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1.
Gut Microbes ; 16(1): 2308049, 2024.
Article in English | MEDLINE | ID: mdl-38299318

ABSTRACT

Infectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.


Subject(s)
Enterobacteriaceae Infections , Enterohemorrhagic Escherichia coli , Gastrointestinal Microbiome , Type II Secretion Systems , Child , Humans , Animals , Mice , Child, Preschool , Citrobacter rodentium/genetics , Virulence Factors/genetics , Virulence Factors/metabolism , Enterobacteriaceae Infections/microbiology
2.
Br J Dermatol ; 186(4): 713-720, 2022 04.
Article in English | MEDLINE | ID: mdl-34783007

ABSTRACT

BACKGROUND: In xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR). Protection is most important for the face. OBJECTIVES: We aimed to assess how well patients with XP adhere to medical advice to protect against UVR by objectively estimating the mean daily dose of UVR to the face. METHODS: We objectively estimated the UVR dose to the face in 36 patients with XP and 25 healthy individuals over 3 weeks in the summer. We used a new methodology which combined UVR dose measurements from a wrist-worn dosimeter with an activity diary record of face photoprotection behaviour for each 15-min period spent outside. A protection factor was associated with each behaviour, and the data were analysed using a negative binomial mixed-effects model. RESULTS: The mean daily UVR dose (weighted for DNA damage capacity) to the face in the patients with XP was 0·13 standard erythemal doses (SEDs) (mean in healthy individuals = 0·51 SED). There was wide variation between patients (range < 0·01-0·48 SED/day). Self-caring adult patients had a very similar UVR dose to the face as cared-for patients (0·13 vs. 0·12 SED/day), despite photoprotecting much more poorly when outside, because the self-caring adults were outside in daylight much less. CONCLUSIONS: Photoprotection behaviour varies widely within the XP group indicating that nonadherence to photoprotection advice is a significant issue. The timing and duration of going outside are as important as photoprotective measures taken when outside, to determine the UVR exposure to the face. This new methodology will be of value in identifying the sources of UVR exposure in other conditions in which facial UVR exposure is a key outcome, particularly in patients with multiple nonmelanoma skin cancers.


Subject(s)
Skin Neoplasms , Xeroderma Pigmentosum , Adult , Face , Health Behavior , Humans , Skin Neoplasms/etiology , Skin Neoplasms/prevention & control , Ultraviolet Rays/adverse effects
4.
Nurse Educ Pract ; 43: 102697, 2020 Jan 14.
Article in English | MEDLINE | ID: mdl-31981971

ABSTRACT

It is important to evaluate stakeholder feedback regarding any change to a clinical supervision model to maintain quality. The Quality Practical Experience (QPE) instruments offer both the nurse on the ward involved with supervising student learning and the student nurse the opportunity to evaluate their satisfaction with the supervision model. This paper reports on the evaluation of the construct validity and the reliability of the QPE instruments measuring nurse and nursing student satisfaction with the clinical supervision model. Methodological design for the reliability and validation of a measuring instrument. The nurse and the student QPE instruments were tested with convenience samples of 488 nurses and 1116 student nurses, respectively. Psychometric tests included internal reliability, test-retest reliability and factor analyses. Exploratory factor analysis for both QPEs supported a three-factor solution; the nurse QPE explained 48% and student nurse QPE 45% of variance. Internal reliability and test-retest reliability were stable over time (nurse QPE ICC = 0.82; student nurse QPE ICC = 0.71). Both QPE instruments were found to be valid and reliable. Feedback from all stakeholders involved with supporting student nurses during clinical placement is important.

5.
J Contemp Brachytherapy ; 12(6): 586-592, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33437307

ABSTRACT

PURPOSE: AccuBoost is a complex non-invasive brachytherapy procedure for breast treatment. This technique requires a radiation oncologist to manually select applicator grid position and size by overlaying transparencies over a mammographic image to encompass surgical clips and resected tumor bed. An algorithm was developed in MATLAB™ to automate the selection of round applicators based on surgical clip position. MATERIAL AND METHODS: A total of 42 mammograms belonging to 10 patients were retrospectively analyzed. Images were pre-processed by masking imprinted localization grid and regions around the grid. A threshold was applied to isolate high-intensity pixels and generate a binary image. A set of morphological operations including region dilation, filling, clearing border structures, and erosion were performed to segment the different regions. A support vector machine classification model was trained to categorize segmented regions as either surgical clips or miscellaneous objects based on different region properties (area, perimeter, eccentricity, circularity, minor axis length, and intensity-derived quantities). Applicator center position was determined by calculating the centroid of detected clips. Size of the applicator was determined with the smallest circle that encompassed all clips with an isotropic 1.0 cm margin. RESULTS: The clip identification model classified 946 regions, with a sensitivity of 96.6% and a specificity of 98.2%. Applicator position was correctly predicted for 20 of 42 fractions and was within 0.5 cm of physician-selected position for 33 of 42 fractions. Applicator size was correctly predicted for 25 out of 42 fractions. CONCLUSIONS: The proposed algorithm provided a method to quantitatively determine applicator position and size for AccuBoost treatments, and may serve as a tool for independent verifications. The discrepancy between physician-selected and algorithm-predicted determinations of applicator position and size suggests that the methodology may be further improved by considering radiomic features of breast tissue in addition to clip position.

6.
Insect Mol Biol ; 28(4): 455-472, 2019 08.
Article in English | MEDLINE | ID: mdl-30652367

ABSTRACT

Gut microbiota research is an emerging field that improves our understanding of the ecological and functional dynamics of gut environments. The honey bee gut microbiota is a highly rewarding community to study, as honey bees are critical pollinators of many crops for human consumption and produce valuable commodities such as honey and wax. Most significantly, unique characteristics of the Apis mellifera gut habitat make it a valuable model system. This review discusses methods and pipelines used in the study of the gut microbiota of Ap. mellifera and closely related species for four main purposes: identifying microbiota taxonomy, characterizing microbiota genomes (microbiome), characterizing microbiota-microbiota interactions and identifying functions of the microbial community in the gut. The purpose of this contribution is to increase understanding of honey bee gut microbiota, to facilitate bee microbiota and microbiome research in general and to aid design of future experiments in this growing field.


Subject(s)
Bacteria , Bacterial Physiological Phenomena , Bacteriological Techniques/methods , Bees/microbiology , Gastrointestinal Microbiome/physiology , Animals , Bacteria/classification , Bacteria/genetics , Entomology/methods , Gastrointestinal Microbiome/genetics
7.
Methods Enzymol ; 585: 217-243, 2017.
Article in English | MEDLINE | ID: mdl-28109431

ABSTRACT

Massively parallel sequencing is revealing species genomes faster than ever before, but the value of the raw sequence is limited unless the genes can be accurately annotated. This is typically achieved using gene prediction algorithms which, despite continual improvement, still require substantial verification and refinement. For example, in silico methods struggle with annotating splice isoforms accurately and empirical methods are needed to refine and verify the initial bioinformatic gene predictions. RNA-seq is an excellent way to confirm exon-exon boundaries and transcript termini, while mass spectrometry (MS) offers definitive proof that a gene is translated and a secondary means of confirming exon expression, protein termini, and posttranslational modifications. Furthermore, both methods can potentially identify entirely novel genes that were missed by conventional gene predictors. This chapter describes a proteogenomics procedure using information from the proteome, transcriptome, and genome-thus utilizing each component of the central dogma-to annotate genetic elements in eukaryotes. We also discuss gene modeling, integration of RNA-seq and MS data, minimizing false discoveries, proteogenomics software, functional annotation, and sequence validation. We hope that the procedure described here will assist efforts to annotate the genomes of newly sequenced species, as well as sharpen those that have been annotated in the past.


Subject(s)
Computational Biology/methods , Proteogenomics/methods , Proteomics/methods , Genome/genetics , Molecular Sequence Annotation
8.
Sci Total Environ ; 579: 1399-1409, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27913017

ABSTRACT

Growing evidence suggests that anthropogenic litter, particularly plastic, represents a highly pervasive and persistent threat to global marine ecosystems. Multinational research is progressing to characterise its sources, distribution and abundance so that interventions aimed at reducing future inputs and clearing extant litter can be developed. Citizen science projects, whereby members of the public gather information, offer a low-cost method of collecting large volumes of data with considerable temporal and spatial coverage. Furthermore, such projects raise awareness of environmental issues and can lead to positive changes in behaviours and attitudes. We present data collected over a decade (2005-2014 inclusive) by Marine Conservation Society (MCS) volunteers during beach litter surveys carried along the British coastline, with the aim of increasing knowledge on the composition, spatial distribution and temporal trends of coastal debris. Unlike many citizen science projects, the MCS beach litter survey programme gathers information on the number of volunteers, duration of surveys and distances covered. This comprehensive information provides an opportunity to standardise data for variation in sampling effort among surveys, enhancing the value of outputs and robustness of findings. We found that plastic is the main constituent of anthropogenic litter on British beaches and the majority of traceable items originate from land-based sources, such as public littering. We identify the coast of the Western English Channel and Celtic Sea as experiencing the highest relative litter levels. Increasing trends over the 10-year time period were detected for a number of individual item categories, yet no statistically significant change in total (effort-corrected) litter was detected. We discuss the limitations of the dataset and make recommendations for future work. The study demonstrates the value of citizen science data in providing insights that would otherwise not be possible due to logistical and financial constraints of running government-funded sampling programmes on such large scales.


Subject(s)
Environmental Monitoring/methods , Waste Products/analysis , Water Pollution/statistics & numerical data , Bathing Beaches/statistics & numerical data , Plastics/analysis , Waste Products/statistics & numerical data , Water Pollutants/analysis
9.
AJNR Am J Neuroradiol ; 38(1): 84-89, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27765740

ABSTRACT

BACKGROUND AND PURPOSE: Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features. MATERIALS AND METHODS: Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0-2 end points at 90 days for endovascular therapy-treated M2 occlusions were analyzed. Post hoc analyses of the relationship of outcomes to multiple baseline angiographic M2 and M1 subgroup characteristics were performed. RESULTS: Of 83 participants with M2 occlusion who underwent endovascular therapy, 41.0% achieved mRS 0-2 at 90 days, including 46.6% with modified TICI 2-3 reperfusion compared with 26.1% with modified TICI 0-1 reperfusion (risk difference, 20.6%; 95% CI, -1.4%-42.5%). mRS 0-2 outcome was associated with reperfusion for M2 trunk (n = 9) or M2 division (n = 42) occlusions, but not for M2 branch occlusions (n = 28). Of participants with trunk and division occlusions, 63.2% with modified TICI 2a and 42.9% with modified TICI 2b reperfusion achieved mRS 0-2 outcomes; mRS 0-2 outcomes for M2 trunk occlusions (33%) did not differ from distal (38.2%) and proximal (26.9%) M1 occlusions. CONCLUSIONS: mRS 0-2 at 90 days was dependent on reperfusion for M2 trunk but not for M2 branch occlusions. For M2 division occlusions, good outcome with modified TICI 2b reperfusion did not differ from that in modified TICI 2a. M2 segment definition and occlusion location may contribute to differences in revascularization and good outcome between Interventional Management of Stroke III and other endovascular therapy studies.


Subject(s)
Arterial Occlusive Diseases/therapy , Cerebral Revascularization/methods , Cerebrovascular Disorders/therapy , Endovascular Procedures/methods , Stroke/therapy , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome
10.
Front Neurosci ; 10: 432, 2016.
Article in English | MEDLINE | ID: mdl-27757072

ABSTRACT

The recent success of olfactory ensheathing cell (OEC) assisted regeneration of injured spinal cord has seen a rising interest in the use of these cells in tissue-engineered systems. Previously shown to support neural cell growth through glial scar tissue, OECs have the potential to assist neural network formation in living electrode systems to produce superior neuroprosthetic electrode surfaces. The following study sought to understand the influence of biphasic electrical stimulation (ES), inherent to bionic devices, on cell survival and function, with respect to conventional metallic and developmental conductive hydrogel (CH) coated electrodes. The CH utilized in this study was a biosynthetic hydrogel consisting of methacrylated poly(vinyl-alcohol) (PVA), heparin and gelatin through which poly(3,4-ethylenedioxythiophene) (PEDOT) was electropolymerised. OECs cultured on Pt and CH surfaces were subjected to biphasic ES. Image-based cytometry yielded little significant difference between the viability and cell cycle of OECs cultured on the stimulated and passive samples. The significantly lower voltages measured across the CH electrodes (147 ± 3 mV) compared to the Pt (317 ± 5 mV), had shown to influence a higher percentage of viable cells on CH (91-93%) compared to Pt (78-81%). To determine the functionality of these cells following electrical stimulation, OECs co-cultured with PC12 cells were found to support neural cell differentiation (an indirect measure of neurotrophic factor production) following ES.

11.
AJNR Am J Neuroradiol ; 37(8): 1393-8, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26988811

ABSTRACT

BACKGROUND AND PURPOSE: The importance of time in acute stroke is well-established. Using the Interventional Management of Stroke III trial data, we explored the effect of multimodal imaging (CT perfusion and/or CT angiography) versus noncontrast CT alone on time to treatment and outcomes. MATERIALS AND METHODS: We examined 3 groups: 1) subjects with baseline CTP and CTA (CTP+CTA), 2) subjects with baseline CTA without CTP (CTA), and 3) subjects with noncontrast head CT alone. The demographics, treatment time intervals, and clinical outcomes in these groups were studied. RESULTS: Of 656 subjects enrolled in the Interventional Management of Stroke III trial, 90 (13.7%) received CTP and CTA, 216 (32.9%) received CTA (without CTP), and 342 (52.1%) received NCCT alone. Median times for the CTP+CTA, CTA, and NCCT groups were as follows: stroke onset to IV tPA (120.5 versus 117.5 versus 120 minutes; P = .5762), IV tPA to groin puncture (77.5 versus 81 versus 91 minutes; P = .0043), groin puncture to endovascular therapy start (30 versus 38 versus 44 minutes; P = .0001), and endovascular therapy start to end (63 versus 46 versus 74 minutes; P < .0001). Compared with NCCT, the CTA group had better outcomes in the endovascular arm (OR, 2.12; 95% CI, 1.36-3.31; adjusted for age, NIHSS score, and time from onset to IV tPA). The CTP+CTA group did not have better outcomes compared with the NCCT group. CONCLUSIONS: Use of CTA with or without CTP did not delay IV tPA or endovascular therapy compared with NCCT in the Interventional Management of Stroke III trial.


Subject(s)
Multimodal Imaging/methods , Stroke/diagnostic imaging , Stroke/therapy , Time-to-Treatment , Aged , Cerebral Angiography/methods , Computed Tomography Angiography , Endovascular Procedures , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Tissue Plasminogen Activator/therapeutic use , Tomography, X-Ray Computed/methods
12.
Sci Rep ; 6: 20572, 2016 Feb 08.
Article in English | MEDLINE | ID: mdl-26853562

ABSTRACT

Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stresses in high energy environments relies on their skeletal structure which is composed of high Mg-calcite. High Mg-calcite is, however, the most soluble form of calcium carbonate and therefore potentially vulnerable to the change in carbonate chemistry resulting from the absorption of anthropogenic CO2 by the ocean. We examine the geochemistry of the cold water coralline alga Lithothamnion glaciale grown under predicted future (year 2050) high pCO2 (589 µatm) using Electron microprobe and NanoSIMS analysis. In the natural and control material, higher Mg calcite forms clear concentric bands around the algal cells. As expected, summer growth has a higher Mg content compared to the winter growth. In contrast, under elevated CO2 no banding of Mg is recognisable and overall Mg concentrations are lower. This reduction in Mg in the carbonate undermines the accuracy of the Mg/Ca ratio as proxy for past temperatures in time intervals with significantly different carbonate chemistry. Fundamentally, the loss of Mg in the calcite may reduce elasticity thereby changing the structural properties, which may affect the ability of L. glaciale to efficiently function as a habitat former in the future ocean.


Subject(s)
Calcium Carbonate/chemistry , Carbon Dioxide/metabolism , Rhodophyta/metabolism , Calcium Carbonate/metabolism , Carbon Dioxide/chemistry , Ecosystem , Magnesium/chemistry , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanotechnology , Rhodophyta/growth & development , Seasons , Spectrometry, Mass, Secondary Ion , Temperature , X-Ray Diffraction
13.
mBio ; 7(1): e01862-15, 2016 Jan 12.
Article in English | MEDLINE | ID: mdl-26758180

ABSTRACT

UNLABELLED: The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we investigated the influence of PKA on the composition of the intracellular proteome to obtain a comprehensive understanding of the regulation that underpins virulence. Through quantitative proteomics, enrichment and bioinformatic analyses, and an interactome study, we uncovered a pattern of PKA regulation for proteins associated with translation, the proteasome, metabolism, amino acid biosynthesis, and virulence-related functions. PKA regulation of the ubiquitin-proteasome pathway in C. neoformans showed a striking parallel with connections between PKA and protein degradation in chronic neurodegenerative disorders and other human diseases. Further investigation of proteasome function with the inhibitor bortezomib revealed an impact on capsule production as well as hypersusceptibility for strains with altered expression or activity of PKA. Parallel studies with tunicamycin also linked endoplasmic reticulum stress with capsule production and PKA. Taken together, the data suggest a model whereby expression of PKA regulatory and catalytic subunits and the activation of PKA influence proteostasis and the function of the endoplasmic reticulum to control the elaboration of the polysaccharide capsule. Overall, this study revealed both broad and conserved influences of the cAMP/PKA pathway on the proteome and identified proteostasis as a potential therapeutic target for the treatment of cryptococcosis. IMPORTANCE: Fungi cause life-threatening diseases, but very few drugs are available to effectively treat fungal infections. The pathogenic fungus Cryptococcus neoformans causes a substantial global burden of life-threatening meningitis in patients suffering from HIV/AIDS. An understanding of the mechanisms by which fungi deploy virulence factors to cause disease is critical for developing new therapeutic approaches. We employed a quantitative proteomic approach to define the changes in the protein complement that occur upon modulating the cAMP signaling pathway that regulates virulence in C. neoformans. This approach identified a conserved role for cAMP signaling in the regulation of the ubiquitin-proteasome pathway and revealed a link between this pathway and elaboration of a major virulence determinant, the polysaccharide capsule. Targeting the ubiquitin-proteasome pathway opens new therapeutic options for the treatment of cryptococcosis.


Subject(s)
Cryptococcus neoformans/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Fungal Capsules/metabolism , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Cyclic AMP/metabolism , Proteome/analysis , Proteomics
14.
J Phys Act Health ; 13(6): 587-93, 2016 06.
Article in English | MEDLINE | ID: mdl-26594820

ABSTRACT

BACKGROUND: Innovative methods are warranted to optimize prenatal outcomes. This study's objective was to determine if a web-based behavioral intervention (BI) can prevent excessive gestational weight gain (GWG) by increasing physical activity (PA). METHODS: Participants were randomized to usual care (UC; n = 21) or BI (n = 24) between 10 to 14 weeks gestation. GWG, PA, and diet were assessed at baseline, mid-, and late pregnancy. RESULTS: No differences in GWG or adherence to GWG recommendations presented between groups. Total UC MET-minutes significantly decreased from baseline to late-pregnancy (1,234 ± 372 MET-minutes, P = .013). Mid-pregnancy sustained PA was greater for BI than UC (20-minute PA bouts: 122 ± 106 vs. 46 ± 48 minutes/week, P = .005; 30-minute PA bouts: 74 ± 70 vs. 14 ± 24 minutes/week, P < .001), and greater for BI at mid-pregnancy compared with baseline (20-minute PA bouts: 61.3 ± 21.9; 30-minute PA bouts: 39.6 ± 14.8, both P < .05). BI energy intake at mid-pregnancy significantly increased from baseline (336 ± 127 kcals, P = .04) and was significantly greater than UC (2,503 ± 703 vs. 1,894 ± 594, P = .005). CONCLUSIONS: Sedentary pregnant women should increase PA but may need additional dietary counseling to prevent excessive GWG.


Subject(s)
Behavior Therapy/methods , Exercise/physiology , Internet/statistics & numerical data , Pregnancy Complications/prevention & control , Prenatal Care/methods , Weight Gain/physiology , Adolescent , Adult , Counseling , Diet , Female , Humans , Middle Aged , Pregnancy , Sedentary Behavior , Young Adult
15.
Methods Enzymol ; 565: 97-121, 2015.
Article in English | MEDLINE | ID: mdl-26577729

ABSTRACT

The use of microbial biosynthesis to produced deuterated recombinant proteins is a well-established practice in investigations of the relationship between molecular structure and function using neutron scattering and nuclear magnetic resonance spectroscopy. However, there have been few reports of using microbial synthetic capacity to produce labeled native biopolymers. Here, we describe methods for the production of deuterated polyhydroxyalkanoate biopolyesters in bacteria, the polysaccharide chitosan in the yeast Pichia pastoris, and cellulose in the bacterium Gluconacetobacter xylinus. The resulting molecules offer not only multiple options in creating structural contrast in polymer blends and composites in structural studies but also insight into the biosynthetic pathways themselves.


Subject(s)
Biopolymers/chemistry , Deuterium/chemistry , Isotope Labeling , Culture Media , Hydroxybutyrates/metabolism , Neutrons , Pichia/metabolism , Polyesters/metabolism , Scattering, Radiation
16.
AJNR Am J Neuroradiol ; 36(11): 2074-81, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26228892

ABSTRACT

BACKGROUND AND PURPOSE: Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). MATERIALS AND METHODS: We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. RESULTS: Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. CONCLUSIONS: While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation.


Subject(s)
Contrast Media/adverse effects , Iohexol/adverse effects , Iopamidol/adverse effects , Stroke/diagnostic imaging , Triiodobenzoic Acids/adverse effects , Adult , Aged , Aged, 80 and over , Endovascular Procedures/methods , Female , Humans , Male , Middle Aged , Prospective Studies , Radiography , Stroke/surgery
17.
Br Dent J ; 218(7): 423-8; discussion 428, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25858740

ABSTRACT

OBJECTIVE: To analyse the factors affecting the clinical performance and those influencing the survival of resin-retained bridgework provided at a UK dental teaching hospital between 1994 and 2001. DESIGN: A prospective analysis of restorations provided at a single centre using case notes with all patients invited for review to corroborate findings. SETTING: Department of Restorative Dentistry, University of Bristol Dental Hospital and School, Bristol, United Kingdom. SUBJECTS AND METHODS: Between January 1994 and December 2001, data regarding 1,000 consecutive resin-retained bridges provided at Bristol Dental Hospital and School were recorded. Data was available for 805 patients at the time of the study. Following invitation, 621 patients attended for a review appointment. Life table and Kaplan-Meir survival analysis were carried out for all restorations provided. RESULTS: The five-year and ten-year survival rates estimated by the life-table method are 80.8% (95% confidence interval 78.0-83.6%) and 80.4% (95% confidence interval 77.6-83.2%) respectively. The median survival cannot be estimated for this study as the survival probability remains above 80% even at the longest follow-up. Analysis of clinical variables influencing survival revealed that design of the restoration and experience of the operator providing the restoration were significant factors. Resin-retained bridges made with minimal tooth preparation are shown to be superior in terms of longevity than those for which other types of tooth preparation is made. Patient satisfaction with their treatment was high.


Subject(s)
Dental Restoration Failure/statistics & numerical data , Denture, Partial, Fixed, Resin-Bonded/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Hospitals, Teaching/statistics & numerical data , Humans , Male , Middle Aged , Patient Satisfaction/statistics & numerical data , Prospective Studies , United Kingdom , Young Adult
18.
BJOG ; 122(1): 57-62, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24935560

ABSTRACT

BACKGROUND: Antenatal depression can have harmful consequences for the mother and fetus. Exercise may be a useful intervention to prevent and treat antenatal depression. OBJECTIVES: This systematic review aims to establish whether there is sufficient evidence to conclude that exercise is an effective intervention for preventing and treating antenatal depression. SEARCH STRATEGY: Searches using electronic databases from MEDLINE, Cochrane Library, CINAHL, EMBASE, AMED and PsycINFO were performed. SELECTION CRITERIA: Randomised controlled trials (RCT) that compared any type of exercise intervention with any comparator in pregnant women were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Meta-analysis was performed calculating standardised mean differences (SMD). MAIN RESULTS: Six trials (seven comparisons) were eligible for inclusion. Meta-analysis showed a significant reduction in depression scores (SMD -0.46, 95% CI -0.87 to -0.05, P = 0.03, I(2) = 68%) for exercise interventions relative to comparator groups. The test for subgroup differences in women who were non-depressed (one trial) (SMD -0.74, 95%CI -1.22 to -0.27, P = 0.002) and depressed (five trials) (SMD -0.41, 95% CI -0.88 to 0.07, P = 0.09) at baseline was not significant (P = 0.32). The test for subgroup differences between aerobic (one trial) and non-aerobic exercise (five trials) was also nonsignificant (P = 0.32). AUTHORS' CONCLUSIONS: We found some evidence that exercise may be effective in treating depression during pregnancy but this conclusion is based on a small number of low-moderate quality trials with significant heterogeneity and wide confidence intervals.


Subject(s)
Depression/prevention & control , Depressive Disorder/prevention & control , Exercise Therapy/methods , Pregnancy Complications/prevention & control , Depression/therapy , Depressive Disorder/therapy , Female , Humans , Pregnancy , Pregnancy Complications/therapy , Treatment Outcome
19.
Bone Marrow Transplant ; 49(11): 1426-31, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25068430

ABSTRACT

Hematopoietic cell transplantation (HCT) has become an established standard of care for many older patients with hematologic malignancies. The effect of transplantation on the quality of life (QOL) of older patients, however, has not been well studied. We thus analyzed QOL in patients ⩾60 undergoing an allogeneic HCT compared with patients <60 years. Prospective psychometric instruments were administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric data were assessed longitudinally by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory and the Profile of Mood State-Short Form. Patients ⩾60 reported better social (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better total scores, (P=0.043) across all time points. When adjusted for baseline QOL scores as a covariate, social well-being remained significantly better, whereas the other scores became non-significant. With a median follow-up of 49 months, there were no significant differences in OS, relapse-free survival, relapse or chronic GVHD. This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older patients achieved comparable QOL when compared with younger patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Quality of Life , Surveys and Questionnaires , Aged , Aged, 80 and over , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Survival Rate
20.
Biomed Res Int ; 2014: 741408, 2014.
Article in English | MEDLINE | ID: mdl-24900983

ABSTRACT

Electrospinning can produce nanofibrous scaffolds that mimic the architecture of the extracellular matrix and support cell attachment for tissue engineering applications. In this study, fibrous membranes of polyhydroxybutyrate (PHB) with various loadings of poly(L-lactide-co-ε-caprolactone) (PLCL) were successfully prepared by electrospinning. In comparison to PLCL scaffolds, PLCL blends with PHB exhibited more irregular fibre diameter distributions and higher average fibre diameters but there were no significant differences in pore size. PLCL/PHB scaffolds were more hydrophilic (<120°) with significantly reduced tensile strength (ca. 1 MPa) compared to PLCL scaffolds (150.9 ± 2.8° and 5.8 ± 0.5 MPa). Increasing PLCL loading in PHB/PLCL scaffolds significantly increased the extension at break, (4-6-fold). PLCL/PHB scaffolds supported greater adhesion and proliferation of olfactory ensheathing cells (OECs) than those exhibiting asynchronous growth on culture plates. Mitochondrial activity of cells cultivated on the electrospun blended membranes was enhanced compared to those grown on PLCL and PHB scaffolds (212, 179, and 153%, resp.). Analysis showed that PLCL/PHB nanofibrous membranes promoted cell cycle progression and reduced the onset of necrosis. Thus, electrospun PLCL/PHB composites promoted adhesion and proliferation of OECs when compared to their individual PLCL and PHB components suggesting potential in the repair and engineering of nerve tissue.


Subject(s)
Biocompatible Materials/chemistry , Hydroxybutyrates/chemistry , Nanofibers/chemistry , Polyesters/chemistry , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/pharmacology , Cell Adhesion/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Hydroxybutyrates/pharmacology , Materials Testing/methods , Mice , Mitochondria/drug effects , Polyesters/pharmacology , Tensile Strength/drug effects , Tissue Engineering/methods
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