The NF-κB signalling pathway plays a critical role in inflammation, immunity, cell proliferation, apoptosis, and muscle metabolism. NF-κB is activated by extracellular signals and intracellular ...changes in Ca2+, Pi, H+, metabolites and reactive oxygen and nitrogen species (RONS). However, it remains unknown how NF-κB signalling is activated during exercise and how metabolite accumulation and PO2 influence this process. Eleven active men performed incremental exercise to exhaustion (IE) in normoxia and hypoxia (PIO2:73 mmHg). Immediately after IE, the circulation of one leg was instantaneously occluded (300 mmHg). Muscle biopsies from m. vastus lateralis were taken before (Pre), and 10s (Post, occluded leg) and 60s after exercise from the occluded (Oc1m) and free circulation (FC1m) legs simultaneously together with femoral vein blood samples. NF-κB signalling was activated by exercise to exhaustion, with similar responses in normoxia and acute hypoxia, as reflected by the increase of p105, p50, IKKα, IκBβ and glutathione reductase (GR) protein levels, and the activation of the main kinases implicated, particularly IKKα and CaMKII δD, while IKKβ remained unchanged. Postexercise ischaemia maintained and stimulated further NF-κB signalling by impeding muscle reoxygenation. These changes were quickly reverted at the end of exercise when the muscles recovered with open circulation. Finally, we have shown that Thioredoxin 1 (Trx1) protein expression was reduced immediately after IE and after 1 min of occlusion while the protein expression levels of glutathione peroxidase 1 (Gpx1) and thioredoxin reductase 1 (TrxR1) remained unchanged. These novel data demonstrate that exercising to exhaustion activates NF-κB signalling in human skeletal muscle and regulates the expression levels of antioxidant enzymes in human skeletal muscle. The fast regulation of NF-κB at exercise cessation has implications for the interpretation of published studies and the design of new experiments.
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•NF-κB plays a critical role in inflammation, immunity, cell proliferation, apoptosis and muscle metabolism.•Exercise to exhaustion in normoxia and severe hypoxia activates NF-κB signalling similarly.•This activation entails increases of p105, p50, IKKα, IκBβ, and glutathione reductase protein levels and CaMKII δD phosphorylation.•These changes are reverted within 60 s from the end of the exercise unless immediate ischaemia is applied at exhaustion.•The fast regulation of the NF-κB signalling with the cessation of exercise should be considered to interpret published studies.
Providing validated instruments in higher education on social support perceived by students allows research and improvement of university policies aimed at developing the psychosocial well-being of ...future social workers. The objective of the study was to evaluate the psychometric properties of the social provisions scale (SPS) in a sample of uniiversity students of social work in Spain. The results obtained through structural equation modeling confirmed the structure of six correlated factors and adequate levels of reliability; and factorial invariance analysis indicates that the SPS remains stable up to the level of metric invariance for the sex variable.
Abstract
Objectives
Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country ...data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe.
Methods
A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM).
Results
Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models.
Conclusions
Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.
Abstract
Objectives
To determine associations between farm- and flock-level antimicrobial usage (AMU), farm biosecurity status and the abundance of faecal antimicrobial resistance genes (ARGs) on ...broiler farms.
Methods
In the cross-sectional pan-European EFFORT study, conventional broiler farms were visited and faeces, AMU information and biosecurity records were collected. The resistomes of pooled faecal samples were determined by metagenomic analysis for 176 farms. A meta-analysis approach was used to relate total and class-specific ARGs (expressed as fragments per kb reference per million bacterial fragments, FPKM) to AMU (treatment incidence per DDD, TIDDDvet) per country and subsequently across all countries. In a similar way, the association between biosecurity status (Biocheck.UGent) and the resistome was explored.
Results
Sixty-six (38%) flocks did not report group treatments but showed a similar resistome composition and roughly similar ARG levels to antimicrobial-treated flocks. Nevertheless, we found significant positive associations between β-lactam, tetracycline, macrolide and lincosamide, trimethoprim and aminoglycoside antimicrobial flock treatments and ARG clusters conferring resistance to the same class. Similar associations were found with purchased products. In gene-level analysis for β-lactams and macrolides, lincosamides and streptogramins, a significant positive association was found with the most abundant gene clusters blaTEM and erm(B). Little evidence was found for associations with biosecurity.
Conclusions
The faecal microbiome in European broilers contains a high diversity of ARGs, even in the absence of current antimicrobial selection pressure. Despite this, the relative abundance of genes and the composition of the resistome is positively related to AMU in European broiler farms for several antimicrobial classes.
In polymorphous optical burst-switched (POBS) networks, the burst control packets (BCPs) of conventional just-enough-time based signalling OBS networks are given extended properties which enable them ...not only to reserve fixed time-slots for asynchronous data bursts, but also to allocate TDM reservations for periodic streams of data, and even a complete wavelength for high-bandwidth demanding services. This allows POBS to provide a flexible, yet transparent, approach for supporting the idiosyncrasies of today's most popular services over the same underlying network architecture. In POBS, the spare gaps in between synchronous TDM reservations can be used for the allocation of best-effort data bursts, leading to a more efficient utilisation of the optical capacity. This work shows how to extend the well-known Erlang fixed point procedure to evaluate the performance behavior of POBS networks, whereby asynchronous data bursts coexist with high-priority periodic TDM reservations. The performance evaluation algorithm is applied to a number of case scenarios, showing the benefits arisen due to the flexibility of POBS networks.
We aimed to demonstrate the feasibility of 90-day cardiac monitoring with an external Holter device and to find a target population able to benefit from such a technique. Cryptogenic stroke patients ...were continuously monitored for 90 days with a textile wearable Holter (TWH). Compliance and quality of the monitoring were assessed by the number of hours of ECG stored per month. Mean predictors of pAF, including age, gender, stroke severity, and atrial size (LAVI), were evaluated. One-year follow-up assessed pAF detection outside per protocol monitoring. Out of 224 patients included in 5 stroke centers, 163 patients (72.76%) fulfilled the criteria for the protocol. Median monitoring time was similar among the three months. Per protocol pAF detection reached 35.37% at 90 days. The age (OR 1.095; 95% CI 1.03–1.14) and the LAVI (OR 1.055; 95% CI 1.01–1.09) independently predicted pAF. The cut-off point of 70 years (AUC 0.68) (95% CI 0.60–0.76) predicted pAF with a sensitivity of 75.8% and specificity of 50.5%. The LAVI cut-off point of 28.5 (AUC 0.67) (95% CI 0.56–0.77) had a sensitivity of 63.6% and a specificity of 61.8% to detect pAF. The combination of both markers enhanced the validity of pAF detection sensitivity to 89.6%, with a specificity of 27.59%. These patients had increased risk of pAF during the 90-day monitoring HR 3.23 (
χ
2
7.15) and beyond 90 days (
χ
2
5.37). Intensive 90-days TWH monitoring detected a high percentage of pAF. However, a significant number of patients did not complete the monitoring. Patients older than 70 years and with enlarged left atria benefitted more from the protocol.
Background Our goal is to evaluate whether the administration of thrombolytic treatment has varying effects on clinical and radiological outcomes in patients with large‐vessel occlusion stroke, based ...on the type of stroke center where the treatment was given (thrombectomy‐capable center versus local stroke center). Methods We included patients with an acute ischemic large‐vessel occlusion stroke who were directly admitted to thrombectomy‐capable centers and treated with endovascular thrombectomy, or were transferred from local stroke centers as thrombectomy candidates, in Catalonia, Spain, between 2017 and 2021. The primary outcome was the shift analysis on the modified Rankin scale score at 90 days. Secondary outcomes included death at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse‐probability weighting clustered at the type of stroke center was used to estimate the effects. Results The analysis included 2268 patients directly admitted to thrombectomy‐capable centers, of whom 975 (49%) were treated with thrombolysis, and 938 patients transferred from local stroke centers, of whom 580 (66%) were treated with thrombolysis and 616 (67%) were treated with thrombectomy. Mean age was 72 (SD ±13) years, median National Institute of Health Stroke Scale score was 17 (interquartile range, 12–21), and 1363 patients were women (48%). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image, higher Alberta Stroke Program Early Computed Tomography Score, and lower rates of wake‐up stroke, atrial fibrillation, and anticoagulation intake. Patients treated with thrombolysis had better functional outcome at 90 days, with no difference between patients directly admitted to thrombectomy‐capable centers (adjusted common odds ratio acOR, 1.50 95% CI, 1.24–1.81) and patients transferred from local stroke centers (acOR, 1.44 95% CI, 1.04–2.01). Patients treated with intravenous thrombolysis had lower death rate, higher rate of parenchymal hematoma, and similar rate of successful reperfusion, with no difference according to type of center ( P interaction >0.1). Conclusion Administration of intravenous thrombolysis in patients with a large‐vessel stroke with intention of thrombectomy was associated with lower degrees of disability, lower death rate, and higher rates of parenchymal hematoma both in thrombectomy‐capable centers and in local stroke centers.
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