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The high recurrence rate of feline meningioma despite the generally benign histomorphology warrants additional markers of clinical aggressiveness. The Ki-67 index is commonly used as prognostic marker for meningioma recurrence in people. Osteopontin (OPN) is a protein involved in tumor progression and may be a potential malignancy marker. To date, osteopontin expression has not been investigated in feline meningioma. The aim of this study was to evaluate the extent of Ki-67 and osteopontin immunostaining of feline meningioma and to find possible associations with WHO (World Health Organization) grades and subtypes. Fifty-three feline meningioma samples were graded according to the human WHO classification and underwent immunohistochemical examination for Ki-67 and OPN. Fifty samples were classified as WHO grade I and three as WHO grade II. The mean Ki-67 ratio was 9.19 ± 9.47. Osteopontin expression was correspondingly high with a mean OPN IHC score of 150.17 (0–242.8), and a median Allred score of 7 (0–8). There was no significant correlation with Ki-67 index, osteopontin expression, WHO grades, or subtypes. The overall high expressions of osteopontin and Ki-67 may help explain the tendency for recurrence of feline meningioma. The human WHO grading system may not be sufficient to accurately estimate the clinical behavior of meningioma in this species.

Background: The evaluation of canine vaginal bacteria during proestrus and estrus and the chosen parameters will help to prevent the misuse of antibiotics in veterinary medicine. Methods: This study carried out a retrospective analysis to obtain microbiological examination results for vaginal swabs from 696 healthy dogs, all of whom were patients from one clinic. Age, body weight, fur length (long or short hair), the time of sampling of vaginal swabs, the duration of proestrus/estrus, progesterone (P4) concentration (the first and last samples), and bacteriological findings were evaluated. Results: Only 3.7% (26/696) of the samples were negative for bacteria. The impact of fur length was low. However, the calculation of the odds ratios revealed that the chance for a high-grade growth of Escherichia (E.) coli and Mycoplasma (M.) canis increases with body weight class. The earlier the sampling was performed, the lower the number of high-grade cultures (p < 0.01). The duration between the first and last measurement of progesterone (P4) was positively related to the cultural detection of Pasteurellaceae, Streptococcus spp., and Enterococcus spp. (p < 0.05) and negatively to the cultivation of Mycoplasma spp. (p < 0.01). Conclusions: Our findings reflect some likely factors contributing to the variability of the physiological vaginal flora in dogs, which may help interpret cultured bacteriological findings.

Increasing evidence suggests that dalbavancin is an effective long-term treatment for ventricular assist device (VAD) infections, with various prolonged dosing regimens currently in use. This retrospective study aimed to assess dalbavancin pharmacokinetics in VAD patients and identify optimal, feasible dosing regimens for long-term suppressive outpatient therapy. Data from Heidelberg University Hospital’s VAD register were analyzed using non-linear mixed-effects modeling for pharmacokinetic analysis and dosing simulations (Lixoft®). The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated for different protein-binding scenarios considering the minimum inhibitory concentration (MIC) distribution of Staphylococcus aureus. Using data from 13 patients with 38 blood samples, a two-compartment model best described the dalbavancin pharmacokinetics, with a typical value for clearance of 0.050 L/h, central volume of distribution of 6.5 L, and peripheral volume of 15.4 L. No covariates significantly improved the model fit. The observed protein binding varied between 96 and 98%. Dosing simulations demonstrated that 1500 mg every 3 weeks ensured the target attainment for stasis at MIC values of 0.125 mg/L (PTA ≥ 90%) up to a protein binding of 99%. Considering the CRF, longer dosing intervals up to 5 weeks might be possible. Depending on individual MICs and protein binding, a dalbavancin regimen of 1500 mg every 3 to 5 weeks therefore appears to be a valuable option for outpatient therapy of VAD infections. Therapeutic drug monitoring should be considered to manage inter-individual variability and to support clinicians in long-term treatments of subacute and chronic infections.

The aim of this study was to determine whether horses exhibiting unilateral hindlimb lameness unload (rest) the lame limb more than the contralateral limb. The resting/unloading of the hindlimbs and the time spent lying down were measured using accelerometers. Ten non-lame horses and 20 lame horses were recruited for participation and monitored for 11 h overnight with accelerometers (MSR145, sampling rate: 1 Hz, and measuring range: ±15 g) attached to the lateral metatarsal and metacarpal regions of each limb. Metatarsal and metacarpal orientation were used to determine whether the limb was unloaded (rested) or loaded, respectively, or whether the horses were lying down. The relation of resting time between non-lame and lame limbs (non-lame/lame: 0.85 ± 1.2) of the lame horses differed significantly (p = 0.035) from that of the non-lame horses (right/left: 1.08 ± 0.47). Non-lame horses rested their hindlimbs evenly (left: 15 ± 10%; right: 17 ± 16%). Horses with unilateral hindlimb lameness unloaded the lame limb longer (lame limb: 61.8 ± 25.3%, non-lame limb: 38.2 ± 25.3%) than their contralateral limb. The lame horses (13 ± 11%) lay down longer (p = 0.012) than the non-lame horses (3 ± 6%). The degree of lameness determined by the participating veterinarians (Vet Score) (r = −0.691, p < 0.01) and the asymmetry evaluated by the lameness locator (ALL) (r = −0.426, p = 0.019) correlated with the resting ratio (rest time ratio). Both factors were also correlated with the time spent lying down (Vet Score (r = 0.364, p = 0.048) and the ALL (r = 0.398, p = 0.03)). The ALL and VET Score were significantly correlated (r = 0.557, p = 0.01). The results of this study provide a good baseline for future research into how individual resting patterns may help to detect pain.

IntroductionCanine Parvovirus 2 (CPV-2) infection poses a significant global health risk to susceptible dogs. Hypocobalaminemia, defined as reduced serum cobalamin (CBL) concentrations, is a recognized complication in chronic enteropathies in adult dogs but remains poorly understood in the context of acute enteropathies, especially in young dogs. The aim of this study was to investigate the frequency and severity of hypocobalaminemia in young dogs with parvovirus enteritis and evaluation of CBL as a predictor of outcome.Materials and methodsThirty client-owned dogs diagnosed with parvovirus infection and thirty healthy controls were enrolled. Clinical, hematological, and biochemical tests, including CBL and serum methylmalonic acid (MMA) concentrations, were assessed.ResultsResults indicated a significantly higher prevalence of hypocobalaminemia in dogs with parvovirus enteritis compared to healthy controls, as well as a significant correlation with a disease severity score. Moreover, survivors demonstrated higher CBL concentrations than non-survivors, suggesting an eventual prognostic value of CBL status. However, parenteral CBL supplementation showed no significant effect on serum CBL or MMA concentrations, highlighting potential challenges in CBL uptake at the cellular level.DiscussionHypocobalaminemia in this population is caused by multiple factors such as reduced nutritional absorption, gastrointestinal losses, and increased metabolic demands. Further research is needed to develop tailored management strategies, evaluate the effectiveness of CBL supplementation, and understand the mechanisms behind hypocobalaminemia in parvovirus infection.

Abstract Objectives The standard treatment for canine and feline meningiomas includes radiotherapy, surgical excision or combined therapy. However, new therapeutic approaches are required due to the possible recurrence or progression of meningiomas despite initial therapy. Adjunctive therapy with synthetic long‐acting somatostatin (SST) analogues has been described in humans with SST‐expressing tumours. The expression of SST receptors (SSTRs) by feline meningiomas is currently unknown, and there are little data about canine meningiomas. We hypothesized that SSTR is expressed by canine and feline meningiomas (S1). Methods Seven canines and 11 felines with histologically confirmed meningiomas underwent STTR screening. RNA expressions of SSTR1, SSTR2, SSTR3 and SSTR5 (canine) and SSTR1–SSTR 5 (feline) in fresh frozen and formalin‐fixed and paraffin‐embedded (FFPE) samples were investigated using real‐time (RT)‐qPCR. The expression of SSTR1 and SSTR2 in FFPE samples was evaluated using immunohistochemistry (IHC). The specificity of applied antibodies for canine and feline species was confirmed by western blotting. Results In canine meningiomas (n = 7), RNA expression of SSTR1, SSTR2 and SSTR5 was detected in all samples; SSTR3 RNA expression was detected in only 33% of samples. In feline meningiomas (n = 12), RNA expression of SSTR1, SSTR4, SSTR5 and SSTR2 was detected in 91%, 46%, 46% and 36% of samples, respectively; SSTR3 was not expressed. Overall, the detection rate was lower in FFPE samples. IHC revealed the expression of SSTR1 and SSTR2 in all samples from both species. However, it is important to exercise caution when interpreting IHC results due to the presence of diffuse background staining. Conclusions SSTRs are widely expressed in canine and feline meningiomas, thereby encouraging further studies investigating SSTR expression to conduct trials about the effect of adjunctive therapy with long‐acting SST‐analogues.

The automated detection of individuals within vehicles, with minimal to no human intervention, hold multifaceted implications in contemporary contexts. These applications span from aiding emergency responders and optimising transportation networks to facilitating automated crash response mechanisms and enforcing regulations concerning High Occupancy Vehicle and High Occupancy Toll lanes. In this paper, we introduce our camera system designed for passenger counting, leveraging five IP cameras equipped with a range of optical filters, employing image registration techniques, and integrating the YOLOv8 object detection model. The Surveillance Camera Array Network (SCAN) operates within the near-infrared domain of the electromagnetic spectrum in conjunction with the visible part. Four VIVOTEK IP cameras are outfitted with near-infrared, neutral density, polarising, and ultraviolet optical filters, while the final camera retains its stock lens. Our primary challenge lies in managing variable lighting conditions throughout the day. However, during nighttime, we achieve nearly perfect image capture of vehicles. To mitigate noise, glare, and other impediments, we initially apply camera calibration, image preprocessing, cropping, image registration, and finally, image fusion. Our findings demonstrate that our cost-effective SCAN system adeptly detects passengers in cars equipped with window tinting. The results obtained during testing conditions resulted in an 66% true positive rate, 8% false positive rate and 26% false negative rate within best dataset. Additionally, we provide created datasets displaying passengers inside Suzuki Vitara, Jaguar XF, and Honda CRV vehicles with various levels of window tinting, to facilitate future community endeavors in addressing this challenging task.

Navigation services and other traffic applications are nowadays widespread, and their use is very common. These applications have an impact on traffic flow, driver awareness, and driver safety; however, a determination of the actual position of the end device is required. Most of such applications use Global Navigation Satellite Systems (GNSS), which cover a significant part of the transport infrastructure. However, in a GNSS-denied environment, these commonly used methods are either unavailable or significantly limited.For example, in road tunnels, signals are blocked by the tunnel structure itself. Nevertheless, tunnels are part of critical infrastructure and, in addition, have higher requirements to ensure safety compared to other transport routes. This article proposes an alternative method to determine position using data from additional Bluetooth Low Energy infrastructure. Furthermore, the localization approaches are presented together with the evaluation and its accuracy and stability assessment. The localization infrastructure was tested at various speeds during tunnel closure and during the real traffic scenario. The median positioning error ranges between 15-20m and decreases with distance, providing a stable, reliable, and cost-effective solution, particularly suited for long tunnels with varying curvatures. Therefore, it offers a practical use with significant impact on traffic safety and efficiency.

Abstract Neuromodulatory signaling via G protein-coupled receptors (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. The recent development of optogenetic tools to induce G protein-mediated signaling provides the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimize the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). These optoDopRs exhibit high signaling specificity and light sensitivity in vitro. In vivo, we show receptor and cell type-specific effects of dopaminergic signaling in various behaviors, including the ability of optoDopRs to rescue the loss of the endogenous receptors. This work demonstrates that optoXRs can enable optical control of neuromodulatory receptor-specific signaling in functional and behavioral studies.

Abstract Significance Two of the leading causes of death worldwide are cancer and cardiovascular diseases. Most cancer patients suffer from a metabolic wasting syndrome known as cancer‐induced cardiac cachexia, resulting in death in up to 30% of cancer patients. Main symptoms of this disease are severe cardiac muscle wasting, cardiac remodeling, and cardiac dysfunction. Metabolic alterations, increased inflammation, and imbalance of protein homeostasis contribute to the progression of this multifactorial syndrome, ultimately resulting in heart failure and death. Cancer‐induced cardiac cachexia is associated with decreased quality of life, increased fatiguability, and decreased tolerance to therapeutic interventions. Recent advances While molecular mechanisms of this disease are not fully understood, researchers have identified different stages of progression of this disease, as well as potential biomarkers to detect and monitor the development. Preclinical and clinical studies have shown positive results when implementing certain pharmacological and non‐pharmacological therapy interventions. Critical issues There are still no clear diagnostic criteria for cancer‐mediated cardiac cachexia and the condition remains untreated, leaving cancer patients with irreversible effects of this syndrome. While traditional cardiovascular therapy interventions, such as beta‐blockers, have shown some positive results in preclinical and clinical research studies, recent preclinical studies have shown more successful results with certain non‐traditional treatment options that have not been further evaluated yet. There is still no clinical standard of care or approved FDA drug to aid in the prevention or treatment of cancer‐induced cardiac cachexia. This review aims to revisit the still not fully understood pathophysiological mechanisms of cancer‐induced cardiac cachexia and explore recent studies using novel treatment strategies. Future directions While research has progressed, further investigations might provide novel diagnostic techniques, potential biomarkers to monitor the progression of the disease, as well as viable pharmacological and non‐pharmacological treatment options to increase quality of life and reduce cancer‐induced cardiac cachexia‐related mortality.

Abstract Astronauts are exposed to harsh conditions, including cosmic radiation and microgravity. Spaceflight elongates human telomeres in peripheral blood, which shorten upon return to Earth and approach baseline levels during postflight recovery. Astronauts also encounter muscle atrophy, losing up to 20% loss of muscle mass on spaceflights. Telomere length changes in muscle cells of astronauts remain unexplored. This study investigates telomere alterations in grounded mice experiencing radiation exposure and muscle atrophy, via a hindlimb unloading spaceflight mimicking model. We find telomere lengthening is present in muscle stem cells and in myofiber nuclei, but not in muscle-resident endothelial cells. We further assessed telomere length in the model following hindlimb unloading recovery. We find that telomere length failed to return to baseline values. Our results suggest a role for telomeres in muscle acclimatization, which is relevant for the well-being of astronauts in space, and upon their return to Earth.

Abstract Background As calves are born without circulating immunoglobulin G (IgG) they depend on transfer of passive immunity via colostrum within the first hours of life. If calves are not sufficiently supplied with high qualitative colostrum they suffer from Failure of Transfer of Passive Immunity (FTPI). The objectives of this study were to evaluate a calf-side point-of-care test to detect calves with FTPI and to evaluate the cut-offs for a positive test result. Two hundred fifty calves from 11 dairy farms (born between September 2021 and September 2022) were included, whereof 23 were excluded due to incomplete data. Twelve to 16 h post partum the farmers carried out a point-of-care test (FASTest® IgG bovine, Megacor, Austria) using a whole blood sample. Between the 3rd and the 6th day of age, all calves were physically examined and blood samples were collected to carry out further point-of-care tests using whole blood supernatant and plasma and for measuring the Brix values in serum and plasma. Brix values in serum were used as reference for the evaluation of the point-of-care test between the 3rd and the 6th day of age, as radial immunodiffusion assays could not be conducted simultaneously. Results Brix values were not normally distributed (median at 8.6% and 9.3% in serum and plasma). In this study, the cut-off values for the point-of-care tests using whole blood supernatant and plasma were at 8.3% Brix in serum. FASTest® IgG bovine shows high sensitivities of 90% and 84% and specificities of 70% and 72% for whole blood supernatant and plasma. Conclusions Of the 227 investigated calves, 39.7% showed Brix values of

IntroductionCenter of pressure (COP) parameters are frequently assessed to analyze movement disorders in humans and animals. Methodological discrepancies are a major concern when evaluating conflicting study results. This study aimed to assess the inter-observer reliability and test-retest reliability of body COP parameters including mediolateral and craniocaudal sway, total length, average speed and support surface in healthy dogs during quiet standing on a pressure plate. Additionally, it sought to determine the minimum number of trials and the shortest duration necessary for accurate COP assessment.Materials and methodsTwelve clinically healthy dogs underwent three repeated trials, which were analyzed by three independent observers to evaluate inter-observer reliability. Test-retest reliability was assessed across the three trials per dog, each lasting 20 seconds (s). Selected 20 s measurements were analyzed in six different ways: 1 × 20 s, 1 × 15 s, 2 × 10 s, 4 × 5 s, 10 × 2 s, and 20 × 1 s.ResultsResults demonstrated excellent inter-observer reliability (ICC ≥ 0.93) for all COP parameters. However, only 5 s, 10 s, and 15 s measurements achieved the reliability threshold (ICC ≥ 0.60) for all evaluated parameters.DiscussionThe shortest repeatable durations were obtained from either two 5 s measurements or a single 10 s measurement. Most importantly, statistically significant differences were observed between the different measurement durations, which underlines the need to standardize measurement times in COP analysis. The results of this study aid scientists in implementing standardized methods, thereby easing comparisons across studies and enhancing the reliability and validity of research findings in veterinary medicine.

Introduction Up to 15% of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases, penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.Methods and analysis This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale.Ethics and dissemination Because individual patient-related data are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal.