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Objective: Evaluation of noninvasive left ventricular (LV) myocardial work (MW) enables insights into cardiac contractility and efficacy beyond conventional echocardiography. However, there is limited intraoperative data on patients undergoing surgical aortic valve replacement (AVR). The aim of this study was to describe the feasibility and the intraoperative course of this technique of ventricular function assessment in these patients and compare it to conventional two (2D)- and three-dimensional (3D) echocardiographic measurements and strain analysis., Design: Prospective observational study., Setting: Single university hospital., Participants: Twenty-five patients scheduled for isolated AVR with preoperative preserved left and right ventricular function, sinus rhythm, without significant other heart valve disease or pulmonary hypertension, and an uneventful intraoperative course., Interventions: Transesophageal echocardiography was performed after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3). Evaluation was performed in stable hemodynamics, in sinus rhythm or atrial pacing and vasopressor support with norepinephrine ≤ 0.1 µg/kg/min., Measurements and Main Results: EchoPAC v206 software (GE Vingmed Ultrasound AS, Norway) was used for analysis of 2D and 3D LV ejection fraction (EF), LV global longitudinal strain (GLS), LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), and LV global work efficiency (GWE). Estimation of myocardial work was feasible in all patients. Although there was no significant difference in the values of 2D and 3D EF, GWI and GCW decreased significantly after AVR (T1 v T2, 1,647 ± 380 mmHg% v 1,021 ± 233 mmHg%, p < 0.001; T1 v T2, 2,095 ± 433 mmHg% v 1,402 ± 242 mmHg%, p < 0.001, respectively), while GWW remained unchanged (T1 v T2, 296 mmHg% [IQR 178-452) v 309 mmHg% [IQR 255-438), p = 0.97). This resulted in a decreased GWE directly after bypass (T1 v T2, 84% ± 6% v 78% ± 5%, p < 0.001), but GWE already improved at the end of surgery (T2 v T3, 78% ± 5% v 81% ± 5%, p = 0.003). There was no significant change in the values of GWI, GCW, or 2D and 3D LVEF before and after sternal closure (T2 v T3)., Conclusion: LV MW analysis showed a reduction of LV workload after bypass in our group of patients, which was not detected by conventional echocardiographic measures. This evolving technique provides deeper insights into cardiac energetics and efficiency in the perioperative course of aortic valve replacement surgery., Competing Interests: Declaration of competing interest Bernd W. Böttiger is treasurer of the European Resuscitation Council (ERC), Founder of the ERC Research NET, Chairman of the German Resuscitation Council (GRC), Member of the „Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR), Member of the Executive Committee of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), Founder of the “Deutsche Stiftung Wiederbelebung”, Federal Medical Advisor of the German Red Cross (DRK), Member of the Advisory Board of the “Deutsche Herzstiftung”, Co-Editor of “Resuscitation”, Editor of the Journal “Notfall + Rettungsmedizin”, Co-Editor of the Brazilian Journal of Anesthesiology. He received fees for lectures from the following companies: Forum für medizinische Fortbildung (FomF), Baxalta Deutschland GmbH, ZOLL Medical Deutschland GmbH, C.R. Bard GmbH, GS Elektromedizinische Geräte G. Stemple GmbH, Novartis Pharma GmbH, Philips GmbH Market DACH, Bioscience Valuation BSV GmbH. The other authors declare there are no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Digital recording and storage of health data are becoming increasingly important in the fields of both human and veterinary medicine. There is currently a lack of information on the level of digitalisation among equine veterinarians in Germany and their attitudes towards advanced digitalisation., Objectives: To collect opinions of equine veterinarians about (1) digital data collection in pre-purchase examinations (PPEs), and (2) the establishment of an equine health database in Germany., Study Design: Cross-sectional survey., Methods: An online survey was developed and distributed via email exclusively to equine veterinarians in Germany. After 40 days of data collection, answers were used for descriptive statistical analyses., Results: The survey was sent to 1055 recipients, of which 147 (13.9%) participated and 130 survey responses from equine veterinarians could be used for analyses. Most respondents were working in an equine practice (77.9%) and performing PPEs (93.8%), for which they mostly used printed protocols (86.0%). The PPE protocol of the German Equine Veterinary Association as a paper print was the format most frequently used (47.1%). The majority of participating equine veterinarians (90.2%) would use a digital protocol for PPEs if available. Concerns were expressed about user-friendliness (55.9%) and integration into the daily veterinary routine (54.6%). Regarding the establishment of an equine health database, 72.3% of the respondents stated they would appreciate it. However, about one-third would support such a development only under certain conditions: guaranteed data safety, collection of objective data or involving the opinion of other stakeholders., Main Limitations: Low response rate, potential non-response bias and wide range of question topics., Conclusion: A positive attitude towards digital PPEs and an equine health database in Germany became apparent. To facilitate further progress, it would be crucial to consider the concerns and conditions identified in this study to generate maximum compliance., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: To determine whether sensory nerve conduction stimulus threshold measurements of the infraorbital nerve are able to differentiate horses with idiopathic trigeminal-mediated headshaking (i-TMHS) from healthy horses and from horses with secondary trigeminal-mediated headshaking (s-TMHS). In a prospective trial, headshaking horses were examined using a standardized diagnostic protocol, including advanced diagnostics such as computed tomography and 3-Tesla-magnetic resonance imaging (MRI), to differentiate s-TMHS from i-TMHS. Clinically healthy horses served as controls. Within this process, patients underwent general anesthesia, and the minimal sensory nerve conduction stimulus threshold (SNCT) of the infraorbital nerve was measured using a bipolar concentric needle electrode. Sensory nerve action potentials (SNAP) were assessed in 2.5-5 mA intervals. Minimal SNCT as well as additional measurements were calculated., Results: In 60 horses, SNAP could be recorded, of which 43 horses had i-TMHS, six had suspected s-TMHS, three horses had non-facial headshaking, and eight healthy horses served as controls. Controls had a minimal SNCT ≥ 15 mA, whereas 14/43 horses with i-TMHS and 2/6 horses with s-TMHS showed a minimal SNCT ≤ 10 mA. Minimal SNCT ≤ 10 mA showed 100% specificity to distinguish TMHS from controls, but the sensitivity was only 41%., Conclusion: A minimal SNCT of the infraorbital nerve ≤ 10 mA was able to differentiate healthy horses from horses with TMHS. Nevertheless, a higher minimal SNCT did not exclude i-TMHS or s-TMHS and minimal SNCT does not distinguish s-TMHS from i-TMHS., (© 2024. The Author(s).)

Background: In horses with trigeminal-mediated headshaking (TMHS), clinical signs are likely to be expression of neuropathic facial pain. Currently, subjective assessment of disease severity is used as measure of compromise of animal's welfare., Objectives: To develop and validate a precise scoring system for TMHS: History, Rest and Exercise Score (HRE-S). The HRE-S consists of three subscores: history score (H-S), resting score (R-S) and exercise score (E-S)., Study Design: Retrospective observational study., Methods: Seven masked observers with different experience used HRE-S to score 40 video recordings taken during rest and lungeing including five duplicates. Video recordings were taken from nine horses with TMHS and three controls. Inter- and intraobserver reliability and practicability of HRE-S were assessed. For every video recording severity of clinical signs was graded by every observer using an intuitive global-type-scale and interobserver reliability was calculated. Convergent validity was evaluated comparing HRE-S to groups created by an existing score (grade 0-3). Discriminant validity was analysed comparing HRE-S to groups created by intuitive global-type-scale., Results: Reliability for HRE-S was excellent, irrespective of observers experience: Spearman's Rho = 0.946, p < 0.001 (intraobserver reliability) and intraclass correlation coefficient = 0.98, p < 0.001 (interobserver reliability). Interobserver reliability for intuitive global-type-scale was fair to substantial: Fleiss' κappa = 0.48 (R-S) -0.63 (E-S). Groups created by intuitive global-type-scale had significantly different R-S and E-S (p < 0.05), demonstrating discriminant validity. Convergent validity was proven as horses with grade 3/3 had significantly higher average E-S and total scores compared with an existing score than those with grade 0/3 or 1/3 (p < 0.001)., Main Limitations: Retrospective nature, video recordings, sample size., Conclusions: HRE-S is a valid and reliable score evaluating disease severity in TMHS, independent of observers' experience., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Horses with trigeminal-mediated headshaking (TMHS) exhibit different headshaking patterns (HSPs), electric shock-like jerking, signs of nasal irritation, and painful facial expressions. The History Rest and Exercise Score (HRE-S) was developed to objectively clarify the severity of the condition in affected horses. This score considers the history and severity of clinical signs at rest and exercise. This study aimed to assess the frequency of different clinical signs and their individual associations with diagnosis, treatment, and outcome in horses diagnosed with TMHS.The clinical records of horses presented with headshaking (HS) at the Clinic for Horses, University of Veterinary Medicine Hannover, between 2006 and 2021 were assessed retrospectively for clinical signs, diagnosis, and treatment. A total of 140 horses were included in the study. Video recordings were evaluated using the HRE-S and compared to the score described by Talbot. Following discharge, owners were interviewed via telephone about the outcome. Correlations between the presence and severity of clinical signs, diagnosis, and outcome were evaluated., Results: The following clinical signs were significantly correlated with a higher HRE-S and grade by Talbot: HS at walk (independently of HSP) (52.9%, 74/140), increased total number of demonstrated HSP (independent of the dominant HSP) (more than one HSP per horse in 91.4%, 128/140), signs of nasal irritation (75.9%, 104/137), painful facial expression (67.8%, 80/118), and electric shock-like jerking (77.5%, 107/138). Diagnosis and outcome do not correlate with the presence of the above-mentioned clinical signs., Conclusion: The HRE-S was confirmed as a valid tool to evaluate disease severity in a cohort of 140 horses with HS. Additionally, clinical signs identified as indicators for higher disease severity may have a stronger negative effect on patient welfare, but they do not correlate with diagnosis or outcome., 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 © 2024 Kloock, Hellige, Kloock, Feige and Niebuhr.)

Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive HAD (XHED). Whole genome and Sanger sequencing of cDNA showed a perfect association of the missense mutation g.85716041G>A (ss2019497443, rs1114816375) within the EDA gene with all three cases following an X-linked recessive inheritance, but normal EDAR and EDARADD . This mutation causes an exchange of glycine (G) with arginine (R) at amino acid position 227 (p.227G>R) in the second collagen triple helix repeat domain of EDA. The EDA variant was associated with a significant reduction and underdevelopment of hair follicles along with a reduced outgrowth of hairs, a complete loss of seromucous nasolabial and mucous tracheal and bronchial glands and a malformation of and reduction in number of teeth. Thermostability of EDA G227R was reduced, consistent with a relatively mild hair and tooth phenotype. However, incisors and canines were more severely affected in one of the calves, which correlated with the presence of a homozygous missense mutation of RNF111 (g.51306765T>G), a putative candidate gene possibly associated with tooth number in EDA -deficient Fleckvieh calves.

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus, which can infect humans and animals, sometimes even with a fatal outcome. Since many decades, TBEV is endemic in southern Germany, while only sporadic occurrence has been noted in northern parts of the country so far. Nevertheless, autochthonous human clinical cases are increasing in the federal state of Lower Saxony in north-western Germany, and several natural foci of TBEV transmission have recently been detected in this federal state. In order to shed more light on the current distribution of TBEV in Lower Saxony, the present study examined blood samples from wild and domestic animals for antibodies against TBEV. Overall, samples from 4,085 animals were tested by ELISA, including wild boar (N = 1,208), roe deer (N = 149), red deer (N = 61), fallow deer (N = 18), red foxes (N = 9), nutria (N = 9), raccoon dogs (N = 3), raccoons (N = 3), badgers (N = 1), European pine martens (N = 1), horses (N = 574), sheep (N = 266), goats (N = 67), dogs (N = 1,317) and cats (N = 399). Samples with an ELISA result of ≥60 Vienna units (VIEU)/ml were subjected to confirmatory serum neutralization tests (SNT). In total, 343 of 4,085 (8.4%) animals tested positive for anti-TBEV-IgG by ELISA, of which 60 samples were confirmed by SNT. Samples of 89 animals showed a cytotoxic effect in the SNT and were excluded from seroprevalence calculation, resulting in an overall seroprevalence of 1.5% (60/3,996). Seroprevalence was higher among wild animals (wild boar: 2.9% [34/1,190], roe deer: 2.7% [4/149], red deer: 1.7% [1/60], fallow deer: 5.6% [1/18]) than among domestic animals (dogs: 1.1% [15/1,317], horses: 0.8% [4/505], sheep: 0.4% [1/266]). No anti-TBEV-antibodies were detected in the other wild animal species as well as goats and cats. A notable clustering of positive samples was observed in districts where TBEV transmission foci have been described. Further clusters in other districts suggest the existence of so far undetected transmission foci, underlining the fact that both wild and domestic animals are useful sentinels for monitoring the spread of TBEV., Competing Interests: Declaration of Competing Interest SP is an employee of Elanco Deutschland GmbH, BS is an employee of Elanco Animal Health. Study data collection and interpretation is completely independent from the company's opinion and the authors declare that there is no conflict with commercial interests. The remaining authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier GmbH.)

The measurement of the blood insulin concentration, and comparison to cut-offs, is essential in diagnosing insulin dysregulation, a common equine endocrinopathy. However, different insulin assays provide disparate results. We aimed to ease comparison between assays by compiling original and published data into a web app to convert insulin measurements from one assay to another. Data were available for ADVIA Centaur insulin chemiluminescent immunoassay (CLIA), Beckman Coulter insulin radioimmunoassay (RIA), Immulite 1000 CLIA, Immulite 2000 CLIA, Immulite 2000 XPi CLIA, Mercodia equine insulin enzyme-linked immunosorbent assay (ELISA), and Millipore porcine insulin RIA. Linear models were fitted for 13 assay pairs using non-decreasing splines, and integrated into this app. Assay comparisons including data from several studies showed a lower performance. This indicates technical variation between laboratories, which has not been described before, but is relevant when diagnostic measurements and cut-offs are provided by different laboratories. Nevertheless, the models' overall high performance (median r 2 = 0.94; range 0.57-1.00) supports their use to interpret results from diagnostic insulin measurements when the reference assay is unavailable, and to compare values obtained from different assays.

The newly discovered group of Jingmenviruses has been shown to infect a wide range of hosts and has been associated with febrile illness in humans. During a survey for Jingmenviruses in ticks from Lower Saxony, Germany, Alongshan virus (ALSV) was identified in Ixodes spp. ticks. Additional virus screenings revealed the presence of ALSV in the bodies and saliva of ticks collected at several locations in Lower Saxony. Vector competence studies that included Ixodes ricinus and Dermacentor reticulatus validated the replication of ALSV within those tick species. In vitro feeding experiments with ALSV-injected Ixodes ricinus demonstrated effective viral transmission during blood feeding. To evaluate the potential viral transmission during a natural blood meal, sera from wild game and domestic animals were investigated. One serum sample from a red deer was found to be positive for ALSV RNA, while serological screenings in game and domestic animals revealed the presence of ALSV-specific antibodies at different locations in Lower Saxony. Overall, those results demonstrate the broad distribution of ALSV in ticks in Lower Saxony and hypothesize frequent exposure to animals based on serological investigations. Hence, its potential risk to human and animal health requires further investigation.

The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high-performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX-207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX-207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors., (© 2020 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Background: A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging., Hypothesis/objectives: To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets., Animals: University and privately-owned horses and ponies (n = 157) comprised of 31 breeds and both sexes., Methods: Multicenter cohort study. A custom-produced glycemic pellet was offered for free intake at 0.5 g/kg BW soluble carbohydrate and serum insulin and blood glucose concentrations measured before and after (60, 120, and 180 minutes) the pellets were offered. Pellet acceptance and intake time (those that finished within 10 minutes) were determined to assess palatability., Results: The pellets were palatable to 132/157 animals, and ponies found the pellets more (P = .004) palatable than horses. The median intake time (4 [3-6] minutes) was positively correlated with acceptance grade (r = .51; P < .0001). Consumption of the pellets elicited peak blood glucose (6.6 [5.8-7.8] mmol/L) and serum insulin (40.5 [19-99.8] μIU/mL) responses at 120 minutes. At 120 minutes the optimal cut-off was 83 μIU/mL (95% CI: 70-99 μIU/mL) for the IMMULITE 2000XPi assay., Conclusions and Clinical Importance: The pellets were palatable and a suitable, novel carbohydrate source for the OGT., (© 2022 Boehringer Ingelheim Vetmedica Gmbh. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Oral glycemic challenge (GC) tests are recommended for diagnosis of insulin dysregulation (ID). Various protocols are used, but all have limitations in terms of palatability, ease of use, variable composition, geographic availability, or some combination of these., Hypothesis/objective: To evaluate newly developed formulations with defined carbohydrate composition for use as oral GCs., Animals: Thirty-four horses and ponies in various metabolic states., Methods: Our objectives were carried out in 2 separate cross-over experiments. First, the palatability and acceptance of various GCs (2 syrups, 1 granulate) offered for free intake were compared to glucose mixed in a chaff-based diet. Subsequently, syrups were administered by syringe and compared to an oral glucose test using naso-gastric tubing (tube OGT) to investigate the glycemic and insulinemic responses. Second, these variables were compared in the best performing GC-formulations (granulate further optimized to pelleted formulation and 1 syrup) and a tube OGT. All GCs were administered with equivalent amounts of 0.5 g glycemic carbohydrates per kg body weight., Results: Only the GC pellets were consumed completely by all horses (consumption time 5 ± 2 min). When administered by syringe, the GC syrup also was well accepted. The insulin concentrations at 120 min correlated significantly between tube OGT and GC pellets (r = .717; P < .001) or GC syrup (r = .913; P < .001). The new GC syrup and GC pellets discriminate between healthy and ID horses., Conclusions and Clinical Significance: The GC pellets (DysChEq)™ and GC syrup can be used as palatable and well-accepted oral GC tests for assessment of ID in horses., (© 2023 Boehringer Ingelheim Vetmedica GmbH and The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).

Most horses affected by headshaking (HS) are diagnosed with idiopathic trigeminal-mediated headshaking (i-TMHS) when no underlying disease is found. Diagnosis is made by the exclusion of differentials considering history, clinical signs, and diagnostic investigations. Therefore, in horses presented with headshaking, many diagnostic procedures and therapies are conducted. Retrospectively, the digital patient records of 240 horses with HS were analysed regarding the impact of diagnostic procedures on diagnosis, therapy, and outcome. Horses were extensively examined using a standardised protocol including clinical (ophthalmologic, orthopaedic, neurologic, dental) examination, blood analysis, and imaging techniques (endoscopy, radiographs, computed tomography (CT), and magnetic resonance imaging). Many findings were revealed but were of clinical relevance in only 6% of the horses. These horses were, therefore, diagnosed with secondary headshaking (s-HS). In addition, all of these horses demonstrated a positive outcome. The CT of the head revealed 9/10 of the clinically relevant findings. Other diagnostic procedures had no major additional impact. Conclusively, the diagnostic investigation of horses with HS should aim at differentiating i-TMHS from s-HS. The clinical relevance of findings should be verified through diagnostic anaesthesia or targeted therapy depending on risks, invasiveness, and expected benefits. To reduce the multitude of examinations, diagnostic investigations should focus on the CT of the head in those horses with suspicion of i-TMHS based on typical history, clinical signs, and physical examination.

More than 70 million people worldwide are still infected with the hepatitis C virus 30 years after its discovery, underscoring the need for a vaccine. To develop an effective prophylactic vaccine, detailed knowledge of the correlates of protection and an immunocompetent surrogate model are needed. In this study, we describe the minimum dose required for robust equine hepacivirus (EqHV) infection in equids and examined how this relates to duration of infection, seroconversion, and transcriptomic responses. To investigate mechanisms of hepaciviral persistence, immune response, and immune-mediated pathology, we inoculated eight EqHV naive horses with doses ranging from 1-2 copies to 1.3 × 10 6 RNA copies per inoculation. We characterized infection kinetics, pathology, and transcriptomic responses via next generation sequencing. The minimal infectious dose of EqHV in horses was estimated at 13 RNA copies, whereas 6 to 7 copies were insufficient to cause infection. Peak viremia did not correlate with infectious dose, while seroconversion and duration of infection appeared to be affected. Notably, seroconversion was undetectable in the low-dose infections within the surveillance period (40 to 50 days). In addition, transcriptomic analysis revealed a nearly dose-dependent effect, with greater immune activation and inflammatory response observed in high-dose infections than in low-dose infections. Interestingly, inoculation with 6-7 copies of RNA that did not result in productive infection, but was associated with a strong immune response, similar to that observed in the high-dose infections. IMPORTANCE We demonstrate that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. Hence, inoculation with low doses may enable EqHV to evade strong immune responses in the early phase and therefore promote robust, long-lasting infection.

Insulin dysregulation (ID) is a determinant of equine metabolic syndrome. Among the sphingolipids, ceramides contribute to the development of ID; however, the cross talk between the liver and adipose tissue (AT) depots and the variation among AT depots in terms of ceramide metabolism are not well understood. We aimed to characterize the sphingolipidome of plasma, liver, and AT (nuchal, NUAT; subcutaneous, SCAT; omental, OMAT; retroperitoneal, RPAT) and their associations with insulin response to oral glucose testing (OGT) in normoinsulinemic and hyperinsulinemic horses. Plasma, liver, and AT samples were collected from 12 Icelandic horses upon euthanasia and analyzed by liquid chromatography-mass spectrometry. Eighty-four targeted compounds were effectively quantified. Comparing the AT depots, greater (false discovery rate, FDR < 0.05) ceramide, dihydroceramide, and sphingomyelin concentrations and lower glucosyl- and galactosyl-ceramides were found in RPAT and OMAT than in NUAT and SCAT. Hyperinsulinemic response to OGT was associated with sphingolipidome alterations primarily in the RPAT and OMAT, whereas the NUAT sphingolipidome did not show signs of ceramide accumulation, which was inconsistent with the previously proposed role of nuchal adiposity in ID. The plasma sphingolipidome was not significantly associated with the liver or AT sphingolipidomes, indicating that plasma profiles are determined by an interplay of various organs. Furthermore, hepatic sphingolipid profiles were not correlated with the profiles of AT depots. Finally, statistically valid partial least square regression models predicting insulin response were found in the plasma ( Q 2 = 0.58, R 2 = 0.98), liver ( Q 2 = 0.64, R 2 = 0.74), and RPAT ( Q 2 = 0.68, R 2 = 0.79) sphingolipidome, but not in the other adipose tissues.

Background: The Equine Hepacivirus (EqHV) is an equine-specific and liver-tropic virus belonging to the diverse genus of Hepaciviruses. It was recently found in a large donkey (Equus asinus) cohort with a similar seroprevalence (30%), but lower rate of RNA-positive animals (0.3%) compared to horses. These rare infection events indicate either a lack of adaptation to the new host or a predominantly acute course of infection., Methods: In order to analyze the susceptibility and the course of EqHV infection in donkeys, we inoculated two adult female donkeys and one control horse intravenously with purified EqHV from a naturally infected horse. Liver biopsies were taken before and after inoculation to study changes in the transcriptome., Results: Infection kinetics were similar between the equids. All animals were EqHV PCR-positive from day three. EqHV RNA-levels declined when the animals seroconverted and both donkeys cleared the virus from the blood by week 12. Infection did not have an impact on the clinical findings and no significant histopathological differences were seen. Blood biochemistry revealed a mild increase in GLDH at the time of seroconversion in horses, which was less pronounced in donkeys. Transcriptomic analysis revealed a distinct set of differentially expressed genes, including viral host factors and immune genes., Conclusion: To summarize, our findings indicate that donkeys are a natural host of EqHV, due to the almost identical infection kinetics. The different immune responses do however suggest different mechanisms in reacting to hepaciviral infections., (© 2022. The Author(s).)

Cardioprotection encompasses a variety of strategies protecting the heart against myocardial injury that occurs during and after inadequate blood supply to the heart during myocardial infarction. While restoring reperfusion is crucial for salvaging myocardium from further damage, paradoxically, it itself accounts for additional cell death-a phenomenon named ischemia/reperfusion injury. Therefore, therapeutic strategies are necessary to render the heart protected against myocardial infarction. Ischemic pre- and postconditioning, by short periods of sublethal cardiac ischemia and reperfusion, are still the strongest mechanisms to achieve cardioprotection. However, it is highly impractical and far too invasive for clinical use. Fortunately, it can be mimicked pharmacologically, for example, by volatile anesthetics, noble gases, opioids, propofol, dexmedetomidine, and phosphodiesterase inhibitors. These substances are all routinely used in the clinical setting and seem promising candidates for successful translation of cardioprotection from experimental protocols to clinical trials. This review presents the fundamental mechanisms of conditioning strategies and provides an overview of the most recent and relevant findings on different concepts achieving cardioprotection in the experimental setting, specifically emphasizing pharmacological approaches in the perioperative context.

In order to make material design processes more efficient in the future, the underlying multidimensional process parameter spaces must be systematically explored using digitalisation techniques such as machine learning (ML) and digital simulation. In this paper we shortly review essential concepts for the digitalisation of electrodeposition processes with a special focus on chromium plating from trivalent electrolytes. [ABSTRACT FROM AUTHOR]

The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials suggest various comorbidities interact with inducible cardioprotective properties of RIPC. In the present study, we went back from bedside to bench to investigate, in male patients undergoing CABG surgery, whether (1) humoral factors are released after RIPC during propofol-free anesthesia and/or (2) DM interacts with plasma factor release. Blood samples were taken from male patients with and without DM undergoing CABG surgery before (control) and after RIPC (RIPC). To investigate the release of cardioprotective humoral factors into the plasma, isolated perfused hearts of young rats ( n = 5 per group) were used as a bioassay. The hearts were perfused with patients' plasma without (Con) and with RIPC (RIPC) for 10 min (1% of coronary flow) before global ischemia and reperfusion. In additional groups, the plasma of patients with DM was administered (Con DM, RIPC DM). Infarct size was determined by TTC staining. Propofol-free RIPC plasma of male patients without DM showed an infarct size of 59 ± 5% compared to 61 ± 13% with Con plasma ( p = 0.973). Infarct sizes from patients with DM showed similar results (RIPC DM: 55 ± 3% vs. Con DM: 56 ± 4%; p = 0.995). The release of humoral factors into the blood after RIPC in patients receiving propofol-free anesthesia undergoing CABG surgery did not show any cardioprotective properties independent of a pre-existing diabetes mellitus.

The osmodiuretic agent Mannitol exerts cardioprotection against ischemia and reperfusion (I/R) injury when applied as a pre- and/or postconditioning stimulus. Previously, we demonstrated that these properties are mediated via the activation of mitochondrial ATP-sensitive potassium (mK ATP ) channels. However, considering Mannitol remains in the extracellular compartment, the question arises as to which receptor and intracellular signaling cascades are involved in myocardial protection by the osmodiuretic substance. Protein kinase B (Akt) and G (PKG), as part of the reperfusion injury salvage kinase (RISK) and/or endothelial nitric oxide (eNOS)/PKG pathway, are two well-investigated intracellular targets conferring myocardial protection upstream of mitochondrial potassium channels. Adenosine receptor subtypes have been shown to trigger different cardioprotective pathways, for example, the reperfusion injury. Further, Mannitol induces an increased activation of the adenosine 1 receptor (A1R) in renal cells conferring its nephroprotective properties. Therefore, we investigated whether (1) Akt and PKG are possible signaling targets involved in Mannitol-induced conditioning upstream of the mK ATP channel and/or whether (2) cardioprotection by Mannitol is mediated via activation of the A1R. All experiments were performed on male Wistar rats in vitro employing the Langendorff isolated heart perfusion technique with infarct size determination as the primary endpoint. To unravel possible protein kinase activation, Mannitol was applied in combination with the Akt (MK2206) or PKG (KT5823) inhibitor. In further groups, an A1R blocker (DPCPX) was given with or without Mannitol. Preconditioning with Mannitol (Man) significantly reduced the infarct size compared to the control group. Co-administration of the A1R blocker DPXPC fully abolished myocardial protection of Mannitol. Interestingly and in contrast to the initial hypothesis, neither administration of the Akt nor the PKG blocker had any impact on the cardioprotective properties of Mannitol-induced preconditioning. These results are quite unexpected and show that the protein kinases Akt and PKG-as possible targets of known protective signaling cascades-are not involved in Mannitol-induced preconditioning. However, the cardioprotective effects of Mannitol are mediated via the A1R.

The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.