The effect of the size of gold nanoparticle contrast agents on CT imaging of the gastrointestinal tract and inflammatory bowel disease.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. CT is a common imaging modality for evaluating IBD, especially in patients with acute abdominal pain presenting to emergency departments. CT's major limitation lies in its lack of specificity for imaging UC, as the commonly used agents are not well-suited for inflamed areas. Recent studies gastrointestinal tract (GIT) in UC. Further systemic research is needed to explore novel contrast agents that can specifically image disease processes in this disease setting.

Esomeprazole induces structural changes and apoptosis and alters function of in vitro canine neoplastic mast cells.

Histamine-2 receptor antagonists such as famotidine and proton pump inhibitors such as esomeprazole are commonly used in canine MCT disease, but direct effects on dog MCs have not been evaluated. Omeprazole is a proton pump inhibitor which has been demonstrated to cause structural and functional changes to in vitro murine mast cells (MCs). It has not yet been determined if esomeprazole, the commercially available and commonly prescribed S-isomer of omeprazole, has similar effects. Our primary study objective was to evaluate and compare the effects of acid suppressants (esomeprazole and famotidine) on MC ultrastructure, viability, and function in vitro using both healthy and neoplastic MCs. Murine bone marrow derived mast cells (BMMC), human LAD2, and canine C2 and BR cells, were used for these studies, representing a single healthy (i.e., BMMCs) MC model and multiple neoplastic MC models (i.e., LAD2, C2, BR), respectively. The rat basophilic leukemic (RBL-2H3) and canine B cell lymphoma 17-71 cell lines served as granulocytic and agranulocytic control lines for experiments, respectively. The treatment effect of acid suppressants on MC ultrastructure was assessed via both light and transmission electron microscopy. Differences in MC viability was assessed between groups via MTS-based, colorimetric assays and flow cytometry. Degranulation was assessed by quantification of ß-hexosaminidase (i.e., LAD2 and RBL-2H3). Esomeprazole-treated MCs of all lines exhibited dramatic time and concentration-dependent alterations in ultrastructure (i.e., increased vacuolization, compromise of cell membrane), increased apoptosis, and altered degranulation responses in comparison to famotidine and vehicle-treated cells. The canine B cell lymphoma cells consistently exhibited either no significant (i.e., cytotoxicity assays) or greatly diminished treatment responses (i.e., apoptosis) compared to MCs. Esomeprazole, but not famotidine, induces significant cytotoxicity, as well as alterations to cell structure and function to multiple lines of in vitro neoplastic MCs. Continued in vitro work investigating the specific mechanisms by which proton pump inhibitors induce these effects, as well as prospective, in vivo work comparing the treatment effects of acid suppressants on canine MCTs, are warranted.

Feline eosinophilic sclerosing fibroplasia - a characteristic inflammatory response in sites beyond the gastrointestinal tract: case report and proposed nomenclature.

Case summary: An adult male neutered Russian Blue cat presented for a right-sided nasal mass with bilateral retropharyngeal and right mandibular lymphadenomegaly. Medial retropharyngeal lymph node excision with nasal mass biopsy revealed eosinophilic sclerosing lymphadenitis and eosinophilic and lymphoplasmacytic rhinitis, respectively. Bacterial culture of the lymph node grew Pseudomonas aeruginosa, and treatment with pradofloxacin was started. Despite initial improvement, clinical signs recurred after 9 months, and fine-needle aspirates of the right mandibular and left medial retropharyngeal lymph nodes showed eosinophilic and mastocytic infiltration. Bacterial culture of the left medial retropharyngeal lymph node grew P aeruginosa, and treatment with anti-inflammatory doses of prednisolone and, later, marbofloxacin was instituted. Relevance and novel information: This report describes a case of feline eosinophilic sclerosing lymphadenitis diagnosed outside of the abdominal cavity and is the first case reported to be associated with P aeruginosa. Feline eosinophilic sclerosing lymphadenitis should be considered as a differential for lymphadenopathy occurring in areas other than the abdominal cavity. Feline eosinophilic sclerosing lymphadenitis may develop in cats due to a species-specific inflammatory response to chronic bacterial and fungal infections.

SARS-CoV-2 Delta Variant (AY.3) in the Feces of a Domestic Cat.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species have been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors' knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States.

Detection and Interspecies Comparison of SARS-CoV-2 Delta Variant (AY.3) in Feces from a Domestic Cat and Human Samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species has been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors' knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States.

Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma.

Equine asthma is a naturally occurring lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling, and lower airway inflammation. Asthma is currently divided into two major groups, mild to moderate asthma (mEA) and severe asthma (sEA), but further subtyping by phenotype (i.e., clinical presentation) and/or endotype (i.e., cellular mechanisms) may be warranted. For this study, we were interested in further investigation of cellular and inflammatory characteristics of EA, including airway mast cells. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. We hypothesized that there would be significant differences in the cellular mast cell phenotypes (i.e., mucosal vs. connective tissue) and cytokine profiles in the BALF of asthmatic vs. healthy horses and across asthma groups. We assert these characteristics may inform additional subtypes of equine asthma. Adult horses were recruited from the institution's teaching herd and clinical caseload. Mast cell protease gene expression of the BALF cellular component and multiplex bead immunoassay for cytokine concentrations in the BALF supernatant were investigated. Airway mast cells primarily expressed tryptase, with low levels of chymase. No significant changes in protease expression were detected across groups. Horses with severe asthma had increased TNF-α, CXCL-8, and IFN-γ concentrations in BALF supernatant. Multidimensional analysis demonstrated healthy and mEA horses have overlapping characteristics, with sEA separating from the other groups. This difference was primarily due to BALF neutrophil and lymphocyte concentrations. These study results further inform understanding of EA immunopathology, and future studies designed to investigate asthma phenotypes and endotypes. Ultimately, a better understanding of these groups could help identify novel therapeutic strategies.

Diagnosis of bacterial urinary tract infection: Utility of urine myeloperoxidase concentration to predict urine culture results in dogs.

Suspected bacterial urinary tract infections (UTI) are a common cause of overuse and misuse of antimicrobials. A bedside diagnostic test that could accurately predict urine culture results would prevent antimicrobial overuse, but accurate biomarkers have not yet been identified in veterinary medicine. The objective of this study was to evaluate urine myeloperoxidase (uMPO) as a rapidly available, accurate marker to predict urine culture results. We hypothesized that uMPO would be higher in dogs with a positive urine culture than in dogs with a negative urine culture, and that uMPO could be used to aid in the accurate diagnosis of significant bacteriuria. Urine samples were collected from a veterinary university clinical pathology lab. uMPO concentration was measured using a commercially available canine myeloperoxidase (MPO) enzyme-linked immunosorbent assay (ELISA). Following validation, samples from 98 dogs that had a urinalysis and urine culture performed as part of their diagnostic investigation were included. Forty-seven dogs had a negative urine culture and fifty-one dogs had a positive urine culture. uMPO levels were significantly higher in samples that had a positive culture (median 2.13 ng/ml; IQR 0.98-7.07) versus samples that had a negative culture (median 1.07 ng/ml; IQR 0.52-1.84)(p < 0.005). Based on receiver-operator characteristic, a cutoff of 0.55 ng/ml was chosen to maximize sensitivity and specificity. Using a cutoff of 0.55 ng/ml, uMPO had a sensitivity of 70% and specificity of 69% to determine the presence of a positive culture. However, the degree of overlap between groups may preclude the use of this test as a surrogate for urine culture in a clinical setting.

S. Typhimurium challenge in juvenile pigs modulates the expression and localization of enteric cholinergic proteins and correlates with mucosal injury and inflammation.

The cholinergic system plays a central role in regulating critical gastrointestinal functions, including motility, secretion, barrier and immune function. In rodent models of acute, non-infectious gastrointestinal injury, the cholinergic system functions to inhibit inflammation; however, during inflammation local expression and regulation of the cholinergic system is not well known, particularly during infectious enteritis. The objective of this study was to determine the intrinsic expression of the enteric cholinergic system in pig ileum following an acute challenge with Salmonella enterica serovar Typhimurium DT104 (S. Typhimurium). At 2 d post-challenge, a three-fold reduction in ileal acetylcholine (ACh) levels was observed in challenged animals, compared with controls. Ileal acetylcholinesterase (AChE) activity was decreased (by four-fold) while choline acetyltransferase (ChAT) expression was increased in both the ileum and mesenteric lymph nodes. Elevated ChAT found to localize preferentially to mucosa overlying lymphoid follicles of the Peyers patch in challenged pigs, with more intense labeling for ChAT in S. Typhimurium challenged pigs compared to controls. Ileal mRNA gene expression of muscarinic receptor 1 and 3 was also increased in challenged pigs, while muscarinic receptor 2 and the nicotinic receptor alpha 7 subunit gene expression were unaffected. A positive correlation was observed between ChAT protein expression in the ileum, rectal temperature, and histopathological severity in challenged animals. These data show that inflammation from S. Typhimurium challenge alters enteric cholinergic expression by down-regulating acetylcholine concentration and acetylcholine degrading enzymes while increasing acetylcholine synthesis proteins and receptors. Given the known anti-inflammatory role of the cholinergic system, the divergent expression of cholinergic genes may represent an attempt to limit tissue damage by preserving cholinergic signaling in the face of low ligand availability.

Infant twins' social interactions with caregivers and same-age siblings.

The study of twin behavior offers the opportunity to study differential patterns of social and communicative interactions in a context where the adult partner and same-age peer are equally familiar. We investigated the development of social engagement, communicative gestures, and imitation in 7- to 25-month-old twins. Twin dyads (N=20 pairs) participated in 10-min, semi-structured play sessions, with the mother seated in a chair completing paperwork for half the session, and on the floor with her children for the other half. Overall, twins engaged more with their mothers than with their siblings: they showed objects and imitated speech and object use more frequently when interacting with their mothers than with their siblings. When the mother was otherwise engaged, the twins played with toys separately, observed each other's toy play, or were unengaged. These results demonstrate that adult scaffolding of social interactions supports increased communicative bids even in a context where both familiar peers and adults are available as communicative partners.

Retrospective evaluation of risk factors and outcome predictors in cats with diabetic ketoacidosis (1997-2007): 93 cases.

OBJECTIVES: To determine risk factors and outcome predictors in cats with diabetic ketoacidosis (DKA). DESIGN: Retrospective study. Inclusion in the DKA group required blood glucose concentration > 13.9 mmol/L (250 mg/dL), venous pH < 7.35, and urine or serum acetoacetate concentration greater than 1.5 mmol/L (15 mg/dL). Signalment and weight were recorded in all cats with uncomplicated diabetes mellitus (DM) without DKA and in all other nondiabetic cats examined during the study period. Clinicopathologic variables, concurrent disorders, and initial insulin intravenous (IV) continuous-rate infusion (CRI) concentration of 1.1 or 2.2 U/kg/240 mL bag of 0.9% NaCl, were examined for a possible association with outcome. SETTING: University teaching hospital. ANIMALS: Ninety-three cats with DKA, 682 cats with uncomplicated DM, and 16,926 cats without DM or DKA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cats with DKA were younger (median age 9.4 years; range, 1-17.9 years) than cats with uncomplicated DM (median 11.6 years; range 0.7-19.5 years, P < 0.0003). Siamese cats were overrepresented in the DKA group compared to the uncomplicated DM or nondiabetic group (P = 0.038 and P = 0.01, respectively). Poor outcome (defined as death due to disease or by euthanasia) in 36 cats with DKA (39%) was associated with increased initial creatinine, BUN, total serum magnesium, and total bilirubin concentrations (P = 0.007, P = 0.005, P = 0.03, P = 0.03, respectively). Cats treated with a higher concentration of insulin were less likely to have a poor outcome compared to cats treated with a lower concentration of insulin (odds ratio 0.14, 95% confidence interval 0.02-1.16, P = 0.02). CONCLUSIONS: Cats with DKA are more likely to be Siamese than cats with uncomplicated DM. Poor outcome of cats with DKA is associated with increased initial creatinine, BUN, total magnesium, and total bilirubin concentrations. Good outcome was associated with a higher concentration of IV insulin CRI.

Neonatal brainstem function and 4-month arousal-modulated attention are jointly associated with autism.

The authors evaluated the contribution of initially abnormal neonatal auditory brainstem responses (ABRs) and 4-month arousal-modulated attention visual preference to later autism spectrum disorder (ASD) behaviors in neonatal intensive care unit (NICU) graduates. A longitudinal study design was used to compare NICU graduates with normal ABRs (n = 28) to those with initially abnormal ABRs (n = 46) that later resolved. At 4 months postterm age, visual preference (measured after feeding) for a random check pattern flashing at 1, 3, or 8 Hz and gestational age (GA) served as additional predictors. Outcome measures were PDD Behavior Inventory (PDDBI) scores at 3.4 years (standard deviation = 1.2), and developmental quotients (DQ) obtained around the same age with the Griffiths Mental Development Scales (GMDS). Preferences for higher rates of stimulation at 4 months were highly correlated with PDDBI scores (all P-values < 0.01) and the GMDS Hearing and Speech DQ, but only in those with initially abnormal ABRs. Effects were strongest for a PDDBI social competence measure most associated with a diagnosis of autism. For those with abnormal ABRs, increases in preference for higher rates of stimulation as infants were linked to nonlinear increases in severity of ASD at 3 years and to an ASD diagnosis. Abnormal ABRs were associated with later reports of repetitive and ritualistic behaviors irrespective of 4-month preference for stimulation. The joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at 4 months, both indices of early brainstem dysfunction, may be a marker for the development of autism in this cohort.

The development of selective attention and inhibition in NICU graduates during the preschool years.

Neonatal intensive care unit (NICU) graduates have a higher incidence of attention problems including attention deficit hyperactivity disorder (ADHD). Thus, we examined the effect of risk factors (birth weight (BW), central nervous system (CNS) injury, gender, maternal education) on attention/inhibition during reaction time, continuous performance and Go/No-Go tasks at 42, 51, and 60 months (n = 271). Very low BW NICU graduates (<1,500 g) performed worse than typical BW ones (>2,500 g), displaying poorer target/non-target discrimination. Males responded faster than females, but made more false alarms and random responses. Despite short duration tasks, attention waned. Performance improved with age, but even at 60 months children had difficulty inhibiting random responding.

Early medical and behavioral characteristics of NICU infants later classified with ASD.

OBJECTIVES: Recent evidence suggests higher prevalence of autism spectrum disorder (ASD) in NICU graduates. This aim of this study was to identify retrospectively early behaviors found more frequently in NICU infants who went on to develop ASD. METHODS: Twenty-eight NICU graduates who later received a diagnosis of ASD were compared with 2169 other NICU graduates recruited from 1994 to 2005. They differed in gender, gestational age, and birth cohort. These characteristics were used to draw a matched control sample (n=112) to determine which, if any, early behaviors discriminated subsequent ASD diagnosis. Behavioral testing at targeted ages (adjusted for gestation) included the Rapid Neonatal Neurobehavioral Assessment (hospital discharge, 1 month), Arousal-Modulated Attention (hospital discharge, 1 and 4 months), and Bayley Scales of Infant Development (multiple times, 4-25 months). RESULTS: At 1 month, children with ASD but not control children had persistent neurobehavioral abnormalities and higher incidences of asymmetric visual tracking and arm tone deficits. At 4 months, children with ASD had continued visual preference for higher amounts of stimulation than did control children, behaving more like newborns. Unlike control children, children with ASD had declining mental and motor performance by 7 to 10 months, resembling infants with severe central nervous system involvement. CONCLUSIONS: Differences in specific behavior domains between NICU graduates who later receive a diagnosis of ASD and matched NICU control children may be identified in early infancy. Studies with this cohort may provide insights to help understand and detect early disabilities, including ASD.

Parent PDD behavior inventory profiles of young children classified according to autism diagnostic observation schedule-generic and autism diagnostic interview-revised criteria.

Quantitative variations in score profiles from the parent version of the PDD Behavior Inventory (PDDBI) were examined in young Autism and PDD-NOS groups defined by ADOS-G and ADI-R criteria, relative to a not spectrum (NS) group of similar age. Both the Autism and the PDD-NOS group profiles markedly differed from the NS group. The most sensitive measures of group differences were those domain and composite scores that assessed social communication competence, as well as the overall Autism Composite score. Sensitivity, specificity and positive and negative predictability measures were quite good for these measures. It was concluded that the PDDBI is useful in assisting in the differential diagnosis of autism spectrum disorder.

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005).

OBJECTIVE: To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. DESIGN: Retrospective case-control study. ANIMALS: 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. PROCEDURES: Sensitivity and specificity of basal serum or plasma cortisol concentrations of either 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is

Desmoglein-1 is a minor autoantigen in dogs with pemphigus foliaceus.

The majority of human patients with pemphigus foliaceus (PF) have circulating IgG autoantibodies that target conformational epitopes on the desmosomal cadherin desmoglein-1 (dsg1). Limited studies using immunoblot techniques suggested that the principal autoantigen in dogs with PF might also be dsg1. It was the objective of this study to test this hypothesis. A comprehensive survey of canine PF sera was conducted using a novel screening strategy that detects conformational epitopes. This method consists of the ectopic expression of canine dsg1 at the surface of human 293T epithelial kidney cells and their live screening, i.e. prior to fixation. Out of seven control human PF sera that bound to canine epidermis, three (57%) contained IgG autoantibodies that recognized ectopically expressed canine dsg1 with a membrane and punctate pattern. Out of 83 canine PF sera only five (6%) contained IgG that recognized canine dsg1. Consistent with findings for human PF sera obtained in this study, autoantibody binding was conformation- and glycosylation-dependent as demonstrated by calcium chelation with EDTA and tunicamycin or wheat germ agglutinin treatment, respectively. In conclusion, these studies establish canine dsg1 as a minor autoantigen for canine PF. Antigenic epitopes appear to be conformation- and glycosylation-dependent.