Analysis of sprint cross-country skiing using a differential global navigation satellite system

The purpose was to examine skiing velocities, gear choice (G2–7) and cycle rates during a skating sprint time trial (STT) and their relationships to performance, as well as to examine relationships between aerobic power, body composition and maximal skiing velocity versus STT performance. Nine male elite cross-country skiers performed three tests on snow: (1) Maximum velocity test (V _max) performed using G3 skating, (2) V _max test performed using double poling (DP) technique and (3) a STT over 1,425 m. Additional measurements of VO_2max during roller skiing and body composition using iDXA were made. Differential global navigation satellite system data were used for position and velocity and synchronized with video during STT. The STT encompassed a large velocity range (2.9–12.9 m s⁻¹) and multiple transitions (21–34) between skiing gears. Skiing velocity in the uphill sections was related to gear selection between G2 and G3. STT performance was most strongly correlated to uphill time (r = 0.92, P < 0.05), the percentage use of G2 (r = −0.72, P < 0.05), and DP V _max (r = −0.71, P < 0.05). The velocity decrease in the uphills from lap 1 to lap 2 was correlated with VO_2max (r = −0.78, P < 0.05). V _max in DP and G3 were related to percent of racing time using G3. In conclusion, the sprint skiing performance was mainly related to uphill performance, greater use of the G3 technique, and higher DP and G3 maximum velocities. Additionally, VO_2max was related to the ability to maintain racing velocity in the uphills and lean body mass was related to starting velocity and DP maximal speed.     

Do adverse histopathologic findings in colorectal cancer patients explain disparate outcomes?

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist.     

Molecular identification of Tritrichomonas foetus-like organisms as coinfecting agents of human Pneumocystis pneumonia

Trichomonads closely related to the bovid parasite Tritrichomonas foetus were identified in the bronchoalveolar lavage sample from a patient with AIDS in association with Pneumocystis pneumonia. This human case of T. foetus-like infection emphasizes the zoonotic potential of trichomonads, although the existence of a human-host-adapted T. foetus strain cannot be excluded.     

Characterization of inhibitors of glucocorticoid receptor nuclear translocation: a model of cytoplasmic dynein-mediated cargo transport

Agonist-induced glucocorticoid receptor [GR] transport from the cytoplasm to the nucleus was used as a model to identify dynein-mediated cargo transport inhibitors. Cell-based screening of the library of pharmacologically active compound (LOPAC)-1280 collection identified several small molecules that stalled the agonist-induced transport of GR-green fluorescent protein (GFP) in a concentration-dependent manner. Fluorescent images of microtubule organization, nuclear DNA staining, expression of GR-GFP, and its subcellular distribution were inspected and quantified by image analysis to evaluate the impact of compounds on cell morphology, toxicity, and GR transport. Given the complexity of the multi-protein complex involved in dynein-mediated cargo transport and the variety of potential mechanisms for interruption of that process, we therefore developed and validated a panel of biochemical assays to investigate some of the more likely intracellular target(s) of the GR transport inhibitors. Although the apomorphine enantiomers exhibited the most potency toward the ATPase activities of cytoplasmic dynein, myosin, and the heat-shock proteins (HSPs), their apparent lack of specificity made them unattractive for further study in our quest. Other molecules appeared to be nonspecific inhibitors that targeted reactive cysteines of proteins. Ideally, specific retrograde transport inhibitors would either target dynein itself or one of the other important proteins associated with the transport process. Although the hits from the cell-based screen of the LOPAC-1280 collection did not exhibit this desired profile, this screening platform provided a promising phenotypic system for the discovery of dynein/HSP modulators.     

Mapping structural landmarks, ligand binding sites, and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions, and variation in phenotypes in inherited diseases affecting basement membranes

Collagen IV is the major protein found in basement membranes. It comprises three heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity.We constructed linear maps of the collagen IV heterotrimers ("interactomes") that indicated major structural landmarks, known and predicted ligand-binding sites, and missense mutations, in order to identify functional and disease-associated domains, potential interactions between ligands, and genotype–phenotype relationships. The maps documented more than 30 known ligand-binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin, and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and haemostasis, and disease domains for autoimmunity, tumor growth and inhibition, infection, and glycation. Cooperative ligand interactions were indicated by binding site proximity, for example, between integrins, matrix metalloproteinases, and heparin. The maps indicated that mutations affecting major ligand-binding sites, for example, for Von Hippel Lindau (VHL) protein in the α1 chain or integrins in the α5 chain, resulted in distinctive phenotypes (Hereditary Angiopathy, Nephropathy, Aneurysms, and muscle Cramps [HANAC] syndrome, and early-onset Alport syndrome, respectively). These maps further our understanding of basement membrane biology and disease, and suggest novel membrane interactions, functions, and therapeutic targets.     

The effects of 6-week-decoupled bi-pedal cycling on submaximal and high intensity performance in competitive cyclists and triathletes

Aim of this work was to examine the effects of decoupled two-legged cycling on (1) submaximal and maximal oxygen uptake, (2) power output at 4 mmol L⁻¹ blood lactate concentration, (3) mean and peak power output during high intensity cycling (30 s sprint) and (4) isometric and dynamic force production of the knee extensor and flexor muscles. 18 highly trained male competitive male cyclists and triathletes (age 24 ± 3 years; body height 179 ± 11 cm; body mass 78 ± 8 kg; peak oxygen uptake 5,070 ± 680 mL min⁻¹) were equally randomized to exercise on a stationary cycle equipped either with decoupled or with traditional crank system. The intervention involved 1 h training sessions, 5 times per week for 6 weeks at a heart rate corresponding to 70% of VO_2peak. VO₂ at 100, 140, 180, 220 and 260 and power output at 4 mmol L⁻¹ blood lactate were determined during an incremental test. VO_2peak was recorded during a ramp protocol. Mean and peak power output were assessed during a 30 s cycle sprint. The maximal voluntary isometric strength of the quadriceps and biceps femoris muscles was obtained using a training machine equipped with a force sensor. No differences were observed between the groups for changes in any variable (P = 0.15–0.90; effect size = 0.00–0.30). Our results demonstrate that a 6 week (30 sessions) training block using decoupled crank systems does not result in changes in any physiological or performance variables in highly trained competitive cyclists.