Blood-based assessment of oxidative stress, inflammation, endocrine and metabolic adaptations in eventing horses accounting for plasma volume shift after exercise

Background After submaximal exercise, blood values of eventing horses show physiological reactions. Objectives This prospective longitudinal study investigated blood parameters in 20 elite eventing horses before and after two–four-star cross-country rides. Methods Using a mixed model adjusting for plasma volume shift, we assessed exercise-dependent parameters and compared blood values with reference ranges for healthy horses at rest. Results Following exercise, cortisol, triiodothyronine (T3) and thyroxine (T4) showed short-term increases, and superoxide-dismutase showed a small short-term increase. Hepatic values showed short-term (haemoglobin [HGB], globulins) or sustained increases (bilirubin, glutamate dehydrogenase, alanine aminotransferase). Digestion-related parameters showed small short-term increases (α-amylase, triglycerides) or decreases (cholesterol, DGGR-lipase), apparent through plasma shift adjustment. Zinc decreased in the short term, and iron showed a delayed decrease. White blood cell count increased persistently after training, whereas serum amyloid A remained unchanged. Conclusions Exercised eventing horses had consistently elevated HGB and cortisol levels 10 and 30 min after submaximal exercise, exceeding the reference ranges for healthy horses at rest. Exercise activates the hypothalamic–pituitary–adrenocortical and hypothalamic–pituitary–thyroid axes. Antioxidant activity was observed. Increased energy requirements led to the mobilization of energy reserves, and a sustained increase in liver enzymes indicated hepatocellular injury. Mild haemolysis suggested increased muscle metabolism, whereas signs of inflammation were subtle. Further research is needed to identify which horses deviate from mean values

Blood-Based Markers for Skeletal and Cardiac Muscle Function in Eventing Horses before and after Cross-Country Rides and How They Are Influenced by Plasma Volume Shift

Horses competing in cross-country tests are subjected to high physical demands. Within the scope of this prospective longitudinal study, blood values of 20 elite eventing horses were examined before and after two- to four-star cross-country rides. The aim was to find out whether blood-based markers for skeletal muscle and cardiac muscle function change after cross-country exercise. Parameters that provide information about fluid balance, muscle enzymes, metabolites and cardiac muscle-specific markers were investigated. We developed an approach to eliminate the concentration changes caused by reduced plasma volume. Parameters were measured pre, 10 and 30 min post exercise and the next morning and were evaluated using a mixed model. Thirty minutes after exercise, most parameter concentrations changed in an exercise-dependent manner. The next morning, most exercise-related markers recovered rapidly, while creatine kinase (CK) (26% increase; p = 0.008) and lactate dehydrogenase (LDH) (15% increase; p < 0.001) showed a declining but sustained increase. Cardiac troponin I (cTnI) increased above the reference range in 40 of the 55 rides (73%) and in 18 of 20 horses in the morning after exercise

Spatial proteomics revealed a CX3CL1-dependent crosstalk between the urothelium and relocated macrophages through IL-6 during an acute bacterial infection in the urinary bladder

The urothelium of the urinary bladder represents the first line of defense. However, uropathogenic E. coli (UPEC) damage the urothelium and cause acute bacterial infection. Here, we demonstrate the crosstalk between macrophages and the urothelium stimulating macrophage migration into the urothelium. Using spatial proteomics by MALDI-MSI and LC-MS/MS, a novel algorithm revealed the spatial activation and migration of macrophages. Analysis of the spatial proteome unravelled the coexpression of Myo9b and F4/80 in the infected urothelium, indicating that macrophages have entered the urothelium upon infection. Immunofluorescence microscopy additionally indicated that intraurothelial macrophages phagocytosed UPEC and eliminated neutrophils. Further analysis of the spatial proteome by MALDI-MSI showed strong expression of IL-6 in the urothelium and local inhibition of this molecule reduced macrophage migration into the urothelium and aggravated the infection. After IL-6 inhibition, the expression of matrix metalloproteinases and chemokines, such as CX3CL1 was reduced in the urothelium. Accordingly, macrophage migration into the urothelium was diminished in the absence of CX3CL1 signaling in Cx3cr1gfp/gfp mice. Conclusively, this study describes the crosstalk between the infected urothelium and macrophages through IL-6-induced CX3CL1 expression. Such crosstalk facilitates the relocation of macrophages into the urothelium and reduces bacterial burden in the urinary bladder. © 2020, The Author(s)

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Physiological response to training and competition in 1-star to 4-star eventing horses

Abstract 034 – Physiological response to training and competition in 1-star to 4-star eventing horses – Post Review Authors’ names and affiliations Author 1: Katharina Kirsch* (German Olympic Committee for Equestrian Sports, Germany and PhD Student, University of Liège, Belgium) Author 2: Michael Düe (German Equestrian Federation, Germany) Author 3: Hermann Holzhausen (Olympic Support Center Westphalia – Warendorf, Germany) Author 4: Stephanie Horstmann (German Olympic Committee for Equestrian Sports, Germany) Author 5: Markus Scharmann (German Equestrian Federation, Germany) Author 6: Charlotte Sandersen (University of Liège, Belgium) *Address of the presenting author: Katharina Kirsch, Freiherr-von-Langen-Str. 15, 48231 Warendorf, GERMANY E-mail of the presenting author: [email protected] Abstract Physiological response to training and competition in 1-star to 4-star eventing horses To prepare horses for the requirements of international eventing competitions and simultaneously maintain their health and welfare, appropriate training is mandatory. Specific training and competition management necessitates information about exercise intensities and fitness, which are usually assessed by standardized exercise tests. Our purpose was to identify parameters whose measurement can be largely integrated in the daily training and competition routine and which provide information on fitness and adequacy of applied training. Further, we evaluated training and competition intensities of eventing horses, based on data generated by a proportionally large group of horses over several years. Data of 187 horses from 1-star to 4-star level over a time period of six years were collected during 410 training sessions and 916 Cross Country rides, including measurement of covered distance and speed (GPS, Fidelak EquiPILOT), continuously recording of heart rate (HR) (Polar T52H) and determination of blood lactate concentrations (BLC) (Dr. Lange photometer). Characteristics of the track, altitude profile, ambient temperature and humidity were recorded at each session. The results of the one-way ANOVA indicated a significant effect of competition level on HR (F3,373=23.29; p<0.001) and BLC (F3,763=46.12; p<0.001). Under competition conditions, HR and BLC increased from 1-star to 3-star level (1-star: HR=194±9 bpm, BLC=7.7±5.6 mmol/l; 2-star: HR=198±9 bpm, BLC=9.6±6.2 mmol/l; 3-star: HR=205±10, BLC=15.6±9.8 mmol/l; 4-star: HR=207±2 bpm, BLC=12.4±9.3 mmol/l), while under training conditions, they decreased with increasing competition level (1-star: HR=184±29 bpm; BLC=18.9±11.1 mmol/l; 2-star: HR=182±19 bpm; BLC=12.1±9.0; 3-star: HR=174±25 bpm; BLC=6.9±7.1 mmol/l; 4-star: HR=161±24 bpm, BLC=4.0±5.6 mmol/l). On 1-/2-star level, BLCs after training exceeded those after competition. Reverse applied for 3-/4-star level. On 3-star level, the percentage of HRs above 200 bpm during Cross Country was considerably greater than on lower levels (1-star: 33%; 2-star: 54%; 3-star: 94%). The competition format (CCI/CIC) had no significant effect on the progress of HR. The altitude profile however, had a significant effect on HR (F1,201=26.72, p<0.001) and BLC (F1,89=25.56; p<0.001). Evaluation of physiological response to training and competition through implementation of measurement technology allows an assessment of the different impacts on exercise intensities and should be more commonly used to assess appropriateness of training and competition management in eventing horses. It should be further investigated if the detected discrepancies in the response to training and competition between levels are a result of different fitness ore varying training strategies. LP To meet the demands of international Eventing competitions, a systematic training of horses is necessary. Close monitoring of physiological response to exercise during training and competition can help to improve training. Keywords Exercise physiology; training; eventing; heart rate; lactate

Advances in remote sensing of emperor penguins: first multi-year time series documenting trends in the global population

International audienceLike many polar animals, emperor penguin populations are challenging to monitor because of the species' life history and remoteness. Consequently, it has been difficult to establish its global status, a subject important to resolve as polar environments change. To advance our understanding of emperor penguins, we combined remote sensing, validation surveys and using Bayesian modelling, we estimated a comprehensive population trajectory over a recent 10-year period, encompassing the entirety of the species’ range. Reported as indices of abundance, our study indicates with 81% probability that there were fewer adult emperor penguins in 2018 than in 2009, with a posterior median decrease of 9.6% (95% credible interval (CI) −26.4% to +9.4%). The global population trend was −1.3% per year over this period (95% CI = −3.3% to +1.0%) and declines probably occurred in four of eight fast ice regions, irrespective of habitat conditions. Thus far, explanations have yet to be identified regarding trends, especially as we observed an apparent population uptick toward the end of time series. Our work potentially establishes a framework for monitoring other Antarctic coastal species detectable by satellite, while promoting a need for research to better understand factors driving biotic changes in the Southern Ocean ecosystem

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature

SIMPLE SUMMARY: Meningiomas are the most common tumours of the central nervous system (CNS). Despite their benign histology, proximity to critical neurovascular structures may lead to significant morbidity with tumour growth. This is the case for cavernous sinus meningiomas (CSMs), as their growth may surround critical neuro-vascular structures and cause significant morbidity. Radical microsurgical resection carries a high risk of additional neurological deficits, as well as the risk of death. Current management of these tumours, where treatment is indicated, has moved away from radical surgery towards radiotherapy/radiosurgery. This is particularly the case for patients who have residual or recurring tumours after previous surgery. There are many reports that describe the effectiveness of using stereotactic radiosurgery (SRS) for CSMs; however, large cohort analyses are lacking. This multicentre analysis reports the outcome data of over 1000 patients with CSMs who were treated with SRS. SRS shows a high local tumour control rate with few complications. These results agree with previous reports in the literature. SRS is a valuable primary or adjuvant treatment option for CSMs. ABSTRACT: Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term

Supplementary Materials from Advances in remote sensing of emperor penguins: first multi-year time series documenting trends in the global population

Figures S1-S2 and Tables S1-S4, showing posterior predictive checks, modeled indices, simulation results, a description of the population model, summary of parameters, and locations of apparent colony absence