Long-distance dispersal in the short-distance dispersing house sparrow (Passer domesticus).

The house sparrow (Passer domesticus) is a small passerine known to be highly sedentary. Throughout a 30-year capture-mark-recapture study, we have obtained occasional reports of recoveries far outside our main metapopulation study system, documenting unusually long dispersal distances. Our records constitute the highest occurrence of long-distance dispersal events recorded for this species in Scandinavia. Such long-distance dispersals radically change the predicted distribution of dispersal distances and connectedness for our study metapopulation. Moreover, it reveals a much greater potential for colonization than formerly recorded for the house sparrow, which is an invasive species across four continents. These rare and occasional long-distance dispersal events are challenging to document but may have important implications for the genetic composition of small and isolated populations and for our understanding of dispersal ecology and evolution.

Bacterial micro-aggregates as inoculum in animal models of implant-associated infections.

Is it time to rethink the inoculum of animal models of implant-associated infections (IAI)? Traditionally, animal models of IAI are based on inoculation with metabolically active overnight cultures of planktonic bacteria or pre-grown surface-attached biofilms. However, such inoculums do not mimic the clinical initiation of IAI. Therefore, the present study aimed to develop a clinically relevant inoculum of low metabolic micro-aggregated bacteria. The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth (TSB) for seven days to facilitate the formation of low metabolic micro-aggregates. Subsequently, the aggregated culture underwent filtration using cell strainers of different pore sizes to separate micro-aggregates. Light microscopy was used to evaluate the aggregate formation and size in the different fractions, while isothermal microcalorimetry was used to disclose a low metabolic activity. The micro-aggregate fraction obtained with filter size 5-15 µm (actual measured mean size 32 µm) was used as inoculum in a porcine implant-associated osteomyelitis (IAO) model and compared to a standard overnight planktonic inoculum and a sham inoculum of 0.9 % saline. The micro-aggregate and planktonic inoculums caused IAO with the re-isolation of S. aureus from soft tissues, bones, and implants. However, compared to their planktonic counterpart, neither of the micro-aggregate inoculated animals showed signs of osteomyelitis, i.e., sequester, osteolysis, and pus at gross inspection. Furthermore, inoculation with low metabolic micro-aggregates resulted in a strong healing response with pronounced osteoid formation, comparable to sham animals. In conclusion, the formation and separation of low metabolic bacterial micro-aggregates into various size fractions is possible, however, planktonic bacteria were still seen in all size fractions. Inoculation with micro-aggregates caused a less-aggressive osteomyelitis i.e. combination of infected tissue and strong healing response. Therefore, the use of low metabolic micro-aggregates could be a relevant inoculum for animal models of less-aggressive and thereby slower developing IAI and add in to our understanding of the host-implant-bacteria interactions in slow-onset low-grade infections.

Prevalence and characterisation of band-shaped tail lesions in Holstein cows.

The aim of the study was to characterise and determine the prevalence of band-shaped tail lesions in Holstein cows. Lesions were present either as wounds or by epithelised granulation/connective tissue formations. Both types were characterised by a median localisation 7 cm from the tip of the tail, and they occurred on the dorsal aspect of the tail. From here they encircled the tail either completely or in varying degrees, and they were often present as isolated lesions (93%). The prevalence of band-shaped tail lesions was found to be 25% among 2099 cows examined in 16 Danish Holstein herds with a variation from 18 to 40% between herds. In the herds, the wound lesions and the connective tissue formations accounted for 22% and 78% of all band-shaped tail lesions, respectively. Among 458 Holstein cows examined at an abattoir the prevalence of band-shaped tail lesions was 23%, i.e. similar to the prevalence within the herds. At the abattoir the share of band-shaped wound lesions was 67% and the band-shaped connective tissue formation 33%. Associations between the occurrence of band-shaped tail lesions and parity and lack of the tail tip were observed.

Cutaneous squamous cell carcinoma characterized by MALDI mass spectrometry imaging in combination with machine learning.

Cutaneous squamous cell carcinoma (SCC) is an increasingly prevalent global health concern. Current diagnostic and surgical methods are reliable, but they require considerable resources and do not provide metabolomic insight. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) enables detailed, spatially resolved metabolomic analysis of tissue samples. Integrated with machine learning, MALDI-MSI could yield detailed information pertaining to the metabolic alterations characteristic for SCC. These insights have the potential to enhance SCC diagnosis and therapy, improving patient outcomes while tackling the growing disease burden. This study employs MALDI-MSI data, labelled according to histology, to train a supervised machine learning model (logistic regression) for the recognition and delineation of SCC. The model, based on data acquired from discrete tumor sections (n = 25) from a mouse model of SCC, achieved a predictive accuracy of 92.3% during cross-validation on the labelled data. A pathologist unacquainted with the dataset and tasked with evaluating the predictive power of the model in the unlabelled regions, agreed with the model prediction for over 99% of the tissue areas. These findings highlight the potential value of integrating MALDI-MSI with machine learning to characterize and delineate SCC, suggesting a promising direction for the advancement of mass spectrometry techniques in the clinical diagnosis of SCC and related keratinocyte carcinomas.

Bidirectional Association Between Atrial Fibrillation and Myocardial Infarction, and Relation to Mortality in the Framingham Heart Study.

BACKGROUND: Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. METHODS AND RESULTS: We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new-onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable-adjusted Cox proportional hazards models. Interim diseases were modeled as time-varying variables. For the analysis of new-onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new-onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new-onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32-1.94]) and interim MI (HR, 3.96 [95% CI, 3.18-4.91]). Both ST-segment-elevation MI and non-ST-segment-elevation MI were associated with new-onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new-onset MI (HR, 2.21 [95% CI, 1.67-2.92]). Interim AF was associated with both ST-segment-elevation MI and non-ST-segment-elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. CONCLUSIONS: We report a bidirectional association between AF and MI, which was observed for both non-ST-segment-elevation MI and ST-segment-elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

Assessment of abdominal lesions in pigs with wounded umbilical outpouchings transported to slaughter.

BACKGROUND: Umbilical outpouchings (UOs) in pigs are of welfare and production concern in Danish pig herds. One of the challenges is the transportation of these animals due to the size of the UOs and ulcerations on them. With certain precautions and an approval from a veterinarian, pigs with UOs may be transported, however, UOs are associated with several intra-abdominal lesions, e.g. peritonitis and incarceration, which may worsen during the process of transportation. The prevalence and characterization of intra-abdominal lesions associated with UOs following transportation has not been investigated. Therefore, the objective of the present study was to evaluate lesions associated with the intestines and peritoneum in slaughter pigs with wounded UOs following transportation to an abattoir. RESULTS: A cross-sectional study involving three conventional Danish pig herds was conducted comprising 96 slaughter pigs with wounded UOs transported to an abattoir. Following slaughter the UOs with accompanying intestines were examined pathologically. Three distinct morphological categories were present: hernia, enterocystoma and herniating enterocystoma. Intra-abdominal lesions were present in 72% of the animals, representing 65% (44/68) of the hernias, 77% (10/13) of the enterocystomas, and 100% (15/15) of the herniating enterocystomas. Several different lesions were found like bleedings, acute/chronic peritonitis and hypertrophy of the intestinal muscular layers. CONCLUSIONS: The prevalence of intra-abdominal lesions in pigs transported with a wounded UO was found to be high independent of the underlying condition, and it is clear that these pigs possess a vulnerable group of animals, especially during physical stressful situations like transportation. More information is needed regarding the prevalence of intra-abdominal lesions in UO pigs without wounds on the UO. The results provide valuable knowledge, that can be used when examining and evaluating UO pigs before transportation.

Randomised, Placebo-Controlled Investigation of the Impact of Probiotic Consumption on Gut Microbiota Diversity and the Faecal Metabolome in Seniors.

Aging has been associated with a changed composition and function of the gut microbiota (GM). Here, we investigate the effects of the multi-strain probiotic HOWARU® Restore on GM composition and function in seniors. Ninety-eight healthy adult volunteers aged ≥75 years were enrolled in a randomised, double-blinded intervention (NCT02207140), where they received HOWARU Restore (1010 CFU) or the placebo daily for 24 weeks, with 45 volunteers from each group completing the intervention. Questionnaires monitoring the effects on gastro-intestinal discomfort and bowel movements were collected. Faecal samples for GM characterisation (qPCR, 16S rRNA gene amplicon sequencing) and metabolomics (GC-FID, 1H NMR) were collected at the baseline and after 24 weeks. In the probiotic group, self-reported gastro-intestinal discomfort in the form of flatulence was significantly decreased during the intervention. At the baseline, 151 'core species' (present in ≥95% of samples) were identified. Most core species belonged to the Lachnospiraceae and Ruminococcaceae families. Neither alpha diversity nor beta diversity or faecal metabolites was affected by probiotic intake. On the contrary, we observed high intra-individual GM stability, with 'individual' accounting for 72-75% of variation. In conclusion, 24 weeks of HOWARU Restore intake reduced gastro-intestinal discomfort in the form of flatulence in healthy seniors without significantly influencing GM composition or activity.

Taylor Dispersion-Induced Phase Separation for the Efficient Characterisation of Protein Condensate Formation.

Biomolecular condensates have emerged as important structures in cellular function and disease, and are thought to form through liquid-liquid phase separation (LLPS). Thorough and efficient in vitro experiments are therefore needed to elucidate the driving forces of protein LLPS and the possibility to modulate it with drugs. Here we present Taylor dispersion-induced phase separation (TDIPS), a method to robustly measure condensation phenomena using a commercially available microfluidic platform. It uses only nanoliters of sample, does not require extrinsic fluorescent labels, and is straightforward to implement. We demonstrate TDIPS by screening the phase behaviour of two proteins that form biomolecular condensates in vivo, PGL-3 and Ddx4. Uniquely accessible to this method, we find an unexpected re-entrant behaviour at very low ionic strength, where LLPS is inhibited for both proteins. TDIPS can also probe the reversibility of assemblies, which was shown for both α-synuclein and for lysozyme, relevant for health and biotechnology, respectively. Finally, we highlight how effective inhibition concentrations and partitioning of LLPS-modifying compounds can be screened highly efficiently.

Group Structure as a Foundation for Entropies.

Entropy can signify different things. For instance, heat transfer in thermodynamics or a measure of information in data analysis. Many entropies have been introduced, and it can be difficult to ascertain their respective importance and merits. Here, we consider entropy in an abstract sense, as a functional on a probability space, and we review how being able to handle the trivial case of non-interacting systems, together with the subtle requirement of extensivity, allows for a systematic classification of the functional form.

The potential of sheep in preclinical models for bone infection research - A systematic review.

Background: Reliable animal models are critical for preclinical research and should closely mimic the disease. With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical characteristics to humans. Their use in bone research is established, however their use in bone infection research is limited. This systematic review will summarise the key features of the available bone infection models using sheep, providing a reference for further development, validation, and application. Method: This systematic review was designed according to the PRISMA guidelines and registered with PROSPERO. Quality was assessed using SYRICLE's risk of bias tool adapted for animal studies. PubMed, MEDLINE, Web of Science and EMBASE were searched until March 2022.1921 articles were screened by two independent reviewers, and 25 were included for analysis. Results: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of models, typically inoculating 108 colony forming units in tibial or femoral cortical defects. Infection was established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most studies used both radiological and microbiological analyses to confirm osteomyelitis. Conclusions: There is convincing evidence supporting the use of sheep in bone infection models of clinical disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the success for translating in vivo results to successful therapies. The Translational potential of this article: In the realm of preclinical research, the translation to viable clinical therapies is often perilous, and the quest for reliable and representative animal models remains paramount. This systematic review accentuates the largely untapped potential of sheep as large animal models, especially in bone infection research. The anatomical and biomechanical parallels between sheep and human bone structures position sheep as an invaluable asset for studying osteomyelitis and periprosthetic joint infection. This comprehensive exploration of the literature demonstrates the robustness and translational promise of these models. Furthermore, this article underscores the potential applicability for sheep in developing effective therapeutic strategies for human bone infections.

Neuroborreliosis interpreted as multiple sclerosis by MRI.

Lyme neuroborreliosis (LNB) is the most prevalent nervous system bacterial infection in Denmark. In a young man with LNB, brain MRI and cerebrospinal fluid (CSF) demonstrated findings compatible with multiple sclerosis. This case report underlines the requirement for testing for intrathecal Borrelia antibody production when the number of cells in the CSF is low or even normal. It also demonstrates the unchanged diagnostic delay of NBL observed during the last 20 years.

Calling Structural Variants with Confidence from Short-Read Data in Wild Bird Populations.

Comprehensive characterization of structural variation in natural populations has only become feasible in the last decade. To investigate the population genomic nature of structural variation, reproducible and high-confidence structural variation callsets are first required. We created a population-scale reference of the genome-wide landscape of structural variation across 33 Nordic house sparrows (Passer domesticus). To produce a consensus callset across all samples using short-read data, we compare heuristic-based quality filtering and visual curation (Samplot/PlotCritic and Samplot-ML) approaches. We demonstrate that curation of structural variants is important for reducing putative false positives and that the time invested in this step outweighs the potential costs of analyzing short-read-discovered structural variation data sets that include many potential false positives. We find that even a lenient manual curation strategy (e.g. applied by a single curator) can reduce the proportion of putative false positives by up to 80%, thus enriching the proportion of high-confidence variants. Crucially, in applying a lenient manual curation strategy with a single curator, nearly all (>99%) variants rejected as putative false positives were also classified as such by a more stringent curation strategy using three additional curators. Furthermore, variants rejected by manual curation failed to reflect the expected population structure from SNPs, whereas variants passing curation did. Combining heuristic-based quality filtering with rapid manual curation of structural variants in short-read data can therefore become a time- and cost-effective first step for functional and population genomic studies requiring high-confidence structural variation callsets.

Multigenerational Fitness Effects of Natural Immigration Indicate Strong Heterosis and Epistatic Breakdown in a Wild Bird Population.

AbstractThe fitness of immigrants and their descendants produced within recipient populations fundamentally underpins the genetic and population dynamic consequences of immigration. Immigrants can in principle induce contrasting genetic effects on fitness across generations, reflecting multifaceted additive, dominance, and epistatic effects. Yet full multigenerational and sex-specific fitness effects of regular immigration have not been quantified within naturally structured systems, precluding inference on underlying genetic architectures and population outcomes. We used four decades of song sparrow (Melospiza melodia) life history and pedigree data to quantify fitness of natural immigrants, natives, and their F1, F2, and backcross descendants and test for evidence of nonadditive genetic effects. Values of key fitness components (including adult lifetime reproductive success and zygote survival) of F1 offspring of immigrant-native matings substantially exceeded their parent mean, indicating strong heterosis. Meanwhile, F2 offspring of F1-F1 matings had notably low values, indicating surprisingly strong epistatic breakdown. Furthermore, magnitudes of effects varied among fitness components and differed between female and male descendants. These results demonstrate that strong nonadditive genetic effects on fitness can arise within weakly structured and fragmented populations experiencing frequent natural immigration. Such effects will substantially affect the net degree of effective gene flow and resulting local genetic introgression and adaptation.

Clinicopathologic evaluation of congenital idiopathic megaesophagus in a Gordon Setter puppy: a case report and development and application of peripherin immunohistochemistry for detection of ganglion cells.

We examined a case of congenital idiopathic megaesophagus (CIM) in a 5-wk-old female Gordon Setter puppy by means of contrast radiography, autopsy, histopathology, and immunohistochemistry. Clinical and radiologic findings included weight stagnation and marked generalized esophageal dilation with ventral displacement of the heart and lungs. These findings were confirmed at autopsy, and segments of the thoracic esophagus were sampled for histopathology. On histopathology, diffuse esophageal muscular atrophy, mucosal erosions, mononuclear inflammation, and a marked reduction in the number of myenteric plexus structures and number of ganglion cells were present (aganglionosis). The latter was determined immunohistochemically using an anti-peripherin antibody as the primary reagent, which provides a strong tool for the histologic confirmation of CIM. The histologic findings share some similarities to lesions associated with megaesophagus in Friesian foals, as well as esophageal achalasia and Hirschsprung disease in humans.

The genetic basis of dispersal in a vertebrate metapopulation.

Dispersal affects evolutionary processes by changing population size and genetic composition, influencing the viability and persistence of populations. Investigating which mechanisms underlie variation in dispersal phenotypes and whether populations harbour adaptive potential for dispersal is crucial to understanding the eco-evolutionary dynamics of this important trait. Here, we investigate the genetic architecture of dispersal among successfully recruited individuals in an insular metapopulation of house sparrows. We use an extensive long-term individual-based ecological data set and high-density single-nucleotide polymorphism (SNP) genotypes for over 2500 individuals. We conducted a genome-wide association study (GWAS), and found a relationship between dispersal probability and a SNP located near genes known to regulate circadian rhythm, glycogenesis and exercise performance, among other functions. However, this SNP only explained 3.8% of variance, suggesting that dispersal is a polygenic trait. We then used an animal model to estimate heritable genetic variation (σA 2 ), which composes 10% of the total variation in dispersal probability. Finally, we investigated differences in σA 2 across populations occupying ecologically relevant habitat types (farm vs. non-farm) using a genetic groups animal model. We found different adaptive potentials across habitats, with higher mean breeding value, σA 2 , and heritability for the habitat presenting lower dispersal rates, suggesting also different roles of environmental variation. Our results suggest a complex genetic architecture of dispersal and demonstrate that adaptive potential may be environment dependent in key eco-evolutionary traits. The eco-evolutionary implications of such environment dependence and consequent spatial variation are likely to become ever more important with the increased fragmentation and loss of suitable habitats for many natural populations.

Patient Preferences in the Treatment of Moderate-to-severe Atopic Dermatitis.

Atopic dermatitis is a chronic, inflammatory skin disease. A variety of systemic treatments are available for patients with moderate-to-severe atopic dermatitis. The efficacy, safety and administration profile of these treatments vary, and determining the optimal treatment strategy may require weighing the benefits and drawbacks of therapies with diverse characteristics. This study used an online discrete choice experiment survey to investigate treatment preferences among adults with atopic dermatitis from Denmark, France, the UK, or Canada. Participants were identified through existing online panels. The survey included questions regarding different treatment attributes, defined based on currently approved treatments for moderate to severe atopic dermatitis. Treatment preferences were measured as the relative importance of different treatment attributes. A total of 713 respondents met the inclusion criteria and completed the survey. The discrete choice experiment identified a significant preference for avoiding the risk of severe adverse events, and for oral pill every day compared with biweekly injections. The time to full effect was not rated as being important. These findings suggest that patients with moderate-to-severe atopic dermatitis prioritize safety as most important, followed by ease of administration in their treatment preferences, while time to full effect and monitoring requirements were the least important attributes.

Performance Measures and Plasma Biomarker Levels in Patients with Multiple Sclerosis after 14 Days of Fampridine Treatment: An Explorative Study.

Peripheral cytokine levels may serve as biomarkers for treatment response and disease monitoring in patients with multiple sclerosis (pwMS). The objectives were to assess changes in plasma biomarkers in PwMS after 14 days of fampridine treatment and to explore correlations between changes in performance measures and plasma biomarkers. We included 27 PwMS, 14 women and 13 men, aged 52.0 ± 11.6 years, with a disease duration of 17 ± 8.5 years, and an Expanded Disability Status Scale of 6 [IQR 5.0/6.5]. Gait and hand function were assessed using performance tests completed prior to fampridine and after 14 days of treatment. Venous blood was obtained, and chemiluminescence analysis conducted to assess plasma cytokines and neurodegenerative markers. All performance measures demonstrated improvements. Biomarkers showed decreased tumor necrosis factor (TNF) receptor-2 levels. Associations were found between change scores in (i) Six Spot Step Test and Interleukin (IL)-2, IL-8, and IL-17 levels; (ii) timed 25-foot walk and interferon-γ, IL-2, IL-8, TNF-α, and neurofilament light levels, and (iii) 12-Item Multiple Sclerosis Walking Scale and IL-17 levels. The associations may reflect increased MS-related inflammatory activity rather than a fampridine-induced response or that a higher level of inflammation induces a better response to fampridine.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Pathological Diagnosis of Pulmonary Aspergillosis.

Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of Aspergillus. The broad spectrum of pathological manifestations associated with pulmonary aspergillosis necessitates a differentiation of commensalism from saprophytic colonization, hypersensitivity reactions, and true invasive infections, which highlights the importance of histopathology as a gold standard in a diagnostic setting. For the past decades, changes in terminology and contradicting contributions from different diagnostic disciplines have made the classification of pulmonary aspergillosis rather confusing. This review offers a categorization of aspergillosis lesions based on what can be histopathologically identified and distinguished, differentiating between acute invasive infection and forms of subacute, chronic, and allergic diseases and coinfections, and summarizes important manifestations of lesions associated with the different forms of pulmonary aspergillosis.