Tabanus chrysurus is a potential biological vector of Trypanosoma (Megatrypanum) theileri in Japan.

Several species of horse flies (Diptera: Tabanidae) are known as vectors of Trypanosoma (Megatrypanum) theileri and T. theileri-like trypanosomes; these host-parasite relationships were established based on the developmental stages of these parasites discovered in the hindgut of horse flies. T. theileri and T. theileri-like trypanosomes have been detected in cattle and wild deer in Japan; however, the vector horse fly species remains unidentified. Therefore, in this study, we aimed to identify the potential horse fly species serving as vectors of T. theileri in Japan. A total of 176 horse flies were collected between June to September 2020 and 2021 in Tokachi, Hokkaido, Japan. The T. theileri infection in the captured horse flies was determined by PCR and microscopic analyses of their midgut and hindgut. Additionally, the trypanosome, microscopically detected in a horse fly, was molecularly characterized and phylogenetically analyzed using 18S rRNA and partial cathepsin L-like protein gene (CATL) sequence of the trypanosome. The microscopy and PCR analyses revealed 0.57% and 35.8% prevalence of T. theileri in horse flies, respectively. Epimastigote stages of T. theileri, adhered to the hindgut epithelial cells of Tabanus chrysurus via flagella or actively moving in the lumen of the gut, were detected. Phylogenetic analysis revealed the connection of isolated trypanosomes with T. theileri in the TthI clade. These results suggest that Ta. chrysurus is a potential vector of T. theileri.

Contrast arthrography of the equine temporomandibular joint.

Background: Disorders of the equine temporomandibular joint (TMJ) cause clinical problems and detailed investigations of this joint are becoming more common. Specialist radiographic projections have the potential to highlight osseous abnormalities; however, the ability to assess the intra-articular soft tissue structures is currently limited to computed tomography (with, or without contrast enhancement) or magnetic resonance imaging. Both modalities are expensive and not readily accessible. Objective: To develop a technique of contrast arthrography of both compartments of the equine TMJ in cadavers and then perform the refined technique in three living horses as a proof-of-principle. Study design: A descriptive, experimental, study. Methods: Contrast arthrography of the discomandibular and discotemporal joint compartments of both TMJs was performed in 12 cadaveric equine heads using needles placed in the caudal pouches of the respective joint compartments. Radiographs were taken using previously published techniques, repeated with the mouth open and after air had been injected into the joints, to perform a double-contrast study. The TMJs of three healthy horses were subsequently examined to determine the validity of the procedure in live animals. Results: Single and double-contrast arthrography allowed delineation of the dorsal and ventral surfaces of the intra-articular disc in addition to filling the rostral and caudal joint pouches of the independent joint compartments. Contrast extravasation was common, and in two instances iatrogenic disc penetration resulted in the false diagnosis of pathologic disc perforation. The techniques were well tolerated in all three live horses. Main limitations: Low number of horses. Conclusion: Contrast arthrography allows interpretation of intra-articular soft tissue structures, but caution is advised in diagnosing intra-articular disc perforation. Even with experience, accessing the discomandibular joint can be challenging.

Objective movement asymmetry in horses is comparable between markerless technology and sensor-based systems.

BACKGROUND: A markerless artificial intelligence (AI) system for lameness detection has recently become available but has not been extensively compared with commonly used inertial measurement unit (IMU) systems for detecting asymmetry under field conditions. OBJECTIVE: Comparison of classification of asymmetric limbs under field conditions and comparison of normalised asymmetry data using a markerless AI system (SleipAI; recorded on a tripod mounted iPhone 14pro [SL]); the Equinosis Q Lameness Locator (LL); the EquiMoves (EM); and subjective evaluation (SE). STUDY DESIGN: Descriptive clinical study. METHODS: Straight line trot data were collected from 52 client-owned horses in regular training. Limbs were categorised as symmetric or asymmetric. Number of analysed strides were compared with Wilcoxon's each pairs test. Inter-rater reliability in classification of asymmetric limbs was assessed with Light's Kappa. Bland Altman analysis of normalised asymmetry data was performed. RESULTS: Data from 41 horses were included. Most horses showed mild asymmetry. The EM analysed significantly more strides than the other systems, both for forelimbs and for hindlimbs (53 ± 11 strides for both, respectively; p < 0.006). The LL analysed significantly more hindlimbs strides (45 ± 13) than the SL (27 ± 6; p < 0.001). Moderate inter-rater agreement for asymmetry classification was found between systems (k = 0.59 forelimbs; 0.44 hindlimbs); agreement decreased when including the SE. For the normalised asymmetry data, the strongest agreement was found between the two IMU systems. MAIN LIMITATIONS: Horses were assessed during straight-line trot only. CONCLUSIONS: The objective systems were comparable in classification of asymmetric limbs under field conditions when using defined asymmetry thresholds. Discrepancies stemmed largely from the imposed thresholds (i.e., systems largely identified same-side asymmetry). Overall, the strongest agreement was found between LL and EM. The SL analysed significantly fewer hindlimb strides than the LL and EM which could represent a limitation of the Sleip AI.

Low-field magnetic resonance imaging of sagittal groove disease of the proximal phalanx in non-racing sport horses.

BACKGROUND: Injuries of the sagittal groove of the proximal phalanx (P1) in equine athletes are considered to predominantly occur due to chronic bone stress overload. OBJECTIVES: To describe the range of abnormalities that is present in the sagittal groove in a large group of horses diagnosed with sagittal groove disease (SGD) on low-field MRI. STUDY DESIGN: Retrospective, cross-sectional. METHODS: Medical records were searched to identify initial MRI images of horses diagnosed with SGD and these were blindly evaluated using a semi-quantitative grading scheme and novel SGD MRI classification system reflecting potential pathways of pathological progression and severity of stress injury. RESULTS: A total of 132 limbs from 111 horses were included in the study; predominantly warmbloods competing in showjumping (n = 83) and dressage (n = 18). SGD MRI classifications were: 0 (normal, n = 0), 1 (small subchondral defect, n = 2), 2 (osseous densification, n = 28), 3 (subchondral microfissure with osseous densification, n = 7), 4 (bone oedema-like signal within the subchondral ± trabecular bone and ± subchondral microfissure or demineralisation, n = 72), 5 (incomplete macrofissure/fracture, n = 23) and 6 (complete fracture, n = 0). Classification 4c (bone oedema-like signal with demineralisation) and 5 had higher proportions in the plantar third of hindlimbs (3% and 10%, respectively) compared with forelimbs (0% and 0%, respectively). SGD classification and extent of bone oedema-like signal were not significantly different between lame (n = 116) and non-lame limbs (n = 16) (both p > 0.05). Periosteal new bone and oedema-like signal were identified (either confidently or suspected) at the dorsoproximal aspect of P1 in 25% and 39% of limbs, respectively. MAIN LIMITATIONS: Inclusion via diagnoses in original MRI reports, variable clinical history, small size of some classification groups. CONCLUSIONS: The presence or absence of lameness is not a dependable measure of the severity of SGD. The periosteal oedema-like signal of P1 has not previously been described in MRI of SGD and further supports the concept of bone stress injury.

Comparison of veterinarians and a deep learning tool in the diagnosis of equine ophthalmic diseases.

BACKGROUND/OBJECTIVES: The aim was to compare ophthalmic diagnoses made by veterinarians to a deep learning (artificial intelligence) software tool which was developed to aid in the diagnosis of equine ophthalmic diseases. As equine ophthalmology is a very specialised field in equine medicine, the tool may be able to help in diagnosing equine ophthalmic emergencies such as uveitis. STUDY DESIGN: In silico tool development and assessment of diagnostic performance. METHODS: A deep learning tool which was developed and trained for classification of equine ophthalmic diseases was tested with 40 photographs displaying various equine ophthalmic diseases. The same data set was shown to different groups of veterinarians (equine, small animal, mixed practice, other) using an opinion poll to compare the results and evaluate the performance of the programme. Convolutional Neural Networks (CNN) were trained on 2346 photographs of equine eyes, which were augmented to 9384 images. Two hundred and sixty-one separate unmodified images were used to evaluate the trained network. The trained deep learning tool was used on 40 photographs of equine eyes (10 healthy, 12 uveitis, 18 other diseases). An opinion poll was used to evaluate the diagnostic performance of 148 veterinarians in comparison to the software tool. RESULTS: The probability for the correct answer was 93% for the AI programme. Equine veterinarians answered correctly in 76%, whereas other veterinarians reached 67% probability for the correct diagnosis. MAIN LIMITATIONS: Diagnosis was solely based on images of equine eyes without the possibility to evaluate the inner eye. CONCLUSIONS: The deep learning tool proved to be at least equivalent to veterinarians in assessing ophthalmic diseases in photographs. We therefore conclude that the software tool may be useful in detecting potential emergency cases. In this context, blindness in horses may be prevented as the horse can receive accurate treatment or can be sent to an equine hospital. Furthermore, the tool gives less experienced veterinarians the opportunity to differentiate between uveitis and other ocular anterior segment disease and to support them in their decision-making regarding treatment.

Post-cooling semen processing and sperm re-suspension as an alternative method to circumvent poor semen cooling in stallions.

BACKGROUND: Artificial insemination with cooled-shipped semen is the primary method used in the equine breeding industry; yet, sperm quality and fertility can be suboptimal for some stallions when standard techniques are used. Therefore, there is a critical need to develop alternative approaches for these stallions. OBJECTIVE: To assess sperm quality parameters and fertility of cooled-stored stallion semen processed by SpermFilter® or centrifugation and resuspended in three extenders. STUDY DESIGN: Controlled and field study. METHODS: In Experiment 1, semen was collected from 21 stallions classified as having good ('Good-coolers', n = 8) or poor ('Bad-coolers', n = 13) semen cooling. The semen was extended at 30 million spermatozoa/mL in a skimmed milk-based (SM) diluent, and refrigerated for 24 h. Then, the cooled-stored semen was processed through SpermFilter® or centrifugation, and the resulting sperm pellets were resuspended in SM, SM containing pentoxifylline (SM-P), or an egg yolk-based (EY) extender. Unprocessed cooled-stored semen served as control. Sperm motility parameters, plasma membrane integrity (PMI), and mitochondrial membrane potential (HMMP) were assessed in cooled-semen pre- and post-processing. Experiment 2, cooled semen from 9 stallions classified as Bad-coolers was used to inseminate 18 embryo donor mares at 66 cycles (Unprocessed, n = 22; SpermFilter®/SM-P, n = 16; or SpermFilter®/EY, n = 28). Data were analysed with a mixed model and Tukey's as posthoc, and logistic regression. RESULTS: Processed semen resuspended in EY had superior sperm motility compared to unprocessed, SM and SM-P (p < 0.0001). Semen processed by SpermFilter® resuspended in SM-P was similar to EY (p > 0.05). Pellet resuspension with EY and SM-P improved the HMMP of Bad-cooler stallions (p = 0.0010). Semen processed by SpermFilter® had superior PMI to centrifuged semen (p < 0.0001). Mares inseminated with SpermFilter®/SM-P (50%, 8/16) or SpermFilter®/-EY (68%, 9/28) had higher pregnancy rates than mares bred with unprocessed semen (14%, 3/22) (p < 0.001). MAIN LIMITATIONS: Low number of mares in the fertility trial. CONCLUSION: Sperm quality and fertility of Bad-cooler stallions can be enhanced by SpermFilter® and pellet resuspension with either EY or SM-P.

Horse populations are severely underestimated in a region at risk of Hendra virus spillover.

OBJECTIVE: To identify the size and distribution of the horse population in the Northern Rivers Region of NSW, including changes from 2007 to 2021, to better understand populations at risk of Hendra virus transmission. METHODS: Census data from the 2007 Equine Influenza (EI) outbreak were compared with data collected annually by New South Wales Local Land Services (LLS) (2011-2021), and with field observations via road line transects (2021). RESULTS: The horse populations reported to LLS in 2011 (3000 horses; 0.77 horses/km2) was 145% larger than that reported during the EI outbreak in 2007 (1225 horses; 0.32 horses/km2). This was inconsistent with the 6% increase in horses recorded from 2011 to 2020 within the longitudinal LLS dataset. Linear modelling suggested the true horse population of this region in 2007 was at least double that reported at the time. Distance sampling in 2021 estimated the region's population at 10,185 horses (3.89 per km2; 95% CI = 4854-21,372). Field sampling and modelling identified higher horse densities in rural cropland, with the percentage of conservation land, modified grazing, and rural residential land identified as the best predictors of horse densities. CONCLUSIONS: Data from the 2007 EI outbreak no longer correlates to the current horse population in size or distribution and was likely not a true representation at the time. Current LLS data also likely underestimates horse populations. Ongoing efforts to further quantify and map horse populations in Australia are important for estimating and managing the risk of equine zoonoses.

The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Population genomics provide insight into ancestral relationships and diversity of the feral horses of Theodore Roosevelt National Park.

Theodore Roosevelt National Park (TRNP) manages a herd of feral horses (Equus caballus) which was present on the landscape prior to the establishment of the park. The population presents a unique scenario in that it has experienced fairly intensive and well-documented management since the park's establishment, including herd size reductions, intentional introduction of diversity, and subsequent attempts to remove introduced lineages. This provides an interesting case study on the genetic effects of diverse evolutionary forces on an isolated feral population. To explore the effects of these forces and clarify the relationship of this feral herd with other horses, we used genome-wide markers to examine the population structure of a combined dataset containing common established breeds. Using the Illumina Equine 70k BeadChip, we sampled SNPs across the genome for 118 TRNP horses and evaluated the inbreeding coefficient f and runs of homozygosity (RoH). To identify breed relationships, we compared 23 representative TRNP samples with 792 horses from 35 different breeds using genomic population structure analyses. Mean f of TRNP horses was 0.180, while the mean f for all other breeds in the dataset was 0.116 (SD 0.079). RoH analysis indicates that the TRNP population has experienced recent inbreeding in a timeframe consistent with their management. With Bayesian clustering, PCA, and maximum likelihood phylogeny, TRNP horses show genetic differentiation from other breeds, likely due to isolation, historical population bottlenecks, and genetic drift. However, maximum likelihood phylogeny places them with moderate confidence (76.8%) among draft breeds, which is consistent with the known history of breeds used on early North Dakota ranches and stallions subsequently introduced to the park herd. These findings will help resolve speculation about the origins of the herd and inform management decisions for the TRNP herd.

White horses - non-coding sequences drive premature hair greying and predisposition to melanoma.

The Grey allele in horses is causing premature hair greying and susceptibility to melanoma. The causal mutation is a 4.6 kb tandem duplication in intron 6 of the Syntaxin 17 gene. A recent study demonstrated that the most common allele at the Grey locus (G3) involves three tandem copies of this sequence, whilst a more rare allele (G2) has two tandem copies and the wild-type allele (G1) only one copy. The G3 allele is causing fast greying and high incidence of skin melanoma, whereas the G2 allele is causing slow greying and no obvious increase in melanoma incidence. Further somatic copy number expansion has been documented in melanoma tissue from Grey horses. Functional studies showed that this intronic sequence acts as a weak melanocyte-specific enhancer that becomes substantially stronger by the copy number expansion. The Grey mutation is associated with upregulated expression of both Syntaxin 17 and the neighbouring NR4A3 gene in Grey horse melanomas. It is still an open question which of these genes is most important for the phenotypic effects or if causality is due to the combined effect of upregulation of both genes. Interestingly, RNAseq data in the Human Protein Atlas give support for a possible role of NR4A3 because it is particularly upregulated in human skin cancer, and it belongs to a cluster of genes associated with skin cancer and melanin biosynthesis. The Grey mutation and its association with melanoma provide a possibility to study the path to tumour development in numerous Grey horses carrying exactly the same predisposing mutation.

Intraarticular treatment with integrin α10ß1-selected mesenchymal stem cells affects microRNA expression in experimental post-traumatic osteoarthritis in horses.

Osteoarthritis (OA) remains a major cause of lameness in horses, which leads to lost days of training and early retirement. Still, the underlying pathological processes are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that serve as regulators of many biological processes including OA. Analysis of miRNA expression in diseased joint tissues such as cartilage and synovial membrane may help to elucidate OA pathology. Since integrin α10ß1-selected mesenchymal stem cell (integrin α10-MSC) have shown mitigating effect on equine OA we here investigated the effect of integrin α10-MSCs on miRNA expression. Cartilage and synovial membrane was harvested from the middle carpal joint of horses with experimentally induced, untreated OA, horses with experimentally induced OA treated with allogeneic adipose-derived MSCs selected for the marker integrin α10-MSCs, and from healthy control joints. miRNA expression in cartilage and synovial membrane was established by quantifying 70 pre-determined miRNAs by qPCR. Differential expression of the miRNAs was evaluated by comparing untreated OA and control, untreated OA and MSC-treated OA, and joints with high and low pathology score. A total of 60 miRNAs were successfully quantified in the cartilage samples and 55 miRNAs were quantified in the synovial membrane samples. In cartilage, miR-146a, miR-150 and miR-409 had significantly higher expression in untreated OA joints than in control joints. Expression of miR-125a-3p, miR-150, miR-200c, and miR-499-5p was significantly reduced in cartilage from MSC-treated OA joints compared to the untreated OA joints. Expression of miR-139-5p, miR-150, miR-182-5p, miR-200a, miR-378, miR-409-3p, and miR-7177b in articular cartilage reflected pathology score. Several of these miRNAs are known from research in human patients with OA and from murine OA models. Our study shows that these miRNAs are also differentially expressed in experimental equine OA, and that expression depends on OA severity. Moreover, MSC treatment, which resulted in less severe OA, also affected miRNA expression in cartilage.

Closure of the neuro-central synchondrosis and other physes in foal cervical spines.

BACKGROUND: The neuro-central synchondrosis (NCS) is a physis responsible for the growth of the dorsal third of the vertebral body and neural arches. When the NCS of pigs is tethered to model scoliosis, stenosis also ensues. It is necessary to describe the NCS for future evaluation of its potential role in equine spinal cord compression and ataxia (wobbler syndrome). OBJECTIVES: To describe the NCS, including when it and other physes closed in computed tomographic (CT) scans of the cervical spine of foals, due to its potential role in vertebral stenosis. STUDY DESIGN: Post-mortem cohort study. METHODS: The cervical spine of 35 cases, comprising both sexes and miscellaneous breeds from 153 gestational days to 438 days old, was examined with CT and physes scored from 6: fully open to 0: fully closed. The dorsal physis, physis of the dens and mid-NCS were scored separately, whereas the cranial and caudal NCS portions were scored together with the respective cranial and caudal vertebral body physes. RESULTS: The NCS was a pair of thin physes located in a predominantly dorsal plane between the vertebral body and neural arches. The mid-NCS was closed in C1 from 115 days of age, and in C2-C7 from 38 days of age. The dorsal physis closed later than the NCS in C1, and earlier than the NCS in C2-C7. The dens physis was closed from 227 days of age. The cranial and caudal physes were closing, but not closed from different ages in the different vertebrae of the oldest cases. MAIN LIMITATIONS: Hospital population. CONCLUSIONS: The NCS was a thin physis that contributed mainly to height-wise growth, but also width- and length-wise growth of the vertebral body and neural arches. The mid-NCS was closed in all cervical vertebrae from 115 days of age. The NCS warrants further investigation in the pathogenesis of vertebral stenosis.

HISTORIAL: La sincondrosis neuro­central (NCS) es la fisis responsable del crecimiento del tercio dorsal del cuerpo vertebral y de los arcos neurales. Cuando la NCS en cerdos se asocia a un modelo de escoliosis, también se produce estenosis. Es necesario describir la NCS para la futura evaluación de su rol potencial en la comprensión de la medula espinal equina y ataxia (síndrome de Wobbler). OBJETIVOS: Describir la NCS incluyendo cuando ella y otras fisis se cierran, por tomografía computarizada (CT) de la columna cervical de potrillos, debido a su rol potencial en la estenosis vertebral. DISEÑO DEL ESTUDIO: Estudio de cohorte post­mortem. MÉTODOS: La columna cervical de 35 casos, incluyendo ambos sexos y diferentes razas, desde 153 días gestacionales hasta 438 días de edad, fueron examinadas por CT y las fisis fueron dadas un puntaje de, 6: completamente abiertas a, 0: completamente cerradas. La fisis dorsal, la fisis del hueso odontoides y NCS media fueron evaluadas en forma separada, mientras las porciones de NCS craneal y caudal fueron evaluadas juntas con las respectiva fisis del cuerpo vertebral craneal y caudal. RESULTADOS: La NCS es un par de fisis delgadas localizadas predominantemente en el plano dorsal entre el cuerpo vertebral y los arcos vertebrales. La NCS media estaba cerrada en C1 desde los días 115 de edad, y en C2­C7 a partir de los 38 días de edad. La fisis dorsal se cerró más tarde que la NCS en C1, y antes que la NCS en C2­C7. La fisis del hueso odontoides estaba cerradas a partir de los 227 días de edad. Las fisis craneal y caudal estaban cerrándose, pero no estaban cerradas a distintas edades en las diferentes vertebras en los casos mayores de edad. LIMITACIONES PRINCIPALES: Población de hospital CONCLUSIONES: La NCS es una fisis delgada que contribuye principalmente al crecimiento en altura, pero también en ancho y largo del cuerpo vertebral y arcos vertebrales. La NCS media estaba cerrada en todas las vértebras cervicales a partir de los 115 días de edad. La NCS merece ser investigada más en la patogénesis de la estenosis vertebral. Palabras Clave: ataxia, tomografía computarizada, caballo, osteocondrosis, estenosis, crecimiento vertebral.

Twin management in the mare: A review.

Twin gestation in the mare is undesirable and can have disastrous consequences. As in many cases, the key to success in twin management lies in a thorough follow-up and accurate recording of clinical findings in the pre-breeding examination. A pregnancy diagnosis in the mobility phase is imperative for a good outcome in the event of twin reduction. If a twin gestation is not diagnosed during this early pregnancy stage, several other procedures exist for managing post-fixation twins (>16 days) with varying degrees of success. Most twin pregnancies are the result of multiple ovulations (dizygotic twins). However, monozygotic twins are also sporadically diagnosed, due to the increasing number of transferred in vitro produced equine embryos. In these cases, the most optimal treatment strategy still needs to be determined. This review provides an overview of the various twin reduction techniques described with the expected prognosis as well as of some less reported techniques with their results. In addition, physiological events and the reduction techniques are demonstrated to the user in virtual 3-dimensional illustrations.

Caught in action: how MSCs modulate atherosclerotic plaque.

Atherosclerosis (AS) is a medical condition marked by the stiffening and constriction of the arteries. This is caused by the accumulation of plaque, a substance made up of fat, cholesterol, calcium, and other elements present in the blood. Over time, this plaque solidifies and constricts the arteries, restricting the circulation of oxygen-rich blood to the organs and other body parts. The onset and progression of AS involve a continuous inflammatory response, including the infiltration of inflammatory cells, foam cells derived from monocytes/macrophages, and inflammatory cytokines and chemokines. Mesenchymal stromal cells (MSCs), a type of multipotent stem cells originating from various body tissues, have recently been demonstrated to have a protective and regulatory role in diseases involving inflammation. Consequently, the transplantation of MSCs is being proposed as a novel therapeutic strategy for atherosclerosis treatment. This mini-review intends to provide a summary of the regulatory effects of MSCs at the plaque site to lay the groundwork for therapeutic interventions.

Translation Research in Therapeutic Approaches from Conventional to Novel Nano-therapeutics for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis is a systemic autoimmune disorder related to joint inflammation, bone erosion, and deformity. Numerous studies indicate that the causes and consequences of RA are still being debated, and therapeutic strategies are in the translation stage. Non-steroidal anti-inflammatory drugs continue to be often used to relieve pain. Still, due to their poor efficacy, failure to halt the spread of the disease, and undesirable adverse effects, they are no longer regarded as first-line treatments. The development of biologic DMRDs designed to reduce the inflammatory response led to substantial changes to the strategy for managing this disease. Although biologic DMRDs have made significant strides in the management of Rheumatoid arthritis, certain patients' lack of response to biological approaches and therapy cessation due to systemic toxicity are unresolved problems. Therefore, to improve the in vivo effect and reduce systemic adverse effects, new approaches are needed to proactively target and transport therapeutic molecules to target sites. The intriguing method of nanotechnology enables the encapsulation of drugs to prevent their deterioration and systemic adverse effects. The next generation of Rheumatoid arthritis therapies might be based on advances in nanomaterial-based drug delivery, Trojan horse, and antibody targeting approaches. This article presents an overview of the advancements in Rheumatoid arthritis therapy, ranging from traditional methods to recent cutting-edge, ongoing pre-clinical and clinical approaches.

Medical management and positive outcome after prolonged recumbency in a case of equine herpesvirus myeloencephalopathy.

A 17-year-old mare presenting with acute fever, weakness and bladder dysfunction was diagnosed with equine herpesvirus myeloencephalopathy (EHM). The mare become transiently recumbent, underwent parenteral fluid therapy, plasma infusion, steroidal/nonsteroidal anti-inflammatory drugs (SAID/NSAIDs) and bladder catheterization. After 10 days the mare was hospitalized. Neurological evaluation revealed ataxia and proprioceptive deficits mainly in the hind limbs. The mare was able to stand but unable to rise from recumbency or walk. Secondary complications included Escherichia coli cystitis, corneal ulcers and pressure sores. A full-body support sling was used for 21 days. Medical treatment included systemic antimicrobials, NSAIDs, gradual discontinuation of SAIDs, parenteral fluid therapy and bladder lavage. The mare tested positive for Varicellovirus equidalpha 1 (EHV-1) DNA in nasal swab and blood samples on day 13 and in urine samples on days 13 and 25 after the onset of fever. Neurological signs improved over a period of 34 days and the mare was discharged with mild hind limb weakness/ataxia. Secondary complications resolved within 2 weeks. At the eight-month follow-up, marked improvement in locomotory function had been achieved.

Infrared Spectroscopy of Synovial Fluid Shows Accuracy as an Early Biomarker in an Equine Model of Traumatic Osteoarthritis.

Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction of OA (Day 0) and weekly until Day 63. IR absorbance spectra were acquired from dried SF films. Following spectral pre-processing, predictive models using random forests were used to differentiate OA, Sham, and Control samples. The accuracy for distinguishing between OA and any other joint group was 80%. The classification accuracy by sampling day was 87%. For paired classification tasks, the accuracies by joint were 75% for OA vs. OA Control and 70% for OA vs. Sham. The accuracy for separating horses by group (OA vs. Sham) was 68%. In conclusion, SF IR spectroscopy accurately discriminates traumatically induced OA joints from controls.

Treatment Comparison for Medial Femoral Condyle Subchondral Cystic Lesions and Prognosis in Yearling Thoroughbred Racehorse Prospects.

Subchondral cystic lesions (SCL) in the medial femoral condyle are a usual finding in Thoroughbred survey and auction repository radiographs. Several treatments with different outcomes have been studied over the years to improve soundness and racing prognosis. Our objective was to report the racing prognosis in Thoroughbred yearlings intended for racing that were diagnosed with SCL in the medial femoral condyle and were treated using four current and different techniques: intralesional injection of corticosteroids, SCL debridement through the joint with a drill bit, translesional cortical screw placement, and absorbable hydroxyapatite implant placement. Data from 182 Thoroughbred yearlings treated for SCL in the medial femoral condyle were collected from 2014 to 2020. Limb affected, age at surgery, sex, and radiographic measurements of the SCL were recorded. Auction price and racing performance were collected for treated horses and compared to 154 maternal siblings free of medial femoral condyle SCL. Analyses were conducted to assess if racing prognosis was affected by SCL size, to detect differences in auction price and selected flat racing outcome parameters between cases and controls, and to compare racing prognosis between the studied treatments. Mares and lesions located in the right stifle were significantly overrepresented. The auction price of treated horses was significantly lower than that of their siblings. Horses treated for SCL had significantly lower chances to start in a race than controls (59% vs. 74% respectively). Wider SCL negatively affected the chances to start at least in one race, and negatively affected the earnings made in the 2-year-olds' racing year. Horses with SCL treated using a bioabsorbable implant had a significantly higher median in starts as 3-year-olds (seven starts) than horses that had the SCL debrided with a drill bit (three starts). In conclusion, Thoroughbred yearlings treated for a medial femoral condyle SCL had lower auction prices and decreased ability to start a race compared to siblings' wider cysts had worse prognosis to start a race and might affect earnings as 2-year-olds; and horses treated with bioabsorbable composite implant placement had more starts as 3-year-olds than with other techniques.

Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu.

We studied the Escherichia coli outer membrane protein Fiu, a presumed transporter of monomeric ferric catecholates, by introducing Cys residues in its surface loops and modifying them with fluorescein maleimide (FM). Fiu-FM bound iron complexes of the tricatecholate siderophore enterobactin (FeEnt) and glucosylated enterobactin (FeGEnt), their dicatecholate degradation product Fe(DHBS)2 (FeEnt*), the monocatecholates dihydroxybenzoic acid (FeDHBA) and dihydroxybenzoyl serine (FeDHBS), and the siderophore antibiotics cefiderocol (FDC) and MB-1. Unlike high-affinity ligand-gated porins (LGPs), Fiu-FM had only micromolar affinity for iron complexes. Its apparent KD values for FeDHBS, FeDHBA, FeEnt*, FeEnt, FeGEnt, FeFDC, and FeMB-1 were 0.1, 0.7, 0.7, 1.0, 0.3, 0.4, and 4 µM, respectively. Despite its broad binding abilities, the transport repertoires of E. coli Fiu, as well as those of Cir and FepA, were less broad. Fiu only transported FeEnt*. Cir transported FeEnt* and FeDHBS (weakly); FepA transported FeEnt, FeEnt*, and FeDHBA. Both Cir and FepA bound FeGEnt, albeit with lower affinity. Related transporters of Acinetobacter baumannii (PiuA, PirA, BauA) had similarly moderate affinity and broad specificity for di- or monomeric ferric catecholates. Both microbiological and radioisotopic experiments showed Fiu's exclusive transport of FeEnt*, rather than ferric monocatecholate compounds. Molecular docking and molecular dynamics simulations predicted three binding sites for FeEnt*in the external vestibule of Fiu, and a fourth site deeper in its interior. Alanine scanning mutagenesis in the outermost sites (1a, 1b, and 2) decreased FeEnt* binding affinity as much as 20-fold and reduced or eliminated FeEnt* uptake. Finally, the molecular dynamics simulations suggested a pathway of FeEnt* movement through Fiu that may generally describe the process of metal transport by TonB-dependent receptors.