Publications by authors named "Daniel Thomas"

585 Publications

Health anxiety and attentional control interact to predict uncertainty-related attentional biases.

J Behav Ther Exp Psychiatry 2021 Oct 16;74:101697. Epub 2021 Oct 16.

Auburn University, USA. Electronic address:

Background And Objectives: Current theories of health anxiety and a growing body of empirical literature suggest that those high in health anxiety symptoms might find uncertainty itself threatening and demonstrate attentional biases for uncertainty-related information (ABU). Moreover, a dual processes model of attention would suggest that individual differences in attentional control might modify such a relationship. The present study was designed to explore this proposed health anxiety-ABU relationship and also to consider attentional control as a moderator of theoretical and clinical relevance.

Methods: Undergraduate participants (N = 148) completed a self-report measure of health anxiety symptoms and two performance-based tasks to assess ABU and attentional control.

Results: Hierarchical regression analyses showed a significant interaction between health anxiety and attention control in predicting attentional disengagement from, but not engagement with, uncertainty-related words. Specifically, results of the simple slopes analysis suggested that those with elevated health anxiety symptoms and better attentional control may use top-down attentional control processes to disengage their attention from distressing uncertainty-related stimuli faster than those with worse attentional control.

Limitations: The analogue sample is a study limitation.

Conclusions: Results provide new insights into the nature of attentional biases within health anxiety. Results are discussed in light of recent work on attentional control and avoidance-based psychopathology.
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http://dx.doi.org/10.1016/j.jbtep.2021.101697DOI Listing
October 2021

Helium Nanodroplet Infrared Action Spectroscopy of the Proton-Bound Dimer of Hydrogen Sulfate and Formate: Examining Nuclear Quantum Effects.

J Phys Chem A 2021 Oct 15. Epub 2021 Oct 15.

Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.

The proton-bound dimer of hydrogen sulfate and formate is an archetypal structure for ionic hydrogen-bonding complexes that contribute to biogenic aerosol nucleation. Of central importance for the structure and properties of this complex is the location of the bridging proton connecting the two conjugate base moieties. The potential energy surface for bridging proton translocation features two local minima, with the proton localized at either the formate or hydrogen sulfate moiety. However, electronic structure methods reveal a shallow potential energy surface governing proton translocation, with a barrier on the order of the zero-point energy. This shallow potential complicates structural assignment and necessitates a consideration of nuclear quantum effects. In this work, we probe the structure of this complex and its isotopologues, utilizing infrared (IR) action spectroscopy of ions captured in helium nanodroplets. The IR spectra indicate a structure in which a proton is shared between the hydrogen sulfate and formate moieties, HSO···H···OOCH. However, because of the nuclear quantum effects and vibrational anharmonicities associated with the shallow potential for proton translocation, the extent of proton displacement from the formate moiety remains unclear, requiring further experiments or more advanced theoretical treatments for additional insight.
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http://dx.doi.org/10.1021/acs.jpca.1c05705DOI Listing
October 2021

Hospitalizations for cardiovascular diseases attributable to tobacco smoking in France in 2015.

Eur J Prev Cardiol 2021 Oct;28(12):1327-1333

Non-Communicable Diseases and Trauma Division, Santé Publique France, Saint Maurice, France.

Aims: Tobacco smoking is a major risk factor for many cardiovascular diseases. In France, the daily smoking prevalence is among the highest in high-income European countries. This study estimated the number of hospitalizations for cardiovascular diseases attributable to smoking in France in 2015, and the number of stays that could have been avoided if there had been 10% less current smokers or if the prevalence of current smokers had been 20%.

Methods: Age- and sex-specific attributable fractions were calculated by combining relative risks extracted from the literature with the prevalence of smoking estimated in the 2014 Health Barometer, a national representative survey. These fractions were applied to hospitalization stays with a primary diagnosis for a cardiovascular disease whose risk is known to increase with smoking.

Results: In France in 2015, 250,813 hospital stays (95% uncertainty interval=234,869-269,807) related to a cardiovascular condition were estimated as attributable to smoking. This represented 21% of all stays for a cardiovascular condition. Ischemic heart disease accounted for the largest share of smoking-related stays (39%). If the number of current smokers had been 10% lower or if the prevalence of smoking in the population had dropped to below 20%, 5867 stays and 25,911 stays, respectively, would have been prevented.

Conclusions: In France, a large number of hospital stays for cardiovascular disease are attributable to tobacco smoking. A 10% reduction in smoking would avoid nearly 6000 hospital stays per year; more than 25,000 annual hospital stays if only 20% of the French population smoked.
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http://dx.doi.org/10.1177/2047487319885462DOI Listing
October 2021

Tobacco-related cardiovascular risk in women: New issues and therapeutic perspectives.

Arch Cardiovasc Dis 2021 Sep 27. Epub 2021 Sep 27.

Team Physiopathlogy and Epidemiology Cerebro-Cardiovascular (PEC2), EA 7460, University of Burgundy Franche-Comté, Faculté des Sciences de Santé, 7, boulevard Jeanne d'Arc, 21000 Dijon, France. Electronic address:

Background: Smoking is the main modifiable risk factor for stroke and myocardial infarction, particularly in women; its prevalence in France is evolving, and new patterns of nicotine consumption have emerged.

Aims: To present contemporary data on smoking prevalence and the use of electronic cigarettes, and to describe current knowledge of the cardiovascular risk specificities and the effectiveness of withdrawal methods in women.

Method: We identified studies by searching the MEDLINE bibliographic database between 1995 and 2020, and the Weekly Epidemiological Bulletin (Bulletin Épidémiologique Hebdomadaire) published by the French health authorities.

Result: In recent years, smoking prevalence among French women has decreased overall, except in the oldest age group (aged>55 years). At the same time, the incidence of hospitalization for cardiovascular events has increased worryingly among women smokers aged<65 years. Active smoking in women is associated with an increased risk of premature myocardial infarction, and a risk of stroke that increases with the number of cigarettes consumed per day; it is also responsible for increased cardiovascular events in women taking oestrogen-progestin contraception. Quitting smoking reverses these effects in the long term, and women are just as likely to quit smoking as men.

Conclusions: Stopping smoking must be a priority objective for women smokers, for primary and secondary prevention, and they should systematically be offered a validated method of cessation or even electronic cigarettes.
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http://dx.doi.org/10.1016/j.acvd.2021.06.013DOI Listing
September 2021

Evaluation of the Thermo Scientific SureTect Salmonella Species PCR Assay in a Broad Range of Foods and Select Environmental Surfaces: Pre-Collaborative and Collaborative Study: First Action 2021.02.

J AOAC Int 2021 Sep 29. Epub 2021 Sep 29.

Thermo Fisher Scientific, Wade Road, Basingstoke, Hampshire, RG24 8PW, United Kingdom.

Background: The Thermo Scientific™ SureTect™ Salmonella species PCR Assay utilizes Solaris™ reagents for performing PCR for the rapid and specific detection of Salmonella species in a broad range of foods and select environmental surfaces.

Objectives: To demonstrate reproducibility of the Thermo Scientific SureTect Salmonella species PCR Assay in a collaborative study using a challenging matrix, cocoa powder. To extend the scope of the method.

Method: In the collaborative study, the candidate method was compared to the U.S. Food and Drug Administration/Bacteriological Analytical Manual (FDA/BAM) Chapter 5 Salmonella reference method. The candidate method used two PCR thermocyclers, the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR instrument (QS5) and the Applied Biosystems 7500 Fast Real-Time PCR instrument (7500 Fast). Fourteen participants from 9 laboratories located within the United States and Europe were solicited for the collaborative study, with 12 participants submitting valid data. Three levels of contamination were evaluated for each matrix. Statistical analysis was conducted according to the probability of detection (POD) statistical model. In addition, 11 matrix studies were performed comparing the candidate method to the FDA/BAM Chapter 5 or U.S. Department of Agriculture, Food Safety and Inspection Service, Microbiology Laboratory Guidebook (USDA FSIS MLG) 4.10 Isolation and Identification of Salmonella from Meat, Poultry, Pasteurized Egg, and Siluriformes (Fish) Products and Carcass and Environmental Sponges reference method. Nine of these matrices were also compared to the EN ISO 6579-1:2017/Amd.1:2020(E) Microbiology of the food chain-Horizontal method for the detection, enumeration and serotyping of Salmonella-Part 1: Detection of Salmonella spp.-AMENDMENT 1: Broader range of incubation temperatures, amendment to the status of Annex D, and correction of the composition of MSRV and SC reference method.

Results: In the collaborative study, the difference in laboratory results indicate equivalence between the candidate method and reference method for the matrix evaluated and the method demonstrated acceptable inter-laboratory reproducibility as determined in the collaborative evaluation. False positive and false negative rates were determined for the matrix and produced values of < 2%. The two PCR thermocyclers (QS5, 7500 Fast) performed equivalently. There were no result differences between candidate method confirmations and reference method confirmations. In the pre-collaborative matrix extension, the results from the matrix studies showed a comparable performance between the candidate method and the tested reference methods.

Conclusion: Based on the data generated, the method demonstrated acceptable inter-laboratory reproducibility data and statistical analysis.

Highlights: Due to the Covid-19 pandemic, some participants had to be trained remotely. Additionally, 375 g cocoa powder is known to be a challenging matrix for PCR methods. No unusual cross-contamination or false positive/negative data was reported, highlighting the ease of use, reproducibility, and robustness of the method.
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http://dx.doi.org/10.1093/jaoacint/qsab122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500116PMC
September 2021

Development of an intracellular quantitative assay to measure compound binding kinetics.

Cell Chem Biol 2021 Sep 11. Epub 2021 Sep 11.

Medicine Design, Medicinal Science and Technology, GlaxoSmithKline, Stevenage SG1 2NY, UK; GSK-Francis Crick Institute Linklabs, Medicinal Science and Technology, GlaxoSmithKline, Stevenage SG1 2NY, UK. Electronic address:

Contemporary drug discovery typically quantifies the effect of a molecule on a biological target using the equilibrium-derived measurements of IC, EC, or K. Kinetic descriptors of drug binding are frequently linked with the effectiveness of a molecule in modulating a disease phenotype; however, these parameters are yet to be fully adopted in early drug discovery. Nanoluciferase bioluminescence resonance energy transfer (NanoBRET) can be used to measure interactions between fluorophore-conjugated probes and luciferase fused target proteins. Here, we describe an intracellular NanoBRET competition assay that can be used to quantify cellular kinetic rates of compound binding to nanoluciferase-fused bromodomain and extra-terminal (BET) proteins. Comparative rates are generated using a cell-free NanoBRET assay and by utilizing orthogonal recombinant protein-based methodologies. A screen of known pan-BET inhibitors is used to demonstrate the value of this approach in the investigation of kinetic selectivity between closely related proteins.
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http://dx.doi.org/10.1016/j.chembiol.2021.07.018DOI Listing
September 2021

Learning to feed in the dark: how light level influences feeding in the hawkmoth .

Biol Lett 2021 09 15;17(9):20210320. Epub 2021 Sep 15.

Department of Biology, University of Washington, Seattle, Washington.

Nocturnal insects like moths are essential for pollination, providing resilience to the diurnal pollination networks. Moths use both vision and mechanosensation to locate the nectary opening in the flowers with their proboscis. However, increased light levels due to artificial light at night (ALAN) pose a serious threat to nocturnal insects. Here, we examined how light levels influence the efficacy by which the crepuscular hawkmoth locates the nectary. We used three-dimensional-printed artificial flowers fitted with motion sensors in the nectary and machine vision to track the motion of hovering moths under two light levels: 0.1 lux (moonlight) and 50 lux (dawn/dusk). We found that moths in higher light conditions took significantly longer to find the nectary, even with repeated visits to the same flower. In addition to taking longer, moths in higher light conditions hovered further from the flower during feeding. Increased light levels adversely affect learning and motor control in these animals.
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http://dx.doi.org/10.1098/rsbl.2021.0320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440038PMC
September 2021

Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode.

J Med Chem 2021 Sep 11;64(18):13780-13792. Epub 2021 Sep 11.

Medicines Research Centre, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage SG1 2NY, U.K.

Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clinical candidate compound (GSK251). Removal of an embedded Ames-positive heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound . Further optimization to avoid glutathione trapping, to enhance potency and selectivity, and to optimize an oral pharmacokinetic profile led to the discovery of compound (GSK215) that had a low predicted daily dose (45 mg, b.i.d) and a rat toxicity profile suitable for further development.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01102DOI Listing
September 2021

Determinants for hospitalisations, intensive care unit admission and death among 20,293 reported COVID-19 cases in Portugal, March to April 2020.

Euro Surveill 2021 Aug;26(33)

Comprehensive Health Research Centre, Universidade Nova de Lisboa.

BackgroundDeterminants of hospitalisation, intensive care unit (ICU) admission and death are still unclear for COVID-19. Few studies have adjusted for confounding for different clinical outcomes including all reported cases within a country.AimWe used routine surveillance data from Portugal to identify risk factors for severe COVID-19 outcomes, and to support risk stratification, public health interventions, and planning of healthcare resources.MethodsWe conducted a retrospective cohort study including 20,293 laboratory-confirmed cases of COVID-19 reported between 1 March and 28 April 2020 through the national epidemiological surveillance system. We calculated absolute risk, relative risk (RR) and adjusted relative risk (aRR) to identify demographic and clinical factors associated with hospitalisation, ICU admission and death using Poisson regressions.ResultsIncreasing age (≥ 60 years) was the major determinant for all outcomes. Age ≥ 90 years was the strongest determinant of hospital admission (aRR: 6.1), and 70-79 years for ICU (aRR: 10.4). Comorbidities of cardiovascular, immunodeficiency, kidney and lung disease (aRR: 4.3, 2.8, 2.4, 2.0, respectively) had stronger associations with ICU admission, while for death they were kidney, cardiovascular and chronic neurological disease (aRR: 2.9, 2.6, 2.0).ConclusionsOlder age was the strongest risk factor for all severe outcomes. These findings from the early stages of the COVID-19 pandemic support risk-stratified public health measures that should prioritise protecting older people. Epidemiological scenarios and clinical guidelines should consider this, even though under-ascertainment should also be considered.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.33.2001059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380973PMC
August 2021

Ethnic variation in outcome of people hospitalised during the first COVID-19 epidemic wave in Wales (UK): an analysis of national surveillance data using Onomap, a name-based ethnicity classification tool.

BMJ Open 2021 08 18;11(8):e048335. Epub 2021 Aug 18.

Public Health Wales, Health Protection Division, Cardiff, UK.

Objective: To identify ethnic differences in proportion positive for SARS-CoV-2, and proportion hospitalised, proportion admitted to intensive care and proportion died in hospital with COVID-19 during the first epidemic wave in Wales.

Design: Descriptive analysis of 76 503 SARS-CoV-2 tests carried out in Wales to 31 May 2020. Cohort study of 4046 individuals hospitalised with confirmed COVID-19 between 1 March and 31 May. In both analyses, ethnicity was assigned using a name-based classifier.

Setting: Wales (UK).

Primary And Secondary Outcomes: Admission to an intensive care unit following hospitalisation with a positive SARS-CoV-2 PCR test. Death within 28 days of a positive SARS-CoV-2 PCR test.

Results: Using a name-based ethnicity classifier, we found a higher proportion of black, Asian and ethnic minority people tested for SARS-CoV-2 by PCR tested positive, compared with those classified as white. Hospitalised black, Asian and minority ethnic cases were younger (median age 53 compared with 76 years; p<0.01) and more likely to be admitted to intensive care. Bangladeshi (adjusted OR (aOR): 9.80, 95% CI 1.21 to 79.40) and 'white - other than British or Irish' (aOR: 1.99, 95% CI 1.15 to 3.44) ethnic groups were most likely to be admitted to intensive care unit. In Wales, older age (aOR for over 70 years: 10.29, 95% CI 6.78 to 15.64) and male gender (aOR: 1.38, 95% CI 1.19 to 1.59), but not ethnicity, were associated with death in hospitalised patients.

Conclusions: This study adds to the growing evidence that ethnic minorities are disproportionately affected by COVID-19. During the first COVID-19 epidemic wave in Wales, although ethnic minority populations were less likely to be tested and less likely to be hospitalised, those that did attend hospital were younger and more likely to be admitted to intensive care. Primary, secondary and tertiary COVID-19 prevention should target ethnic minority communities in Wales.
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http://dx.doi.org/10.1136/bmjopen-2020-048335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375451PMC
August 2021

Acetylation of the Catalytic Lysine Inhibits Kinase Activity in PI3Kδ.

ACS Chem Biol 2021 09 16;16(9):1644-1653. Epub 2021 Aug 16.

Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.

Covalent inhibition is a powerful strategy to develop potent and selective small molecule kinase inhibitors. Targeting the conserved catalytic lysine is an attractive method for selective kinase inactivation. We have developed novel, selective inhibitors of phosphoinositide 3-kinase δ (PI3Kδ) which acylate the catalytic lysine, Lys779, using activated esters as the reactive electrophiles. The acylating agents were prepared by adding the activated ester motif to a known selective dihydroisobenzofuran PI3Kδ inhibitor. Three esters were designed, including an acetate ester which was the smallest lysine modification evaluated in this work. Covalent binding to the enzyme was characterized by intact protein mass spectrometry of the PI3Kδ-ester adducts. An enzymatic digest coupled with tandem mass spectrometry identified Lys779 as the covalent binding site, and a biochemical activity assay confirmed that PI3Kδ inhibition was a direct result of covalent lysine acylation. These results indicate that a simple chemical modification such as lysine acetylation is sufficient to inhibit kinase activity. The selectivity of the compounds was evaluated against lipid kinases in cell lysates using a chemoproteomic binding assay. Due to the conserved nature of the catalytic lysine across the kinome, we believe the covalent inhibition strategy presented here could be applicable to a broad range of clinically relevant targets.
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http://dx.doi.org/10.1021/acschembio.1c00225DOI Listing
September 2021

A mechanism for sarcomere breathing: volume change and advective flow within the myofilament lattice.

Biophys J 2021 09 10;120(18):4079-4090. Epub 2021 Aug 10.

School of Physics & School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia. Electronic address:

During muscle contraction, myosin motors anchored to thick filaments bind to and slide actin thin filaments. These motors rely on energy derived from ATP, supplied, in part, by diffusion from the sarcoplasm to the interior of the lattice of actin and myosin filaments. The radial spacing of filaments in this lattice may change or remain constant during contraction. If the lattice is isovolumetric, it must expand when the muscle shortens. If, however, the spacing is constant or has a different pattern of axial and radial motion, then the lattice changes volume during contraction, driving fluid motion and assisting in the transport of molecules between the contractile lattice and the surrounding intracellular space. We first create an advective-diffusive-reaction flow model and show that the flow into and out of the sarcomere lattice would be significant in the absence of lattice expansion. Advective transport coupled to diffusion has the potential to substantially enhance metabolite exchange within the crowded sarcomere. Using time-resolved x-ray diffraction of contracting muscle, we next show that the contractile lattice is neither isovolumetric nor constant in spacing. Instead, lattice spacing is time varying, depends on activation, and can manifest as an effective time-varying Poisson ratio. The resulting fluid flow in the sarcomere lattice of synchronous insect flight muscles is even greater than expected for constant lattice spacing conditions. Lattice spacing depends on a variety of factors that produce radial force, including cross-bridges, titin-like molecules, and other structural proteins. Volume change and advective transport varies with the phase of muscle stimulation during periodic contraction but remains significant at all conditions. Although varying in magnitude, advective transport will occur in all cases in which the sarcomere is not isovolumetric. Akin to "breathing," advective-diffusive transport in sarcomeres is sufficient to promote metabolite exchange and may play a role in the regulation of contraction itself.
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http://dx.doi.org/10.1016/j.bpj.2021.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510861PMC
September 2021

Wing structure and neural encoding jointly determine sensing strategies in insect flight.

PLoS Comput Biol 2021 Aug 11;17(8):e1009195. Epub 2021 Aug 11.

Department of Biology, University of Washington, Seattle, Washington, United States of America.

Animals rely on sensory feedback to generate accurate, reliable movements. In many flying insects, strain-sensitive neurons on the wings provide rapid feedback that is critical for stable flight control. While the impacts of wing structure on aerodynamic performance have been widely studied, the impacts of wing structure on sensing are largely unexplored. In this paper, we show how the structural properties of the wing and encoding by mechanosensory neurons interact to jointly determine optimal sensing strategies and performance. Specifically, we examine how neural sensors can be placed effectively on a flapping wing to detect body rotation about different axes, using a computational wing model with varying flexural stiffness. A small set of mechanosensors, conveying strain information at key locations with a single action potential per wingbeat, enable accurate detection of body rotation. Optimal sensor locations are concentrated at either the wing base or the wing tip, and they transition sharply as a function of both wing stiffness and neural threshold. Moreover, the sensing strategy and performance is robust to both external disturbances and sensor loss. Typically, only five sensors are needed to achieve near-peak accuracy, with a single sensor often providing accuracy well above chance. Our results show that small-amplitude, dynamic signals can be extracted efficiently with spatially and temporally sparse sensors in the context of flight. The demonstrated interaction of wing structure and neural encoding properties points to the importance of understanding each in the context of their joint evolution.
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http://dx.doi.org/10.1371/journal.pcbi.1009195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382179PMC
August 2021

Establishing the impact of COVID-19 on the health outcomes of domiciliary care workers in Wales using routine data: a protocol for the OSCAR study.

Int J Popul Data Sci 2020 14;5(4):1656. Epub 2021 Jul 14.

Centre for Trials Research, Cardiff University, Cardiff, CF14 4YS.

Introduction: Domiciliary care workers (DCWs) continued providing social care to adults in their own homes throughout the COVID-19 pandemic. Evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed, probably reflecting methodological limitations of existing studies. The risk of COVID-19 to workers providing care in people's homes remains unknown.

Objectives: To quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, to explore causes of variation, and to extrapolate to the rest of the UK DCW population.

Methods: Mixed methods design comprising cohort study of DCWs and exploratory qualitative interviews. Data for all registered DCWs in Wales is available via the SAIL Databank using a secured, privacy-protecting encrypted anonymisation process. Occupational registration data for DCWs working during the pandemic will be combined with EHR outcome data within the SAIL Databank including clinical codes that identify suspected and confirmed COVID-19 cases. We will report rates of suspected and confirmed COVID-19 infections and key health outcomes including mortality and explore variation (by factors such as age, sex, ethnicity, deprivation quintile, rurality, employer, comorbidities) using regression modelling, adjusting for clustering of outcome within Health Board, region and employer. A maximum variation sample of Welsh DCWs will be approached for qualitative interview using a strategy to include participants that vary across factors such as sex, age, ethnicity and employer. The interviews will inform the quantitative analysis modelling. We will generalise the quantitative findings to other UK nations.

Discussion: Using anonymised linked occupational and EHR data and qualitative interviews, the OSCAR study will quantify the risk of COVID-19 on DCWs' health and explore sources of variation. This will provide a secure base for informing public health policy and occupational guidance.
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http://dx.doi.org/10.23889/ijpds.v5i4.1656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280712PMC
July 2021

Elucidating the resonance Raman spectra of psittacofulvins.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 3;262:120146. Epub 2021 Jul 3.

Chemistry Department, University of Otago, Dunedin, New Zealand. Electronic address:

Spectroscopic studies into the identification and characterisation of psittacofulvins were performed using resonance Raman spectroscopy. It was confirmed that red colour regions display Raman band wavenumber shifts with excitation wavelength, whereas yellow regions do not. There was, however, one yellow region (Calyptorhynchus banksii) that did display wavenumber shifting with excitation wavelength. The data in Raman band wavenumber shifting is observed may be interpreted as probing sample volumes in which a number of dyes of differing length are present in which comparative resonance Raman signals select out the dyes to differing extents depending on their absorption profile, structurally changes between the ground and excited state and the Raman scattering of particular modes. The observed spectral features suggest the presence of a psittacofulvin with greater conjugation than has been reported previously.
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http://dx.doi.org/10.1016/j.saa.2021.120146DOI Listing
December 2021

Artificially intelligent virtual humans for improving the outcome of complex surgery.

Authors:
Daniel J Thomas

Int J Surg 2021 Aug 12;92:106022. Epub 2021 Jul 12.

Vexon 3D Technologies, Cambridge Science Park, Cambridge, UK. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.106022DOI Listing
August 2021

Neonatal heel prick mass spectrometry identifies metabolic predictors of AML latency.

Leuk Res 2021 Oct 15;109:106644. Epub 2021 Jun 15.

Adelaide Medical School, The University of Adelaide, South Australian Health and Medical Research Institute, Adelaide, SA, Australia. Electronic address:

Ongoing research efforts that consider cancer as a disease of dramatically altered cellular metabolism have accelerated interest in snapshot metabolomics in various human tissues. In this issue of Leukemia Research, Petrick et al performed metabolomic analysis on newborn blood spots and found a number of unexpected ceramide and sphingolipid compounds that may play a role in the development and latency of pediatric acute myeloid leukemia (AML). The chemical complexity and range of cellular metabolites massively exceeds the relatively limited building blocks of the transcriptome or the proteome and has high potential to find novel leukemia-specific macromolecular synthesis pathways, metabolic vulnerabilities and biomarkers.
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http://dx.doi.org/10.1016/j.leukres.2021.106644DOI Listing
October 2021

Women, tobacco, and human rights.

Tob Induc Dis 2021 10;19:48. Epub 2021 Jun 10.

Action on Smoking and Health, Washington, United States.

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http://dx.doi.org/10.18332/tid/137473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191568PMC
June 2021

Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology.

Cell Rep 2021 Jun;35(10):109228

School of Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK. Electronic address:

The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We show that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterized by increased βgal activity, a senescence-associated transcriptional signature, and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. The prevention of early microglial proliferation hinders the development of senescence and DAM, impairing the accumulation of Aβ, as well as associated neuritic and synaptic damage. Overall, our results indicate that excessive microglial proliferation leads to the generation of senescent DAM, which contributes to early Aβ pathology in AD.
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http://dx.doi.org/10.1016/j.celrep.2021.109228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206957PMC
June 2021

Engineering regenerative tissue systems using 3D bioprinting technology. A golden era for reconstructive surgery.

Authors:
Daniel J Thomas

Int J Surg 2021 06 1;90:105982. Epub 2021 Jun 1.

NASA Johnson Space Center, Houston, TX, United States. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.105982DOI Listing
June 2021

Detailed cell-level analysis of sperm nuclear quality among the different hypo-osmotic swelling test (HOST) classes.

J Assist Reprod Genet 2021 Sep 2;38(9):2491-2499. Epub 2021 Jun 2.

Département de Génétique Médicale, Sorbonne Université, INSERM, Maladies génétiques d'expression pédiatrique, APHP, Hôpital d'Enfants Armand Trousseau, 26 avenue du Dr Arnold Netter, F-75012, Paris, France.

Purpose: We studied the quality differences between the different hypo-osmotic swelling test (HOST) classes, as measured by criteria of DNA fragmentation, DNA decondensation, and nuclear architecture. The aim was to find particular HOST classes associated with good-quality metrics, which may be potentially used in ICSI (intra-cytoplasmic sperm injection).

Methods: Ten patients from the Department of Reproductive Medicine at Tenon Hospital (Paris, France) were included. Their semen samples were collected and divided into two fractions: one was incubated in a hypo-osmotic solution as per HOST protocol and sorted by sperm morphology, and a second was incubated without undergoing the HOST protocol to serve as an unsorted baseline. Three parameters were assessed: DNA fragmentation (TUNEL assay), DNA decondensation (chromomycin A3 assay), and nuclear architecture (FISH, with telomeric and whole chromosome painting probes). The different HOST classes were evaluated for these three parameters, and statistical analysis was performed for each class versus the unsorted non-HOST-treated sperm. Results with p<0.05 were considered statistically significant.

Results: For each of the parameters evaluated, we found significant differences between HOST-selected spermatozoa and non-selected spermatozoa. Overall, spermatozoa of HOST classes B and B+ exhibited the highest quality based on four metrics (low DNA fragmentation, low DNA decondensation, short inter-telomeric distance, and small chromosome 1 territory area), while spermatozoa of HOST classes A and G exhibited the poorest quality by these metrics.

Conclusion: In addition to their pathophysiological interest, our results open possibilities of sperm selection prior to ICSI, which may allow for optimization of reproductive outcomes in heretofore unstudied patient populations.
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http://dx.doi.org/10.1007/s10815-021-02232-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490589PMC
September 2021

Genome-wide genetic screen identifies host ubiquitination as important for Legionella pneumophila Dot/Icm effector translocation.

Cell Microbiol 2021 Oct 8;23(10):e13368. Epub 2021 Jun 8.

Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.

The Dot/Icm system of Legionella pneumophila is essential for virulence and delivers a large repertoire of effectors into infected host cells to create the Legionella containing vacuole. Since the secretion of effectors via the Dot/Icm system does not occur in the absence of host cells, we hypothesised that host factors actively participate in Dot/Icm effector translocation. Here we employed a high-throughput, genome-wide siRNA screen to systematically test the effect of silencing 18,120 human genes on translocation of the Dot/Icm effector, RalF, into HeLa cells. For the primary screen, we found that silencing of 119 genes led to increased translocation of RalF, while silencing of 321 genes resulted in decreased translocation. Following secondary screening, 70 genes were successfully validated as 'high confidence' targets. Gene set enrichment analysis of siRNAs leading to decreased RalF translocation, showed that ubiquitination was the most highly overrepresented category in the pathway analysis. We further showed that two host factors, the E2 ubiquitin-conjugating enzyme, UBE2E1, and the E3 ubiquitin ligase, CUL7, were important for supporting Dot/Icm translocation and L. pneumophila intracellular replication. In summary, we identified host ubiquitin pathways as important for the efficiency of Dot/Icm effector translocation by L. pneumophila, suggesting that host-derived ubiquitin-conjugating enzymes and ubiquitin ligases participate in the translocation of Legionella effector proteins and influence intracellular persistence and survival.
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http://dx.doi.org/10.1111/cmi.13368DOI Listing
October 2021

Fluid flow in the sarcomere.

Arch Biochem Biophys 2021 07 21;706:108923. Epub 2021 May 21.

Department of Biology, University of Washington, Seattle, WA 98195, United States.

A highly organized and densely packed lattice of molecular machinery within the sarcomeres of muscle cells powers contraction. Although many of the proteins that drive contraction have been studied extensively, the mechanical impact of fluid shearing within the lattice of molecular machinery has received minimal attention. It was recently proposed that fluid flow augments substrate transport in the sarcomere, however, this analysis used analytical models of fluid flow in the molecular machinery that could not capture its full complexity. By building a finite element model of the sarcomere, we estimate the explicit flow field, and contrast it with analytical models. Our results demonstrate that viscous drag forces on sliding filaments are surprisingly small in contrast to the forces generated by single myosin molecular motors. This model also indicates that the energetic cost of fluid flow through viscous shearing with lattice proteins is likely minimal. The model also highlights a steep velocity gradient between sliding filaments and demonstrates that the maximal radial fluid velocity occurs near the tips of the filaments. To our knowledge, this is the first computational analysis of fluid flow within the highly structured sarcomere.
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http://dx.doi.org/10.1016/j.abb.2021.108923DOI Listing
July 2021

Social media for field epidemiologists (#SoMe4epi): How to use Twitter during the #COVID19 pandemic.

Int J Infect Dis 2021 May 19. Epub 2021 May 19.

European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, (ECDC), Stockholm, Sweden; Public Health Wales, Communicable Disease Surveillance Centre, Cardiff, United Kingdom. Electronic address:

The COVID-19 pandemic has fundamentally changed the way that public health professionals work and communicate. Over a very short time span, remote working arrangements have become the norm, and meetings have shifted online. Physical distancing measures have accelerated a trend toward digital communication and social exchange. At the same time, the work of epidemiologists has been held under a magnifying glass by journalists, governments and the general public, in a way not previously seen. With social media becoming an integral part of our society over the last decade, Twitter is now a key communication tool and platform for social networking among epidemiologists (#EpiTwitter). In this article, we reflect on the use of Twitter by field epidemiologists and public health microbiologists for rapid professional exchange, public communication of science and professional development during the pandemic and the associated risks. For those field epidemiologists new to social media, we discuss how Twitter can be used in a variety of ways, both at their home institutions and during field deployment. These include information dissemination, science communication and public health advocacy, professional development, networking and experience exchange.
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http://dx.doi.org/10.1016/j.ijid.2021.05.035DOI Listing
May 2021

Glue Embolization of Gastroesophageal Varices during Transjugular Intrahepatic Portosystemic Shunt (TIPS) Improves Survival Compared to Coil-only Embolization-A Single-Center Retrospective Study.

Cardiovasc Intervent Radiol 2021 Aug 21;44(8):1240-1250. Epub 2021 May 21.

Department of Radiology, University Hospital Bonn, Bonn, Germany.

Purpose: To compare the safety and effectiveness of coil versus glue embolization of gastroesophageal varices during transjugular intrahepatic portosystemic shunt (TIPS) creation.

Materials And Methods: In this monocentric retrospective study 104 (males: 67 (64%)) patients receiving TIPS with concomitant embolization of GEV and a minimum follow-up of one year (2008-2017) were included. Primary outcome parameter was overall survival (6 week; 1 year). Six-week overall survival was assessed as a surrogate for treatment failure as proposed by the international Baveno working group. Secondary outcome parameters were development of acute-on-chronic liver failure (ACLF), variceal rebleeding and hepatic encephalopathy (HE). Survival analysis was performed using Kaplan-Meier with log-rank test and adjusted Cox regression analysis.

Results: Indications for TIPS were refractory ascites (n = 33) or variceal bleeding (n = 71). Embolization was performed using glue with or without coils (n = 40) (Group G) or coil-only (n = 64) (Group NG). Overall survival was significantly better in group G (p = 0.022; HR = -3.333). Six-week survival was significantly lower in group NG (p = 0.014; HR = 6.945). Rates of development of ACLF were significantly higher in group NG after 6 months (NG = 14; G = 6; p = 0.039; HR = 3.243). Rebleeding rates (NG = 6; G = 3; p = 0.74) and development of HE (NG = 22; G = 15; p = 0.75) did not differ significantly between groups.

Conclusion: Usage of glue in embolization of GEV may improve overall survival, reduce treatment failure and may be preferable over coil embolization alone.
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http://dx.doi.org/10.1007/s00270-021-02852-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249301PMC
August 2021

Controlled underdilation using novel VIATORR® controlled expansion stents improves survival after transjugular intrahepatic portosystemic shunt implantation.

JHEP Rep 2021 Jun 3;3(3):100264. Epub 2021 Mar 3.

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Background & Aims: Smaller 8-mm diameter transjugular intrahepatic portosystemic shunts (TIPS) appear to be more beneficial than larger 10-mm TIPS stent-grafts, but lack the ability for secondary dilation in cases of clinical ineffectiveness. Underdilated VIATORR® TIPS stent grafts (VTS) expand passively, whereas novel VIATORR Controlled Expansion (VCX) stent grafts do not. This study evaluated the impact on survival of underdilated VCX compared with VTS in patients with decompensated cirrhosis.

Methods: This was a prospective case-control study including patients with cirrhosis receiving TIPS using 10-mm VCX underdilated to 8 mm. Patients with cirrhosis receiving 10-mm VTS underdilated to 8 mm were matched for age, sex, indication for TIPS, and liver function.

Results: A total of 114 patients (47 VCX, 47 VTS, and 20 fully dilated VCX/VTS) were included. After TIPS implantation, underdilated VCX diameter was 8.0 (7.8-9.2) mm at a median time of 359 (87-450) days, compared with VTS at 9.9 (9.7-10.0) mm ( <0.001). The portosystemic pressure gradient immediately after TIPS procedure and after 7 days did not change significantly in VCX [mean 9.4 (± 0.8) 10.4 (± 0.7) mmHg,  = 0.115). Hospital readmission rates for hepatic encephalopathy were 23% (n = 11) 51% (n = 24) for VCX and VTS ( <0.001), respectively. Patients with VCX had significantly lower rates of large-volume paracentesis (n = 5 [11%] n = 10 [21%],  = 0.017) and heart failure (n = 1 [2%] n = 7 [15%],  = 0.015). One-year mortality for underdilated VCX and VTS was 15% (n = 7) and 30% (n = 14) and, for fully dilated VCX/VTS, was 45% (n = 9) (log-rank  = 0.008), respectively.

Conclusions: This study demonstrated that VCX stent grafts underdilated to 8 mm do not passively expand to nominal diameter and suggests reduced hospital readmissions because of hepatic encephalopathy, uncontrolled ascites, and heart failure, and improved 1-year survival compared with underdilated VTS.

Lay Summary: Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in selected patients with liver cirrhosis and acute variceal bleeding or refractory ascites. Smaller 8-mm diameter TIPS stent grafts appear to improve patient outcome compared with larger 10-mm diameter stent grafts. Novel VIATORR® Controlled Expansion (VCX) stent grafts facilitate safe and stable underdilation to 8 mm of large 10-mm diameter stent grafts with improved patient outcome (survival, hepatic encephalopathy, ascites and heart failure) compared with legacy VIATORR TIPS stent graft (VTS). Thus, the use of underdilated VCX could preserve heart function.

Clinical Trials Registration: The study is registered at Clinicaltrials.govNCT03628807.
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http://dx.doi.org/10.1016/j.jhepr.2021.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113713PMC
June 2021

Increasing cognitive load attenuates the moderating effect of attentional inhibition on the relationship between posttraumatic stress symptoms and threat-related attention bias variability.

J Anxiety Disord 2021 06 9;81:102416. Epub 2021 May 9.

Westfield State University, United States.

Theory and empirical evidence suggest that those with higher posttraumatic stress (PTS) symptoms and better attentional control (i.e., the strategic control of higher-order executive attention in regulating bottom-up, stimulus driven responses to prepotent stimuli; Sarapas et al., 2017) can use that ability to disengage and shift attention away from threat stimuli and reduce threat-related attentional dysregulation (i.e., avoidance/overcontrollers). Those with relatively worse attentional control lack the requisite resources to do this, leading to prolonged attentional engagement with threat stimuli and threat-related attention dysregulation (i.e., maintenance/undercontrollers). Given that attentional control is a limited resource, strategic avoidance of threat information or reduced threat-related attention dysregulation may not be possible among those with relatively higher attentional control when cognitive load is relatively high. To test this hypothesis, the interaction between PTS symptoms, attentional control, and cognitive load was examined as a predictor of threat-related attentional bias and threat-related attention bias variability. Participants (N = 125 undergraduate students) were randomly assigned to high or low load conditions. Participants completed self-report measures of PTS symptoms, a behavioral measure of attentional control, and a novel task that assessed threat-related attentional bias via eye movements and threat-related attention bias variability via button press. The results of a series of hierarchical regressions showed that attentional control moderated the relationship between PTS symptoms and threat-related attention bias variability in the low, but not high, load condition. This moderation effect was not observed for threat-related attentional bias assessed via eye-tracking. Consistent with theory, under conditions of higher cognitive load, overcontrollers may not be able to use attentional control to consistently regulate threat-related attention. Study findings suggest that it may be important to consider contextual factors that increase cognitive load, as well as individual differences in attentional control, when developing attention bias modification interventions to reduce PTS symptomatology.
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http://dx.doi.org/10.1016/j.janxdis.2021.102416DOI Listing
June 2021

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany.

BMC Cancer 2021 May 10;21(1):526. Epub 2021 May 10.

Department of Integrated Oncology, CIO Bonn, Center for Integrated Oncology ABCD, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany.

Methods: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression).

Results: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives.

Conclusion: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.
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http://dx.doi.org/10.1186/s12885-021-08141-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108356PMC
May 2021

is associated with roots of the perennial grass in Pacific Northwest prairies.

Mycologia 2021 Jul-Aug;113(4):693-702. Epub 2021 May 6.

Institute of Ecology and Evolution, University of Oregon, Eugene, 5289, Oregon 97403.

Prairies in the Pacific Northwest are dominated by perennial bunchgrasses. A in the complex was observed to tightly co-occur with bunchgrasses at several prairie study sites. Mapping and spatial statistics showed that it was strongly and significantly associated with tussocks. We further found that this fungus is attached to roots (17/17 examined) and both specific primers and next-generation DNA sequencing established that the fungus is in the roots, suggesting that may be endophytic or biotrophic in some contexts, and not simply saprotrophic. These results combined with a literature review indicate that species are often found as endophytes in grass roots. Given the importance of grasses and grasslands for humans, this ecological association deserves further study.
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http://dx.doi.org/10.1080/00275514.2021.1884814DOI Listing
May 2021

Phylogenomics resolves deep subfamilial relationships in Malvaceae s.l.

G3 (Bethesda) 2021 Apr 23. Epub 2021 Apr 23.

Institute of Parasitology, Biology Centre CAS, Branišovská 1160/31, 37005 České Budějovice, Czech Republic.

Malvaceae s.l., the most diverse family within Malvales, includes well-known species of great economic importance like cotton, cacao, and durian. Despite numerous phylogenetic analyses employing multiple markers, relationships between several of its nine subfamilies, particularly within the largest lineage/Malvadendrina, remain unclear. In this study, we attempted to resolve the relationships within the major clades of Malvaceae s.l. using plastid genomes of 48 accessions representing all subfamilies. Maximum likelihood and Bayesian analyses recovered a fully resolved and well-supported topology confirming the split of the family into/Byttneriina (/Grewioideae +/Byttnerioideae) and/Malvadendrina. Within/Malvadendrina,/Helicteroideae occupied the earliest branching position, followed by/Sterculioideae./Brownlowioideae,/Tiliodeae, and/Dombeyoideae formed a clade sister to/Malvatheca (/Malvoideae +/Bombacoideae), a grouping morphologically supported by the lack of androgynophore. Results from dating analyses suggest that all subfamilies originated during hot or warm phases in the Late Cretaceous to Paleocene. This study presents a well-supported phylogenetic framework for Malvaceae s.l. that will aid downstream revisions and evolutionary studies of this economically important plant family.
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http://dx.doi.org/10.1093/g3journal/jkab136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496235PMC
April 2021
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