Osteoarthritis

Osteoarthritis is a common and important problem in performance horses and symptoms include lameness accompanied with heat, pain and joint swelling. Several different diagnostic methods exist. However, detection of early stages of inflammation is problematic; hence assays for biochemical markers, such as the cytokines, are considered a possible way to monitor inflammation. Many of the cytokines are mediators released in the process of inflammation and one important example is tumor necrosis factor alpha (TNFα). In this pilot study of five horses, an ELISA was used to measure TNFα in synovial fluid from fetlock joints. This was performed in order to evaluate if any inflammatory reaction against intra-articularly injected hyaluronan X (hyaluronic acid) was present. Hyaluronan X is a new product with a higher molecular weight compared to hyaluronic suspensions commonly used in equine practice for the treatment of osteoarthritis. All the horses showed clinical signs of joint inflammation at some point. However, only one of the five horses presented a detectable level of TNFα in synovial fluid from the fetlock joint. Unfortunately, the hyaluronan X had been contaminated with ethanol during the manufacture and hence no conclusions about the side effects of this new hyaluronic suspension could be drawn. In future studies, a revised study design with repeated sampling of synovial fluid from experimental joints as well as control joints must be developed. In addition, the manufacturing of the hyaluronic suspension must be improved.Ledinflammation (osteoartrit) är ett viktigt problem hos arbetande hästar och manifesteras som hälta med associerad värme, smärta och ledsvullnad. Flera olika diagnostiska metoder finns att tillgå men tidiga stadier av inflammation är svåra att upptäcka. Därför analyseras olika biokemiska och inflammatoriska markörer i både ledvätska och serum. Dessa markörer inkluderar de olika mediatorer som frisätts i samband med den inflammatoriska processen i leden och ett viktigt exempel är inflammationscytokinen tumör-nekros-faktor alfa (TNFα). I den nedan beskrivna pilotstudien med fem hästar injicerades kotleden i ett framben med hyaluronsyra X och den kontralaterala leden användes som kontroll. Hyaluronsyra X är en ny produkt med högre molekylvikt än de som idag används vid behandling av osteoartrit hos häst. En hästspecifik ELISA användes sedan för mätning av TNFα i ledvätska. Tanken med detta var att utvärdera huruvida injektionen av hyaluronsyra X gav upphov till en inflammatorisk reaktion i leden. Alla fem hästarna i studien visade kliniska tecken på ledinflammation men bara en av dem hade ett förhöjt värde av TNFα i kotleden. Tyvärr var hyaluronsyrasuspensionen vid ett par tillfällen kontaminerad av etanol vilket i sig kan leda till inflammation i leden. Därför kan inga slutsatser om eventuella biverkningar av preparatet dras från denna studie. Inför uppföljande studier bör tillverkningen av hyaluronsyra X förbättras och kvalitetssäkras. Dessutom måste studiedesignen förändras så att upprepade ledvätskeprover tas från både försöksleden och kontrolleden vid samma tillfällen

Endemic aleutian disease

Aleutian disease (AD) is a common global disease in farmed mink caused by infection with Aleutian disease virus (ADV). This thesis investigated the use of ADV antibody ELISA as a tool to reduce the impact on welfare and reproduction of mink in ADV endemic areas. First, two ELISA systems were compared. The ELISA system based on VP2 antigen detected ADV antibodies in serum with high sensitivity and specificity when compared to counter immunoelectrophoresis (CIEP). In contrast, the ELISA system based on ADV-G antigen did not perform as well and had a low sensitivity compared to CIEP. The VP2 ELISA also detected antibodies to ADV in dried whole blood eluted from filter paper (DBS) with a preserved high sensitivity and specificity and with good correlation to antibody levels in serum. The ADV antibody levels were comparable over a period of two weeks which may correspond to the time needed to sample all mink in large herds. The correlation between the estimated antibody level in DBS and the ratio of albumin: gamma globulins (A:γG) in serum in individual mink was generally high but superior for DBS compared to serum samples from the same mink. The use of DBS VP2 ELISA was therefore concluded to be the preferable indirect method for estimating hypergammaglobulinemia in mink. Further, the association between the reproductive performance and the antibody level was also investigated at an individual level. For the primiparous mink, the risk of being barren was associated with the AD status prior to mating. Diseased mink had a higher risk of being barren than non-diseased mink. In addition, the litter size of the primiparous non-barren female mink was also associated with the AD status prior to mating, where diseased mink had a 5% reduced litter size. For older mink, on the other hand, no difference due to AD status was found but they had approximately 5 % larger litters than primiparous mink irrespective of AD status. To aid selection of future breeders, the female mink could be categorized into two or three different disease categories depending on the mean antibody level in the herd. Selection of healthy mink for breeding can be expected to be beneficial for the welfare of the female mink, the overall breeding performance of the herd, as well as the production economy

Bisphenol A, phthalate metabolites and glucose homeostasis in healthy normal-weight children

Introduction: Bisphenol A and several of the most commonly used phthalates have been associated with adverse metabolic health effects such as obesity and diabetes. Therefore, we analyzed these man-made chemicals in first morning urine samples from 107 healthy normal-weight Danish children and adolescents. Method: This was a cross-sectional study. Participants were recruited as part of the Copenhagen Puberty Study. The subjects were evaluated by an oral glucose tolerance test (OGTT), a dual-energy X-ray absorptiometry (DXA) scan, direct oxygen uptake measurement during cycle ergometry and fasting blood samples. First morning urine was collected and phthalate metabolites and BPA were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS) with prior enzymatic deconjugation. Individual chemical concentrations were divided into tertiles and analyzed in relation to biological outcome. Results: Children in the lowest tertile of urinary BPA had significantly higher peak insulin levels during OGTT (P = 0.01), lower insulin sensitivity index (P < 0.01), higher leptin (P = 0.03), triglyceride (P < 0.01) and total cholesterol levels (P = 0.04), lower aerobic fitness (P = 0.02) and a tendency toward higher fat mass index (P = 0.1) compared with children in the highest tertile for uBPA. No significant differences in anthropometrics, body composition or glucose metabolism were associated with any of the phthalate metabolites measured. Conclusion: This pilot study on healthy normal-weight children suggests an inverse association between BPA and insulin resistance. Our findings contrast other cross-sectional studies showing a positive association for BPA, which may be due to confounding or reverse causation because diet is an important source of both BPA exposure and obesity

Hospital Acquired MRSA Penumonia

Background: Antibiotic resistance is a growing problem and particularly of concern in nosocomial infections. Nosocomial pneumonia occurs in 0.4—1.1% of hospitalized patients. It is the most common infection in intensive care units. Bacterial colonization of the upper airway followed by micro aspiration or macro inspiration into the lungs is considered the primary mechanism for development of nosocomial pneumonia. More than 90% of cases of nosocomial pneumonia are caused by bacteria, 15—30% represented with staphylococcus aureus. Following the data of a 4-year long period the resistance to methicillin was identified in ≈32% with a tendency of increasing percentage of MRSA isolates up to 35%, originated from samples taken among patients from ICU in the Clinical Center of Skopje

Health studies: opportunities for the development of Human Biomonitoring in Europe

Introduction: Human Biomonitoring (HBM) and health studies are very similar in terms of the infrastructure and procedures necessary for their implementation, as in either type of studies data is collected through fieldwork, which constitutes one of the largest expenditures for such studies. Thus, combined studies could result in more cost-effective ways to conduct health and environmental monitoring. As such, within the HBM4EU project an inventory of the health studies available which could include an HBM component was performed. Methods: An online questionnaire was developed to collect information on recently conducted, ongoing and planned health studies, which could be linked to an HBM study. The link to the questionnaire was distributed with the help of the National Hub Contact Points of the HBM4EU project. Results: From the 58 different studies included in this inventory, half were longitudinal and presented the possibility of introducing an HBM component in the future. Most of the studies for which data was reported had public funding, either from the government or from public grants (national or European). The vast majority of the studies included the collection of biological samples and the most frequently stored samples were blood, plasma, serum or DNA. More than 50% of the studies reported that the measurement of chemicals was already performed or was planned to be performed. The most frequently measured chemicals were phthalates, bisphenols and cadmium. Conclusions: In vast majority of the studies included in the inventory biological samples are collected and stored, posing the opportunity to use them in HBM studies for the analyses of chemicals of interest. About 50% of these studies already had ethical approval to measure chemicals from collected samples. Funding: HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement 733032).HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032.N/

Serum COMP-C3b complexes in rheumatic diseases and relation to anti-TNF-alpha treatment

Introduction: Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of RA patients, but not in healthy controls. We now set out to elaborate on the information provided by this marker in a variety of diseases and larger patient cohorts. Methods: COMP-C3b levels in sera were measured by using an enzyme-linked immunosorbent assay (ELISA) capturing COMP and detecting C3b. Serum COMP was measured by using ELISA. Results: COMP-C3b levels were significantly elevated in patients with RA as well as in systemic lupus erythematosus (SLE), compared with healthy controls. SLE patients with arthritis had significantly higher COMP-C3b levels than did those without. COMP-C3b was furthermore elevated in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, systemic sclerosis, and OA. COMP-C3b did not correlate with COMP in any of the patient groups. COMP-C3b correlated with disease activity in RA, but not in other diseases. COMP-C3b levels in RA patients decreased on treatment with tumor necrosis factor (TNF)-alpha inhibitors, whereas the levels increased in patients with AS or PsA. The changes of COMP-C3b did not parallel the changes of C-reactive protein (CRP). Conclusions: COMP-C3b levels are elevated in several rheumatologic diseases and correlate with inflammatory measures in RA. COMP-C3b levels in RA decrease during TNF-alpha inhibition differently from those of CRP, suggesting that formation of COMP-C3b relates to disease features not reflected by general inflammation measures

Cross-sectional analysis of sleep hours and quality with sex hormones in men

Background: Reduced total hours of sleep and low quality of sleep have been suggested to be associated with low levels of male hormones. Few studies have examined the association between excessive sleep and male reproductive hormones. Objective: To investigate the association of total hours of sleep and quality of sleep with serum levels of total, bioavailable and free testosterone (tT, bT and fT), sex hormone-binding globulin (SHBG) and dehydroepiandrosteron-sulfate (DHEAS). Methods: Serum levels of tT, SHBG and DHEAS were measured with immunoassays in a cross-sectional population-based study of 2095 males. bT and fT were calculated in accordance with Vermeulens method. Information on total hours of sleep and sleep quality was obtained by questionnaire. Linear regression was used to calculate hormones according to total hours of sleep and the results were expressed as β-estimates and 95% confidence intervals (CI). The adjustment in the multivariable models was constructed taking age, BMI, smoking, alcohol intake and physical activity into account. Results: Excessive sleep (>9 h) compared to 7–9 h of sleep was significantly associated with lower tT, bT and fT, but not with SHBG or DHEAS, after multivariable adjustment. These significant associations were also found in our analyses with hormones as continuous variables but no associations were found in our general additive model analyses. Conclusions: In this cross-sectional study in men, excessive sleep associated with lower levels of male reproductive hormones. Longitudinal studies are needed to determine the causal direction of the observed association between excessive sleep and lower male reproductive hormones levels

Early postnatal nutrition after preterm birth and cardiometabolic risk factors in young adulthood

Objectives Adults born preterm at very low birthweight (VLBW; Study design The Helsinki Study of VLBW Adults includes 166 VLBW and preterm infants born between 1978 and 1985. We collected postnatal nutrition data among 125 unimpaired subjects, who attended two study visits at the mean ages of 22.5 and 25.1 years. We evaluated the effects of energy and macronutrient intakes during the first three 3-week periods of life on key cardiometabolic risk factors with multiple linear regression models. We also report results adjusted for prenatal, postnatal and adult characteristics. Results Macronutrient and energy intakes were not associated with blood pressure, heart rate, or lipid levels in adulthood. Intakes were neither associated with fasting glucose or most other markers of glucose metabolism. An exception was that the first-three-weeks-of-life intakes predicted higher fasting insulin levels: 1 g/kg/day higher protein intake by 37.6% (95% CI: 8.0%, 75.2%), and 10 kcal/kg/day higher energy intake by 8.6% (2.6%, 14.9%), when adjusted for sex and age. These early intakes similarly predicted the adult homeostasis model assessment index. Further adjustments strengthened these findings. Conclusions Among VLBW infants with relatively low early energy intake, early macronutrient and energy intakes were unrelated to blood pressure, lipid levels and intravenous glucose tolerance test results. Contrary to our hypothesis, a higher macronutrient intake during the first three weeks of life predicted higher fasting insulin concentration in young adulthood.Peer reviewe

Beta: an experiment in funded undergraduate start up

This paper reports on an evaluation of a funded undergraduate project designed to enable student business start-up. The programme, entitled 'Beta', provides undergraduate students with £1,500 of seed-corn funding. The key objective of the project is for the participants to exit it with a viable and legal business entity through which they can start trading on completion of the course. The study adopts a case study approach and evaluates all aspects of the Beta programme, the actors involved and its processes and practices. The authors examine the development of the project and the challenges and hurdles that were identified and overcome to realize the project's goals