Changes in biomechanics of skiing at maximal velocity caused by simulated 20-km skiing race using V2 skating technique.

This study investigated how the fatigue caused by a 20-km simulated skating cross-country skiing race on snow affects the final spurt performance from a biomechanical perspective. Subjects performed a 100-m maximal skiing trial before and at the end of the simulated race. Cycle characteristics, ground reaction forces from skis and poles, and muscle activity from eight muscles were recorded during each trial. Results showed that subjects were in a fatigued state after the simulated race manifested by 11.6% lower skiing speed (P<.01). The lower skiing speed was related to an 8.0% decrease in cycle rate (P<.01), whereas cycle length was slightly decreased (tendency). In temporal patterns, relative kick time was increased (10.9%, P<.01) while relative poling time was slightly decreased (tendency). Vertical ski force production decreased by 8.3% while pole force production decreased by 26.0% (both, P<.01). Muscle activation was generally decreased in upper (39.2%) and lower body (30.7%) (both, P<.01). Together these findings show different responses to fatigue in the upper and lower body. In ski forces, fatigue was observed via longer force production times while force production levels decreased only slightly. Pole forces showed equal force production times in the fatigued state while force production level decreased threefold compared to the ski forces.

Two-Segment Foot Model for the Biomechanical Analysis of Squat.

Squat exercise is acquiring interest in many fields, due to its benefits in improving health and its biomechanical similarities to a wide range of sport motions and the recruitment of many body segments in a single maneuver. Several researches had examined considerable biomechanical aspects of lower limbs during squat, but not without limitations. The main goal of this study focuses on the analysis of the foot contribution during a partial body weight squat, using a two-segment foot model that considers separately the forefoot and the hindfoot. The forefoot and hindfoot are articulated by the midtarsal joint. Five subjects performed a series of three trials, and results were averaged. Joint kinematics and dynamics were obtained using motion capture system, two force plates closed together, and inverse dynamics techniques. The midtarsal joint reached a dorsiflexion peak of 4°. Different strategies between subjects revealed 4° supination and 2.5° pronation of the forefoot. Vertical GRF showed 20% of body weight concentrated on the forefoot and 30% on the hindfoot. The percentages varied during motion, with a peak of 40% on the hindfoot and correspondently 10% on the forefoot, while the traditional model depicted the unique constant 50% value. Ankle peak of plantarflexion moment, power absorption, and power generation was consistent with values estimated by the one-segment model, without statistical significance.

Biomechanics of simulated versus natural cross-country sit skiing.

The purpose of this study was to investigate the biomechanics of cross-country sit-skiing in simulated and natural skiing. Thirteen international level athletes participated in a ski ergometer test (simulated conditions) and a test on snow in a ski-tunnel (natural conditions) using their personal sit-ski. Tests in both conditions were performed at individual maximal speed. When comparing the two conditions the main results were: (1) maximal speed in simulated conditions was lower (p<0.05) but correlated well with the natural condition (r=0.79, p<0.001); (2) no differences in pole force variables were found; peak force (r=0.77, p<0.01) and average force (r=0.78, p<0.01) correlated well; (3) recovery time and time to peak did not differ and time to impact correlated with each other (r=0.88, p<0.01); (4) no differences were found in peak electromyography (EMG) and average EMG for Triceps, Pectoralis, and Erector Spinae; Rectus Abdominis did not differ in peak. EMG peak and average EMG of all muscles were correlated between the two conditions (r=0.65-0.94; p<0.05-0.01). Although some differences were observed, this study demonstrated that technical skill proficiency in natural and simulated cross-country skiing is comparable from a force production and muscle activation perspective.

Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

IBM's Health Analytics and Clinical Decision Support.

OBJECTIVES: This survey explores the role of big data and health analytics developed by IBM in supporting the transformation of healthcare by augmenting evidence-based decision-making. METHODS: Some problems in healthcare and strategies for change are described. It is argued that change requires better decisions, which, in turn, require better use of the many kinds of healthcare information. Analytic resources that address each of the information challenges are described. Examples of the role of each of the resources are given. RESULTS: There are powerful analytic tools that utilize the various kinds of big data in healthcare to help clinicians make more personalized, evidenced-based decisions. Such resources can extract relevant information and provide insights that clinicians can use to make evidence-supported decisions. There are early suggestions that these resources have clinical value. As with all analytic tools, they are limited by the amount and quality of data. CONCLUSION: Big data is an inevitable part of the future of healthcare. There is a compelling need to manage and use big data to make better decisions to support the transformation of healthcare to the personalized, evidence-supported model of the future. Cognitive computing resources are necessary to manage the challenges in employing big data in healthcare. Such tools have been and are being developed. The analytic resources, themselves, do not drive, but support healthcare transformation.

Shoulder rotation characteristics in professional tennis players.

Aim of this study was to assess the glenohumeral joint internal and external rotational range of motion using an ultrasound based kinematic measurement device. Twenty-seven male professional tennis players were bilaterally measured for internal and external rotation at 90 degrees of shoulder abduction while avoiding scapulothoracic motion. The control group consisted of 20 asymptomatic volunteers not involved in overhead sports activities. The dominant arm (playing arm) had a significantly greater range of external rotation than the non-dominant arm, while their internal rotation showed a significant deficit as compared to the non-dominant arm. The dominant arm total rotational range of motion was also significantly reduced in comparison to the non-dominant arm and to the controls. No significant difference was found between the dominant and non-dominant extremity in the control group. For objective measurement of glenohumeral rotational range of motion ultrasound based real time motion analysis is a new application for the diagnostic testing of specific shoulder parameters in orthopedics and sports physical therapy. It is therefore concluded that the specific methodology aiming at isolated glenohumeral motion may have clinical application for the development of rehabilitation and preventative programs.

A manufacturer's perspective: Hewlett Packard Y2K action plan.

Medical device manufacturers must ensure that their devices are safe and effective including investigating issues involved with the century rollover. Manufacturers must begin early to evaluate their products in order to allow time to correct and distribute these product corrections and communicate to their customers so they can prepare for the Y2K event.

A new hybrid resin for stepwise screening of peptide libraries combined with single bead Edman sequencing.

A library system was developed for the discovery of bioactive peptides. Library synthesis and peptide sequencing was performed on a solid support while the screening for bioactivity was done with peptides in solution. The peptides were synthesized by split and mix, one-bead-one-peptide library synthesis, using a Tentagel S-NH2 solid support with a loading of approximately 100 pmol/bead. The major part of the peptide was connected to the support by a single acid-labile linker and a minor part of the peptide was acid-stabile attached to the polymer. The percentage of acid-stabile attached peptides could easily be controlled during modification of the amino functionalities of the resin at the start of the process. The cleavage rate of the acid-labile attached peptide from the resin depends on the composition of the cleavage mixture. When cleavage conditions were carefully controlled, a three-step partial cleavage protocol allowed for convergent bioactivity screening on peptide libraries using only one type of acid-labile linker. The partial cleavage and convergent screening procedure was repeated three times, after which the bead containing the bioactive peptide was sequenced. As such a bead still contained acid-stabile attached peptide, the Edman sequencing was straightforward and repetitive yields were excellent because the immobilized peptide was not washed out.

Coloured peptides: synthesis, properties and use in preparation of peptide sub-library kits.

Several methods were developed for the solid-phase synthesis (SPPS) of coloured peptides and peptide libraries. At first a bifunctional red compound, 4-(4-(N-ethyl-N-(3-(tert-butyloxycarbonyl)aminopropyl)amino)phenylazo)be nzoic acid (Boc-EPAB), was coupled with chloromethyl resin to obtain a new solid support suitable for SPPS using Boc chemistry. Peptides synthesized on this coloured resin had the chromophore at their C-termini. N-terminally coloured peptides were synthesized on a traditional solid support, coupled with chromophoric carboxylic acid before cleavage. A model pentapeptide, Phe-Ala-Val-Leu-Gly, and its ten derivatives were synthesized and their properties studied. It was found that the presence of chromophores decreases the water solubility of peptides. However, insertion of solubilizing tags (penta-lysine sequences or polyoxyethyl chains) into the molecule of any coloured derivative resulted in enhancement of the solubility. The RP-HPLC hydrophobicity indexes (phi0) of the coloured peptides were also determined because phi0 values are closely related to their water solubility. A coloured pentapeptide library was synthesized using the portioning-mixing method. Each component of this library contained the red azo dye (EPAB) and the penta-lysine tag. Before the last coupling step the samples were not mixed. All of the 19 sub-libraries obtained after cleavage were readily soluble in water, giving intense red solutions. The effect of chromophore (EPAB) and/or penta-lysine solubilizing tag on the biological activity was also studied. Potencies of the bovine neurotensin 8-13 fragment and its different coloured and penta-lysine derivatives were compared in isolated longitudinal muscle strips of guinea pig ileum. It was shown that the hexapeptide with penta-lysine tag had almost the same activity as the 8-13 fragment itself. The activity of the EPAB-derivative was found to be rather low. However, the presence of the solubilizing tag in the coloured hexapeptide compensated the negative effect of the chromophore.

Maize contains a Lon protease gene that can partially complement a yeast pim1-deletion mutant.

We have identified a gene in maize that encodes a product belonging to the Lon protease family. In yeast and mammals, Lon-type proteases catalyze the ATP-dependent degradation of mitochondrial matrix proteins. The maize gene, which we have designated LON1, is predicted to encode a protein with a molecular mass of 97.7 kDa. Lon1p is more similar in sequence to bacterial Lon proteases than to the yeast and human mitochondrial Lon proteases. LON1 transcripts are present in shoots of 4-day-old etiolated maize seedlings, and transcript levels decrease when these seedlings are heat-shocked. LON1 transcripts are also present at comparable levels in leaves and roots of 2-week-old greenhouse-grown seedlings. In yeast, the mitochondrial Lon-type protease, Pim1p, has been implicated in mitochondrial protein turnover, the assembly of mitochondrial enzyme complexes, and mitochondrial DNA maintenance, and it is essential for respiratory function. We show that maize Lon1p can replace the Pim1p function in yeast for maintaining mitochondrial DNA integrity, but not in the assembly of cytochrome a x a3 complexes.

Changes in reflex excitability following isometric contraction in humans.

Enhancement of muscle stretch following isometric contraction has been thought to occur as a result of inhibitory reflex mechanisms. Experiments with electrical stimulation (H-reflex) have demonstrated maximal H-reflex suppression during force relaxation followed by gradual recovery over the following 20 s. There has been considerable speculation as to whether electrical and mechanical stimulation elicit similar response behaviour. The present study examined postisometric reflex modulation following both stimulation modalities. In ten subjects dorsiflexion stimuli varying in speed and amplitude were applied after 30% and 60% maximal voluntary contraction (MVC). Modulation of the mechanically and electrically evoked responses following isometric plantarflexion was investigated. Reflex responses following both stimulation modalities were depressed during the course of force relaxation. A rather fast recovery was observed in mechanical stimulation. Postisometric response modulation was neither altered by the amount of isometric plantarflexion, nor by the amplitude of the applied stretch stimulus. With increasing velocity of the applied dorsiflexion, however, the shape of the reflex modulation persisted, but the magnitude of the responses was significantly enhanced. In electrical stimulation, however, recovery was delayed. It is suggested that postisometric reflex modulation is due to presynaptic inhibition. Moreover, possible peripheral mechanisms resulting from alpha-gamma-coactivation may also affect the stretch receptor itself because of inherent stiffness properties. The latter possibility particularly would explain the differences between mechanical and electrical stimulus modalities. With respect to practical implications, the very fast recovery (< 400 ms) of the stretch responses to control values strongly contradicts the interpretation that after isometric precontraction, suppression of reflex activity might be used for more efficient stretching of the tendomuscle system.

Solid phase synthesis of hydantoins by thermal cyclization and screening of reaction conditions using APOS 1200.

A novel strategy for solid-phase synthesis of hydantoins with high optical purity is described using a thermal pH-neutral cyclization and simultaneous release from resin. Hereby even hydantoins bearing a pH-sensitive side chain (protection) are available. The reaction conditions are well screened applying the parallel organic synthesizer APOS 1200.

Lipopeptide-polyoxyethylene conjugates as mitogens and adjuvants.

Two lipopeptide analogues of the Escherichia coli lipoprotein rendered water-soluble by polyoxyethylene were tested for mitogenicity in vitro in murine and human B lymphocytes and for adjuvant activity in vivo in mice. These highly amphiphilic lipopeptides retained the biological activity other lipopeptides usually exerted which supports the hypothesis of specific interactions of lipopeptides with membranes of reactive cells. The activation of human B lymphocytes by these lipopeptides was much less pronounced compared to that of murine cells. However, given in combination with anti-CD40 antibodies plus interleukin-4, human B lymphocytes could synergistically be stimulated to proliferate. As an adjuvant, the polyoxyethylene linked lipopeptides were almost as potent as Freund's adjuvants and other basic lipopeptides. Being water-soluble, these novel analogues are easy to apply and they are suitable for field studies as adjuvants when sonication can not usually be provided.

Immunization and affinity purification of antibodies using resin-immobilized lysine-branched synthetic peptides.

A new method has been developed to raise antibodies against synthetic peptides. A multiple antigenic peptide system (MAP) containing a branched oligolysine was synthesized on a beaded polystyrene polyoxyethylene graft copolymer resin, which acts as a synthetic hapten carrier for use in immunization. The peptides, already attached to the carrier, can be used directly after final deprotection without any further purification steps. The utility of this peptide-carrier conjugate is highlighted by its additional application for affinity purification of antibodies generated.

Architecture of the maize mitochondrial atp1 promoter as determined by linker-scanning and point mutagenesis.

Plant mitochondrial promoters are poorly conserved but generally share a loose consensus sequence spanning approximately 17 nucleotides. Using a homologous in vitro transcription system, we have previously shown that an 11-nucleotide sequence within this region comprises at least part of the maize mitochondrial atp1 promoter (W. Rapp and D. Stern, EMBO J. 11:1065-1073, 1992). We have extended this finding by using a series of linker-scanning and point mutations to define the atp1 promoter in detail. Our results show that mutations at positions -12 to +5, relative to the major transcription start site, can decrease initiation rates to between < 10 and 40% of wild-type levels. Some mutations, scattered throughout this region, have lesser effects or no effect. Taken together, our data suggest a model in which the atp1 promoter consists of a central domain extending from -7 to +5 and an upstream domain of 1 to 3 bp that is centered around -11 to -12. Because many mutations within this promoter region are tolerated in vitro, the maize atp1 promoter is distinct from the highly conserved yeast mitochondrial promoters.

Orthotic devices in functional treatment of ankle sprain. Stabilizing effects during real movements.

Various orthotic devices generally employed for therapy of ankle sprain were tested under functional conditions. The experimental setup comprised inversion stimuli of 20 and 30 degrees (13 subjects) while standing on a tiltplatform as well as running movements of 8 and 12 km.h-1 on a treadmill (12 subjects). Ankle joint displacements were registered together with the surface EMGs from mm. peroneus long., tibialis ant., gastrocnemius med. and vastus med. In an additional study the relation between achilles tendon angle and talar tilt was determined under static conditions. Ten subjects with chronical instability were examined both in uni- and bipedal stance with the foot inverted to 20, 30 and 40 degrees. None of the tested devices could reduce achilles tendon angle movements completely neither during a sudden inversion nor during running. However, there were significant differences among the tested devices in the dorsal-plantar and in the eversion-inversion plane. In bipedal stance talar tilts were observed only when the foot was inverted more than 30 degrees. In unipedal stance these tilts were clearly reduced or disappeared totally. It is concluded that for functional rehabilitation, loading of the ankle joint is desirable in order to increase joint stability. The central importance of the treatment by orthotic devices may be regarded in an optimal passive joint stabilization combined with a correct fitting in order to preserve proprioceptive neuromuscular function for an active muscular stabilization.

Recovery of stretch reflex responses following mechanical stimulation.

The recovery behaviour of mechanically evoked stretch responses was investigated. Stimuli which promoted identical dorsiflexing movements around the ankle joint were applied to ten subjects in two positions, seated and upright. The experimental sets comprised single as well as double dorsiflexing displacements. In the latter the stimuli were elicited for durations of either 100, 200 or 400 ms. Stretch responses following the first displacements were related to the stretch velocity but not to the amplitude. The responses of the plantar flexors following the second mechanical dorsiflexion were reduced with respect to the delay time between the first and second displacement. In addition, the magnitudes of these responses depended on the functional task: the stretch responses recovered much faster in the standing position when the triceps surae muscle was only slightly activated, whereas in the relaxed sitting position the reflexes remained suppressed. Both reciprocal inhibition, as well as the time course of the reformation of intrafusal cross-bridge links, may help to explain the depression of the monosynaptic stretch reflex.

Acute and chronic effects of low dose almitrine bismesylate in the treatment of chronic bronchitis and emphysema.

OBJECTIVES: Study of the acute and chronic effects of low-dose almitrine therapy in stable hypoxaemic patients with chronic bronchitis and emphysema. METHODS: A low daily dose of 75 mg almitrine bismesylate was administered for six months in 23 patients with chronic bronchitis and emphysema. Nine patients (group 1) were placed on oral almitrine bismesylate 25 mg t.i.d. after they had received a single intravenous dose of 60 mg almitrine three months earlier. Fourteen additional patients, seven receiving almitrine (group 2) and seven placebo (group 3) were randomized for a 6 month double-blind evaluation of both acute and chronic effects of 75 mg almitrine on pulmonary gas exchange and on pulmonary haemodynamics. All patients were followed-up with regular measurements of blood gases, body plethysmography and with evaluation of peripheral nerve function. RESULTS: Acute effects of almitrine were a significant increase in arterial oxygen tension by 14 mmHg after intravenous (p < 0.001) and by 15 mmHg after oral administration (p < 0.001), amelioration of hypercapnia, a slight transient increase in mean pulmonary artery pressure from 26 +/- 7 to 29 +/- 6 mmHg (NS) and a decrease of shunt due to improvement in ventilation/perfusion mismatching. In contrast, no acute changes in blood gases and pulmonary pressures were seen in the placebo group. A combination of almitrine with oxygen (8-10 L/min) was most effective in amelioration of hypoxaemia and shunt. With chronic almitrine therapy, the improvements in gas exchange persisted without elevation of pulmonary artery pressure (26 +/- 8 mmHg), whereas a negative trend in change of blood gases and pulmonary artery pressure occurred in the placebo treated group (NS). No significant changes in external ventilation, other spirometric parameters or adverse effects concerning peripheral nerve function were seen after almitrine or placebo treatment. The elimination of almitrine was fitted to a three compartment model and the terminal half-life in the patient population was found to be 32 +/- 29 days after intravenous dosing. CONCLUSION: Acute and six-month almitrine bismesylate therapy at a low daily dose of 75 mg is found to be safe, even in severely compromised patients, with regard to pulmonary haemodynamics and peripheral nerve function. The agent is beneficial to pulmonary gas exchange, with reduction of hypercapnia, of intrapulmonary shunt and also with regard to sustained elevation of arterial oxygen tension. A combination with inhaled oxygen seems especially efficacious.

Radiation therapy of para-aortic lymph nodes in gynaecologic cancers: techniques, results and complications.

From 1965 to 1986 the para-aortic lymph nodes of 141 patients with gynaecologic cancers were irradiated directly after initial treatment of the primary site was completed. Another 32 patients only received para-aortic radiation treatment when para-aortic metastases became clinically apparent some time later. Radiation therapy was performed using a biaxial-four-segmental-rotating-field-technique. Crude survival of the group with initial para-aortic radiation treatment is far better than of the second group. Only five cases of severe complications due to para-aortic treatment were reported. In order to analyze the reason for such a low number of complications, CT-treatment planning for a typical patient was performed for different methods as they have been described in the literature, also referring to treatment data such as success, total dose and dose-distribution, thus influencing the complication rate. Obviously, the biaxial-four-segmental-rotating-field-technique is a method allowing to deposit a certain dose into the target volume without considerably damaging tissues in the vicinity.