Comparison between a complete preconditioning programme and conventional conduct on behaviour, health and performance of young bulls from small cow-calf herds.

Bovine respiratory diseases (BRDs) have major socioeconomic impacts in the beef sector. Antimicrobials have been traditionally used to prevent the development of BRDs upon arrival in fattening units. Currently, from a "One Health and One Welfare" perspective, alternative solutions are being investigated. Preconditioning programmes that aim at reducing stress and reinforcing immune functions have been proposed to decrease BRDs incidence. In this study, we assessed the effect of a preconditioning protocol set up in nine commercial beef herds on young bulls' behaviour, health, and performance. Preconditioned bulls (PREC) were weaned indoors 50 days before departure, and progressively fed a concentrate diet supplemented with vitamins and trace elements. They also received an anthelmintic treatment, and two doses of a trivalent vaccine against respiratory pathogens at 4-week intervals. In contrast, controls (CTRL) were kept on pasture with their dams with no vaccination or particular diets. All calves were transported together to a single sorting facility to be sorted by experimental groups, origins, and BW, forming new groups before dispatch to four fattening units. At arrival, CTRL were treated with anthelmintic drugs and received one injection of the same BRDs vaccine. No intervention was performed on PREC bulls. BRD-scores were 0.73 in PREC versus 0.07 in CTRL (P = 0.01) during the preconditioning period and 0.96 in PREC versus 0.54 in CTRL (P = 0.41) after 15 days in the fattening units. Morbidity estimates were 18% in PREC versus 1% in CTRL (P < 0.001) during the preconditioning period and 32% in PREC versus 19% (P = 0.07) in CTRL after 15 days in the fattening units. Poor housing conditions during preconditioning and a different aetiology could partly explain these results. At arrival to fattening, the average daily gain (ADG) was 1 605 g for PREC versus 1 140 g (P = 0.012) for CTRL. After fattening for 180 days, differences in BW, ADG, carcass weight and conformation were inconclusive. In Europe, preconditioning programmes including vaccination must be set up coherently with good husbandry practices and with a global adaptation of batch management of the beef sector otherwise, they may be less effective than expected.

A theory for context-dependent effects of mammalian trampling on ecosystem nitrogen cycling.

Large mammalian herbivores substantially impact ecosystem functioning. As their populations are dramatically altered globally, disentangling their consumptive and non-consumptive effects is critical to advance mechanistic understanding and improve prediction of effects over ecosystem and Earth-system spatial extents. Mathematical models have played an important role in clarifying potential mechanisms of herbivore zoogeochemistry, based mostly on their consumptive effects as primary consumers and recyclers of organic and inorganic matter via defecation and urination. Trampling is a ubiquitous effect among walking vertebrates, but the consequences and potential mechanisms of trampling in diverse environments remain poorly understood. We derive a novel mathematical model of large mammalian herbivore effects on ecosystem nitrogen cycling, focusing on how trampling and environmental context impact soil processes. We model herbivore trampling with a linear positive or negative additive effect on soil-mediated nitrogen cycling processes. Combining analytical and numerical analyses, we find trampling by large mammalian herbivores is likely to decrease nitrogen mineralisation rate across diverse environments, such as temperate grassland and boreal forest. These effects are mediated by multiple potential mechanisms, including trampling-induced changes to detritivore biomass and functioning (e.g. rate of organic matter consumption). We also uncover scenarios where trampling can increase nitrogen mineralisation rate, contingent on the environment-specific relative sensitivity of detritivore mineral-nitrogen release and detritivore mortality, to trampling. In contrast to some consumptive mechanisms, our results suggest the pace of soil nitrogen cycling prior to trampling has little influence over the direction of the trampling net effect on nitrogen mineralisation, but that net effects may be greater in slow-cycling systems (e.g. boreal forests) than in fast-cycling systems (e.g. grasslands). Our model clarifies the potential consequences of previously overlooked mechanisms of zoogeochemistry that are common to all terrestrial biomes. Our results provide empirically testable predictions to guide future progress in empirical and theoretical studies of herbivore effects in diverse environmental contexts. Resolving ecological contingencies around animal consumptive and non-consumptive effects will improve whole-ecosystem management efforts such as restoration and rewilding.

Safety and tolerance of combination of monoamine oxidase inhibitors and direct dopamine agonists in adults and older adults with highly resistant depression.

INTRODUCTION: Dopamine (DA) is likely to be involved in some depressive dimensions, such as anhedonia and amotivation, which account for a part of treatment-resistant forms. Monoamine oxidase inhibitors (MAOI) and direct D2 and D3 receptors agonists (D2/3r-dAG) are known to help, but we lack safety data about their combined usage. We report on safety and tolerance of the MAOI+D2r-dAG combination in a clinical series. METHOD: All patients referred to our recourse center for depression between 2013 and 2021 were screened to select those who did receive the combo. Data were extracted from clinical files. RESULTS: Sixteen patients of 60±17 years of age (8 women, 7 with age>65years, all suffered from treatment resistant depression, 7 with bipolar disorder) received the combo. There were no life-threatening adverse effects (AE). However, AE were reported by 14 patients (88%) most of which were mild and consisted of insomnia, nausea, nervousness, confusion, impulse control disorder and/or "sleep attacks". One patient presented a serious AE requiring a short hospitalization for confusion. Intolerance led to failure to introduce treatment in two patients (13%). The retrospective non-interventional design, the variety of molecules, and the modest sample size limited the scope of these results. CONCLUSION: There was no life-threatening safety issue in combining MAOI and D2/3r-dAG, especially regarding cardiovascular side effects. The systematic screening of AE might account for their frequency, but these precluded the treatment in only two patients. Comparative studies are needed to assess the efficacy of this new combination.

A new high-pressure high-temperature deformation apparatus to study the brittle to ductile transition in rocks.

Understanding the micro-mechanisms underlying the localized-ductile transition (LDT) as well as the brittle-plastic transition (BPT) has become crucial for our wider understanding of crustal processes and seismicity. Given how difficult in situ observations of these transitions are to perform, laboratory experiments might be our only way to investigate the processes active under these conditions (high T and high P). Here, we present Triaxial AppaRatus for GEoThermal energy, a new gas-based triaxial apparatus located at EPFL in Switzerland that was specifically designed to operate under conditions where both the LDT and BPT can occur in geomaterials. We show that the machine is capable of deforming rock samples at confining pressures of up to 400 MPa, temperatures of up to 800 °C, and pore pressures (liquid or gas) of up to 300 MPa while keeping the temperature gradient along samples of 40 mm in length and 20 mm in diameter minimal (less than 30 at 700 °C). Most importantly, the maximum load is 1000 kN (stresses as high as 2.2 GPa on 24 mm samples and 3 GPa on 20 mm samples), allowing for the deformation of very competent rock samples. Moreover, during deformation, the pair of syringe pore pressure pumps allow for continuous permeability or dilatancy recording. We benchmarked our machine against existing data in the literature and show that it accurately and precisely records stress, strain, permeability, pressure, and temperature.

Towards a mechanistic understanding of animal-ecosystem interactions.

Research Highlight: Ferraro, K. M., Welker, L., Ward, E. B., Schmitz, O. J., & Bradford, M. A. (2023). Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.14002. Animals play large roles in ecosystem elemental cycling but predicting effects in diverse contexts remains a substantial challenge. Fundamental to progress is (1) identifying mechanisms by which animals impact nutrient distribution and cycling, and (2) disentangling how environmental context mediates the operation of alternative mechanisms. In an elegant field experiment, Ferraro et al. (2023) provide the first detailed exploration of the impact of nutrient inputs from mammalian parturition on soil functioning and the stoichiometry of plant tissues. The authors find that nitrogen from experimental additions of ungulate parturition material (natal fluids) is rapidly incorporated into microsite soil organic pools and plant tissues. They also find that soil processes (soil microbial biomass, rates of carbon mineralization, nitrogen mineralization and nitrification) and the nitrogen content of plant tissues above- and belowground are increased by addition of parturition material. Notably, the authors identify that increases in some soil processes and plant tissue nitrogen are weaker in microsites dominated by ericoid mycorrhizal plants than those dominated by ectomycorrhizal plants. These findings demonstrate that parturition depositions, a ubiquitous but overlooked mechanism of mammalian impacts on ecosystems, impact ecosystem processes and plant tissue stoichiometry. Furthermore, plant-fungal associations are a predictive axis of context dependency mediating zoogeochemical effects at fine scales. Ferraro et al.'s (2023) novel approach simultaneously advances mechanistic understanding of animal-ecosystem interactions at fine scales and facilitates prediction of ungulate effects on nutrient availability at landscape extents.

The experiences of doctorally prepared nurses and doctoral nursing students with being mentored in the Nurse-Lead programme: A focus group study.

AIM: to explore experiences of being mentored and the contribution of the mentoring to leadership and professional development of doctorally prepared nurses and doctoral nursing students participating in the Nurse-Lead programme. BACKGROUND: Mentoring is considered important for career development of academic nurses. Doctorally prepared nurses need a wide range of professional competences to develop sustainable careers. Therefore, they may benefit from a larger network of mentors, outside their own organization, to support their professional development. Therefore, a web-based leadership and mentoring programme was developed - the Nurse Lead programme. DESIGN: A descriptive study with semi-structured focus groups. METHOD: Three focus groups were conducted during an on-site programme meeting in 2019 with twenty-one doctorally prepared nurses and doctoral nursing students. The interview guide included questions about mentoring relationships and meaning of mentoring for leadership and professional development. The interviews were thematically analysed. RESULTS: Five themes were identified: "Preferred characteristics of mentors", "Developing trusting relationships", "Engagement of the mentors", "Becoming a proficient researcher and team leader" and "Becoming an empowered and confident professional". CONCLUSION: Mentoring supported the leadership and professional development of doctorally prepared nurses and doctoral nursing students. Participants were engaged in rewarding mentoring trajectories. The results indicate that a similar approach could be followed when developing mentoring programmes in the future.

Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels.

Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80-100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduces muscle FA uptake, raises circulating FAs, which remain in blood vessels, and lowers glucose, mimicking prominent Cd36-/- mice phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.

Reproducible determination of transpulmonary pressures.

Oesophageal pressures, as measured in an oesophageal balloon catheter, are a validated substitute for pleural pressures. Transpulmonary pressures, indispensable to improve our understanding of ventilatory physiology, are therefore typically calculated as the difference between airway and oesophageal pressures. The oesophageal pressure signal, however, features a superimposed oscillation due to cardiac motion, not representative for pleural pressure. Additionally, oesophageal contractions or surgical manipulation can alter the signal. In practice, transpulmonary pressures are therefore manually determined from the pressure-time graphic by visual inspection of the waves and averaging a limited number of samples. We suggest an approach to extract the end-expiratory transpulmonary pressure from the raw monitoring data.•Our approach reproducibly determines end-expiratory transpulmonary pressures at a given level of set positive end-expiratory pressure at the ventilator.•Our approach ignores surgical disturbance and cardiac oscillations in the oesophageal pressure signal.

[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

WhatsApp-propriate? A retrospective content analysis of WhatsApp use and potential breaches in confidentiality among a team of doctors at a district hospital, South Africa.

BACKGROUND: There has been a steady increase in the use of electronic media and instant messaging among healthcare professionals, where it has been almost universally adopted in the workplace. The use of WhatsApp and its perceived benefits in healthcare have been extensively studied; however, there are concerns regarding the potential for ethical breaches in confidentiality through shared electronic patient information. OBJECTIVES: To identify the usage characteristics and incidence of shared patient information with WhatsApp use in a team of medical doctors in an unobserved and unregulated setting. METHODS: We conducted a retrospective cross-sectional content analysis of WhatsApp messages (n=3 340) among a team of 20 doctors in a South African district hospital over 6 months. All messages found within this time period were allocated unique identifiers. The text and image messages were thematically grouped into four categories, i.e. clinical care, resource allocation, social and administrative. Messages that contained patient-identifying information were included in the analysis. RESULTS: Of a total of 3 340 messages sent, 220 (6.6%) contained patient-identifying information. Of these, 109 (3.3%) contained non-anonymised patient information, while in 111 (3.3%) messages, the information was anonymised. The likelihood of sharing patient identifiers was proportionally much higher in shared images (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.2 - 8.2; p<0.0001) compared with text messages, and in messages that related to clinical care (OR 9.3; 95% CI 2.2 - 38.8; p=0.0023) compared with those sent for resource allocation, and social or administrative purposes. CONCLUSIONS: Non-anonymised patient identifiers were found in 3.3% of messages, constituting the potential for breaching patient confidentiality. While WhatsApp groups have significant utility in co-ordinating aspects of clinical care, resource allocation, as well as social and administrative functions, the safe use of WhatsApp should be promoted to ensure that patient confidentiality is maintained.

Patients with atherosclerotic peripheral arterial disease have a high risk of lung cancer: Systematic review and meta-analysis of literature.

PURPOSE: Lung cancer and atherosclerosis share common risk factors. Literature data suggest that the prevalence of lung malignancy in patients with peripheral arterial disease (PAD) is higher than in the general population. Our goal was to determine, through a systematic literature review, the prevalence of lung cancer in patients with PAD. METHODS: We consulted available publications in the Cochrane library, MEDLINE, PUBMED, EMBASE, and ClinicalTrials.gov. We included all articles, written in English or French, published between 1990 and 2020 reporting the prevalence of lung cancer in patients with PAD (atherosclerotic aortic aneurysm or peripheral occlusive diseases). Patients with coronary artery disease, cardiac valvulopathy or carotid stenosis were not included. We did not include case reports. We performed a critical analysis of each article. Data were collected from two independent readers. A fixed effect model meta-analysis allowed to estimate a summary prevalence rate. RESULTS: We identified 303 articles, and selected 19 articles according to selection criteria. A total of 16849 patients were included (mean age 68.3 years, 75.1% of males). Aortic aneurysms were found in 29% of patients and atherosclerotic occlusive disease in 66% of patients. Lung cancer was identified in 538 patients, representing a prevalence of 3%. DISCUSSION: Lung cancer is found in 3% of patients with atherosclerotic PAD. This prevalence is higher than that found in lung cancer screening programs performed in the general population of smokers and former smokers. These patients should be screened for lung cancer. Their selection may dramatically increase the benefit of lung cancer screening.

Progressive clinical case-based multiple-choice questions: An innovative way to evaluate and rank undergraduate medical students.

INTRODUCTION: In France, at the end of the sixth year of medical studies, students take a national ranking examination including progressive clinical case-based multiple-choice questions (MCQs). We aimed to evaluate the ability of these MCQs for testing higher-order thinking more than knowledge recall, and to identify their characteristics associated with success and discrimination. METHODS: We analysed the 72 progressive clinical cases taken by the students in the years 2016-2019, through an online platform. RESULTS: A total of 72 progressive clinical cases (18 for each of the 4 studied years), corresponding to 1059 questions, were analysed. Most of the clinical cases (n=43, 60%) had 15 questions. Clinical questions represented 89% of all questions, whereas basic sciences questions accounted for 9%. The most frequent medical subspecialties were internal medicine (n=90, 8%) and infectious diseases (n=88, 8%). The most frequent question types concerned therapeutics (26%), exams (19%), diagnosis (14%), and semiology (13%). Level 2 questions ("understand and apply") accounted for 59% of all questions according to the Bloom's taxonomy. The level of Bloom's taxonomy significantly changed over time with a decreasing number of level 1 questions ("remember") (P=0.04). We also analysed the results of the students among 853 questions of training ECNi. Success and discrimination significantly decreased when the number of correct answers increased (P<0.0001 both). The success, discrimination, mean score, and mean number of discrepancies did not differ according to the diagnosis, exam, imaging, semiology, or therapeutic type of questions. CONCLUSION: Progressive clinical case-based MCQs represent an innovative way to evaluate undergraduate students.

Behavioural performance improvement in visuomotor learning correlates with functional and microstructural brain changes.

A better understanding of practice-induced functional and structural changes in our brains can help us design more effective learning environments that provide better outcomes. Although there is growing evidence from human neuroimaging that experience-dependent brain plasticity is expressed in measurable brain changes that are correlated with behavioural performance, the relationship between behavioural performance and structural or functional brain changes, and particularly the time course of these changes, is not well characterised. To understand the link between neuroplastic changes and behavioural performance, 15 healthy participants in this study followed a systematic eye movement training programme for 30 min daily at home, 5 days a week and for 6 consecutive weeks. Behavioural performance statistics and eye tracking data were captured throughout the training period to evaluate learning outcomes. Imaging data (DTI and fMRI) were collected at baseline, after two and six weeks of continuous training, and four weeks after training ended. Participants showed significant improvements in behavioural performance (faster task completion time, lower fixation number and fixation duration). Spatially overlapping reductions in microstructural diffusivity measures (MD, AD and RD) and functional activation increases (BOLD signal) were observed in two main areas: extrastriate visual cortex (V3d) and the frontal part of the cerebellum/Fastigial Oculomotor Region (FOR), which are both involved in visual processing. An increase of functional activity was also recorded in the right frontal eye field. Behavioural, structural and functional changes were correlated. Microstructural change is a better predictor for long-term behavioural change than functional activation is, whereas the latter is superior in predicting instantaneous performance. Structural and functional measures at week 2 of the training programme also predict performance at week 6 and 10, which suggests that imaging data at an early stage of training may be useful in optimising practice environments or rehabilitative training programmes.

[Psychopharmacotherapeutic guidelines : a challenge during health crisis]. / Recommandations psychopharmacothérapeutiques : un défi en temps de crise sanitaire.

The construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward.

Réaliser des recommandations pharmacothérapeutiques est une démarche complexe, plus encore dans une période de crise sanitaire, comme celle que nous traversons avec la pandémie liée au SARS-CoV-2. En psychiatrie, les préconisations formulées se doivent de rappeler la légitime prudence à adopter dans le maniement des psychotropes, dans un contexte qui, par ailleurs, présente certaines de ces médications comme potentiellement prophylactiques de la COVID-19. Ces enjeux contradictoires sont débattus, les concepts méthodologiques de l'élaboration des recommandations sont rappelés.