Search Results (12)

Background/Objectives: Our prior epigenome-wide association study (EWAS) on multiple sclerosis (MS) identified myeloid-associated methylation signatures and an association with enhancer regions. Here we compared differential DNA methylation across three central nervous system inflammatory disorders: MS, neuromyelitis optica (NMO), and neurologic post-acute sequelae of COVID-19 (neuro-PASC). Methods: Whole-blood DNA was profiled on Infinium MethylationEPIC arrays. Analyses included EWAS at the CpG level, differentially methylation region (DMR) analysis, and gene regulatory-element enrichment using Locus Overlap Analysis (LOLA). Limma linear models were adjusted for race, EPIC array version, age, sex, disease-modifying treatment class, and blood cell composition. Results: All three diseases were associated with broad CpG-level differential methylation. The most robust findings were disease-specific DMR signatures in gene regulatory regions. All three diseases shared Lamin B1-anchored chromatin states as an architectural genomic feature but differed in immune regulatory transcription factor binding sites (TFBS), RNA polymerase (Pol II) occupancy, and DNase accessibility. MS was enriched for TFBS in myeloid CEBPB and SPI1/PU.1 and lymphocyte-associated RUNX3, EBF1, and BATF. MS hypomethylated DMRs were concentrated at active enhancers and myeloid TFBS, suggestive of chronic myeloid activation. NMO showed the clearest promoter and B lymphocyte associated profile. Neuro-PASC was associated with hematopoietic DNase accessibility and TFBS for BATF and EBF1. Conclusions: These results suggest that DNA methylation in MS, NMO, and neuro-PASC differ meaningfully in regulatory architecture rather than conforming to a single shared disease-associated methylation model. A long-term goal is to develop immune therapies for newly recognized diseases such as neuro-PASC. Full article

This study explored ultrastructural changes and the expression of oxidative stress-related genes and proteins in the laminar tissue of dairy cows with acute laminitis induced by oligofructose (OF) overload. Twelve clinically healthy, non-pregnant Chinese Holstein cows were randomly allocated into two groups: the OF-overload group (n = 6) and the control group (n = 6). 17 g/kg BW of oligofructose (OF) dissolved in 20 mL/kg BW of deionized water was provided to the OF-treated group, while the control group received 20 mL/kg BW of deionized water via a stomach tube. Laminar tissue samples were collected at 72 h post-OF administration. RT-qPCR revealed significantly increased Keap1 mRNA expression (p = 0.0097) and significantly decreased Nrf2 (p < 0.0001), Ho1 (p < 0.0001), and Nqo1 (p = 0.0101) mRNA expression in the OF group compared to the control group. Western blot analysis confirmed corresponding protein-level changes, with significantly increased Keap1 (p = 0.0062) and significantly decreased Nrf2 (p = 0.0008), Ho1 (p = 0.0297), and Nqo1 (p = 0.0004) in the OF group compared with the control group. Immunohistochemical analysis revealed significantly increased cytoplasmic Keap1 distribution (p = 0.0200) and significantly decreased nuclear Nrf2 localization (p = 0.0032) in the OF group than the control group. Ultrastructural examination revealed significant pathological changes in the OF group, including a reduced number of hemidesmosomes (p < 0.01), an increased distance from epidermal basal cells to the lamina densa (p < 0.01), thickened and damaged lamina densa with disorganized collagen fibers, and deformed basal cell nuclei with reduced chromatin relative to the control group. In conclusion, these findings demonstrate that OF-induced acute laminitis is associated with significant dysregulation of the Keap1-Nrf2 antioxidant pathway and severe ultrastructural damage to the dermal–epidermal interface, suggesting that oxidative stress contributes to laminar tissue injury in dairy cows. Full article

This case report detailed a rare co-infection of Pseudomonas asiatica and Enterobacter hormaechei in a 9-year-old warmblood mare, leading to severe cellulitis and secondary lymphangitis following traditional hoof blood-letting therapy. The mare exhibited acute limb swelling, fever, cutaneous ulceration, lymphatic dysfunction and unknown anemia. Comprehensive diagnostics, including bacterial culture, whole-genome sequencing, anti-elastin antibody (AEAb) ELISA, and diagnostic imaging, confirmed the pathogens causing cellulitis and secondary lymphangitis. AEAb levels were elevated, correlating with lymphatic degradation, while radiography and lymphangiography ruled out laminitis but identified tortuous lymphatic vessels. The treatment integrated systemic antimicrobials, anti-inflammatory therapy, combined decongestive therapy, and traditional Chinese herbal medicine, resulting in resolution of infection, improved hematological parameters, and restored athletic performance. The therapeutic regimen primarily included gentamicin, enrofloxacin, oxytetracycline, and the Wei Qi Booster. The case highlights the critical role of pathogen-directed antimicrobial selection and the potential benefits of combining conventional and holistic therapies. This report emphasizes the necessity of early, multifaceted interventions to prevent life-threatening complications in equine cellulitis–lymphangitis cases. Full article

The objective of this retrospective case-control study was to examine the relationship between E. coli-induced mastitis and acute laminitis in dairy cows. Correspondingly, the medical records of 93 cows diagnosed with E. coli mastitis between 2012 and 2023 were analysed. The cows were categorised into three groups: (1) cows with mastitis scores of 1 or 2 without signs of acute laminitis; (2) cows with a mastitis score of 3 without signs of acute laminitis; (3) cows with a mastitis score of 3 and exhibiting symptoms of acute laminitis. Out of the 93 cows with E. coli mastitis, 19 were assigned to group 1 (20.4%), 46 to group 2 (49.5%), and 28 to group 3 (30.1%). A total of 74 cows (79.6%) scored 3 for mastitis, but 28 cows (37.8%) were also diagnosed with acute laminitis. A higher mastitis score was significantly associated with a higher incidence of acute laminitis (p = 0.0004). E. coli mastitis showed a higher incidence in parity ≥ 3 (73.3% to 78.6%) and occurred in cows of all three groups mainly during the first third of lactation (53.6% to 75.6%). Cows in group 1 had a median survival time of 512 days, while for cows in groups 2 and 3, these values were 93 and 178 days, respectively. Regarding survival times, only a trend but no statistically significant difference (p = 0.221) was found among the cows in the three groups. This could possibly be explained by the fact that additional comorbidities were diagnosed in 53.6% to 65.2% of the cows from all three groups. It is concluded that cows with severe coliform mastitis have a higher risk of developing acute laminitis, and that a thorough clinical examination of the claws should always be performed to avoid overlooking acute laminitis, which accompanied the E. coli mastitis in approximately 38% of cases. Full article

Systemic inflammatory response syndrome (SIRS) in donkeys is observed to be secondary to colic, diarrhea or pleuropneumonia, among other disorders. Horses with SIRS develop secondary disturbances such as hyperlipemia, laminitis, disseminated intravascular coagulopathy, and hemodynamic and cardiac derangements, which impair their prognosis and increase the mortality rate. In donkeys, no information is available on the effect of experimentally induced endotoxemia in the cardiovascular system. Acute experimental endotoxemia was induced by lipopolysaccharide (LPS) infusion in six healthy adult non-pregnant jennies. Physical signs, arterial (systolic, diastolic and mean) and central venous pressure were monitored during 360 min. Cardiac troponin I (cTnI) concentrations were measured in blood samples, and echocardiography was performed. LPS infusion caused an increase in cTnI, hypotension and diminution of central venous pressure, cardiac dysfunction, with a decrease in stroke volume (SV), cardiac output (CO) and cardiac index, and impairment of ultrasonographic ventricular function parameters. Intravenous meloxicam administration prevented the cTnI increase, hypotension, diminution of SV and CO, and changes in ultrasonographic parameters related to ventricular dysfunction. Thus, meloxicam could be proposed as an effective therapeutical option to control the hemodynamic and cardiac derangements observed in donkeys with SIRS. Full article

This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5–5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3–6 months after an episode of SARA. Depressed milk-fat content is commonly used as a diagnostic tool for SARA. A normal milk-fat test in Holstein dairy cows is >4%, so a milk-fat test of <3% can indicate SARA. However, bulk tank testing of milk fat is inappropriate to diagnose SARA at the herd level, so when >4 cows out of 12 and <60 days in milk are suspected to have SARA it can be considered that the herd has a problem. The rapid or abrupt introduction of fresh cows to high-concentrate diets is the most common cause of SARA. Changes in ruminal bacterial populations when exposed to higher concentrate rations require at least about 3 weeks, and it is recommended that concentrate levels increase by no more than 400 g/day during this period to avoid SARA. Ketosis, a prevalent metabolic disorder in dairy cattle, is scrutinized with a focus on its etiological factors and the physiological changes leading to elevated ketone bodies. In total mix ration-fed herds, an increased risk of mastitis and reduced fertility are usually the first clinical signs of ketosis. All dairy cows in early lactation are at risk of ketosis, with most cases occurring in the first 2–4 weeks of lactation. Cows with a body condition score ≥3.75 on a 5-point scale at calving are at a greater risk of ketosis than those with lower body condition scores. The determination of serum or whole blood acetone, acetoacetate, beta-hydroxybutyrate (BHB) concentration, non-esterified fatty acids (NEFA), and liver biopsies is considered the best way to detect and monitor subclinical ketosis, while urine or milk cowside tests can also be used in on-farm monitoring programs. Concentrations >1.0 mmol/L or 1.4 mmol/L blood or serum BHB are considered diagnostic of subclinical ketosis. The standard threshold used for blood is 1.2 mmol/L, which corresponds to thresholds of 100 mcmol/L for milk and 15 mg/dL for urine. Oral administration of propylene glycol (250–400 g, every 24 h for 3–5 days) is the standard and most efficacious treatment, as well as additional therapy with bolus glucose treatment. Hypocalcemia is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis that occurs most commonly at or soon after parturition. Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. Cows with hypocalcemia have a more profound decrease in blood calcium concentration—typically below 5.5 mg/dL. The prevention of parturient paresis has been historically approached by feeding cows low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation. Calcium intake must be limited to <20 g per day for calcium restriction to be effective. The most practical and proven method for monitoring hypocalcemia is by feeding cows an acidogenic diet for ~3 weeks before calving. Throughout the review, emphasis is placed on the importance of early diagnosis and proactive management strategies to mitigate the impact of these metabolic diseases on dairy cattle health and productivity. The comprehensive nature of this paper aims to serve as a valuable resource for veterinarians, researchers, and dairy farmers seeking a deeper understanding of these prevalent metabolic disorders in dairy cattle. Full article

This study was aimed at determining the autophagy activity in the laminar tissue of dairy cows with oligofructose-induced laminitis. Twelve healthy non-pregnant Holstein cows were randomly divided into two groups of six cows each, entitled the control group and the oligofructose overload group (OF group), respectively. At 0 h, cows in the OF group were gavaged with oligofructose (17 g/kg BW) dissolved in warm deionized water (20 mL/kg BW) through an oral rumen tube, and the dairy cows in the control group were gavaged with the same volume of deionized water by the same method. At −72 h before, as well as 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after perfusion, clinical evaluations of both groups were monitored. After 72 h, the laminar tissues of the dairy cows in both groups were collected to examine the genes and proteins. The gene expression of ATG5, ATG12, and Beclin1 significantly increased (p < 0.05), whereas that of P62 and mTOR significantly decreased (p < 0.01) in the OF group relative to the control group. The protein expression of Beclin-1 significantly increased (p < 0.05), while that of LC3II significantly decreased (p < 0.05) in the OF group relative to the control group. However, the protein expression of P62 non-significantly reduced (p > 0.05) in the OF group comparative to the control group. Furthermore, the distribution of the Beclin1 protein in the laminar tissue significantly increased (p < 0.01), while that of the P62 protein significantly decreased (p < 0.05) in the OF group than the control group. These findings indicate that the imbalanced gene and protein-level status of autophagy-related markers may be the basic cause for the failure of the epidermal attachment. However, a more detailed gene and protein-level study is needed to further clarify the role of autophagy in the pathogenesis of bovine laminitis. Full article

(1) Background: Hydatidosis, or human cystic echinococcosis, is a zoonotic disease. Endemic in some areas, recently it has an increasing incidence in wider regions, determined by population migration. Clinical features depend on the localization and level of infection: asymptomatic or with signs related to hypersensitivity, organic functional deficiencies, expanding mass effects, cyst infection and sudden death. In rare cases, the rupture of a hydatid cyst causes emboli formation by the residual laminated membrane. (2) Methods: We performed an extensive literature review, starting from the case of a 25-year-old patient presenting with neurologic symptoms relevant for acute stroke, associating right upper limb ischemia. (3) Results: Imaging investigations revealed the source of the emboli as the rupture of a hydatid cyst, the patient presenting multiple pericardial and mediastinal localizations. Cerebral imaging confirmed an acute left occipital ischemic lesion, with complete recovery of the neurological deficit after therapy, while surgery for acute brachial artery ischemia had a favorable postoperative evolution. Specific anthelmintic therapy was initiated. An extensive literature review using available databases revealed the scarcity of data on embolism as a consequence of cyst rupture, highlighting the significant risk of clinicians overlooking this possible etiology. (4) Conclusions: An associated allergic reaction should raise the hypothesis of a hydatid cyst rupture as a cause of any level acute ischemic lesion. Full article

Surface disinfection is part of a larger mitigation strategy to prevent the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus causing coronavirus disease-2019 (COVID-19). Research evaluating the time, nature, and extent of surface disinfection of replication-competent viruses is needed. We evaluated the efficacy of two disinfectants against a replication-competent SARS-CoV-2 surrogate on three common public surfaces. Vesicular stomatitis virus expressing green fluorescent protein (VSV-GFP) was our replication-competent SARS-CoV-2 surrogate. Disinfection occurred using Super Sani-Cloth Germicidal Disposable Wipes and Oxivir Tb spray per manufacturer instructions to test the efficacy at reducing the presence, viability, and later replication of VSV-GFP on stainless steel, laminate wood, and porcelain surfaces using standardized methods after recovery and toxicity testing. During the main trials, we placed 100 µL spots of VSV-GFP at viral titers of 10⁸, 10⁷, and 10⁶ PFU/mL on each surface prior to disinfection. Trials were completed in triplicate and post-disinfection measurements on each surface were compared to the measurements of non-disinfected surfaces. Disinfectants were considered efficacious when ≥3-log₁₀ reduction in the number of infectious VSV-GFP virus units was observed on a given surface during all trials. Both disinfectants produced a ≥3.23-log₁₀ reduction in infectious VSV-GFP virus unit numbers, with all trials showing no viable, replication-competent VSV-GFP present on any tested surface. The two disinfectants eliminated the presence, viability, and later replication of VSV-GFP, our SARS-CoV-2 surrogate, on all surfaces. This information suggests that, if following manufacturer instructions, overcleaning surfaces with multiple disinfectant solutions may be unnecessary. Full article

Acute ruminal acidosis (ARA) is caused by the excessive intake of highly fermentable carbohydrates, followed by the massive production of D-lactate and the appearance of neutrophilic aseptic polysynovitis. Bovines with ARA develop different lesions, such as ruminitis, polioencephalomalacia (calves), liver abscess and lameness. Lameness in cattle with ARA is closely associated with the presence of laminitis and polysynovitis. However, despite decades of research in bovine lameness as consequence of ruminal acidosis, the aetiology and pathogenesis remain unclear. Fibroblast-like synoviocytes (FLSs) are components of synovial tissue, and under pathological conditions, FLSs increase cytokine production, aggravating inflammatory responses. We hypothesized that D-lactate could induce cytokine production in bovine FLSs. Analysis by qRT-PCR and ELISA revealed that D-lactate, but not L-lactate, increased the expression of IL-6 and IL-8 in a monocarboxylate transporter-1-dependent manner. In addition, we observed that the inhibition of the p38, ERK1/2, PI3K/Akt, and NF-κB pathways reduced the production of IL-8 and IL-6. In conclusion, our results suggest that D-lactate induces an inflammatory response; this study contributes to the literature by revealing a potential key role of D-lactate in the polysynovitis of cattle with ARA. Full article

The objective of this study was to characterize oligofructose-induced acute rumen lactic acidosis and its consequences in zebu cattle. We used 29 Nellore heifers which were submitted to experimental induction of laminitis by oligofructose excess. During the induction period, the animals underwent clinical examination, including laminitis diagnosis (hoof pressure testing and locomotion score) and blood and ruminal fluid sampling every six hours (over the initial 24 h) and every 12 h (up to 72 h), after the highest dose. Almost half of the animals (48.1%) required treatment with bicarbonate and saline to correct metabolic acidosis and dehydration. Due to this treatment, the animals were analyzed in treated (n = 13) and non-treated (n = 14) groups. The induction model promoted marked reduction in rumen pH, rumen anaerobiosis, carbon dioxide pressure, and increase in rumen lactate, blood osmolarity, and cortisol concentration. The animals treated had lower values of rumen pH and marked dehydration, evidenced by the increase in globular volume and serum urea. The clinical condition caused by excess oligofructose is severe, with the differential of the appearance of ephemeral fever and respiratory compensation against systemic acidosis, in addition to the frequent appearance of laminitis. Full article

Acute laminitis is a common equine disease characterized by intense foot pain, both acutely and chronically. The Obel grading system is the most widely accepted method for describing the severity of laminitis by equine practitioners, however this method requires movement (walk and trot) of the horse, causing further intense pain. The recently developed Horse Grimace Scale (HGS), a facial-expression-based pain coding system, may offer a more effective means of assessing the pain associated with acute laminitis. The aims of this study were: to investigate whether HGS can be usefully applied to assess pain associated with acute laminitis in horses at rest, and to examine if scoring HGS using videos produced similar results as those obtained from still images. Ten horses, referred as acute laminitis cases with no prior treatment, were included in the study. Each horse was assessed using the Obel and HGS (from images and videos) scales: at the admission (before any treatment) and at seven days after the initial evaluation and treatment. The results of this study suggest that HGS is a potentially effective method to assess pain associated with acute laminitis in horses at rest, as horses showing high HGS scores also exhibited higher Obel scores and veterinarians classified them in a more severe painful state. Furthermore, the inter-observer reliability of the HGS total score was good for both still images and video evaluation. There was no significant difference in HGS total scores between the still images and videos, suggesting that there is a possibility of applying the HGS in clinical practice, by observing the horse for a short time. However, further validation studies are needed prior to applying the HGS in a clinical setting. Full article