Messung von Herzfrequenzen und Kotcortisolmetaboliten bei Pferden am Zürcher Sechseläuten

The Zurich’s Sechseläuten is a traditional festival of the Zurich guilds, in which around 500 horses take part. After a parade through the old town of Zurich, the riders gather at a big square to canter around a burning woodpile topped with an exploding effigy (the «Böögg»). The level of stress experienced by the horses partaking in this event is subjected to increasing scrutiny. The aim of this study was to evaluate the stress load of the horses participating in the Sechseläuten procession more objectively by measuring heart rate and faecal cortisol metabolites. Twenty-three horse-rider pairs were voluntarily recruited from the guilds for participation in the study. For comparison purposes, three sections of the procession were simulated in terms of gait and distance travelled in a normal riding environment during a test day and observed during the Sechseläuten itself 16 days later: Counter march Bahnhofstrasse, parade Limmatquai and parade around the burning «Böögg». All horses were equipped with a heart rate measuring system with GPS tracking (Polar Team Pro®, Polar Electro Oy, Finland). Faecal samples for measuring cortisol metabolites were taken rectally immediately before and 24 hours after the events. Thirteen of the 23 horses were sedated during the Sechseläuten (Acepromazine, 0,1–0,2 mg/kg p.o.). The differences between the observation periods and groups (sedated/unsedated) were tested by analysis of variance (P<0,05). Walking and cantering speeds in the three sections did not differ between the test day and the Sechseläuten itself. Compared to the test day, the average heart rate was increased in all sections of the real event. However, neither the initial cortisol metabolite value nor the increase after the events showed a significant difference between the test day and the Sechseläuten. The average heart rate of the sedated group did not differ from the unsedated group during the walking sections but was elevated during canter around the Böögg. The increase in heart rate at the Sechseläuten indicated a stress load, but together with the unchanged cortisol responses, this can be classified as moderate. The influence of a sedation were inconclusive and should be further investigated

Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis

Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics, and improve the diagnostic pathway in what is a clinically heterogeneous syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA, and transfer RNA present in human biofluids, we sought to identify whether non-coding RNA in serum could be biomarkers for amyotrophic lateral sclerosis. Serum samples from our Oxford Study for Biomarkers in MND/ALS discovery cohort of amyotrophic lateral sclerosis patients (n=48), disease mimics (n=16), and age- and sex-matched healthy controls (n=24) were profiled for non-coding RNA expression using RNA-sequencing, which showed a wide range of non-coding RNA to be dysregulated. We confirmed significant alterations with reverse transcription-quantitative PCR in the expression of hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-92a-3p, hsa-piR-33151, TRV-AAC4-1.1, and TRA-AGC6-1.1. Furthermore, hsa-miR-206, a previously identified amyotrophic lateral sclerosis biomarker, showed a binary-like pattern of expression in our samples. Using the expression of these non-coding RNA, we were able to discriminate amyotrophic lateral sclerosis samples from healthy controls in our discovery cohort using a random forest analysis with 93.7% accuracy with promise in predicting progression rate of patients. Importantly, cross-validation of this novel signature using a new geographically distinct cohort of samples from the United Kingdom and Germany with both amyotrophic lateral sclerosis and control samples (n=156) yielded an accuracy of 73.9%. The high prediction accuracy of this non-coding RNA-based biomarker signature, even across heterogeneous cohorts, demonstrates the strength of our approach as a novel platform to identify and stratify amyotrophic lateral sclerosis patients

Sirolimus and kidney growth in autosomal dominant polycystic kidney disease

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care. All patients had an estimated creatinine clearance of at least 70 ml per minute. Serial magnetic resonance imaging was performed to measure the volume of polycystic kidneys. The primary outcome was total kidney volume at 18 months on blinded assessment. Secondary outcomes were the glomerular filtration rate and urinary albumin excretion rate at 18 months. RESULTS: At randomization, the median total kidney volume was 907 cm(3) (interquartile range, 577 to 1330) in the sirolimus group and 1003 cm(3) (interquartile range, 574 to 1422) in the control group. The median increase over the 18-month period was 99 cm(3) (interquartile range, 43 to 173) in the sirolimus group and 97 cm(3) (interquartile range, 37 to 181) in the control group. At 18 months, the median total kidney volume in the sirolimus group was 102% of that in the control group (95% confidence interval, 99 to 105; P=0.26). The glomerular filtration rate did not differ significantly between the two groups; however, the urinary albumin excretion rate was higher in the sirolimus group. CONCLUSIONS: In adults with ADPKD and early chronic kidney disease, 18 months of treatment with sirolimus did not halt polycystic kidney growth. (ClinicalTrials.gov number, NCT00346918.

A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection

The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity

A hybrid-dimensional coupled pore-network/free-flow model including pore-scale slip and its application to a micromodel experiment

Modeling coupled systems of free flow adjacent to a porous medium by means of fully resolved Navier-Stokes equations is limited by the immense computational cost and is thus only feasible for relatively small domains. Coupled, hybrid-dimensional models can be much more efficient by simplifying the porous domain, e.g., in terms of a pore-network model. In this work, we present a coupled pore-network/free-flow model taking into account pore-scale slip at the local interfaces between free flow and the pores. We consider two-dimensional and three-dimensional setups and show that our proposed slip condition can significantly increase the coupled model’s accuracy: compared to fully resolved equidimensional numerical reference solutions, the normalized errors for velocity are reduced by a factor of more than five, depending on the flow configuration. A pore-scale slip parameter βpore required by the slip condition was determined numerically in a preprocessing step. We found a linear scaling behavior of βpore with the size of the interface pore body for three-dimensional and two-dimensional domains. The slip condition can thus be applied without incurring any run-time cost. In the last section of this work, we used the coupled model to recalculate a microfluidic experiment where we additionally exploited the flat structure of the micromodel which permits the use of a quasi-3D free-flow model. The extended coupled model is accurate and efficient.Projekt DEALDeutsche Forschungsgemeinschaf

The effect of induced forelimb lameness on thoracolumbar kinematics during treadmill locomotion

Reasons for performing study: Lameness has often been suggested to result in altered movement of the back, but there are no detailed studies describing such a relationship in quantitative terms. Objectives: To quantify the effect of induced subtle forelimb lameness on thoracolumbar kinematics in the horse. Methods: Kinematics of 6 riding horses was measured at walk and at trot on a treadmill before and after the induction of reversible forelimb lameness grade 2 (AAEP scale 1-5). Ground reaction forces (GRF) for individual limbs were calculated from kinematics. Results: The horses significantly unloaded the painful limb by 11.5% at trot, while unloading at walk was not significant. The overall flexion-extension range of back motion decreased on average by 0.2° at walk and increased by 3.3° at trot (P<0.05). Changes in angular motion patterns of vertebral joints were noted only at trot, with an increase in flexion of 0.9° at T10 (i.e. angle between T6, T10 and T13) during the stance phase of the sound diagonal and an increase in extension of the thoracolumbar area during stance of the lame diagonal (0.7° at T13, 0.8° at T17, 0.5° at L1, 0.4° at L3 and 0.3° at L5) (P<0.05). Lameness further caused a lateral bending of the cranial thoracic vertebral column towards the lame side (1.3° at T10 and 0.9° at T13) (P<0.05) during stance of the lame diagonal. Conclusions: Both range of motion and vertebral angular motion patterns are affected by subtle forelimb lameness. At walk, the effect is minimal, at trot the horses increased the vertebral range of motion and changed the pattern of thoracolumbar motion in the sagittal and horizontal planes, presumably in an attempt to move the centre of gravity away from the lame side and reduce the force on the affected limb. Potential relevance: Subtle forelimb lameness affects thoracolumbar kinematics. Future studies should aim at elucidating whether the altered movement patterns lead to back and/or neck dysfunction in the case of chronic lameness

Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment

Shared mental models and intra-team psychophysiological patterns: A test of the juggling paradigm

We explored implicit coordination mechanisms underlying the conceptual notion of "shared mental models" (SMM) through physiological (i.e., breathing and heart rates) and affective-cognitive (i.e., arousal, pleasantness, attention, self-efficacy, other's efficacy) monitoring of two professional jugglers performing a real-time interactive task of increasing difficulty. There were two experimental conditions: "individual" (i.e., solo task) and "interactive" (i.e., two jugglers established a cooperative interaction by juggling sets of balls with each other). In both conditions, there were two task difficulties: “easy” and “hard”. Descriptive analyses revealed that engaging in a dyadic cooperative motor task (interactive condition) required greater physiological effort (Median Cohen’s d = 2.13) than performing a solo motor task (individual condition) of similar difficulty. Our results indicated a strong positive correlation between the jugglers’ heart rate for the easy (r = .87) and hard tasks (r = .77). The relationship between the jugglers’ breathing rate was significant for the easy task (r = .73) but non-significant for the hard task. The findings are interpreted based on research on SMM and Theory of Mind. Practitioners should advance the notion of “shared-regulation” in the context of team coordination through the use of biofeedback training