Feline leishmaniosis due to Leishmania infantum (syn. L. chagasi)

Από τις αρχές του 20ου αιώνα έχουν καταγραφεί, σε διάφορες περιοχές, περιστατικά φυσικής μόλυνσης τηςγάτας από οκτώ τουλάχιστον είδη του γένους Leishmania. Για τις μεσογειακές χώρες, ιδιαίτερο ενδιαφέρον έχει η μόλυνσηαπό την L. infantum, που είναι το αίτιο της λεϊσμανίωσης του σκύλου και της σπλαγχνικής ή δερματικής λεϊσμανίασης τουανθρώπου και για τις οποίες η γάτα θα μπορούσε να αποτελεί «δευτερογενή δεξαμενή» του παρασίτου. Αν και το ποσοστότων μολυσμένων γατών μπορεί, σε ορισμένες περιπτώσεις, να ξεπερνά ακόμη και το 60%, τα συμπτωματικά ζώα είναι σπάνια,επειδή η γάτα είναι ανθεκτικότερη στη λεϊσμανίωση σε σύγκριση με το σκύλο. Οι μολυσμένες, όμως, γάτες ενδέχεται ναεμφανίσουν δερματικές και οφθαλμικές αλλοιώσεις ή/και συμπτώματα από διάφορα εσωτερικά όργανα. Τα έλκη και τα οζίδιαπου εντοπίζονται κατά κύριο λόγο στα βλεννογονοδερματικά όρια, το επιρρίνιο, το πρόσωπο και τα πτερύγια των αυτιώνείναι οι δερματικές εκείνες αλλοιώσεις που εμφανίζονται συχνότερα στην πράξη. Λιγότερο συχνές είναι η αποφολιδωτικήδερματίτιδα και η ποδοδερματίτιδα, ενώ άγνωστο παραμένει εάν για τις βλατίδες, τις εφελκίδες και την αλωπεκία, που έχουνπαρατηρηθεί σε ορισμένα μολυσμένα ζώα, θα μπορούσε πράγματι να ενοχοποιηθεί η λεϊσμανίωση. Στις οφθαλμικές αλλοιώσειςπεριλαμβάνονται η επιπεφυκίτιδα, η (ελκώδης) κερατίτιδα, η πρόσθια και οπίσθια ραγοειδίτιδα, η χοριοαμφιβληστροειδίτιδακαι η πανοφθαλμίτιδα. Από τα συμπτώματα και τις παθολογικές καταστάσεις από τα εσωτερικά όργανα, τα μόνα που θαμπορούσαν να αποδοθούν στη λεϊσμανίωση της γάτας είναι η περιφερική λεμφαδενομεγαλία, η σπληνομεγαλία, η ηπατομεγαλίακαι η νεφρίτιδα που ενδέχεται να οδηγήσει σε χρόνια νεφρική ανεπάρκεια. Από τα εργαστηριακά ευρήματα, το πλέον χαρακτηριστικόείναι η υπερσφαιριναιμία που συνήθως είναι πολυκλωνική και σπανιότερα μονοκλωνική. Η λεϊσμανίωση της γάταςσυχνά συνυπάρχει με πολλά άλλα νοσήματα και παθήσεις, που θα μπορούσαν να μεταβάλουν την κλινική εικόνα και ενδεχομένωςνα καταστείλουν το ανοσοποιητικό σύστημα των μολυσμένων ζώων. Όπως και στο σκύλο, η διάγνωση της λεϊσμανίωσης στηγάτα στηρίζεται στην αλυσιδωτή αντίδραση της πολυμεράσης (PCR), την κυτταρολογική, ιστοπαθολογική και ανοσοϊστοχημικήεξέταση, την καλλιέργεια σε ειδικά υποστρώματα και τις ορολογικές εξετάσεις. Όλες οι παραπάνω διαγνωστικές μέθοδοιπαρουσιάζουν πλεονεκτήματα και μειονεκτήματα, ενώ η ευαισθησία τους ποικίλλει ανάλογα με το διαθέσιμο βιολογικό υλικόκαι την τεχνική που εφαρμόζεται κάθε φορά. Η κυτταρολογική, ιστοπαθολογική ή/και ανοσοϊστοχημική εξέταση από το μυελότων οστών, τα λεμφογάγγλια, τη σπλήνα, τις δερματικές και τις οφθαλμικές αλλοιώσεις στοχεύει στην ανίχνευση των αμαστιγοφόρων μορφών, που όταν βρεθούν, η μόλυνση αποδεικνύεται πέρα από κάθε αμφιβολία. Οι ορολογικές εξετάσεις, ανάλογαμε τη μεθοδολογία και το όριο διαχωρισμού, υποεκτιμούν ή υπερεκτιμούν την πραγματική συχνότητα της μόλυνσης σε γάτεςπου ζουν σε περιοχές στις οποίες η νόσος ενδημεί. Με την PCR, που ανιχνεύει το DNA του παρασίτου στο μυελό των οστών,τα λεμφογάγγλια, τη σπλήνα, το δέρμα και ενδεχομένως το περιφερικό αίμα, φαίνεται ότι εξυπηρετούνται καλύτερα οι επιζωοτιολογικες μελέτες. Μέχρι σήμερα η θεραπευτική αντιμετώπιση της λεϊσμανίωσης της γάτας στηρίζεται κυρίως στημακροχρόνια χορήγηση της αλλοπουρινόλης, σε συνδυασμό με τη θεραπεία των νοσημάτων και των παθήσεων που ενδεχομένωςσυνυπάρχουν.From the beginning of the 20th century, feline infections by at least eight different Leishmania species have been sporadically reported, worldwide. In the Mediterranean countries, feline infection imposed by L. infantum, the aetiological agent of canine leishmaniosis and human visceral and cutaneous leishmaniasis, is of particular importance, because cats may represent a "secondary reservoir" of the parasite in the nature. Although the prevalence of the infection may be as high as 60%, most infected cats are resistant and remain asymptomatic, while only occasionally, they may present cutaneous and/or ocular lesions, and perhaps systemic clinical signs. In feline leishmaniosis, ulcers and nodules, usually localized at mucocutaneous junctions, planum nasale, face and ear pinnae, constitute the mainstream of cutaneous lesions. In a small number of cases, exfoliative dermatitis and pododermatitis have been noted, whereas a cause-and-effect relationship, between feline leishmaniosis and the presence of papules, crusts and generalized alopecia remains speculative. Ocular lesions, such as those associated with conjunctivitis, (ulcerative) keratitis, posterior or anterior uveitis, chorioretinitis and panopthalmitis are relatively common. The only systemic signs that have been constantly associated with feline leishmaniosis are peripheral lymphadenomegaly, splenomegaly, hepatomegaly and chronic nephritis that may lead to chronic renal failure. The most consistent laboratory abnormality is hyperglobulinaemia that is usually polyclonal. Feline leishmaniosis can co-exist with various other infectious and non-infectious diseases that may alter its clinical picture and/or influence the immunological response of the infected cat. Diagnosis is usually based on the results of cytology,histopathology, immunohistochemistry, culture, serology and polymerase chain reaction (PCR). Apart from the advantages and limitations inherent to each of these methods, their diagnostic value depends on many factors, such as the biological sample being used, the reagents and the particular technique employed. Leishmania amastigotes can be detected by applying bone marrow, lymph node, spleen, cutaneous and ocular cytology, histopathology, and/or immunohistochemistry, which are 100% specific. Serology may underestimate or even overestimate the frequency of the infection in the endemic areas, depending on the methodology and the cut-off value, whereas PCR, that can be performed on the tissues mentioned before, plus the peripheral blood may be a better option for epidemiological studies. Although a uniformly effective treatment for symptomatic cats has not been established yet, long-term allopurinol administration, along with the management of any concurrent diseases, is the only treatment to suggest at moment

Structural identifiability of dynamic systems biology models

22 páginas, 5 figuras, 2 tablas.-- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areasAFV acknowledges funding from the Galician government (Xunta de Galiza, Consellería de Cultura, Educación e Ordenación Universitaria http://www.edu.xunta.es/portal/taxonomy/term/206) through the I2C postdoctoral program, fellowship ED481B2014/133-0. AB and AFV were partially supported by grant DPI2013-47100-C2-2-P from the Spanish Ministry of Economy and Competitiveness (MINECO). AFV acknowledges additional funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 686282 (CanPathPro). AP was partially supported through EPSRC projects EP/M002454/1 and EP/J012041/1.Peer reviewe

Lie symmetries, observability and model transformation of nonlinear systems with unknown inputs

This work investigates the use of Lie symmetries for assessing and improving the observability of dynamical systems under examined sensor setups. The framework of Lie symmetry is extended to account for unmeasured and hence unknown inputs. An efficient algorithm is developed to calculate the translation and scaling symmetries of nonlinear systems with unknown inputs. The use of the algorithm to assess the observability of a given nonlinear system is demonstrated, i.e. in theory whether it would be successful to identify the dynamic states, the parameters and the unknown inputs of the system from given measurements. The work further shows the potential application of the calculated symmetries for transforming the model of an unobservable system to an equivalent model with a minimum number of unobservable states and unknown inputs. The proposed method and algorithm are illustrated on the observability properties of a dynamical system with a Bouc-Wen nonlinearity

A discontinuous unscented kalman filter for non-smooth dynamic problems

For a number of applications, including real/time damage diagnostics as well as control, online methods, i.e., methods which may be implemented on-the-fly, are necessary. Within a system identification context, this implies adoption of filtering algorithms, typically of the Kalman or Bayesian class. For engineered structures, damage or deterioration may often manifest in relation to phenomena such as fracture, plasticity, impact, or friction. Despite the different nature of the previous phenomena, they are described by a common denominator: switching behavior upon occurrence of discrete events. Such events include for example, crack initiation, transitions between elastic and plastic response, or between stick and slide modes. Typically, the state-space equations of such models are non-differentiable at such events, rendering the corresponding systems non-smooth. Identification of non-smooth systems poses greater difficulties than smooth problems of similar computational complexity. Up to a certain extent, this may be attributed to the varying identifiability of such systems, which violates a basic requirement of online Bayesian Identification algorithms, thus affecting their convergence for non-smooth problems. Herein, a treatment to this problem is proposed by the authors, termed the Discontinuous D– modification, where unidentifiable parameters are acknowledged and temporarily excluded from the problem formulation. In this work, the D– modification is illustrated for the case of the Unscented Kalman Filter UKF, resulting in a method termed DUKF, proving superior performance to the conventional, and widely adopted, alternative

Lie symmetries of nonlinear systems with unknown inputs

It has been revealed that a dynamical system being unobservable or unidentifiable for a given set of observations is fundamentally related to the existence of Lie symmetries. Lie symmetries thus have the potentiality of providing useful tools to analyze and improve the observability and identifiability properties of dynamical systems from a fundamental perspective. This work proposes a computational framework for finding general Lie symmetries of nonlinear systems in the presence of unknown inputs. The occurring framework does not rely on mathematical Ansatz as the typical setting in the existing methods, and it is therefore capable of computing all the groups of Lie symmetries admitted by the system of interest. To alleviate the computation burden of the general framework, an alternative method is developed which is based on a priori assumptions on the functional forms of Lie symmetries to be calculated. The two proposed computation methods can be used as complementary tools to handle real engineering systems efficiently and robustly. Furthermore, utilization of the calculated Lie symmetries to detect and improve observability properties (with identifiability being the observability of unknown model parameters) is systematically discussed. Effective strategies of changing sensor placement, transforming system model and adding model assumptions are introduced to improve observability, and optimally render an unobservable system observable. The concept, computation and application of Lie symmetries are illustrated through several examples of linear, nonlinear and non-smooth dynamical systems