Clinical outcomes at one year following keratoconus treatment with accelerated transepithelial cross-linking

This study evaluated the clinical outcomes in keratoconus corneas following accelerated transepithelial corneal collagen cross-linking (CXL) (Avedro KXL® system, Waltham, MA, USA) over one year of follow-up. The mean depth of the demarcation line measured by optical coherence tomography (OCT) was 205.19 μm. One month after surgery, a non-statistically significant change was noted in sphere (P=0.18) and in spherical equivalent (P=0.17), whereas a significant improvement was observed in corrected distance visual acuity (P=0.04). A significant change was observed in topographic astigmatism (P=0.03) and posterior corneal a sphericity (P=0.04). Accelerated transepithelial CXL may be a useful technique for the management of progressive keratoconus

Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0–2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84–2.45, P = 2.15 × 10−24) in the total cohort, 2.08 (1.72–2.50, P = 1.30 × 10−14) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37–2.99, P = 4.37 × 10−4) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence

Clinical Validation of Adjusted Corneal Power in Patients with Previous Myopic Lasik Surgery

Purpose. To validate clinically a new method for estimating the corneal power (P,) using a variable keratometric index (nkadj) in eyes with previous laser refractive surgery. Setting. University of Alicante and Medimar International Hospital (Oftalmar), Alicante, (Spain). Design. Retrospective case series. Methods. This retrospective study comprised 62 eyes of 62 patients that had undergone myopic LASIK surgery. An algorithm for the calculation of 11kadj was used for the estimation of the adjusted keratometric corneal power (Pkadj). This value was compared with the classical keratometric corneal power (Pk), the True Net Power (TNP), and the Gaussian corneal power (PcGauss). Likewise, Pkadj was compared with other previously described methods. Results. Differences between PcGauss and P, values obtained with all methods evaluated were statistically significant (p < 0.01). Differences between Pkadj and PcGauss were in the limit of clinical significance (p < 0.01, loA [ - 0.33,0.60] D). Differences between Pkadj and TNP were not statistically and clinically significant (p = 0.319, loA [- 0.50,0.44] D). Differences between Pkadj and previously described methods were statistically significant (p < 0.01), except with PcHaigisL (p = 0.09, loA [ - 0.37,0.29] D). Conclusion. The use of the adjusted keratometric index (nkadj) is a valid method to estimate the central corneal power in corneas with previous myopic laser refractive surgery, providing results comparable to PcHaigisL.This study has been funded by the Project no. GRE12-33 of the University of Alicante

An overview of activity-based probes for glycosidases

As the scope of modern genomics technologies increases, so does the need for informative chemical tools to study functional biology. Activity-based probes (ABPs) provide a powerful suite of reagents to probe the biochemistry of living organisms. These probes, featuring a specificity motif, a reactive chemical group and a reporter tag, are opening-up large swathes of protein chemistry to investigation in vitro, as well as in cellular extracts, cells and living organisms in vivo. Glycoside hydrolases, by virtue of their prominent biological and applied roles, provide a broad canvas on which ABPs may illustrate their functions. Here we provide an overview of glycosidase ABP mechanisms, and review recent ABP work in the glycoside hydrolase field, encompassing their use in medical diagnosis, their application for generating chemical genetic disease models, their fine-tuning through conformational and reactivity insight, their use for high-throughput inhibitor discovery, and their deployment for enzyme discovery and dynamic characterization.Medical BiochemistryBio-organic Synthesi

Increased plasma levels of NT-proBNP, Troponin T and GDF-15 are driven by persistent AF and associated comorbidities:Data from the AF-RISK study

Atrial fibrillation (AF) is a progressive disease, and early recognition and management may reflect an important strategy to reduce its disease burden. In this study, we evaluated plasma levels of three biomarkers - N-terminal pro-brain natriuretic peptide (NTproBNP), Troponin-T, and growth differentiation factor-15 (GDF-15) - in patients with paroxysmal AF (pAF) (≤7 days of continuous AF, n = 323) and persistent AF ((AF duration &gt; 7 days and &lt; 1 year, n = 84) using patients from AF RISK study (NCT01510210). In this AF-RISK sub-study, patients with persistent AF experienced more symptoms (higher European Heart Rhythm Association class (p &lt; 0.001)), had a higher comorbidity burden (p &lt; 0.001), and had more unfavorable echocardiographic parameters (p &lt; 0.001). All three biomarker levels were significantly higher in patients with persistent AF as compared to those with pAF (p &lt; 0.001). Multivariate linear regression analyses showed that age (beta-coefficient for NTproBNP: 0.21; GDF-15: 0.41; Troponin-T: 0.23) and CHA2DS2-VASc (beta-coefficient for NTproBNP: 0.20; GDF-15: 0.25; Troponin-T: 0.27) were determinants of all three biomarkers, and that persistent AF determined NTproBNP (beta-coefficient: 0.34), but not Troponin-T and GDF-15. More detailed analysis of CHA2DS2-VASc score showed that for all three biomarkers age, coronary artery disease and heart failure were determinants of plasma biomarkers levels, whereas sex determined NTproBNP and Troponin T, and hypertension determined NTproBNP and GDF15. Overall, this study therefore suggests that in AF, Troponin T and GDF15, and especially NTproBNP could be used to detect those patients with more persistent form of AF that may warrant more aggressive treatment of AF and concomitant comorbidities. Future studies, however, are essential to evaluate if more aggressive AF treatment and risk factor management will reduce disease progression and holds a novel therapeutic intervention to reduce the burden of AF.</p

Quantitative phase microscopy enables precise and efficient determination of biomolecular condensate composition

Many compartments in eukaryotic cells are protein-rich biomolecular condensates demixed from the cyto- or nucleoplasm. Although much has been learned in recent years about the integral roles condensates play in many cellular processes as well as the biophysical properties of reconstituted condensates, an understanding of their most basic feature, their composition, remains elusive. Here we combined quantitative phase microscopy (QPM) and the physics of sessile droplets to develop a precise method to measure the shape and composition of individual model condensates. This technique does not rely on fluorescent dyes or tags, which we show can significantly alter protein phase behavior, and requires 1000-fold less material than traditional label-free technologies. We further show that this QPM method measures the protein concentration in condensates to a 3-fold higher precision than the next best label-free approach, and that commonly employed strategies based on fluorescence intensity dramatically underestimate these concentrations by as much as 50-fold. Interestingly, we find that condensed-phase protein concentrations can span a broad range, with PGL3, TAF15(RBD) and FUS condensates falling between 80 and 500 mg/ml under typical in vitro conditions. This points to a natural diversity in condensate composition specified by protein sequence. We were also able to measure temperature-dependent phase equilibria with QPM, an essential step towards relating phase behavior to the underlying physics and chemistry. Finally, time-resolved QPM reveals that PGL3 condensates undergo a contraction-like process during aging which leads to doubling of the internal protein concentration coupled to condensate shrinkage. We anticipate that this new approach will enable understanding the physical properties of biomolecular condensates and their function