal, foregut, bariatric, and miscellaneous procedures. Ninety-nine of the cases were completed robotically. Seven patients were readmitted within 30 days. There were 8 complications (7.92%). There were no mortalities and all complications were resolved with good outcomes. The mean operative time was 233.0 minutes. The mean console operative time was 117.6 minutes. A robotic general surgery program can be safely implemented in a small community hospital with extensive training of the surgical team through basic robotic skills courses as well as supplemental educational experiences. Although the use of the robotic platform in general surgery could be limited to complex procedures such as foregut and colorectal surgery, it can also be safely used in a large variety of operations with results similar to those of conventional laparoscopy.
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Date Issued: 2016-07-01
Identifier: FSU_pmch_27667913, 10.4293/JSLS.2016.00056, PMC5027890, 27667913, 27667913, JSLS.2016.00056
Format: Citation

Title: Genetic and environmental associations between body dissatisfaction, weight preoccupation, and binge eating: Evidence for a common factor with differential loadings across symptom type..
Creator: O'Connor, Shannon M, Beam, Christopher R, Luo, Xiaochen, Cohen, L Adelyn, VanHuysse, Jessica L, Emery, Robert E, Turkheimer, Eric, Keel, Pamela K, Burt, S Alexandra, Neale,...
Show moreO'Connor, Shannon M, Beam, Christopher R, Luo, Xiaochen, Cohen, L Adelyn, VanHuysse, Jessica L, Emery, Robert E, Turkheimer, Eric, Keel, Pamela K, Burt, S Alexandra, Neale, Michael, Boker, Steven, Klump, Kelly
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Abstract/Description: Prior twin studies provide support for a single "common factor" that contributes genetic and environmental risk to a range of disordered eating symptoms. However, the common factor may be indexed less well by binge eating (BE) than other symptoms of eating disorders [i.e., body dissatisfaction (BD) and weight preoccupation (WP)]. We sought to explore the presence of a common factor and test whether loadings differed across three key symptoms (i.e., BE, BD, WP). Disordered eating was assessed...
Show morePrior twin studies provide support for a single "common factor" that contributes genetic and environmental risk to a range of disordered eating symptoms. However, the common factor may be indexed less well by binge eating (BE) than other symptoms of eating disorders [i.e., body dissatisfaction (BD) and weight preoccupation (WP)]. We sought to explore the presence of a common factor and test whether loadings differed across three key symptoms (i.e., BE, BD, WP). Disordered eating was assessed via self-report in 631 female twin pairs from the Michigan State University Twin Registry. We detected a common disordered eating factor that was influenced primarily by additive genetic and nonshared environmental influences. However, we observed different loadings on this common factor by symptom type, as factor loadings for BD and WP were stronger than that for BE. Moreover, the residual environmental and/or genetic variances (i.e., those that are independent of the common factor) were larger in BE than those of BD or WP. Although all three symptoms share a common set of genetic and environmental influences, risk for BE may involve additional genetic, biological, and environmental factors that are not shared with other symptoms of eating pathology. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:157-161).
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Date Issued: 2017-02-01
Identifier: FSU_pmch_27636116, 10.1002/eat.22625, PMC5291810, 27636116, 27636116
Format: Citation

Title: Engineering Crack Formation in Carbon Nanotube-Silver Nanoparticle Composite Films for Sensitive and Durable Piezoresistive Sensors.
Creator: Tran Hoang, Phong, Salazar, Nicolas, Porkka, Thomas Nolan, Joshi, Kunal, Liu, Tao, Dickens, Tarik J, Yu, Zhibin
Abstract/Description: We report highly sensitive and reliable strain sensors based on silver nanoparticle (AgNP) and carbon nanotube (CNT) composite thin films. The CNT/AgNP was prepared by a screen printing process using a mixture of a CNT paste and an AgNP ink. It is discovered that the sensitivity of such sensors are highly dependent on the crack formation in the composites. By altering the substrate use and the relative ratios of AgNPs and CNTs, the formation and propagation of cracks can be properly...
Show moreWe report highly sensitive and reliable strain sensors based on silver nanoparticle (AgNP) and carbon nanotube (CNT) composite thin films. The CNT/AgNP was prepared by a screen printing process using a mixture of a CNT paste and an AgNP ink. It is discovered that the sensitivity of such sensors are highly dependent on the crack formation in the composites. By altering the substrate use and the relative ratios of AgNPs and CNTs, the formation and propagation of cracks can be properly engineered, leading to piezoresistive strain sensors with enhanced sensitivity and robustness.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27659951, 10.1186/s11671-016-1626-z, PMC5033798, 27659951, 27659951, 10.1186/s11671-016-1626-z
Format: Citation

Title: Assessing methods for generalizing experimental impact estimates to target populations.
Creator: Kern, Holger L, Stuart, Elizabeth A, Hill, Jennifer, Green, Donald P
Abstract/Description: Randomized experiments are considered the gold standard for causal inference, as they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research, increasing attention is being paid to the potential lack of generalizability of randomized experiments, as the experimental participants may be...
Show moreRandomized experiments are considered the gold standard for causal inference, as they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research, increasing attention is being paid to the potential lack of generalizability of randomized experiments, as the experimental participants may be unrepresentative of the target population of interest. This paper examines whether generalization may be assisted by statistical methods that adjust for observed differences between the experimental participants and members of a target population. The methods examined include approaches that reweight the experimental data so that participants more closely resemble the target population and methods that utilize models of the outcome. Two simulation studies and one empirical analysis investigate and compare the methods' performance. One simulation uses purely simulated data while the other utilizes data from an evaluation of a school-based dropout prevention program. Our simulations suggest that machine learning methods outperform regression-based methods when the required structural (ignorability) assumptions are satisfied. When these assumptions are violated, all of the methods examined perform poorly. Our empirical analysis uses data from a multi-site experiment to assess how well results from a given site predict impacts in other sites. Using a variety of extrapolation methods, predicted effects for each site are compared to actual benchmarks. Flexible modeling approaches perform best, although linear regression is not far behind. Taken together, these results suggest that flexible modeling techniques can aid generalization while underscoring the fact that even state-of-the-art statistical techniques still rely on strong assumptions.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27668031, 10.1080/19345747.2015.1060282, PMC5030077, 27668031, 27668031
Format: Citation

Title: Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men.
Creator: Keglovitz, Kristin, Richardson, Andrew D, Lancki, Nicola, Walsh, Tim, Schneider, John A
Abstract/Description: Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (
Show moreLimited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Results of anal cytology and HPV DNA were gathered for 83 individuals. Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV.
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Date Issued: 2017-02-01
Identifier: FSU_pmch_27673362, 10.1089/lgbt.2016.0049, PMC5278831, 27673362, 27673362
Format: Citation

Title: Pleural effusion: An uncommon manifestation of nitrofurantoin-induced pulmonary injury..
Creator: Davis, Jared W, Jones, Lynn S
Abstract/Description: Nitrofurantoin has been documented as a cause of acute, sub-acute, and chronic pulmonary injury. This is a case of an 82 year-old female who presented with multiple episodes of respiratory symptoms due to recurrent pleural effusions after beginning nitrofurantoin therapy for urinary tract infection prophylaxis. Due to the rarity of pleural effusion as an adverse reaction to nitrofurantoin, the diagnosis was overlooked at first. This led to the patient undergoing multiple invasive procedures...
Show moreNitrofurantoin has been documented as a cause of acute, sub-acute, and chronic pulmonary injury. This is a case of an 82 year-old female who presented with multiple episodes of respiratory symptoms due to recurrent pleural effusions after beginning nitrofurantoin therapy for urinary tract infection prophylaxis. Due to the rarity of pleural effusion as an adverse reaction to nitrofurantoin, the diagnosis was overlooked at first. This led to the patient undergoing multiple invasive procedures and accruing unnecessary healthcare cost before the diagnosis was made. This case demonstrates the need for physicians to remain mindful of rare adverse reactions from medications and maintain a high index of clinical suspicion with any patient presenting with a respiratory complaint while taking nitrofurantoin.
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Date Issued: 2016-07-20
Identifier: FSU_pmch_27625984, 10.1016/j.rmcr.2016.07.009, PMC5010639, 27625984, 27625984, S2213-0071(16)30064-8
Format: Citation

Title: Practice-based Research Networks (PBRNs) Bridging the Gaps between Communities, Funders, and Policymakers.
Creator: Gaglioti, Anne H, Werner, James J, Rust, George, Fagnan, Lyle J, Neale, Anne Victoria
Abstract/Description: In this commentary, we propose that practice-based research networks (PBRNs) engage with funders and policymakers by applying the same engagement strategies they have successfully used to build relationships with community stakeholders. A community engagement approach to achieve new funding streams for PBRNs should include a strategy to engage key stakeholders from the communities of funders, thought leaders, and policymakers using collaborative principles and methods. PBRNs that implement...
Show moreIn this commentary, we propose that practice-based research networks (PBRNs) engage with funders and policymakers by applying the same engagement strategies they have successfully used to build relationships with community stakeholders. A community engagement approach to achieve new funding streams for PBRNs should include a strategy to engage key stakeholders from the communities of funders, thought leaders, and policymakers using collaborative principles and methods. PBRNs that implement this strategy would build a robust network of engaged partners at the community level, across networks, and would reach state and federal policymakers, academic family medicine departments, funding bodies, and national thought leaders in the redesign of health care delivery.
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Date Issued: 2016-09-01
Identifier: FSU_pmch_27613796, 10.3122/jabfm.2016.05.160080, PMC5030066, 27613796, 27613796, 29/5/630
Format: Citation

Title: Correction: Retinopathy and Uveitis Associated with Sofosbuvir Therapy for Chronic Hepatitis C Infection..
Creator: Chin Loy, Katrina, Galaydh, Farah, Shaikh, Saad
Abstract/Description: [This corrects the article DOI: 10.7759/cureus.597.].
Date Issued: 2016-07-14
Identifier: FSU_pmch_27610281, 10.7759/cureus.c3, PMC4999155, 27610281, 27610281
Format: Citation

Title: Risk Factors for Substance Misuse and Adolescents' Symptoms of Depression.
Creator: Siennick, Sonja E, Widdowson, Alex O, Woessner, Mathew K, Feinberg, Mark E, Spoth, Richard L
Abstract/Description: Depressive symptoms during adolescence are positively associated with peer-related beliefs, perceptions, and experiences that are known risk factors for substance misuse. These same risk factors are targeted by many universal substance misuse prevention programs. This study examined whether a multicomponent universal substance misuse intervention for middle schoolers reduced the associations between depressive symptoms, these risk factors, and substance misuse. The study used data from a...
Show moreDepressive symptoms during adolescence are positively associated with peer-related beliefs, perceptions, and experiences that are known risk factors for substance misuse. These same risk factors are targeted by many universal substance misuse prevention programs. This study examined whether a multicomponent universal substance misuse intervention for middle schoolers reduced the associations between depressive symptoms, these risk factors, and substance misuse. The study used data from a place-randomized trial of the Promoting School-Community-University Partnerships to Enhance Resilience model for delivery of evidence-based substance misuse programs for middle schoolers. Three-level within-person regression models were applied to four waves of survey, and social network data from 636 adolescents followed from sixth through ninth grades. When adolescents in control school districts had more symptoms of depression, they believed more strongly that substance use had social benefits, perceived higher levels of substance misuse among their peers and friends, and had more friends who misused substances, although they were not more likely to use substances themselves. Many of the positive associations of depressive symptoms with peer-related risk factors were significantly weaker or not present among adolescents in intervention school districts. The Promoting School-Community-University Partnerships to Enhance Resilience interventions reduced the positive associations of adolescent symptoms of depression with peer-related risk factors for substance misuse.
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Date Issued: 2017-01-01
Identifier: FSU_pmch_27751712, 10.1016/j.jadohealth.2016.08.010, PMC5182119, 27751712, 27751712, S1054-139X(16)30254-3
Format: Citation

Title: An Mcm10 Mutant Defective in ssDNA Binding Shows Defects in DNA Replication Initiation.
Creator: Perez-Arnaiz, Patricia, Kaplan, Daniel L
Abstract/Description: Mcm10 is an essential protein that functions to initiate DNA replication after the formation of the replication fork helicase. In this manuscript, we identified a budding yeast Mcm10 mutant (Mcm10-m2,3,4) that is defective in DNA binding in vitro. Moreover, this Mcm10-m2,3,4 mutant does not stimulate the phosphorylation of Mcm2 by Dbf4-dependent kinase (DDK) in vitro. When we expressed wild-type levels of mcm10-m2,3,4 in budding yeast cells, we observed a severe growth defect and a...
Show moreMcm10 is an essential protein that functions to initiate DNA replication after the formation of the replication fork helicase. In this manuscript, we identified a budding yeast Mcm10 mutant (Mcm10-m2,3,4) that is defective in DNA binding in vitro. Moreover, this Mcm10-m2,3,4 mutant does not stimulate the phosphorylation of Mcm2 by Dbf4-dependent kinase (DDK) in vitro. When we expressed wild-type levels of mcm10-m2,3,4 in budding yeast cells, we observed a severe growth defect and a substantially decreased DNA replication. We also observed a substantially reduced replication protein A- chromatin immunoprecipitation signal at origins of replication, reduced levels of DDK-phosphorylated Mcm2, and diminished Go, Ichi, Ni, and San (GINS) association with Mcm2-7 in vivo. mcm5-bob1 bypasses the growth defect conferred by DDK-phosphodead Mcm2 in budding yeast. However, the growth defect observed by expressing mcm10-m2,3,4 is not bypassed by the mcm5-bob1 mutation. Furthermore, origin melting and GINS association with Mcm2-7 are substantially decreased for cells expressing mcm10-m2,3,4 in the mcm5-bob1 background. Thus, the origin melting and GINS-Mcm2-7 interaction defects we observed for mcm10-m2,3,4 are not explained by decreased Mcm2 phosphorylation by DDK, since the defects persist in an mcm5-bob1 background. These data suggest that DNA binding by Mcm10 is essential for the initiation of DNA replication.
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Date Issued: 2016-11-20
Identifier: FSU_pmch_27751725, 10.1016/j.jmb.2016.10.014, PMC5115986, 27751725, 27751725, S0022-2836(16)30429-6
Format: Citation

Title: Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in .
Creator: Krishnan, Harini C, Gandour, Catherine E, Ramos, Joshua L, Wrinkle, Mariah C, Sanchez-Pacheco, Joseph J, Lyons, Lisa C
Abstract/Description: Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context...
Show moreInsufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk , a relatively simple model system well known for studies of learning and memory. were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish as an effective model system for studying the interactions between sleep and memory formation.
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Date Issued: 2016-12-01
Identifier: FSU_pmch_27748243, 10.5665/sleep.6320, PMC5103805, 27748243, 27748243, sp-00313-16
Format: Citation

Title: Perceived weight discrimination mediates the prospective relation between obesity and depressive symptoms in U.S. and U.K. adults.
Creator: Robinson, Eric, Sutin, Angelina, Daly, Michael
Abstract/Description: Obesity has been shown to increase risk of depression. Persons with obesity experience discrimination because of their body weight. Across 3 studies, we tested for the first time whether experiencing (perceived) weight-based discrimination explains why obesity is prospectively associated with increases in depressive symptoms. Data from 3 studies, including the English Longitudinal Study of Ageing (2008/2009-2012/2013), the Health and Retirement Study (2006/2008-2010/2012), and Midlife in the...
Show moreObesity has been shown to increase risk of depression. Persons with obesity experience discrimination because of their body weight. Across 3 studies, we tested for the first time whether experiencing (perceived) weight-based discrimination explains why obesity is prospectively associated with increases in depressive symptoms. Data from 3 studies, including the English Longitudinal Study of Ageing (2008/2009-2012/2013), the Health and Retirement Study (2006/2008-2010/2012), and Midlife in the United States (1995/1996-2004/2005), were used to examine associations between obesity, perceived weight discrimination, and depressive symptoms among 20,286 U.S. and U.K. adults. Across all 3 studies, Class II and III obesity were reliably associated with increases in depressive symptoms from baseline to follow-up. Perceived weight-based discrimination predicted increases in depressive symptoms over time and mediated the prospective association between obesity and depressive symptoms in all 3 studies. Persons with Class II and III obesity were more likely to report experiencing weight-based discrimination, and this explained approximately 31% of the obesity-related increase in depressive symptoms on average across the 3 studies. In U.S. and U.K. samples, the prospective association between obesity (defined using body mass index) and increases in depressive symptoms in adulthood may in part be explained by perceived weight discrimination. (PsycINFO Database Record
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Date Issued: 2017-02-01
Identifier: FSU_pmch_27748611, 10.1037/hea0000426, PMC5267562, 27748611, 27748611, 2016-49908-001
Format: Citation

Title: Coordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatment..
Creator: Zou, Peng, Liu, Longhua, Zheng, Louise D, Payne, Kyle K, Manjili, Masoud H, Idowu, Michael O, Zhang, Jinfeng, Schmelz, Eva M, Cheng, Zhiyong
Abstract/Description: Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in...
Show moreOveractive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells. This contrast might be owing to enhanced mitochondrial turnover through autophagy, because an increased population of autophagic vacuoles engulfing mitochondria was observed in the cancer cells. Consistently, BNIP3 (a mitochondrial autophagy marker) and autophagic flux were significantly upregulated, indicative of augmented mitochondrial autophagy (mitophagy). The upregulation of Drp1 and BNIP3 was also observed in vivo (human breast carcinomas). Importantly, inhibition of Drp1 significantly suppressed mitochondrial autophagy, metabolic reprogramming, and cancer cell viability. Together, this study reveals coordinated increase of mitochondrial biogenesis and mitophagy in which Drp1 plays a central role regulating breast cancer cell metabolism and survival. Given the emerging evidence of PGC1 contributing to tumor growth, it will be of critical importance to target both mitochondrial biogenesis and mitophagy for effective cancer therapeutics.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27746856, 10.1155/2016/4085727, PMC5056295, 27746856, 27746856
Format: Citation

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