Structural attributes contributing to locomotor performance in the ostrich

As the fastest long-endurance runner, the bipedal ostrich (Struthio camelus) was selected as a prime model organism to investigate the physical attributes underlying this advanced locomotor performance. A specific integrative approach combining morphological, morphometric, kinematic and pedobarographic methods was developed. The comparative morphometric analysis of the hind limbs of all ratite species revealed that leg segment ratios in the ostrich are the most specialised for efficient locomotion, especially when taking into consideration its unique supra-jointed toe posture. In addition, the crural muscle mass is more concentrated towards the hip joint in the ostrich than in its ratite relatives. According to the Law of the Pendulum, this concentration of mass towards the pivot point – in concert with the relatively longest and lightest distal leg elements – represents a mechanical optimisation of limb swinging capacities. While musculature clearly drives limb movement, the passive guidance and constraint of motion range by ligamentous structures combined with joint surface contours allows a high level of energy output efficiency during all stages of locomotion and ensures articular stability during slow locomotion as well as high-speed performance. So far, the influence of these passive effects in locomotion has been largely ignored. In order to quantify the guiding effect of these anatomical structures, kinematic data of adult ostriches during walking and running were collected. Subsequently, these data were compared with results from manual manipulation experiments performed with the limbs of anatomical specimens – both fully intact and with muscles removed – leaving only the ligament system intact. This investigation revealed that the range of motion among leg segments was nearly identical in all sample groups, especially in regard to maximum extension values. This indicates that ostrich hind limb dynamics are managed to a significant degree by passive elements that ensure a controlled swing-plane with minimal deviation from an optimal attitude. Further dissections allowed some of these features to be described in detail, with an emphasis on functional-morphological examination of the intertarsal joint. The intertarsal joint contains a significant locking mechanism, briefly mentioned in historical documents, but described and functionally analysed herein for the first time. The functional examination qualified the interplay of three collateral ligaments, the tendinous M. fibularis brevis and specific joint surface protrusions as the basis for this effect which remains absent in smaller ground-dwelling bird species. A proximate quantification, based on comparative morphological and kinematic data, revealed function of Struthio's passively locked intertarsal joint as a potent stabiliser in the supporting limb during the ground-contact phase of locomotion. During stance phase, it is crucial that the supporting limb is stabilised internally and in relation to the substrate. As yet, no study exists concerning use and loading of the actual ground contact elements. The toes must absorb body mass, guarantee stable grip and provide energetic push off. Obvious specialisations of the ostrich's phalangeal complex include toe reduction (leaving only 3rd and 4th toe), claw reduction (only at 3rd toe) and a permanently elevated metatarsophalangeal joint. Using a relatively new methodology to examine in vivo toe function, pedobarography was employed on specifically trained ostriches to allow extensive collection of Centre of Pressure (CoP) and load distribution (LD) data. In contrast to a relatively predictable CoP trajectory at all speeds, conspicuous LD differences were observed between slow and fast trials. Load was distributed rather inconsistently during walking, while a typical tripod-like toe-print occurred in all running trials to presumably deliver additional stability during the comparatively short stance phase. Significant grip is provided by the highly directed impact of the 3rd toe claw-tip, suggesting its important function as a positional anchor during running. Pedobarographic analysis further showed the importance of the 4th toe as an outrigger to maintain balance, rendering a future reduction highly unlikely. In conclusion, the application of interdisciplinary methodologies allowed comprehensive data collection and integration of the model organism within its ecological context. The data gained from this thesis increases the current knowledge about ostrich locomotion by identifying distinct structural attributes as essential elements for extreme cursorial performance. The present data may alter existing models for calculation of the metabolic cost of terrestrial locomotion and aid in the reconstruction of theropod locomotion, as these branch sciences often overlook the important role of ligaments and passively-coupled motion cycles in reducing the cost of locomotion

Estimated physical activity in Bavaria, Germany, and its implications for obesity risk: Results from the BVS-II Study

BACKGROUND: Adequate physical activity (PA) is considered as a key factor in the fight against the obesity epidemic. Therefore, detailed description of the actual PA and its components in the population is necessary. Additionally, this study aims to investigate the association between PA and obesity risk in a representative population sample in Bavaria, Germany. METHODS: Data from 893 participants (age 13–80 years) of the Bavarian Food Consumption Survey II (BVS II) were used. In each participant, three computer-based 24-hour recalls were conducted by telephone assessing type and duration of PA in the domains occupation, sports, other strenuous leisure time activities (of mostly moderate intensity) as well as TV/PC use in leisure time and duration of sleeping. After assigning metabolic equivalents (METs) to each activity, estimates of energy expenditure (MET*h) and total daily PA level (PAL(est.)) were calculated. In a subgroup of adults (n = 568) with anthropometric measurements logistic regression models were used to quantify the impact of PA on obesity risk. RESULTS: Estimated average PA in women and men was 38.5 ± 5.0 and 40.6 ± 9.3 MET*h/d, respectively, corresponding to PAL(est. )values of 1.66 ± 0.22 and 1.75 ± 0.40. Obese subjects showed lower energy expenditure in the categories sports, occupation, and sleeping, while the time spent with TV/PC during leisure time was highest. This is confirmed in logistic regression analyses revealing a statistically significant association between obesity and TV/PC use during leisure time, while sports activity was inversely related to obesity risk. Overall, less than 1/3 of the study participants reached the recommended PAL of ≥ 1.75. Subjects within the recommended range of PA had an about 60 % (odds ratio = 0.43; 95% CI: 0.21–0.85) reduced risk of obesity as compared to inactive subjects with a PAL(est. )<1.5. CONCLUSION: Based on the results of short-term PA patterns, a major part of the Bavarian adult population does not reach the recommendations (PAL>1.75; moderate PA of > 30 min/d). Despite the limitations of the study design, the existing associations between sports activity, TV/PC use and obesity risk in this population give further support to the recommendation of increasing sports activity and reducing sedentary behaviour in order to prevent rising rates of obesity

Predictive skill of teleconnection patterns in twentieth century seasonal hindcasts and their relationship to extreme winter temperatures in Europe

European winter weather is dominated by several low-frequency teleconnection patterns, the main ones being the North Atlantic Oscillation, East Atlantic, East Atlantic/Western Russia and Scandinavian patterns. We analyze the century-long ERA-20C reanalysis and ASF-20C seasonal hindcast datasets and find that these patterns are subject to decadal variability and fluctuations in predictive skill. Using indices for determining periods of extreme cold or warm temperatures, we establish that the teleconnection patterns are, for some regions, significantly correlated or anti-correlated to cold or heat waves. The seasonal hindcasts are however only partly able to capture these relationships. There do not seem to be significant changes to the observed links between large-scale circulation patterns and extreme temperatures between periods of higher and lower predictive skill

From structure to function – a family portrait of plant subtilases

Subtilases (SBTs) are serine peptidases that are found in all three domains of life. As compared with homologs in other Eucarya, plant SBTs are more closely related to archaeal and bacterial SBTs, with which they share many biochemical and structural features. However, in the course of evolution, functional diversification led to the acquisition of novel, plant-specific functions, resulting in the present-day complexity of the plant SBT family. SBTs are much more numerous in plants than in any other organism, and include enzymes involved in general proteolysis as well as highly specific processing proteases. Most SBTs are targeted to the cell wall, where they contribute to the control of growth and development by regulating the properties of the cell wall and the activity of extracellular signaling molecules. Plant SBTs affect all stages of the life cycle as they contribute to embryogenesis, seed development and germination, cuticle formation and epidermal patterning, vascular development, programmed cell death, organ abscission, senescence, and plant responses to their biotic and abiotic environments. In this article we provide a comprehensive picture of SBT structure and function in plants.Instituto de Fisiología Vegeta

The tomato subtilase family includes several cell death-related proteinases with caspase specificity

Phytaspases are Asp-specific subtilisin-like plant proteases that have been likened to animal caspases with respect to their regulatory function in programmed cell death (PCD). We identified twelve putative phytaspase genes in tomato that differed widely in expression level and tissue-specific expression patterns. Most phytaspase genes are tandemly arranged on tomato chromosomes one, four, and eight, and many belong to taxon-specific clades, e.g. the P69 clade in the nightshade family, suggesting that these genes evolved by gene duplication after speciation. Five tomato phytaspases (SlPhyts) were expressed in N. benthamiana and purified to homogeneity. Substrate specificity was analyzed in a proteomics assay and with a panel of fluorogenic peptide substrates. Similar to animal caspases, SlPhyts recognized an extended sequence motif including Asp at the cleavage site. Clear differences in cleavage site preference were observed implying different substrates in vivo and, consequently, different physiological functions. A caspase-like function in PCD was confirmed for five of the seven tested phytaspases. Cell death was triggered by ectopic expression of SlPhyts 2, 3, 4, 5, 6 in tomato leaves by agro-infiltration, as well as in stably transformed transgenic tomato plants. SlPhyts 3, 4, and 5 were found to contribute to cell death under oxidative stress conditions

The tomato subtilase family includes several cell death-related proteinases with caspase specificity

Phytaspases are Asp-specific subtilisin-like plant proteases that have been likened to animal caspases with respect to their regulatory function in programmed cell death (PCD). We identified twelve putative phytaspase genes in tomato that differed widely in expression level and tissue-specific expression patterns. Most phytaspase genes are tandemly arranged on tomato chromosomes one, four, and eight, and many belong to taxon-specific clades, e.g. the P69 clade in the nightshade family, suggesting that these genes evolved by gene duplication after speciation. Five tomato phytaspases (SlPhyts) were expressed in N. benthamiana and purified to homogeneity. Substrate specificity was analyzed in a proteomics assay and with a panel of fluorogenic peptide substrates. Similar to animal caspases, SlPhyts recognized an extended sequence motif including Asp at the cleavage site. Clear differences in cleavage site preference were observed implying different substrates in vivo and, consequently, different physiological functions. A caspase-like function in PCD was confirmed for five of the seven tested phytaspases. Cell death was triggered by ectopic expression of SlPhyts 2, 3, 4, 5, 6 in tomato leaves by agro-infiltration, as well as in stably transformed transgenic tomato plants. SlPhyts 3, 4, and 5 were found to contribute to cell death under oxidative stress conditions

Early and strong leptin reduction is predictive for long-term weight loss during high-protein, low-glycaemic meal replacement: a subanalysis of the randomised-controlled ACOORH trial

Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria ( = 463) were randomised into two groups and received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6, and 12 months. All datasets providing leptin data ( = 427) were included in this predefined subanalysis. Serum leptin levels significantly correlated with sex, body mass index, weight, and fat mass at baseline ( &lt; 0.0001). Stronger leptin reduction has been observed in the intervention compared to the control group with the lowest levels after 1 month of intervention (estimated treatment difference -3.4 µg/L [1.4; 5.4] for females; -2.2 µg/L [1.2; 3.3] for males; &lt; 0.001 each) and was predictive for stronger reduction of body weight and fat mass ( &lt; 0.001 each) over 12 months. Strongest weight loss was observed after 6 months (-5.9 ± 5.1 kg in females of the intervention group vs. -2.9 ± 4.9 kg in the control group ( &lt; 0.0001); -6.8 ± 5.3 kg vs. -4.1 ± 4.4 kg ( = 0.003) in males) and in those participants with combined leptin and insulin decrease. A meal replacement-based lifestyle intervention effectively reduces leptin which is predictive for long-term weight loss

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat