ABSTRACT
PURPOSE: The purpose of this study is to compare the reconstructed corneal power (RCP) by working backwards from the post-implantation spectacle refraction and toric intraocular lens power and to develop the models for mapping preoperative keratometry and total corneal power to RCP. METHODS: Retrospective single-centre study involving 442 eyes treated with a monofocal and trifocal toric IOL (Zeiss TORBI and LISA). Keratometry and total corneal power were measured preoperatively and postoperatively using IOLMaster 700. Feedforward neural network and multilinear regression models were derived to map keratometry and total corneal power vector components (equivalent power EQ and astigmatism components C0 and C45) to the respective RCP components. RESULTS: Mean preoperative/postoperative C0 for keratometry and total corneal power was -0.14/-0.08 dioptres and -0.30/-0.24 dioptres. All mean C45 components ranged between -0.11 and -0.20 dioptres. With crossvalidation, the neural network and regression models showed comparable results on the test data with a mean squared prediction error of 0.20/0.18 and 0.22/0.22 dioptres2 and on the training data the neural network models outperformed the regression models with 0.11/0.12 and 0.22/0.22 dioptres2 for predicting RCP from preoperative keratometry/total corneal power. CONCLUSIONS: Based on our dataset, both the feedforward neural network and multilinear regression models showed good precision in predicting the power vector components of RCP from preoperative keratometry or total corneal power. With a similar performance in crossvalidation and a simple implementation in consumer software, we recommend implementation of regression models in clinical practice.
ABSTRACT
Microbial fouling involves the physicochemical interactions between microorganisms and solid surfaces. An electromagnetic field (EMF) may change the diffusion rates of microbial cells and the electrical double layer around the cells and contacting surfaces. In the current study, polycardanol exhibiting antibiofouling activity was modified with ferromagnetic iron oxide (IO) to investigate the EMF effects on bacterial adhesion. When there was a flow of electrolyte that contained bacterial cells, flow-induced EMF was generated according to Faraday's principle. It was observed that the IO-ionic solution (IS)-modified surfaces, with an induced current of 44, 53, 66 nA, showed decreases in the adhesion of bacteria cells more than the unmodified (polycardanol) and IO-nanoparticles-modified ones. In addition to the EMF effects, the nano-scale uniform roughness of the modified surfaces appeared to play an important role in the reduction of cell adhesion. The results demonstrated that the IOIS-modified surface (3.2 × 10-6 mM IO) had the highest antibiofouling activity.
Subject(s)
Bacterial Adhesion , Biofouling , Electromagnetic Fields , Phenols , Surface Properties , Biofouling/prevention & control , Bacterial Adhesion/drug effects , Phenols/chemistry , Phenols/pharmacology , Ferric Compounds/chemistry , Biofilms/drug effectsABSTRACT
BACKGROUND: To compare results from different corneal astigmatism measurement instruments; to reconstruct corneal astigmatism from the postimplantation spectacle refraction and toric intraocular lens (IOL) power; and to derive models for mapping measured corneal astigmatism to reconstructed corneal astigmatism. METHODS: Retrospective single centre study involving 150 eyes treated with a toric IOL (Alcon SN6AT, DFT or TFNT). Measurements included IOLMaster 700 keratometry (IOLMK) and total keratometry (IOLMTK), Pentacam keratometry (PK) and total corneal refractive power in 3 and 4 mm zones (PTCRP3 and PTCRP4), and Aladdin keratometry (AK). Regression-based models mapping the measured C0 and C45 components (Alpin's method) to reconstructed corneal astigmatism were derived. RESULTS: Mean C0 components were 0.50/0.59/0.51 dioptres (D) for IOLMK/PK/AK; 0.2/0.26/0.31 D for IOLMTK/PTCRP3/PTCRP4; and 0.26 D for reconstructed corneal astigmatism. All corresponding C45 components ranged around 0. The prediction models had main diagonal elements lower than 1 with some crosstalk between C0 and C45 (nonzero off-diagonal elements). Root-mean-squared residuals were 0.44/0.45/0.48/0.51/0.50/0.47 D for IOLMK/IOLMTK/PK/PTCRP3/PTCRP4/AK. CONCLUSIONS: Results from the different modalities are not consistent. On average IOLMTK/PTCRP3/PTCRP4 match reconstructed corneal astigmatism, whereas IOLMK/PK/AK show systematic C0 offsets of around 0.25 D. IOLMTK/PTCRP3/PTCRP4. Prediction models can reduce but not fully eliminate residual astigmatism after toric IOL implantation.
Subject(s)
Astigmatism , Biometry , Cornea , Corneal Topography , Lens Implantation, Intraocular , Refraction, Ocular , Humans , Astigmatism/physiopathology , Astigmatism/diagnosis , Astigmatism/surgery , Retrospective Studies , Male , Biometry/methods , Refraction, Ocular/physiology , Female , Cornea/diagnostic imaging , Cornea/pathology , Aged , Middle Aged , Corneal Topography/methods , Lenses, Intraocular , Anterior Eye Segment/diagnostic imaging , Visual Acuity/physiology , Aged, 80 and over , Phacoemulsification , AdultABSTRACT
We present methods for making and testing the membrane biophysics of model lipid droplets (LDs). Methods are described for imaging LDs ranging in size from 0.1 to 40 µm in diameter with high-resolution microscopy and spectroscopy. With known LD compositions, membrane binding, sorting, diffusion, and tension were measured via fluorescence correlation spectroscopy (FCS), fluorescence recovery after photobleaching (FRAP), fluorescence lifetime imaging microscopy (FLIM), atomic force microscopy (AFM), and imaging flow cytometry. Additionally, a custom, small-volume pendant droplet tensiometer is described and used to measure the association of phospholipids to the LD surface. These complementary, cross-validating methods of measuring LD membrane behavior reveal the interplay of biophysical processes on lipid droplet monolayers.
Subject(s)
Lipid Droplets , Lipid Droplets/metabolism , Lipid Droplets/chemistry , Microscopy, Atomic Force/methods , Microscopy, Fluorescence/methods , Fluorescence Recovery After Photobleaching/methods , Humans , Flow Cytometry/methods , Spectrometry, Fluorescence/methodsABSTRACT
PURPOSE: To investigate the performance of a simple prediction scheme for the formula constants optimised for a mean refractive prediction error. METHODS: Analysis based on a dataset of 888 eyes before and after cataract surgery with IOL implantation (Hoya Vivinex). IOLMaster 700 biometric data, power of the implanted lens and postoperative spherical equivalent refraction were used to calculate the optimised constants (.)opt for SRKT, HofferQ, Holladay and Haigis formula with an iterative nonlinear optimisation. For detuning start values by ±1.5 from (.)opt, the predicted formula constants (.)pred were calculated and compared with (.)opt. Formula performance metrics mean (MPE), median (MEDPE), mean absolute (MAPE), median absolute (MEDAPE), root mean squared (RMSPE) and standard deviation (SDPE) of the formula prediction error were analysed for (.)opt and (.)pred. RESULTS: (.)pred - (.)opt showed a 2nd order parabolic behaviour with maximal deviations up to 0.09 at the tails of detuning and a minimal deviation up to -0.01 for all formulae. The performance curves of different metrics of PE as functions of detuning variations show that the formula constants for zeroing MPE and MEDPE yield almost identical formula constants, optimisation for MAPE, MEDAPE and RMSPE yielded formula constants very close to (.)opt, and optimisation for SDPE could result in formula constants up to 0.5 off (.)opt which is unacceptable for clinical use. CONCLUSION: This simple prediction scheme for formula constant optimisation for zero mean refraction error performs excellently in our monocentric dataset, even for larger deviations of the start value from (.)opt. Further studies with multicentric data and larger sample sizes are required to investigate the performance in a clinical setting further.
ABSTRACT
Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.
Subject(s)
Homeostasis , Lipid Metabolism , Myelin Sheath , Oligodendroglia , Selenoproteins , Animals , Humans , Mice , Brain/metabolism , Brain/pathology , Lipid Peroxidation , Mice, Knockout , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Oligodendroglia/pathology , Phosphatidylethanolamines/metabolism , Phospholipid Ethers/metabolism , Plasmalogens/metabolism , Selenoproteins/metabolism , Selenoproteins/genetics , Spastic Paraplegia, Hereditary/metabolism , Spastic Paraplegia, Hereditary/genetics , Spastic Paraplegia, Hereditary/pathologyABSTRACT
The Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee designed and created a publicly accessible database with an initial set of 128 pharmacologically defined pharmaceutical agents, many with known cardiotoxic properties. The database includes specific information about each compound that could be useful in evaluating hypotheses around mechanisms of drug-induced cardiac toxicity or for development of novel cardiovascular safety assays. Data on each of the compounds was obtained from published literature and online sources (e.g., DrugBank.ca and International Union of Basic and Clinical Pharmacology (IUPHAR) / British Pharmacological Society (BPS) Guide to PHARMACOLOGY) and was curated by 10 subject matter experts. The database includes information such as compound name, pharmacological mode of action, characterized cardiac mode of action, type of cardiac toxicity, known clinical cardiac toxicity profile, animal models used to evaluate the cardiotoxicity profile, routes of administration, and toxicokinetic parameters (i.e., Cmax). Data from both nonclinical and clinical studies are included for each compound. The user-friendly web interface allows for multiple approaches to search the database and is also intended to provide a means for the submission of new data/compounds from relevant users. This will ensure that the database is constantly updated and remains current. Such a data repository will not only aid the HESI working groups in defining drugs for use in any future studies, but safety scientists can also use the database as a vehicle of support for broader cardiovascular safety studies or exploring mechanisms of toxicity associated with certain pharmacological modes of action.
Subject(s)
Cardiotoxicity , Databases, Pharmaceutical , Drug-Related Side Effects and Adverse Reactions , Animals , Humans , Cardiotoxicity/etiology , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug Evaluation, Preclinical/methods , Databases, Factual , Pharmaceutical PreparationsABSTRACT
Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.
ABSTRACT
PURPOSE: The purpose of this study was to investigate the effect of the corneal back surface by comparing the keratometric astigmatism (K, derived from the corneal front surface) of a modern optical biometer against astigmatism of Total Keratometry (TK, derived from both corneal surfaces) in a large population with cataractous eyes. The results were then used to define linear prediction models to map K to TK. METHODS: From a large dataset containing bilateral biometric measurements (IOLMaster 700) in 9736 patients prior to cataract surgery, the total corneal astigmatism was decomposed into vectors for K, corneal back surface (BS), and TK. A multivariate prediction model (MV), simplified model with separation of vector components (SM) and a constant model (CM) were defined to map K to TK vector components. RESULTS: The K centroid (X/Y) showed some astigmatism with-the-rule (0.1981/-0.0211 dioptre (dpt)) whereas the TK centroid was located around zero (-0.0071/-0.0381 dpt against-the-rule) and the BS centroid showed systematic astigmatism against-the-rule (-0.2367/-0.0145 dpt). The respective TK-K centroid was located at -0.2052/-0.0302 dpt. The MV model showed the same performance (i.e. mean absolute residuum) as the SM did (0.1098 and 0.1099 dpt respectively) while the CM performed only slightly worse (0.1121 dpt mean absolute residuum). CONCLUSION: In cases where tomographic data are unavailable statistical models could be used to consider the overall contribution of the back surface to the total corneal astigmatism. Since the performance of the CM is sufficiently close to that of MV and SM we recommend using the CM which can be directly considered e.g. as surgically induced astigmatism.
Subject(s)
Astigmatism , Cataract Extraction , Corneal Diseases , Humans , Astigmatism/diagnosis , Biometry/methods , Cornea/diagnostic imagingABSTRACT
RATIONALE: The application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to murine lungs is challenging due to the spongy nature of the tissue. Lungs consist of interconnected air sacs (alveoli) lined by a single layer of flattened epithelial cells, which requires inflation to maintain its natural structure. Therefore, a protocol that is compatible with both lung instillation and high spatial resolution is essential to enable multi-omic studies on murine lung disease models using MALDI-MSI. METHODS AND RESULTS: To maintain the structural integrity of the tissue, murine lungs were inflated with 8% (w/v) gelatin for lipid MSI of fresh frozen tissues or 4% (v/v) paraformaldehyde neutral buffer for N-glycan and peptide MSI of FFPE tissues. Tissues were sectioned and prepared for enzymatic digestion and/or matrix deposition. Glycerol-free PNGase F was applied for N-glycan MSI, while Trypsin Gold was applied for peptide MSI using the iMatrixSpray and ImagePrep Station, respectively. For lipid, N-glycan and peptide MSI, α-cyano-4-hydroxycinnamic acid matrix was deposited using the iMatrixSpray. MS data were acquired with 20 µm spatial resolution using a timsTOF fleX MS instrument followed by MS fragmentation of lipids, N-glycans and peptides. For lipid MSI, trapped ion mobility spectrometry was used to separate isomeric/isobaric lipid species. SCiLS™ Lab was used to visualize all MSI data. For analyte identification, MetaboScape®, GlycoMod and Mascot were used to annotate MS fragmentation spectra of lipids, N-glycans and tryptic peptides, respectively. CONCLUSIONS: Our protocol provides instructions on sample preparation for high spatial resolution MALDI-MSI, MS/MS data acquisition and lipid, N-glycan and peptide annotation and identification from murine lungs. This protocol will allow non-biased analyses of diseased lungs from preclinical murine models and provide further insight into disease models.
Subject(s)
Peptides , Tandem Mass Spectrometry , Animals , Mice , Peptides/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Polysaccharides/analysis , Lung/chemistry , LipidsABSTRACT
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Male , Female , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Proteomics/methods , Chromatography, Liquid/methods , Proteome , Tandem Mass Spectrometry , PeptidesABSTRACT
PURPOSE: To investigate surrogate optimisation (SO) as a modern, purely data-driven, nonlinear adaptive iterative strategy for lens formula constant optimisation in intraocular lens power calculation. METHODS: A SO algorithm was implemented for optimising the root mean squared formula prediction error (rmsPE, defined as predicted refraction minus achieved refraction) for the SRKT, Hoffer Q, Holladay, Haigis and Castrop formulae in a dataset of N = 888 cataractous eyes with implantation of the Hoya Vivinex hydrophobic acrylic aspheric lens. A Gaussian Process estimator was used as the model, and the SO was initialised with equidistant datapoints within box constraints, and the number of iterations restricted to either 200 (SRKT, Hoffer Q, Holladay) or 700 (Haigis, Castrop). The performance of the algorithm was compared to the classical gradient-based Levenberg-Marquardt algorithm. RESULTS: The SO algorithm showed stable convergence after fewer than 50/150 iterations (SRKT, HofferQ, Holladay, Haigis, Castrop). The rmsPE was reduced systematically to 0.4407/0.4288/0.4265/0.3711/0.3449 dioptres. The final constants were A = 119.2709, pACD = 5.7359, SF = 1.9688, -a0 = 0.5914/a1 = 0.3570/a2 = 0.1970, C = 0.3171/H = 0.2053/R = 0.0947 for the SRKT, Hoffer Q, Holladay, Haigis and Castrop formula and matched the respective constants optimised in previous studies. CONCLUSION: The SO proves to be a powerful adaptive nonlinear iteration algorithm for formula constant optimisation, even in formulae with one or more constants. It acts independently of a gradient and is in general able to search within a (box) constrained parameter space for the best solution, even where there are multiple local minima of the target function.
Subject(s)
Algorithms , Lenses, Intraocular , Optics and Photonics , Refraction, Ocular , Humans , Refraction, Ocular/physiology , Visual Acuity/physiology , Prosthesis Design , Lens Implantation, Intraocular/methods , Male , Female , Aged , Phacoemulsification/methodsABSTRACT
PURPOSE: This study aimed to estimate the corneal keratometric index in the eyes of cataract surgery patients who received zero-power intraocular lenses (IOLs). METHODOLOGY: This retrospective study analyzed postoperative equivalent spherical refraction and axial length, mean anterior curvature radius and aqueous humor refractive index to calculate the theoretical corneal keratometric index value (nk). Data was collected from 2 centers located in France and Germany. RESULTS: Thirty-six eyes were analyzed. The results revealed a mean corneal keratometric index of 1.329 ± 0.005 for traditional axial length (AL) and 1.331 ± 0.005 for Cooke modified axial length (CMAL). Results ranged from minimum values of 1.318/1.320 to maximum values of 1.340/1.340. CONCLUSION: The corneal keratometric index is a crucial parameter for ophthalmic procedures and calculations, particularly for IOL power calculation. Notably, the estimated corneal keratometric index value of 1.329/1.331 in this study is lower than the commonly used 1.3375 index. These findings align with recent research demonstrating that the theoretical corneal keratometric index should be approximately 1.329 using traditional AL and 1.331 using CMAL, based on the ratio between the mean anterior and posterior corneal curvature radii (1.22).
Subject(s)
Cataract Extraction , Cornea , Lenses, Intraocular , Refraction, Ocular , Humans , Retrospective Studies , Female , Male , Refraction, Ocular/physiology , Aged , Middle Aged , Axial Length, Eye/pathology , Visual Acuity/physiology , Aged, 80 and over , Corneal Topography/methods , Lens Implantation, Intraocular , Prosthesis Design , Follow-Up Studies , Biometry/methodsABSTRACT
Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. ABCC6 sequence variations cause the calcification phenotype of pseudoxanthoma elasticum (PXE) as well as some cases of generalized arterial calcification of infancy, which is otherwise caused by defective ENPP1. ABCC6 is primarily expressed in the liver, which has given the impression that the liver is central to the pathophysiology of PXE/generalized arterial calcification of infancy. The emergence of inflammation as a contributor to the calcification in PXE suggested that peripheral tissues play a larger role than expected. In this study, we investigated whether bone marrow-derived ABCC6 contributes to the calcification in PXE. In Abcc6â/â mice, we observed prevalent mineralization in several lymph nodes and surrounding connective tissues and an extensive network of lymphatic vessels within vibrissae, a calcified tissue in Abcc6â/â mice. Furthermore, we found evidence of lymphangiogenesis in patients with PXE and mouse skin, suggesting an inflammatory process. Finally, restoring wild-type bone marrow in Abcc6â/â mice produced a significant reduction of calcification, suggesting that the liver alone is not sufficient to fully inhibit mineralization. With evidence that ABCC6 is expressed in lymphocytes, we suggest that the adaptative immune system and inflammation largely contribute to the calcification in PXE/generalized arterial calcification of infancy.
Subject(s)
Disease Models, Animal , Multidrug Resistance-Associated Proteins , Pseudoxanthoma Elasticum , Pseudoxanthoma Elasticum/genetics , Pseudoxanthoma Elasticum/pathology , Pseudoxanthoma Elasticum/metabolism , Pseudoxanthoma Elasticum/complications , Animals , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Mice , Humans , Mice, Knockout , Lymphangiogenesis/genetics , Female , Male , Bone Marrow/pathology , Vibrissae , Calcinosis/pathology , Calcinosis/genetics , Calcinosis/etiology , Vascular Calcification/pathology , Vascular Calcification/genetics , Vascular Calcification/etiology , Vascular Calcification/metabolism , Lymphatic Vessels/pathology , Mice, Inbred C57BLABSTRACT
PURPOSE: The purpose of this study was to investigate the repeatability of biometric measures and also to assess the interactions between the uncertainties in these measures for use in an error propagation model, using data from a large patient cohort. METHODS: In this cross-sectional non-randomised study we evaluated a dataset containing 3379 IOLMaster 700 biometric measurements taken prior to cataract surgery. Only complete scans with at least 3 successful measurements for each eye performed on the same day were considered. The mean (Mean) and standard deviations (SD) for each sequence of measurements were derived and analysed. Correlations between the uncertainties were assessed using Spearman rank correlations. RESULTS: In the dataset with 677 eyes matching the inclusion criteria, the within subject standard deviation and repeatability for all parameters match previously published data. The SD of the axial length (AL) increased with the Mean AL, but there was no noticeable dependency of the SD of any of the other parameters on their corresponding Mean value. The SDs of the parameters are not independent of one another, and in particular we observe correlations between those for AL, anterior chamber depth, aqueous depth, lens thickness and corneal thickness. CONCLUSIONS: The SD change over Mean for AL measurement and the correlations between the uncertainties of several biometric parameters mean that a simple Gaussian error propagation model cannot be used to derive the effect of biometric uncertainties on the predicted intraocular lens power and refraction after cataract surgery.
Subject(s)
Cataract , Lenses, Intraocular , Humans , Cross-Sectional Studies , Axial Length, Eye , Prospective Studies , Biometry , Anterior Chamber/diagnostic imagingABSTRACT
The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase â¼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased â¼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.
Subject(s)
B-Lymphocytes , Cell Differentiation , Immunoglobulin M , Lipopolysaccharides , Lymphocyte Activation , Selenoproteins , Animals , Lipopolysaccharides/pharmacology , Immunoglobulin M/blood , Immunoglobulin M/metabolism , Mice , Selenoproteins/metabolism , Selenoproteins/genetics , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Mice, Knockout , Plasma Cells/metabolism , Plasma Cells/immunology , Lipidomics , Up-Regulation , Mice, Inbred C57BLABSTRACT
BACKGROUND: The purpose of this Monte-Carlo study is to investigate the effect of using a thick lens model instead of a thin lens model for the intraocular lens (IOL) on the resulting refraction at the spectacle plane and on the ocular magnification based on a large clinical data set. METHODS: A pseudophakic model eye with a thin spectacle correction, a thick cornea (curvatures for both surfaces and central thickness) and a thick IOL (equivalent power PL derived from a thin lens IOL, Coddington factor CL (uniformly distributed from -1.0 to 1.0), either preset central thickness LT = 0.9 mm (A) or optic edge thickness ET = 0.2 mm, (B)) was set up. Calculations were performed on a clinical data set containing 21 108 biometric measurements of a cataractous population based on linear Gaussian optics to derive spectacle refraction and ocular magnification using the thin and thick lens IOL models. RESULTS: A prediction model (restricted to linear terms without interactions) was derived based on the relevant parameters identified with a stepwise linear regression approach to provide a simple method for estimating the change in spectacle refraction and ocular magnification where a thick lens IOL is used instead of a thin lens IOL. The change in spectacle refraction using a thick lens IOL with (A) or (B) instead of a thin lens IOL with identical power was within limits of around ±1.5 dpt when the thick lens IOL was placed with its haptic plane at the plane of the thin lens IOL. In contrast, the change in ocular magnification from considering the IOL as a thick lens instead of a thin lens was small and not clinically significant. CONCLUSION: This Monte-Carlo simulation shows the impact of using a thick lens model IOL with preset LT or ET on the resulting spherical equivalent refraction and ocular magnification. If IOL manufacturers would provide all relevant data on IOL design data and refractive index for all power steps, this would make it possible to perform direct calculations of refraction and ocular magnification.
Subject(s)
Lens, Crystalline , Lenses, Intraocular , Humans , Refraction, Ocular , Cornea , Computer Simulation , Biometry , Optics and PhotonicsABSTRACT
PURPOSE: The purpose of this study was to investigate the uncertainty in the formula predicted refractive outcome REFU after cataract surgery resulting from measurement uncertainties in modern optical biometers using literature data for within-subject standard deviation Sw. METHODS: This Monte-Carlo simulation study used a large dataset containing 16 667 preoperative IOLMaster 700 biometric measurements. Based on literature Sw values, REFU was derived for both the Haigis and Castrop formulae using error propagation strategies. Using the Hoya Vivinex lens (IOL) as an example, REFU was calculated both with (WLT) and without (WoLT) consideration of IOL power labelling tolerances. RESULTS: WoLT the median REFU was 0.10/0.12 dpt for the Haigis/Castrop formula, and WLT it was 0.13/0.15 dpt. WoLT REFU increased systematically for short eyes (or high power IOLs), and WLT this effect was even more pronounced because of increased labelling tolerances. WoLT the uncertainty in the measurement of the corneal front surface radius showed the largest contribution to REFU, especially in long eyes (and low power IOLs). WLT the IOL power uncertainty dominated in short eyes (or high power IOLs) and the uncertainty of the corneal front surface in long eyes (or low power IOLs). CONCLUSIONS: Compared with published data on the formula prediction error of refractive outcome after cataract surgery, the uncertainty of biometric measures seems to contribute with â to ½ to the entire standard deviation. REFU systematically increases with IOL power and decreases with axial length.
Subject(s)
Cataract , Lenses, Intraocular , Phacoemulsification , Humans , Visual Acuity , Lens Implantation, Intraocular , Uncertainty , Refraction, Ocular , Biometry/methods , Retrospective Studies , Optics and PhotonicsABSTRACT
PURPOSE: To evaluate the interchangeability of different tomography devices used for ray tracing-based intraocular lens (IOL) calculation. SETTING: Eye clinic, Castrop-Rauxel, Germany. DESIGN: Retrospective analysis. METHOD: Measurements from 3 Placido-Scheimpflug devices and 3 optical coherence tomography (OCT) devices were compared in 83 and 161 other eyes after cataract surgery, respectively. 2-dimensional matrices of anterior local corneal curvature and local corneal thickness are transferred to the ray-tracing software OKULIX. Calculations are performed with the same IOL in the same position of an eye with the same axial length. Differences in spherical equivalent (SE), astigmatism, and spherical aberration are evaluated. Furthermore, the influence of the size of the matrices (optical zone) on the accuracy is quantified. RESULTS: For the Placido-Scheimpflug devices, the deviations from the average of three measurements taken for each eye in SE (mean ± SD) were 0.17 ± 0.24 diopters (D), -0.26 ± 0.29 D, and 0.08 ± 0.39 D ( P < .001, analysis of variance [ANOVA]), for the centroids of the astigmatic differences 0.04 D/173 degrees, 0.14 D/93 degrees, and 0.10 D/7 degrees, and for the median of the absolute values of the vector differences 0.31 D, 0.33 D, and 0.29 D. For OCT devices, the corresponding results were 0.01 ± 0.21 D, -0.03 ± 0.21 D, and 0.02 ± 0.20 D ( P = .005, ANOVA); 0.18 D/120 degrees, 0.07 D/70 degrees, and 0.22 D/4 degrees; and 0.26 D, 0.30 D, and 0.33 D. The accuracy of the calculated spherical aberrations allows for an individual selection of the best fitting IOL model in most cases. CONCLUSIONS: The differences are small enough to make the devices interchangeable regarding astigmatism and spherical aberration. Although there are significant differences in SE between Scheimpflug and OCT devices, the differences between OCT devices are also small enough to make them interchangeable, but the differences between Placido-Scheimpflug devices are too large to make these devices interchangeable.
Subject(s)
Astigmatism , Lenses, Intraocular , Phacoemulsification , Humans , Cornea , Astigmatism/surgery , Corneal Topography/methods , Retrospective Studies , Tomography, Optical Coherence/methods , Biometry/methodsABSTRACT
PURPOSE: To investigate the effect of formula constants on predicted refraction and limitations of constant optimization for classical and modern intraocular lens (IOL) power calculation formulae. SETTING: Tertiary care center. DESIGN: Retrospective single-center consecutive case series. METHODS: This analysis is based on a dataset of 888 eyes before and after cataract surgery with IOL implantation (Hoya Vivinex). Spherical equivalent refraction predSEQ was predicted using IOLMaster 700 data, IOL power, and formula constants from IOLCon ( https://iolcon.org ). The formula prediction error (PE) was derived as predSEQ minus achieved spherical equivalent refraction for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulae. The gradient of predSEQ (gradSEQ) as a measure for the effect of the constants on refraction was calculated and used for constant optimization. RESULTS: Using initial formula constants, the mean PE was -0.1782 ± 0.4450, -0.1814 ± 0.4159, -0.1702 ± 0.4207, -0.1211 ± 0.3740, and -0.1912 ± 0.3449 diopters (D) for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulas, respectively. gradSEQ for all formula constants (except gradSEQ for the Castrop R) decay with axial length because of interaction with the effective lens position (ELP). Constant optimization for a zero mean PE (SD: 0.4410, 0.4307, 0.4272, 0.3742, 0.3436 D) results in a change in the PE trend over axial length in all formulae where the constant acts directly on the ELP. CONCLUSIONS: With IOL power calculation formulae where the constant(s) act directly on the ELP, a change in constant(s) always changes the trend of the PE according to gradSEQ. Formulae where at least 1 constant does not act on the ELP have more flexibility to zero the mean or median PE without coupling with a PE trend error over axial length.