Publications by authors named "Kevin Lewis"

106 Publications

A RARE CASE OF NON-ISLET CELL TUMOUR HYPOGLYCAEMIA.

Authors:
Kevin Lewis

Ulster Med J 2021 01 26;90(1):46-47. Epub 2021 Feb 26.

Microbiology Department, Craigavon Area Hospital, 68 Lurgan Road, Portadown, Craigavon, BT63 5QQ.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931147PMC
January 2021

pH-dependent sedimentation of DNA in the presence of divalent, but not monovalent, metal ions.

Anal Biochem 2021 03 31;616:114099. Epub 2020 Dec 31.

Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX, 78666, USA; Materials Science, Engineering and Commercialization Program, Texas State University, San Marcos, TX, 78666, USA. Electronic address:

Precipitation of DNA is performed frequently in molecular biology laboratories for the purpose of purification and concentration of samples and also for transfer of DNA into cells. Metal ions are used to facilitate these processes, though their precise functions are not well characterized. In the current study we have investigated the precipitation of double-stranded DNA by group 1 and group 2 metal ions. Double-stranded DNAs were not sedimented efficiently by metals alone, even at high concentrations. Increasing the pH to 11 or higher caused strong DNA precipitation in the presence of the divalent group 2 metals magnesium, calcium, strontium and barium, but not group 1 metals. Group 2 sedimentation profiles were distinctly different from that of the transition metal zinc, which caused precipitation at pH 8. Analysis of DNAs recovered from precipitates formed with calcium revealed that structural integrity was retained and that sedimentation efficiency was largely size-independent above 400 bp. Several tests supported a model whereby single-stranded DNA regions formed by denaturation at high pH became bound by the divalent metal cations. Neutralization of negative surface charges reduced the repulsive forces between molecules, leading to formation of insoluble aggregates that could be further stabilized by cation bridging (ionic crosslinking).
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http://dx.doi.org/10.1016/j.ab.2020.114099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849029PMC
March 2021

Clarifying what forward flow is (and isn't): Reply to Rossiter (2020).

Am Psychol 2020 Jul-Aug;75(5):727-728

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill.

Forward flow is a new measure that quantifies free thought and predicts creativity (Gray et al., 2019). In his comment, Rossiter (2020) raises some conceptual and measurement concerns about this measure. We believe these concerns are specious, resting on fundamental misunderstandings about our aim and approach. This reply clarifies the nature of forward flow and dispels these concerns. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/amp0000700DOI Listing
July 2020

The Structural Basis of the Binding of Various Aminopolycarboxylates by the Periplasmic EDTA-Binding Protein EppA from sp. BNC1.

Int J Mol Sci 2020 May 30;21(11). Epub 2020 May 30.

Department of Chemistry, Washington State University, Pullman, WA 99163, USA.

The widespread use of synthetic aminopolycarboxylates, such as ethylenediaminetetraacetate (EDTA), as chelating agents has led to their contamination in the environment as stable metal-chelate complexes. Microorganisms can transport free EDTA, but not metal-EDTA complexes, into cells for metabolism. An ABC-type transporter for free EDTA uptake in sp. BNC1 was investigated to understand the mechanism of the ligand selectivity. We solved the X-ray crystal structure of the periplasmic EDTA-binding protein (EppA) and analyzed its structure-function relations through isothermal titration calorimetry, site-directed mutagenesis, molecular docking, and quantum chemical analysis. EppA had high affinities for EDTA and other aminopolycarboxylates, which agrees with structural analysis, showing that its binding pocket could accommodate free aminopolycarboxylates. Further, key amino acid residues involved in the binding were identified. Our results suggest that EppA is a general binding protein for the uptake of free aminopolycarboxylates. This finding suggests that bacterial cells import free aminopolycarboxylates, explaining why stable metal-chelate complexes are resistant to degradation, as they are not transported into the cells for degradation.
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http://dx.doi.org/10.3390/ijms21113940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312458PMC
May 2020

Structure and Function of the Cytochrome P450 Monooxygenase Cinnamate 4-hydroxylase from .

Plant Physiol 2020 07 24;183(3):957-973. Epub 2020 Apr 24.

Department of Chemistry, Washington State University, Pullman, Washington 99164

Cinnamate 4-hydroxylase (C4H; CYP73A) is a cytochrome P450 monooxygenase associated externally with the endoplasmic reticulum of plant cells. The enzyme uses NADPH-cytochrome P450 reductase as a donor of electrons and hydroxylates cinnamic acid to form 4-coumaric acid in phenylpropanoid metabolism. In order to better understand the structure and function of this unique class of plant P450 enzymes, we have characterized the enzyme C4H1 from lignifying tissues of sorghum (), encoded by Here we report the 1.7 Å resolution crystal structure of CYP73A33. The obtained structural information, along with the results of the steady-state kinetic analysis and the absorption spectroscopy titration, displays a high degree of similarity of the structural and functional features of C4H to those of other P450 proteins. Our data also suggest the presence of a putative allosteric substrate-binding site in a hydrophobic pocket on the enzyme surface. In addition, comparing the newly resolved structure with those of well-investigated cytochromes P450 from mammals and bacteria enabled us to identify those residues of critical functional importance and revealed a unique sequence signature that is potentially responsible for substrate specificity and catalytic selectivity of C4H.
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http://dx.doi.org/10.1104/pp.20.00406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333690PMC
July 2020

Structural and biochemical characterization of iminodiacetate oxidase from Chelativorans sp. BNC1.

Mol Microbiol 2019 12 13;112(6):1863-1874. Epub 2019 Nov 13.

School of Molecular Biosciences, Washington State University, Pullman, WA, 99164-4660, USA.

Ethylenediaminetetraacetate (EDTA) is the most abundant organic pollutant in surface water because of its extensive usage and the recalcitrance of stable metal-EDTA complexes. A few bacteria including Chelativorans sp. BNC1 can degrade EDTA with a monooxygenase to ethylenediaminediacetate (EDDA) and then use iminodiacetate oxidase (IdaA) to further degrade EDDA into ethylenediamine in a two-step oxidation. To alleviate EDTA pollution into the environment, deciphering the mechanisms of the metabolizing enzymes is an imperative prerequisite for informed EDTA bioremediation. Although IdaA cannot oxidize glycine, the crystal structure of IdaA shows its tertiary and quaternary structures similar to those of glycine oxidases. All confirmed substrates, EDDA, ethylenediaminemonoacetate, iminodiacetate and sarcosine are secondary amines with at least one N-acetyl group. Each substrate was bound at the re-side face of the isoalloxazine ring in a solvent-connected cavity. The carboxyl group of the substrate was bound by Arg and Arg . The catalytic residue, Tyr , is under the hydrogen bond network to facilitate its deprotonation acting as a general base, removing an acetate group of secondary amines as glyoxylate. Thus, IdaA is a secondary amine oxidase, and our findings improve understanding of molecular mechanism involved in the bioremediation of EDTA and the metabolism of secondary amines.
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http://dx.doi.org/10.1111/mmi.14399DOI Listing
December 2019

Structural and Functional Characterization of Dynamic Oligomerization in HMG-CoA Reductase.

Biochemistry 2019 09 10;58(38):3960-3970. Epub 2019 Sep 10.

Department of Chemistry and Biochemistry , Gonzaga University , Spokane , Washington 99258 , United States.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), in most organisms, catalyzes the four-electron reduction of the thioester ()-HMG-CoA to the primary alcohol ()-mevalonate, utilizing NADPH as the hydride donor. In some organisms, including the opportunistic lung pathogen , it catalyzes the reverse reaction, utilizing NAD as a hydride acceptor in the oxidation of mevalonate. HMGR has been previously shown to exist as an ensemble of multiple non-additive oligomeric states, each with different levels of enzymatic activity, suggesting that the enzyme exhibits characteristics of the morpheein model of allostery. We have characterized a number of factors, including pH, substrate concentration, and enzyme concentration, that modulate the structural transitions that influence the interconversion among the multiple oligomers. We have also determined the crystal structure of HMGR in the hexameric state bound to coenzyme A and ADP. This hexameric assembly provides important clues about how the transition among oligomers might occur, and why HMGR, unique among characterized HMGRs, exhibits morpheein-like behavior.
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http://dx.doi.org/10.1021/acs.biochem.9b00494DOI Listing
September 2019

Professional Standards: Where are We Now?

Authors:
Kevin Lewis

Prim Dent J 2019 Aug;8(2):16-21

This article discusses the use and misuse of standards in the dental professional environment and reviews their fitness for purpose. it provides an overview of the legal, regulatory and professional framework within which such standards are likely to be used and applied, and examines the differing needs of the various parties within that framework.
The consequences of poorly constructed and ill-communicated standards, including those whose intention and context is not made clear, are considered from the perspectives of the public and patients, the individual clinician, the wider profession and other stakeholders in the professional environment.
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http://dx.doi.org/10.1308/205016819827103421DOI Listing
August 2019

Quantitative assessment of changes in cell growth, size and morphology during telomere-initiated cellular senescence in Saccharomyces cerevisiae.

Exp Cell Res 2019 08 7;381(1):18-28. Epub 2019 May 7.

Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA. Electronic address:

Telomerase-deficient cells of the budding yeast S. cerevisiae experience progressive telomere shortening and undergo senescence in a manner similar to that seen in cultured human fibroblasts. The cells exhibit a DNA damage checkpoint-like stress response, undergo changes in size and morphology, and eventually stop dividing. In this study, a new assay is described that allowed quantitation of senescence in telomerase-deficient est2 cells with applied statistics. Use of the new technique revealed that senescence was strongly accelerated in est2 mutants that had homologous recombination genes RAD51, RAD52 or RAD54 co-inactivated, but was only modestly affected when RAD55, RAD57 or RAD59 were knocked out. Additionally, a new approach for calculating population doublings indicated that loss of growth capacity occurred after approximately 64 generations in est2 cells but only 42 generations in est2 rad52 cells. Phase contrast microscopy experiments demonstrated that senescing est2 cells became enlarged in a time-dependent manner, ultimately exhibiting a 60% increase in cell size. Progressive alterations in physical properties were also observed, including striking changes in light scattering characteristics and cellular sedimentation rates. The results described herein will facilitate future studies of genetic and environmental factors that affect telomere shortening-associated cell senescence rates using the yeast model system.
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http://dx.doi.org/10.1016/j.yexcr.2019.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563841PMC
August 2019

Risk factors for hypogonadism in young men with erectile dysfunction.

J Chin Med Assoc 2019 Jun;82(6):477-481

Departments of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: The objective of this study is to evaluate the hormone profile of young men with the chief complaint of erectile dysfunction (ED) and determine the comorbidities in this population.

Methods: A retrospective chart review of men aged 18 to 40 years who presented with ED and had a hormone evaluation but without prior medication for hormone manipulation from 2002 to 2016 was performed at a tertiary care institution. Data were obtained on demographics, comorbidities, medications, and hormonal evaluations.

Results: A total of 2292 men with ED were identified and 2130 of them received testosterone level evaluation. The most common comorbidities that men were actively being treated for were depression (22.3%), anxiety (16.1%), hypertension (15.6%), diabetes (7.2%), cancer (6.2%), and cardiovascular disease (3.3%). The average total testosterone level was 368 ± 160 ng/dL; 10.7% of men had hypogonadism. Multivariate analysis demonstrated age, body mass index (BMI), depression, and cancer predicted a hypogonadal status. Patients with BMI > 28.2 kg/m, age > 34 years, cancer diagnosis, or depression were 3.350-fold, 1.447-fold, 2.317-fold, or 1.420-fold more likely to be diagnosed hypogonadal than nonoverweight, age ≤ 34 years, noncancer, or nondepressive patients.

Conclusion: The majority of men under the age of 40 with ED exhibit a normal hormonal milieu. Young ED men with BMI > 28.2 kg/m, age >34 years, cancer diagnosis, or depression are at risk for hypogonadism.
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http://dx.doi.org/10.1097/JCMA.0000000000000099DOI Listing
June 2019

A surface gravity traverse on Mars indicates low bedrock density at Gale crater.

Science 2019 02;363(6426):535-537

School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85281, USA.

Gravimetry, the precise measurement of gravitational fields, can be used to probe the internal structure of Earth and other planets. The Curiosity rover on Mars carries accelerometers normally used for navigation and attitude determination. We have recalibrated them to isolate the signature of the changing gravitational acceleration as the rover climbs through Gale crater. The subsurface rock density is inferred from the measured decrease in gravitational field strength with elevation. The density of the sedimentary rocks in Gale crater is 1680 ± 180 kilograms per cubic meter. This value is lower than expected, indicating a high porosity and constraining maximum burial depths of the rocks over their history.
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http://dx.doi.org/10.1126/science.aat0738DOI Listing
February 2019

"Forward flow": A new measure to quantify free thought and predict creativity.

Am Psychol 2019 Jul-Aug;74(5):539-554. Epub 2019 Jan 21.

Department of Sociology, University of California-San Diego.

When the human mind is free to roam, its subjective experience is characterized by a continuously evolving stream of thought. Although there is a technique that captures people's streams of free thought-free association-its utility for scientific research is undermined by two open questions: (a) How can streams of thought be quantified? (b) Do such streams predict psychological phenomena? We resolve the first issue-quantification-by presenting a new metric, "forward flow," that uses latent semantic analysis to capture the semantic evolution of thoughts over time (i.e., how much present thoughts diverge from past thoughts). We resolve the second issue-prediction-by examining whether forward flow predicts creativity in the lab and the real world. Our studies reveal that forward flow predicts creativity in college students (Study 1) and a representative sample of Americans (Study 2), even when controlling for intelligence. Studies also reveal that membership in real-world creative groups-performance majors (Study 3), professional actors (Study 4) and entrepreneurs (Study 5)-is predicted by forward flow, even when controlling for performance on divergent thinking tasks. Study 6 reveals that forward flow in celebrities' social media posts (i.e., on Twitter) predicts their creative achievement. In addition to creativity, forward flow may also help predict mental illness, emotional experience, leadership ability, adaptability, neural dynamics, group productivity, and cultural success. We present open-access online tools for assessing and visualizing forward flow for both illustrative and large-scale data analytic purposes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/amp0000391DOI Listing
June 2020

Inconsistent Adoption of World Health Organization V (2010) Semen Analysis Reference Ranges in the United States Eight Years After Publication.

Urology 2019 04 31;126:96-101. Epub 2018 Dec 31.

Northwestern University, Feinberg School of Medicine, Department of Urology, Chicago, IL. Electronic address:

Objective: To determine the percentage of laboratories in the United States that have adopted the World Health Organization 2010 (WHO 5) semen analysis (SA) reference values 6years after their publication.

Methods: Laboratories were identified via 3 approaches: using the Clinical Laboratory Improvement Amendments (CLIA) website, the CDC's 2015 Assisted Reproductive Technology Fertility Clinical Success Rate Report, and automated web searches. Laboratories were contacted by phone or email to obtain de-identified SA reports and reference ranges.

Results: We contacted 617 laboratories in 46 states, of which 208 (26.7%) laboratories in 45 states were included in our analysis. 132 (63.5%) laboratories used WHO 5 criteria, 57 (27.4%) used WHO 4 criteria, and 19 (9.1%) used other criteria. WHO 5 criteria adoption rates varied by geographic region, ranging from 87.5% (35/40) in the Midwest to 50.0% (33/66) in the West. There was a greater adoption rate of WHO 5 reference values in academic affiliated (23/26, 88.5%) compared to non-academic affiliated laboratories (110/182, 60.4%) (P = .028).

Conclusion: While the majority of laboratories have adopted WHO 5 criteria following its release 6years ago, a large percentage (36.5%) use what is now considered outdated criteria. This variability could result in the characterization of a male's semen values as being "within reference range" at one center and "outside of reference range" at another. This inconsistency in classification may result in confusion for the both patient and physician and potentially shift the burden of infertility evaluation and treatment to the female partner.
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http://dx.doi.org/10.1016/j.urology.2018.09.041DOI Listing
April 2019

Horizontal Agarose Gel Mobility Shift Assay for Protein-RNA Complexes.

Methods Mol Biol 2019 ;1855:363-370

Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA.

Recent advances in agarose gel electrophoresis protocols established conditions for the high-resolution separation of DNA and RNA using higher voltages combined with short run times. We subsequently developed a protocol for using these conditions to measure the binding affinity of a protein for an RNA ligand on an agarose gel. This native gel mobility shift assay is highly accessible, using common molecular biology reagents found in most laboratories. Here, we describe the protocol for carrying out native agarose gel electrophoresis to characterize the binding affinity of a protein for an RNA ligand. The electrophoresis time is less than 10 min, which minimizes the dissociation of protein and ligand. We have used the p19 siRNA binding protein and its cognate dsRNA ligand to demonstrate strategies for identifying optimal conditions to measure apparent binding constants using this agarose gel shift system.
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http://dx.doi.org/10.1007/978-1-4939-8793-1_31DOI Listing
June 2019

Molecular parallelism in fast-twitch muscle proteins in echolocating mammals.

Sci Adv 2018 09 26;4(9):eaat9660. Epub 2018 Sep 26.

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Detecting associations between genomic changes and phenotypic differences is fundamental to understanding how phenotypes evolved. By systematically screening for parallel amino acid substitutions, we detected known as well as novel cases (Strc, Tecta, and Cabp2) of parallelism between echolocating bats and toothed whales in proteins that could contribute to high-frequency hearing adaptations. Our screen also showed that echolocating mammals exhibit an unusually high number of parallel substitutions in fast-twitch muscle fiber proteins. Both echolocating bats and toothed whales produce an extremely rapid call rate when homing in on their prey, which was shown in bats to be powered by specialized superfast muscles. We show that these genes with parallel substitutions (, , , and ) are expressed in the superfast sound-producing muscle of bats. Furthermore, we found that the calcium storage protein calsequestrin 1 of the little brown bat and the bottlenose dolphin functionally converged in its ability to form calcium-sequestering polymers at lower calcium concentrations, which may contribute to rapid calcium transients required for superfast muscle physiology. The proteins that our genomic screen detected could be involved in the convergent evolution of vocalization in echolocating mammals by potentially contributing to both rapid Ca transients and increased shortening velocities in superfast muscles.
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http://dx.doi.org/10.1126/sciadv.aat9660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157964PMC
September 2018

The Medusae Fossae Formation as the single largest source of dust on Mars.

Nat Commun 2018 07 20;9(1):2867. Epub 2018 Jul 20.

Department of Earth Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada.

Transport of fine-grained dust is one of the most widespread sedimentary processes occurring on Mars today. In the present climate, eolian abrasion and deflation of rocks are likely the most pervasive and active dust-forming mechanism. Martian dust is globally enriched in S and Cl and has a distinct mean S:Cl ratio. Here we identify a potential source region for Martian dust based on analysis of elemental abundance data. We show that a large sedimentary unit called the Medusae Fossae Formation (MFF) has the highest abundance of S and Cl, and provides the best chemical match to surface measurements of Martian dust. Based on volume estimates of the eroded materials from the MFF, along with the enrichment of elemental S and Cl, and overall geochemical similarity, we propose that long-term deflation of the MFF has significantly contributed to the global Martian dust reservoir.
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http://dx.doi.org/10.1038/s41467-018-05291-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054634PMC
July 2018

Clinical effectiveness and versatility of a sealing hemostatic patch (HEMOPATCH) in multiple surgical specialties.

Expert Rev Med Devices 2018 May 26;15(5):367-376. Epub 2018 Apr 26.

a Global Medical Affairs , Baxter Healthcare Corporation , Deerfield , IL , USA.

Introduction: Intraoperative surgical sealants and hemostatic agents have been shown to reduce postoperative complications, transfusions, and hospital resource utilization. Despite availability of these agents, the incidence and burden of bleeding remains high and surgeons' requirements for hemostatic control continue to evolve. A burgeoning class of hemostatic agents are hemostatic patches, which offer package-to-patient readiness and direct application. In addition, hemostatic patches may provide tissue sealing capabilities. Areas covered: This review focuses on the clinical effectiveness, versatility, and surgical efficiency of HEMOPATCH as a surgical sealant and hemostatic agent in various surgical specialties including: cardiac, digestive (hepatic, gastrointestinal, pancreatic), urological, neurological, and endocrine. Expert commentary: Among hemostatic patches, HEMOPATCH is a valuable tool to stop bleeding without adverse events across various surgical specialties. Clinical evidence demonstrates the safety, clinical effectiveness, and versatility of HEMOPATCH as a unique surgical adjunct in patients undergoing complex and routine surgical procedures. Larger randomized-controlled clinical studies, or clinical registries, will continue to be used to evaluate its performance and versatility, particularly for sealing tissues and closing the dura. In the current field of surgical sealing and hemostasis, however, HEMOPATCH represents the next step in improving patient outcomes.
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http://dx.doi.org/10.1080/17434440.2018.1464909DOI Listing
May 2018

Intraoperative Nerve Blocks Fail to Improve Quality of Recovery after Tissue Expander Breast Reconstruction: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.

Plast Reconstr Surg 2018 03;141(3):590-597

Chicago, Ill.

Background: The authors' study represents the first level I evidence to assess whether intraoperative nerve blocks improve the quality of recovery from immediate tissue expander/implant breast reconstruction.

Methods: A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in which patients undergoing immediate tissue expander/implant breast reconstruction were randomized to either (1) intraoperative intercostal and pectoral nerve blocks with 0.25% bupivacaine with 1:200,000 epinephrine and 4 mg of dexamethasone or (2) sham nerve blocks with normal saline. The 40-item Quality of Recovery score, pain score, and opioid use in the postoperative period were compared statistically between groups. Power analysis ensured 80 percent power to detect a 10-point (clinically significant) difference in the 40-item Quality of Recovery score.

Results: Forty-seven patients were enrolled. Age, body mass index, laterality, mastectomy type, and lymph node dissection were similar between groups. There were no statistical differences in quality of recovery, pain burden as measured by visual analogue scale, opioid consumption, antiemetic use, or length of hospital stay between groups at 24 hours after surgery. Mean global 40-item Quality of Recovery scores were 169 (range, 155 to 182) for the treatment arm and 165 (range, 143 to 179) for the placebo arm (p = 0.36), indicating a high quality of recovery in both groups.

Conclusion: Although intraoperative nerve blocks can be a safe adjunct to a comprehensive postsurgical recovery regimen, the authors' results indicate no effect on overall quality of recovery from tissue expander/implant breast reconstruction.

Clinical Question/level Of Evidence: Therapeutic, I.
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http://dx.doi.org/10.1097/PRS.0000000000004104DOI Listing
March 2018

Hemostatic Comparison of a Polysaccharide Powder and a Gelatin Powder.

J Invest Surg 2019 Aug 8;32(5):393-401. Epub 2018 Feb 8.

a Baxter Healthcare Corporation, One Baxter Parkway , Deerfield , IL , USA.

Powdered hemostats have been widely adopted for their ease-of-use; however, their efficacy has been limited resulting in applications restricted to low-level bleeds. This study investigates the use of bovine-derived gelatin particles (BGP) as a standalone hemostatic powder and compare BGP to commercially available microporous polysaccharide hemospheres (MPH). The powders were investigated for their hemostatic efficacy in a heparinized pre-clinical bleeding model limited to grade 1 and 2 bleeds on a validated intraoperative bleeding scale, which represents the accepted, clinical use of hemostatic powders. At 10 minutes, the hemostatic success of lesions treated with BGP were 78% while MPH were 22%. The odds ratio for hemostatic success of BGP relative to MPH was 15.18 (95% CI: 7.37, 31.27). The 95% lower limit of the odds ratio was greater than 1. This indicates that BGP are superior to MPH ( < 0.001). The median time to hemostasis for BGP was 1.6 minutes and MPH was 14.5 minutes. The ratio for time to hemostasis of MPH relative to BGP was 9.23 (95% CI: 6.99, 12.19). This indicates that BGP achieve significantly faster time to hemostasis ( < 0.001). Characterization of tissue explant ultrastructure, particle size, and swelling revealed differences in the materials. BGP, in addition to absorbing fluid and concentrating clotting factors and platelets, integrate into the clot and stabilize the fibrin matrix. BGP have advantages over MPH in terms of speed and efficacy. BGP are a favorable biomaterial for further research that greatly improve the limited efficacy of powdered hemostats.
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http://dx.doi.org/10.1080/08941939.2017.1423421DOI Listing
August 2019

Factors affecting the association of single- and double-stranded RNAs with montmorillonite nanoclays.

Int J Biol Macromol 2018 Apr 22;109:551-559. Epub 2017 Dec 22.

Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX, 78666, United States. Electronic address:

Montmorillonite (MMT) nanoclays exist as single and stacked sheet-like structures with large surface areas that can form stable associations with many naturally occurring biomolecules, including nucleic acids. They have been utilized successfully as vehicles for delivery of both drugs and genes into cells. Most previous studies have focused on interactions of MMT with DNA. In the current study, we have investigated the binding of small RNAs similar to those used for RNA interference (RNAi) therapy to two major forms of the clay, Na-MMT and Ca-MMT. Association of both forms of MMT with several double-stranded RNAs (dsRNAs), including 25mers, 54mers and cloverleaf-shaped transfer RNAs, was weak and increased only slightly after addition of Mg ions to the binding reactions. By contrast, ssRNA 25mers and 54mers bound poorly to Na-MMT but interacted strongly with Ca-MMT. The weak binding of ssRNAs to Na-MMT could be strongly enhanced by addition of Mg ions. The strength of MMT-ssRNA interactions was also examined using inorganic anion competition and displacement assays, as well as electrophoretic mobility shift assays (EMSAs). The aggregate results point to a cation-bridging mechanism for binding of ssRNAs, but not dsRNAs, in the presence of divalent metal cations.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.12.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247799PMC
April 2018

Cost-effectiveness analysis of a sealing hemostat patch (HEMOPATCH) vs standard of care in cardiac surgery.

J Med Econ 2018 Mar 7;21(3):273-281. Epub 2017 Dec 7.

c Baxter Healthcare Corporation , Zurich , Switzerland.

Background: A recent randomized controlled trial showed that patients undergoing ascending aorta surgery treated with HEMOPATCH to control bleeding had a significantly better hemostasis success rate than with dry or wet gauze compression or similar standard of care (SOC).

Objective: To compare the cost-effectiveness using two different agents for hemostasis (HEMOPATCH vs dry or wet gauze compression or similar SOC) in cardiac surgery from the European hospital perspective.

Methods: A literature-based cost-effectiveness model estimating average cost per successful hemostasis event was developed based on the hemostasis efficacy difference (HEMOPATCH = 97.6%, SOC = 65.8%, p < .001). Additional clinically significant end-points studied in the trial (blood transfusions and surgical revisions) were also analyzed. It was assumed that each surgery utilized two units of HEMOPATCH (dimensions of 4.5 × 9 cm) and two units of SOC. Product acquisition costs for HEMOPATCH and SOC were included along with outcome-related costs derived from the literature and inflation-adjusted to 2017 EUR and GBP. Results are presented for an average hospital with an annual case load of 574 cardiac surgeries. One-way and probabilistic sensitivity analyses were performed.

Results: Considering only product acquisition cost, HEMOPATCH had an incremental cost-effectiveness ratio (ICER) of €1,659, €1,519, €1,623, and £1,725 per hemostasis success when compared to SOC for Italy, Spain, France, and the UK, respectively. However, when considering the cost and potential difference in the frequency of transfusions and revisions compared to SOC, the use of HEMOPATCH was associated with an annual reduction of six revisions and 60 transfusions, improving the ICER to €1,440, €1,222, €1,461, and £1,592, respectively. Sensitivity analysis demonstrated model robustness.

Conclusions: This analysis supports the use of HEMOPATCH over SOC in cardiac surgery in European hospitals to improve hemostasis success rates and potential cost offsets from reduced transfusions, complications, and surgical revisions.
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http://dx.doi.org/10.1080/13696998.2017.1400977DOI Listing
March 2018

Clinical symptoms that predict the presence of Obstructive Sleep Apnea.

Int J Pediatr Otorhinolaryngol 2017 Apr 21;95:139-144. Epub 2017 Feb 21.

Division of Otolaryngology Head and Neck Surgery, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, United States; Department of Otolaryngology Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. Electronic address:

Objective: To determine if a set of clinical symptoms can help in determining the presence and severity of OSA.

Setting: Tertiary urban pediatric hospital.

Methods: Parents of children undergoing an overnight PSG answered a 56 item questionnaire based on their child's symptoms. The responses to the questionnaire were compared between patients with different severities of OSA (s determined by PSG) and those without OSA. Responses to questionnaire were also analyzed between obese and non-obese patients.

Results: 235 children were included (140 male and 95 female) with a mean age of 5.76 ± 2.78 years. The mean Apnea Hypopnea Index (AHI) was 7.78 ± 14.50 events/hour (range 0-110 events/h). 74 (31.5%) children had mild-OSA (AHI between 1 and 4.99 events/h), 31 (13.19%) had moderate-OSA (AHI between 5 and 9.99 events/h), 58 (24.7%) had severe-OSA (AHI≥10events/h) and the remaining 72 (30.64%) had No-OSA (AHI≤1event/h). 87 (37%) patients were obese. Eight clinical symptoms in non-obese and six clinical symptoms in obese patients predicted the mild to severe OSA. Sixteen symptoms in non-obese patients and nine symptoms in obese patients predicted the presence of severe OSA in these patients.

Conclusion: Clinical symptoms reported in this study are useful to predict the presence of and the severity of OSA in children. Clinical symptoms can also predict the presence and severity of OSA in children who are obese, however, the symptoms required to make the prediction are different in obese children.
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http://dx.doi.org/10.1016/j.ijporl.2017.02.018DOI Listing
April 2017

Safety and Efficacy of a Novel, Self-Adhering Dural Substitute in a Canine Supratentorial Durotomy Model.

Neurosurgery 2018 03;82(3):397-406

Baxter Healthcare Corporation, Deer-field, Illinois.

Background: Cerebrospinal fluid (CSF) leaks increase postoperative risk for complication, likelihood of reoperation, and costs.

Objective: To investigate a novel, self-adhering polyethylene glycol-coated collagen pad (PCC) as a dural substitute relative to Duragen XS (DGX; Integra LifeSciences Corporation, Plainsboro, New Jersey) and as a dural sealant relative to Tachosil (Takeda Austria GmbH, Linz, Austria), a fibrinogen and thrombin-coated collagen pad (FTC).

Methods: A canine supratentorial durotomy surgical model was used to investigate the safety and efficacy of PCC. For safety, 4 animals were bilaterally treated with DGX or PCC and recovered for 1, 8, or 16 wk; total 24 animals. Each animal underwent physical and neurological examinations weekly and 16-wk animals underwent a magnetic resonance imaging (MRI) examination at each time point. For efficacy, 9 animals were unilaterally treated with FTC or PCC and underwent a burst pressure test intraoperatively or 14 d postoperatively; total 36 animals.

Results: In the safety study, no abnormal clinical signs or changes were noted on physical and neurological examinations, or in clinical pathology, CSF analysis or histopathology of DGX or PCC-treated animals. No consistent signs of cerebral compression, CSF leak, hemorrhage, or hydrocephalus were noted on MRI. In the efficacy study, no significant difference was found between FTC and PCC at each time point or overall (13.9 vs 12.3 mm Hg, n = 18 per group, P = .46).

Conclusion: PCC is safe for use as a dural substitute and effective as a dural sealant. The novel, self-adhering combination of a polyethylene glycol-based sealant and a collagen pad may offer unique benefits to the advancement of duraplasty.
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http://dx.doi.org/10.1093/neuros/nyx216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018778PMC
March 2018

Comparison of Efficacy and Complications Among Various Spacer Grafts in the Treatment of Lower Eyelid Retraction: A Systematic Review.

Aesthet Surg J 2017 Jul;37(7):743-754

Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Lower eyelid retraction is a difficult problem to treat, but it is a prevalent condition and a common complication of blepharoplasty. The use of spacer grafts to increase eyelid height and improve symptoms has been described for a long time, but the optimal choice of spacer graft material is unknown.

Objectives: The authors reviewed the currently available evidence to determine the best available spacer graft material in terms of efficacy and complications.

Methods: A systematic review of all available literature published between 1985 and the present was performed using the Pubmed, Ovid MEDLINE, and Cochrane library databases. Inclusion criteria were that the studies contain original content assessing the treatment of lower eyelid retraction in humans using a spacer graft and provide quantitative outcomes data.

Results: One hundred and twelve articles were reviewed following an initial screen using titles, and 19 articles were chosen for inclusion in this systematic review. Analysis of these articles revealed no spacer graft material that is clearly superior to others.

Conclusions: Due to a lack of high quality evidence, this review did not reveal one spacer graft material that is clearly superior to others. However, a narrative summary of the available evidence reveals unique sets of advantages and disadvantages associated with the various materials currently available. Further research in the form of well-designed studies will be necessary to further clarify advantages of certain spacer graft materials over others.

Level Of Evidence: 5.
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http://dx.doi.org/10.1093/asj/sjx003DOI Listing
July 2017

Building the Class 2 CRISPR-Cas Arsenal.

Mol Cell 2017 Feb;65(3):377-379

Department of Molecular Biology and Genetics, Cornell University, 251 Biotechnology Building, Ithaca, NY 14853, USA. Electronic address:

Adaptation of CRISPR-Cas9 for genome-editing applications has revolutionized biomedical research. New single-component effector CRISPR systems are emerging from the bioinformatics pipeline. How can we best harness their power? Three new studies will no doubt facilitate this transition by generating the C2c1 and C2c2 structure snapshots in different functional states.
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http://dx.doi.org/10.1016/j.molcel.2017.01.024DOI Listing
February 2017

Determining the differential impact of cancer and cancer therapies on male reproductive health: aiming for enhanced prognostic specificity.

Fertil Steril 2017 02 29;107(2):336-337. Epub 2016 Dec 29.

Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

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http://dx.doi.org/10.1016/j.fertnstert.2016.11.023DOI Listing
February 2017

Enhancing yields of low and single copy number plasmid DNAs from Escherichia coli cells.

J Microbiol Methods 2017 02 23;133:46-51. Epub 2016 Dec 23.

Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX 78666, United States. Electronic address:

Many plasmids used for gene cloning and heterologous protein expression in Escherichia coli cells are low copy number or single copy number plasmids. The extraction of these types of plasmids from small bacterial cell cultures produces low DNA yields. In this study, we have quantitated yields of low copy and single copy number plasmid DNAs after growth of cells in four widely used broths (SB, SOC, TB, and 2xYT) and compared results to those obtained with LB, the most common E. coli cell growth medium. TB (terrific broth) consistently generated the greatest amount of plasmid DNA, in agreement with its ability to produce higher cell titers. The superiority of TB was primarily due to its high levels of yeast extract (24g/L) and was independent of glycerol, a unique component of this broth. Interestingly, simply preparing LB with similarly high levels of yeast extract (LB24 broth) resulted in plasmid yields that were equivalent to those of TB. By contrast, increasing ampicillin concentration to enhance plasmid retention did not improve plasmid DNA recovery. These experiments demonstrate that yields of low and single copy number plasmid DNAs from minipreps can be strongly enhanced using simple and inexpensive media.
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http://dx.doi.org/10.1016/j.mimet.2016.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286560PMC
February 2017