Cytokine Profiles in Toxoplasmic and Viral Uveitis

BackgroundUveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context MethodsUsing a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract ResultsFive mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-γ, IL-6, and macrophage inflammatory protein-1β were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis ConclusionsWe found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatmen

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Nonlinear Multilayered Representation of Graph-Signals

We propose a nonlinear multiscale decomposition of signals defined on the vertex set of a general weighted graph. This decomposition is inspired by the hierarchical multiscale (BV, L 2) decomposition of Tadmor, Nezzar, and Vese (Multiscale Model. Simul. 2(4):554–579, 2004). We find the decomposition by iterative regularization using a graph variant of the classical total variation regularization (Rudin et al, Physica D 60(1–4):259–268, 1992). Using tools from convex analysis, and in particular Moreau’s identity, we carry out the mathematical study of the proposed method, proving the convergence of the representation and providing an energy decomposition result. The choice of the sequence of scales is also addressed. Our study shows that the initial scale can be related to a discrete version of Meyer’s norm (Meyer, Oscillating Patterns in Image Processing and Nonlinear Evolution Equations, 2001) which we introduce in the present paper. We propose to use the recent primal-dual algorithm of Chambolle and Pock (J. Math. Imaging Vis. 40:120–145, 2011) in order to compute both the minimizer of the graph total variation and the corresponding dual norm. By applying the graph model to digital images, we investigate the use of nonlocal methods to the multiscale decomposition task. Since the only assumption needed to apply our method is that the input data is living on a graph, we are also able to tackle the task of adaptive multi

Minimal topology for a radial basis functions neural network for pattern classification

In the context of pattern classification, the success of a classification scheme often depends on the geometrical properties of the pattern classes under consideration. As radial basis functions (RBF) neural networks have largely been applied in pattern classification problems, in this paper we present a brief overview of different trends in radial basis functions neural networks and their applications. The meanings of the weights and the processing units for a RBF network applied for pattern classification are given. A new learning algorithm for a RBF neural network is proposed in this paper. This algorithm gives a solution for classifying configurations of patterns in a feature space providing the minimum number of hidden units for the network implementation. The learning is based on the backpropagation algorithm. The performance of the proposed algorithm is assessed on different artificial and real applications. The algorithm is successfully applied for estimating a distribution, as well as for separating signals in a multiple access communication system and for recognizing static speech. © 1994 Academic Press. All rights reserved