Evaluation of five circulating strains of variant infectious bursal disease virus (varIBDV) for their immunogenicity as broiler breeder vaccines and protective efficacy in neonatal broiler chicks

The majority of infectious bursal disease virus (IBDV) strains circulating in the broiler chicken industry in Canada are variant strains (varIBDV). Despite high levels of maternally derived antibodies (MtAb), the circulating varIBDVs can establish infection and cause severe immunosuppression in broiler chicks. The objective of this study was to evaluate circulating varIBDVs as broiler breeder vaccine candidates and investigate their protective efficacy against varIBDV challenge in their progeny chicks. Six groups of breeders (20 females/group) were vaccinated with varIBDV strains, SK09, SK10, SK11, SK12, and SK13 or saline at the age of 13 weeks and antibody response was determined by ELISA at 3–7-, and 20- weeks post-vaccination. We also included commercial chicks for the comparison. Results showed that SK-09 is the most antigenic strain, followed by SK-10, SK-12, and SK-13. In contrast, SK-11 showed the lowest antibody response, and over time, antibody titers steadily decreased. Eggs from breeders were collected at 21-week post-vaccination and incubated to produce their respective progenies. The serum antibody titer in day-old chicks showed a successful MtAb transfer. Progeny chicks (n = 40/group) were orally challenged with varIBDV-SK-09 strain at 6 days of age and serum antibody titer (19 d and 35 d of age), bursa to body weight ratio (19 d and 35 d of age), bursal viral load (9 d and 19 d of age) was examined to assess the protection against IBDV. Following the challenge, we found a significant increase in the antibody titers in MtAb-free and commercial vaccine groups than in the varIBDV groups, both at 19 d and 35 d of age. The BBW ratio and viral load data indicated a significant homologous and heterologous protection against varIBDV-SK-09 challenge by SK-09 and SK-10 MtAbs, respectively. Overall, this study demonstrated the feasibility of developing breeder vaccines using circulating varIBDV as candidate vaccine antigens.     

Application of computer-generated images to train pattern recognition used in semiquantitative immunohistochemistry scoring

This study aimed to clarify whether the pattern recognition involved in scoring proliferation fractions can be trained by abstract computerized images of virtual tissues. Twenty computer-generated images with randomly distributed blue or red dots were scored by 12 probands (all co-workers or collaborators of the Institute of Pathology, University of Bonn). Afterward, the probands underwent a training phase during which they received an immediate feedback on the actual rate of positivity after each image. Finally, the initial testing series was rescored. In a second round with 15 different probands, 20 Ki-67 immunohistochemistry images of tonsil tissue were scored, followed by the same training phase with computer-generated images, before the immunohistochemistry slides were scored again. Paired t-tests were used to compare the differences in mean rates pre- and post-training. Concerning computerized images, untrained probands scored the percentages of positive dots with a mean deviation from the true rates of 8.2%. Following training, the same testing series was scored significantly better with a mean deviation of 4.9% (mean improvement 3.3%, p < 0.001). Scoring real immunohistochemistry slides, the training with computerized images also improved correct estimations, albeit to a lesser degree (mean improvement 1%, p = 0.03). Abstract computerized images of virtual tissues may be a useful tool to train and improve the accuracy of pattern recognition involved in semiquantitative scoring of immunohistochemistry slides. As a side results, this study highlights the value of computer-generated images to verify the performance of image-analysis software.     

Avian mud nest architecture by self-secreted saliva

Mud nests built by swallows (Hirundinidae) and phoebes (Sayornis) are stable granular piles attached to cliffs, walls, or ceilings. Although these birds have been observed to mix saliva with incohesive mud granules, how such biopolymer solutions provide the nest with sufficient strength to support the weight of the residents as well as its own remains elusive. Here, we elucidate the mechanism of strong granular cohesion by the viscoelastic paste of bird saliva through a combination of theoretical analysis and experimental measurements in both natural and artificial nests. Our mathematical model considering the mechanics of mud nest construction allows us to explain the biological observation that all mud-nesting bird species should be lightweight.

Bird nests come in a variety of forms made from diverse building materials (1, 2). Each type of bird nest is subjected to mechanical constraints imposed by material characteristics. To overcome these constraints, birds have devised brilliant architectural technologies, which provide inspiration for a novel materials processing scheme and help us to better understand animal behavior.For instance, some birds including storks (Cicioniidae) and eagles (Accipitidae) build nests by piling up hard filamentary materials such as twigs, harnessing their friction as the cohesion mechanism (3). Weaverbirds (Ploceidae) weave soft filamentary materials such as grass and fine leaves into a woven nest tied to a tree branch. Some bird species use their own saliva in nest building, which Darwin considered an example of natural selection (4). An extreme case is the Edible-nest Swiftlets, which build their nest purely of self-secreted saliva so that it can be attached to cliff walls and cave ceilings where the above twig piles and tied leaves are not allowed (5).Swallows (Hirundinidae), phoebes (Sayornis), and other mud nesters have developed a unique building material, a mixture of mud and their own saliva, in contrast to those made of purely collected or self-secreted materials (6) (Fig. 1). During construction, mud nesters repeatedly pile a beakful of wet mud on the nest, and liquid bridges are formed in the nest due to evaporation. While building a nest usually takes several weeks, a transition from wet to dry structures can occur within a few hours. Hence, the capillary forces of liquid bridges temporarily provide cohesion such as those in sandcastles. However, unlike sandcastles, dehydrated saliva comes into play for permanent cohesion after complete evaporation (SI Appendix, Supplementary Note 1).Open in a separate windowFig. 1.A nest of the barn swallow (H. rustica). (A) Photograph of a barn swallow nest, taken from under the ceiling of a house in Suwon-si, Gyunggi-do, South Korea (37°16′13.5″N 126°59′01.0″E). (B) SEM image of the nest surface. (C) Chemical composition analysis of the surface shown in B by EDS. The red area indicates a region containing mostly carbon atoms, which may originate from bird saliva. The green area indicates a region containing mostly the silicon atoms of clay particles.Mud itself cannot confer sufficient cohesion and adhesion in mud nests. The ability of mud nests to bear tensile loads originates from the gluing agent in the bird''s saliva, which permeates into granules as a liquid and binds them as a solid after solvent evaporation (6–8) (SI Appendix, Supplementary Note 2). The gluing agent is called mucin, a family of large glycoproteins that are ubiquitous in animal organs and form a mucus gel with versatile functionality (9). Fig. 1B shows the scanning electron microscopy (SEM) image of a barn swallow’s mud nest consisting of platelet clay particles and larger grains. Energy-dispersive spectroscopy (EDS) mapping image of Fig. 1C clearly shows regions corresponding to organic material which is presumed to be from bird’s saliva.Of particular interest and worth biophysical investigation are the tensile strength of the mud nest with hardened saliva, design principles associated with the saliva-originated strength, and the resulting effects on the evolution of these mud-nesting birds. Principles behind cohesion in granular materials, such as wet sands (10), cemented powder aggregates (11), construction materials (12), and pharmaceutical tablets (13), have been studied to date, exploring the stress transmission, elasticity, and failure (14–18), and the formation of solidified bridges (19–21). However, little attention has been paid to the cohesion effects of self-secreted polymer materials upon evaporation and the biologically constructed granular architecture like birds’ mud nests. Here we devised experimental techniques to measure the strength of the relatively small and fragile nest specimens in order to mechanically characterize birds’ mud nests. We elucidate how solutes from bird saliva generate solid bridges that give rise to macroscopic tensile strength, which has long awaited physicochemical explanation since its first observation (4). To characterize the design principle of bird''s mud nests, we investigated natural and three-dimensional (3D)-printed artificial nests with various tools for visualization and mechanical testing. Along with the experimental studies, we theoretically investigated the effects of biopolymer concentration on nest strength. This combination of theory and experiment suggests that there is a size limit for mud-nesting birds, which is supported by biological data.     

Filling the gaps on stroke research: Focus on inflammation and immunity

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19.We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.     

Prognostic models for mortality after cardiac surgery in patients with infective endocarditis: a systematic review and aggregation of prediction models

BackgroundThere are several prognostic models to estimate the risk of mortality after surgery for active infective endocarditis (IE). However, these models incorporate different predictors and their performance is uncertain.ObjectiveWe systematically reviewed and critically appraised all available prediction models of postoperative mortality in patients undergoing surgery for IE, and aggregated them into a meta-model.Data sourcesWe searched Medline and EMBASE databases from inception to June 2020.Study eligibility criteriaWe included studies that developed or updated a prognostic model of postoperative mortality in patient with IE.MethodsWe assessed the risk of bias of the models using PROBAST (Prediction model Risk Of Bias ASsessment Tool) and we aggregated them into an aggregate meta-model based on stacked regressions and optimized it for a nationwide registry of IE patients. The meta-model performance was assessed using bootstrap validation methods and adjusted for optimism.ResultsWe identified 11 prognostic models for postoperative mortality. Eight models had a high risk of bias. The meta-model included weighted predictors from the remaining three models (EndoSCORE, specific ES-I and specific ES-II), which were not rated as high risk of bias and provided full model equations. Additionally, two variables (age and infectious agent) that had been modelled differently across studies, were estimated based on the nationwide registry. The performance of the meta-model was better than the original three models, with the corresponding performance measures: C-statistics 0.79 (95% CI 0.76–0.82), calibration slope 0.98 (95% CI 0.86–1.13) and calibration-in-the-large –0.05 (95% CI –0.20 to 0.11).ConclusionsThe meta-model outperformed published models and showed a robust predictive capacity for predicting the individualized risk of postoperative mortality in patients with IE.Protocol registrationPROSPERO (registration number CRD42020192602).     

Pattern of injuries due to wild animal attack among patients presenting to the emergency department: A retrospective observational study

PurposeThe human-wildlife conflicts (HWCs) causing nuisances and injuries are becoming a growing public health concern over recent years worldwide. We aimed to study the demographic profile, mode of injury, pattern of injury, and outcome of wild animal attack victims presented to the emergency department.MethodsThis retrospective cross-sectional study was conducted in the emergency department of a tertiary-care hospital in Eastern India. Data were retrieved from the medical records from May 2017 to May 2021. Patients of all ages and genders attacked by wild animals and secondary injuries were included in this study. Patients with incomplete data, injuries due to the attack of stray and domestic animals and trauma due to other causes were excluded. Demographic profile, mode of injury, the pattern of injury, injury severity score (ISS), radiological pattern, and outcome were recorded. Statistical analysis with R (version 3.6.1.) was conducted.ResultsA total of 411 wild animal attack victims were studied, of which 374 (90.9%) were snakebite injuries and 37 (9.1%) were wild mammalian (WM) attack injuries. The mean age of WM attack victims was 46 years, and the male-to-female ratio was 4:1. Elephant attack injury (40.5%) was the most common WM attack injury reported. Most WM attacks (43.2%) occurred between 4:00 a.m. to 8:00 a.m. The median ISS was 18.5 (13–28), where 54.2% of patients had polytrauma (ISS>15). Elephant attack was associated with a higher ISS, but the difference was not significant compared to other animal types (p = 0.2). Blunt trauma was common pattern of injury in the elephant attack injury cases. Lacerations and soft tissue injuries were common patterns in other animal attacks. Among snakebites, neurotoxic was the most common type (55.4%), and lower extremity was the most common site involved.ConclusionThe young male population is the major victim of HWCs; and elephant is the most common animal involved. There is a need to design scientifically sound preventive strategies for HWCs and to strengthen the preparedness in health establishments to manage victims effectively.