Immunophenotype investigation in feline intestinal non-B-cell lymphoma.

Lymphoma is the most common tumour of domestic cats, developing most frequently in the small intestine. Feline small intestinal lymphoma predominantly demonstrates a T-cell immunophenotype identified by standard immunopositivity for T cells with CD3 or immunopositivity for B cells with CD20. In contrast, a wide spectrum of immunohistochemical antibodies are applied in humans to diagnose the various specific lymphoma subtypes according to the WHO classification. Our aim was to augment our knowledge of immunophenotypes in feline non-B-cell lymphomas forming macroscopic masses in the intestinal tract. We evaluated the combined immunohistochemistry and flow cytometry findings from 15 cases. Neoplastic lymphoid cells were immunopositive for CD3 in 93% (14/15), granzyme B in 87% (13/15), CD5 in 20% (3/15), CD8 in 13% (2/15), CD4 in 7% (1/15) and CD56 in 7% (1/15) of cases. Cytotoxic granules indicating a cytotoxic origin of the neoplastic cells were identified by histopathology only in 13% (2/15) and by cytology in 47% (7/15) of the cases. Without immunohistochemical labelling of the cytotoxic protein granzyme B, the cytotoxic status would have been missed in 46% (6/13) of the cytological and in 85% (11/13) of the histopathological slides. These findings suggest that more complex immunophenotyping may advance our understanding and help prognosticate small intestinal T-cell lymphoma in cats.

Characterization of the plasma proteome from healthy adult dogs.

Introduction: Bloodwork is a widely used diagnostic tool in veterinary medicine, as diagnosis and therapeutic interventions often rely on blood biomarkers. However, biomarkers available in veterinary medicine often lack sensitivity or specificity. Mass spectrometry-based proteomics technology has been extensively used in the analysis of biological fluids. It offers excellent potential for a more comprehensive characterization of the plasma proteome in veterinary medicine. Methods: In this study, we aimed to identify and quantify plasma proteins in a cohort of healthy dogs and compare two techniques for depleting high-abundance plasma proteins to enable the detection of lower-abundance proteins via label-free quantification liquid chromatography-mass spectrometry. We utilized surplus lithium-heparin plasma from 30 healthy dogs, subdivided into five groups of pooled plasma from 6 randomly selected individuals each. Firstly, we used a commercial kit to deplete high-abundance plasma proteins. Secondly, we employed an in-house method to remove albumin using Blue-Sepharose. Results and discussion: Among all the samples, some of the most abundant proteins identified were apolipoprotein A and B, albumin, alpha-2-macroglobulin, fibrinogen beta chain, fibronectin, complement C3, serotransferrin, and coagulation factor V. However, neither of the depletion techniques achieved significant depletion of highly abundant proteins. Despite this limitation, we could detect and quantify many clinically relevant proteins. Determining the healthy canine proteome is a crucial first step in establishing a reference proteome for canine plasma. After enrichment, this reference proteome can later be utilized to identify protein markers associated with different diseases, thereby contributing to the diagnosis and prognosis of various pathologies.

Plasma proteome signature of canine acute haemorrhagic diarrhoea syndrome (AHDS).

Acute haemorrhagic diarrhoea is a common complaint in dogs. In addition to causes like intestinal parasites, dietary indiscretion, intestinal foreign bodies, canine parvovirus infection, or hypoadrenocorticism, acute haemorrhagic diarrhoea syndrome (AHDS) is an important and sometimes life-threatening differential diagnosis. There is some evidence supporting the link between Clostridium perfringens toxins and AHDS. These toxins may be partially responsible for the epithelial cell injury, but the pathogenesis of AHDS is still not fully understood. Recent studies have suggested that severe damage to the intestinal mucosa and associated barrier dysfunction can trigger chronic gastrointestinal illnesses. Besides bloodwork and classical markers for AHDS such as protein loss and intestinal bacterial dysbiosis, we focused mainly on the plasma-proteome to identify systemic pathological alterations during this disease and searched for potential biomarkers to improve the diagnosis. To accomplish the goals, we used liquid chromatography-mass spectrometry. We compared the proteomic profiles of 20 dogs with AHDS to 20 age-, breed-, and sex-matched control dogs. All dogs were examined, and several blood work parameters were determined and compared, including plasma biochemistry and cell counts. We identified and quantified (relative quantification) 207 plasmatic proteins, from which dozens showed significantly altered levels in AHDS. Serpina3, Lipopolysaccharide-binding protein, several Ig-like domain-containing proteins, Glyceraldehyde-3-phosphate dehydrogenase and Serum amyloid A were more abundant in plasma from AHDS affected dogs. In contrast, other proteins such as Paraoxonase, Selenoprotein, Amine oxidases, and Apolipoprotein C-IV were significantly less abundant. Many of the identified and quantified proteins are known to be associated with inflammation. Other proteins like Serpina3 and RPLP1 have a relevant role in oncogenesis. Some proteins and their roles have not yet been described in dogs with diarrhoea. Our study opens new avenues that could contribute to the understanding of the aetiology and pathophysiology of AHDS.

Traces of Canine Inflammatory Bowel Disease Reflected by Intestinal Organoids.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats and dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these organoids show phenotypic traits of the disease compared with control organoids obtained from healthy donors. To this aim, IBD and control organoids were subjected to quantitative proteomics analysis via liquid chromatography-mass spectrometry. The obtained data revealed notable differences between the two groups. The IBD organoids exhibited several alterations at the levels of multiple proteins that are consistent with some known IBD alterations. The observed phenotype in the IBD organoids to some degree mirrors the corresponding intestinal condition, rendering them a compelling approach for investigating the disease and advancing drug exploration. Additionally, our study revealed similarities to some human IBD biomarkers, further emphasizing the translational and comparative value of dogs for future investigations related to the causes and treatment of IBD. Relevant proteins such as CALU, FLNA, MSN and HMGA2, which are related to intestinal diseases, were all upregulated in the IBD duodenal organoids. At the same time, other proteins such as intestinal keratins and the mucosal immunity PIGR were depleted in these IBD organoids. Based on these findings, we propose that these organoids could serve as a valuable tool for evaluating the efficacy of therapeutic interventions against canine IBD.

Dysregulation of intestinal epithelial electrolyte transport in canine chronic inflammatory enteropathy and the role of the renin-angiotensin-aldosterone-system.

Chronic diarrhea is a hallmark sign of canine chronic inflammatory enteropathy (CIE), leading to fluid and electrolyte losses. Electrolyte homeostasis is regulated by the renin-angiotensin-aldosterone-system (RAAS), which might be involved in (counter-)regulating electrolyte losses in canine CIE. Whether and which electrolyte transporters are affected or if RAAS is activated in canine CIE is unknown. Thus, intestinal electrolyte transporters and components of the RAAS were investigated in dogs with CIE. Serum RAAS fingerprint analysis by mass spectrometry was performed in 5 CIE dogs and 5 healthy controls, and mRNA levels of intestinal electrolyte transporters and local RAAS pathway components were quantified by RT-qPCR in tissue biopsies from the ileum (7 CIE, 10 controls) and colon (6 CIE, 12 controls). Concentrations of RAAS components and mRNA expression of electrolyte transporters were compared between both groups of dogs and were tested for associations among each other. In dogs with CIE, associations with clinical variables were also tested. Components of traditional and alternative RAAS pathways were higher in dogs with CIE than in healthy controls, with statistical significance for Ang I, Ang II, and Ang 1-7 (all p < 0.05). Expression of ileal, but not colonic electrolyte transporters, such as Na+/K+-ATPase, Na+/H+-exchanger 3, Cl- channel 2, down-regulated in adenoma, and Na+-glucose-cotransporter (all p < 0.05) was increased in CIE. Our results suggest that the dys- or counter-regulation of intestinal electrolyte transporters in canine CIE might be associated with a local influence of RAAS. Activating colonic absorptive reserve capacities may be a promising therapeutic target in canine CIE.

Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans.

Chronic idiopathic intestinal inflammation is an increasing worldwide problem that affects companion animals, especially dogs, and human patients. Although these disease entities have been intensely investigated recently, many questions remain, and alternative therapeutic options are needed. Diarrhea caused by dysregulation of intestinal electrolyte transport and subsequent fluid and electrolyte losses often leads to secondary consequences for the patient. Currently, it is not exactly clear which mechanisms are involved in the dysregulation of intestinal fluid absorption, but differences in intestinal electrolyte shifts between human and canine patients suggest species-specific regulatory or counterregulatory mechanisms. Several intestinal electrolyte transporters are differentially expressed in human patients with inflammatory bowel disease (IBD), whereas there are virtually no studies on electrolyte transporters and their endocrine regulation in canine chronic inflammatory enteropathy. An important mechanism involved in regulating fluid and electrolyte homeostasis is the renin-angiotensin-aldosterone-system (RAAS), which may affect intestinal Na+ transport. While RAAS has previously been considered a systemic regulator of blood pressure, additional complex roles of RAAS in inflammatory processes have been unraveled. These alternative RAAS pathways may pose attractive therapeutic targets to address diarrhea and, thus, electrolyte shifts in human IBD and canine chronic inflammatory enteropathy. This article comparatively summarizes the current knowledge about electrolyte transport in human IBD and canine chronic inflammatory enteropathy and the role of RAAS and offers perspectives for novel therapeutic avenues.

Formerly bile-farmed bears as a model of accelerated ageing.

Bear bile-farming is common in East and Southeast Asia and this farming practice often results in irreversible health outcomes for the animals. We studied long-term effects of chronic bacterial and sterile hepatobiliary inflammation in 42 Asiatic black bears (Ursus thibetanus) rescued from Vietnamese bile farms. The bears were examined under anesthesia at least twice as part of essential medical interventions. All bears were diagnosed with chronic low-grade sterile or bacterial hepatobiliary inflammation along with pathologies from other systems. Our main finding was that the chronic low-grade inflammatory environment associated with bile extraction in conjunction with the suboptimal living conditions on the farms promoted and accelerated the development of age-related pathologies such as chronic kidney disease, obese sarcopenia, cardiovascular remodeling, and degenerative joint disease. Through a biomimetic approach, we identified similarities with inflammation related to premature aging in humans and found significant deviations from the healthy ursid phenotype. The pathological parallels with inflammageing and immuno-senescence induced conditions in humans suggest that bile-farmed bears may serve as animal models to investigate pathophysiology and deleterious effects of lifestyle-related diseases.

Gut microbiome signatures of Yorkshire Terrier enteropathy during disease and remission.

The role of the gut microbiome in developing Inflammatory Bowel Disease (IBD) in humans and dogs has received attention in recent years. Evidence suggests that IBD is associated with alterations in gut microbial composition, but further research is needed in veterinary medicine. The impact of IBD treatment on the gut microbiome needs to be better understood, especially in a breed-specific form of IBD in Yorkshire Terriers known as Yorkshire Terrier Enteropathy (YTE). This study aimed to investigate the difference in gut microbiome composition between YTE dogs during disease and remission and healthy Yorkshire Terriers. Our results showed a significant increase in specific taxa such as Clostridium sensu stricto 1, Escherichia-Shigella, and Streptococcus, and a decrease in Bacteroides, Prevotella, Alloprevotella, and Phascolarctobacterium in YTE dogs compared to healthy controls. No significant difference was found between the microbiome of dogs in remission and those with active disease, suggesting that the gut microbiome is affected beyond clinical recovery.

Microbial dysbiosis and fecal metabolomic perturbations in Yorkshire Terriers with chronic enteropathy.

Dysbiosis and perturbations of fecal metabolic profiles have been reported in dogs with inflammatory bowel disease. Currently the incidence of dysbiosis and the fecal metabolomic profile in Yorkshire Terriers with chronic enteropathy (YTE) and the effects of treatment are unknown. This prospective observational study analyzed the dysbiosis index (DI) and fecal bile acid, sterol and fatty acid profiles in 14 Yorkshire Terriers with active YTE, 11 dogs in clinical remission, and 26 healthy Yorkshire Terriers. YTE was associated with dysbiosis and a significant increase in fatty acids (docosanoate, p = 0.002; gondoate, p = 0.026; erucate, p < 0.001; nervonate, p < 0.001; linolenate, p < 0.001), and plant sterols (campesterol, p < 0.001; brassicasterol, p = 0.024). The abundances of Fusobacterium (p < 0.001) and Cl. hiranonis (p = 0.018) and the concentrations of the secondary bile acid ursodeoxycholic acid (p = 0.033) and the plant sterol sitostanol (p = 0.003) were significantly decreased compared to healthy dogs. Dysbiosis, abundances of Fusobacterium, Cl. hiranonis and fecal concentrations of bile acids and sterols did not recover after treatment, while fecal fatty acid concentrations decreased in treated dogs. YTE is associated with dysbiosis and changes in bile acid, fatty acid, and sterol metabolism. These changes only recovered partially despite clinical remission. They might be breed-specific and involved in the pathogenesis of YTE.

Electromechanical Photophysics of GFP Packed Inside Viral Protein Cages Probed by Force-Fluorescence Hybrid Single-Molecule Microscopy.

Packing biomolecules inside virus capsids has opened new avenues for the study of molecular function in confined environments. These systems not only mimic the highly crowded conditions in nature, but also allow their manipulation at the nanoscale for technological applications. Here, green fluorescent proteins are packed in virus-like particles derived from P22 bacteriophage procapsids. The authors explore individual virus cages to monitor their emission signal with total internal reflection fluorescence microscopy while simultaneously changing the microenvironment with the stylus of atomic force microscopy. The mechanical and electronic quenching can be decoupled by ≈10% each using insulator and conductive tips, respectively. While with conductive tips the fluorescence quenches and recovers regardless of the structural integrity of the capsid, with the insulator tips quenching only occurs if the green fluorescent proteins remain organized inside the capsid. The electronic quenching is associated with the coupling of the protein fluorescence emission with the tip surface plasmon resonance. In turn, the mechanical quenching is a consequence of the unfolding of the aggregated proteins during the mechanical disruption of the capsid.

Utility of a canine TSH assay for diagnosis and monitoring of feline hyperthyroidism.

OBJECTIVE: This retrospective study was initiated to evaluate the utility of TSH measurements using a common canine TSH assay to diagnose and monitor feline hyperthyroidism after radioiodine or thyreostatic drug treatment. MATERIAL AND METHODS: The electronic database of the University of Veterinary Medicine Vienna was searched for combined TSH and T4 measurements. 217 pairs of TSH and T4 from 136 cats with possible hyperthyroidism were assigned to group A (untreated; n = 24) and B (treated; n = 193). Measurements in group B were then subcategorized according to T4 concentrations (reference range 15-50 nmol/L): group B1 = elevated T4 (n = 46), group B2 = normal T4 (n = 84) and group B3 = decreased T4 (n = 63). Group B2 was further divided into cats with low normal (group B2a; n = 35), medium normal (group B2b; n = 29) and high normal (group B2c; n = 20) T4 concentrations. RESULTS: TSH was detectable in 4 (17 %) of the 24 untreated cats (group A) and did not return to normal despite seemingly successful therapy in two. Increased TSH concentrations were observed in 3.6 % of the treated cats in group B2 and 2.9 %, 6.9 %, and 0 % in subgroups B2a, B2b and B2c, respectively. Forty-four percent of the treated cats with a decreased T4 (group B3) had an increased TSH concentration. TSH correlated with treatment length (r = 0.358, p = 0.004) and was significantly higher in cats treated for more than 3 months (p = 0.008). CONCLUSION: TSH was detectable in a significant number of untreated hyperthyroid cats and thus this parameter should not be used to definitively rule out feline hyperthyroidism. Furthermore, the very low prevalence of increased TSH concentrations in treated hyperthyroid cats with a normal T4 and cost benefit calculations do not support the routine measurement of TSH in these cats. The fact that TSH correlated with time since treatment start and 56 % of the cats with a decreased T4 had TSH concentrations within the reference limits, suggests delayed recovery of the pituitary thyrotrophs which might explain the low prevalence of subclinical hypothyroidism in the present study. CLINICAL RELEVANCE: TSH measurement in cats with suspected or treated hyperthyroidism using a canine assay lacks diagnostic sensitivity and can only complement therapeutic decision-making.

Chronic cholecystitis: Diagnostic and therapeutic insights from formerly bile-farmed Asiatic black bears (Ursus thibetanus).

Across Southeast Asia and China, more than 17000 Asian bears are kept under suboptimal conditions and farmed for their bile to meet the consumer demand for traditional medicine products. Years of unsterile and repetitive bile extraction contribute to the development of chronic sterile or bacterial cholecystitis, a pathology commonly diagnosed in formerly bile-farmed bears. In both human and veterinary medicine, the diagnostic value of the macroscopic bile examination for assessing gallbladder disease is unclear. The objective of this study is to identify the role of gallbladder bile color, viscosity, and turbidity, while comparing them with established markers of cholecystitis. Moreover, it aims to define the optimal duration of oral antibiotic treatment for chronic bacterial cholecystitis in bears associated with bile farming. Thirty-nine adult, formerly bile-farmed Asiatic black bears (Ursus thibetanus) were examined under anesthesia and underwent percutaneous ultrasound guided cholecystocentesis. A total of 59 bile samples were collected with 20 animals sampled twice to evaluate the therapeutic success. All bile aspirates were assessed macroscopically and microscopically followed by submission for bacterial culture and antimicrobial sensitivity. In the majority of bears, samples with cytological evidence of bactibilia lacked inflammatory cells and did not always correlate with positive bacterial cultures. The most common bacterial isolates were Enterococcus spp, Streptococcus spp and Escherichia coli. Based on our findings, the optimal duration of antibiotic treatment for chronic bacterial cholecystitis is 30 days. Moreover, unlike Gamma-glutamyl Transferase (GGT) and gallbladder wall thickness, the organoleptic properties of bile were found to be reliable markers of chronic gallbladder inflammation with color and turbidity indicating cholestasis. The current study highlights the importance of cholecystocentesis for the management of gallbladder disease and provides initial results on the possible diagnostic value of macroscopic bile examination.

A Preliminary Metabolomic Study of Yorkshire Terrier Enteropathy.

Perturbations of metabolite profiles in human and canine enteropathies have been reported before. However, data in dogs are scarce and inconsistent. Currently, the metabolite profile in Yorkshire Terrier enteropathy (YTE) and the impact of treatment is unknown. The objective of this study was to investigate the plasma metabolome of 13 Yorkshire Terriers with YTE and compare it to 20 healthy Yorkshire Terriers. Furthermore, we studied the impact of treatment on the metabolome. In this prospective observational study, plasma metabolite profiles were analyzed by flow injection analysis-tandem mass spectrometry (FIA-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a targeted metabolomics kit. Metabolite analysis revealed that YTE is accompanied by changes in lipid and bile acid metabolism. YTE was associated with a significant decrease of long-chain fatty acids (octadecenoic acid, eicosadienoic acid, eicosatrienoic acid) and lower levels of long-chain acylcarnitines (tetradecanoylcarnitine, hexadecanoylcarnitine, hexadecenoylcarnitine, octadecenoylcarnitine) compared with healthy controls. Furthermore, taurodeoxycholic acid, a secondary bile acid, was decreased in plasma from YTE patients. These changes might be breed-specific and might be involved in the pathogenesis of YTE. Interestingly, changes in metabolite levels were not recovered after treatment and differed considerably from healthy controls.

Pathobiology of highly pathogenic H5 avian influenza viruses in naturally infected Galliformes and Anseriformes in France during 2015-2016.

In late 2015, an epizootic of Highly Pathogenic Avian Influenza (H5Nx) was registered in Southwestern France, including more than 70 outbreaks in commercial poultry flocks. Phylogenetic analyses suggested local emergence of H5 viruses which differed from A/goose/Guangdong/1/1996 clade 2.3.4.4b lineage and shared a unique polybasic cleavage site in their hemagglutinin protein. The present work provides an overview of the pathobiological picture associated with this epizootic in naturally infected chickens, guinea fowls and ducks. Upon necropsy examination, selected tissues were sampled for histopathology, immunohistochemistry and quantitative Real Time Polymerase Chain Reaction. In Galliformes, HPAIVs infection manifested as severe acute systemic vasculitis and parenchymal necrosis and was associated with endothelial expression of viral antigen. In ducks, lesions were mild and infrequent, with sparse antigenic detection in respiratory and digestive mucosae and leukocytes. Tissue quantifications of viral antigen and RNA were higher in chickens and guinea fowls compared to duck. Subsequently, recombinant HA (rHA) was generated from a H5 HPAIV isolated from an infected duck to investigate its glycan-binding affinity for avian mucosae. Glycan-binding analysis revealed strong affinity of rHA for 3'Sialyl-LacNAc and low affinity for Sialyl-LewisX, consistent with a duck-adapted virus similar to A/Duck/Mongolia/54/2001 (H5N2). K222R and S227R mutations on rHA sequence shifted affinity towards Sialyl-LewisX and led to an increased affinity for chicken mucosa, confirming the involvement of these two mutations in the glycan-binding specificity of the HA. Interestingly, the rHA glycan binding pattern of guinea fowl appeared intermediate between duck and chicken. The present study presents a unique pathobiological description of the H5 HPAIVs outbreaks that occurred in 2015-2016 in Southwestern France.

Proliferation Activity in Canine Gastrointestinal Lymphoma.

Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine gastrointestinal lymphoma samples according to the latest World Health Organization classification and to determine the Ki67 proliferation index by manual counting, digital image analysis and visual estimation. The Ki67 index was then correlated with subtype, immunophenotype, mitotic index, grade and tumour location. The mitotic index correlated positively with the Ki67 index. A significantly higher number of Ki67-positive cells was found in enteropathy-associated T-cell lymphoma type I and in diffuse large B-cell lymphoma compared with enteropathy-associated T-cell lymphoma type II. There was also a significant difference in Ki67 immunolabelled cells between grade 1 and grade 2 lymphomas. Moderate agreement was found between the Ki67 index as obtained by manual counting and visual estimation, but there was strong agreement between manual counting and digital image analysis. The user-friendly digital imaging system used in this study could have potential for future determination of the Ki67 index in lymphoid neoplasms.

A Recurrent STAT5BN642H Driver Mutation in Feline Alimentary T Cell Lymphoma.

Alimentary lymphomas arising from T cells are rare and aggressive malignancies in humans. In comparison, they represent the most common anatomical form of lymphoma in cats. Due to the low prevalence in humans, the underlying pathomechanism for these diseases is poorly characterised, limiting experimental analysis and therapeutic exploration. To date, activating mutations of the JAK/STAT core cancer pathway and particularly the STAT5B oncoprotein have been identified in human enteropathy-associated T cell lymphoma. Here, we describe a high homology of human and feline STAT3 and STAT5B proteins and strong conservation at the genomic level. Analysis of 42 samples of feline T cell alimentary lymphoma reveals broad activation of STAT3 and STAT5B. Screening for known activating mutations in STAT3 or STAT5B identifies the presence of the STAT5BN642H driver mutation in feline enteropathy-associated T cell lymphoma in 7 out of 42 (16.67%) samples in total. Regarding lymphoma subtypes, the majority of mutations with 5 out of 17 (29.41%) cases were found in feline enteropathy-associated lymphoma type II (EATL II). This identification of an oncogenic STAT5B driver mutation in felines recapitulates the genetic situation in the corresponding human disease, thereby establishing the cat as a potential new model for a rare and incurable human T cell disease.

Aldosterone Is Positively Associated With Circulating FGF23 Levels in Chronic Kidney Disease Across Four Species, and May Drive FGF23 Secretion Directly.

BACKGROUND: Chronic kidney disease (CKD) is accompanied by increases in circulating fibroblast growth factor 23 (FGF23) and aldosterone levels. Here, we tested the hypothesis that aldosterone may be one of the driving forces behind increased FGF23 secretion in CKD. METHODS: Using data from a prospective study in humans, a retrospective study in dogs and cats, and an experimental study in 5/6-nephrectomized mice, we analyzed the relationship between circulating FGF23 and serum aldosterone levels in CKD across four species. To assess the effects of acute inhibition of aldosterone signaling on circulating FGF23, we acutely treated mice with established CKD with the mineralocorticoid receptor blocker canrenone (50 mg/kg iv/sc), and measured intact FGF23 before and 24 h as well as 72 h after start of administration of the drug. RESULTS: We found a tight positive association between circulating intact FGF23 and serum aldosterone in human, canine, and feline CKD patients, as well as in experimental murine CKD (humans: r S = 0.57, p = 0.0368; dogs: r S = 0.66, p = 0.0019; cats: r S = 0.75, p = 0.0003; mice: r S = 0.49, p = 0.0004). Injection of canrenone in mice with established CKD did not lead to changes in FGF23 levels within 24 h, but reduced FGF23 in all mice at 72 h. CONCLUSION: Aldosterone may drive enhanced FGF23 secretion in CKD, possibly explaining the tight positive association between circulating intact FGF23 and aldosterone in human, canine, and feline CKD patients as well as in experimental CKD models.

Upregulation of signal transducer and activator of transcription 3 in dogs with chronic inflammatory enteropathies.

BACKGROUND: In inflammatory bowel disease (IBD) in humans, phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is upregulated in mucosal epithelial cells and correlates with clinical severity. HYPOTHESIS/OBJECTIVE: To investigate the expression pattern of pSTAT3 in the mucosa of dogs with chronic inflammatory enteropathy (CIE) and explore correlations between its expression and clinical and histopathological severity scoring. ANIMALS: Twenty-eight canine CIE patients grouped into food-responsive enteropathy (FRE; 9), steroid-responsive enteropathy (SRE; 10), and protein-losing enteropathy (PLE; 9). Ten healthy beagle dogs served as controls (CO). METHODS: Retrospective case control study. Immunohistochemistry was used to detect pSTAT3 in canine duodenal mucosa samples. RESULTS: Compared to CO, SRE (P < .001) and PLE (P < .001) dogs had significantly higher pSTAT3 expression in the villus epithelium. The SRE group had a significantly higher expression in the villus lamina propria (VLP) compared to controls (P = .009). In the crypt epithelium (CE), all CIE dogs had significantly higher pSTAT3 expression (FRE, P = .002; SRE, P = .003; PLE, P < .001) compared to CO. In the lamina propria crypt region (CLP), dogs with FRE (P = .04) and SRE (P = .03) had significantly upregulated pSTAT3 compared to controls. A positive correlation was found between canine chronic enteropathy clinical activity index (CCECAI) scoring and pSTAT3 expression for both epithelial (rho = .541; P < .001) and crypt regions (rho = .32; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: pSTAT3 is upregulated in CIE in dogs, correlates with clinical severity, and may be helpful as a clinical marker in dogs with CIE.

Burnout, resilience and work engagement among Dutch intensivists in the aftermath of the COVID-19 crisis: A nationwide survey.

PURPOSE: The COVID-19 crisis put a strain on intensive care resources everywhere in the world increasing the risk of burnout. Previously, the prevalence of burnout among Dutch intensivists was found to be low. Engagement and resilience among intensivists have not previously been studied quantitatively, however, both are related to burnout and provide a possible way to mitigate burnout. Our objective was to study burnout and its association with work engagement and resilience among Dutch intensivists in the aftermath of the COVID-19 crisis. METHODS: An online questionnaire was sent to all Dutch intensivists. The questionnaire consisted of questions on personal and work-related characteristics and validated questionnaires: the Maslach Burnout Inventory, the Utrecht Work Engagement Scale, and the Resilience Evaluation Scale. RESULTS: The response rate was 27.2% with 162 evaluable responses. Thirteen respondents (8.0%) were classified as having burnout, 63 (38.9%) respondents were reporting high work engagement. Burnout was found to be negatively associated with both work engagement and resilience. CONCLUSION: In the aftermath of the 2020 COVID-19 crisis, we found a raised prevalence of burnout among intensivists, however this is still low in international comparisons. Intensivists with burnout scored low on resilience and low on work engagement.