Distal limb osteoarthritis in the horse

The aim of this thesis was to study two objective methods of osteoarthritis (OA) diagnosis in horses and use them on the assessment of new intra-articular treatments. The studied methods were a new inertial-sensor based system of lameness detection and cartilage biomarkers in serum. It was found that distal limb flexion is significantly correlated to the presence of metacarpo-phalangeal OA in hind limbs and that inertial-sensors are sensitive in detecting asymmetry in these cases. A positive and significant correlation was observed between Coll2-1 concentration in serum and the presence of joint disease in males and young horses. Fib3-2 measurement has good potential to be used since it is not influenced by sex or age. Using an experimental model of OA, adipose stem cells pre-activated with interferon-gamma decreased joint inflammation and radiographic lesions. In clinical cases, a single injection of high-concentrated and high-molecular weight hyaluronic-acid decreased joint inflammation and biomarkers’ concentration; OSTEOARTRITE DO MEMBRO DISTAL NO CAVALO Resumo: A finalidade desta tese foi estudar dois métodos de diagnóstico objetivo de osteoartrite (OA) em equinos e aplicá-los na avaliação de novas terapias intra-articulares. Utilizou-se um sistema de sensores de movimento e foi avaliada a concentração de biomarcadores de cartilagem no soro. Concluiu-se que a flexão distal positiva está correlacionada com OA na articulação metacarpofalângica nos membros posteriores e que os sensores são sensíveis na detecção de assimetria nestes casos. Existe uma correlação positiva e significativa entre as concentrações de Coll2-1 e a presença de doença articular, sobretudo em machos e jovens. A dosagem de Fib3-2 tem utilidade por não ser influenciada pelo sexo nem idade. Num modelo experimental da doença, a terapia à base de células estaminais reduziu a inflamação articular e as lesões radiográficas. Em casos clínicos, o tratamento com ácido-hialurónico de alta concentração e peso molecular provoca uma diminuição da inflamação articular e dos biomarcadores no soro.

Cow, farm, and management factors during the dry period that determine the rate of clinical mastitis after calving

The purpose of the research was to investigate cow characteristics, farm facilities, and herd management strategies during the dry period to examine their joint influence on the rate of clinical mastitis after calving. Data were collected over a 2-yr period from 52 commercial dairy farms throughout England and Wales. Cows were separated for analysis into those housed for the dry period (8,710 cow-dry periods) and those at pasture (9,964 cow-dry periods). Multilevel models were used within a Bayesian framework with 2 response variables, the occurrence of a first case of clinical mastitis within the first 30 d of lactation and time to the first case of clinical mastitis during lactation. A variety of cow and herd management factors were identified as being associated with an increased rate of clinical mastitis and these were found to occur throughout the dry period. Significant cow factors were increased parity and at least one somatic cell count ≥200,000 cells/mL in the 90 d before drying off. A number of management factors related to hygiene were significantly associated with an increased rate of clinical mastitis. These included measures linked to the administration of dry-cow treatments and management of the early and late dry-period accommodation and calving areas. Other farm factors associated with a reduced rate of clinical mastitis were vaccination with a leptospirosis vaccine, selection of dry-cow treatments for individual cows within a herd rather than for the herd as a whole, routine body condition scoring of cows at drying off, and a pasture rotation policy of grazing dry cows for a maximum of 2 wk before allowing the pasture to remain nongrazed for a period of 4 wk. Models demonstrated a good ability to predict the farm incidence rate of clinical mastitis in a given year, with model predictions explaining over 85% of the variability in the observed data. The research indicates that specific dry-period management strategies have an important influence on the rate of clinical mastitis during the next lactation.

Variabilidade da frequência cardíaca após treinamento concorrente : comparação entre homens e mulheres de meia-idade = Heart rate variability after concurrent training : comparison between middle-aged men and women

Universidade Estadual de Campinas . Faculdade de Educação Física

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy

Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.

Ringo: Discordance between the molecular and clinical manifestation in a Golden Retriever Muscular Dystrophy dog

Of the various genetic homologues to Duchenne Muscular Dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog, which presents a variable but usually severe and progressive muscle weakness, has the closest relevance to DMD in both clinical severity and histopathological change. Among 77 GRMD dogs born in our colony in Brazil, we have identified a very mildly affected dog, Ringo, born July 2003. Among his descendants, at least one male, Suflair, is also showing a mild course. In an attempt to better characterize these two dogs, we studied the pattern of muscle proteins expression in Ringo and Suflair, as compared to severely affected and normal control dogs. Dystrophin was absent in both and utrophin was overexpressed in a pattern similar to the observed in severely affected dogs. Understanding the mechanism that is protecting Ringo and Suflair from the deleterious effect of the dystrophin gene mutation is of utmost interest, In addition it points out that the clinical impact of therapeutic trials should be interpreted with caution. (C) 2009 Elsevier B.V. All rights reserved.

Effects of Exercise Training in Patients with Chronic Heart Failure and Sleep Apnea

Study Objectives: To test the effects of exercise training on sleep and neurovascular control in patients with systolic heart failure with and without sleep disordered breathing. Design: Prospective interventional study. Setting: Cardiac rehabilitation and exercise physiology unit and sleep laboratory. Patients: Twenty-five patients with heart failure, aged 42 to 70 years, and New York Heart Association Functional Class I-III were divided into 1 of 3 groups: obstructive sleep apnea (n = 8), central sleep apnea (n 9) and no sleep apnea (n = 7). Interventions: Four months of no-training (control) followed by 4 months of an exercise training program (three 60-minute, supervised, exercise sessions per week). Measures and Results: Sleep (polysomnography), microneurography, forearm blood flow (plethysmography), peak VO(2). and quality of life were evaluated at baseline and at the end of the control and trained periods. No significant changes occurred in the control period. Exercise training reduced muscle sympathetic nerve activity (P < 0.001) and increased forearm blood flow (P < 0.01), peak VO(2) (P < 0.01), and quality of life (P < 0.01) in all groups, independent of the presence of sleep apnea. Exercise training improved the apnea-hypopnea index, minimum O(2) saturation, and amount stage 3-4 sleep (P < 0.05) in patients with obstructive sleep apnea but had no significant effects in patients with central sleep apnea. Conclusions. The beneficial effects of exercise training on neurovascular function, functional capacity, and quality of life in patients with systolic dysfunction and heart failure occurs independently of sleep disordered breathing. Exercise training lessens the severity of obstructive sleep apnea but does not affect central sleep apnea in patients with heart failure and sleep disordered breathing.

Veterinary parasitology teaching in eastern Australia

There are tendencies in universities globally to change undergraduate teaching in veterinary parasitology. To be able to give considered advice to universities, faculties, governmental bodies and professional societies about a discipline and to establish how particular changes may impact on the quality of a course, is the requirement to record and review its current status. The present paper contributes toward this objective by providing a snap-shot of the veterinary parasitology courses at the Universities of Melbourne, Sydney and Queensland in eastern Australia. It includes a description of the veterinary science curriculum in each institution, and provides an outline of its veterinary parasitology course, including objectives, topics covered, course delivery, student examination procedures and course evaluation. Student contact time in veterinary parasitology during the curriculum is currently higher in Melbourne (183 h) compared with Sydney and Queensland (106-110 h). In the teaching of parasitology, Melbourne adopts a taxonomic approach (in the pre-clinical period) followed by a combined disciplinary and problem-based approach in the clinical semesters, whereas both Sydney and Queensland focus more on presenting parasites on a host species-basis followed by a problem-based approach. (C) 2002 Elsevier Science B.V. All rights reserved.

Demand for and availability of online support to stop smoking

OBJECTIVES: Estimate the frequency of online searches on the topic of smoking and analyze the quality of online resources available to smokers interested in giving up smoking. METHODS: Search engines were used to revise searches and online resources related to stopping smoking in Brazil in 2010. The number of searches was determined using analytical tools available on Google Ads; the number and type of sites were determined by replicating the search patterns of internet users. The sites were classified according to content (advertising, library of articles and other). The quality of the sites was analyzed using the Smoking Treatment Scale- Content (STS-C) and the Smoking Treatment Scale - Rating (STS-R). RESULTS: A total of 642,446 searches was carried out. Around a third of the 113 sites encountered were of the 'library' type, i.e. they only contained articles, followed by sites containing clinical advertising (18.6) and professional education (10.6). Thirteen of the sites offered advice on quitting directed at smokers. The majority of the sites did not contain evidence-based information, were not interactive and did not have the possibility of communicating with users after the first contact. Other limitations we came across were a lack of financial disclosure as well as no guarantee of privacy concerning information obtained and no distinction made between editorial content and advertisements. CONCLUSIONS: There is a disparity between the high demand for online support in giving up smoking and the scarcity of quality online resources for smokers. It is necessary to develop interactive, customized online resources based on evidence and random clinical testing in order to improve the support available to Brazilian smokers.

Experimental characterization of the out-of-plane performance of regular stone masonry walls, including test setups and axial load influence

Stone masonry is one of the oldest and most worldwide used building techniques. Nevertheless, the structural response of masonry structures is complex and the effective knowledge about their mechanical behaviour is still limited. This fact is particularly notorious when dealing with the description of their out-of-plane behaviour under horizontal loadings, as is the case of the earthquake action. In this context, this paper describes an experimental program, conducted in laboratory environment, aiming at characterizing the out-of-plane behaviour of traditional unreinforced stone masonry walls. In the scope of this campaign, six full-scale sacco stone masonry specimens were fully characterised regarding their most important mechanic, geometric and dynamic features and were tested resorting to two different loading techniques under three distinct vertical pre-compression states; three of the specimens were subjected to an out-of-plane surface load by means of a system of airbags and the remaining were subjected to an out-of-plane horizontal line-load at the top. From the experiments it was possible to observe that both test setups were able to globally mobilize the out-of-plane response of the walls, which presented substantial displacement capacity, with ratios of ultimate displacement to the wall thickness ranging between 26 and 45 %, as well as good energy dissipation capacity. Finally, very interesting results were also obtained from a simple analytical model used herein to compute a set of experimental-based ratios, namely between the maximum stability displacement and the wall thickness for which a mean value of about 60 % was found.

Efeito do carregamento cíclico e da pré-fendilhação do betão no comportamento de lajes de betão armado reforçadas à flexão com laminados de CFRP inseridos

Dissertação de mestrado integrado em Engenharia Civil

Insights into bacterial colony morphology evolution and diversification during infection development in cystic fibrosis

Tese de Doutoramento em Engenharia Biomédica.

Graphical simulators for AUV development

A long development time is needed from the design to the implementation of an AUV. During the first steps, simulation plays an important role, since it allows for the development of preliminary versions of the control system to be integrated. Once the robot is ready, the control systems are implemented, tuned and tested. The use of a real-time simulator can help closing the gap between off-line simulation and real testing using the already implemented robot. When properly interfaced with the robot hardware, a real-time graphical simulation with a "hardware in the loop" configuration, can allow for the testing of the implemented control system running in the actual robot hardware. Hence, the development time is drastically reduced. These paper overviews the field of graphical simulators used for AUV development proposing a classification. It also presents NEPTUNE, a multi-vehicle, real-time, graphical simulator based on OpenGL that allows hardware in the loop simulations

Serial QuantiFERON-TB Gold In-Tube assay and tuberculin skin test to diagnose latent tuberculosis in household Mexican contacts: conversion and reversion rates and associated factors using conventional and borderline zone definitions

A cohort of 123 adult contacts was followed for 18‐24 months (86 completed the follow-up) to compare conversion and reversion rates based on two serial measures of QuantiFERON (QFT) and tuberculin skin test (TST) (PPD from TUBERSOL, Aventis Pasteur, Canada) for diagnosing latent tuberculosis (TB) in household contacts of TB patients using conventional (C) and borderline zone (BZ) definitions. Questionnaires were used to obtain information regarding TB exposure, TB risk factors and socio-demographic data. QFT (IU/mL) conversion was defined as <0.35 to ≥0.35 (C) or <0.35 to >0.70 (BZ) and reversion was defined as ≥0.35 to <0.35 (C) or ≥0.35 to <0.20 (BZ); TST (mm) conversion was defined as <5 to ≥5 (C) or <5 to >10 (BZ) and reversion was defined as ≥5 to <5 (C). The QFT conversion and reversion rates were 10.5% and 7% with C and 8.1% and 4.7% with the BZ definitions, respectively. The TST rates were higher compared with QFT, especially with the C definitions (conversion 23.3%, reversion 9.3%). The QFT conversion and reversion rates were higher for TST ≥5; for TST, both rates were lower for QFT <0.35. No risk factors were associated with the probability of converting or reverting. The inconsistency and apparent randomness of serial testing is confusing and adds to the limitations of these tests and definitions to follow-up close TB contacts.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Knowledge management for systems biology a general and visually driven framework applied to translational medicine

Background: To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data. Different approaches to this challenge exist but so far none has proven entirely satisfactory. Results: To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies. Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases. From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data. Conclusions: We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects. The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation. Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development.