Purpose: To develop a perimetric test strategy, Structure Estimation of Minimum Uncertainty (SEMU), that uses structural information to drive stimulus choices.
Methods: Structure Estimation of Minimum Uncertainty uses retinal nerve fiber layer (RNFL) thickness data as measured by optical coherence tomography to predict perimetric sensitivity. This prediction is used to set suprathreshold levels that then alter a prior probability distribution of the final test output. Using computer simulation, we studied SEMU’s performance under three different patient error response conditions: No Error, Typical False Positive errors, and Extremely Unreliable patients. In experiment 1, SEMU was compared with an existing suprathreshold cum thresholding combination test procedure, Estimation of Minimum Uncertainty (EMU), on single visual field locations. We used these results to finalize SEMU parameters. In experiment 2, SEMU was compared with full threshold (FT) on 163 glaucomatous visual fields.
Results: On individual locations, SEMU has similar accuracy to EMU, but is, on average, one presentation faster than EMU. For the typical false-positive error condition, SEMU has significantly lower error compared with FT (SEMU average 0.33 dB lower; p < 0.001) and the 90% measured sensitivity range for SEMU is also smaller than that for FT. For unreliable patients, however, FT has lower mean and SD of error. Structure Estimation of Minimum Uncertainty makes significantly fewer presentations than FT (1.08 presentation on average fewer in a typical false-positive condition; p < 0.001). Assuming that a location in the field is marked abnormal if it falls below the 5th percentile of normal, SEMU has a false-positive rate of less than 10% for all error conditions compared with FT’s rate of 20% or more.
Conclusions: On average, simulations show that using RNFL information to guide stimulus placement in a perimetric test procedure maintains accuracy, improves precision, and decreases test duration for patients with less than 15% false-positive rates.
Sefat, Farshid; Khaghani, Seyed A.; Nejatian, T.; Genedy, Mohamed A.; Abdeldayem, Ali I.A.; Moghaddam, Z.S.; Denyer, Morgan C.T.; Youseffi, Mansour(2015-12)
Bone repair and wound healing are modulated by different stimuli. There is evidence that Transforming Growth Factor-beta (TGF-β) super-family of cytokines have significant effects on bone structure by regulating the replication and differentiation of chondrocytes, osteoblasts and osteoclasts. There is also significant evidence that interactions with extracellular matrix molecules influence cell behaviour. In this study cell surface attachment was examined via a trypsinization assay using various TGF-β isomers in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. Three TGF-β isomers (TGF-β1, 2 and 3), four combined forms (TGF-β(1 + 2), TGF-β(1 + 3), TGF-β(2 + 3) and TGF-β(1 + 2 + 3)) along with four different controls (BSA, HCl, BSA/HCl and negative control) were investigated in this study. The results indicated that treatment with TGF-β1, 2, 3 and HCl decreased cell attachment, however, this effect was significantly greater in the case of TGF-β3 (p < 0.001) indicating perhaps that TGF-β3 does not act alone in cell detachment, but instead functions synergistically with signalling pathways that are dependent on the availability of hydrogen ions. Widefield Surface Plasmon Resonance (WSPR) microscope was also used to investigate cell surface interactions.
Polymorphism of crystalline drugs is a common phenomenon. However, the number of
reported polymorphic cocrystals is very limited. In this work, the synthesis and solid state
characterisation of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-
aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the
SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was
formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal
was discovered which could also be obtained by solvent evaporation from ethanol and
acetone. Structure determination of the form II cocrystal was calculated using high resolution
X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the
pH and predicted by a model established for a two amphoteric component cocrystal. The form
I cocrystal was found to be thermodynamically more stable in aqueous solution than form II,
which showed transformation to form I. Dissolution studies revealed that the dissolution rate
of SD from both cocrystals was enhanced when compared to a physical equimolar mixture
and pure SD.
In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Soon, Chin Fhong; Tee, K.S.; Youseffi, Mansour; Denyer, Morgan C.T.(2015-01-05)
Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT) system can be used in conjunction with a bespoke cell traction force mapping (CTFM) software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.
BACKGROUND: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to pound1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. METHODS/DESIGN: AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. DISCUSSION: The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. TRIAL REGISTRATION: The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).
Dul, M.; Paluch, Krzysztof J.; Kelly, H.; Healy, A.M.; Sasse, A.; Tajber, L.(2015-06-05)
The aim of this work was to investigate the feasibility of cross-linker free polyelectrolyte complex formation at the nanoscale between carrageenan (CAR) and protamine (PROT). The properties of CAR/PROT nanoparticles (NPs) were dependent on the carrageenan type: kappa (KC), iota (IC) and lambda (LC), concentration of components, addition of divalent cations, weight mixing ratio (WMR) of constituents and mode of component addition. In the case of 0.1% w/v solutions, IC-based NPs had the smallest particle sizes (100-150nm) and low polydispersity indices (0.1-0.4). A decrease in the solution concentration from 0.1% to 0.05% w/v enabled the formation of KC/PROT NPs. All carrageenans exhibited the ability to form NPs with surface charge ranging from -190 to 40mV. The inclusion of divalent cations caused an increase in the particle size and zeta potential. Infrared analysis confirmed the presence of a complex between CAR and PROT and showed that IC chains undergo structural changes when forming NPs. Colloidal stability of NPs was related to the initial surface charge of particles and was time- and pH-dependent. IC was found to be the most suitable type of CAR when forming nanoplexes with PROT.
Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed.
Microcarrier cell culture systems provide an attractive alternative to the conventional monolayer cell culture for cell amplification, due to their high surface area-to-volume ratio. Unlike enzymatic methods for removing cells from microcarriers after cell culture, which can lead to irreversible damage of the cells, microcarriers which release cells by temperature adjustment have been developed. This was achieved by grafting a temperature-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), on the microcarrier surface. This review comprehensively presents various methods to prepare such thermo-responsive microcarriers based on PNIPAAm. These methods include the grafting-to technique, grafting-from technique, grafting-through technique, along with methods leading to PNIPAAm hydrogel beads, seeded polymerization, and non-covalent adsorption. The methods for controlling PNIPAAm grafting density, molecular weight and molecular architecture are also outlined. Further, the efficiency of cell attachment, proliferation and thermally-induced detachment of such thermo-responsive microcarriers is introduced and compared. (C) 2015 Elsevier Ltd. All rights reserved.
The export option will allow you to export the current search results of the entered query to a file. Different
formats are available for download. To export the items, click on the button corresponding with the preferred download format.
By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.
To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export.
The amount of items that can be exported at once is similarly restricted as the full export.
After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.