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At the GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany, a prototype cryomodule (advanced demonstrator) for the superconducting (SC) continuous wave (CW) Helmholtz Linear Accelerator (HELIAC) is under construction. A transport line, comprising quadrupole lenses, rebuncher cavities, beam correctors, and adequate beam instrumentation has been built to deliver the beam from the GSI 1.4 MeV/u High Charge Injector (HLI) to the advanced demonstrator, which offers a test environment for SC CW multigap cavities. In order to achieve proper phase space matching, the beam from the HLI must be characterized in detail. In a dedicated machine experiment the bunch shape has been measured with a nondestructive bunch shape monitor (BSM). Therefore, different bunch projections were obtained by altering the voltage of two rebunchers. These measurements were combined with dedicated beam dynamics simulations using the particle tracking code dynamion. The longitudinal bunch shape and density distribution at the beginning of the matching line are fully characterized by a tomographic reconstruction method based on a non-negative least square minimization approach.

Abstract Background Calprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE. Results Mucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P

Very compact accelerating-focusing structures, as well as short focusing periods, high accelerating gradients and short drift spaces are strongly required for superconducting (sc) accelerator sections operating at low and medium energies for continuous wave (cw) heavy ion beams. To keep the GSI-super heavy element (SHE) program competitive on a high level and even beyond, a standalone sc cw linac (Helmholtz linear accelerator) in combination with the GSI high charge state injector (HLI), upgraded for cw operation, is envisaged. Recently the first linac section (financed by Helmholtz Institute Mainz (HIM) and GSI) as a demonstration of the capability of 217 MHz multigap crossbar H-mode structures (CH) has been commissioned and extensively tested with heavy ion beam from the HLI. The demonstrator setup reached acceleration of heavy ions up to the design beam energy. The required acceleration gain was achieved with heavy ion beams even above the design mass to charge ratio at high beam intensity and full beam transmission. This paper presents systematic beam measurements with varying rf amplitudes and phases of the CH cavity, as well as phase space measurements for heavy ion beams with different mass to charge ratio. The worldwide first and successful beam test with a superconducting multigap CH cavity is a milestone of the R&D work of HIM and GSI in collaboration with IAP in preparation of the HELIAC project and other cw-ion beam applications.

The 40 years old GSI-UNILAC (Universal Linear Accelerator) as well as the heavy ion synchrotron SIS18 will serve as a high current heavy ion injector for the new FAIR (Facility for Antiproton and Ion Research) synchrotron SIS100. In the context of an advanced machine investigation program in combination with the ongoing UNILAC upgrade program, a new uranium beam intensity record (11.5 emA, U^{29+}) at very high beam brilliance was achieved recently in a machine experiment campaign. This is an important step paving the way to fulfill the FAIR heavy ion high intensity beam requirements. Results of high current uranium beam measurements applying a newly developed pulsed hydrogen gas stripper (at 1.4 MeV/u) will be presented in detail.

Abstract Background Brachyspira (B.) pilosicoli is a zoonotic pathogen, able to infect different animal species such as pigs, poultry, and rodents, causing intestinal spirochetosis. An association of gastrointestinal clinical signs, such as diarrhea, with the isolation of B. pilosicoli from fecal samples or rectal swabs has not been proven in dogs. Other Brachyspira species commonly isolated from dogs, such as “B. canis” and “B. pulli”, are considered commensals. This study investigated the occurrence of different Brachyspira species in rectal swabs and fecal samples in an independent canine cohort in central Germany. These included samples from shelter dogs, hunting dogs, and dogs presenting at regional small animal practices with various clinical signs. Data about the dogs, including potential risk factors for Brachyspira isolation, were obtained using a standardized questionnaire. The study also longitudinally investigated a colony of Beagle dogs for Brachyspira over 5 years. Results The rate of Brachyspira spp. isolation was 11% and included different Brachyspira species (“B. canis”, “B. pulli”, and B. pilosicoli). “B. canis” was detected in 18 dogs, whereas B. pilosicoli was only isolated from 1 dog in the independent cohort (not including the Beagle colony). Risk factors for shedding Brachyspira and “B. canis” were being less than 1 year of age and shelter origin. Gastrointestinal signs were not associated with the shedding of Brachyspira. B. pilosicoli and “B. canis” were isolated from several dogs of the same Beagle colony in 2017 and again in 2022, while Brachyspira was not isolated at multiple sampling time points in 2021. Conclusions Shedding of B. pilosicoli in dogs appears to be uncommon in central Germany, suggesting a low risk of zoonotic transmission from dogs. Commensal status of “B. canis” and “B. pulli” is supported by the results of this study. Findings from the longitudinal investigation of the Beagle colony agree with an asymptomatic long-term colonization of dogs with “B. canis” and B. pilosicoli and suggest that introducing new animals in a pack can trigger an increased shedding of B. pilosicoli.

Abstract Background Prostatic carcinoma (PCA) is a rare but severe condition in dogs that is similar to the androgen-independent form of PCA in men. In contrast to humans, PCA is difficult to diagnose in dogs as reliable biomarkers, available for PCA screening in human medicine, are currently lacking in small animal oncology. Calprotectin (S100A8/A9) and S100A12 are Ca2+-binding proteins of the innate immune system with promising potential to distinguish malignant from benign urogenital tract conditions, similar to the blood neutrophil-to-lymphocyte-ratio (NLR). However, both have not yet been extensively investigated in dogs with PCA. Thus, this study aimed to evaluate the expression of the S100/calgranulins (calprotectin, S100A12, and their ratio [Cal-ratio]) in prostatic biopsies from nine dogs with PCA and compare them to those in dogs with benign prostatic lesions (eight dogs with prostatitis and ten dogs with benign prostatic hyperplasia [BPH]) as well as five healthy controls. In addition, blood NLRs were investigated in twelve dogs with PCA and 22 dogs with benign prostatic conditions. Results Tissue S100A8/A9+ cell counts did not differ significantly between tissue from PCA and prostatitis cases (P = 0.0659) but were significantly higher in dogs with prostatitis than BPH (P = 0.0013) or controls (P = 0.0033). S100A12+ cell counts were significantly lower in PCA tissues than in prostatitis tissue (P = 0.0458) but did not differ compared to BPH tissue (P = 0.6499) or tissue from controls (P = 0.0622). Cal-ratios did not differ significantly among the groups but were highest in prostatitis tissues and significantly higher in those dogs with poor prostatitis outcomes than in patients that were still alive at the end of the study (P = 0.0455). Blood NLR strongly correlated with prostatic tissue S100A8/A9+ cell counts in dogs with PCA (ρ = 0.81, P = 0.0499) but did not differ among the disease groups of dogs. Conclusions This study suggests that the S100/calgranulins play a role in malignant (PCA) and benign (prostatic inflammation) prostatic conditions and supports previous results in lower urinary tract conditions in dogs. These molecules might be linked to the inflammatory environment with potential effects on the inflammasome. The blood NLR does not appear to aid in distinguishing prostatic conditions in dogs. Further investigation of the S100/calgranulin pathways and their role in modulation of tumor development, progression, and metastasis in PCA is warranted.

Chronic inflammatory enteropathies (CIEs) are an important group of diseases in dogs and involve complex pathogenetic aspects. Endoscopy and histopathology are vital for documenting the disease but are less useful for subclassifying CIEs and predicting the response to treatment. However, healing of the mucosal disease process (deep remission) and ultrastructural evaluation of the mucosa have received little attention in canine CIE. Given that canine CIE shares many similarities with inflammatory bowel diseases (IBDs) in human patients—and presents a good spontaneous disease model for human IBD—this perspective article evaluates the literature on ultrastructural lesions in canine CIE and human IBD and offers future directions for the study of ultrastructural mucosal lesions in canine CIE. Such lesions might have a higher sensitivity of detection than structural changes revealed upon light microscopy and may even precede or remain after the resolution of the clinical signs and histologic lesions.

Feline chronic enteropathies (FCE) are challenging to diagnose and monitor for progression and response to treatment. Fecal calprotectin might be a useful non-invasive marker to evaluate clinical endpoints of therapeutic monitoring in FCE. We evaluated fecal calprotectin concentrations in cats with FCE before and after initiation of treatment comprised of immunomodulation and/or dietary intervention. Included were 17 cats with FCE and 18 healthy controls. Clinical investigation of FCE cases included clinical severity grading (feline chronic enteropathy activity index, FCEAI) in all cats, abdominal ultrasonography in 15 cats, and gastrointestinal biopsies in 6 cats. Fecal calprotectin was measured in samples from 12 cats with FCE before treatment, all 17 FCE cats ≥6 weeks after treatment initiation, and all healthy controls. Fecal calprotectin concentrations in FCE cases before treatment (median: 61 μg/g) were significantly higher than after treatment initiation (median: 15 μg/g; p = 0.0098) and compared to controls (median: 6 μg/g; p = 0.0235) and correlated with the FCEAI scores (ρ = 0.54, p = 0.0316). Fecal calprotectin concentrations after treatment initiation were higher with more severe duodenal/proximal jejunal pathology (ρ = 0.83, p = 0.0427) and shorter intervals between sampling time points (ρ = −0.54, p = 0.0250). Relevant decreases in initially increased fecal calprotectin concentrations are seen in cats with FCE on varying treatment strategies that significantly improve or have remission of clinical signs. This supports the utility of fecal calprotectin as a surrogate biomarker to assess disease severity in FCE cases. Further studies need to evaluate fecal calprotectin concentrations longitudinally in relation to mucosal healing vs. clinical response.

Brachyspira pilosicoli (B. pilosicoli) is a pathogen in pigs, poultry, and humans causing colitis, diarrhea, and poor growth rates. Its role as a canine pathogen is controversial, and the seroprevalence of specific IgG antibodies against B. pilosicoli in dogs is unknown. A further, not yet officially recognized Brachyspira species in dogs is “Brachyspira canis” (“B. canis“), which is proposed to be apathogenic. This study evaluates enzyme-linked immunosorbent assays (ELISAs) measuring serum IgG antibodies specific for B. pilosicoli or “B. canis” and investigates levels of specific IgG antibodies against B. pilosicoli and “B. canis” in a cohort of clinical patients presented at an animal referral clinic. These ELISAs use detergent-extracted antigens from B. pilosicoli and “B. canis”. To increase analytic specificity, we precipitated the antigens with trichloroacetic acid (TCA) to isolate and concentrate the respective protein fraction. Our results indicate that a large number of serum IgG antibodies bind to shared epitopes of detergent-extracted antigens of the two spirochaetes. Our data also suggest that dogs might not only carry B. pilosicoli but also have “B. canis”-specific serum IgG antibodies.

The neutrophil-to-lymphocyte ratio (NLR) can help in assessing inflammatory diseases, sepsis, and chronic hepatic conditions in humans. Dogs with congenital portosystemic shunts (PSSs) have signs of generalized inflammation, and the clinical signs can overlap with other conditions, including hypoadrenocorticism (HOC). Thus, the potential diagnostic and prognostic value of leukocyte ratios as surrogate markers was assessed in a retrospective case–control study including 106 dogs diagnosed with PSSs. The disease control groups were dogs with parenchymal hepatopathy (PH; n = 22) or HOC (n = 31). In the PSS dogs, the blood NLRs were associated with the severity of systemic inflammation but not with the shunt type, hepatoencephalopathy, systemic infection, or hypoglycemia. The baseline NLRs did not differ between the three disease groups, between medically and surgically treated PSS dogs, or between those with successful PSS ligation and dogs experiencing peri-/post-surgical complications. However, dogs requiring two consecutive surgical interventions had significantly higher NLRs, and an NLR of

Abstract Background Miniature Schnauzers (MS) commonly have idiopathic hypertriglyceridemia (HTGL), which is associated with insulin resistance (IR) and a subclinical inflammatory phenotype. Objectives Determine the association between indicators of IR and inflammatory biomarkers in MS with and without HTGL and identify how indicators of IR are affected by dietary intervention in MS with HTGL. Animals Seventy MS with HTGL and 79 MS without HTGL. In addition, 15 MS with HTGL were placed on a low‐fat diet. Methods Serum concentrations of triglycerides, cholesterol, calprotectin, insulin, and glucose were compared between groups. Results Serum glucose and calprotectin concentrations (shown to be higher in MS with HTGL than in MS without HTGL) were inversely correlated (ρ = −.28; P

Toxoplasma (T.) gondii is an obligate intracellular parasite with felids, including domestic cats, as definitive hosts. In immunocompetent individuals, T. gondii infection is usually asymptomatic. However, under immunosuppression, it may have severe pathological impacts, which often result from the reactivation of a chronic infection. In this case study, a 21-month-old female domestic shorthair cat—diagnosed with primary immune-mediated hemolytic anemia three months prior and treated with cyclosporine and prednisolone—presented with acute tachypnea, dyspnea, diarrhea, and anorexia. Thoracic radiography suggested severe pneumonia. Testing for Mycoplasma spp., Anaplasma spp., Ehrlichia spp., and lungworm infection was negative. Serology for T. gondii revealed seroconversion of IgG, but not of IgM, indicating previous exposure to T. gondii. The cat remained stable but tachypneic for three days, followed by an acute onset of dyspnea and clinical deterioration, after which euthanasia was elected. Numerous protozoa were present in a postmortem transtracheal bronchoalveolar lavage and fine-needle aspiration of the lung. Microsatellite typing classified the extracted DNA as T. gondii type II variant TgM-A. This case demonstrates that T. gondii reactivation, leading to fulminant pneumonia, can be a sequela of immunosuppressive treatment in cats and should, therefore, be considered as a differential diagnosis in immunosuppressed cats with acute-onset respiratory signs. Rapid diagnosis may prevent fatal consequences.

Measuring C-reactive protein (CRP) in serum is a useful surrogate marker for assessing disease progression and treatment response in dogs with autoinflammatory diseases. Affected dogs often receive high-dose glucocorticoid treatment, but the effect of such treatment alone on serum CRP concentrations is unknown. We evaluated serum CRP concentrations via immunoassay (sandwich enzyme-linked immunosorbent assay and particle-enhanced turbidimetric immunoassay) in 12 healthy beagle dogs administered high-dose hydrocortisone (8 mg/kg q12 h) per os vs. placebo over 28 days (days 0, 1, 5, and 28) in a randomized parallel study design. Serum CRP concentrations slightly decreased during treatment or placebo but without a significant association with hydrocortisone administration (p = 0.761). Compared to baseline, serum CRP concentrations were decreased by >2.7-fold (minimum critical difference) in three hydrocortisone-treated dogs and two dogs in the placebo group on day 28, whereas an increase to >2.7-fold was seen in one dog receiving placebo. These results suggest a lack of confounding effects of high-dose hydrocortisone administration on serum CRP concentrations in healthy dogs. This might also hold in dogs with autoinflammatory conditions and/or administration of other high-dose corticosteroids, suggesting that CRP presents a suitable biomarker to monitor inflammatory disease processes. However, this needs confirmation by further studies evaluating corticosteroid-induced cellular (e.g., hepatic) transcriptome and proteome changes.

Miniature Schnauzers are predisposed to develop pancreatitis, with familial hypertriglyceridemia (HTG) described as a potential risk factor. Diagnosing pancreatitis in dogs is based on the integration of serum canine-specific pancreatic lipase (cPLI) concentration, clinical presentation, and diagnostic imaging findings. However, markers of systemic inflammation and antiprotease activity have not been extensively investigated in the characterization and prognostication of pancreatitis in dogs. Serum concentrations of alpha1-proteinase inhibitor (α1PI; as a marker of systemic antiprotease response) and calprotectin and S100A12 (as markers of systemic inflammation) were measured in serum samples from 35 Miniature Schnauzers diagnosed with pancreatitis (serum cPLI concentration >400 μg/L, clinical signs, abdominal imaging findings). These markers were evaluated for possible associations with patient characteristics, clinical presentation, risk factors for pancreatitis, and outcome. The study showed that biomarkers of systemic inflammation and antiprotease activity are commonly increased in Miniature Schnauzers with pancreatitis. Whereas serum calprotectin and S100A12 concentrations were found to have limited utility in differentiating pancreatitis presentations, serum α1PI concentrations and potentially also the serum calprotectin-to-S100A12 ratio might be non-invasive surrogate markers of disease severity in dogs with pancreatitis.

Diagnosis of feline chronic inflammatory enteropathies (CIE) and the differentiation from small cell intestinal lymphoma (SCL) can be challenging. Intestinally expressed calprotectin (S100A8/A9 protein complex) appears to be part of the complex pathogenesis of feline chronic enteropathies (FCE). Fecal calprotectin is a non-invasive biomarker for intestinal inflammation in humans and dogs but has not yet been evaluated in cats. We hypothesized that fecal calprotectin (fCal) concentrations are increased in FCE, correlate with clinical and/or histologic disease severity, and distinguish cases of CIE from SCL. This case–control study included fecal samples and patient data from cats with CIE (n = 34), SCL (n = 17), other gastrointestinal (GI) diseases (n = 16), and cats with no clinical signs of GI disease (n = 32). fCal concentrations were measured using the immunoturbidimetric fCal turbo assay (Bühlmann Laboratories). Compared to healthy cats, fCal concentrations were significantly increased in CIE, SCL, and other diseases (all p < 0.0001), but were not different between these three groups (all p > 0.05), or between cats with extra-GI diseases and healthy controls. These findings suggest that fCal may have utility as a clinical biomarker for FCE but not for intestinal disease differentiation. It further supports the role of calprotectin in the pathogenesis of the spectrum of FCE, which includes CIE and SCL.

Chronic inflammatory enteropathy (CE) is a common cause of persistent gastrointestinal signs and intestinal inflammation in dogs. Since evidence links dysbiosis to mucosal inflammation, probiotics, prebiotics, or their combination (synbiotics) may reduce intestinal inflammation and ameliorate dysbiosis in affected dogs. This study’s aim was to investigate the effects of the synbiotic-IgY supplement on clinical signs, inflammatory indices, and mucosal microbiota in dogs with CE. Dogs with CE were enrolled in a randomized prospective trial. Twenty-four client-owned dogs were fed a hydrolyzed diet and administered supplement or placebo (diet) for 6 weeks. Dogs were evaluated at diagnosis and 2- and 6-week post-treatment. Outcome measures included clinical activity, endoscopic and histologic scores, inflammatory markers (fecal calprotectin, C-reactive protein), and composition of the mucosal microbiota via FISH. Eleven supplement- and nine placebo-treated dogs completed the trial. After 6 weeks of therapy, clinical activity and endoscopic scores decreased in both groups. Compared to placebo-treated dogs, dogs administered supplement showed decreased calprotectin at 2-week post-treatment, decreased CRP at 2- and 6-week post-treatment increased mucosal Clostridia and Bacteroides and decreased Enterobacteriaceae in colonic biopsies at trial completion. Results suggest a beneficial effect of diet and supplements on host responses and mucosal microbiota in dogs with CE.

Non-steroidal anti-inflammatory drugs (NSAIDs) may cause enteropathy in dogs and probiotics may be one option to prevent this. The objective of this study was to determine whether the administration of canine-obtained lactic acid bacteria (LAB) has an effect on the frequency of diarrhea, the composition of the fecal microbiota, and/or markers of gastrointestinal inflammation in dogs receiving NSAIDs when compared to dogs given NSAIDs and a placebo. A total of 22 dogs treated with NSAIDs for various clinical indications were enrolled in a seven-day randomized, double-blinded placebo-controlled interventional study. Dogs were randomized to receive either placebo or LAB, a product containing Limosilactobacillus fermentum, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum. Fecal samples were collected on days one and seven. The fecal microbiota was evaluated using the fecal dysbiosis index (DI) and individual bacterial taxa. Fecal calprotectin (CP) and S100A12/Calgranulin C concentrations were used as markers of gastrointestinal inflammation. There was a difference in frequency of diarrhea between groups, with it affecting 4/12 dogs (33%) in the placebo group and 1/10 dogs (10%) in the LAB group, but this difference did not reach statistical significance (p = 0.32). There was a correlation between S100A12 and CP (p < 0.001), and Clostridium perfringens correlated with S100A12 (p < 0.015). Neither treatment significantly affected S100A12 (p = 0.37), CP (p = 0.12), or fecal DI (p = 0.65). This study suggests that LAB is a safe supplement to use for short-term treatment in NSAID-treated dogs, but further studies are needed to determine its potential to prevent NSAID-induced enteropathy in dogs.

Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9+ and S100A12+ cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12+ cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12+ cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9+ cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL.

Feline morbilliviruses (FeMV) are fairly newly discovered paramyxoviruses found in cats. The first description indicated an association with widely distributed chronic kidney disease (CKD) in the host species. In various studies, a global prevalence and a further genotype, designated FeMV-2, and the involvement of other organ systems in infected individuals were shown. Using an immunofluorescence assay, we detected an overall seroprevalence of FeMV in almost half of the cats investigated (n = 380), with a significantly increased proportion in younger animals. In comparison to European Shorthair cats, the rate of seropositivity is higher in pedigree cats. Regardless of the breed, FeMV infection was associated with increased blood creatinine concentrations, suggesting an association with CKD. Further analysis indicated that this association was the strongest in animals having high IFA titers against FeMV-2. In addition, a significant association between FeMV-positive status and the prevalence of feline lower urinary tract disease (FLUTD, or idiopathic cystitis) was detected. This association was dominated by cats having antibodies against FeMV-1 only. To further evaluate the positive correlation between FeMV seroprevalence and CKD as well as FLUTD, consideration of additional clinical characteristics and laboratory parameters is warranted, and controlled infection studies with both FeMV genotypes are necessary. Clinicians should, however, be aware of a possible link between renal and lower urinary tract disease and FeMV infections.