Femoropatellar Joint Reaction Detected During a 4486 KM Ultramarathon with Mobile MRI.

Almost nothing is known about the condition of the knee joints of multistage ultra-marathon (MSUM) runner. This is first image-based investigation of the femoropatellar joint (FPJ) using a mobile 1.5T MRI accompanying the MSUM TransEurope Foot-Race (TEFR) 64 stages over 4486 km. Twenty-two (20 male) subjects got a knee MRI-protocol at defined measurement intervals during TEFR: T2*-mapping (FLASH T2*-GRE), TIRM, and fat saturated PD -sequence. In the FPJ 12 different regions were evaluated regarding cartilage T2* and thickness changes and cartilage lesions in course of TEFR and a test on possible compounding factors (running burden, BMI, age) was done if being appropriate. No significant changes in cartilage thickness- and T2*-values were found during TEFR. In 8 runners, at least one single cartilage lesion (Grade 2-3) was found at baseline, but no significant race-related adjacent T2*-changes or progress of the defects could be detected. Analyses on compounding factors were negative. In knees with MPP (5) significantly lower adjacent T2*-values were found. The extreme running burden of a MSUM seems not to have a relevant negative influence on the FPJ tissues, even if cartilage lesions are present.

MRI Cartilage Assessment of the Subtalar and Midtarsal Joints During a Transcontinental Ultramarathon - New Insights into Human Locomotion.

MR measurements can be accurately performed during 4486 km of running, opening a window into in vivo assessment of hindfoot articular cartilage under extreme ultra-endurance loading. This observational cross-sectional study included 22 randomized participants of TransEurope FootRace between Italy and the North Cape, which was accompanied by a trailer-mounted 1.5T MRI scanner over 9 weeks. Four follow up MR examinations of subtalar and midtarsal joints were performed. Statistics of cartilage T2* and thickness were obtained. Nearly all observed joints showed an initial significant mean T2* increase of 20.9% and 26.3% for the left and right side, followed by a relative decrease of 28.5% and 16.0% during the second half, respectively. It could be demonstrated that mobile MRI field studies allow in vivo functional tissue observations under extreme loading. Elevated T2* values recovered during the second half of the ultramarathon supported the evidence that this response is a physiological adaptive mechanism of chondrocyte function via upregulation of de novo synthesis of proteoglycans and collagen. These changes occurred in a distinct asymmetric pattern leaving a "biochemical signature" of articular cartilage that allows in vivo insight into joint loading. In conclusion, the normal articular cartilage of the hindfoot is resilient and adaptive, leaving extreme endurance activities up to limitless human ambition.

Characteristics, changes and influence of body composition during a 4486 km transcontinental ultramarathon: results from the TransEurope FootRace mobile whole body MRI-project.

BACKGROUND: Almost nothing is known about the medical aspects of runners doing a transcontinental ultramarathon over several weeks. The results of differentiated measurements of changes in body composition during the Transeurope Footrace 2009 using a mobile whole body magnetic resonance (MR) imager are presented and the proposed influence of visceral and somatic adipose and lean tissue distribution on performance tested. METHODS: 22 participants were randomly selected for the repeated MR measurements (intervals: 800 km) with a 1.5 Tesla MR scanner mounted on a mobile unit during the 64-stage 4,486 km ultramarathon. A standardized and validated MRI protocol was used: T1 weighted turbo spin echo sequence, echo time 12 ms, repetition time 490 ms, slice thickness 10 mm, slice distance 10 mm (breath holding examinations). For topographic tissue segmentation and mapping a modified fuzzy c-means algorithm was used. A semi-automatic post-processing of whole body MRI data sets allows reliable analysis of the following body tissue compartments: Total body volume (TV), total somatic (TSV) and total visceral volume (TVV), total adipose (TAT) and total lean tissue (TLT), somatic (SLT) and visceral lean tissue (VLT), somatic (SAT) and visceral adipose tissue (VAT) and somatic adipose soft tissue (SAST). Specific volume changes were tested on significance. Tests on difference and relationship regarding prerace and race performance and non-finishing were done using statistical software SPSS. RESULTS: Total, somatic and visceral volumes showed a significant decrease throughout the race. Adipose tissue showed a significant decrease compared to the start at all measurement times for TAT, SAST and VAT. Lean adipose tissues decreased until the end of the race, but not significantly. The mean relative volume changes of the different tissue compartments at the last measurement compared to the start were: TV -9.5% (SE 1.5%), TSV -9.4% (SE 1.5%), TVV -10.0% (SE 1.4%), TAT -41.3% (SE 2.3%), SAST -48.7% (SE 2.8%), VAT -64.5% (SE 4.6%), intraabdominal adipose tissue (IAAT) -67.3% (SE 4.3%), mediastinal adopose tissue (MAT) -41.5% (SE 7.1%), TLT -1.2% (SE 1.0%), SLT -1.4% (SE 1.1%). Before the start and during the early phase of the Transeurope Footrace 2009, the non-finisher group had a significantly higher percentage volume of TVV, TAT, SAST and VAT compared to the finisher group. VAT correlates significantly with prerace training volume and intensity one year before the race and with 50 km- and 24 hour-race records. Neither prerace body composition nor specific tissue compartment volume changes showed a significant relationship to performance in the last two thirds of the Transeurope Footrace 2009. CONCLUSIONS: With this mobile MRI field study the complex changes in body composition during a multistage ultramarathon could be demonstrated in detail in a new and differentiated way. Participants lost more than half of their adipose tissue. Even lean tissue volume (mainly skeletal muscle tissue) decreased due to the unpreventable chronic negative energy balance during the race. VAT has the fastest and highest decrease compared to SAST and lean tissue compartments during the race. It seems to be the most sensitive morphometric parameter regarding the risk of non-finishing a transcontinental footrace and shows a direct relationship to prerace-performance. However, body volume or body mass and, therefore, fat volume has no correlation with total race performances of ultra-athletes finishing a 4,500 km multistage race.

Association of Mediterranean diet, dietary supplements and alcohol consumption with breast density among women in South Germany: a cross-sectional study.

BACKGROUND: Effects of dietary factors, such as adherence to Mediterranean diet, multivitamin-multimineral supplements use and alcohol consumption on mammographic breast density, an important biomarker of breast cancer risk, are not sufficiently consistent to elaborate preventive recommendations. This study aims to investigate the association between current diet and mammographic density. METHODS: We performed a cross-sectional study in 424 pre- and post-menopausal women aged 21 to 84 years. Current Mediterranean dietary pattern, multivitamin-multimineral supplements use, alcohol consumption and potential confounders were assessed with a self-administered questionnaire in the University Hospital Ulm (2007-2008). Radiologists evaluated mammographic density according to the American College of Radiology (ACR) classification, which was summarized in low = ACR1/2 and high = ACR3/4 mammographic density. Logistic regression models were used to assess the association between current diet and mammographic density. RESULTS: Adherance to Mediterranean dietary pattern was inversely associated with mammographic density in the models adjusted for age and BMI (per 1 unit increase of score OR 0.95; 95%CI 0.90-0.997). Current use of multivitamin-multimineral supplements was also inversely associated with mammographic density (OR 0.53; 95%CI 0.34-0.83). Further adjustment revealed similar point estimates but the associations were no longer statistically significant. Compared to non-drinkers, excessive alcohol consumption (<10 g/d) was positively associated with mammographic density (OR 1.47; 95%CI 0.82-2.63). CONCLUSIONS: Our results show that dietary factors are associated with mammographic density. Adherence to Mediterranean diet and current use of multivitamin-multimineral supplements could be inversely associated with mammographic density and may suggest a protective effect against breast cancer, whereas high alcohol consumption was associated with increased mammographic density.

Femoral head-neck offset measurements in 339 subjects: distribution and implications for femoroacetabular impingement.

PURPOSE: The α-angle is a frequently used measurement to quantify head-neck offset pathology in cam-type femoroacetabular impingement. However, diverging norm values and reference intervals have been described, especially in men. METHODS: The α-angle, the head-neck offset ratio and the triangular index were measured on anteroposterior and lateral radiographs of 339 (170 men and 169 women) subjects without evident underlying hip pathology. RESULTS: For male subjects, the mean α-angle was 49.4° (SD 10.5°) on anteroposterior and 49.1° (SD 10.6°) on lateral radiographs, whereas for female subjects, it was 45.0° (SD 8.0°) and 46.1° (SD 9.9°), respectively. Thus, calculated upper limits of reference intervals in the population screened were 70° for both radiographic projections in men and 61° (anteroposterior) and 66° (lateral) in women. CONCLUSION: These data substantiate recent findings that the pathological threshold of the α-angle in male subjects may be lower than that previously assumed. LEVEL OF EVIDENCE: Diagnostic, Level III.

Reduced head-neck offset in nontraumatic osteonecrosis of the femoral head.

INTRODUCTION: Risk factors for nontraumatic osteonecrosis of the femoral head have in common that they trigger intravascular coagulation and thus lead to devascularization of the femoral head. In part of the patients, however, no risk factors seem to be evident. Mechanical reasons contributing to nontraumatic osteonecrosis have not been discussed so far. We hypothesized that recurrent traumatization of the vessels supplying the femoral head by a cam-type mechanism as in femoroacetabular impingement could add to intravascular coagulation. We, therefore, asked whether structural abnormalities at the femoral head-neck junction indicative of such a mechanism could be observed in radiographs of patients with osteonecrosis of the femoral head. MATERIALS AND METHODS: The preoperative anteroposterior and lateral radiographs of 77 patients who underwent surgery because of osteonecrosis of the femoral head were retrospectively screened for a reduced head-neck offset by measuring the α-angle. For comparison, the α-angle was measured on anteroposterior and lateral radiographs of 339 control subjects without evident underlying hip pathology. RESULTS: The mean α-angle was 62.8° (SD 18.7°) for anteroposterior and 67.6° (SD 13.2°) for lateral radiographs in patients with nontraumatic osteonecrosis of the femoral head, whereas in control subjects, the mean α-angle was 47.2° (SD 9.6°) (p < 0.0001) and 47.6° (SD 10.3°) (p < 0.0001), respectively. CONCLUSIONS: A reduced head-neck offset in patients with nontraumatic osteonecrosis of the femoral head may act as a mechanical (co-)factor in developing osteonecrosis of the femoral head.

Ultra-marathon runners are different: investigations into pain tolerance and personality traits of participants of the TransEurope FootRace 2009.

INTRODUCTION: Susceptibility to pain varies among individuals and may predispose to a higher risk for pain disorders. Thus, it is of interest to investigate subjects who exhibit higher resistance to pain. We therefore tested pain tolerance and assessed personality traits of ultra-marathon athletes who are able to run 4487 km (2789 mi) over 64 days without resting days and compare the results to controls. METHODS: After approval of the local ethics committee and with informed consent, 11 participants of the TransEurope FootRace (TEFR09 participants) and 11 matched (age, sex, and ethnicity) controls without marathon experience in the last 5 years were enrolled. They were tested for cold pain tolerance (cold pressor [CP] test), and the 240 item trait and character inventory (TCI) as well as the general self-efficacy (GSE) test were obtained. RESULTS: TransEurope FootRace participants had a highly significant greater cold pain tolerance in the CP test than controls (P = 0.0002). While the GSE test showed no differences, the TCI test provided TEFR09 participants to be less cooperative and reward dependent but more spiritually transcendent than the controls. Significant positive correlations were found between the CP test pain score at 180 seconds and several TCI subscales showing that higher pain scores correlate with higher reward dependence, dependence, cooperativeness, empathy, and pure-hearted conscience. CONCLUSIONS: Personality profiles as well as pain tolerance of our sample of TEFR09 participants differ from normal controls and-as obtained in previous studies-probably also from chronic pain patients. Low pain perception may predispose a person to become a long-distance runner. It remains unclear, however, whether low pain perception is cause or consequence of continuous extreme training.

Substantial and reversible brain gray matter reduction but no acute brain lesions in ultramarathon runners: experience from the TransEurope-FootRace Project.

BACKGROUND: During the extremely challenging 4,487 km ultramarathon TransEurope-FootRace 2009, runners showed considerable reduction of body weight. The effects of this endurance run on brain volume changes but also possible formation of brain edema or new lesions were explored by repeated magnetic resonance imaging (MRI) studies. METHODS: A total of 15 runners signed an informed consent to participate in this study of planned brain scans before, twice during, and about 8 months after the race. Because of dropouts, global gray matter volume analysis could only be performed in ten runners covering three timepoints, and in seven runners who also had a follow-up scan. Scanning was performed on three identical 1.5 T Siemens MAGNETOM Avanto scanners, two of them located at our university. The third MRI scanner with identical sequence parameters was a mobile MRI unit escorting the runners. Volumetric 3D datasets were acquired using a magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. Additionally, diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR) imaging was performed. RESULTS: Average global gray matter volume as well as body weight significantly decreased by 6% during the race. After 8 months, gray matter volume returned to baseline as well as body weight. No new brain lesions were detected by DWI or FLAIR imaging. CONCLUSIONS: Physiological brain volume reduction during aging is less than 0.2% per year. Therefore a volume reduction of about 6% during the 2 months of extreme running appears to be substantial. The reconstitution in global volume measures after 8 months shows the process to be reversible. As possible mechanisms we discuss loss of protein, hypercortisolism and hyponatremia to account for both substantiality and reversibility of gray matter volume reductions. Reversible brain volume reduction during an ultramarathon suggests that extreme running might serve as a model to investigate possible mechanisms of transient brain volume changes. However, despite massive metabolic load, we found no new lesions in trained athletes participating in a multistage ultramarathon.See related commentary http://www.biomedcentral.com/1741-7015/10/171.

The TransEurope FootRace Project: longitudinal data acquisition in a cluster randomized mobile MRI observational cohort study on 44 endurance runners at a 64-stage 4,486 km transcontinental ultramarathon.

BACKGROUND: The TransEurope FootRace 2009 (TEFR09) was one of the longest transcontinental ultramarathons with an extreme endurance physical load of running nearly 4,500 km in 64 days. The aim of this study was to assess the wide spectrum of adaptive responses in humans regarding the different tissues, organs and functional systems being exposed to such chronic physical endurance load with limited time for regeneration and resulting negative energy balance. A detailed description of the TEFR project and its implemented measuring methods in relation to the hypotheses are presented. METHODS: The most important research tool was a 1.5 Tesla magnetic resonance imaging (MRI) scanner mounted on a mobile unit following the ultra runners from stage to stage each day. Forty-four study volunteers (67% of the participants) were cluster randomized into two groups for MRI measurements (22 subjects each) according to the project protocol with its different research modules: musculoskeletal system, brain and pain perception, cardiovascular system, body composition, and oxidative stress and inflammation. Complementary to the diverse daily mobile MR-measurements on different topics (muscle and joint MRI, T2*-mapping of cartilage, MR-spectroscopy of muscles, functional MRI of the brain, cardiac and vascular cine MRI, whole body MRI) other methods were also used: ice-water pain test, psychometric questionnaires, bioelectrical impedance analysis (BIA), skinfold thickness and limb circumference measurements, daily urine samples, periodic blood samples and electrocardiograms (ECG). RESULTS: Thirty volunteers (68%) reached the finish line at North Cape. The mean total race speed was 8.35 km/hour. Finishers invested 552 hours in total. The completion rate for planned MRI investigations was more than 95%: 741 MR-examinations with 2,637 MRI sequences (more than 200,000 picture data), 5,720 urine samples, 244 blood samples, 205 ECG, 1,018 BIA, 539 anthropological measurements and 150 psychological questionnaires. CONCLUSIONS: This study demonstrates the feasibility of conducting a trial based centrally on mobile MR-measurements which were performed during ten weeks while crossing an entire continent. This article is the reference for contemporary result reports on the different scientific topics of the TEFR project, which may reveal additional new knowledge on the physiological and pathological processes of the functional systems on the organ, cellular and sub-cellular level at the limits of stress and strain of the human body. Please see related articles: http://www.biomedcentral.com/1741-7015/10/76 and http://www.biomedcentral.com/1741-7015/10/77.

Automatic detection of the carotid artery boundary on cross-sectional MR image sequences using a circle model guided dynamic programming.

BACKGROUND: Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present. METHODS: We propose a fully automated algorithm to analyze the cross-sectional area of the carotid artery in MR image sequences. It contains two phases: (1) position detection of the carotid artery, (2) accurate boundary identification of the carotid artery. In the first phase, we use intensity, area size and shape as features to discriminate the carotid artery from other tissues and vessels. In the second phase, the directional gradient, Hough transform, and circle model guided dynamic programming are used to identify the boundary accurately. RESULTS: We test the system stability using contrast degraded images (contrast resolutions range from 50% to 90%). The unsigned error ranges from 2.86% ± 2.24% to 3.03% ± 2.40%. The test of noise degraded images (SNRs range from 16 to 20 dB) shows the unsigned error ranging from 2.63% ± 2.06% to 3.12% ± 2.11%. The test of raw images has an unsigned error 2.56% ± 2.10% compared to the manual tracings. CONCLUSIONS: We have proposed an automated system which is able to detect carotid artery cross sectional boundary in MRI sequences during heart cycles. The accuracy reaches 2.56% ± 2.10% compared to the manual tracings. The system is stable, reliable and results are reproducible.

Long distance running - Can bioprofiling predict success in endurance athletes?

The TransEuropeFootRace (TEFR) was one of the most extreme multistage competitions worldwide. The ultramarathon took the runners over a distance of 4487 km, from Bari, Italy, to the North Cape, Norway, in 64 days. The participating ultra-long-distance runners had to complete almost two marathons per day (~70 km). The race was accompanied by a research team analysing adaptations of different organ systems of the human body that were exposed to a chronic lack of regeneration time. Here, we analyzed runner's urine using mass spectrometric profiling of thousands of low-molecular weight compounds. The results indicated that pre-race molecular factors can predict finishers and separate them from nonfinishers already before the race. These observations were related to the training volume as finishers ran about twice as many kilometers per week before TEFR than nonfinishers, thus apparently achieving a higher performance level and resistance against overuse. While this hypothesis needs to be validated in future long-distance races, the bioprofiling experiments suggest that the competition readiness of the runners is measurable and might be adjustable.

Cardiac structure and function in response to a multi-stage marathon over 4486 km.

AIMS: To investigate whether participation in the Trans Europe Foot Race 2009 (TEFR), an ultramarathon race held over 64 consecutive days and 4486 km, led to changes in cardiac structure and function. METHODS: Cardiac magnetic resonance imaging was performed in 20 of 67 participating runners (two women; mean ± SD age 47.8 ± 10.4 years) at three time points (baseline scan at 294 ± 135 km (B), scan two at 1735 ± 86 km (T1) and scan three at 3370 ± 90 km (T2)) during the TEFR. Imaging included an assessment of left ventricular structure (mass) and function (strain). In parallel, cardiac troponin I, NT-pro-BNP, myostatin and GDF11 were determined in venous blood samples. A subsample of ten runners returned for a follow-up scan eight months after the race. RESULTS: Left ventricular mass increased significantly (B, 158.5 ± 23.8 g; T1, 165.1 ± 23.2 g; T2, 167 ± 24.6 g; p < 0.001) over the course of the race, although no significant change was seen in the remaining structural and functional parameters. Serum concentrations of cardiac troponin I and NT-proBNP significantly increased 1.5 - and 3.5-fold, respectively, during the first measurement interval, with no further increase thereafter (cardiac troponin I, 6.8 ± 3.1 (B), 16.9 ± 10.4 (T1) and 17.1 ± 9.7 (T2); NT-proBNP, 30.3 ± 22.8 (B), 135.9 ± 177.5 (T1) and 111.2 ± 87.3 (T2)), whereas the growth markers myostatin and GDF11 did not change. No association was observed with functional parameters, including the ejection fraction and the volume of both ventricles. The follow-up scans showed a reduction to baseline values (left ventricular mass 157 ± 19.3 g). CONCLUSIONS: High exercise-induced cardiac volume load for >2 months in ultra-endurance runners results in a physiological structural adaptation with no sign of adverse cardiovascular remodelling.

A mobile MRI field study of the biochemical cartilage reaction of the knee joint during a 4,486 km transcontinental multistage ultra-marathon using T2* mapping.

Nearly nothing is known about the consequences of ultra-long-distance running on knee cartilage. In this mobile MRI field study, we analysed the biochemical effects of a 4,486 km transcontinental multistage ultra-marathon on femorotibial joint (FTJ) cartilage. Serial MRI data were acquired from 22 subjects (20 male, 18 finisher) using a 1.5 T MR scanner mounted on a 38-ton trailer, travelling with the participants of the TransEurope FootRace (TEFR) day by day over 64 stages. The statistical analyses focused on intrachondral T2* behaviour during the course of the TEFR as the main outcome variable of interest. T2* mapping (sagittal FLASH T2* weighted gradient echo) is a validated and highly accurate method for quantitative compositional cartilage analysis of specific weightbearing areas of the FTJ. T2* mapping is sensitive to changes in the equilibrium of free intrachondral water, which depends on the content and orientation of collagen and the proteoglycan content in the extracellular cartilage matrix. Within the first 1,100 km, a significant running load-induced T2* increase occurred in all joint regions: 44.0% femoral-lateral, 42.9% tibial-lateral, 34.9% femoral-medial, and 25.1% tibial-medial. Osteochondral lesions showed no relevant changes or new occurrence during the TEFR. The reasons for stopping the race were not associated with knee problems. As no further T2* elevation was found in the second half of the TEFR but a decreasing T2* trend (recovery) was observed after the 3,500 km run, we assume that no further softening of the cartilage occurs with ongoing running burden over ultra-long distances extending 4,500 km. Instead, we assume the ability of the FTJ cartilage matrix to reorganize and adapt to the load.

Pre-race determinants influencing performance and finishing of a transcontinental 4486-km ultramarathon.

BACKGROUND: Pre-race determinants influencing performance and finishing of one of the largest transcontinental multistage ultramarathons were investigated. METHODS: Forty-four participants of the TransEurope FootRace 2009 (TEFR), running 4486 km in 64 stages (average 70.1 km daily) were analyzed regarding training and running history. This included years of regular endurance running (PRY), number of finished marathons, ultramarathons (UM) and multistage ultramarathons (MSUM), pre-race records (PRR) for marathon and specific UM races and the extent of pre-race training (PRT) in the last year before TEFR: volume (km/week), duration (h/week) and intensity (km/h). RESULTS: Mean total running speed during TEFR was 8.25 km/h.Seventy-one percent of subjects finished the race. The mean PRT-volume extends 5500 km. Finishers and non-finishers of the TEFR did not show significant difference in any tested pre-race determinants. There was no association between PRY, number of finished marathons, UM, and MSUM and TEFR performance. There was very strong positive correlation between PRT-intensity and TEFR performance. PRT volume correlated with a medium effect size to TEFR performance. PRR in specific ultra-races (6-hour, 50-km, 100-km races) showed a high correlation to TEFR performance. Performance in ultramarathon correlates inversely with age. CONCLUSIONS: Like in other endurance disciplines with shorter distances, in ultra-long multistage endurance running the athletes also need a stage-specific pre-race experience, training and adaptation if he wants to end up with a good performance. But dropping out of a MSUM seems not to be consistent with regard to specific pre-race experience. Further research results of TEFR project may reveal potential risk factors for non-finishing a transcontinental footrace.

Serological evidence for Borna disease virus infection in humans, wild rodents and other vertebrates in Finland.

BACKGROUND: Borna disease virus (BDV) can infect many vertebrate species, including humans. BDV infection may lead to meningoencephalomyelitis in animals. An association with human neuropsychiatric diseases has been reported, but the causal relationship between BDV and human disease remains unclear. OBJECTIVES AND STUDY DESIGN: To find out whether BDV is present in Finland and to look for a potential reservoir, we examined a large panel of blood samples from different vertebrate species with immunofluorescence assay. Samples from horses, cats, dogs, sheep, cattle, large predators, grouse, wild rodents and humans were included. Most positive results were confirmed by other specific methods and in other laboratories. RESULTS AND CONCLUSIONS: BDV-specific antibodies were detected in 10 horses, 2 cats, as well as 2 horses and 1 dog from farms housing a previously detected seropositive horse. Interestingly, BDV-specific antibodies were further detected in three wild rodents. In humans, BDV-specific antibodies were detected in a veterinarian and in two patients suspected to have a Puumala hantavirus infection. Our serological analysis suggests that BDV infects various vertebrates in Finland, including humans. Furthermore, our data indicate for the first time that BDV infects also wild rodents.

Changes in Cartilage Biomarker Levels During a Transcontinental Multistage Footrace Over 4486 km.

BACKGROUND: Cartilage turnover and load-induced tissue changes are frequently assessed by quantifying concentrations of cartilage biomarkers in serum. To date, information on the effects of ultramarathon running on articular cartilage is scarce. HYPOTHESIS: Serum concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, COL2-3/4C long mono (C2C), procollagen type II C-terminal propeptide (CPII), and C2C:CPII will increase throughout a multistage ultramarathon. STUDY DESIGN: Descriptive laboratory study. METHODS: Blood samples were collected from 36 runners (4 female; mean age, 49.0 ± 10.7 years; mean body mass index, 23.1 ± 2.3 kg/m2 [start] and 21.4 ± 1.9 kg/m2 [finish]) before (t0) and during (t1: 1002 km; t2: 2132 km; t3: 3234 km; t4: 4039 km) a 4486-km multistage ultramarathon. Serum COMP, MMP-1, MMP-3, MMP-9, C2C, and CPII levels were assessed using commercial enzyme-linked immunosorbent assays. Linear mixed models were used to detect significant changes in serum biomarker levels over time with the time-varying covariates of body weight, running speed, and daily running time. RESULTS: Serum concentrations of COMP, MMP-9, and MMP-3 changed significantly throughout the multistage ultramarathon. On average, concentrations increased during the first measurement interval (MI1: t1-t0) by 22.5% for COMP (95% CI, 0.29-0.71 ng/mL), 22.3% for MMP-3 (95% CI, 0.24-15.37 ng/mL), and 95.6% for MMP-9 (95% CI, 81.7-414.5 ng/mL) and remained stable throughout MI2, MI3, and MI4. Serum concentrations of MMP-1, C2C, CPII, and C2C:CPII did not change significantly throughout the multistage ultramarathon. Changes in MMP-3 were statistically associated with changes in COMP throughout the ultramarathon race (MMP-3: Wald Z = 3.476, P = .001). CONCLUSION: Elevated COMP levels indicate increased COMP turnover in response to extreme running, and the association between load-induced changes in MMP-3 and changes in COMP suggests the possibility that MMP-3 may be involved in the degradation of COMP. CLINICAL RELEVANCE: These results suggest that articular cartilage is able to adapt even to extreme physical activity, possibly explaining why the risk of degenerative joint disease is not elevated in the running population.

High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins.

BACKGROUND: The recent observation that Borna disease virus (BDV)-reactive antibodies from psychiatric patients exhibit only low avidity for BDV antigen called into question their diagnostic value and raised the possibility that antigenically related microorganisms or self antigens caused the production of these antibodies. We further characterized the specificity of these antibodies. METHODS: We established a peptide array-based screening test that allows the identification of antibodies directed against linear epitopes of the two major BDV proteins, the nucleoprotein (N) and the phosphoprotein (P). RESULTS: Initial tests employing sera of BDV-infected mice and rats or horses with Borna disease revealed a high specificity and sensitivity of this test. All sera recognized epitopes of N, P, or both. Sera of noninfected rats, mice, and horses showed no signals on either peptide array. Several human sera that recognized BDV antigen by indirect immunofluorescence contained antibodies that recognized various linear epitopes of one or even both BDV proteins. Remarkably, antibodies purified from such human serum by matrix-immobilized peptides showed high-avidity binding to BDV antigens when assayed by IFA or Western blotting. CONCLUSIONS: These data suggest that reactive antibodies found in psychiatric patients indeed indicate infection with BDV or a BDV-like agent. However, the poor affinity maturation of BDV-specific human antibodies remains unexplained.

Regionally accentuated reversible brain grey matter reduction in ultra marathon runners detected by voxel-based morphometry.

BACKGROUND: During the 4,487 km ultra marathon TransEurope-FootRace 2009 (TEFR09), runners showed catabolism with considerable reduction of body weight as well as reversible brain volume reduction. We hypothesized that ultra marathon athletes might have developed changes to grey matter (GM) brain morphology due to the burden of extreme physical training. Using voxel-based morphometry (VBM) we undertook a cross sectional study and two longitudinal studies. METHODS: Prior to the start of the race 13 runners volunteered to participate in this study of planned brain scans before, twice during, and 8 months after the race. A group of matched controls was recruited for comparison. Twelve runners were able to participate in the scan before the start of the race and were taken into account for comparison with control persons. Because of drop-outs during the race, VBM could be performed in 10 runners covering the first 3 time points, and in 7 runners who also had the follow-up scan after 8 months. Volumetric 3D datasets were acquired using an MPRAGE sequence. A level of p < 0.05, family-wise corrected for multiple comparisons was the a priori set statistical threshold to infer significant effects from VBM. RESULTS: Baseline comparison of TEFR09 participants and controls revealed no significant differences regarding GM brain volume. During the race however, VBM revealed GM volume decreases in regionally distributed brain regions. These included the bilateral posterior temporal and occipitoparietal cortices as well as the anterior cingulate and caudate nucleus. After eight months, GM normalized. CONCLUSION: Contrary to our hypothesis, we did not observe significant differences between TEFR09 athletes and controls at baseline. If this missing difference is not due to small sample size, extreme physical training obviously does not chronically alter GM.However, during the race GM volume decreased in brain regions normally associated with visuospatial and language tasks. The reduction of the energy intensive default mode network as a means to conserve energy during catabolism is discussed. The changes were reversible after 8 months.Despite substantial changes to brain composition during the catabolic stress of an ultra marathon, the observed differences seem to be reversible and adaptive.

The foot in multistage ultra-marathon runners: experience in a cohort study of 22 participants of the Trans Europe Footrace Project with mobile MRI.

OBJECTIVES: 67 runners participated in the Trans Europe FootRace 2009 (TEFR09), a 4487 km (2789 mi) multistage ultra-marathon covering the south of Europe (Bari, Italy) to the North Cape. Reports on ultra-marathons are lacking, but the literature reports overuse injuries in athletes, especially to the Achilles tendon (AT), ankle or hind foot. Bone oedema may be related to exposure and is present in fatigue fractures. Therefore, the aim of this study was to determine prospectively if sustained maximal load during an ultra-marathon leads to damage to the foot. DESIGN AND PARTICIPANTS: In a cohort study, repeated scanning of the 22 athletes participating in the study was performed before and during (approximately every 1000 km) the race. Using the obtained fat saturated inversion recovery sequence, two experienced readers blinded to the clinical data rated the images regarding foot lesions. Statistical analysis included regression analysis and computation of the inter-rater reliability. SETTING: The TEFR09 course. MRI scanning was performed according to prearranged schedules for every participant, using a mobile 1.5 Tesla MRI unit on a trailer following the race. PRIMARY OUTCOME MEASURES: MRI data such as AT diameter, bone or tendon lesions, subcutaneous, plantar fascia or intraosseous oedema. RESULTS: The 22 study participants did not differ significantly from the total of the 67 TEFR09 runners regarding height, weight and age. The AT diameter increased significantly from 6.8 to 7.8 mm as did intraosseous signal, bone lesions and subcutaneous oedema. However, finishers differed only regarding plantar aponeurosis and subcutaneous oedema from participants aborting the TEFR09. Inter-rater reliability was 0.88-0.98. CONCLUSION: Under the extreme stress of the TEFR09, an increase of the AT diameter as well as bone signal are thought to be adaptive since only subcutaneous oedema and plantar fascia oedema were related to abortion of the race. TRIAL REGISTRATION NUMBER: University of Ulm, Germany Ethics Committee Number 78/08-UBB/se.

CT-guided lung biopsy: incidence of pneumothorax after instillation of NaCl into the biopsy track.

This study was conducted to evaluate whether instillation of NaCl 0.9% solution into the biopsy track reduces the incidence of pneumothoraces after CT-guided lung biopsy. A total of 140 consecutive patients with pulmonary lesions were included in this prospective study. All patients were alternatingly assigned to one of two groups: group A in whom the puncture access was sealed by instillation of NaCl 0.9% solution during extraction of the guide needle (n = 70) or group B for whom no sealing was performed (n = 70). CT-guided biopsy was performed with a 18-G coaxial system. Localization of lesion (pleural, peripheral, central), lesion size, needle-pleural angle, rate of pneumothorax and alveolar hemorrhage were evaluated. In group A, the incidence of pneumothorax was lower compared to group B (8%, 6/70 patients vs. 34%, 24/70 patients; P < 0.001). All pneumothoraces occurred directly post punctionem after extraction of the guide needle. One patient in group A and eight patients in group B developed large pneumothoraces requiring chest tube placement (P = 0.01). The frequency of pneumothorax was independent of other variables. After CT-guided biopsy, instillation of NaCl 0.9% solution into the puncture access during extraction of the needle significantly reduces the incidence of pneumothorax.