Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

Duration of constant rate infusion with diazepam or propofol for canine cluster seizures and status epilepticus.

Introduction: Constant rate infusion (CRI) of benzodiazepines or propofol (PPF) is a therapeutic option for cluster seizures (CS) and status epilepticus (SE) in canine patients non-responding to first-line benzodiazepines or non-anesthetics. However, specific indications for optimal duration of CRI are lacking. The aim of this study was to determine the effect of duration of anesthetic CRI on outcome and length of hospital stay in dogs with refractory seizure activity of different etiology. Study design: Open-label non-randomized clinical trial. Materials and methods: Seventy-three client-owned dogs were enrolled. Two groups [experimental (EXP) vs. control (CTRL)] were compared. The EXP group received diazepam (DZP) or PPF CRI for 12 h (±1 h) and the CTRL group received DZP or PPF CRI for 24 h (±1 h) in addition to a standardized emergency treatment protocol identical for both study groups. The historical control group was made up of a population of dogs already reported in a previously published paper by the same authors. Favorable outcome was defined as seizure cessation after CRI, no seizure recurrence, and clinical recovery. Poor outcome was defined as seizure recurrence, death in hospital or no return to acceptable clinical baseline. Univariate statistical analysis was performed. Results: The study sample was 73 dogs: 45 (62%) received DZP CRI and 28 (38%) received PPF CRI. The EXP group was 39 dogs (25 DZP CRI and 14 PPF CRI) and the CTRL group 34 dogs (20 DZP CRI and 14 PPF CRI). We found no statistically significant difference in outcomes between the groups. The median length of stay was 56 h (IQR, 40-78) for the ALL EXP group and 58.5 h (IQR, 48-74.5) for the ALL CTRL group (p = 0.8). Conclusion: Even though a shorter DZP or PPF CRI duration was not associated with a worse outcome, the study failed to identify a clear superiority of shorter CRI duration on outcome or length of hospital stay in dogs with refractory seizure activity of different etiology.

A novel machine learning-based web application for field identification of infectious and inflammatory disorders of the central nervous system in cattle.

BACKGROUND: Central nervous system (CNS) infections in cattle are a major cause of economic loss and mortality. Machine learning (ML) techniques are gaining widespread application in solving predictive tasks in both human and veterinary medicine. OBJECTIVES: Our primary aim was to develop and compare ML models that could predict the likelihood of a CNS disorder of infectious or inflammatory origin in neurologically-impaired cattle. Our secondary aim was to create a user-friendly web application based on the ML model for the diagnosis of infection and inflammation of the CNS. ANIMALS: Ninety-eight cattle with CNS infection and 86 with CNS disorders of other origin. METHODS: Retrospective observational study. Six different ML methods (logistic regression [LR]; support vector machine [SVM]; random forest [RF]; multilayer perceptron [MLP]; K-nearest neighbors [KNN]; gradient boosting [GB]) were compared for their ability to predict whether an infectious or inflammatory disease was present based on demographics, neurological examination findings, and cerebrospinal fluid (CSF) analysis. RESULTS: All 6 methods had high prediction accuracy (≥80%). The accuracy of the LR model was significantly higher (0.843 ± 0.005; receiver operating characteristic [ROC] curve 0.907 ± 0.005 ) than the other models and was selected for implementation in a web application. CONCLUSION AND CLINICAL IMPORTANCE: Our findings support the use of ML algorithms as promising tools for veterinarians to improve diagnosis. The open-access web application may aid clinicians in achieving correct diagnosis of infectious and inflammatory neurological disorders in livestock, with the added benefit of promoting appropriate use of antimicrobials.

Ocular Ultrasonography in Healthy Calves with Different Transducers.

Ocular ultrasonography is seldom performed in cattle. Here, we compared three ultrasound probes (linear, convex, transrectal gynecological) for the measurement of eight eye biometry parameters on vertical and horizontal scans. The sample population was 20 healthy calves (n = 10 Holstein, n = 10 Piedmontese breed). Intragroup (same probe for vertical vs. horizontal scanning) and intergroup (different probes measuring the same biometric parameter) comparisons were performed using Student's t-test and the Mann-Whitney U test. Statistical significance was set at p ≤ 0.05. Intragroup comparison revealed few significant differences. Ultrasound examination with the convex transducer detected more differences than either of the two other probes on vertical (linear six out of eight; transrectal gynecological four out of eight) and horizontal (linear six out of eight; transrectal gynecological six out of eight) scans. Similar results were obtained for both breeds. More non-valuable parameters on the horizontal (77 out of 320, 24%) and the vertical (85 out of 320, 26%) (p ≤ 0.001) scans were obtained with the convex transducer. Both linear transducers were found comparable for ocular ultrasonography in field conditions. However, given its widespread application in the field, the transrectal gynecological transducer may offer veterinarians the added advantage of familiarity and ease-of-use without any additional costs.

Feasibility of 16S rRNA sequencing for cerebrospinal fluid microbiome analysis in cattle with neurological disorders: a pilot study.

Bacterial infection of the central nervous system (CNS) in cattle requires prompt and adequate antimicrobial treatment. The current gold standard for antemortem etiological diagnosis is cerebrospinal fluid (CSF) culture, which often yields false negative results. CSF has long been considered a sterile district in healthy patients, but this notion has been recently challenged. For this pilot study, we used 16S rRNA gene sequencing to investigate the microbial composition of CSF of cattle presenting with CNS disorders and to compare it between subjects with CNS infections and with CNS disorders of other nature. The study sample was 10 animals: 4 presenting with CNS infectious-inflammatory diseases and 6 with other CNS disorders, based on definitive diagnosis. Since the initial round of a standard 16S rRNA PCR did not yield sufficient genetic material for sequencing in any of the samples, the protocol was modified to increase its sensitivity. Bacterial genetic material was identified in 6 animals and 2 groups were formed: an infectious inflammatory (n = 3) and a noninfectious inflammatory group (n = 3). The most frequently expressed bacterial families were Pseudomonadaceae (44.61%), Moraxellaceae (19.54%), Mycobacteriaceae (11.80%); the genera were Pseudomonas (45.42%), Acinetobacter (19.91%), Mycobacterium (12.01%). There were no detectable differences in the CSF microbial composition of the samples from the two groups. Sequencing of bacterial DNA present in the CSF was possible only after increasing PCR sensitivity. The results of 16S rRNA sequencing showed the presence of a microbial community in the CSF in cattle with neurological disorders. Further studies, in which CSF samples from healthy animals and samples from the environment are included as controls, are needed.

Constant rate infusion of diazepam or propofol for the management of canine cluster seizures or status epilepticus.

Introduction: Cluster seizures (CS) and status epilepticus (SE) in dogs are severe neurological emergencies that require immediate treatment. Practical guidelines call for constant rate infusion (CRI) of benzodiazepines or propofol (PPF) in patients with seizures not responding to first-line treatment, but to date only few studies have investigated the use of CRI in dogs with epilepsy. Study design: Retrospective clinical study. Methods: Dogs that received CRI of diazepam (DZP) or PPF for antiepileptic treatment during hospitalization at the Veterinary Teaching Hospital of the University of Turin for CS or SE between September 2016 and December 2019 were eligible for inclusion. Favorable outcome was defined as cessation of clinically visible seizure activity within few minutes from the initiation of the CRI, no seizure recurrence within 24 h after discontinuation of CRI through to hospital discharge, and clinical recovery. Poor outcome was defined as recurrence of seizure activity despite treatment or death in hospital because of recurrent seizures, catastrophic consequences of prolonged seizures or no return to an acceptable neurological and clinical baseline, despite apparent control of seizure activity. Comparisons between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex, previous AED therapy and dose of PPF CRI were carried out. Results: A total of 37 dogs, with 50 instances of hospitalization and CRI administered for CS or SE were included in the study. CRI of diazepam (DZP) or PPF was administered in 29/50 (58%) and in 21/50 (42%) instances of hospitalization, respectively. Idiopathic epilepsy was diagnosed in 21/37 (57%), (13/21 tier I and 8/21 tier II); structural epilepsy was diagnosed in 6/37 (16%) of which 4/6 confirmed and 2/6 suspected. A metabolic or toxic cause of seizure activity was recorded in 7/37 (19%). A total of 38/50 (76%) hospitalizations were noted for CS and 12/50 (24%) for SE. In 30/50 (60%) instances of hospitalization, the patient responded well to CRI with cessation of seizure activity, no recurrence in the 24 h after discontinuation of CRI through to hospital discharge, whereas a poor outcome was recorded for 20/50 (40%) cases (DZP CRI in 12/50 and PPF CRI in 8/50). Comparison between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex and previous AED therapy was carried out but no statistically significant differences were found. Conclusions: The present study is the first to document administration of CRI of DZP or PPF in a large sample of dogs with epilepsy. The medications appeared to be tolerated without major side effects and helped control seizure activity in most patients regardless of seizure etiology. Further studies are needed to evaluate the effects of CRI duration on outcome and complications.

Analysis of Early Assessable Risk Factors for Poor Outcome in Dogs With Cluster Seizures and Status Epilepticus.

Status epileptics (SE) and cluster seizures (CS) are serious neurological emergencies associated with poor outcome in epileptic patients. Data on risk factors associated with outcome in epileptic patients affected by CS and SE have not been studied extensively to date. In the present retrospective study potential risk factors predictive of negative outcome in a population of dogs affected by CS and SE were analyzed. Ninety-three dogs were included in the study: 21/93 patients (23%) presented with SE and 72/93 (77%) with CS. Based on multivariate statistical analysis, factors statistically associated with a poor outcome were the occurrence of the first epileptic seizure outside the defined idiopathic interval (6 months-6 years), a condition of hyperthermia at presentation and the absence of previous antiepileptic drugs (AEDs) in case of previous history of seizures. The results of the present study implement data on risk factors associated with poor outcome in dogs affected by CS or SE and can aid in the creation of an ad hoc scoring system, similar to systems currently applied in human medicine upon hospital admission to benchmark performances and establish protocols for triage and therapeutic management.