BIOMECHANICAL AND PHYSIOLOGICAL ASPECTS OF RIFLE SHOOTING IN SIMULATED BIATHLON COMPETITION

In biathlon competition heart rate levels are commonly approximately 93 % of individual maximum heart rate during skiing. During the shooting heart rate level usually decreases to 61-73 % of maximum (Hoffman & Street, 1992). The result of biathlon competition is mostly affected by VO2max and upper body capacity (Rundell & Bacharach, 1995) and shooting performance including shooting time and accuracy (Hoffman, Gilson, Westenburg & Spencer, 1992). Shooting performance is affected by stability of shooting stance and rifle hold, especially in standing shooting (Groslambert, Candau, Hoffman, Bardy, & Rouillon, 1999). Physical loading diminishes shooting performance the more upper body muscles are involved in exercise (Hoffman, et al. 1992; Groslambert, Candau, Gillot & Rouillon, 1996; Groslambert, et al. 1999). Physical exercise and increasing muscle fatigue results poorer control of balance and shooting posture. Balance control agilities of biathlon athletes have been investigated only by Bozsik, Bretz and Kaske (1995), but connection between balance agilities and shooting result have not been established by any research. The aim of this project was to develop methods for measuring shooting performance in biathlon

Detection of microsatellite instability with Idylla MSI assay in colorectal and endometrial cancer

Universal testing of microsatellite instability (MSI) is recommended for colorectal cancer (CRC) and endometrial cancer (EC) to screen for Lynch syndrome and to aid in assessing prognosis and optimal treatment. We compared the performance of Idylla MSI test to immunohistochemistry (IHC) of mismatch repair (MMR) proteins in consecutive series of 100 CRC and 108 EC samples, as well as in retrospective series of 28 CRC and 33 EC specimens with known deficient MMR protein expression. The concordance between the Idylla test and IHC was 100% in all CRC samples (n=128) but lower in EC samples (87.2%; n=141). In the EC samples, sensitivity of Idylla test was 72.7% and specificity 100%. EC MSI/dMMR agreement was 85.4% for MLH1, 87.5% for MSH2, and only 35.3% for MSH6. When we analyzed 14 EC samples that were discrepant, i.e., dMMR using IHC and microsatellite stable using Idylla, with microsatellite markers BAT25 and BAT26, we found four cases to be replication error (RER) positive. All RER positive cases were deficient for MSH6 protein expression. We also re-analyzed EC samples with variable tumor cellularity to determine the limit of detection of the Idylla test and found that a 30% or higher tumor cellularity is required. We conclude that Idylla MSI test offers a sensitive and specific method for CRC diagnostics but is less sensitive in EC samples especially in the case of MSH6 deficiency.Peer reviewe

N-glycomic profiling of colorectal cancer according to tumor stage and location

Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer and can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways regardless of tumor location.Peer reviewe

Multiple components of PKA and TGF-beta pathways are mutated in pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP. These exome sequencing results were validated with an ultra-deep amplicon sequencing method, leading to 14 validated variants. The validated results contain seven genes that contribute to the protein kinase A (PKA) pathway. PKA pathway, which also contains GNAS, is a major player of overproduction of mucin, which is the characteristic feature of PMP. In addition to PKA pathway, we identified mutations in six genes that belong to the transforming growth factor beta (TGF-beta) pathway, which is a key regulator of cell proliferation. Since either GNAS mutation or an alternative mutation in the PKA pathway was identified in 8/9 patients, inhibition of the PKA pathway might reduce mucin production in most of the PMP patients and potentially suppress disease progression.Peer reviewe

Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers

Gene fusions can act as oncogenic drivers and offer targets for cancer therapy. Since fusions are rare in colorectal cancer (CRC), their universal screening seems impractical. Our aim was to investigate gene fusions in 62 CRC cases with deficient MLH1 (dMLH1) and BRAFV600E wild-type (wt) status from a consecutive real-life series of 2079 CRCs. First, gene fusions were analysed using a novel FusionPlex Lung v2 RNA-based next-generation sequencing (NGS) panel, and these results were compared to a novel Idylla GeneFusion assay and pan-TRK immunohistochemistry (IHC). NGS detected seven (7/62, 11%) NTRK1 fusions (TPM3::NTRK1, PLEKHA6::NTRK1 and LMNA::NTRK1, each in two cases, and IRF2BP2::NTRK1 in one case). In addition, two ALK, four RET and seven BRAF fusions were identified. Idylla detected seven NTRK1 expression imbalances, in line with the NGS results (overall agreement 100%). Furthermore, Idylla detected the two NGS-identified ALK rearrangements as one specific ALK fusion and one ALK expression imbalance, whilst only two of the four RET fusions were discovered. However, Idylla detected several expression imbalances of ALK (n = 7) and RET (n = 1) that were found to be fusion negative with the NGS. Pan-TRK IHC showed clearly detectable, fusion partner-dependent staining patterns in the seven NTRK1 fusion cases. Overall agreement for pan-TRK antibody clone EPR17341 was 98% and for A7H6R 100% when compared to the NGS. Of the 62 CRCs, 43 were MLH1 promoter hypermethylated (MLH1ph) and 39 were RASwt. All fusion cases were both MLH1ph and RASwt. Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS.Peer reviewe

A new laboratory test method for estimating anaerobic performance charasteristics with special reference to sprint running

The present study was aimed at developing a new laboratory test method, which could be used to determine both the metabolic and neuromuscular components of maximal anaerobic running performance and which could provide training prescription for sports with short duration and high power output. A total of 60 male athletes (400-m, middle and long distance runners and power athletes), 8 female 400-m runners and 34 physically active men volunteered to participate in tests for the study. The new maximal anaerobic running test (MART) consisted of n x 20-s runs on a treadmill with a 100-s recovery between the runs. The speed of the treadmill was increased after each consecutive run until exhaustion but the slope of the treadmill was kept constant (1°, 3°, 4°, 5° or 7°). In order to determine the blood lactate vs. O₂ demand curve, blood lactate concentration was measured at rest and after each run. The height of counter-movement jump was measured at rest (CMJᵣₑₛₜ) and after exhaustion. Correlation and regression analyses revealed that the most important determinants of the maximal anaerobic work capacity were maximal running velocity on a track, power at 10 mmol · 1⁻¹ blood lactate level (P₁₀ₘм) and peak blood lactate concentration (peak BLa). Present results showed that the grade of the treadmill affects the results of the MART since maximal (Pₘₐₓ) and submaxirnal power (P₁₀ₘм and P₅ₘм) indices increased when the treadmill inclination increased from 1° to 7°. Furthermore, the relative weight of the metabolic component to determine the P max increased and the relative weight of the force-velocity component of the neuromuscular system decreased with the increased grade in the MART. High Pₘₐₓ, peak BLa and contribution of anaerobic energy yield, as well as significant correlations between the corresponding variables of the MART and Wingate test, suggested that the MART is a valid maximal anaerobic running performance test. Reliability figures of the MART variables also indicated that the MART is a reliable test. Furthermore, the present results showed that sprint training increased the P max in well-trained sprint runners. Moreover, correlation analyses showed that individual changes in submaxirnal power (P₃ₘм), peak BLa, Pₘₐₓ and CMJᵣₑₛₜ were related to the volume of corresponding training methods, suggesting that the MART is a sensitive test method for sprint running

Diagnostic performance of Idylla MSI test in colorectal cancer biopsies

Universal testing for microsatellite instability (MSI) is recommended in colorectal cancer (CRC) to screen for Lynch syndrome and to guide optimal treatment and follow-up of the patients. Especially in neoadjuvant setting, where immuno-oncological treatments have recently shown excellent responses, identification of MSI status at biopsy is a prerequisite. Idylla MSI test offers a rapid and automated test to assess MSI-status from formalin-fixed paraffin-embedded tumor tissue sections. In this study, we compared the performance of the Idylla MSI test to mismatch repair (MMR) protein immunohistochemistry (IHC) using 117 CRC biopsies with previously known deficient MMR status. The concordance between Idylla and IHC was 99.0% (95/96) for biopsies with the recommended >= 20% tumor cell content. Further, 85.7% (18/21) of suboptimal CRC biopsy specimens (tumor cell content 5-15%) were diagnosed as MSI. Overall, we identified four discrepant cases of which three had tumor cell content less than 20%, explaining the discordant result. Our study shows that the Idylla MSI test offers a competent tool for MSI screening in CRC biopsy specimens.Peer reviewe