Experimental infection of pigs and ferrets with "pre-pandemic," human-adapted, and swine-adapted variants of the H1N1pdm09 influenza A virus reveals significant differences in viral dynamics and pathological manifestations.

Influenza A viruses are RNA viruses that cause epidemics in humans and are enzootic in the pig population globally. In 2009, pig-to-human transmission of a reassortant H1N1 virus (H1N1pdm09) caused the first influenza pandemic of the 21st century. This study investigated the infection dynamics, pathogenesis, and lesions in pigs and ferrets inoculated with natural isolates of swine-adapted, human-adapted, and "pre-pandemic" H1N1pdm09 viruses. Additionally, the direct-contact and aerosol transmission properties of the three H1N1pdm09 isolates were assessed in ferrets. In pigs, inoculated ferrets, and ferrets infected by direct contact with inoculated ferrets, the pre-pandemic H1N1pdm09 virus induced an intermediary viral load, caused the most severe lesions, and had the highest clinical impact. The swine-adapted H1N1pdm09 virus induced the highest viral load, caused intermediary lesions, and had the least clinical impact in pigs. The human-adapted H1N1pdm09 virus induced the highest viral load, caused the mildest lesions, and had the least clinical impact in ferrets infected by direct contact. The discrepancy between viral load and clinical impact presumably reflects the importance of viral host adaptation. Interestingly, the swine-adapted H1N1pdm09 virus was transmitted by aerosols to two-thirds of the ferrets. Further work is needed to assess the risk of human-to-human aerosol transmission of swine-adapted H1N1pdm09 viruses.

Avian and Human Influenza A Virus Receptors in Bovine Mammary Gland.

An outbreak of influenza A (H5N1) virus was detected in dairy cows in the United States. We detected influenza A virus sialic acid -α2,3/α2,6-galactose host receptors in bovine mammary glands by lectin histochemistry. Our results provide a rationale for the high levels of H5N1 virus in milk from infected cows.

Increased preload and echocardiographic assessment of diastolic function.

AIMS: Echocardiographic diastolic parameters are used to diagnose and monitor increased left ventricular filling pressure (LVFP) and we hypothesized that increased loading conditions cause increased E/e'. Our aim was to assess the effect of preload augmentation on diastolic parameters among both healthy subjects and subjects with known cardiac disease. METHODS AND RESULTS: We included 129 subjects merged from two cohorts; one dialysis cohort (n = 47) and one infusion cohort (n = 82). Echocardiography was performed immediately before and after hemodialysis (HD) or saline infusion, under low and high loading conditions. Elevated LVFP was defined as septal E/e' ≥ 15 and/or lateral E/e' ≥ 13 at high-loading conditions. The population was divided according to elevated LVFP (n = 31) and normal LVFP (n = 98). The load difference for the population was 972 ± 460 mL, with no differences in load difference between elevated and normal LVFP (p NS). The subjects with elevated LVFP were older (63 ± 11 vs. 46 ± 16 years, p < .001), and had lower LV ejection fraction (50 ± 14 vs. 59 ± 8.1%, p < .01). After augmented preload, EDV increased in the normal LVFP group (p < .01) but remained unchanged in the elevated LVFP group (p NS). Both E and e' increased among the subjects with normal LVFP, whereas E/e' remained unchanged (∆E/e' +.1 [-.5-1.2]), p NS). Among the subjects with elevated, LVFP we observed increased E but not e', resulting in significantly increased E/e' (∆ average E/e' +2.4 [0-4.0], p < .01). CONCLUSION: Augmented preload does not seem to affect E/e' among subjects with normal LVFP, whereas E/e' seems to increase significantly among subjects with elevated LVFP.

Right Ventricular and Pulmonary Vascular Function are Influenced by Age and Volume Expansion in Healthy Humans.

BACKGROUND: Patients with heart failure (HF) often show signs of right ventricular (RV) dysfunction. The RV function of coupled with the pulmonary circulation (tricuspid annular plane systolic excursion [TAPSE]/pulmonary arterial systolic pressure [PASP]) has been shown to divide HF patients into distinct prognostic strata, but less is known about which factors influence this prognostic marker, and whether those factors can be modified. We sought to obtain normative values and discern the individual effects of age, sex, and fluid overload on RV function. METHODS AND RESULTS: Sixty healthy subjects aged 20-80 years were enrolled in this prospective study. Right heart catheterization with hemodynamic measurements were performed at rest after a rapid saline solution infusion (10 mL/kg, 150 mL/min). Linear regression and Spearman correlation models were used to estimate associations between TAPSE/PASP and relevant variables. In healthy persons of all ages, the median (5th-95th percentiles) normative TASPE-PASP ratio was 1.25 (0.81-1.78) mm/mm Hg. The correlation between progressive age and declining TAPSE/PASP was significant (r = -0.35; P = .006). Sex did not influence TAPSE/PASP (P = .30). Rapid fluid expansion increased central venous pressure from 5 ± 2 mm Hg to 11 ± 4 mm Hg after fluid infusion (P < .0001). This resulted in a 32% decrease in the TAPSE-PASP ratio after fluid infusion, compared to baseline (P < .0001). CONCLUSIONS: The TAPSE-PASP ratio was affected by age, but not sex. TAPSE/PASP is not only a reflection of intrinsic RV function and pulmonary vascular coupling, but fluid status also dynamically affects this index of RV function. Normative values with invasive measurements were obtained for future assessment of HF patients.

Longitudinal field studies reveal early infection and persistence of influenza A virus in piglets despite the presence of maternally derived antibodies.

A longitudinal study was performed in three Danish farrow to grower (30 kilos) herds over a 4-month period to investigate the dynamics and clinical impacts of influenza A virus (IAV) infections. In each herd, four batches consisting of four sows each with five ear-tagged piglets were included. Nasal swabs and/or blood were sampled from the sows and/or the piglets prior to farrowing and at weeks 1, 3, and 5 and at the end of the nursery period. Clinical examinations were performed at each sampling time. The sows and piglets were tested for IAV and IAV antibodies in nasal swabs and blood samples, respectively. The results revealed three enzootically infected herds, where the majority of the pigs were infected during the first 5 weeks after birth. Infected piglets of only 3 days of age were detected in the farrowing unit, where the sows were also shedding virus. In all herds, low to moderate numbers of infected pigs (ranging from 3.6 to 20.7%) were found to be virus positive in nasal swabs at two consecutive sampling times. Furthermore, clinical signs of respiratory disease were associated with IAV detection. The findings of this study documented that IAV can persist in herds and that piglets as young as 3 days can be infected despite the presence of maternally derived antibodies.

Antimicrobial prescription data in Danish national database validated against treatment records in organic pig farms and analysed for associations with lesions found at slaughter.

BACKGROUND: Antimicrobial use (AMU) in livestock is a debated topic, mainly due to the risk of associated development of antimicrobial resistance. There is focus on reducing AMU in the Danish pig production, which accounts for the largest proportion of AMU for animals in Denmark. Due to special restriction on AMU in organic pig production, the AMU in organic pig production is lower than in conventional pig production. There is concern that reduced AMU could jeopardize animal health and welfare, if it reflects insufficient treatment of sick animals, which might be reflected by the prevalence and types of lesions found at meat inspection. However, little is known about the associations between AMU and meat inspection findings in pigs from organic farms. Furthermore, excess amount of antimicrobial product after a treatment cannot be re-prescribed in organic pig herds. The initial prescription is recorded in the national database VetStat, but the unused amount is not deducted leading to uncertainty when reporting AMU. The objectives of this study were to 1) describe AMU patterns based on prescription data for organic pig production and compare with those of the conventional pig production for year 2016, 2) study the associations between herd-level AMU prescription data and meat inspection data for organic pig herds and 3) validate herd-level AMU prescription data in VetStat against treatment records collected on-farm in organic Danish pig herds. RESULTS AND CONCLUSIONS: Gastrointestinal indications account for the largest proportion of AMU in both organic pig herds (65 and 54% of treatment doses for weaners and finishers, respectively) and conventional pig herds (80 and 68% of doses for weaners and finishers, respectively). A larger proportion is prescribed for respiratory indications in organic than conventional weaners and arthropathic indications in finishers. No associations between AMU and meat inspection data were found. This needs further investigation as the prevalence of lesions at slaughter was slightly (non-significantly) higher in herds with no registered AMU than with AMU prescriptions. Only 8 out of 31 herds had recorded their AMU sufficiently detailed to compare, and using VetStat as a proxy for AMU led to 9-88% overestimation of the actual use in 7 out of these 8 herds and 120% underestimation in one herd.

Global longitudinal strain before cardiac surgery: Improving feasibility, reproducibility, and variability.

BACKGROUND: Global longitudinal strain (GLS) is a predictor of outcome after cardiac surgery. If integrated into clinical decision-making and timing of surgery, it is important to evaluate the feasibility, reproducibility, and variation of GLS in this selection of patients, where poor image quality and nontraceable segments are frequent. METHODS AND RESULTS: Two-dimensional strain analysis was performed on 250 patients planned to undergo open-heart surgery. Intra- and inter-examiner retest variability was assessed in 50 consecutive patients. All myocardial segments were traceable in 119 patients, and GLS of those served as a reference in comparison with alternative strain models with nontraceable segments. Global longitudinal strain estimation by the recommended method of a maximum of one nontraceable segment per view was only feasible in 64% of cases (mean GLS -16%). Reproducibility was moderate (intra-observer coefficient of variation [CV] 8%; inter-observer CV 10%) and variation of GLS showed bias ± 95% limits of agreement (LOA) of 0.6 ± 1.1 (P < .05). Accepting three nontraceable segments in total increased feasibility to 77% with similar reproducibility (intra-observer CV 8%; inter-observer CV 11%) and variation (bias ± LOA: 0.6 ± 1.3, P < .05). A model with a maximum of one apical, one mid, and one basal nontraceable segment increased feasibility to 72% with similar reproducibility (intra-observer CV 8%; inter-observer CV 10%) and variation (bias ± LOA: 0.4 ± 1.2, P < .05). CONCLUSION: Global longitudinal strain estimation in patients prior to cardiac surgery is challenged by moderate feasibility, retest variation as well as variation in cases of nontraceable segments. We suggest alternative strain models with improved feasibility without compromising reproducibility and variation.

Semi-automated estimation of left ventricular ejection fraction by two-dimensional and three-dimensional echocardiography is feasible, time-efficient, and reproducible.

PURPOSE: To compare two-dimensional (2D) and three-dimensional (3D) methods to estimate left ventricular ejection fraction (LVEF) with respect to feasibility, time consumption, and retest reproducibility. METHODS: A total of 100 patients planned to undergo coronary artery bypass grafting and/or aortic valve replacement were included consecutively. 2D and 3D echocardiography was performed on all patients. Acquisition and analysis time as well as intra- and inter-examiner variability were assessed in 50 consecutive patients with 3 repeated echocardiographic examinations and analyses. LVEF was estimated by five different methods: uniplane, biplane, and single-beat triplane (SB3P), as well as semi-automated biplane (AutoEF) and 3D volumetric tracings (4D Auto LVQ). All methods were compared to Simpson's biplane method and feasibility was determined. RESULTS: Feasibility of Simpson's uniplane method, Simpson's biplane method, AutoEF, SB3P, and 4D Auto LVQ was 97%, 92%, 86%, 70%, and 89%, respectively. All methods evaluated were 18%-33% faster (P < 0.001) than Simpson's biplane method (115 seconds, standard deviation 15 seconds). Compared to Simpson's biplane method mean LVEF was slightly underestimated by 4D Auto LVQ (-2 ± 8%, P = 0.02), but not significantly different when assessed by the other methods. AutoEF and 4D Auto LVQ showed the lowest test variability (intra-examiner coefficient of variation (CV) 10%-11%; inter-examiner CV 10%-12% vs intra-examiner CV 12%-18%; inter-examiner CV 12%-20%). CONCLUSIONS: Estimation of LVEF by modern semi-automated 2D and 3D echocardiographic modalities is feasible, time-efficient, and reproducible.

Spatial analysis and temporal trends of porcine reproductive and respiratory syndrome in Denmark from 2007 to 2010 based on laboratory submission data.

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) has been a cause for great concern to the Danish pig industry since it was first diagnosed in 1992. The causative agent of PRRS is an RNA virus which is divided into different genotypes. The clinical signs, as well as its morbidity and mortality, is highly variable between herds and regions. Two different genotypes of PRRS virus (PRRSV) are found in Denmark: type 1 and type 2. Approximately 40% of Danish swine herds are seropositive for one or both PRRSV types. The objective of this study was to describe the temporal trend and spatial distribution of PRRSV in Danish swine herds from 2007 to 2010, based on type-specific serological tests from the PRRS surveillance and control program in Denmark using the results stored in the information management system at the National Veterinary Institute, Technical University of Denmark (DTU Vet). RESULTS: The average monthly seroprevalence of PRRSV type 1 was 9% (minimum of 5%; maximum of 13%) in breeding herds, and 20% (minimum of 14%; maximum of 26%) in production herds; PRRSV type 2 had an average seroprevalence of 3% (minimum of 1%; maximum of 9%) in breeding herds and of 9% (minimum of 5%; maximum of 13%) within production herds. The seroconversion rate followed a similar and consistent pattern, being higher for type 1 than for type 2 for both PRRSV types. Regarding the spatiotemporal results, the relative risk distribution maps changed over time as a consequence of the changes in PRRSV seroprevalence, suggesting a general decline in the extent of areas with higher relative risk for both type 1 and 2. Local spatial analysis results demonstrated the existence of statistically significant clusters in areas where the relative risk was higher for both herds. CONCLUSIONS: PRRSV type 1 seroprevalence was constantly higher than for PRRSV type 2 in both herd types. Significant spatial clusters were consistently found in Denmark, suggesting that PRRSV is endemic in these areas. Furthermore, relative risk distribution maps revealed different patterns over time as a consequence of the changes in seroprevalence.

The avian influenza A virus receptor SA-α2,3-Gal is expressed in the porcine nasal mucosa sustaining the pig as a mixing vessel for new influenza viruses.

Influenza A viruses (IAVs) originate from wild birds but have on several occasions jumped host barriers and are now also circulating in humans and mammals. The IAV host receptors (glycans with galactose linked to a sialic acid (SA) in an α2,3 or α2,6 linkage) are crucial host factors restricting inter-species transmission. In general, avian-origin IAVs show a preference for SA-α2,3 (avian receptor), whereas IAVs isolated from humans and pigs prefer SA-α2,6 (human receptor). N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two major SAs. Neu5Ac is expressed in all species, whereas Neu5Gc is only expressed in a limited number of domestic species such as pigs and horses, but not in humans. Despite that previous studies have shown that the IAV host receptor distribution appears to be similar in pigs and humans, none of these studies have investigated the expression of Neu5Gc-α2,6 in situ in porcine tissues. Thus, the aim of this study was to elucidate the distribution of IAV host receptors expressed in the porcine respiratory tract and relate the expression to the viral tropism of diverse host-adapted IAVs. The IAV receptor (SA-α2,3 and SA-α2,6) distribution and the presence of specifically Neu5Gc-α2,6 in the porcine nasal, tracheal, and lung tissues was investigated by lectin histochemistry. Furthermore, IAV immunohistochemistry was performed on tissues from pigs experimentally infected with IAVs, either adapted to pigs or humans, to investigate the significance of the IAV host receptors and the tropism of the diverse host-adapted IAVs. We document for the first time the expression of the avian receptor on the surface of the porcine nasal mucosa and an equal expression of Neu5Ac-α2,6 and Neu5Gc-α2,6 on the surface of the tracheal epithelium and alveoli. In all IAV-infected pigs, we found a low amount of IAV-positive cells in the trachea despite a high expression of the human receptor. Cumulatively, these findings suggest that optimal IAV replication involves a complex interplay between the viruses and their host receptors and that there might be other less clearly defined host factors that determine the site of replication.

Evaluation of the 2023 Duke-ISCVID criteria for infective endocarditis in patients referred to the Lund infective endocarditis team.

BACKGROUND: The Duke criteria for diagnosing infective endocarditis (IE) were recently updated by the International Society for Cardiovascular Infectious Diseases (ISCVID) with the purpose of enhancing diagnostic specificity and sensitivity. This study investigated the performance of the Duke-ISCVID criteria in relation to previous criteria. METHOD: This retrospective single centre cohort study included patients referred to the Lund IE Team (LIET) between 2017 and 2022, and compared episodes classified according to the 2000 modified Duke, European Society of Cardiology (ESC) 2015, and 2023 Duke-ISCVID criteria. The LIET's decision to treat episodes as IE served as the reference standard. RESULTS: The study cohort comprised 661 episodes of potential IE. The LIET classified 498 (75%) episodes as IE. The Duke-ISCVID criteria classified a slightly higher proportion of episodes as definite IE (56.4%) compared to the ESC 2015 criteria (54.9%), and the modified Duke (51.1%). The Duke-ISCVID criteria had higher sensitivity (72.5%) for definite IE compared to ESC 2015 (70.7%, p = .57) and modified Duke (66.1%, p = .033). The specificities were similar for the Duke-ISCVID criteria (92.6%), compared to ESC 2015 (93.9%, p = .83) and the modified Duke criteria (95.0%, p = .49). When considering both definite and possible IE positive, specificity for all criteria was low: 32.5% for the Duke-ISCVID criteria, 41.7% for ESC 2015 (p = .086), and 42.3% for modified Duke criteria (p = .11), while the sensitivity was not significantly lower. DISCUSSION: The Duke-ISCVID criteria demonstrated slightly improved sensitivity for diagnosing IE whereas specificity remained unchanged. Further refinement of the Duke-ISCVID criteria is needed to balance sensitivity and specificity.

Umbilical outpouchings in Danish piglets and weaners: prevalence and clinical characteristics-a cross-sectional study at herd level.

BACKGROUND: Umbilical outpouchings (UO) in pigs present a welfare concern because of ulceration risk and complications. Danish legislation requires pigs with larger UOs to be housed in sick pens with soft bedding, and some UO pigs might not be suited for transport. Because of this, many UO pigs are euthanized, adding to the costs of pig production. The true prevalence of UO is unknown as no scientific reports with randomly sampled herds exist. This study aimed to estimate the prevalence of UO in Danish piglets and weaners and describe their clinical characteristics: size, texture, reducibility, and occurrence of ulcers. Lastly, risk factors for the occurrence of ulcers on UOs were investigated. RESULTS: A cross-sectional study was conducted in 30 Danish conventional herds, with at least 800 weaned pigs and 200 sows. The herds were selected randomly from the Danish Husbandry Register and visited once between September 2020 and May 2021. Piglets were examined during their last week in the farrowing unit, and weaners were examined between weeks three and eight after weaning. The abdominal area was palpated on all pigs, and all irregularities were recorded; the results presented are umbilical outpouchings measuring at least 2 × 2 cm. The within-herd prevalence of piglets with UO averaged 4.2% with a range from 0.8 to 13.6% between herds. The within-herd prevalence of weaners with UO averaged 2.9%, ranging from 1.0 to 5.3% between herds. Approximately 80% of the UOs were classified as small or medium (< 7 cm piglets/ < 11cm weaners). Large outpouchings had significantly higher odds of ulcer occurrence (OR = 9.9, p < 0.001). CONCLUSION: UOs are common in Denmark, with a prevalence of 2.9% in weaners and an estimated annual production of 32 million Danish pigs almost a million pigs are affected yearly. Most of these pigs will have a small or medium UO. If the pigs have large UOs the odds of ulcer occurrence increase significantly. Numerous of these pigs are wasted, challenging sustainability and economy. UOs might also affect the welfare of the pigs. More research is therefore needed, especially in the prevention of UOs.

Prevention of umbilical outpouchings and mortality in pigs: Meloxicam, tying, cutting, and chlorhexidine versus amoxicillin or no treatment? A clinical field trial.

BACKGROUND: Umbilical outpouchings (UOs) are common in Danish pigs. Neonatal antibiotics are therefore used with the hope of reducing umbilical infections and subsequently UOs. However, the effect of neonatal antibiotics on preventing UO has been the subject of mixed conclusions, and secondly, treating all animals with antibiotics might exacerbate the development of antimicrobial resistance. This study analysed the effects of different treatments on the prevalence of umbilical outpouchings and mortality from birth to nursery unit. All treatment was on the day of birth. The groups were: a negative control group, an antibiotic group receiving amoxicillin, and an experimental group where the piglets had their umbilical cord disinfected with chlorhexidine, followed by tying and clipping, and lastly, injection with meloxicam. The pigs were examined six weeks after weaning, and all pigs that died during the study were autopsied. RESULTS: There were 5494 pigs divided across the three groups. There were no statistically significant differences in UO prevalence between the groups: control 3.9%, antibiotic 4.2%, and experimental 4.0% (p = 0.87). The only variable affecting the prevalence of UOs in this study was sex with females being at higher risk. There were no statistically significant differences in mortality between the groups from birth until departure from the nursery unit: control 22.9%, antibiotic 21%, and experimental 21.4% (p = 0.33). The variables affecting mortality were sex, intrauterine growth restriction (IUGR), birth weight, and cross fostering. Males had higher odds of dying, as had piglets recorded with some degree of IUGR. Also, low birth weight increased the odds of dying for all weight quartiles compared to the fourth (the heaviest piglets > 1.6 kg), as well as cross fostering increased the odds ratio of dying. CONCLUSIONS: This study found no significant differences in the prevalence of UOs and mortality following different treatments at birth. The study showed that the prevalence of UO and mortality was not reduced following the administration of amoxicillin or meloxicam in combination with disinfection and tying of the umbilical cord.

Sex-and age-related variations in myocardial tissue composition of the healthy heart: a native T1 mapping cohort study.

AIMS: Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. METHODS AND RESULTS: CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8---84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24-68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000 ± 22 ms in males and 1022 ± 23 ms in females [mean difference (MD) = 22 ms, 95% confidence interval (CI) (17, 27)]. Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 [ß=10 ms, 95% CI (3.4, 15.8)]. There was no significant interaction between sex and age (P = 0.27). Further, age was not associated with native T1 [ß=0.1 ms, 95% CI (-0.02, 0.2)], and native T1 did not change during a 1-year period [MD -4 ms, 95% CI (-11, 3)]. CONCLUSION: Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition.

Multi-omics analysis reveals the impact of influenza a virus host adaptation on immune signatures in pig tracheal tissue.

Introduction: Influenza A virus (IAV) infection is a global respiratory disease, which annually leads to 3-5 million cases of severe illness, resulting in 290,000-650,000 deaths. Additionally, during the past century, four global IAV pandemics have claimed millions of human lives. The epithelial lining of the trachea plays a vital role during IAV infection, both as point of viral entry and replication as well as in the antiviral immune response. Tracheal tissue is generally inaccessible from human patients, which makes animal models crucial for the study of the tracheal host immune response. Method: In this study, pigs were inoculated with swine- or human-adapted H1N1 IAV to gain insight into how host adaptation of IAV shapes the innate immune response during infection. In-depth multi-omics analysis (global proteomics and RNA sequencing) of the host response in upper and lower tracheal tissue was conducted, and results were validated by microfluidic qPCR. Additionally, a subset of samples was selected for histopathological examination. Results: A classical innate antiviral immune response was induced in both upper and lower trachea after infection with either swine- or human-adapted IAV with upregulation of genes and higher abundance of proteins associated with viral infection and recognition, accompanied by a significant induction of interferon stimulated genes with corresponding higher proteins concentrations. Infection with the swine-adapted virus induced a much stronger immune response compared to infection with a human-adapted IAV strain in the lower trachea, which could be a consequence of a higher viral load and a higher degree of inflammation. Discussion: Central components of the JAK-STAT pathway, apoptosis, pyrimidine metabolism, and the cytoskeleton were significantly altered depending on infection with swine- or human-adapted virus and might be relevant mechanisms in relation to antiviral immunity against putative zoonotic IAV. Based on our findings, we hypothesize that during host adaptation, IAV evolve to modulate important host cell elements to favor viral infectivity and replication.

Bacillus subtilis-597 induces changes in lung pathology and inflammation during influenza A virus infection in pigs.

In recent years, it has become apparent that imbalances in the gastrointestinal system can impact organs beyond the intestine such as the lungs. Given the established ability of probiotics to modulate the immune system by interacting with gastrointestinal cells, our research aimed to investigate whether administering the probiotic strain Bacillus subtilis-597 could mitigate the outcome of influenza virus infection in pigs. Pigs were fed a diet either with or without the probiotic strain B. subtilis-597 for 14 days before being intranasally inoculated with a swine influenza A H1N2 strain (1 C.2 lineage). Throughout the study, we collected fecal samples, blood samples, and nasal swabs to examine viral shedding and immune gene expression. After seven days of infection, the pigs were euthanized, and lung and ileum tissues were collected for gene expression analysis and pathological examination. Our findings indicate that the administration of B. subtilis-597 exhibit potential in reducing lung lesions, possibly attributable to a general suppression of the immune system as indicated by reduced C-reactive protein (CRP) levels in serum, decreased expression of interferon-stimulated genes (ISGs), and localized reduction of the inflammatory marker serum amyloid A (SAA) in ileum tissue. Notably, the immune-modulatory effects of B. subtilis-597 appeared to be unrelated to the gastrointestinal microbiota, as the composition remained unaltered by both the influenza infection and the administration of B. subtilis-597.

The Influence of Food Intake and Preload Augmentation on Cardiac Functional Parameters: A Study Using Both Cardiac Magnetic Resonance and Echocardiography.

(1) Background: To investigate how food intake and preload augmentation affect the cardiac output (CO) and volumes of the left ventricle (LV) and right ventricle (RV) assessed using cardiac magnetic resonance (CMR) and trans-thoracic echocardiography (TTE). (2) Methods: Eighty-two subjects with (n = 40) and without (n = 42) cardiac disease were assessed using both CMR and TTE immediately before and after a fast infusion of 2 L isotonic saline. Half of the population had a meal during saline infusion (food/fluid), and the other half were kept fasting (fasting/fluid). We analyzed end-diastolic (EDV) and end-systolic (ESV) volumes and feature tracking (FT) using CMR, LV global longitudinal strain (GLS), and RV longitudinal strain (LS) using TTE. (3) Results: CO assessed using CMR increased significantly in both groups, and the increase was significantly higher in the food/fluid group: LV-CO (ΔLV-CO: +2.6 ± 1.3 vs. +0.7 ± 1.0 p < 0.001), followed by increased heart rate (HR) (ΔHR: +12 ± 8 vs. +1 ± 6 p < 0.001). LV and RV achieved increased stroke volume (SV) through different mechanisms. For the LV, through increased contractility, increased LV-EDV, decreased LV-ESV, increased LV-FT, and GLS were observed. For the RV, increased volumes, increased RV-EDV, increased RV-ESV, and at least for the fasting/fluid group, unchanged RV-FT and RV-LS were reported. (4) Conclusions: Preload augmentation and food intake have a significant impact on hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake of fluid and food before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.

Atrial fibrillation in aortic stenosis--echocardiographic assessment and prognostic importance.

BACKGROUND: Atrial fibrillation (AFib) exists more frequently in patients with aortic stenosis (AS) than in patients without, and AFib may be a sign of progressive deterioration of AS. Echocardiographic assessment of AS in sinus rhythm is well documented, however, little is known about AFib in AS since such patients often are excluded from clinical echocardiographic trials. AIM: The purpose of this study was to assess the prognostic importance of AFib in AS. METHODS: The study was designed as a single-center case-control study. Patients with AS and AFib were enrolled as cases (n = 103) and subsequently matched to controls (103 patients with AS but sinus rhythm). Cases and controls were matched according to age, gender and severity of AS. Primary outcome was all cause mortality and follow-up was 100% complete. RESULTS: Compared to controls the group with AFib had lower mean ejection fraction (42% vs. 49%; p < 0.001) and stroke volume (47 mL vs. 55 mL; p = 0.004), but higher heart rate (81 bpm vs. 68 bpm; p < 0.001) and no significant difference with regard to cardiac output (3.8 L vs. 4.0 L; p = 0.29). Accordingly, aortic jet velocity and gradients were significantly lower in AFib compared to controls but there were no differences (p = 0.38) in aortic valve area calculated by the continuity equation. During a median follow-up of 2.3 years (IQR: 1.2-3.6), 70 (34%) patients with AS died: 42 patients with AFib and 28 patients with sinus rhythm (p < 0.02). After adjusting for echocardiographic significant differences, AFib remained an independent predictor of mortality (HR 2.72 (95% CI: 1.12-6.61), p < 0.03). There was no significant interaction (p = 0.62) between AFib and AS on the risk of mortality, indicating that AFib predicted bad outcome regardless of the severity of AS. CONCLUSIONS: AFib is an independent risk factor in patients with AS and the prognostic impact of AFib seems to be the same despite the severity of AS.

Non-specific effects of maternal and offspring rabies vaccination on mortality and antibiotic use in a Danish pig herd: A randomized trial.

INTRODUCTION: Human non-live vaccines have been associated with detrimental non-specific effects (NSE), particularly in females. A large trial found 2-fold increased overall mortality in girls receiving a new malaria vaccine compared to the rabies vaccine used as a coontrol; a beneficial NSE of the rabies vaccine was proposed. Conversely, in dogs increased mortality was seen in females but not males following rabies vaccination of puppies born to immunized mothers. We investigated NSE of non-live rabies vaccine in piglets and the potential modifying effect of maternal priming with rabies vaccine. METHODS: In a Danish herd of commercial rabies virus-free pigs, 575 pregnant sows (2-3 weeks before scheduled farrowing) and 5747 of their offspring (median 6-day-old) were allocated (1:1) to non-live rabies vaccine (Versiguard rabies vet) or no rabies vaccine. Outcomes were overall mortality and antibiotic treatment until departure from the nursery (approximately age 12 weeks/30 kgs). RESULTS: Until weaning, overall offspring mortality was 2.2% (127 piglets died, rabies vaccine: n = 69; control: n = 58), the proportion ratio (PR) being 1.19 (95% confidence interval: 0.84-1.68). Until end of follow-up, mortality was 4.1% (233, rabies vaccine: n = 115; control = 118, PR: 0.97 (0.76-1.25)). Prior sow rabies vaccination did not affect piglet mortality. For mortality as well as risk of antibiotic treatment before weaning, there was indication of a beneficial effect of rabies vaccine in female piglets, but a negative effect in (castrated) male piglets from rabies-naïve sows. Prior sow vaccination significantly modified the vaccine effect estimate in female piglets toward a detrimental effect of rabies vaccine on treatment risk. These effects had waned by 12 weeks of age. CONCLUSION: The study did not support the hypothesized beneficial NSE of rabies vaccine. Although under-powered for subgroup analyses, the study indicated effect modification by sex and maternal vaccination. Results could be different in a herd with higher mortality and infectious burden.

A new method to quantify left ventricular mass by 2D echocardiography.

Increased left ventricular mass (LVM) is a strong independent predictor for adverse cardiovascular events, but conventional echocardiographic methods are limited by poor reproducibility and accuracy. We developed a novel method based on adding the mean wall thickness from the parasternal short axis view, to the left ventricular end-diastolic volume acquired using the biplane model of discs. The participants (n = 85) had various left ventricular geometries and were assessed using echocardiography followed immediately by cardiac magnetic resonance, as reference. We compared our novel two-dimensional (2D) method to various conventional one-dimensional (1D) and other 2D methods as well as the three-dimensional (3D) method. Our novel method had better reproducibility in intra-examiner [coefficients of variation (CV) 9% vs. 11-14%] and inter-examiner analysis (CV 9% vs. 10-20%). Accuracy was similar to the 3D method (mean difference ± 95% limits of agreement, CV): Novel: 2 ± 50 g, 15% vs. 3D: 2 ± 51 g, 16%; and better than the "linear" 1D method by Devereux (7 ± 76 g, 23%). Our novel method is simple, has considerable better reproducibility and accuracy than conventional "linear" 1D methods, and similar accuracy as the 3D-method. As the biplane model forms part of the standard echocardiographic protocol, it does not require specific training and provides a supplement to the modern echocardiographic report.