Ex vivo evaluation of the soft tissue components of the equine stifle using 3 Tesla magnetic resonance imaging under flexion, extension, and loading.

High-field MRI of the equine stifle provides high-resolution information about soft tissues that is useful in the diagnosis of stifle lameness. The aim of this prospective anatomic study was to describe the appearance, position, size, and shape of the equine femorotibial ligaments, meniscal ligaments, and menisci using 3 Tesla MRI under extended, extended-loaded, and flexed conditions. Additionally, histologic examination of the collateral and cruciate ligaments (CLs) of a single stifle was performed to compare with MRI images. In extension, mild variations in MRI signal intensity were apparent in the CLs, and the cranial had two distinct longitudinal regions indicating two ligament bundles. Flexion had minor effects on CL signal intensity and altered the tibial angles of attachment. Histology indicated that both CLs were comprised of two fiber bundles. The collateral ligaments were the same low-signal intensity. The medial collateral ligament had a smaller cross-sectional area than the lateral, and flexion increased the length of the medial collateral ligament and the cross-sectional area of the lateral. Low loads in extension did not affect the MRI appearance of stifle soft tissues. Flexion of the stifle impacted cruciate ligament insertion angles and the size and shape of collateral ligaments. This study provides support for the use of MRI to understand the anatomy and function of stifle ligaments.

Predicting subacute ruminal acidosis from milk mid-infrared estimated fatty acids and machine learning on Canadian commercial dairy herds.

Our objective was to validate the possibility of detecting SARA from milk Fourier transform mid-infrared spectroscopy estimated fatty acids (FA) and machine learning. Subacute ruminal acidosis is a common condition in modern commercial dairy herds for which the diagnostic remains challenging due to its symptoms often being subtle, nonexclusive, and not immediately apparent. This observational study aimed at evaluating the possibility of predicting SARA by developing machine learning models to be applied to farm data and to provide an estimated portrait of SARA prevalence in commercial dairy herds. A first data set composed of 488 milk samples of 67 cows (initial DIM = 8.5 ± 6.18; mean ± SD) from 7 commercial dairy farms and their corresponding SARA classification (SARA+ if rumen pH <6.0 for 300 min, else SARA-) was used for the development of machine learning models. Three sets of predictive variables: i) milk major components (MMC), ii) milk FA (MFA), and iii) MMC combined with MFA (MMCFA) were submitted to 3 different algorithms, namely Elastic net (EN), Extreme gradient boosting (XGB), and Partial least squares (PLS), and evaluated using 3 different scenarios of cross-validation. Accuracy, sensitivity, and specificity of the resulting 27 models were analyzed using a linear mixed model. Model performance was not significantly affected by the choice of algorithm. Model performance was improved by including fatty acids estimations (MFA and MMCFA as opposed to MMC alone). Based on these results, one model was selected (algorithm: EN; predictive variables: MMCFA; 60.4, 65.4, and 55.3% of accuracy, sensitivity, and specificity, respectively) and applied to a large data set comprising the first test-day record (milk major components and FA within the first 70 DIM of 211,972 Holstein cows (219,503 samples) collected from 3001 commercial dairy herds. Based on this analysis, the within-herd SARA prevalence of commercial farms was estimated at 6.6 ± 5.29% ranging from 0 to 38.3%. A subsequent linear mixed model was built to investigate the herd-level factors associated to higher within-herd SARA prevalence. Milking system, proportion of primiparous cows, herd size and seasons were all herd-level factors affecting SARA prevalence. Furthermore, milk production was positively, and milk fat yield negatively associated with SARA prevalence. Due to their moderate levels of accuracy, the SARA prediction models developed in our study, using data from continuous pH measurements on commercial farms, are not suitable for diagnostic purpose. However, these models can provide valuable information at the herd level.

NeuroLab 2.0: An Alternative Storyline Design Approach for Translating a Research-Based Summer Experience into an Advanced STEM+M Curriculum Unit that Supports Three-Dimensional Teaching and Learning in the Classroom.

In this case study, we describe an alternative storyline design approach that we adopted to translate an informal, out-of-school summer science experience with a strong emphasis on developmental neuroscience and data literacy into a more inclusive, replicable, and scalable experience for formal high school science instruction. Combining elements of problem- and project-based learning, a storyline is a curriculum model that engages students in the application of investigative science and engineering practices to incrementally build conceptual models that explain an observable (anchoring) phenomenon. Published reports on the storyline design process describe procedures and tools that are well suited to the creation of novel instructional units. However, these design methods are difficult to apply to projects aimed at translating pre-existing science experiences and resources into classroom storyline units. In this descriptive case study, we discuss a series of alternative design procedures that we utilized to achieve this adaptation. Our overarching project goal was to create the resources necessary to engage high school students in the construction of a multidimensional explanatory model for an unusual movement disorder that assimilates converging lines of behavioral, neuroanatomical, neurophysiological, molecular genetic, developmental, and cellular data. The methods described in this case study establish a design template for other biomedical scientists who are interested in adopting a storyline approach to bring aspects of their work or educational projects into science classrooms and into closer alignment with a new vision for science teaching and learning articulated in the National Research Council's A Framework for K-12 Science Education and the Next Generation Science Standards.

Association between ATP luminometry of feeding equipment and environmental and health parameters of preweaned calves on dairy farms.

The objective of this study was to examine the influence of different environmental factors on ATP luminometry measurements of feeding equipment and to investigate associations with health of preweaned calves and the levels of ATP identified through luminometry. On 50 commercial dairy farms in Quebec, Canada, ATP luminometry measurements (in relative light units (RLU)) were obtained using the direct swabbing technique with Hygiena UltraSnap swabs and a liquid rinsing technique with the same swab for automatic milk feeders (AMF), bottles, buckets, esophageal tube feeders (ET), milk replacer, nipples and water. During this visit, environmental factors (including temperature, air draft, humidity, ammonia, and bacterial count) were collected and a clinical examination (including respiratory score and fecal score) was performed for all preweaned calves present at the farm. This process was repeated 4 times in a year, leading to collection of luminometer results, environmental parameters, and overall health of calves for each season per farm. Overall, a difference in luminometer results was seen between the different periods sampled for all feeding equipment (except the ET), milk replacer and water, showing higher RLU values in spring and summer and lower values in autumn and winter. When comparing RLU measurements with environmental factors, only a low to negligible correlation could be found. When feeding equipment was classified as not contaminated or contaminated based on previously described cut-off values, a good agreement within a farm for the different seasons was noticed only for nipples (Gwet's agreement AC1 = 0.64), with a poor to moderate agreement for other feeding equipment. Regarding the different models of nipples, 'Peach Teat' nipples showed higher RLU values compared with 'Merricks' nipples models. An association was seen between the proportion of preweaned calves suffering from diarrhea on the farm and the contamination of AMF based on ATP luminometry (logistic regression estimate = 0.52, P = 0.04). For other feeding equipment, milk replacer and water, no significant associations were found. This study showed that ATP luminometry measurements of feeding equipment from preweaned calves are susceptible to seasonality and type of nipple. Thus, these factors should be taken into consideration when interpreting results. Additionally, an association could be made between diarrhea in preweaned calves and the contamination of AMF based on ATP luminometry, showing the potential clinical importance of this on-farm hygiene assessment tool.

Radiographic analysis in Thoroughbreds reveals morphological changes in healthy maturing stifle joints and possible association between subchondral lesions and femoral condyle width.

OBJECTIVE: Assess femorotibial features in foals with and without medial femoral condyle (MFC) subchondral radiolucencies (SR+ and SR-). METHODS: 3 independent, sequential radiographic studies were performed. Study 1 retrospectively measured femorotibial morphological parameters in repository radiographs (SR- and SR+). Study 2 qualitatively compared drawings of intercondylar notch shape in postmortem radiographs (SR-). Study 3 prospectively measured femorotibial parameters in 1-month-old foals (SR-). In studies 1 and 3, 13 morphologic parameters were measured. Limb directional asymmetry was assessed in 2 age groups (< 7 or ≥ 7 months). RESULTS: Study 1 (SR- group; n = 183 radiographs) showed increased femoral measurements with maturation, except the distal femoral intercondylar notch width (FINwal), which decreased. In contrast, in SR+ stifles (53 radiographs), 3 femoral parameters (MFC width [MFCwpf], MFC height, or FINwal) showed no changes. Tibial plateau width alone increased with maturation in both groups. Interobserver reliability was good to excellent. Study 2 (n = 53 radiographs) confirmed a distal FINw decrease in SR- foals. In study 1, left SR- stifles in greater than or equal to 7-month-old fillies had significantly larger femoral bicondylar width and FINw, while right SR+ stifles in fillies greater than or equal to 7 months had a significantly larger MFCw. In study 3 of 1-month-old foals (n = 94 SR- radiographs), the MFCw, femoral condyle bicondylar width, and lateral femoral condyle height were all greater on the left, whereas the intercondylar intereminence space width was larger on the right. CLINICAL RELEVANCE: In SR+ stifles, the distal femur exhibited divergent maturation, indicating a wider MFC in the right stifle in older foals. As SR lesions are more common on the right, this suggests a potential association with MFC morphology.

Farm-level risk factors associated with increased milk ß-hydroxybutyrate and hyperketolactia prevalence on farms with automated milking systems.

The objectives of this study were to determine the farm-level hyperketolactia (HKL) prevalence, as diagnosed from milk ß-hydroxybutyrate (BHB) concentration, on dairy farms milking with an automatic milking system (AMS) and to describe the farm-level housing, management, and nutritional risk factors associated with increased farm-average milk BHB and the within-herd HKL prevalence in the first 45 DIM. Canadian AMS farms (n = 162; eastern Canada n = 8, Quebec n = 23, Ontario n = 75, western Canada n = 55) were visited once between April to September 2019 to record housing and herd management practices. The first test milk data for each cow under 45 DIM were collected, along with the final test of the previous lactations for all multiparous cows, from April 1, 2019 to September 30, 2020. The first test milk BHB was then used to classify each individual cow as having HKL (milk BHB ≥ 0.15 mmol/L) at the time of testing. Milk fat and protein content, milk BHB, and HKL prevalence were summarized by farm and lactation group (all, primiparous, and multiparous). During this same time period, formulated diets for dry and lactating cows, including ingredients and nutrient composition, and AMS milking data were collected. Data from the AMS were used to determine milking behaviors and milk production of each herd during the first 45 DIM. Multivariable regression models were used to associate herd-level housing, feeding management practices, and formulated nutrient composition with first test milk BHB concentrations and within-herd HKL levels separately for primiparous and multiparous cows. The within-herd HKL prevalence for all cows was 21.8%, with primiparous cows having a lower mean prevalence (12.2 ± 9.2%) than multiparous cows (26.6 ± 11.3%). Milk BHB concentration (0.095 ± 0.018 mmol/L) and HKL prevalence for primiparous cows were positively associated with formulated prepartum DMI and forage content of the dry cow diet while being negatively associated with formulated postpartum DMI, the major ingredient in the concentrate supplemented through the AMS, and the PMR-to-AMS concentrate ratio. However, multiparous cows' milk BHB concentration (0.12 ± 0.023 mmol/L) and HKL prevalence were positively associated with the length of the previous lactation, milk BHB at dry off, prepartum diet nonfiber carbohydrate content, and the major forage fed on farm, while tending to be negatively associated with feed bunk space during lactation. This is the first study to determine the farm-level risk factors associated with herd-level prevalence of HKL in AMS dairy herds, thus helping optimize management and guide diet formulation to promote the reduction of HKL prevalence.

[Digital environment and population health]. / Environnement digital et santé des populations.

Health and risk of disease are determined by exposure to the physical, socio-economic, and political environment and to this has been added exposure to the digital environment. Our increasingly digital lives have major implications for people's health and its monitoring, as well as for prevention and care. Digital health, which encompasses the use of health applications, connected devices and artificial intelligence medical tools, is transforming medical and healthcare practices. Used properly, it could facilitate patient-centered, inter-professional and data-driven care. However, its implementation raises major concerns and ethical issues, particularly in relation to privacy, equity, and the therapeutic relationship.

La santé et le risque de maladies sont déterminés par l'exposition aux environnements physiques, socio-économiques et politiques, et à cela s'est ajouté l'exposition à l'environnement digital. Notre vie digitale a des implications majeures, d'une part, sur la santé des populations et son monitoring et, d'autre part, sur la prévention et les soins. Ainsi, la santé digitale (digital health), qui englobe l'utilisation d'applications de santé, d'appareils connectés, ou d'outils médicaux d'intelligence artificielle, modifie les pratiques médico-soignantes. Bien utilisée, elle pourrait faciliter les soins centrés sur le patient, interprofessionnels et guidés par les données. Cependant, sa mise en œuvre soulève d'importants craintes et enjeux éthiques en lien notamment avec la protection des données, l'équité et la relation thérapeutique.

[Avoiding medication administration errors: feedback from Pepper robot assistance for double-checking]. / Éviter les erreurs d'administration médicamenteuse : retour d'expérience de l'assistance du robot Pepper pour le double contrôle.

Safety during drug administration remains a major concern in nursing, particularly when it comes to calculating doses. The Institut et Haute école de la santé La Source in Lausanne, in partnership with the Avatarion company, has set up a co-development project using the humanoid robot Pepper as an assistant for double-checking dose calculations. Feedback from test users has been positive, although there is room for improvement.

Uranium Biogeochemistry in the Rhizosphere of a Contaminated Wetland.

The objective of this study was to determine if U sediment concentrations in a U-contaminated wetland located within the Savannah River Site, South Carolina, were greater in the rhizosphere than in the nonrhizosphere. U concentrations were as much as 1100% greater in the rhizosphere than in the nonrhizosphere fractions; however and importantly, not all paired samples followed this trend. Iron (but not C, N, or S) concentrations were significantly enriched in the rhizosphere. XAS analyses showed that in both sediment fractions, U existed as UO22+ coordinated with iron(III)-oxides and organic matter. A key difference between the two sediment fractions was that a larger proportion of U was adsorbed to Fe(III)-oxides, not organic matter, in the rhizosphere, where significantly greater total Fe concentrations and greater proportions of ferrihydrite and goethite existed. Based on 16S rRNA analyses, most bacterial sequences in both paired samples were heterotrophs, and population differences were consistent with the generally more oxidizing conditions in the rhizosphere. Finally, U was very strongly bound to the whole (unfractionated) sediments, with an average desorption Kd value (Usediment/Uaqueous) of 3972 ± 1370 (mg-U/kg)/(mg-U/L). Together, these results indicate that the rhizosphere can greatly enrich U especially in wetland areas, where roots promote the formation of reactive Fe(III)-oxides.

Farm-level nutritional factors associated with milk production and milking behavior on Canadian farms with automated milking systems.

The objective of this study was to describe the nutritional strategies used on Canadian dairy farms with automated milking systems (AMS), both at the feed bunk and the concentrate offered at the AMS, as well as to determine what dietary components and nutrients, as formulated, were associated with milk production and milking behaviors on those farms. Formulated diets (including ingredients and nutrient content) and AMS data were collected from April 1, 2019, until September 30, 2020, on 160 AMS farms (eastern Canada [East] = 8, Ontario [ON] = 76, Quebec [QC] = 22, and western Canada [West] = 54). Both partial mixed ration (PMR) and AMS concentrate samples were collected from May 1 to September 30, 2019, on 169 farms (East = 12, ON = 63, QC = 42, West = 52). We collected AMS milking data for 154 herds. For each farm (n = 161), milk recording data were collected and summarized by farm to calculate average milk yield and components. Multivariable regression models were used to associate herd-level formulated nutrient composition and feeding management practices with milk production and milking behavior. Milk yield (mean ± SD = 37.0 ± 0.3 kg/d) was positively associated with the PMR ether extract (EE) concentration (+0.97 kg/d per percentage point [p.p.] increase) and with farms that fed barley silage as their major forage source (n = 16; +2.18 kg/d) as compared with haylage (n = 42), whereas farms that fed corn silage (n = 96; +1.23 kg/d) tended to produce more milk than farms that fed haylage. Greater milk fat content (4.09 ± 0.28%) was associated with a greater PMR-to-AMS concentrate ratio (+0.02 p.p. per unit increase) and total diet net energy for lactation (+0.046 p.p. per 0.1 Mcal/kg increase), but a lesser percentage of NFC of the PMR (-0.016 p.p. per p.p. increase of NFC percentage). Milk protein content (3.38 ± 0.14%) was positively associated with the forage percentage of the PMR (+0.003 p.p. per p.p. increase of forage percentage) and the total diet starch percentage (+0.009 p.p. per p.p. increase of starch percentage), but was negatively associated with farms feeding corn silage (-0.1 p.p. compared with haylage) as their major forage. Greater milking frequency (2.77 ± 0.40 milkings/d) was observed on farms with free-flow cow traffic systems (+0.62 milkings/d) and was positively associated with feed push-up frequency (+0.013 milkings/d per additional feed push-up), but negatively associated with PMR NFC content and forage percentage of the total ration (-0.017 milkings/d per p.p. increase of forage percentage). Lastly, greater milking refusal frequency (1.49 ± 0.82 refusals/d) was observed on farms with free-flow cow traffic systems (+0.84 refusals/d) and farms feeding barley silage (+0.58 refusals/d) than with guided flow and farms feeding either corn silage or haylage, respectively. These data give insight into the ingredients, nutrient formulations and type of diets fed on AMS dairy farms across Canada and the association of those factors with milk production and milking behaviors.

Evaluating the impact of a blended interprofessional education course on students' attitudes towards interprofessional education: a pre-post study.

BACKGROUND: Since 2011, five educational and healthcare institutions have implemented a short interprofessional education (IPE) course to bring together undergraduates from five disciplines. To meet the logistical challenges of IPE implementation, more specifically, the large number of classrooms needed to gather students together and the need for human resources to guide learning activities, a face-to-face IPE course was redesigned into a blended (online and face-to-face collaborative learning activities) IPE course. In March 2023, 183 medical, 378 nursing, 46 radiologic technology, 69 physiotherapy, and 74 occupational therapy students participated in a one-day IPE blended course to learn interprofessional team functioning and dynamics, role clarification and responsibilities of other professions, and interprofessional communication skills. This study aimed to assess students' changes in attitudes towards IPE after being involved in a large-scale interprofessional blended learning course. METHODS: A before-after study was conducted using a French translation of the validated questionnaire "University of West of England Interprofessional Questionnaire" (UWE-IP questionnaire). Students' attitudes towards interprofessional (IP) relationships and IP learning were measured before and after the course. In March 2023, two hundred fifty-six students from five professions answered two subscales of the UWE-IP questionnaire before and after the course (response rate 34%). RESULTS: Students' attitudes towards IP relationships improved significantly after the course. The score on this subscale (min 8; max 24) changed from 11.18 (SD 2,67) before the course to 10,38 (SD 2,55) after the course, indicating a significant improvement in attitudes towards IP relationships (p < 0,001). More specifically, students had more positive attitudes on the item "I have a good understanding of the roles of different health and social care professionals." and the item "I feel that I am respected by people from other health and social care disciplines." after the course. A positive change in students' attitudes towards IP learning was observed, but the results were not significative. CONCLUSION: A face-to-face IPE course redesigned as a blended course helped overcome existing challenges to implementing an IPE course. The results suggest a blended IPE course improves students' attitudes towards interprofessionality.

Exploring herd-level perinatal calf mortality risk factors in eastern Canadian dairy farms.

This closed cohort study aimed to identify the associations between dairy calf management practices and herd-level perinatal calf mortality risk. From February 2020 to June 2021, predominantly Holstein dairy farms in Québec (n = 1,832) and New Brunswick (n = 52), Canada, that were registered in the dairy herd improvement program were visited once. A questionnaire covering all aspects of precalving, calving, and colostrum management was administered. Data regarding perinatal mortality were retrieved from the dairy herd improvement program database for each farm for 2021. Perinatal mortality was calculated for each farm as the proportion of calves dead at birth or dying within 24 h after birth. A multivariable negative binomial model was used to assess herd-level factors associated with the risk of perinatal mortality. The final model included the lying surface in the calving area, the typical time to first colostrum intake, typical cow-calf contact time, the proportion of males born, the proportion of assisted calvings, and herd size. Herd-level perinatal mortality risk ranged from 0% to 38.1% (mean ± SE = 7.6% ± 0.1%). A greater proportion of males born, a higher proportion of assisted calvings, and delayed colostrum feeding were associated with increased herd-level perinatal mortality. Factors associated with a decreased herd-level perinatal mortality risk were having a typical cow-calf contact time between 7 and 12 h after calving compared with reduced cow-calf contact time, soft lying surfaces in the calving area compared with concrete and mat-lying surfaces, and an increased number of calvings per year. Our results show that although some of the significant risk factors are not well understood (i.e., calving area lying surface, typical cow-calf contact time), Canadian farmers could focus on the factors under their control (i.e., time to first colostrum feeding, proportion of difficult calvings, males born, and calvings per year) to reduce the risk of perinatal mortality. Future work should focus on qualitative research to understand the dairy farmer motivations and limitations to implementing practices identified in this and other studies to reduce perinatal mortality.

Equine subchondral lucencies: Knowledge from the medial femoral condyle.

Equine subchondral lucencies (SCL) have been described since the first availability of suitable radiographic equipment. The initial clinical sign can be lameness, but SCLs are often first found on surveys of juvenile horses and are primarily a radiographic concern for public auctions. When lameness is present, it varies from subtle to obvious and can be intermittent. Some SCLs heal spontaneously, and some remain blemishes, but when the SCL and lameness are persistent, further damage to the joint and limitations to an athletic career are likely. SCLs were initially described in the distal limb followed by the stifle, and the medial femoral condyle (MFC) is now considered the most common location. The aim of this review is to highlight the initial pathology and discuss the clinical and experimental information available on equine SCLs. SCL treatment has evolved from rest alone and has progressed to debridement, grafting, intralesional injection, and most recently, transcondylar screw and absorbable implant placement. Comparison of success rates between techniques is difficult due to variations in follow-up and outcome measures, and no single technique is best for all SCLs. Treatment appears to increase success by 15%-20% over rest alone, but the method chosen depends on many factors. This review emphasizes the need for further work to fully understand SCL formation and all aspects of trabecular bone healing to optimize surgical therapy and improve treatment success.

Structure, composition and anisotropic swelling of the bovine acetabular labrum.

The fibro-cartilaginous labrum surrounds the acetabular rim and is important for hip joint stability and sealing. Sealing may be enhanced by swelling pressure within the normal labrum. Swelling of the degenerated or torn labrum might occur and potentially contribute to the development of osteoarthritis, through altered load transmission. This study aimed to characterize the three-dimensional swelling behaviour, the collagen fiber orientation and spatial proteoglycan distribution of the bovine acetabular labrum. Specimens were harvested from bovine donors (192-652 days, male, n = 6 donors). Structure was analyzed by scanning electron microscopy, histology, and dimethylmethylene blue assay. Specimen dimensions were measured before and after incubation in phosphate buffered saline to assess the swelling. Results showed that the articulating surface is composed of a collagen mesh network. Collagen fiber bundles showed a low degree of alignment close to the surface and were circumferentially aligned in the deep tissue. Proteoglycans were identified clustered between the collagen bundles. Glycosaminoglycan content was 10 x lower than that of cartilage (23.1 ± 6.4 compared to 299.5 ± 19.1 µg/mg dry weight) with minor regional differences. Specimens swelled significantly more in the orthogonal direction (swelling ratio 124.7 ± 10.2%) compared to the swelling parallel to the articulating surface (108.8 ± 6.1% and 102.8 ± 4.1%). In the deep tissue, swelling was also restricted in the main collagen fiber bundle direction (circumferentially), with a swelling ratio of 109.5 ± 4.0% in the main fiber bundle direction compared to 126.8 ± 7.3 % and 122.3 ± 5.8% radially. The findings demonstrate that the labrum shows anisotropic swelling properties, which reflect the anisotropy in the tissue structure and inter-fiber localisation of proteoglycans.

Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.

Introduction: The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses. Methods: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations. Results: A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The fAUC/MIC or fT>MIC were calculated with a free BP fraction set at 0.4. For fAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. For fT>MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, a fT>MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L. Discussion: The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.

eHealth profile of patients with diabetes.

Background: Digital health technology can be useful to improve the health of patients with diabetes and to support patient-centered care and self-management. In this cross-sectional study, we described the eHealth profile of patients with diabetes, based on their use of digital health technology, and its association with sociodemographic characteristics. Methods: We used data from the "Qualité Diabète Valais" cohort study, conducted in one region of Switzerland (Canton Valais) since 2019. Participants with type 1 or type 2 diabetes completed questionnaires on sociodemographic characteristics and on the use of digital health technology. We defined eHealth profiles based on three features, i.e., ownership or use of (1) internet-connected devices (smartphone, tablet, or computer), (2) mHealth applications, and (3) connected health tools (activity sensor, smart weight scale, or connected blood glucose meter). We assessed the association between sociodemographic characteristics and participants' eHealth profiles using stratified analyses and logistic regression models. Results: Some 398 participants (38% women) with a mean age of 65 years (min: 25, max: 92) were included. The vast majority (94%) were Swiss citizens or bi-national and 68% were economically inactive; 14% had a primary level education, 51% a secondary level, and 32% a tertiary level. Some 75% of participants had type 2 diabetes. Some 90% of the participants owned internet-connected devices, 43% used mHealth applications, and 44% owned a connected health tool. Older age and a lower educational level were associated with lower odds of all features of the eHealth profile. To a lesser extent, having type 2 diabetes or not being a Swiss citizen were also associated with a lower use of digital health technology. There was no association with sex. Conclusion: While most participants owned internet-connected devices, only about half of them used mHealth applications or owned connected health tools. Older participants and those with a lower educational level were less likely to use digital health technology. eHealth implementation strategies need to consider these sociodemographic patterns among patients with diabetes.

Systemic application of bone-targeting peptidoglycan hydrolases as a novel treatment approach for staphylococcal bone infection.

IMPORTANCE: The rising prevalence of antimicrobial resistance in S. aureus has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria.

Eyelid Closure Behavior of Patients with Idiopathic and Nonorganic Hypersomnia, Narcolepsy-Cataplexy, and Healthy Controls in the Maintenance of Wakefulness Test.

Purpose: Differential diagnosis of central disorders of hypersomnolence remains challenging, particularly between idiopathic (IH) and nonorganic hypersomnia (NOH). We hypothesized that eyelid closure behavior in the maintenance of wakefulness test (MWT) could be a valuable biomarker. Patients and Methods: MWT recordings of patients with IH, NOH, narcolepsy-cataplexy (NC), and healthy sleep-deprived controls (H) were retrospectively analyzed (15 individuals per group). For each MWT trial, visual scoring of face videography for partial (50-80%) and full eyelid closure (≥80%) was performed from "lights off" to the first microsleep episode (≥3 s). Results: In all groups, the frequency and cumulative duration of periods with partial and full eyelid closure gradually increased toward the first microsleep episode. On the group level, significant differences occurred for the latency to the first microsleep episode (IH 21 min (18-33), NOH 23 min (17-35), NC 11 min (7-19), H 10 min (6-25); p = 0.009), the ratio between partial and full eyelid closure duration (IH 2.2 (0.9-3.1), NOH 0.5 (0-1.2), NC 2.8 (1.1-5), H 0.7 (0.4-3.3); p = 0.004), and the difference between full and partial eyelid closure duration in the five minutes prior to the first microsleep episode (∆full - partial eyelid closure duration: IH -16 s (-35 to 28); NOH 46 s (9-82); NC -6 s (-26 to 5); H 10 s (-4 to 18); p = 0.007). IH and NOH significantly differed comparing the ratio between partial and full eyelid closure (p = 0.005) and the difference between ∆full - partial eyelid closure duration in the five minutes prior to the first microsleep episode (p = 0.006). Conclusion: In the MWT, eyelid closure behavior (∆full - partial) in the period prior to the first microsleep episode could be of value for discriminating NOH from other etiologies of excessive daytime sleepiness, particularly IH.

Outcome prediction in pediatric fever in neutropenia: Development of clinical decision rules and external validation of published rules based on data from the prospective multicenter SPOG 2015 FN definition study.

BACKGROUND: Fever in neutropenia (FN) remains a serious complication of childhood cancer therapy. Clinical decision rules (CDRs) are recommended to help distinguish between children at high and low risk of severe infection. The aim of this analysis was to develop new CDRs for three different outcomes and to externally validate published CDRs. PROCEDURE: Children undergoing chemotherapy for cancer were observed in a prospective multicenter study. CDRs predicting low from high risk infection regarding three outcomes (bacteremia, serious medical complications (SMC), safety relevant events (SRE)) were developed from multivariable regression models. Their predictive performance was assessed by internal cross-validation. Published CDRs suitable for validation were identified by literature search. Parameters of predictive performance were compared to assess reproducibility. RESULTS: In 158 patients recruited between April 2016 and August 2018, 360 FN episodes were recorded, including 56 (16%) with bacteremia, 30 (8%) with SMC and 72 (20%) with SRE. The CDRs for bacteremia and SRE used four characteristics (type of malignancy, severely reduced general condition, leucocyte count <0.3 G/L, bone marrow involvement), the CDR for SMC two characteristics (severely reduced general condition and platelet count <50 G/L). Eleven published CDRs were analyzed. Six CDRs showed reproducibility, but only one in both sensitivity and specificity. CONCLUSIONS: This analysis developed CDRs predicting bacteremia, SMC or SRE at presentation with FN. In addition, it identified six published CDRs that show some reproducibility. Validation of CDRs is fundamental to find the best balance between sensitivity and specificity, and will help to further improve management of FN.

Hygiene management practices and adenosine triphosphate luminometry of feeding equipment in preweaning calves on dairy farms in Quebec, Canada.

The objective of this study was to describe the cleaning practices currently used for preweaning calves on dairy farms in Quebec, Canada. In addition, contamination of feeding equipment for preweaning calves was described using ATP (expressed as relative light units, RLU), visual assessment, and bacteriological analysis. A questionnaire was administered on 50 commercial dairy farms in Quebec, Canada, regarding the self-reported cleaning protocol used for feeding equipment of preweaning calves. During the visit, a visual score was given to the feeding equipment available at the farm. Afterward, ATP luminometry measurements were obtained using Hygiene UltraSnap and MicroSnap swabs (Hygiene, Camarillo, CA), and the liquid rinsing technique for buckets, nipples, bottles, esophageal tube feeders (ET), the tube of automatic milk feeders (AMF), water samples, and milk replacer. An additional direct swabbing technique was performed on buckets and nipples. The fluid retrieved from the liquid rinsing technique was also used to determine the total bacterial count (TBC) and total coliform count. Based on the bacteriological analysis, optimal RLU cutoff values to determine contamination were obtained. The median (interquartile range) luminometer measurements using the UltraSnap and direct technique for buckets and nipples were 2,082 (348-7,410) and 3,462 (462-7,518) RLU, respectively; and, using the liquid technique for bottles, ET, AMF, water, and milk replacer were 43 (4-974), 15 (4-121), 301 (137-1,323), 190 (71-358), and 94 (38-218) RLU, respectively. Overall, for all equipment and both techniques used, higher RLU values were seen in UltraSnap samples compared with MicroSnap samples. Additionally, for buckets and nipples, higher RLU values were obtained for the direct swabbing method compared with the liquid sampling method for both swabs used. No differences in the level of contamination were seen between the different feeding equipment used within a farm. Overall, a higher correlation with bacteriological results was noticed for ATP luminometry compared with the visual score, with a high correlation for nipples and bottles using the UltraSnap and liquid technique. Based on the classification of "contaminated" (TBC ≥100,000 cfu/mL) or "not contaminated" (TBC <100,000 cfu/mL), optimal ATP luminometer cutoff values for buckets, nipples, bottles, AMF, water, and milk replacer were 798, 388, 469, 282, 1,432, and 93 RLU, respectively. No clear association was found between ATP measurements and the self-reported cleaning protocol. This study gave new insights into the current cleaning procedures and contamination of feeding equipment for preweaning calves on dairy farms in Quebec. In addition, ATP luminometry cutoff values could help benchmark farms regarding cleaning practices and provide customized advice, improving the overall hygiene management, and thus the health, of preweaning calves on dairy farms.