Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty^® (Pfizer-BioNTech) (n = 11), Vaxzevria^® (AstraZenica) (n = 2) and Janssen^® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4⁺ and CD8⁺ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4⁺ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.     

Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and local intramammary metabolism in dairy cows

Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-dl-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2 h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8 h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-dl-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased in controls and decreased also slightly in the BHBA-infused animals because the BHBA concentration could not be fully maintained despite a rapid increase in BHBA infusion rate. The change in mRNA abundance of citrate synthase in LPS quarters was significant between the 2 treatment groups. The results indicate that elevated circulating BHBA concentration inhibits gluconeogenesis before and during immune response to LPS challenge, likely because BHBA can replace glucose as an energy source.     

Viral infections and asthma

PURPOSE: The aim of this study was to classify the human IgG autoantibody repertoire of sera from patients suffering from endocrine ophthalmopathy (EOP) and healthy subjects (CTRL) for diagnostic purposes using the recently developed Megablot technique. This technique allows for the simultaneous and quantitative screening of a large set of antigens and uses multivariate statistical techniques and an artificial neural network. METHODS: Sera were tested against Western blots (WBs) of SDS-PAGE preparations of proteins from human extraorbital eye muscle (EOP: n = 16; CTRL: n = 11). Digital image analysis was performed. The blots were subsequently analyzed by multivariate statistical techniques (analysis of discriminance) and an artificial neural network (probalistic neural network). RESULTS: The sera of both the EOP and CTRL groups showed a complex staining pattern against WBs of SDS-PAGEs from human eye muscle. Using the multivariate statistical technique for classification, all of the known samples and 85% of the unknown samples (not presented during calculation) were assigned to their correct clinical group. Using the artificial neural network as classifier, all of the samples presented during training and 96.3% of the unknown samples (not trained) were assigned correctly. CONCLUSIONS: The artificial neural network exceeds the ability of multivariate statistical techniques such as analysis of discriminance to assign unknown samples to their correct predefined group. Thus, the neural network exceeds other methods in generalizing some similarities of blots used for classification. This study reveals that our new technique and its evaluation using a neural network can be used as a helpful diagnostic tool in autoimmune diseases such as endocrine ophthalmopathy.     

Time‐multiplexed tiled projection system with improved pixel and spatial resolution

We propose two methods to increase the pixel and spatial resolution of Digital Micromirror Devices (DMD)‐based projectors by utilizing the large bandwidth provided by their high pattern rates. By varying the intensity of the illumination for each binary pattern displayed on the DMD, the time required to display an 8‐bit grayscale image can be reduced by up to factor 32 compared to using constant illumination and binary pulse‐width modulation (BPWM). The high image rate projection is then spatially separated by either using a galvanometer scanner or sequentially illuminating the DMD from different directions, thus creating multiple independently addressable projections which are then tiled to form a larger, higher resolution image.     

Transport of testosterone and estrogen from dairy-farm waste lagoons to groundwater

Although concentrated animal feeding operations constantly generate physiologically active steroidal hormones, little is known of their environmental fate. Estrogen and testosterone concentrations in groundwater and their distribution in sediments below a dairy-farm wastewater lagoon were therefore determined and compared to a reference site located upgradient of the farm. Forward simulations of flow as well as estrogen and testosterone transport were conducted based on data from the sediment profile obtained during drilling of a monitoring well belowthe dairy-farm waste lagoon. Testosterone and estrogen were detected in sediments to depths of 45 and 32 m, respectively. Groundwater samples were directly impacted by the dairy farm, as evidenced by elevated concentrations of nitrate, chloride, testosterone, and estrogen as compared to the reference site. Modeling potential transport of hormones in the vadose zone via advection, dispersion, and sorption could not explain the depths at which estrogen and testosterone were found, suggesting that other transport mechanisms influence hormone transport under field conditions. These mechanisms may involve interactions between hormones and manure as well as preferential flow paths, leading to enhanced transport rates. These types of interactions should be further investigated to understand the processes regulating hormone transport in the subsurface environment and parametrized to forecast long-term fate and transport of steroidal hormones.     

Consequences of dietary energy source and energy level on energy balance,lactogenic hormones,and lactation curve characteristics of cows after a short or omitted dry period

Omitting the dry period (DP) generally reduces milk production in the subsequent lactation. The aim of this study was to evaluate the effect of dietary energy source—glucogenic (G) or lipogenic (L)—and energy level—standard (std) or low—on milk production; energy balance (EB); lactogenic hormones insulin, insulin-like growth factor 1 (IGF-1), and growth hormone (GH); and lactation curve characteristics between wk 1 and 44 postpartum in cows after a 0-d or 30-d DP. Cows (n = 110) were assigned randomly to 3 transition treatments: a 30-d DP with a standard energy level required for expected milk yield [30-d DP(std)], a 0-d DP with the same energy level as cows with a 30-d DP [0-d DP(std)], and a 0-d DP with a low energy level [0-d DP(low)]. In wk 1 to 7, cows were fed the same basal ration but the level of concentrate increased to 6.7 kg/d for cows fed the low energy level and to 8.5 kg/d for cows fed the standard energy level in wk 4. From wk 8 postpartum onward, cows received a G ration (mainly consisting of corn silage and grass silage) or an L ration (mainly consisting of grass silage and sugar beet pulp) with the same energy level contrast (low or std) as in early lactation. Cows fed the G ration had greater milk, lactose, and protein yields, lower milk fat percentage, greater dry matter and energy intakes, and greater plasma IGF-1 concentration compared with cows fed the L ration. Dietary energy source did not affect EB or lactation curve characteristics. In cows with a 0-d DP, the reduced energy level decreased energy intake, EB, and weekly body weight gain, but did not affect milk production or lactation curve characteristics. A 30-d DP resulted in a greater total predicted lactation yield, initial milk yield after calving, peak milk yield, energy intake, energy output in milk, days to conception [only when compared with 0-d DP(low)], plasma GH concentration [only when compared with 0-d DP(std)], and decreased weekly body weight gain compared with a 0-d DP. A 30-d DP decreased both the increasing and the declining slope parameters of the lactation curve and the relative rate of decline in milk yield (indicating greater lactation persistency) compared with a 0-d DP, and decreased plasma insulin and IGF-1 concentration, and EB. In conclusion, feeding a G ration after wk 7 in milk improved energy intake and milk production, but did not affect EB compared with an L ration. For cows without a DP, a reduced dietary energy level did not affect milk production and lactation curve characteristics, but did decrease EB and weekly body weight gain. A 30-d DP increased milk yield and lactation persistency, but decreased milk fat and protein content, EB, and plasma insulin and IGF-1, compared with a 0-d DP.     

Deriving a particle system from continuum mechanics for the animation of deformable objects

Mass-spring and particle systems have been widely employed in computer graphics to model deformable objects because they allow fast numerical solutions. In this work, we establish a link between these discrete models and classical mathematical elasticity. It turns out that discrete systems can be derived from a continuum model by a finite difference formulation and approximate classical continuum models unless the deformations are large. In this work, we present the derivation of a particle system from a continuum model, compare it to the models of classical elasticity theory, and assess its accuracy. In this way, we gain insight into the way discrete systems work and we are able to specify the correct scaling when the discretization is changed. Physical material parameters that describe materials in continuum mechanics are also used in the derived particle system.