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2-deoxy-D-glucose (2DG) is a glycolysis and protein N-glycosylation inhibitor with promising anti-tumor and immunomodulatory effects. However, 2DG can also suppress T cell function, including IFN-γ secretion. Few human T cell studies have studied low-dose 2DG, which can increase IFN-γ in a Jurkat clone. We therefore investigated 2DG's effect on IFN-γ in activated human T cells from PBMCs, with 2DG treatment commenced either concurrently with activation or 48 h after activation. Concurrent 2DG treatment decreased IFN-γ secretion in a dose-dependent manner. However, 2DG treatment of pre-activated T cells had a hormetic effect on IFN-γ, with 0.15-0.6 mM 2DG (achievable in vivo) increasing and >2.4 mM 2DG reducing its secretion. In contrast, IL-2 levels declined monotonously with increasing 2DG concentration. Lower 2DG concentrations reduced PD-1 and increased CD69 expression regardless of treatment timing. The absence of increased T-bet or Eomes expression or IFNG transcription suggests another downstream mechanism. 2DG dose-dependently induced the unfolded protein response, suggesting a possible role in increased IFN-γ secretion, possibly by increasing the ER folding capacity for IFN-γ via increased chaperone expression. Overall, low-dose, short-term 2DG exposure could potentially improve the T cell anti-tumor response., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Animal experimentation is required to investigate complex physiological relationships and facilitates development of evidence-based knowledge. However, experimental protocols can interfere with the daily routine of the animals, result in stress and pain, and have adverse effects on health and production. The goal of this study was to investigate the effects of an intensive experimental protocol on health traits and production in transition dairy cows. Eighty experimental dairy Holstein cows (EXP group) underwent serial protocol-based clinical and ultrasonographic examinations, puncture of the jugular vein for blood collection or drug application, and liver biopsy samples, 14 d before until 42 d after parturition. Controls (CTR group) included 206 cows from the same herd, which fulfilled the same inclusion criteria and were kept under the same production management but were not handled for the purpose of this study. Procedure-related effects with a potentially negative effect on health and production were recorded. Furthermore, production, fertility and culling traits of the 2 groups (CTR, EXP) were compared. Most procedure-related adverse effects were associated with transcutaneous liver biopsies and included diffuse inflammation of the skin incision in 11.9% (42 of 320), abscessation of the skin or subcutis in 4.6% (11 of 240), and increased liver echogenicity of the biopsy site in 10.4% (27 of 240). The experimental procedures had a negative effect on milk yield at the start [days in milk (DIM) 5-50, difference: 2.3 kg, standard error (SE): 0.8 kg] and end of lactation (DIM 251-300, difference: 2.0 kg, SE: 1.0 kg; DIM 301-350, difference: 2.3 kg, SE: 1.2 kg) resulting in a lower 305-d milk yield in the EXP group than in the CTR group (difference: 472 kg, SE 214 kg). The milk fat % was higher in the EXP group than in the CTR group from 251 DIM onward (DIM 251-300, difference: 0.20%, SE: 0.09%; DIM 301-350, difference: 0.41%, SE: 0.17%). Also, the somatic cell score was higher in the EXP group than in the CTR group, during early (5-50 DIM, difference: 0.43, SE: 0.22) and from mid-lactation onward (DIM 151-200, difference: 0.43, SE: 0.2; DIM 201-250, difference: 0.49, SE: 0.22; DIM 251-300, difference: 0.55, SE: 0.25; DIM 301-350, difference: 0.61, SE: 0.28). Experimental procedures had no effect on first service conception rate and time to pregnancy, but had a positive effect on stillbirth rate with fewer stillbirths in the CTR group (0%) than in the EXP group (3.9%). Furthermore, experimental handling had no effect on time to culling or type of culling, whereby poor production was a more frequent reason noted for culling in the EXP group. Procedure-associated impairment of production in dairy cows is rarely reported and allows the estimation of the effects of such a study protocol on animal health and production. As a limitation for the interpretation of the results, the number of animals included and conduction in one single herd have to be considered., (© 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Fatty liver syndrome (FLS) is a common disease in high-producing dairy cows. Studies in humans suggest that the different hepatic lipid fractions play a role in this context. In dairy cows, little is known about the composition of fat stored in the liver, its periparturient dynamics, and the effect of cows' age. Therefore, our goal was to generate primary data in healthy cows to serve as reference values for future studies. Eight healthy German Holstein cows (2nd lactation, n = 3; ≥3rd lactation, n = 5) were examined 14 d antepartum and 7, 28, and 42 d postpartum. The examinations included clinical assessment, liver biopsy, blood sampling, and recording of milk yield. Total lipids (TL) in liver tissue were measured gravimetrically. The TL were separated into lipid fractions (triacylglycerol, TAG; phospholipids, PL; non-esterified fatty acids, NEFA; and cholesterol esters) using thin-layer chromatography, followed by gas chromatography for fatty acid determination. Concentrations of NEFA, ß-hydroxybutyrate, and cholesterol were analyzed in blood. Concentrations of TL, TAG, NEFA, and cholesterol esters in liver tissue and NEFA in blood increased in the periparturient period. The older cows had higher hepatic TL, TAG, and PL concentrations, higher relative hepatic concentrations of TAG in TL, higher NEFA concentrations in blood, a greater decrease in body condition, and higher milk yields between d 9 and 40 than the younger cows. We proposed that due to higher milk yield, older cows mobilized and deposited more fat in the liver, and the increase in hepatic TAG concentration was longer-lasting than in younger cows. Higher levels of structural lipids (PL) in older cows could be explained by higher demand for storage of TAG and cholesterol esters in lipid droplets or for the export of TAG via very-low-density lipoproteins. Results show that hepatic fat storage is a reversible process and does not necessarily cause clinical disease. Nevertheless, older cows have a more sustained and greater increase in hepatic TAG concentration, which may explain their increased risk of FLS. The results are limited in their extrapolation due to the small sample size and thereby possible selection bias but present a valuable basis for future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Theinert, Snedec, Pietsch, Theile, Leonhardt, Spilke, Pichelmann, Bannert, Reichelt, Dobeleit, Fuhrmann, Baumgartner, Schären-Bannert and Starke.)

Objective: Clinical ketosis is common during the dairy cows' transition period and is responsible for considerable economic loss. Early identification of cows with subclinical ketosis is the first step for maintaining the health and productivity of dairy cows. The goals of the study were two-fold: The first was to examine the usefulness of a mobile test device as a cow-side test; and the second was to compare BHB concentrations measured by the ketometer using capillary blood and blood collected from the coccygeal vessels with values determined by a reference method in the laboratory using jugular blood., Material and Methods: Blood samples were collected from a jugular vein or the coccygeal vessels in 81 dairy cows at 7 time points (14 and 7 days pre-partum and 7, 14, 21, 28, and 42 days post-partum) for kinetic enzymatic measurement of BHB concentration in the laboratory. Blood samples were concurrently collected from the coccygeal vessels or by pricking the vulvar lip at the transition of the skin to the mucosa (capillary blood) to determine BHB concentration using the WellionVet BELUA ketometer (MED TRUST GmbH, Marz, Austria)., Results: Initial errors in operating the ketometer were quickly eliminated with experience. BHB concentrations of jugular blood measured in the laboratory were 0.07 mmol/l lower than those measured in coccygeal blood. The mean BHB concentration measured in coccygeal and capillary blood using the WellionVet BELUA ketometer did not significantly differ but were 0.13 and 0.12 mmol/l respectively, lower than the mean jugular vein concentrations measured in the laboratory., Conclusion: The WellionVet BELUA ketometer is useful for determination of BHB concentration in cows provided that the manufacturer's specifications are followed. Capillary blood is best collected at the transition from the vulvar skin to its mucosa. The device generates rapid results that correlate well with BHB concentrations determined in the laboratory and with the results obtained from different blood collection sites. It is ideally suited for monitoring dairy cows for subclinical ketosis using capillary or coccygeal blood., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Recumbent cows are a diagnostic challenge because of a wide range of differential diagnoses, which include trauma, neurological and metabolic disorders, malnutrition and mineral deficiencies. This case report describes recumbent suckler cows that presented as a herd problem. In addition to weakness due to inanition, Cu and Se deficiencies were considered as possible aetiologies of the recumbency. Furthermore, Trypanosoma (T.) theileri, a blood parasite of unknown importance in Germany, was detected in the blood of some cows., Case Presentation: Three recumbent cows were referred to the Clinic for Ruminants and Swine, Faculty of Veterinary Medicine of the University of Leipzig. They were unable to rise and had low body condition scores and rough hair coats. Haematological and serum biochemical analyses showed neutrophilia, electrolyte imbalances, increased activities of muscle and liver enzymes and decreased concentrations of trace elements, especially Copper (Cu) and Selenium (Se). T. theileri was detected in a routine blood smear from one cow. The cows did not respond to an intensive care protocol, which included intravenous fluids and electrolytes, mineral substitution, non-steroidal anti-inflammatories and antibiotics, and were therefore euthanized or died. Postmortem examination showed cachexia, subcutaneous and scleral oedema and muscular dystrophy, especially in the hind limbs. Follow-up examination of the herd of origin produced similar findings including the detection of T. theileri in a large proportion of the herd. Ration analysis revealed considerable undersupply of several nutrients., Conclusions: Based on all findings, an aetiological diagnosis of trace mineral and nutrient deficiency with possible involvement of T. theileri was made.