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Abstract Background In chronic pulmonary diseases characterized by inflammation and airway obstruction, such as asthma and COPD, there are unmet needs for improved treatment. Quinolines is a group of small heterocyclic compounds that have a broad range of pharmacological properties. Here, we investigated the airway relaxant and anti-inflammatory properties of a novel quinoline (RCD405). Methods The airway relaxant effect of RCD405 was examined in isolated airways from humans, dogs, rats and mice. Murine models of ovalbumin (OVA)-induced allergic asthma and LPS-induced airway inflammation were used to study the effects in vivo. RCD405 (10 mg/kg) or, for comparisons in selected studies, budesonide (3 mg/kg), were administered intratracheally 1 h prior to each challenge. Airway responsiveness was determined using methacholine provocation. Immune cell recruitment to bronchi was measured using flow cytometry and histological analyses were applied to investigate cell influx and goblet cell hyperplasia of the airways. Furthermore, production of cytokines and chemokines was measured using a multiplex immunoassay. The expression levels of asthma-related genes in murine lung tissue were determined by PCR. The involvement of NF-κB and metabolic activity was measured in the human monocytic cell line THP-1. Results RCD405 demonstrated a relaxant effect on carbachol precontracted airways in all four species investigated (potency ranking: human = rat > dog = mouse). The OVA-specific IgE and airway hyperresponsiveness (AHR) were significantly reduced by intratracheal treatment with RCD405, while no significant changes were observed for budesonide. In addition, administration of RCD405 to mice significantly decreased the expression of proinflammatory cytokines and chemokines as well as recruitment of immune cells to the lungs in both OVA- and LPS-induced airway inflammation, with a similar effect as for budesonide (in the OVA-model). However, the effect on gene expression of Il-4, IL-5 and Il-13 was more pronounced for RCD405 as compared to budesonide. Finally, in vitro, RCD405 reduced the LPS-induced NF-κB activation and by itself reduced cellular metabolism. Conclusions RCD405 has airway relaxant effects, and it reduces AHR as well as airway inflammation in the models used, suggesting that it could be a clinically relevant compound to treat inflammatory airway diseases. Possible targets of this compound are complexes of mitochondrial oxidative phosphorylation, resulting in decreased metabolic activity of targeted cells as well as through pathways associated to NF-κB. However, further studies are needed to elucidate the mode of action.

Abstract Wildlife tracking studies have become ubiquitous in ecology and now provide previously unobtainable data regarding individual movement, vital rates, and population demographics. However, tracking devices can potentially reduce survival of study subjects, generating biases in the vital rates they seek to measure. Previous studies have found that greater sage‐grouse (Centrocercus urophasianus) fitted with Global Positioning System (GPS) tracking devices may experience reduced survival, relative to those tracked with traditional radio transmitters, and have documented skin abrasions and lacerations associated with typical backpack‐style GPS harnesses. We implemented an experimental study comparing survival and harness retention between 2 different backpack‐style GPS transmitter harnesses. We captured female sage‐grouse at 3 study sites in the northwest Great Basin of Oregon, Nevada, and California during 2019–2021. We fit each individual, following previously published recommendations, with either a standard backpack harness or a modified harness hypothesized to reduce skin abrasion and laceration. We used known‐fate models in Program MARK to model variation in survival and harness retention separately as a function of harness type, year, age, a linear effect of time, and the ratio of the device to individual body mass. Neither survival nor retention varied systematically by harness type, however retention decreased as a function of body mass ratio. We echo previous recommendations for standardized harness attachment protocols and studies designed to isolate and test potential mechanisms by which tracking devices and attachment methods might affect survival and well‐being of sage‐grouse and other tracked species.

Birds face strong selective pressures to complete individual nesting attempts as quickly as possible to minimize exposure of nests to predators and weather, maximize rcnesting potential, and maximize hatching success. As a result, the duration of developmental periods and of overall nest periods are often relatively constant within species. However, birds may sometimes be subject to acute energetic constraints that may preclude them from initiating incubation at the optimal time. We report an extraordinary case of delayed incubation by a female Burrowing Owl (Athene cunicularid) in Oregon, USA, which contrasted sharply with a large sample of nests monitored by motionactivated video cameras in western North America from 2015 to 2018. The focal female delayed incubation by 11 d following clutch completion and subsequently experienced near total hatching failure of her clutch. This observation corroborates previous experimental studies regarding the limits to egg viability and trade-offs between the timing of incubation onset and hatching success. These findings illustrate the acute trade-offs faced by nesting birds, and the cost of delayed incubation that we observed in this owl could help explain the cause of asynchronous hatching. Received 15 September 2022. Accepted 9 September 2023. Key words: clutch size, egg viability, energetic constraint, hatching asynchrony, hatching failure. Las aves enfrentan fuertes presiones selectivas para completar sus intentos de anidamiento individuales tan rapido como sea posible, para minimizar la exposicion del nido a depredadores y al tiempo, maximizar potencial de reanidamiento y maximizar exito de eclosion. Como resultado, la duracion de los periodos de desarrollo y los periodos de anidamiento generales son a menudo relativamente constantes dentro de las especies. Sin embargo, las aves pueden a veces estar sometidas a limitaciones energeticas agudas que pueden impedirles iniciar la incubacion en un tiempo optimo. Reportamos un caso extraordinario de retraso de incubacion de una hembra de buho Athene cunicularia en Oregon, Estados Unidos, que contrasto fuertemente con una muestra grande de nidos monitoreados por video camaras activadas por movimiento en el oeste de Norteamerica de 2015 a 2018. La hembra focal postergo la incubacion 11 dias despues de la puesta y a continuacion experimento una perdida casi total de la puesta. Esta observacion corrobora estudios experimentales previos acerca del limite de viabilidad de los huevos y la compensacion entre el tiempo de incubacion y el exito de eclosion. Estos hallazgos ilustran las fuertes compensaciones que enfrentan las aves ponedoras y el costo del retraso de la incubacion que observamos en este buho podria ayudar a explicar la causa de su eclosion asincronica. Palabras clave: asincronia de eclosion, fallo en eclosion, limitaciones energeticas, tamano de puesta, viabilidad de huevos., The duration of a typical nest cycle varies dramatically among bird species, with incubation periods ranging from as few as 10 d in small passerines to 2 months in some [...]

Abstract Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness of previous MEG results, although a correlation in the low beta band (13–20 Hz) to MSNA inhibition was found (p = 0.021). The predictive power is summarized in a receiver-operating-characteristics curve. The optimum threshold yielded sensitivity and false-positive rate of 0.74 and 0.33 respectively. A plausible confounder is myogenic noise. A more complicated experimental and/or analysis approach is required for differentiating MSNA-inhibitors from non-inhibitors based on EEG, as compared to MEG.

A high proportion of horses in training, perceived as free from lameness by their owner, exhibit vertical movement asymmetries. These types of asymmetries are sensitive measures of lameness, but their specificity as indicators of orthopaedic pathology or locomotor function remains unclear. Equine athletes performing at a high level could be assumed to exhibit a higher degree of movement symmetry compared with the general horse population, but this has not been confirmed. This study investigated the prevalence of movement asymmetries in horses performing at a high level in three equestrian disciplines; show jumping, dressage and eventing, as well as the association between riders' perception of horse sidedness and said movement asymmetries. Using an inertial measurement unit-based system (Equinosis), gait analysis was performed on 123 high-performing horses. The mean difference between the two vertical minimum and between the two maximum values of each stride was recorded for the head (HDmin, HDmax) and pelvis (PDmin, PDmax). The horses were defined as asymmetric if one or multiple asymmetry parameters exceeded an absolute trial mean of: >6mm for HDmin or HDmax, and >3mm for PDmin or PDmax, with standard deviation less than the respective mean value. Based on the results, 70% of the horses were classified as asymmetric, which is similar to previous findings for young riding horses and horses competing at a lower level. More than one-third of these high-performing horses had asymmetry values of similar magnitude to those seen in clinically lame horses. No clear associations were observed between rider-perceived sidedness and the vertical movement asymmetry values, indicating that the perceived unevenness between sides is not a determinant of vertical movement asymmetry. Longitudinal studies on movement asymmetries in relation to training intensity and full clinical examinations with local or systemic analgesic testing are desired as further research to determine whether these movement asymmetries indicate a welfare problem.

Abstract Background Nerve growth factor (NGF) is a neurotrophin that is increased in osteoarthritic joints of horses. In humans, NGF has been associated with pain, and both synovial and serum NGF concentrations are increased in osteoarthritic patients. Studies in humans also have shown that serum NGF concentration can increase with stress. Serum NGF concentration should be evaluated in horses with osteoarthritis‐associated lameness. Objectives Quantify and compare serum NGF concentration in horses with osteoarthritis‐associated lameness and sound horses. Additionally, the impact of short‐term stress on serum NGF concentration was investigated. Animals Lame horses with radiographic evidence of osteoarthritis (n = 20), lame horses without radiographic changes in the affected joint (n = 20) and sound horses (n = 20). In addition, horses with acute fractures (n = 9) were sampled. To determine the effect of stress, serum from horses subjected to a stressful event (transportation, n = 5; stress confirmed by increased serum cortisol concentration) was analyzed. Methods Cross‐sectional clinical study (lame, sound, and fracture cohorts) and experimental longitudinal study (stress cohort). Serum NGF concentration was determined using a quantitative sandwich ELISA. Results Serum NGF concentration was increased in lame horses with radiographic evidence of osteoarthritis (P

Background: Psychological First Aid (PFA) is practiced worldwide. This practice in English is guided through a small collection of training manuals. Despite ubiquitous practice and formal training materials, little is known about what topics are covered and in what depth in these influential manuals. As such, we analyzed the topic structure of these training manuals. Objective: To model the PFA manuals’ topics with the goal of identifying a set of topics with recurrent themes and evaluating the extent to which each manual demonstrated those themes. Method: This machine learning study employed an unsupervised topic modelling design using Latent Dirichlet Allocation. The variables are (1) the distribution of a word across documents and (2) the distribution of a word across topics. The level of measurement for all variables is continuous. The unit of analysis is words. Preprocessing and data analysis were carried out using the Orange Data Mining Toolbox (Demšar et al., ). This programme is a Python GUI. Results: Results indicated a ten-topic structure to the universe of the English PFA training manuals. These topics were: (1) Refugees, (2) Orientation Activities, (3) Community-Based Applications, (4) PTSD & Other Psychological Issues, (5) Training Materials, (6) Specific Helper Instructions, (7) PFA Scholarship, (8) MHPSS, (9) General Curriculum, and (10) Australian Specific Delivery. The depth of discourse on each topic varied widely between manuals. Conclusions: The Academics of the PFA topic shows a strong representation of the corpus and suggests current training manuals have stayed true to its evidence-supported practice. The topic of Community-Based Applications strongly represents the corpus and suggests that training models incorporate community-based applications. The scientific foundation and practical implementation of the training guides are essential elements. Limitations and implications were also discussed.

Objectives Elite youth football players miss out on a large part of seasonal training due to injury. Limited research suggests an association between external and internal training load (TL) and injury incidence in elite youth football. This study analysed external and internal TL variables and their association with injury incidence in a group of male elite youth football players over four seasons.Methods Measures of external and internal TL and injury incidence of 56 male elite youth football players (age 17–19 years) were collected throughout four seasons. Heart rate, session rating of perceived exertion andGlobal Positioning System (GPS) variables were analysed. Individual players’ TL during the 30 days leading up to injury was compared with 30-day injury-free control periods. Change in TL through the periods was also analysed.Results Eighty-five injuries were included for analysis, showing that for most TL variables, the average levels were significantly lower during the period leading up to injury. Significant increases for the majority of TL variables were also found during the periods leading up to injury, while the control periods did not show any significant change.Conclusion A lower and/or increasing average TL volume over 30 days might increase the risk of injury in male elite youth football players. Avoiding long-term drops in TL and balance increases in TL might be beneficial to reduce injury risk.

AbstractBackground Advance care planning (ACP) is a process involving conversations about values and preferences regarding future care at the end-of-life. ACP has led to positive outcomes, both in relation to quality of life and with increased use of palliative care, less life-sustaining treatment and fewer hospital admissions. Sweden has yet to embrace the practice systematically, but scattered initiatives exist.Aim To study implementation of a routine for ACP in NH settings in Sweden by exploring healthcare professionals’ experiences of engaging in ACP following this implementation.Methods The study followed a qualitative inductive design with convenience and snowball sampling. Semi-structured group and individual interviews with registered healthcare professionals were analysed using qualitative content analysis.Findings Organisational support for sustainable ACP implementation was found to be essential. This included sufficient training, facilitation, collaboration and uniform work routines across providers and professionals. Engaging in ACP conversations following the implemented routine was found to be a process of preparing, being, talking, deciding and sharing.Conclusions Successful implementation of ACP in NHs requires a carefully planned implementation strategy. ACP in NHs tend to be medically focused at the expense of residents’ psychosocial care-planning needs. Widespread uptake of ACP in Sweden could be useful in the national effort to adopt more person-centred care in Swedish healthcare.KEY POINTS While advance care planning has been implemented in many other countries, Sweden lacks a national strategy on advance care planning and Swedish healthcare settings have yet to systematically implement this practice. • This study is the first to report on professionals’ experiences of engaging in sustainable advance care planning, following top-down implementation of the practice in one Swedish region. • Successful implementation of advance care planning in nursing homes requires a system-level approach, and shortcomings of the implementation process are highlighted.

Abstract We analyse the short‐ and long‐term consequences for atmospheric greenhouse gas (GHG) concentrations of forest management strategies and forest product uses in Sweden by comparing the modelled consequences of forest resource use vs. increased conservation at different levels of GHG savings from carbon sequestration and product substitution with bioenergy and other forest products. Increased forest set‐asides for conservation resulted in larger GHG reductions only in the short term and only when substitution effects were low. In all other cases, forest use was more beneficial. In all scenarios, annual carbon dioxide (CO2) sequestration rates declined in conservation forests as they mature, eventually approaching a steady state. Forest set‐asides are thus associated with increasing opportunity costs corresponding to foregone wood production and associated mitigation losses. Substitution and sequestration rates under all other forest management strategies rise, providing support for sustained harvest and cumulative mitigation gains. The impact of increased fertilization was everywhere beneficial to the climate and surpassed the mitigation potential of the other scenarios. Climate change can have large—positive or negative—influence on outcomes. Despite uncertainties, the results indicate potentially large benefits from forest use for wood production. These benefits, however, are not clearly linked with forestry in UNFCCC reporting, and the European Union's Land Use, Land‐Use Change and Forestry carbon accounting, framework may even prevent their full realization. These reporting and accounting frameworks may further have the consequence of encouraging land set‐asides and reduced forest use at the expense of future biomass production. Further, carbon leakage and resulting biodiversity impacts due to increased use of more GHG‐intensive products, including imported products associated with deforestation and land degradation, are inadequately assessed. Considerable opportunity to better mobilize the climate change mitigation potential of Swedish forests therefore remains.

Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34–100%). The remaining 16 showed no inhibition (mean 5%, range –31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated. NEW & NOTEWORTHY: Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause. [ABSTRACT FROM AUTHOR]