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Abstract Background Inulin and inulin-derived fructooligosaccharides (FOS) are well-known prebiotics for use in companion animals and livestock. The mechanisms by which FOS contribute to health has not been fully established. Further, the fine chemistry of fructan structures from diverse sources, such as graminan-type fructans found in cereal crops, has not been fully elucidated. New methods to study fructan structure and microbial responses to these complex carbohydrates will be key for evaluating the prebiotic potency of cereal fructans found in cattle feeds. As the rumen microbiome composition is closely associated with their metabolic traits, such as feed utilization and waste production, prebiotics and probiotics represent promising additives to shift the microbial community toward a more productive state. Results Within this study, inulin, levan, and graminan-type fructans from winter wheat, spring wheat, and barley were used to assess the capacity of rumen-derived Bifidobacterium boum, Bifidobacterium merycicum, and Lactobacillus vitulinus to metabolize diverse fructans. Graminan-type fructans were purified and structurally characterized from the stems and kernels of each plant. All three bacterial species grew on FOS, inulin, and cereal crop fructans in pure cultures. L. vitulinus was the only species that could metabolize levan, albeit its growth was delayed. Fluorescently labelled polysaccharides (FLAPS) were used to demonstrate interactions with Gram-positive bacteria and confirm fructan metabolism at the single-cell level; these results were in agreement with the individual growth profiles of each species. The prebiotic potential of inulin was further investigated within naïve rumen microbial communities, where increased relative abundance of Bifidobacterium and Lactobacillus species occurred in a dose-dependent and temporal-related manner. This was supported by in situ analysis of rumen microbiota from cattle fed inulin. FLAPS probe derived from inulin and fluorescent in situ hybridization using taxon-specific probes confirmed that inulin interacts with Bifidobacteria and Lactobacilli at the single-cell level. Conclusion This research revealed that rumen-derived Bifidobacteria and Lactobacilli vary in their metabolism of structurally diverse fructans, and that inulin has limited prebiotic potential in the rumen. This knowledge establishes new methods for evaluating the prebiotic potential of fructans from diverse plant sources as prebiotic candidates for use in ruminants and other animals.

ABSTRACT Colistin resistance in Escherichia coli is of public health significance for its use to treat multidrug-resistant Gram-negative infections. Amino acid variations in PmrB have been implicated in colistin resistance in E. coli. In this cross-sectional study, 288 generic E. coli isolates from surveillance of broiler chicken and feedlot cattle feces, retail meat, wastewater, and well water were whole-genome sequenced. Phylogroup designation and screening for two amino acid substitutions in PmrB putatively linked to colistin resistance (Y358N, E123D) were performed in silico. Three additional data sets of publicly available E. coli assemblies were similarly scrutinized: (i) E. coli isolates from studies identifying the Y358N or E123D substitutions, (ii) colistin-susceptible E. coli isolates reported in the literature, and (iii) a random sampling of 14,700 E. coli assemblies available in the National Center for Biotechnology Information public database. Within all data sets, ≥95% of phylogroup B1 and C isolates have the PmrB Y358N variation. The PmrB E123D amino acid substitution was only identified in phylogroup B2 isolates, of which 94%–100% demonstrate the substitution. Both PmrB amino acid variations were infrequent in other phylogroups. Among published colistin susceptible isolates, colistin minimum inhibitory concentrations (MICs) were not higher in isolates bearing the E123D and Y358N amino acid variations than in isolates without these PmrB substitutions. The E123D and Y358N PmrB amino acid substitutions in E. coli appear strongly associated with phylogroup. The previously observed associations between Y358N and E123D amino acid substitutions in PmrB and colistin resistance in E. coli may be spurious.IMPORTANCEColistin is a critical last-resort treatment for extensively drug-resistant Gram-negative infections in humans. Therefore, accurate identification of the genetic mechanisms of resistance to this antimicrobial is crucial to effectively monitor and mitigate the spread of resistance. Examining over 16,000 whole-genome sequenced Escherichia coli isolates, this study identifies that PmrB E123D and Y358N amino acid substitutions previously associated with colistin resistance in E. coli are strongly associated with phylogroup and are alone not sufficient to confer a colistin-resistant phenotype. This is a critical clarification, as both substitutions are identified as putative mechanisms of colistin resistance in many publications and a common bioinformatic tool. Given the potential spurious nature of initial associations of these substitutions with colistin resistance, this study's findings emphasize the importance of appropriate experimental design and consideration of relevant biological factors such as phylogroup when ascribing causal mechanisms of resistance to chromosomal variations.

We present a deep-learning-based software pipeline for reconstructing and segmenting large sets of time-resolved micro-computed tomography (µCT) image data. We construct and train a convolutional neural network (CNN) to consistently, rapidly, and autonomously segment the time-resolved tomography data. The preceding CT reconstruction steps are parametrized for optimal image quality for segmentation. We demonstrate how to discriminate materials with similar radiographic densities in the presence of different media, such as air and water. Our approach can be used out of the box for similar µCT data or adapted to any similarly challenging 3D image data by retraining the neural network.

Abstract Parotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p

Three seasonally resolved ice core records covering the 20th century were extracted in 1994, 2004, and 2012 at a nearly identical location from the Col du Dôme (4250 m above sea level, m a.s.l.; Mont Blanc, French Alps) drill site. Here, we complete and combine chemical records of major ions and radiometric measurements of 3H and 210Pb obtained from these three cores with a 3D ice flow model of the Col du Dôme glacier to investigate in detail the origin of discontinuities observed in the depth–age relation of the ice cores drilled in 2004 and 2012. Taking advantage of the granitic bedrock at Col du Dôme, which makes the ice core 210Pb records sensitive to the presence of upstream crevasses, and the fact that the depth–age disturbances are observed at depths for which absolute time markers are available, we draw an overall picture of a dynamic crevasse formation. This can explain the non-disturbed depth–age relation of the ice core drilled in 1994 and the perturbations observed in those drilled in 2004 and 2012. Since crevasses are common at high-Alpine glacier sites, our study points to the important need for rigorous investigations of the depth–age scale and glaciological conditions upstream of drill sites before interpreting high-alpine ice core records in terms of atmospheric changes.

Abstract Forest soils harbor hyper-diverse microbial communities which fundamentally regulate carbon and nutrient cycling across the globe. Directly testing hypotheses on how microbiome diversity is linked to forest carbon storage has been difficult, due to a lack of paired data on microbiome diversity and in situ observations of forest carbon accumulation and storage. Here, we investigated the relationship between soil microbiomes and forest carbon across 238 forest inventory plots spanning 15 European countries. We show that the composition and diversity of fungal, but not bacterial, species is tightly coupled to both forest biotic conditions and a seven-fold variation in tree growth rates and biomass carbon stocks when controlling for the effects of dominant tree type, climate, and other environmental factors. This linkage is particularly strong for symbiotic endophytic and ectomycorrhizal fungi known to directly facilitate tree growth. Since tree growth rates in this system are closely and positively correlated with belowground soil carbon stocks, we conclude that fungal composition is a strong predictor of overall forest carbon storage across the European continent.

Foot and mouth disease (FMD) is a highly contagious infection caused by FMD-virus (FMDV) that affects livestock worldwide with significant economic impact. The main strategy for the control is vaccination with FMDV chemically inactivated with binary ethylenimine (FMDVi). In FMDV infection and vaccination, B cell response plays a major role by providing neutralizing/protective antibodies in animal models and natural hosts. Extracellular vesicles (EVs) and small EVs (sEVs) such as exosomes are important in cellular communication. EVs secreted by antigen-presenting cells (APC) like dendritic cells (DCs) participate in the activation of B and T cells through the presentation of native antigen membrane-associated to B cells or by transferring MHC-peptide complexes to T cells and even complete antigens from DCs. In this study, we demonstrate for the first time that APC activated with the FMDVi O1 Campos vaccine-antigens secrete EVs expressing viral proteins/peptides that could stimulate FMDV-specific immune response. The secretion of EVs-FMDVi is a time-dependent process and can only be isolated within the first 24 h post-activation. These vesicles express classical EVs markers (CD9, CD81, and CD63), along with immunoregulatory molecules (MHC-II and CD86). With an average size of 155 nm, they belong to the category of EVs. Studies conducted in vitro have demonstrated that EVs-FMDVi express antigens that can stimulate a specific B cell response against FMDV, including both marginal zone B cells (MZB) and follicular B cells (FoB). These vesicles can also indirectly or directly affect T cells, indicating that they express both B and T epitopes. Additionally, lymphocyte expansion induced by EVs-FMDVi is greater in splenocytes that have previously encountered viral antigens in vivo. The present study sheds light on the role of EVs derived from APC in regulating the adaptive immunity against FMDV. This novel insight contributes to our current understanding of the immune mechanisms triggered by APC during the antiviral immune response. Furthermore, these findings may have practical implications for the development of new vaccine platforms, providing a rational basis for the design of more effective vaccines against FMDV and other viral diseases.

IntroductionThis study assessed the risk of first treatment for bovine respiratory disease (BRD) given detection of nasopharyngeal bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) and corresponding likelihood of antimicrobial susceptibility (C/S) at two time points during the early feeding period. Relationships between C/S results and later treatment for BRD were evaluated at both the calf-level and pen-level. The association between calf-level and pen-level C/S findings during the early feeding period and subsequent C/S results at BRD treatment were also reported.MethodsAuction-sourced, recently-weaned beef calves (n = 1,599 steers) were placed in adjacent feedlot pens (8 × 100 calves) in two subsequent years. Deep nasopharyngeal (DNP) swabs were collected from all calves at time of arrival processing (1DOF) and before metaphylaxis administration with either tulathromycin or oxytetracycline, 12 days later (13DOF), and at the time of first treatment for BRD. All samples were tested for C/S.ResultsSeveral pen-level and individual calf-level C/S measures of interest were associated with future treatment for BRD and C/S at the time of treatment. The median DOF for first BRD treatment was 24 days following tulathromycin metaphylaxis and 11 days following oxytetracycline. Overall, sampling at 13DOF resulted in the best fit for more models of subsequent treatment for BRD and C/S results at BRD treatment than for sampling at arrival. In individual calves, recovery of M. haemolytica, P. multocida, or H. somni at 13DOF was associated with subsequent treatment for BRD within 45DOF. Pen-level prevalence of Pasteurellacea bacteria with tetracycline or macrolide resistance at arrival and 13DOF were associated with detection of bacteria with antimicrobial resistance (AMR) at BRD treatment, as were individual calf results at 13DOF.DiscussionThese findings suggest that the bacteria and AMR outcomes recovered from cattle near two weeks on feed can inform the prediction of future BRD risk and concurrent antimicrobial susceptibility results at time of first BRD treatment. Notably, the associations between pen-level C/S results from previous testing and corresponding findings in calves with BRD from the same pen suggested potential testing strategies to inform antimicrobial use protocols for feedlot cattle.

ABSTRACT The development and growth of animals coincide with the establishment and maturation of their microbiotas. To evaluate the respiratory and fecal microbiotas of beef calves from birth to weaning, a total of 30 pregnant cows, and their calves at birth, were enrolled in this study. Deep nasal swabs and feces were collected from calves longitudinally, starting on the day of birth and ending on the day of weaning. Nasopharyngeal, vaginal, and fecal samples were also collected from cows, and the microbiotas of all samples were analyzed. The fecal microbiota of calves was enriched with Lactobacillus during the first 8 weeks of life, before being displaced by genera associated with fiber digestion, and then increasing in diversity across time. In contrast, the diversity of calf respiratory microbiota generally decreased with age. At birth, the calf and cow nasal microbiotas were highly similar, indicating colonization from dam contact. This was supported by microbial source-tracking analysis. The structure of the calf nasal microbiota remained similar to that of the cows, until weaning, when it diverged. The changes were driven by a decrease in Lactobacillus and an increase in genera typically associated with bovine respiratory disease, including Mannheimia, Pasteurella, and Mycoplasma. These three genera colonized calves early in life, though Mannheimia was initially transferred from the cow reproductive tract. Path analysis was used to model the interrelationships of calf respiratory and fecal microbiotas. It was observed that respiratory Lactobacillus and fecal Oscillospiraceae UCG-005 negatively affected the abundance of Mannheimia or Pasteurella.IMPORTANCEIn beef cattle production, bovine respiratory disease (BRD) accounts for most of the feedlot morbidities and mortalities. Metaphylaxis is a common management tool to mitigate BRD, however its use has led to increased antimicrobial resistance. Novel methods to mitigate BRD are needed, including microbiota-based strategies. However, information on the respiratory bacteria of beef calves prior to weaning was limited. In this study, it was shown that the microbiota of cows influenced the initial composition of both respiratory and fecal microbiotas in calves. While colonization of the respiratory tract of calves by BRD-associated genera occurred early in life, their relative abundances increased at weaning, and were negatively correlated with respiratory and gut bacteria. Thus, microbiotas of both the respiratory and gastrointestinal tracts have important roles in antagonism of respiratory pathogens and are potential targets for enhancing calf respiratory health. Modulation may be most beneficial, if done prior to weaning, before opportunistic pathogens establish colonization.

Abstract We performed a longitudinal shotgun metagenomic investigation of the plaque microbiome associated with peri-implant diseases in a cohort of 91 subjects with 320 quality-controlled metagenomes. Through recently improved taxonomic profiling methods, we identified the most discriminative species between healthy and diseased subjects at baseline, evaluated their change over time, and provided evidence that clinical treatment had a positive effect on plaque microbiome composition in patients affected by mucositis and peri-implantitis.

Abstract Leptospirosis is a globally distributed zoonotic disease. The standard serological test, known as Microscopic Agglutination Test (MAT), requires the use of live Leptospira strains. To enhance its sensitivity and specificity, the usage of locally circulating strains is recommended. However, to date, no local strain is available from Austria. This study aimed to isolate circulating Leptospira strains from cattle in Austria to enhance the performances of the routine serological test for both humans and animals. We used a statistical approach combined with a comprehensive literature search to profile cattle with greater risk of leptospirosis infection and implemented a targeted sampling between November 2021 and October 2022. Urine and/or kidney tissue were sampled from 410 cattle considered at higher risk of infection. Samples were inoculated into EMJH-STAFF culture media within 2–6 h and a real-time PCR targeting the lipL32 gene was used to confirm the presence/absence of pathogenic Leptospira in each sample. Isolates were further characterised by core genome multilocus sequence typing (cgMLST). Nine out of 429 samples tested positive by PCR, from which three isolates were successfully cultured and identified as Leptospira borgpetersenii serogroup Sejroe serovar Hardjobovis, cgMLST cluster 40. This is the first report on the isolation and genotyping of local zoonotic Leptospira in Austria, which holds the potential for a significant improvement in diagnostic performance in the country. Although the local strain was identified as a cattle-adapted serovar, it possesses significant zoonotic implications. Furthermore, this study contributes to a better understanding of the epidemiology of leptospirosis in Europe.

Key message Evolving societal demands and accelerated ecological dynamics due to global change are rapidly altering forest ecosystems and their services. This has prompted the need for advancing forest inventorying and monitoring initatives to expand their scope, improve data collection, foster scientific understanding, and better inform policy responses. Here, we discuss the collaborative processes followed to develop an Advanced Inventorying and Monitoring (AIM) system for Swiss forests. Further, we provide the key messages that emerged from this process which can be of interest to those involved in similar processes at the national/international level.

Abstract Background Data on antimicrobial resistance (AMR) in cow-calf herds is limited and there have been no Canadian studies examining AMR in Enterococcus in cow-calf herds. Enterococcus is a ubiquitous Gram-positive indicator of AMR for enteric organisms that is also important in human health. The objective of this study was to describe AMR in specific Enterococcus species of interest from cow-calf herds; highlighting differences in AMR among isolates from cows and calves and samples collected in the spring and fall. Isolates (n = 1505) were examined from 349 calves and 385 cows from 39 herds in the spring of 2021 and 413 calves from 39 herds and 358 cows from 36 herds in the fall of 2021. Enterococcus species were identified using Matrix-Assisted Laser Desorption Ionization Time-Of-Flight mass spectrometry (MALDI-TOF MS) and antimicrobial susceptibility testing was completed based on a prioritization scheme for importance to human health and using the National Antimicrobial Resistance Monitoring System (NARMS) Gram positive Sensititre broth microdilution panel. Results Resistance was observed to at least one antimicrobial in 86% (630/734) of isolates from the spring and 84% (644/771) of isolates from the fall. The most common types of resistance across all species were: lincomycin, quinupristin/dalfopristin, daptomycin, ciprofloxacin, and tetracycline. However, the proportion of isolates with AMR varied substantially based on species. Multiclass resistance, defined as resistance to ≥3 antimicrobial classes after excluding intrinsic resistance, was highest in isolates from calves in the spring (6.9%) (24/349) and cows in the fall (6.7%) (24/357). Differences in resistance were seen between cows and calves in the spring and fall as well as across seasons, with no differences seen between cows and calves in the fall. Conclusions While most Enterococcus isolates were resistant to at least one antimicrobial, questions remain regarding species differences in intrinsic resistance and the accuracy of certain antimicrobial breakpoints for specific Enterococcus spp. As a result, some species-specific AMR profiles should be interpreted with caution. Despite these constraints, Enterococcus species are important indicator organisms for AMR and resulting data can be used to inform stewardship initiatives.

Background/Objectives: The implementation of information quality value stream maps (IQ-VSMs) in food animal production systems can increase our understanding of the opportunities and challenges when using laboratory testing for antimicrobial resistance (AMR) to support antimicrobial stewardship (AMS). Our objectives were to (1) explore the implementation of information quality value stream mapping as a continuous improvement tool to inform decisions for bovine respiratory disease (BRD) management and AMS and (2) apply the information quality dimensions to identified Kaizen opportunities for the integration of laboratory data into BRD management systems to assess the appropriateness of BRD treatment plans in western Canadian feedlot production. Methods: A ‘Current State’ IQ-VSM outlined the processes, available information, information processing steps, and control decisions contributing to BRD management and treatment in commercial western Canadian feedlots, recognizing that laboratory BRD pathogens and AMR data are typically not part of BRD management. Results: The ‘Future State’ IQ-VSM incorporated Kaizen opportunities for improvement, including (i) the strategic collection of respiratory samples from representative samples of calves for laboratory analysis, regardless of clinical BRD status, (ii) compilation of laboratory data at the pen and feedlot levels, and (iii) analysis of pen- and feedlot-level laboratory data to inform the veterinarian’s assessment of the appropriateness of current BRD treatment plans. Conclusions: The IQ-VSMs provided a valuable framework to visualize the integration of BRD pathogen and AMR laboratory data to support AMS and address any potential future testing requirements.

IntroductionBovine respiratory disease (BRD) is one of the most important animal health problems in the beef industry. While bacterial culture and antimicrobial susceptibility testing have been used for diagnostic testing, the common practice of examining one isolate per species does not fully reflect the bacterial population in the sample. In contrast, a recent study with metagenomic sequencing of nasal swabs from feedlot cattle is promising in terms of bacterial pathogen identification and detection of antimicrobial resistance genes (ARGs). However, the sensitivity of metagenomic sequencing was impeded by the high proportion of host biomass in the nasal swab samples.MethodsThis pilot study employed a non-selective bacterial enrichment step before nucleic acid extraction to increase the relative proportion of bacterial DNA for sequencing.ResultsNon-selective bacterial enrichment increased the proportion of bacteria relative to host sequence data, allowing increased detection of BRD pathogens compared with unenriched samples. This process also allowed for enhanced detection of ARGs with species-level resolution, including detection of ARGs for bacterial species of interest that were not targeted for culture and susceptibility testing. The long-read sequencing approach enabled ARG detection on individual bacterial reads without the need for assembly. Metagenomics following non-selective bacterial enrichment resulted in substantial agreement for four of six comparisons with culture for respiratory bacteria and substantial or better correlation with qPCR. Comparison between isolate susceptibility results and detection of ARGs was best for macrolide ARGs in Mannheimia haemolytica reads but was also substantial for sulfonamide ARGs within M. haemolytica and Pasteurella multocida reads and tetracycline ARGs in Histophilus somni reads.DiscussionBy increasing the proportion of bacterial DNA relative to host DNA through non-selective enrichment, we demonstrated a corresponding increase in the proportion of sequencing data identifying BRD-associated pathogens and ARGs in deep nasopharyngeal swabs from feedlot cattle using long-read metagenomic sequencing. This method shows promise as a detection strategy for BRD pathogens and ARGs and strikes a balance between processing time, input costs, and generation of on-target data. This approach could serve as a valuable tool to inform antimicrobial management for BRD and support antimicrobial stewardship.

Cow-calf surveillance data provide critical information about changing herd demographics, productivity, health, and management as well as the opportunity to investigate the impact of differing management practices. A national cow-calf network was established to collect baseline information on herd health, production performance measures, and management. Questionnaires were used to collect information on herd attributes as well as data for the calving season, breeding, pregnancy testing, and weaning for herds from across Canada. From 2018 to 2022, a total of 565 calving record questionnaires, representing 110,658 calving female records from 171 herds were returned, along with 543 herd breeding to weaning questionnaires. Suggested benchmark values based on the 25th percentiles from Western and Eastern Canada were determined to be

Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare bone disorder featuring fibroblast growth factor-23 (FGF23)-mediated hypophosphatemic rickets. We report a 2-year, 10-month-old girl with CSHS treated with burosumab, a novel human monoclonal antibody targeting FGF23. This approach was associated with rickets healing, improvement in growth and lower limb deformity, and clinically significant benefit to her functional mobility and motor development. This case report provides evidence for the effective use of FGF23-neutralizing antibody therapy beyond the classic FGF23-mediated disorders of X-linked hypophosphatemia and tumor-induced osteomalacia.

Abstract Background Medical specialty certification exams are high-stakes summative assessments used to determine which doctors have the necessary skills, knowledge, and attitudes to treat patients independently. Such exams are crucial for patient safety, candidates’ career progression and accountability to the public, yet vary significantly among medical specialties and countries. It is therefore of paramount importance that the quality of specialty certification exams is studied in the scientific literature. Methods In this systematic literature review we used the PICOS framework and searched for papers concerning medical specialty certification exams published in English between 2000 and 2020 in seven databases using a diverse set of search term variations. Papers were screened by two researchers independently and scored regarding their methodological quality and relevance to this review. Finally, they were categorized by country, medical specialty and the following seven Ottawa Criteria of good assessment: validity, reliability, equivalence, feasibility, acceptability, catalytic and educational effect. Results After removal of duplicates, 2852 papers were screened for inclusion, of which 66 met all relevant criteria. Over 43 different exams and more than 28 different specialties from 18 jurisdictions were studied. Around 77% of all eligible papers were based in English-speaking countries, with 55% of publications centered on just the UK and USA. General Practice was the most frequently studied specialty among certification exams with the UK General Practice exam having been particularly broadly analyzed. Papers received an average of 4.2/6 points on the quality score. Eligible studies analyzed 2.1/7 Ottawa Criteria on average, with the most frequently studied criteria being reliability, validity, and acceptability. Conclusions The present systematic review shows a growing number of studies analyzing medical specialty certification exams over time, encompassing a wider range of medical specialties, countries, and Ottawa Criteria. Due to their reliance on multiple assessment methods and data-points, aspects of programmatic assessment suggest a promising way forward in the development of medical specialty certification exams which fulfill all seven Ottawa Criteria. Further research is needed to confirm these results, particularly analyses of examinations held outside the Anglosphere as well as studies analyzing entire certification exams or comparing multiple examination methods.

Jordan J Huang,1 Derek Waldner,1,2 Jaxon J Huang,3 Joshua M Huang,1 Paul Huang,1,2 Joshua C Teichman,4,5 Mahshad Darvish-Zargar,6 Patrick Gooi2 1Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 2Division of Ophthalmology, University of Calgary, Calgary, Alberta, Canada; 3John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; 4Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada; 5Division of Ophthalmology, Trillium Health Partners, Mississauga, Ontario, Canada; 6Division of Ophthalmology, McGill University, Montreal, Quebec, CanadaCorrespondence: Jordan J Huang, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada, Tel +1 403 991 8897, Email jordanhuang8@gmail.comPurpose: To assess the face and content validity of an artificial eye model for secondary intraocular lens (IOL) fixation via the Yamane technique.Methods: Ophthalmologists and residents participated in a 90-minute simulation session on secondary IOL fixation via the Yamane technique. Hands-on practice of this technique was performed on an artificial eye, the Bioniko Okulo BR8. After, all ophthalmologists answered an 18-question survey assessing the face and content validity of the model. Survey responses were recorded on a 5-point double-headed Likert scale, ranging from strongly agree (1)-to-strongly disagree (5) (Figure 1).Results: Twenty-three surveys were completed. Respondents rated the survey with a median response of 1 (strongly agree)-to-3 (neutral). Highest ratings for the model were received for “usefulness for training residents”, and “easier to set up and clean-up compared to a cadaver”. Lowest ratings were received for realism of the model compared to cadaveric eyes. Statistical analysis revealed no significant difference among identified groups. Ratings for face and content validity were viewed favorably, both with an overall median response of 2.00 (agree).Conclusion: The Bioniko Okulo BR8 shows promise as a valid tool for practicing secondary IOL fixation via the Yamane technique. Considering recent guidelines in competency-based ophthalmology education programs, this model may be a valuable tool over traditional techniques for teaching and improving surgical skill amongst trainees.Keywords: training, cataracts, Bioniko, Okulo, model

Objectives: Parkinson’s disease is characterized by motor and non-motor symptoms. Tremor is one of the motor symptoms that can affect manual skills and have an impact on daily activities. The aim of the current study is to investigate the effect of upper limb training provided by a specific vibratory device (Armshake®, Move It GmbH - Bochum, Germany) on tremor and motor functionality in patients with Parkinson’s disease. Furthermore, the training effect on global cognitive functioning is assessed. Design: An uncontrolled before-after clinical trial. Patients: Individuals with diagnosis of Parkinson’s disease, motor upper limbs deficits, and absence of dementia. Methods: Participants underwent a 3-week programme (3 times a week) and was evaluated before, after, and at 1 month follow-up by motor (Fahn Tolosa Marin Tremor Rating Scale, Unified Parkinson’s Disease Rating Scale – part III, Purdue Pegboard Test, Disability of the Arm, Shoulder and Hand Questionnaire) and cognitive (Montreal Cognitive Assessment) scales. Results: Twenty subjects are included. After treatment a statistically significant improvement in tremor, manual dexterity and activities of daily living was found. The data indicated no effects on global cognitive functioning. Conclusion: These findings suggest positive effects of vibratory stimulation training on upper limb motor symptoms in Parkinson’s disease.

The mechanism governing pharmaceutical tablet disintegration is far from fully understood. Despite the importance of controlling a formulation's disintegration process to maximize the active pharmaceutical ingredient's bioavailability and ensure predictable and consistent release profiles, the current understanding of the process is based on indirect or superficial measurements. Formulation science could, therefore, additionally deepen the understanding of the fundamental physical principles governing disintegration based on direct observations of the process. We aim to help bridge the gap by generating a series of time-resolved X-ray micro-computed tomography (μCT) images capturing volumetric images of a broad range of mini-tablet formulations undergoing disintegration. Automated image segmentation was a prerequisite to overcoming the challenges of analyzing multiple time series of heterogeneous tomographic images at high magnification. We devised and trained a convolutional neural network (CNN) based on the U-Net architecture for autonomous, rapid, and consistent image segmentation. We created our own μCT data reconstruction pipeline and parameterized it to deliver image quality optimal for our CNN-based segmentation. Our approach enabled us to visualize the internal microstructures of the tablets during disintegration and to extract parameters of disintegration kinetics from the time-resolved data. We determine by factor analysis the influence of the different formulation components on the disintegration process in terms of both qualitative and quantitative experimental responses. We relate our findings to known formulation component properties and established experimental results. Our direct imaging approach, enabled by deep learning-based image processing, delivers new insights into the disintegration mechanism of pharmaceutical tablets.

It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called ‘metabolic imaging’ tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as 18F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Multispectral optoacoustic tomography (MSOT) allows non-invasive molecular disease activity assessment in adults with inflammatory bowel disease (IBD). In this prospective pilot-study, we investigated, whether increased levels of MSOT haemoglobin parameters corresponded to inflammatory activity in paediatric IBD patients, too. 23 children with suspected IBD underwent MSOT of the terminal ileum and sigmoid colon with standard validation (e.g. endoscopy). In Crohn`s disease (CD) and ulcerative colitis (UC) patients with endoscopically confirmed disease activity, MSOT total haemoglobin (HbT) signals were increased in the terminal ileum of CD (72.1 ± 13.0 a.u. vs. 32.9 ± 15.4 a.u., p = 0.0049) and in the sigmoid colon of UC patients (62.9 ± 13.8 a.u. vs. 35.1 ± 16.3 a.u., p = 0.0311) as compared to controls, respectively. Furthermore, MSOT haemoglobin parameters correlated well with standard disease activity assessment (e.g. SES-CD and MSOT HbT (rs =0.69, p = 0.0075). Summarizing, MSOT is a novel technology for non-invasive molecular disease activity assessment in paediatric patients with inflammatory bowel disease.