Improving keratoconus management with central corneal regularization and corneal collagen cross-linking protocol treatment

Purpose. To evaluate safety and efficacy of customized central corneal regularization (CCR), together with simultaneous accelerated corneal collagen cross-linking (A-CXL) - CCR-CXL protocol, to treat keratoconus-related corneal ectasia. Design. Retrospective, comparative observational case series. Methods. Patients that had undergone combined CCR-CXL protocol. Main inclusion criteria were keratoconus visual acuity deterioration and contact lens intolerance. All patients underwent complete ophthalmological evaluation, corrected distance visual acuity (CDVA) and Scheimpflug-corneal tomography. Central corneal regularization was performed by ablation using flying spot laser. Subsequently, the stroma was saturated with 0.17% riboflavin-5-phosphate added every 2 minutes, followed by A-CXL 9 mW/cm2 for 10 minutes. CDVA, medium keratometry value (Kmed), and total corneal morphological irregularity index (CMI) of patients were analyzed before surgery and after 1, 3 and 12 months. A P value of.05 or less was considered statistically significant. Results. 46 eyes of 39 keratoconus patients were treated. At 1 month, the mean CDVA (LogMar) increased from 0.19 ± 0.02 to 0.12 ± 0.02 (P < .05), and the difference remained stable at month 12. Kmax decrease was statistically significant from 57.02 ± 5.65 to 50.21 ± 4.48 (P < .05). CMI decreased significantly from 47.8 ± 2.84 to 30.1 ± 2.4 (P < .01). Conclusions. CCR-CXL protocol is safe and effective in arresting keratectasia progression and increasing corneal optic regularity in keratoconus. These findings showed a significant improvement in CDVA, keratometry values and corneal optical aberrations after being treated with the CCR-CXL protocol. Copyright © Società Editrice Universo (SEU

Hemodialysis: effects of preload reduction on novel echocardiographic parameters of left ventricular function

Abstract Funding Acknowledgements Type of funding sources: None. Background Echocardiography has been widely used to study cardiac function in patients with end-stage renal disease on hemodialysis (HD), but cardiac function assessment by measuring cardiac dimensions and their rate of change is load dependent, therefore it is influenced by volume depletion. Effects of acute volume reduction on left (LV) and right ventricular (RV) function are still not well understood. Some studies investigated myocardial mechanics after dialysis using speckle tracking echocardiography (STE) but their relative load-dependency makes STE indices unable to account for changes in pre- and afterload. Myocardial work (MW) incorporates both deformation and load into its analysis and is an emerging tool to study LV myocardial function. There are no data about the effects of hemodialysis on LV MW. Purpose This study aimed to evaluate acute changes of novel echocardiographic indices of both LV and RV function after a HD session. Methods Patients with end-stage renal disease undergoing HD were prospectively enrolled. A transthoracic echo, including STE calculation of LV global longitudinal strain (GLS) and free wall RV strain, was performed before and after hemodialysis. Parameters of MW such as global work index (GWI), global constructive work (GCW), global work efficiency (GWE) and global wasted work (GWW) were quantified using a commercially available software package. Results 27 patients were enrolled, mean baseline parameters were: LV end-diastolic volume 136 ± 38 mL, LV ejection fraction (LVEF) 56.9 ± 7.5%, LV GLS -17.1 ± 4.1%, RV free wall strain -26.9 ± 5.6%, GWI 2117 ± 602 mmHg%, GCW 2299 ± 633 mmHg%, GWW 137 ± 88 mmHg, GWE 93 ± 3.6%, systolic arterial pressure 145 ± 26 mmHg and diastolic pressure 80 ± 16mmHg. After hemodialysis we observed a significative reduction in LV GLS (p = 0.04), RV strain (p = 0.002), GWI (p = 0.002, Figure I) and GCW (p = 0.004). No significative changes in LVEF and blood pressure were observed. Comparing patients using a LVEF cut-off of 55% (19 patients with LVEF≥55%, 8 patients <55%) we observed a significative reduction of LV GLS (p = 0.004), GWI (p < 0.001), GCW (p < 0.001) only in patients with LVEF ≥55% while RV strain and LV volume showed a reduction in both groups. We observed no significative differences in extracted volumes between the groups (2.6 vs 2.1 liters,p = 0.3). Patients with normal LVEF showed a significative negative variation (D) of LVEF (-1 vs 3%), GWI (-551 vs 38 mmHg%) and GCW (-522 vs 11 mmHg%). Correlations were found between DGWI and extracted volume (r= 0.46, p = 0.01), basal GWI and both DLVEF (r= 0.39, p = 0.04) and DLV GLS (r= 0,42, p = 0.02), basal LV GLS and DLVEF (r= 0.5, p < 0.01). Conclusions Our preliminary data show that, immediately after the HD session, there is a reduction in biventricular STE-derived systolic parameters. Patients with normal LV systolic function are more sensitive to acute volume changes and entity of volume depletion seems to be correlated with MW reduction. Abstract Figure

Misalignment of hemodynamic forces in the left ventricle is associated with adverse remodeling following STEMI

Abstract Funding Acknowledgements Type of funding sources: None. Background Infarct size (IS), area at risk (AAR) and microvascular obstruction (MVO) are well known predictors of adverse remodeling (aLVr) following acute myocardial infarction, while the pathogenic role of left ventricular (LV) hemodynamic forces (HDFs) is still unknown. Recent evidence suggests the role of HDFs in negative remodeling after pathogenic events. Purpose To identify LV HDFs patterns associated with aLVr in reperfused ST-segment elevation MI (STEMI) patients. Methods Forty-nine acute STEMI patients underwent CMR at 1 week (baseline) and 4 months (follow-up) after MI. The following parameters were measured: left ventricular end-diastolic and end-systolic volume index for body surface area (LVEDVi and LVESVi), left ventricular ejection fraction (LVEF) and LV mass index, AAR and IS. LV HDFs were computed at baseline from cine CMR long axis datasets using a novel method based on LV endocardial boundary tracking. LV HDFs were calculated both in apex-base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs were evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio %). All HDFs parameters are computed over the entire heartbeat, in systole and diastole. aLVr was defined as an absolute increase in LVESV of at least 15% (ΔLV-ESV ≥15%). Results Patients with aLVr (n = 18; 37%) had significant greater value of AAR (32 ± 23 vs 22 ± 18; p = 0.03) and slightly larger IS (23 ± 16 vs 15 ± 11; p= 0.07) at baseline. In patients with aLVr at FU, baseline systolic L-S HDF were lower (2.7 ± 0.9 vs 3.6 ± 1; p = 0.027) while diastolic L-S/A-B HDF ratio was significantly higher (28 ± 14 vs 19 ± 6; p = 0.03), reflecting higher grade of diastolic HDFs misalignment. At univariate logistic regression analysis, higher IS [Odd ratio (OR) 1.05; 95% confidence interval (95% CI) 1.01-1.1; p= 0.04] L-S HDFs (OR 0.41; 95% CI 0.2-0.9; p= 0.04] and higher diastolic L-S/A-B HDFs ratio (OR 1.1; 95% CI 1.01-1.2; p= 0.05) were associated with aLVr at FU (Table). At multivariate logistic regression analysis, L-S/A-B HDF ratio remained the only independent predictor of adverse LV remodeling after correction for other baseline determinants. Conclusion Misalignment of diastolic HDFs following STEMI is associated with aLVr observed after 4 months. Predictors of adverse remodeling Univariate Multivariate Parameter OR (95% CI) P OR (95% CI) P IS (%) 1.05 (1.01-1.1) 0.042 - - Systolic L-S HDF 0.41 (0.2-0.9) 0.04 - - Diastolic L-S/A-B HDF Ratio 1.1 (1.01-1.2) 0.05 1.1 (1.01-1.2) 0.04 A-B:apex-base; L-S: latero-septal; HDFs: hemodynamic forces Abstract Figure. Diastolic HDFs distribution and aLV

A Variational Procedure for Time-Dependent Processes

A simple variational Lagrangian is proposed for the time development of an arbitrary density matrix, employing the "factorization" of the density. Only the "kinetic energy" appears in the Lagrangian. The formalism applies to pure and mixed state cases, the Navier-Stokes equations of hydrodynamics, transport theory, etc. It recaptures the Least Dissipation Function condition of Rayleigh-Onsager {\bf and in practical applications is flexible}. The variational proposal is tested on a two level system interacting that is subject, in one instance, to an interaction with a single oscillator and, in another, that evolves in a dissipative mode.Comment: 25 pages, 4 figure

Determination of deoxynivalenol and nivalenol producing chemotypes of Fusarium graminearum isolated from durum wheat in different Italian regions

Durum wheat production in Italy is economically of great importance. Fusarium graminearum is the main fusarium head blight (FHB) causal agent in wheat, reducing both yield and grain quality. F. graminearum produces several mycotoxins and, among trichothecenes, deoxynivalenol (DON) and nivalenol (NIV) are the most studied for their toxicity towards humans and animals. DON-producing isolates can be further distinguished on the basis of the predominant acetyl-DON derivative in 3-acetyldeoxynivalenol (3-ADON) or 15acetyldeoxynivalenol (15-ADON). In order to evaluate possible mycotoxin contamination risks in food, it is very important to know which chemotype is the prevalent in a F. graminearum population. F. graminearum sensu stricto strains were collected from symptomatic durum wheat heads and grains of several naturally infected fields located mostly in Emilia – Romagna, The Marche, Lazio, Tuscany and Umbria. A multiplex PCR in the region of genes Tri12, located in the terminal gene cluster of trichothecenes, was used to characterize 187 single-spore isolates of F. graminearum as NIV, 3-ADON and 15-ADON chemotypes. All the three chemotypes were present in the F. graminearum population studied. The most frequent chemotype was 15-ADON (83.4%), followed by 3-ADON (10.7%) and NIV (5.9%). NIV-producing isolates were found only in Emilia-Romagna (3.5%), Umbria (33.3%) and The Marche (5.7%)

SUBA: the Arabidopsis Subcellular Database

Knowledge of protein localisation contributes towards our understanding of protein function and of biological inter-relationships. A variety of experimental methods are currently being used to produce localisation data that need to be made accessible in an integrated manner. Chimeric fluorescent fusion proteins have been used to define subcellular localisations with at least 1100 related experiments completed in Arabidopsis. More recently, many studies have employed mass spectrometry to undertake proteomic surveys of subcellular components in Arabidopsis yielding localisation information for ∼2600 proteins. Further protein localisation information may be obtained from other literature references to analysis of locations (AmiGO: ∼900 proteins), location information from Swiss-Prot annotations (∼2000 proteins); and location inferred from gene descriptions (∼2700 proteins). Additionally, an increasing volume of available software provides location prediction information for proteins based on amino acid sequence. We have undertaken to bring these various data sources together to build SUBA, a SUBcellular location database for Arabidopsis proteins. The localisation data in SUBA encompasses 10 distinct subcellular locations, >6743 non-redundant proteins and represents the proteins encoded in the transcripts responsible for 51% of Arabidopsis expressed sequence tags. The SUBA database provides a powerful means by which to assess protein subcellular localisation in Arabidopsis ()

Semiclassical Quantum Gravity: Obtaining Manifolds from Graphs

We address the "inverse problem" for discrete geometry, which consists in determining whether, given a discrete structure of a type that does not in general imply geometrical information or even a topology, one can associate with it a unique manifold in an appropriate sense, and constructing the manifold when it exists. This problem arises in a variety of approaches to quantum gravity that assume a discrete structure at the fundamental level; the present work is motivated by the semiclassical sector of loop quantum gravity, so we will take the discrete structure to be a graph and the manifold to be a spatial slice in spacetime. We identify a class of graphs, those whose vertices have a fixed valence, for which such a construction can be specified. We define a procedure designed to produce a cell complex from a graph and show that, for graphs with which it can be carried out to completion, the resulting cell complex is in fact a PL-manifold. Graphs of our class for which the procedure cannot be completed either do not arise as edge graphs of manifold cell decompositions, or can be seen as cell decompositions of manifolds with structure at small scales (in terms of the cell spacing). We also comment briefly on how one can extend our procedure to more general graphs.Comment: 16 pages, 5 figure

Bacillus anthracis Lethal Toxin Disrupts TCR Signaling in CD1d-Restricted NKT Cells Leading to Functional Anergy

Exogenous CD1d-binding glycolipid (α-Galactosylceramide, α-GC) stimulates TCR signaling and activation of type-1 natural killer–like T (NKT) cells. Activated NKT cells play a central role in the regulation of adaptive and protective immune responses against pathogens and tumors. In the present study, we tested the effect of Bacillus anthracis lethal toxin (LT) on NKT cells both in vivo and in vitro. LT is a binary toxin known to suppress host immune responses during anthrax disease and intoxicates cells by protective antigen (PA)-mediated intracellular delivery of lethal factor (LF), a potent metalloprotease. We observed that NKT cells expressed anthrax toxin receptors (CMG-2 and TEM-8) and bound more PA than other immune cell types. A sub-lethal dose of LT administered in vivo in C57BL/6 mice decreased expression of the activation receptor NKG2D by NKT cells but not by NK cells. The in vivo administration of LT led to decreased TCR-induced cytokine secretion but did not affect TCR expression. Further analysis revealed LT-dependent inhibition of TCR-stimulated MAP kinase signaling in NKT cells attributable to LT cleavage of the MAP kinase kinase MEK-2. We propose that Bacillus anthracis–derived LT causes a novel form of functional anergy in NKT cells and therefore has potential for contributing to immune evasion by the pathogen