Publications by authors named "Michael Simpson"

292 Publications

Single session transcranial direct current stimulation to the primary motor cortex fails to enhance early motor sequence learning in Parkinson's disease.

Behav Brain Res 2021 Oct 8:113624. Epub 2021 Oct 8.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong. Electronic address:

Introduction: Explicit motor sequence learning is impaired in Parkinson's disease (PD). Transcranial direct current stimulation (tDCS) applied over the motor cortex in healthy can improve explicit motor learning, but comparative effects in PD are unknown. This exploratory study aims to examine the effect of single session tDCS on explicit motor sequence learning in PD.

Methods: Thirty-three people with mild to moderate PD learnt a short and long finger tapping sequence with their right hand. Participants received either anodal, cathodal, or sham tDCS applied over the left primary motor cortex during task practice. Single- and dual-task finger tapping performance was assessed before and after task practice and functional near-infrared spectroscopy used to measure task related changes of oxygenated haemoglobin.

Results: Finger tapping performance of short and long sequences under single-task conditions significantly improved following practice (p = 0.010 and p < 0.001, respectively). A condition-by-time interaction trend was observed for the long finger tapping sequence (p = 0.069) driven by improved performance in the cathodal (p = 0.001) and sham (p < 0.001) tDCS conditions, but not anodal tDCS (p = 0.198). The primary and premotor cortex and supplementary motor area were active in all tasks. No interaction or main effects were observed for task related changes of oxygenated haemoglobin.

Conclusions: PD patients retain the capacity to learn an explicit sequence of movements. Motor cortex tDCS does not improve explicit motor learning in PD and anodal tDCS may even suppress the rate of learning.
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http://dx.doi.org/10.1016/j.bbr.2021.113624DOI Listing
October 2021

Bridge to Sapien: Mechanical Circulatory Support as a Bridge to Transcatheter Mitral Intervention.

Ann Thorac Surg 2021 Sep 22. Epub 2021 Sep 22.

Division of Cardiothoracic Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY.

Veno-arterial membrane oxygenation (VA-ECMO) can be used as a rescue therapy for patients in refractory cardiogenic shock. While there is experience as a bridge-to-transplant and bridge-to-ventricular assist device in the heart failure population, there are not reports of its use as a bridge to definitive valvular intervention. Here we present a case of VA-ECMO as a bridge to transcatheter mitral valve-in-valve (TMVIV) with a Sapien aortic prosthesis (Edwards Life Sciences, Irvine, CA).
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http://dx.doi.org/10.1016/j.athoracsur.2021.08.030DOI Listing
September 2021

The Effect of a 7.0 mm Intraocular Lens Optic on Peripheral Retinal Illumination with Implications for Negative Dysphotopsia.

J Cataract Refract Surg 2021 Sep 21. Epub 2021 Sep 21.

From the Department of Ophthalmology, Mayo Clinic, Rochester, MN Simpson Optics LLC, Arlington, TX.

Purpose: To use optical modeling to compare 6.0 mm and 7.0 mm intraocular lens (IOL) optic diameters on peripheral retinal illumination with implications for negative dysphotopsia.

Setting: Mayo Clinic, Rochester, MN, and Simpson Optics LLC, Arlington, TX.

Design: Model eye.

Methods: Ray-trace software was used to simulate retinal illumination from an extended light source for a pseudophakic eye with in-the-bag biconvex IOLs (Refractive Index [n] 1.46 and 1.55) and a 2.5 mm pupil. Ray-tracing diagrams and simulated retina illumination profiles were compared using 6.0 mm and 7.0 mm optic diameter IOLs. Retinal locations were scaled to relative visual angles from 70° - 110° horizontally.

Results: A 7.0 mm optic (n 1.46) expands the image field by 2.8° compared to a 6.0 mm optic. High angle input light misses a 7.0 mm optic at a larger visual angle than a 6.0 mm optic, shifting illumination of the peripheral retina by this light anteriorly by 5.6°. Consequently, a region of non-illuminated peripheral nasal retina is enlarged and shifted peripherally using a 7.0 mm optic (visual angle, 86.3°- 96.3°) compared to a 6.0 mm optic (visual angle, 83.5°- 90.7°). Similar illumination changes were seen modeling a 1.55 n IOL.

Conclusions: A narrow dark region in the nasal retina when using a 6.0 mm optic is changed to a broader, more peripheral dark region when using a 7.0 mm optic. An extended, more peripheral dark nasal region may make a temporal shadow less bothersome and explain lower ND rates using a 7.0 mm optic.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000822DOI Listing
September 2021

Nomenclatural revision of (Boraginaceae s. str.) names linked to South American taxa.

PhytoKeys 2021 30;181:29-47. Epub 2021 Aug 30.

Department of Biology, San Diego State University, San Diego, California 92182, USA San Diego State University San Diego United States of America.

During the preparation of the treatment of the genus Lehmann ex G. Don for South America, numerous names were identified as needing typification to stabilize their nomenclature. As a result, lectotypes are designated for 11 names and second-step lectotypes for 20 names. Furthermore, supporting information about the type material of the basionyms of four names already typified by Johnston ( Phil., Phil., Phil., and Phil.) is provided.
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http://dx.doi.org/10.3897/phytokeys.181.69740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421323PMC
August 2021

Corneal power values for use with keratoprostheses and intraocular lenses.

Ophthalmic Physiol Opt 2021 Nov 17;41(6):1285-1291. Epub 2021 Sep 17.

Simpson Optics LLC, Arlington, Texas, USA.

Purpose: To specify a keratoprosthesis (KPro) power value for use with an intraocular lens (IOL).

Methods: Raytracing software was used to determine the imaging properties of both the natural cornea and conceptual KPro designs, and IOL power calculation methods were reviewed. Traditional calculations use 'thick lens' models for the overall eye, while also using 'thin lens' approximations for the cornea and IOL. The power of the natural cornea acts approximately at the apex, although this is unlikely to be the case for a KPro. The IOL location is determined using an empirical adjustment that is calculated from clinical results for natural eyes.

Results: The use of a KPro has a similar optical effect to corneal refractive surgery, where the cornea no longer matches the original eye. A modification of the 'double-K' calculation method can be used by specifying the KPro effective power at the original corneal apex, but still estimating the postoperative IOL location using the original corneal power. The KPro power is measured by assembling the KPro with fluid and a window to simulate the way it is used, recording the best focus power at room temperature with a 3 mm diameter aperture, rescaling to the in situ power at 35°C using refractive index changes, and then rescaling again to the power expected relative to the original corneal apex. When expressed as a K value, a keratometer refractive index of 1.332 is proposed. If necessary, clinical results may be used later to make empirical adjustments to the calculation method.

Conclusions: A KPro power can be specified relative to the expected location of the original corneal apex using a keratometer index of 1.332. A double-K calculation can then be used to determine the correct KPro and IOL power values for a pseudophakic eye.
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http://dx.doi.org/10.1111/opo.12886DOI Listing
November 2021

Adsorption of semiflexible polymers in crowded environments.

J Chem Phys 2021 Jul;155(3):034904

Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, Knoxville, Tennessee 37996, USA.

Macromolecular crowding is a feature of cellular and cell-free systems that, through depletion effects, can impact the interactions of semiflexible biopolymers with surfaces. In this work, we use computer simulations to study crowding-induced adsorption of semiflexible polymers on otherwise repulsive surfaces. Crowding particles are modeled explicitly, and we investigate the interplay between the bending stiffness of the polymer and the volume fraction and size of crowding particles. Adsorption to flat surfaces is promoted by stiffer polymers, smaller crowding particles, and larger volume fractions of crowders. We characterize transitions from non-adsorbed to partially and strongly adsorbed states as a function of bending stiffness. The crowding-induced transitions occur at smaller values of the bending stiffness as the volume fraction of crowders increases. Concomitant effects on the size and shape of the polymer are reflected by crowding- and stiffness-dependent changes to the radius of gyration. For various polymer lengths, we identify a critical crowding fraction for adsorption and analyze its scaling behavior in terms of polymer stiffness. We also consider crowding-induced adsorption in spherical confinement and identify a regime in which increasing the bending stiffness induces desorption. The results of our simulations shed light on the interplay of crowding and bending stiffness on the spatial organization of biopolymers in encapsulated cellular and cell-free systems.
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http://dx.doi.org/10.1063/5.0054797DOI Listing
July 2021

Pre-clinical estimation of the intraocular lens A-constant, and its relationship to power, shape factor, and asphericity.

Appl Opt 2021 Jul;60(19):5662-5668

Calculating the intraocular lens power for a particular patient requires an empirical "lens constant" to estimate the final axial location after surgery. This is normally calculated from clinical results for each new lens style, but it can also be estimated without clinical data by comparing a new style to an existing style. The lenses are axially positioned in a model eye at comparable locations, and image distances are used to estimate the change in lens constant. The A-constant used by the SRK/T calculation method is evaluated here, but this can be easily converted for other calculations using an average eye. Raytrace calculations demonstrate the method, and also illustrate the effects that refractive index, shape factor, and asphericity have on the refractive error. Actual lens measurements at 35°C in saline are preferable if details of the reference lens are uncertain.
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http://dx.doi.org/10.1364/AO.426155DOI Listing
July 2021

Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family.

Sci Rep 2021 05 26;11(1):11026. Epub 2021 May 26.

CHU Sainte-Justine Research Center, 3175 Côte Sainte-Catherine, 2.17.026, Montreal, QC, H3T 1C5, Canada.

Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.
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http://dx.doi.org/10.1038/s41598-021-90155-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155187PMC
May 2021

Comment on: Distinct differences in anterior chamber configuration and peripheral aberrations in negative dysphotopsia.

J Cataract Refract Surg 2021 01;47(1):139-140

Simpson Optics LLC, Arlington, Texas, USA.

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http://dx.doi.org/10.1097/j.jcrs.0000000000000432DOI Listing
January 2021

Efficacy and Safety of Tranexamic Acid in Emergency Trauma: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Mar 3;10(5). Epub 2021 Mar 3.

1st Chair and Department of Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland.

In trauma patients, bleeding can lead to coagulopathy, hemorrhagic shock, and multiorgan failure, and therefore is of fundamental significance in regard to early morbidity. We conducted a meta-analysis to evaluate the efficacy and safety of tranexamic acid (TXA) in civil and military settings and its impact on in-hospital mortality (survival to hospital discharge or 30-day survival), intensive care unit and hospital length of stay, incidence of adverse events (myocardial infarct and neurological complications), and volume of blood product transfusion. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic review of the literature using PubMed, Scopus, EMBASE, Web of Science, and the Cochrane Central Register and Controlled Trials (CENTRAL) database was conducted from inception to 10 January 2021. In-hospital mortality was reported in 14 studies and was 15.5% for the TXA group as compared with 16.4% for the non-TXA group (OR = 0.81, 95% CI 0.62-1.06, I = 83%, = 0.12). In a civilian TXA application, in-hospital mortality in the TXA and non-TXA groups amounted to 15.0% and 17.1%, respectively (OR = 0.69, 95% CI 0.51-0.93, = 0.02, I = 78%). A subgroup analysis of the randomized control trial (RCT) studies showed a statistically significant reduction in in-hospital mortality in the TXA group (14.3%) as compared with the non-TXA group (15.7%, OR = 0.89, 95% CI 0.83-0.96, = 0.003, I = 0%). To summarize, TXA used in civilian application reduces in-hospital mortality. Application of TXA is beneficial for severely injured patients who undergoing shock and require massive blood transfusions. Patients who undergo treatment with TXA should be monitored for clinical signs of thromboembolism, since TXA is a standalone risk factor of a thromboembolic event and the D-dimers in traumatic patients are almost always elevated.
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http://dx.doi.org/10.3390/jcm10051030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958951PMC
March 2021

Patients with triple-negative, JAK2V617F- and CALR-mutated essential thrombocythemia share a unique gene expression signature.

Blood Adv 2021 02;5(4):1059-1068

Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.

Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative" (TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n = 6; JAK2V617F, n = 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFκB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPβ and NFκB. For "true" TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFκB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation.
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http://dx.doi.org/10.1182/bloodadvances.2020003172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903233PMC
February 2021

Lessons Learned During a Pandemic Year.

Opflow 2020 Dec 4;46(12):6-7. Epub 2020 Dec 4.

The COVID-19 pandemic has affected the water sector in many ways, shifting industry expectations, priorities, workflows, and more. But through it all, the mission of keeping drinking water safe and readily available remained a priority.
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http://dx.doi.org/10.1002/opfl.1467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753487PMC
December 2020

New Homozygous Missense MSMO1 Mutation in Two Siblings with SC4MOL Deficiency Presenting with Psoriasiform Dermatitis.

Cytogenet Genome Res 2020 6;160(9):523-530. Epub 2020 Nov 6.

Department of Dermatology, School of Medicine, Ankara University, Ankara, Turkey.

Sterol-C4-methyl oxidase (SC4MOL) deficiency was recently described as an autosomal recessive cholesterol biosynthesis disorder caused by mutations in the MSMO1 (sometimes also referred to as SC4MOL) gene. To date, 5 patients from 4 unrelated families with SC4MOL deficiency have been reported. Diagnosis can be challenging as the biochemical accumulation of methylsterols can affect global development and cause skin and ocular pathology. Herein, we describe 2 siblings from a consanguineous Turkish family with SC4MOL deficiency presenting with psoriasiform dermatitis, ocular abnormalities (nystagmus, optic hypoplasia, myopia, and strabismus), severe intellectual disability, and growth and motor delay. We undertook whole-exome sequencing and identified a new homozygous missense mutation c.81A>C; p.Asn27Thr in MSMO1. Segregation analysis in all available family members confirmed recessive inheritance of the mutation. The siblings were treated with a combination of oral and topical statin and cholesterol which resulted in clinical improvement. This study demonstrates how genomics-based diagnosis and therapy can be helpful in clinical practice.
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http://dx.doi.org/10.1159/000511126DOI Listing
December 2020

Crowding-induced interactions of ring polymers.

Soft Matter 2021 Jan 6;17(1):16-23. Epub 2020 Nov 6.

Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, Tennessee 37996, USA.

Macromolecular crowding and the presence of surfaces can significantly impact the spatial organization of biopolymers. While the importance of crowding-induced depletion interactions in biology has been recognized, much remains to be understood about the effect of crowding on biopolymers such as DNA plasmids. A fundamental problem highlighted by recent experiments is to characterize the impact of crowding on polymer-polymer and polymer-surface interactions. Motivated by the need for quantitative insight, we studied flexible ring polymers in crowded environments using Langevin dynamics simulations. The simulations demonstrated that crowding can lead to compaction of isolated ring polymers and enhanced interactions between two otherwise repulsive polymers. Using umbrella sampling, we determined the potential of mean force (PMF) between two ring polymers as a function of their separation distance at different volume fractions of crowding particles, φ. An effective attraction emerged at φ≈ 0.4, which is similar to the degree of crowding in cells. Analogous simulations showed that crowding can lead to strong adsorption of a ring polymer to a wall, with an effective attraction to the wall emerging at a smaller volume fraction of crowders (φ≈ 0.2). Our results reveal the magnitude of depletion interactions in a biologically-inspired model and highlight how crowding can be used to tune interactions in both cellular and cell-free systems.
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http://dx.doi.org/10.1039/d0sm01847cDOI Listing
January 2021

For a prefigurative pandemic politics: Disrupting the racial colonial quarantine.

Authors:
Michael Simpson

Polit Geogr 2021 Jan 4;84:102274. Epub 2020 Sep 4.

School of Geography and Sustainable Development, University of St Andrews, Irvine Building, North Street, St Andrews, KY16 9AL, UK.

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http://dx.doi.org/10.1016/j.polgeo.2020.102274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471852PMC
January 2021

Blaschko-linear lichen planus: Clinicopathological and genetic analysis.

J Dermatol 2020 Nov 12;47(11):e384-e385. Epub 2020 Aug 12.

St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK.

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http://dx.doi.org/10.1111/1346-8138.15546DOI Listing
November 2020

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Nat Med 2020 07 13;26(7):1102-1113. Epub 2020 Jul 13.

Department of Biomedical Engineering, Columbia University, New York, NY, USA.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.
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http://dx.doi.org/10.1038/s41591-020-0971-8DOI Listing
July 2020

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.

Epilepsia 2020 05 29;61(5):995-1007. Epub 2020 May 29.

Meyer Children's Hospital, University of Florence, Florence, Italy.

Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE).

Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies.

Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each.

Significance: MAE is associated with significant neurodevelopmental impairment. MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity.
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http://dx.doi.org/10.1111/epi.16508DOI Listing
May 2020

Macromolecular Crowding Affects Voltage-Dependent Alamethicin Pore Formation in Lipid Bilayer Membranes.

J Phys Chem B 2020 06 10;124(25):5095-5102. Epub 2020 Jun 10.

The Bredesen Center for Interdisciplinary Research, University of Tennessee, Knoxville, Tennessee 37996, United States.

Macromolecular crowding is known to modulate chemical equilibria, reaction rates, and molecular binding events, both in aqueous solutions and at lipid bilayer membranes, natural barriers that enclose the crowded environments of cells and their subcellular compartments. Previous studies on the effects of macromolecular crowding in aqueous compartments on conduction through membranes have focused on single-channel ionic conduction through previously formed pores at thermodynamic equilibrium. Here, the effects of macromolecular crowding on the mechanism of pore formation itself were studied using the droplet interface bilayer (DIB) technique with the voltage-dependent pore-forming peptide alamethicin (alm). Macromolecular crowding was varied using 8 kDa molecular weight polyethylene glycol (PEG8k) or 500 kDa dextran (DEX500k) in two aqueous droplets on both sides of the bilayer membrane. In general, voltage thresholds for pore formation in the presence of crowders in the droplets decreased compared to their values in the absence of crowders, due to excluded volume effects, water binding by PEG, and changes in the ordering of water molecules and hydrogen-bonding interactions involving the polar lipid headgroups. In addition, asymmetric crowder loading (e.g., PEG8k-DEX500k on either side of the membrane) resulted in transmembrane osmotic pressure gradients that either enhanced or degraded the ionic conduction through the pores.
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http://dx.doi.org/10.1021/acs.jpcb.0c01650DOI Listing
June 2020

Techniques for Obtaining High-quality Recordings in Electrocochleography.

Front Syst Neurosci 2020 15;14:18. Epub 2020 Apr 15.

Audiology Incorporated, Arden Hills, MN, United States.

There are several technical challenges to obtaining high-quality recordings of cochlear potentials in human electrocochleography (ECochG). These challenges include electrical artifacts from devices such as acoustic transducers, biological artifacts from excessive myogenic and electroencephalographic potentials, and issues associated with the placement of a tympanic membrane (TM) electrode on the eardrum. This article presents approaches for dealing with these challenges for ECochG measurement using a TM electrode. Emphasis is placed on eliminating stimulus artifact, optimizing the placement of the electrode, and comparing a custom-made electrode with a commercially-available electrode. This comparison revealed that the custom-made electrode results in greater subject comfort, superior ease of placing the electrode on the eardrum, and larger compound action potential (CAP) amplitudes.
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http://dx.doi.org/10.3389/fnsys.2020.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176302PMC
April 2020

Mutations in SPATA13/ASEF2 cause primary angle closure glaucoma.

PLoS Genet 2020 04 27;16(4):e1008721. Epub 2020 Apr 27.

NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.

Current estimates suggest 50% of glaucoma blindness worldwide is caused by primary angle-closure glaucoma (PACG) but the causative gene is not known. We used genetic linkage and whole genome sequencing to identify Spermatogenesis Associated Protein 13, SPATA13 (NM_001166271; NP_001159743, SPATA13 isoform I), also known as ASEF2 (Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor 2), as the causal gene for PACG in a large seven-generation white British family showing variable expression and incomplete penetrance. The 9 bp deletion, c.1432_1440del; p.478_480del was present in all affected individuals with angle-closure disease. We show ubiquitous expression of this transcript in cell lines derived from human tissues and in iris, retina, retinal pigment and ciliary epithelia, cornea and lens. We also identified eight additional mutations in SPATA13 in a cohort of 189 unrelated PACS/PAC/PACG samples. This gene encodes a 1277 residue protein which localises to the nucleus with partial co-localisation with nuclear speckles. In cells undergoing mitosis SPATA13 isoform I becomes part of the kinetochore complex co-localising with two kinetochore markers, polo like kinase 1 (PLK-1) and centrosome-associated protein E (CENP-E). The 9 bp deletion reported in this study increases the RAC1-dependent guanine nucleotide exchange factors (GEF) activity. The increase in GEF activity was also observed in three other variants identified in this study. Taken together, our data suggest that SPATA13 is involved in the regulation of mitosis and the mutations dysregulate GEF activity affecting homeostasis in tissues where it is highly expressed, influencing PACG pathogenesis.
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http://dx.doi.org/10.1371/journal.pgen.1008721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233598PMC
April 2020

Seahorse Hotels: Use of artificial habitats to support populations of the endangered White's seahorse Hippocampus whitei.

Mar Environ Res 2020 May 18;157:104861. Epub 2019 Dec 18.

Fisheries Research, NSW - Department of Primary Industries NSW, 2315, Australia.

The provision of temporary, specially designed artificial habitat may help support populations of the Endangered Whites' seahorse Hippocampus whitei in the face of rapid coastal urbanisation and declining natural habitats. Three designs of artificial habitat (Seahorse Hotels) were installed in Port Stephens, New South Wales, Australia, where natural habitats had significantly declined. Mark recapture surveys were used to assess seahorse site fidelity and population parameters, and the effect of Seahorse Hotel design on seahorse abundance, epibiotic growth and mobile epifaunal seahorse prey was determined. The Seahorse Hotels sustained a substantial population of seahorses (64; 57-72 95% confidence intervals) in comparison to recent local population estimates. There were no significant differences in seahorse abundance, mobile epifauna or epibiotic growth among the three different hotel designs. This research demonstrated that H. whitei will inhabit Seahorse Hotels in absence of natural habitat, and additional complexity in these artificial structures was not necessary to support seahorse populations. Temporary structures such as Seahorse Hotels will be a valuable tool in supporting H. whitei and other Syngnathid populations through infrastructure maintenance or habitat modification.
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http://dx.doi.org/10.1016/j.marenvres.2019.104861DOI Listing
May 2020

Intraocular lens far peripheral vision: image detail and negative dysphotopsia.

J Cataract Refract Surg 2020 03;46(3):451-458

From Simpson Optics LLC, Arlington, Texas, USA.

Purpose: To evaluate negative dysphotopsia in the far periphery of the pseudophakic eye by generating simulated images of text charts.

Setting: Consultancy.

Design: Laboratory study.

Methods: Simulated images of a peripheral text chart were created using a ray-trace model of a pseudophakic eye. The point spread function varies strongly with a radial location. Retinal angles subtended at the second nodal point were used to linearly scale retinal locations to a polar plot in object space, weighting rays by the object luminance, the total transmittance, and a cosine normalization for pupil effects. Improved scaling using a phakic 70-year-old eye was also explored.

Results: Images demonstrate a distinct shadow with a 2.5 mm pupil between the upper limit of the text image formed by the intraocular lens (IOL) and a second larger image due to light missing the IOL. The shadow is rapidly softened by a small increase in pupil diameter.

Conclusions: The images verified characteristics that previously were only inferred indirectly: (1) With a 2.5 mm pupil, there is a prominent dark shadow. (2) Light missing the IOL experiences lower power and forms a larger image and also comes from a lower visual angle. (3) A small increase in pupil diameter causes the shadow to fade. The calculations showed that imaging in the far periphery is very different for the pseudophakic eye in comparison with the phakic eye. The limit of the focused image is probably the primary cause of the shadow, yet relatively few patients find this to be bothersome.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000103DOI Listing
March 2020

Angle alpha orientation and magnitude distribution in a cataract surgery population.

J Cataract Refract Surg 2020 Mar;46(3):372-377

From the Department of Ophthalmology, Mayo Clinic (Mahr, Erie), Rochester, Minnesota, and Simpson Optics LLC (Simpson), Arlington, Texas, USA.

Purpose: To report normative angle alpha orientation and magnitude distribution in a cataract surgery patient population.

Setting: U.S. academic medical center.

Design: Retrospective review.

Methods: A total of 11 871 wavefront aberrometer/corneal topographer angle alpha measurements were performed over 40 months, yielding 8773 bilateral measurements (73.9%) with zero bad wavefront datapoints. The analysis was limited to the first right-eye scan for 3382 unique patients. The angle alpha magnitudes (millimeters) and orientations (degrees) were analyzed for these unique right eyes.

Results: For the 3,382 unique patients, the mean angle alpha magnitude was 0.44 ± 0.15 mm (median, 0.44 mm; 25th and 75th percentiles 0.34 mm, 0.53 mm). Angle alpha orientation was predominantly horizontal (P < .01), with a mean of 186 ± 32 degrees. The expected point of intraocular lens (IOL) centration (EPIC) based on the geometric center of the corneal limbus was temporal to the visual axis in 3212 eyes (95%), nasal in 92 eyes (2.7%), inferior in 56 eyes (1.7%), and superior in 22 eyes (0.6%). The mean angle alpha magnitude was 0.3 mm or less in 607 eyes (18%) and 0.5 mm or greater in 1089 eyes (32%).

Conclusions: Angle alpha is a predominantly horizontal phenomenon with a mean EPIC of 0.44 mm temporal to the visual axis. This information may assist in determining eligibility for patients in multifocal IOL implantation.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000066DOI Listing
March 2020

The Effects of Baduanjin Qigong on Postural Stability, Proprioception, and Symptoms of Patients With Knee Osteoarthritis: A Randomized Controlled Trial.

Front Med (Lausanne) 2019 10;6:307. Epub 2020 Jan 10.

Exercise and Mental Health Laboratory, Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, China.

Knee osteoarthritis is a common disease affecting a large number of old individuals worldwide. This study aimed to explore the effects of Baduanjin Qigong in patients with knee osteoarthritis. Fifty participants with knee osteoarthritis were randomly assigned to either an experimental group ( = 25) or a control group ( = 25). Participants in the experimental group received Baduanjin Qigong training for 12 weeks, with three sessions per week lasting 40 min per session. Participants in the control group did not receive any additional physical training. All of participants completed outcome (proprioception, postural stability, and functional ability) assessments at three time points (baseline, Week 8, 12). Proprioception and Western Ontario and McMaster Universities Osteoarthritis Index function were statistically improved at eighth and 12th week of the intervention in the Baduanjin Qigong group ( < 0.05), while the control group did not have any significant changes. For postural stability at the anterior-posterior direction with eyes closed, Baduanjin Qigong group showed significant improvement compared to controls after the 12 weeks of intervention ( < 0.05). Regular Baduanjin Qigong practice helped the improvement of knee joint proprioception and postural stability, and reduction of pain, stiffness, and functional impairments of old adults with knee osteoarthritis. Well-designed randomized controlled trials with long-term assessment are needed. The trial was registered in Chinese Clinical Trial Registry (ChiCTR-IOR-16010042). URL: http://www.chictr.org.cn/hvshowproject.aspx?id=10550.
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http://dx.doi.org/10.3389/fmed.2019.00307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966958PMC
January 2020

Psoriasis and Genetics.

Acta Derm Venereol 2020 01 30;100(3):adv00030. Epub 2020 Jan 30.

Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.
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http://dx.doi.org/10.2340/00015555-3384DOI Listing
January 2020

Urologic Conditions in Infants and Children: Inguinal Hernia, Hydrocele, and Cryptorchidism.

FP Essent 2020 Jan;488:16-20

LewisGale Medical Center Family Medicine Residency Program, 1900 Electric Rd Salem, VA 24153.

In children, inguinal hernias, hydroceles, and cryptorchidism typically are associated with a patent processus vaginalis. Inguinal hernias occur in 3.5%-5% of full-term newborns and 9%-11% of premature newborns. Inguinal hernias are characterized by an intermittent mass in the groin that may be reducible or incarcerated. Incarcerated hernias usually are painful, can cause vomiting, and require prompt intervention. The definitive treatment is surgery, and urgency depends on symptoms and ability to reduce the hernia. Hydrocele is an accumulation of serous fluid in the tunica vaginalis around the testicle that presents as a painless, fluctuant mass. Most hydroceles resolve spontaneously by age 1 year. Cryptorchidism occurs when one or both testes do not migrate to the scrotum. The diagnosis is made via history and physical examination. Spontaneous descent of the testis may occur before age 6 months but referral to a surgical subspecialist is indicated if descent does not occur.
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January 2020

Urologic Conditions in Infants and Children: Circumcision.

Authors:
Michael Simpson

FP Essent 2020 Jan;488:11-15

LewisGale Medical Center Family Medicine Residency Program, 1900 Electric Rd Salem, VA 24153.

Circumcision is the surgical removal of some or all of the foreskin (ie, prepuce) of the penis. Among high-resource countries, the United States is the only country in which the majority of newborns are circumcised for nonreligious reasons. The rate of circumcision in the United States has been decreasing. Circumcised males have a lower risk of urinary tract infections, penile cancer, and several sexually transmitted infections. The benefit of circumcision is greater for males with certain urologic conditions, such as isolated hydronephrosis, vesicoureteral reflux, and ureteropelvic junction obstruction. Complications develop in approximately 1 of every 200 procedures. The American Academy of Pediatrics and the American Academy of Family Physicians recommend continued access to circumcision on an elective basis and conclude that the benefits outweigh the risks. However, they do not endorse routine neonatal circumcision. Local anesthesia should be used to decrease pain during the procedure. Three devices commonly are used. Each has risks and benefits, and no one device has been proven to be superior to another.
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January 2020

Homozygous Nonsense Mutation in DSC3 Resulting in Skin Fragility and Hypotrichosis.

J Invest Dermatol 2020 06 29;140(6):1285-1288. Epub 2019 Nov 29.

St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.10.015DOI Listing
June 2020

Coagulation Factor XIII-A Subunit Missense Mutation in the Pathobiology of Autosomal Dominant Multiple Dermatofibromas.

J Invest Dermatol 2020 03 4;140(3):624-635.e7. Epub 2019 Sep 4.

St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London, United Kingdom. Electronic address:

Dermatofibromas are common benign skin lesions, the etiology of which is poorly understood. We identified two unrelated pedigrees in which there was autosomal dominant transmission of multiple dermatofibromas. Whole exome sequencing revealed a rare shared heterozygous missense variant in the F13A1 gene encoding factor XIII subunit A (FXIII-A), a transglutaminase involved in hemostasis, wound healing, tumor growth, and apoptosis. The variant (p.Lys679Met) has an allele frequency of 0.0002 and is predicted to be a damaging mutation. Recombinant human Lys679Met FXIII-A demonstrated reduced fibrin crosslinking activity in vitro. Of note, the treatment of fibroblasts with media containing Lys679Met FXIII-A led to enhanced adhesion, proliferation, and type I collagen synthesis. Immunostaining revealed co-localization between FXIII-A and α4β1 integrins, more prominently for Lys679Met FXIII-A than the wild type. In addition, both the α4β1 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine-Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may lead to a conformational change in the FXIII-A protein that enhances α4-integrin binding and provides insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma.
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http://dx.doi.org/10.1016/j.jid.2019.08.441DOI Listing
March 2020
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